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Sample records for flaviviruses correlating variance

  1. Correlating Flavivirus virulence and levels of intrinsic disorder in shell proteins: protective roles vs. immune evasion.

    PubMed

    Goh, Gerard Kian-Meng; Dunker, A Keith; Uversky, Vladimir N

    2016-05-24

    Computational analyses revealed correlations between the intrinsic disorder propensity of shell proteins and case fatality rates (CFRs) among Flaviviruses and within at least two Flavivirus species, such as tick-borne encephalitis virus (TBEV) and dengue virus (DENV). The shell proteins analyzed in this study are capsid (C) and membrane (PrM, Pr, and M) proteins. The highest correlations can be found when regression analyses were conducted using Pr (Flavivirus: r(2) = 0.78, p < 0.01) or M (Flavivirus: r(2) = 0.91, p < 0.01) as an independent variable with C and CFR as co-explanatory and dependent variables, respectively. Interestingly, while predicted intrinsic disorder levels (PIDs) of both C and M are positively correlated with the virulence, the PIDs of Pr and CFR are negatively correlated. This is likely due to the fact that the Pr portion of PrM plays various roles in protecting the virion from damage, whereas M and C are assisted by greater potential in binding promiscuity as a result of greater disorder. The C protein of yellow fever virus (YFV), which is the most virulent virus in the sample, has the highest PID levels, whereas the second most virulent TBEV FE subtype has the second highest PID score due to its C protein, and the least virulent West Nile virus (WNV) has the least disordered C protein. This knowledge can be used while working on the development and identification of attenuated strains for vaccine. Curiously, unlike Flaviviruses, a disordered outer shell was described for hepatitis C virus (HCV), human immunodeficiency virus (HIV), and human simplex virus 2 (HSV-2), which currently have no effective vaccine. PMID:27102744

  2. The Variance of Intraclass Correlations in Three and Four Level

    ERIC Educational Resources Information Center

    Hedges, Larry V.; Hedberg, Eric C.; Kuyper, Arend M.

    2012-01-01

    Intraclass correlations are used to summarize the variance decomposition in popula- tions with multilevel hierarchical structure. There has recently been considerable interest in estimating intraclass correlations from surveys or designed experiments to provide design parameters for planning future large-scale randomized experiments. The large…

  3. Genetic Variance in the SES-IQ Correlation.

    ERIC Educational Resources Information Center

    Eckland, Bruce K.

    1979-01-01

    Discusses questions dealing with genetic aspects of the correlation between IQ and socioeconomic status (SES). Questions include: How does assortative mating affect the genetic variance of IQ? Is the relationship between an individual's IQ and adult SES a causal one? And how can IQ research improve schools and schooling? (Author/DB)

  4. [The correlations between psychological indices and cardiac variance].

    PubMed

    Nikolova, R; Danev, S; Amudzhev, P; Datsov, E

    1995-01-01

    Correlative links between psychologic and psychologic indicators were studied in subjects occupied either in airline transportation or in the chemical industry. Investigations covered three groups of persons: managers of airline traffic (57 subjects); workers at "Vratsa" Chemical plant (14 subjects); and operators at "Vratsa" Chemical plant (14 subjects). The psychologic parameters measured included indicators of cardiac variance: mean--mean value of successive cardiac intervals, SD--standard deviation of mean value of cardiac intervals (R-R), AMo--amplitude of the mode, HI--homeostatic index, Pt--spectral power of R-R related to thermoregulation, Pp--spectral power of R-R related to respiration, IBO--index of centralization; psychologic parameters included: extrovertiveness, introvertiveness, neuroticism, psychoticism, interpersonality conflicts, self-control, social support, self-confidence, work satisfaction, psychosomatic complaints. There was evidence of significant and highly significant correlative links between indicators of cardiac variance and psychologic indicators. There thus appeared to exist certain relationships between the psychologic and psychologic levels during lengthy stressful occupational exposure. PMID:8524754

  5. Flavivirus susceptibility in Aedes aegypti.

    PubMed

    Black, William C; Bennett, Kristine E; Gorrochótegui-Escalante, Norma; Barillas-Mury, Carolina V; Fernández-Salas, Ildefonso; de Lourdes Muñoz, María; Farfán-Alé, José A; Olson, Ken E; Beaty, Barry J

    2002-01-01

    Aedes aegypti is the primary vector of yellow fever (YF) and dengue fever (DF) flaviviruses worldwide. In this review we focus on past and present research on genetic components and environmental factors in Aedes aegypti that appear to control flavivirus transmission. We review genetic relationships among Ae. aegypti populations throughout the world and discuss how variation in vector competence is correlated with overall genetic differences among populations. We describe current research into how genetic and environmental factors jointly affect distribution of vector competence in natural populations. Based on this information, we propose a population genetic model for vector competence and discuss our recent progress in testing this model. We end with a discussion of approaches being taken to identify the genes that may control flavivirus susceptibility in Ae. aegypti. PMID:12234528

  6. Flavivirus-mosquito interactions.

    PubMed

    Huang, Yan-Jang S; Higgs, Stephen; Horne, Kate McElroy; Vanlandingham, Dana L

    2014-11-01

    The Flavivirus genus is in the family Flaviviridae and is comprised of more than 70 viruses. These viruses have a broad geographic range, circulating on every continent except Antarctica. Mosquito-borne flaviviruses, such as yellow fever virus, dengue virus serotypes 1-4, Japanese encephalitis virus, and West Nile virus are responsible for significant human morbidity and mortality in affected regions. This review focuses on what is known about flavivirus-mosquito interactions and presents key data collected from the field and laboratory-based molecular and ultrastructural evaluations. PMID:25421894

  7. Flavivirus-Mosquito Interactions

    PubMed Central

    Huang, Yan-Jang S.; Higgs, Stephen; Horne, Kate McElroy; Vanlandingham, Dana L.

    2014-01-01

    The Flavivirus genus is in the family Flaviviridae and is comprised of more than 70 viruses. These viruses have a broad geographic range, circulating on every continent except Antarctica. Mosquito-borne flaviviruses, such as yellow fever virus, dengue virus serotypes 1–4, Japanese encephalitis virus, and West Nile virus are responsible for significant human morbidity and mortality in affected regions. This review focuses on what is known about flavivirus-mosquito interactions and presents key data collected from the field and laboratory-based molecular and ultrastructural evaluations. PMID:25421894

  8. Flavivirus Entry Inhibitors.

    PubMed

    Wang, Qing-Yin; Shi, Pei-Yong

    2015-09-11

    Many flaviviruses are significant human pathogens that are transmitted by mosquitoes and ticks. Although effective vaccines are available for yellow fever virus, Japanese encephalitic virus, and tick-borne encephalitis virus, these and other flaviviruses still cause thousands of human deaths and millions of illnesses each year. No clinically approved antiviral therapy is available for flavivirus treatment. To meet this unmet medical need, industry and academia have taken multiple approaches to develop antiflavivirus therapy, among which targeting viral entry has been actively pursued in the past decade. Here we review the current knowledge of flavivirus entry and its use for small molecule drug discovery. Inhibitors of two major steps of flaviviral entry have been reported: (i) molecules that block virus-receptor interaction; (ii) compounds that prevent conformational change of viral envelope protein during virus-host membrane fusion. We also discuss the advantages and disadvantages of targeting viral entry for treatment of flavivirus infection as compared to targeting viral replication proteins. PMID:27617926

  9. Genetic resistance to flaviviruses.

    PubMed

    Brinton, Margo A; Perelygin, Andrey A

    2003-01-01

    Resistance to flavivirus-induced disease in mice was first discovered in the 1920s and was subsequently shown to be controlled by the resistant allele of a single dominant autosomal gene. While the majority of current laboratory mouse stains have a homozygous-susceptible phenotype, the resistant allele has been found to segregate in wild mouse populations in many different parts of the world. Resistance is flavivirus specific and extends to both mosquito- and tick-borne flaviviruses. Resistant animals are infected productively by flaviviruses but produce lower virus titers, especially in their brains, as compared to susceptible mice. Decreased virus production is observed in resistant animals even during a lethal infection and the times of disease onset and death are also delayed as compared to susceptible mice. An intact immune response is required to clear flaviviruses from resistant mice. The resistant phenotype is expressed constitutively and does not require interferon induction. The Flv gene was discovered using a positional cloning approach and identified as Oas1b. Susceptible mice produce a truncated Oas1b protein. A C820T transition in the fourth exon of the gene introduced a premature stop codon and was found in all susceptible mouse strains tested. Possible mechanisms by which the product of the resistant allele could confer the resistant phenotype are discussed. PMID:14689691

  10. Temperature and humidity flux-variance relations determined by one-dimensional eddy correlation

    NASA Astrophysics Data System (ADS)

    Weaver, Harold L.

    1990-10-01

    It may be possible to estimate surface fluxes of scalar quantities from measurement of their variance and mean wind speed. The flux-variance relation for temperature and humidity was investigated over prairie and desert-shrub plant communities. Fluxes were measured by one-dimensional eddy correlation, humidity by fast-response wet-bulb psychrometers and Krypton open-path hygrometers, temperature by fine-wire thermocouples, and mean windspeed by a cup anemometer. The quality of the flux-variance relation proved to be good enough for application to flux measurement. Regressions of flux estimated by the variance technique versus measured flux usually had r 2 values greater than 0.97 for sensible heat flux and greater than 0.88 for water vapor flux. More uniform surfaces tended to yield the same flux-variance relations except when fluxes were small. This exception supported the hypothesis that sparse sources of flux may increase variance downwind. Nonuniform surfaces yielded flux-variance relations that were less predictable, although reasonably accurate once determined. The flux-variance relation for humidity was quite variable over dry surfaces with senescent vegetation.

  11. The Variance of Intraclass Correlations in Three- and Four-Level Models

    ERIC Educational Resources Information Center

    Hedges, Larry V.; Hedberg, E. C.; Kuyper, Arend M.

    2012-01-01

    Intraclass correlations are used to summarize the variance decomposition in populations with multilevel hierarchical structure. There has recently been considerable interest in estimating intraclass correlations from surveys or designed experiments to provide design parameters for planning future large-scale randomized experiments. The large…

  12. Detection of rheumatoid arthritis by evaluation of normalized variances of fluorescence time correlation functions

    NASA Astrophysics Data System (ADS)

    Dziekan, Thomas; Weissbach, Carmen; Voigt, Jan; Ebert, Bernd; MacDonald, Rainer; Bahner, Malte L.; Mahler, Marianne; Schirner, Michael; Berliner, Michael; Berliner, Birgitt; Osel, Jens; Osel, Ilka

    2011-07-01

    Fluorescence imaging using the dye indocyanine green as a contrast agent was investigated in a prospective clinical study for the detection of rheumatoid arthritis. Normalized variances of correlated time series of fluorescence intensities describing the bolus kinetics of the contrast agent in certain regions of interest were analyzed to differentiate healthy from inflamed finger joints. These values are determined using a robust, parameter-free algorithm. We found that the normalized variance of correlation functions improves the differentiation between healthy joints of volunteers and joints with rheumatoid arthritis of patients by about 10% compared to, e.g., ratios of areas under the curves of raw data.

  13. A new interpretation and validation of variance based importance measures for models with correlated inputs

    NASA Astrophysics Data System (ADS)

    Hao, Wenrui; Lu, Zhenzhou; Li, Luyi

    2013-05-01

    In order to explore the contributions by correlated input variables to the variance of the output, a novel interpretation framework of importance measure indices is proposed for a model with correlated inputs, which includes the indices of the total correlated contribution and the total uncorrelated contribution. The proposed indices accurately describe the connotations of the contributions by the correlated input to the variance of output, and they can be viewed as the complement and correction of the interpretation about the contributions by the correlated inputs presented in "Estimation of global sensitivity indices for models with dependent variables, Computer Physics Communications, 183 (2012) 937-946". Both of them contain the independent contribution by an individual input. Taking the general form of quadratic polynomial as an illustration, the total correlated contribution and the independent contribution by an individual input are derived analytically, from which the components and their origins of both contributions of correlated input can be clarified without any ambiguity. In the special case that no square term is included in the quadratic polynomial model, the total correlated contribution by the input can be further decomposed into the variance contribution related to the correlation of the input with other inputs and the independent contribution by the input itself, and the total uncorrelated contribution can be further decomposed into the independent part by interaction between the input and others and the independent part by the input itself. Numerical examples are employed and their results demonstrate that the derived analytical expressions of the variance-based importance measure are correct, and the clarification of the correlated input contribution to model output by the analytical derivation is very important for expanding the theory and solutions of uncorrelated input to those of the correlated one.

  14. Estimating the Correlation in Bivariate Normal Data with Known Variances and Small Sample Sizes1

    PubMed Central

    Fosdick, Bailey K.; Raftery, Adrian E.

    2013-01-01

    We consider the problem of estimating the correlation in bivariate normal data when the means and variances are assumed known, with emphasis on the small sample case. We consider eight different estimators, several of them considered here for the first time in the literature. In a simulation study, we found that Bayesian estimators using the uniform and arc-sine priors outperformed several empirical and exact or approximate maximum likelihood estimators in small samples. The arc-sine prior did better for large values of the correlation. For testing whether the correlation is zero, we found that Bayesian hypothesis tests outperformed significance tests based on the empirical and exact or approximate maximum likelihood estimators considered in small samples, but that all tests performed similarly for sample size 50. These results lead us to suggest using the posterior mean with the arc-sine prior to estimate the correlation in small samples when the variances are assumed known. PMID:23378667

  15. Quantum variance: A measure of quantum coherence and quantum correlations for many-body systems

    NASA Astrophysics Data System (ADS)

    Frérot, Irénée; Roscilde, Tommaso

    2016-08-01

    Quantum coherence is a fundamental common trait of quantum phenomena, from the interference of matter waves to quantum degeneracy of identical particles. Despite its importance, estimating and measuring quantum coherence in generic, mixed many-body quantum states remains a formidable challenge, with fundamental implications in areas as broad as quantum condensed matter, quantum information, quantum metrology, and quantum biology. Here, we provide a quantitative definition of the variance of quantum coherent fluctuations (the quantum variance) of any observable on generic quantum states. The quantum variance generalizes the concept of thermal de Broglie wavelength (for the position of a free quantum particle) to the space of eigenvalues of any observable, quantifying the degree of coherent delocalization in that space. The quantum variance is generically measurable and computable as the difference between the static fluctuations and the static susceptibility of the observable; despite its simplicity, it is found to provide a tight lower bound to most widely accepted estimators of "quantumness" of observables (both as a feature as well as a resource), such as the Wigner-Yanase skew information and the quantum Fisher information. When considering bipartite fluctuations in an extended quantum system, the quantum variance expresses genuine quantum correlations among the two parts. In the case of many-body systems, it is found to obey an area law at finite temperature, extending therefore area laws of entanglement and quantum fluctuations of pure states to the mixed-state context. Hence the quantum variance paves the way to the measurement of macroscopic quantum coherence and quantum correlations in most complex quantum systems.

  16. The large-scale correlations of multicell densities and profiles: implications for cosmic variance estimates

    NASA Astrophysics Data System (ADS)

    Codis, Sandrine; Bernardeau, Francis; Pichon, Christophe

    2016-08-01

    In order to quantify the error budget in the measured probability distribution functions of cell densities, the two-point statistics of cosmic densities in concentric spheres is investigated. Bias functions are introduced as the ratio of their two-point correlation function to the two-point correlation of the underlying dark matter distribution. They describe how cell densities are spatially correlated. They are computed here via the so-called large deviation principle in the quasi-linear regime. Their large-separation limit is presented and successfully compared to simulations for density and density slopes: this regime is shown to be rapidly reached allowing to get sub-percent precision for a wide range of densities and variances. The corresponding asymptotic limit provides an estimate of the cosmic variance of standard concentric cell statistics applied to finite surveys. More generally, no assumption on the separation is required for some specific moments of the two-point statistics, for instance when predicting the generating function of cumulants containing any powers of concentric densities in one location and one power of density at some arbitrary distance from the rest. This exact `one external leg' cumulant generating function is used in particular to probe the rate of convergence of the large-separation approximation.

  17. Disentangling Stability, Variability and Adaptability in Human Performance: Focus on the Interplay between Local Variance and Serial Correlation

    ERIC Educational Resources Information Center

    Torre, Kjerstin; Balasubramaniam, Ramesh

    2011-01-01

    We address the complex relationship between the stability, variability, and adaptability of psychological systems by decomposing the global variance of serial performance into two independent parts: the local variance (LV) and the serial correlation structure. For two time series with equal LV, the presence of persistent long-range correlations…

  18. Phylogeny of the Genus Flavivirus

    PubMed Central

    Kuno, Goro; Chang, Gwong-Jen J.; Tsuchiya, K. Richard; Karabatsos, Nick; Cropp, C. Bruce

    1998-01-01

    We undertook a comprehensive phylogenetic study to establish the genetic relationship among the viruses of the genus Flavivirus and to compare the classification based on molecular phylogeny with the existing serologic method. By using a combination of quantitative definitions (bootstrap support level and the pairwise nucleotide sequence identity), the viruses could be classified into clusters, clades, and species. Our phylogenetic study revealed for the first time that from the putative ancestor two branches, non-vector and vector-borne virus clusters, evolved and from the latter cluster emerged tick-borne and mosquito-borne virus clusters. Provided that the theory of arthropod association being an acquired trait was correct, pairwise nucleotide sequence identity among these three clusters provided supporting data for a possibility that the non-vector cluster evolved first, followed by the separation of tick-borne and mosquito-borne virus clusters in that order. Clades established in our study correlated significantly with existing antigenic complexes. We also resolved many of the past taxonomic problems by establishing phylogenetic relationships of the antigenically unclassified viruses with the well-established viruses and by identifying synonymous viruses. PMID:9420202

  19. Variance of speed of sound and correlation with acoustic impedance in canine corneas.

    PubMed

    Tang, Junhua; Liu, Jun

    2011-10-01

    The clinical standard for measuring corneal thickness is ultrasound pachymetry that assumes a constant speed of sound. The purpose of this study was to examine the variance of speed of sound and its relationship with acoustic impedance in healthy eyes of canines with a large age span. Corneal speed of sound and acoustic impedance were measured in 34 canine eyes at room temperature (21 ± 1°C). The mean speed of sound was 1577 ± 10 m/s ranging from 1553 to 1594 m/s. There was a strong correlation between speed of sound and acoustic impedance (R = 0.84, p < 0.001). Corneal speed of sound had a small variance in healthy canines over 1-year-old, but was significantly lower in younger canines suggesting an age effect. The strong correlation between corneal speed of sound and acoustic impedance may offer a potential means to noninvasively detect abnormal speed of sound for more accurate corneal thickness estimation. PMID:21821348

  20. [Reverse genetics system for flaviviruses].

    PubMed

    Suzuki, Ryosuke; Konishi, Eiji

    2013-01-01

    Flaviviruses such as Japanese encephalitis virus, West Nile virus, yellow fever virus, dengue virus, and tick-borne encephalitis virus belong to a family Flaviviridae. These viruses are transmitted to vertebrates by infected mosquitoes or ticks, producing diseases, which have a serious impact on global public health. Reverse genetics is a powerful tool for studying the viruses. Although infectious full-length clones have been obtained for multiple flaviviruses, their early-stage development had the difficulty because of the instability problem of the viral cDNA in E. coli. Several strategies have been developed to circumvent the problem of infectious clone instability. The current knowledge accumulated on reverse genetics system of flaviviruses and its application are summarized in this review. PMID:24769573

  1. Minimum variance imaging based on correlation analysis of Lamb wave signals.

    PubMed

    Hua, Jiadong; Lin, Jing; Zeng, Liang; Luo, Zhi

    2016-08-01

    In Lamb wave imaging, MVDR (minimum variance distortionless response) is a promising approach for the detection and monitoring of large areas with sparse transducer network. Previous studies in MVDR use signal amplitude as the input damage feature, and the imaging performance is closely related to the evaluation accuracy of the scattering characteristic. However, scattering characteristic is highly dependent on damage parameters (e.g. type, orientation and size), which are unknown beforehand. The evaluation error can degrade imaging performance severely. In this study, a more reliable damage feature, LSCC (local signal correlation coefficient), is established to replace signal amplitude. In comparison with signal amplitude, one attractive feature of LSCC is its independence of damage parameters. Therefore, LSCC model in the transducer network could be accurately evaluated, the imaging performance is improved subsequently. Both theoretical analysis and experimental investigation are given to validate the effectiveness of the LSCC-based MVDR algorithm in improving imaging performance. PMID:27155349

  2. Nondestructive probing of means, variances, and correlations of ultracold-atomic-system densities via qubit impurities

    NASA Astrophysics Data System (ADS)

    Elliott, T. J.; Johnson, T. H.

    2016-04-01

    We show how impurity atoms can measure moments of ultracold-atomic-gas densities, using the example of bosons in a one-dimensional lattice. This builds on a body of work regarding the probing of systems by measuring the dephasing of an immersed qubit. We show that this dephasing is captured by a function resembling characteristic functions of probability theory, of which the derivatives at short times reveal moments of the system operator to which the qubit couples. For a qubit formed by an impurity atom, in a system of ultracold atoms, this operator can be the density of the system at the location of the impurity, and thus means, variances, and correlations of the atomic densities are accessible.

  3. Dengue and other flavivirus infections.

    PubMed

    Choumet, V; Desprès, Ph

    2015-08-01

    Flaviviruses are responsible for yellow fever, Zika fever and dengue, all of which are major human diseases found in tropical regions of the globe. They are zoonoses with a transmission cycle that involves primates as reservoirs and mosquitoes of the genus Aedes as vectors. The recent upsurge of urban epidemics of yellow fever, Zika fever and dengue has involved human-to-human transmission with mosquitoes as the vector. This paper is primarily concerned with dengue, which has become the pre-eminent arbovirosis in terms of public health. PMID:26601449

  4. Fast patient-specific Monte Carlo brachytherapy dose calculations via the correlated sampling variance reduction technique

    SciTech Connect

    Sampson, Andrew; Le Yi; Williamson, Jeffrey F.

    2012-02-15

    Purpose: To demonstrate potential of correlated sampling Monte Carlo (CMC) simulation to improve the calculation efficiency for permanent seed brachytherapy (PSB) implants without loss of accuracy. Methods: CMC was implemented within an in-house MC code family (PTRAN) and used to compute 3D dose distributions for two patient cases: a clinical PSB postimplant prostate CT imaging study and a simulated post lumpectomy breast PSB implant planned on a screening dedicated breast cone-beam CT patient exam. CMC tallies the dose difference, {Delta}D, between highly correlated histories in homogeneous and heterogeneous geometries. The heterogeneous geometry histories were derived from photon collisions sampled in a geometrically identical but purely homogeneous medium geometry, by altering their particle weights to correct for bias. The prostate case consisted of 78 Model-6711 {sup 125}I seeds. The breast case consisted of 87 Model-200 {sup 103}Pd seeds embedded around a simulated lumpectomy cavity. Systematic and random errors in CMC were unfolded using low-uncertainty uncorrelated MC (UMC) as the benchmark. CMC efficiency gains, relative to UMC, were computed for all voxels, and the mean was classified in regions that received minimum doses greater than 20%, 50%, and 90% of D{sub 90}, as well as for various anatomical regions. Results: Systematic errors in CMC relative to UMC were less than 0.6% for 99% of the voxels and 0.04% for 100% of the voxels for the prostate and breast cases, respectively. For a 1 x 1 x 1 mm{sup 3} dose grid, efficiency gains were realized in all structures with 38.1- and 59.8-fold average gains within the prostate and breast clinical target volumes (CTVs), respectively. Greater than 99% of the voxels within the prostate and breast CTVs experienced an efficiency gain. Additionally, it was shown that efficiency losses were confined to low dose regions while the largest gains were located where little difference exists between the homogeneous and

  5. Structural and Functional Analyses of a Conserved Hydrophobic Pocket of Flavivirus Methyltransferase*

    PubMed Central

    Dong, Hongping; Liu, Lihui; Zou, Gang; Zhao, Yiwei; Li, Zhong; Lim, Siew Pheng; Shi, Pei-Yong; Li, Hongmin

    2010-01-01

    The flavivirus methyltransferase (MTase) sequentially methylates the N7 and 2′-O positions of the viral RNA cap (GpppA-RNA → m7GpppA-RNA → m7GpppAm-RNA), using S-adenosyl-l-methionine (AdoMet) as a methyl donor. We report here that sinefungin (SIN), an AdoMet analog, inhibits several flaviviruses through suppression of viral MTase. The crystal structure of West Nile virus MTase in complex with SIN inhibitor at 2.0-Å resolution revealed a flavivirus-conserved hydrophobic pocket located next to the AdoMet-binding site. The pocket is functionally critical in the viral replication and cap methylations. In addition, the N7 methylation efficiency was found to correlate with the viral replication ability. Thus, SIN analogs with modifications that interact with the hydrophobic pocket are potential specific inhibitors of flavivirus MTase. PMID:20685660

  6. Structural and Functional Analyses of a Conserved Hydrophobic Pocket of Flavivirus Methyltransferase

    SciTech Connect

    H Dong; L Liu; G Zou; Y Zhao; Z Li; S Lim; P Shi; H Li

    2011-12-31

    The flavivirus methyltransferase (MTase) sequentially methylates the N7 and 2'-O positions of the viral RNA cap (GpppA-RNA {yields} m(7)GpppA-RNA {yields} m(7)GpppAm-RNA), using S-adenosyl-l-methionine (AdoMet) as a methyl donor. We report here that sinefungin (SIN), an AdoMet analog, inhibits several flaviviruses through suppression of viral MTase. The crystal structure of West Nile virus MTase in complex with SIN inhibitor at 2.0-{angstrom} resolution revealed a flavivirus-conserved hydrophobic pocket located next to the AdoMet-binding site. The pocket is functionally critical in the viral replication and cap methylations. In addition, the N7 methylation efficiency was found to correlate with the viral replication ability. Thus, SIN analogs with modifications that interact with the hydrophobic pocket are potential specific inhibitors of flavivirus MTase.

  7. Flavivirus RNA synthesis in vitro.

    PubMed

    Padmanabhan, Radhakrishnan; Takhampunya, Ratree; Teramoto, Tadahisa; Choi, Kyung H

    2015-12-01

    Establishment of in vitro systems to study mechanisms of RNA synthesis for positive strand RNA viruses have been very useful in the past and have shed light on the composition of protein and RNA components, optimum conditions, the nature of the products formed, cis-acting RNA elements and trans-acting protein factors required for efficient synthesis. In this review, we summarize our current understanding regarding the requirements for flavivirus RNA synthesis in vitro. We describe details of reaction conditions, the specificity of template used by either the multi-component membrane-bound viral replicase complex or by purified, recombinant RNA-dependent RNA polymerase. We also discuss future perspectives to extend the boundaries of our knowledge. PMID:26272247

  8. Specificities of human CD4+ T cell responses to an inactivated flavivirus vaccine and infection: correlation with structure and epitope prediction.

    PubMed

    Schwaiger, Julia; Aberle, Judith H; Stiasny, Karin; Knapp, Bernhard; Schreiner, Wolfgang; Fae, Ingrid; Fischer, Gottfried; Scheinost, Ondrej; Chmelik, Vaclav; Heinz, Franz X

    2014-07-01

    Tick-borne encephalitis (TBE) virus is endemic in large parts of Europe and Central and Eastern Asia and causes more than 10,000 annual cases of neurological disease in humans. It is closely related to the mosquito-borne yellow fever, dengue, Japanese encephalitis, and West Nile viruses, and vaccination with an inactivated whole-virus vaccine can effectively prevent clinical disease. Neutralizing antibodies are directed to the viral envelope protein (E) and an accepted correlate of immunity. However, data on the specificities of CD4(+) T cells that recognize epitopes in the viral structural proteins and thus can provide direct help to the B cells producing E-specific antibodies are lacking. We therefore conducted a study on the CD4(+) T cell response against the virion proteins in vaccinated people in comparison to TBE patients. The data obtained with overlapping peptides in interleukin-2 (IL-2) enzyme-linked immunosorbent spot (ELISpot) assays were analyzed in relation to the three-dimensional structures of the capsid (C) and E proteins as well as to epitope predictions based on major histocompatibility complex (MHC) class II peptide affinities. In the C protein, peptides corresponding to two out of four alpha helices dominated the response in both vaccinees and patients, whereas in the E protein concordance of immunodominance was restricted to peptides of a single domain (domain III). Epitope predictions were much better for C than for E and were especially erroneous for the transmembrane regions. Our data provide evidence for a strong impact of protein structural features that influence peptide processing, contributing to the discrepancies observed between experimentally determined and computer-predicted CD4(+) T cell epitopes. Importance: Tick-borne encephalitis virus is endemic in large parts of Europe and Asia and causes more than 10,000 annual cases of neurological disease in humans. It is closely related to yellow fever, dengue, Japanese encephalitis, and

  9. Complete genome sequence of Xishuangbanna flavivirus, a novel mosquito-specific flavivirus from China.

    PubMed

    Fan, Hang; Zhao, Qiumin; Guo, Xiaofang; Sun, Qiang; Zuo, Shuqing; Wu, Chao; Zhou, Hongning; An, Xiaoping; Pei, Guangqian; Tong, Yigang; Zhang, Jiusong; Shi, Taoxing

    2016-06-01

    A new flavivirus, Xishuangbanna flavivirus (XFV), infecting Aedes albopictus mosquitoes in Yunnan Province, China, was isolated and sequenced. The single-stranded RNA genome of 10,884 nt contained two open reading frames (ORFs) encoding the polyprotein and FIFO. The genome had a maximum nucleotide sequence identity of 65 % to Parramatta River virus with coverage of only 27 %. Phylogenetic analysis suggested that this virus is most closely related to recognized classical insect-specific flaviviruses (cISF) and most likely has a similar host range. Sequence comparisons and phylogenetic analysis demonstrated that XFV is a new member of the genus Flavivirus. PMID:27001304

  10. Neural correlates of attentional bias for smoking cues: modulation by variance in the dopamine transporter gene

    PubMed Central

    Wetherill, Reagan R.; Jagannathan, Kanchana; Lohoff, Falk W.; Ehrman, Ronald; O’Brien, Charles P.; Childress, Anna Rose; Franklin, Teresa R.

    2014-01-01

    Cigarette-dependent smokers automatically and involuntarily orient attention towards smoking cues (SCs). This attentional bias is clinically significant, as it may contribute to relapse. Thus, identifying neural and genetic correlates of attentional bias is critical for improving interventions. Our previous studies show that the dopamine transporter (DAT) SLC6A3 genotype exerts profound effects on limbic responses to SCs. One potential mechanism underlying these effects is greater attentional bias for SCs. Here, we explored associations between attentional bias for SCs and neural responses to SCs among ‘sated’ smokers genotyped for the SLC6A3 polymorphism. Pseudo-Continuous arterial spin-labeled (pCASL) perfusion fMR images were acquired during SC exposure in 35 smokers genotyped for the SLC6A3 variable number of tandem repeats (VNTR) polymorphism (n=16, 9-repeats; n=19,10/10-repeats). Participants completed a visual dot-probe attentional bias task, which contained pictures of smoking and non-smoking pictures, to examine whether genetic variation in DAT influences attentional bias and to investigate relationships between attentional bias and neural responses to SCs. Although attentional bias to smoking pictures was not significantly different between 9-repeats and 10/10-repeats, 9-repeats showed a positive correlation between attentional bias and increased SC-induced brain activity in the amygdala; whereas, 10/10-repeats showed an inverse correlation in the medial orbitofrontal cortex (mOFC). In group comparisons, 9-repeats exhibited positive correlations between attentional bias and SCs in the mOFC and amygdala, relative to 10/10-repeats. Findings suggest that genetic variation in the DAT gene influences brain responses associated with attentional bias; thus, providing additional support for a SC-vulnerable endophenotype. PMID:23061530

  11. Variance-based sensitivity indices for stochastic models with correlated inputs

    SciTech Connect

    Kala, Zdeněk

    2015-03-10

    The goal of this article is the formulation of the principles of one of the possible strategies in implementing correlation between input random variables so as to be usable for algorithm development and the evaluation of Sobol’s sensitivity analysis. With regard to the types of stochastic computational models, which are commonly found in structural mechanics, an algorithm was designed for effective use in conjunction with Monte Carlo methods. Sensitivity indices are evaluated for all possible permutations of the decorrelation procedures for input parameters. The evaluation of Sobol’s sensitivity coefficients is illustrated on an example in which a computational model was used for the analysis of the resistance of a steel bar in tension with statistically dependent input geometric characteristics.

  12. Bioinformatics in New Generation Flavivirus Vaccines

    PubMed Central

    Koraka, Penelope; Martina, Byron E. E.; Osterhaus, Albert D. M. E.

    2010-01-01

    Flavivirus infections are the most prevalent arthropod-borne infections world wide, often causing severe disease especially among children, the elderly, and the immunocompromised. In the absence of effective antiviral treatment, prevention through vaccination would greatly reduce morbidity and mortality associated with flavivirus infections. Despite the success of the empirically developed vaccines against yellow fever virus, Japanese encephalitis virus and tick-borne encephalitis virus, there is an increasing need for a more rational design and development of safe and effective vaccines. Several bioinformatic tools are available to support such rational vaccine design. In doing so, several parameters have to be taken into account, such as safety for the target population, overall immunogenicity of the candidate vaccine, and efficacy and longevity of the immune responses triggered. Examples of how bio-informatics is applied to assist in the rational design and improvements of vaccines, particularly flavivirus vaccines, are presented and discussed. PMID:20467477

  13. Joint analysis of beef growth and carcass quality traits through calculation of co-variance components and correlations.

    PubMed

    Mirzaei, H R; Verbyla, A P; Pitchford, W S

    2011-01-01

    A joint growth-carcass model using random regression was used to estimate the (co)variance components of beef cattle body weights and carcass quality traits and correlations between them. During a four-year period (1994-1997) of the Australian "southern crossbreeding project", mature Hereford cows (N = 581) were mated to 97 sires of Jersey, Wagyu, Angus, Hereford, South Devon, Limousin, and Belgian Blue breeds, resulting in 1141 calves. Data included 13 (for steers) and 8 (for heifers) body weight measurements approximately every 50 days from birth until slaughter and four carcass quality traits: hot standard carcass weight, rump fat depth, rib eye muscle area, and intramuscular fat content. The mixed model included fixed effects of sex, sire breed, age (linear, quadratic and cubic), and their interactions between sex and sire breed with age. Random effects were sire, dam, management (birth location, year, post-weaning groups), and permanent environmental effects, and their interactions with linear, quadratic and cubic growth, when possible. Phenotypic, sire and dam correlations between body weights and hot standard carcass weight and rib eye muscle area were positive and moderate to high from birth to feedlot period. Management variation accounted for the largest proportion of total variation in both growth and carcass traits. Management correlations between carcass traits were high, except between rump fat depth and intramuscular fat (r = 0.26). Management correlations between body weight and carcass traits during the pre-weaning period were positive except for intramuscular fat. The correlations were low from birth to weaning, then increased dramatically and were high during the feedlot period. PMID:21425094

  14. Complete Genomic Sequence of Duck Flavivirus from China

    PubMed Central

    Liu, Ming; Liu, Chunguo; Li, Gang; Li, Xiaojun; Yin, Xiuchen; Chen, Yuhuan

    2012-01-01

    We report here the complete genomic sequence of the Chinese duck flavivirus TA strain. This work is the first to document the complete genomic sequence of this previously unknown duck flavivirus strain. The sequence will help further relevant epidemiological studies and extend our general knowledge of flaviviruses. PMID:22354941

  15. Variance components, heritability and correlation analysis of anther and ovary size during the floral development of bread wheat.

    PubMed

    Guo, Zifeng; Chen, Dijun; Schnurbusch, Thorsten

    2015-06-01

    Anther and ovary development play an important role in grain setting, a crucial factor determining wheat (Triticum aestivum L.) yield. One aim of this study was to determine the heritability of anther and ovary size at different positions within a spikelet at seven floral developmental stages and conduct a variance components analysis. Relationships between anther and ovary size and other traits were also assessed. The thirty central European winter wheat genotypes used in this study were based on reduced height (Rht) and photoperiod sensitivity (Ppd) genes with variable genetic backgrounds. Identical experimental designs were conducted in a greenhouse and field simultaneously. Heritability of anther and ovary size indicated strong genetic control. Variance components analysis revealed that anther and ovary sizes of floret 3 (i.e. F3, the third floret from the spikelet base) and floret 4 (F4) were more sensitive to the environment compared with those in floret 1 (F1). Good correlations were found between spike dry weight and anther and ovary size in both greenhouse and field, suggesting that anther and ovary size are good predictors of each other, as well as spike dry weight in both conditions. Relationships between spike dry weight and anther and ovary size at F3/4 positions were stronger than at F1, suggesting that F3/4 anther and ovary size are better predictors of spike dry weight. Generally, ovary size showed a closer relationship with spike dry weight than anther size, suggesting that ovary size is a more reliable predictor of spike dry weight. PMID:25821074

  16. Tembusu-Related Flavivirus in Ducks, Thailand

    PubMed Central

    Thontiravong, Aunyaratana; Ninvilai, Patchareeporn; Tunterak, Wikanda; Nonthabenjawan, Nutthawan; Chaiyavong, Supassma; Angkabkingkaew, Kingkarn; Mungkundar, Chatthapon; Phuengpho, Woranuch; Oraveerakul, Kanisak

    2015-01-01

    Since 2013, outbreaks of disease caused by duck Tembusu virus (DTMUV) have been observed in layer and broiler duck farms in Thailand. The virus is closely related to Chinese DTMUVs and belongs to the Ntaya group of mosquitoborne flaviviruses. These findings represent the emergence of DTMUV in ducks in Thailand. PMID:26584133

  17. Identification of a Flavivirus Sequence in a Marine Arthropod

    PubMed Central

    Conway, Michael J.

    2015-01-01

    Phylogenetic analysis has yet to uncover the early origins of flaviviruses. In this study, I mined a database of expressed sequence tags in order to discover novel flavivirus sequences. Flavivirus sequences were identified in a pool of mRNA extracted from the sea spider Endeis spinosa (Pycnogonida, Pantopoda). Reconstruction of the translated sequences and BLAST analysis matched the sequence to the flavivirus NS5 gene. Additional sequences corresponding to envelope and the NS5 MTase domain were also identified. Phylogenetic analysis of homologous NS5 sequences revealed that Endeis spinosa NS5 (ESNS5) is likely related to classical insect-specific flaviviruses. It is unclear if ESNS5 represents genetic material from an active viral infection or an integrated viral genome. These data raise the possibility that classical insect-specific flaviviruses and perhaps medically relevant flaviviruses, evolved from progenitors that infected marine arthropods. PMID:26717191

  18. Antiviral macrophage responses in flavivirus encephalitis.

    PubMed

    Ashhurst, Thomas Myles; Vreden, Caryn van; Munoz-Erazo, Luis; Niewold, Paula; Watabe, Kanami; Terry, Rachael L; Deffrasnes, Celine; Getts, Daniel R; Cole King, Nicholas Jonathan

    2013-11-01

    Mosquito-borne flaviviruses are a major current and emerging threat, affecting millions of people worldwide. Global climate change, combined with increasing proximity of humans to animals and mosquito vectors by expansion into natural habitats, coupled with the increase in international travel, have resulted in significant spread and concomitant increase in the incidence of infection and severe disease. Although neuroinvasive disease has been well described for some viral infections such as Japanese Encephalitis virus (JEV) and West Nile virus (WNV), others such as dengue virus (DENV) have recently displayed an emerging pattern of neuroinvasive disease, distinct from the previously observed, systemically-induced encephalomyelopathy. In this setting, the immune response is a crucial component of host defence, in preventing viral dissemination and invasion of the central nervous system (CNS). However, subversion of the anti-viral activities of macrophages by flaviviruses can facilitate viral replication and spread, enhancing the intensity of immune responses, leading to severe immune-mediated disease which may be further exacerbated during the subsequent infection with some flaviviruses. Furthermore, in the CNS myeloid cells may be responsible for inducing specific inflammatory changes, which can lead to significant pathological damage during encephalitis. The interaction of virus and cells of the myeloid lineage is complex, and this interaction is likely responsible at least in part, for crucial differences between viral clearance and pathology. Recent studies on the role of myeloid cells in innate immunity and viral control, and the mechanisms of evasion and subversion used by flaviviruses are rapidly advancing our understanding of the immunopathological mechanisms involved in flavivirus encephalitis and will lead to the development of therapeutic strategies previously not considered. PMID:24434318

  19. A review of successful flavivirus vaccines and the problems with those flaviviruses for which vaccines are not yet available.

    PubMed

    Ishikawa, Tomohiro; Yamanaka, Atsushi; Konishi, Eiji

    2014-03-10

    Genus flavivirus comprises many important human pathogens causing public health problems worldwide. Some flavivirus infections are characterized by a relatively high mortality rate and/or high sequelae rate in survivors. Because most flavivirus life cycles are maintained between arthropod vectors and amplifying/reservoir hosts in the absence of humans, eradication of flaviviruses might be extremely difficult. Flavivirus vaccine development is considered a reasonable method to prevent flavivirus infections. Some vaccines have been successfully developed, but others have not, regardless of much effort. This review article describes currently available flavivirus vaccines against yellow fever, Japanese encephalitis, and tick-borne encephalitis. In addition, the current status of dengue and West Nile virus vaccine development is reviewed and problems regarding their development are discussed. PMID:24486372

  20. Stratospheric Assimilation of Chemical Tracer Observations Using a Kalman Filter. Pt. 2; Chi-Square Validated Results and Analysis of Variance and Correlation Dynamics

    NASA Technical Reports Server (NTRS)

    Menard, Richard; Chang, Lang-Ping

    1998-01-01

    A Kalman filter system designed for the assimilation of limb-sounding observations of stratospheric chemical tracers, which has four tunable covariance parameters, was developed in Part I (Menard et al. 1998) The assimilation results of CH4 observations from the Cryogenic Limb Array Etalon Sounder instrument (CLAES) and the Halogen Observation Experiment instrument (HALOE) on board of the Upper Atmosphere Research Satellite are described in this paper. A robust (chi)(sup 2) criterion, which provides a statistical validation of the forecast and observational error covariances, was used to estimate the tunable variance parameters of the system. In particular, an estimate of the model error variance was obtained. The effect of model error on the forecast error variance became critical after only three days of assimilation of CLAES observations, although it took 14 days of forecast to double the initial error variance. We further found that the model error due to numerical discretization as arising in the standard Kalman filter algorithm, is comparable in size to the physical model error due to wind and transport modeling errors together. Separate assimilations of CLAES and HALOE observations were compared to validate the state estimate away from the observed locations. A wave-breaking event that took place several thousands of kilometers away from the HALOE observation locations was well captured by the Kalman filter due to highly anisotropic forecast error correlations. The forecast error correlation in the assimilation of the CLAES observations was found to have a structure similar to that in pure forecast mode except for smaller length scales. Finally, we have conducted an analysis of the variance and correlation dynamics to determine their relative importance in chemical tracer assimilation problems. Results show that the optimality of a tracer assimilation system depends, for the most part, on having flow-dependent error correlation rather than on evolving the

  1. Regulation of Flavivirus RNA synthesis and replication.

    PubMed

    Selisko, Barbara; Wang, Chunling; Harris, Eva; Canard, Bruno

    2014-12-01

    RNA synthesis and replication of the members of the Flavivirus genus (including dengue, West Nile and Japanese encephalitis viruses) is regulated by a wide variety of mechanisms and actors. These include the sequestration of the RNA-dependent RNA polymerase (RdRp) for functions other than RNA synthesis, regulatory interactions with other viral and host proteins within the replication complex (RC), and regulatory elements within the RNA genome itself. In this review, we discuss our current knowledge of the multiple levels at which Flavivirus RNA synthesis is controlled. We aim to bring together two active research fields: the structural and functional biology of individual proteins of the RC and the impressive wealth of knowledge acquired regarding the viral genomic RNA. PMID:25462437

  2. Regulation of Flavivirus RNA synthesis and replication

    PubMed Central

    Selisko, Barbara; Wang, Chunling; Harris, Eva; Canard, Bruno

    2014-01-01

    RNA synthesis and replication of the members of the Flavivirus genus (including dengue, West Nile and Japanese encephalitis viruses) is regulated by a wide variety of mechanisms and actors. These include the sequestration of the RNA-dependent RNA polymerase (RdRp) for functions other than RNA synthesis, regulatory interactions with other viral and host proteins within the replication complex (RC), and regulatory elements within the RNA genome itself. In this review, we discuss our current knowledge of the multiple levels at which Flavivirus RNA synthesis is controlled. We aim to bring together two active research fields: the structural and functional biology of individual proteins of the RC and the impressive wealth of knowledge acquired regarding the viral genomic RNA. PMID:25462437

  3. Risk assessment of flavivirus transmission in Namibia.

    PubMed

    Noden, Bruce H; Musuuo, Milka; Aku-Akai, Larai; van der Colf, Berta; Chipare, Israel; Wilkinson, Rob

    2014-09-01

    The role of arboviruses causing acute febrile illness in sub-Saharan Africa is receiving more attention. Reports of dengue in tourists were published nearly 10 years ago in Namibia, but the current epidemiology of arboviruses is unknown and surveys of mosquito vectors have not been carried out since the 1950s. To begin addressing this knowledge gap, a prospective cross-sectional study was conducted using samples from volunteer blood donors linked to questionnaire. Serum samples were tested using a Dengue IgG Indirect ELISA which measured exposure to dengue virus/flaviviruses. Entomological samples were collected from tires during the rainy season (February-March 2012) in six locations across Namibia's capital city, Windhoek. Among 312 blood donors tested, 25 (8.0%) were positive for dengue virus/flavivirus exposure. The only significant risk factor was age group with high exposure rates among those older than 50 (29%) compared with those below 40 years old (between 2.9% and 8.3%) (P<0.002). Larvae and pupae of Aedes aegypti and Culex pipiens complex accounted for 100% of the 2751 samples collected, of which only 12.2% (n=336) were Ae. aegypti. Each site demonstrated high variability of species composition between sampling times. While the significant dengue virus/flavivirus exposure rate among those above 50 years old is likely indicative of the West Nile epidemic in the 70s and 80s, the low exposure among those under 50 suggests that flaviviruses are still circulating in Namibia. While Ae. aegypti and C. pipiens sp. may play a role in future epidemics, the significance of presence may be reduced due to short rain periods, dry, arid, cold winters and policies and social understandings that limit non-structured storage and use of tires in low income areas. Future studies should further characterize the circulating arboviruses and investigate mosquito ecology nationally to map areas at higher risk for future arbovirus outbreaks. PMID:24865792

  4. Interaction between Flavivirus and Cytoskeleton during Virus Replication

    PubMed Central

    Foo, Kar Yue; Chee, Hui-Yee

    2015-01-01

    Flaviviruses are potentially human pathogens that cause major epidemics worldwide. Flavivirus interacts with host cell factors to form a favourable virus replication site. Cell cytoskeletons have been observed to have close contact with flaviviruses, which expands the understanding of cytoskeleton functions during virus replication, although many detailed mechanisms are still unclear. The interactions between the virus and host cytoskeletons such as actin filaments, microtubules, and intermediate filaments have provided insight into molecular alterations during the virus infection, such as viral entry, in-cell transport, scaffold assembly, and egress. This review article focuses on the utilization of cytoskeleton by Flavivirus and the respective functions during virus replication. PMID:26347881

  5. The Partitioning of Variance Habits of Correlational and Experimental Psychologists: The Two Disciplines of Scientific Psychology Revisited

    ERIC Educational Resources Information Center

    Krus, David J.; Krus, Patricia H.

    1978-01-01

    The conceptual differences between coded regression analysis and traditional analysis of variance are discussed. Also, a modification of several SPSS routines is proposed which allows for direct interpretation of ANOVA and ANCOVA results in a form stressing the strength and significance of scrutinized relationships. (Author)

  6. A glance at subgenomic flavivirus RNAs and microRNAs in flavivirus infections.

    PubMed

    Bavia, Lorena; Mosimann, Ana Luiza Pamplona; Aoki, Mateus Nóbrega; Duarte Dos Santos, Claudia Nunes

    2016-01-01

    The family Flaviviridae comprises a wide variety of viruses that are distributed worldwide, some of which are associated with high rates of morbidity and mortality. There are neither vaccines nor antivirals for most flavivirus infections, reinforcing the importance of research on different aspects of the viral life cycle. During infection, cytoplasmic accumulation of RNA fragments mainly originating from the 3' UTRs, which have been designated subgenomic flavivirus RNAs (sfRNAs), has been detected. It has been shown that eukaryotic exoribonucleases are involved in viral sfRNA production. Additionally, viral and human small RNAs (sRNAs) have also been found in flavivirus-infected cells, especially microRNAs (miRNAs). miRNAs were first described in eukaryotic cells and in a mature and functional state present as single-stranded 18-24 nt RNA fragments. Their main function is the repression of translation through base pairing with cellular mRNAs, besides other functions, such as mRNA degradation. Canonical miRNA biogenesis involves Drosha and Dicer, however miRNA can also be generated by alternative pathways. In the case of flaviviruses, alternative pathways have been suggested. Both sfRNAs and miRNAs are involved in viral infection and host cell response modulation, representing interesting targets of antiviral strategies. In this review, we focus on the generation and function of viral sfRNAs, sRNAs and miRNAs in West Nile, dengue, Japanese encephalitis, Murray Valley encephalitis and yellow fever infections, as well as their roles in viral replication, translation and cell immune response evasion. We also give an overview regarding other flaviviruses and the generation of cellular miRNAs during infection. PMID:27233361

  7. Usutu Virus: An Emerging Flavivirus in Europe

    PubMed Central

    Ashraf, Usama; Ye, Jing; Ruan, Xindi; Wan, Shengfeng; Zhu, Bibo; Cao, Shengbo

    2015-01-01

    Usutu virus (USUV) is an African mosquito-borne flavivirus belonging to the Japanese encephalitis virus serocomplex. USUV is closely related to Murray Valley encephalitis virus, Japanese encephalitis virus, and West Nile virus. USUV was discovered in South Africa in 1959. In Europe, the first true demonstration of circulation of USUV was reported in Austria in 2001 with a significant die-off of Eurasian blackbirds. In the subsequent years, USUV expanded to neighboring countries, including Italy, Germany, Spain, Hungary, Switzerland, Poland, England, Czech Republic, Greece, and Belgium, where it caused unusual mortality in birds. In 2009, the first two human cases of USUV infection in Europe have been reported in Italy, causing meningoencephalitis in immunocompromised patients. This review describes USUV in terms of its life cycle, USUV surveillance from Africa to Europe, human cases, its cellular tropism and pathogenesis, its genetic relationship with other flaviviruses, genetic diversity among USUV strains, its diagnosis, and a discussion of the potential future threat to Asian countries. PMID:25606971

  8. Usutu virus: an emerging flavivirus in Europe.

    PubMed

    Ashraf, Usama; Ye, Jing; Ruan, Xindi; Wan, Shengfeng; Zhu, Bibo; Cao, Shengbo

    2015-01-01

    Usutu virus (USUV) is an African mosquito-borne flavivirus belonging to the Japanese encephalitis virus serocomplex. USUV is closely related to Murray Valley encephalitis virus, Japanese encephalitis virus, and West Nile virus. USUV was discovered in South Africa in 1959. In Europe, the first true demonstration of circulation of USUV was reported in Austria in 2001 with a significant die-off of Eurasian blackbirds. In the subsequent years, USUV expanded to neighboring countries, including Italy, Germany, Spain, Hungary, Switzerland, Poland, England, Czech Republic, Greece, and Belgium, where it caused unusual mortality in birds. In 2009, the first two human cases of USUV infection in Europe have been reported in Italy, causing meningoencephalitis in immunocompromised patients. This review describes USUV in terms of its life cycle, USUV surveillance from Africa to Europe, human cases, its cellular tropism and pathogenesis, its genetic relationship with other flaviviruses, genetic diversity among USUV strains, its diagnosis, and a discussion of the potential future threat to Asian countries. PMID:25606971

  9. Viral Interference and Persistence in Mosquito-Borne Flaviviruses

    PubMed Central

    Salas-Benito, Juan Santiago; De Nova-Ocampo, Mónica

    2015-01-01

    Mosquito-borne flaviviruses are important pathogens for humans, and the detection of two or more flaviviruses cocirculating in the same geographic area has often been reported. However, the epidemiological impact remains to be determined. Mosquito-borne flaviviruses are primarily transmitted through Aedes and Culex mosquitoes; these viruses establish a life-long or persistent infection without apparent pathological effects. This establishment requires a balance between virus replication and the antiviral host response. Viral interference is a phenomenon whereby one virus inhibits the replication of other viruses, and this condition is frequently associated with persistent infections. Viral interference and persistent infection are determined by several factors, such as defective interfering particles, competition for cellular factors required for translation/replication, and the host antiviral response. The interaction between two flaviviruses typically results in viral interference, indicating that these viruses share common features during the replicative cycle in the vector. The potential mechanisms involved in these processes are reviewed here. PMID:26583158

  10. Viral Interference and Persistence in Mosquito-Borne Flaviviruses.

    PubMed

    Salas-Benito, Juan Santiago; De Nova-Ocampo, Mónica

    2015-01-01

    Mosquito-borne flaviviruses are important pathogens for humans, and the detection of two or more flaviviruses cocirculating in the same geographic area has often been reported. However, the epidemiological impact remains to be determined. Mosquito-borne flaviviruses are primarily transmitted through Aedes and Culex mosquitoes; these viruses establish a life-long or persistent infection without apparent pathological effects. This establishment requires a balance between virus replication and the antiviral host response. Viral interference is a phenomenon whereby one virus inhibits the replication of other viruses, and this condition is frequently associated with persistent infections. Viral interference and persistent infection are determined by several factors, such as defective interfering particles, competition for cellular factors required for translation/replication, and the host antiviral response. The interaction between two flaviviruses typically results in viral interference, indicating that these viruses share common features during the replicative cycle in the vector. The potential mechanisms involved in these processes are reviewed here. PMID:26583158

  11. Mercadeo Virus: A Novel Mosquito-Specific Flavivirus from Panama.

    PubMed

    Carrera, Jean-Paul; Guzman, Hilda; Beltrán, Davis; Díaz, Yamilka; López-Vergès, Sandra; Torres-Cosme, Rolando; Popov, Vsevolod; Widen, Steven G; Wood, Thomas G; Weaver, Scott C; Cáceres-Carrera, Lorenzo; Vasilakis, Nikos; Tesh, Robert B

    2015-11-01

    Viruses in the genus Flavivirus (family Flaviviridae) include many arthropod-borne viruses of public health and veterinary importance. However, during the past two decades an explosion of novel insect-specific flaviviruses (ISFs), some closely related to vertebrate pathogens, have been discovered. Although many flavivirus pathogens of vertebrates have been isolated from naturally infected mosquitoes in Panama, ISFs have not previously been reported from the country. This report describes the isolation and characterization of a novel ISF, tentatively named Mercadeo virus (MECDV), obtained from Culex spp. mosquitoes collected in Panama. Two MECDV isolates were sequenced and cluster phylogenetically with cell-fusing agent virus (CFAV) and Nakiwogo virus (NAKV) to form a distinct lineage within the insect-specific group of flaviviruses. PMID:26304915

  12. Novel insect-specific flavivirus isolated from northern Europe

    PubMed Central

    Huhtamo, Eili; Moureau, Gregory; Cook, Shelley; Julkunen, Ora; Putkuri, Niina; Kurkela, Satu; Uzcátegui, Nathalie Y.; Harbach, Ralph E.; Gould, Ernest A.; Vapalahti, Olli; de Lamballerie, Xavier

    2012-01-01

    Mosquitoes collected in Finland were screened for flaviviral RNA leading to the discovery and isolation of a novel flavivirus designated Hanko virus (HANKV). Virus characterization, including phylogenetic analysis of the complete coding sequence, confirmed HANKV as a member of the “insect-specific” flavivirus (ISF) group. HANKV is the first member of this group isolated from northern Europe, and therefore the first northern European ISF for which the complete coding sequence has been determined. HANKV was not transcribed as DNA in mosquito cell culture, which appears atypical for an ISF. HANKV shared highest sequence homology with the partial NS5 sequence available for the recently discovered Spanish Ochlerotatus flavivirus (SOcFV). Retrospective analysis of mitochondrial sequences from the virus-positive mosquito pool suggested an Ochlerotatus mosquito species as the most likely host for HANKV. HANKV and SOcFV may therefore represent a novel group of Ochlerotatus-hosted insect-specific flaviviruses in Europe and further afield. PMID:22999256

  13. Insect-specific flaviviruses in Aedes mosquitoes in Greece.

    PubMed

    Papa, Anna; Papadopoulou, Elpida; Paliwal, Ravish; Kalaitzopoulou, Stella; Mourelatos, Spiros; Niedrig, Matthias

    2016-08-01

    Mosquitoes of the genus Aedes are known vectors of pathogenic flaviviruses, and insect-specific flaviviruses (ISFs) have been detected in members of this genus in numerous parts of the world. In order to gain insight into whether Aedes mosquitoes in Greece are infected by flaviviruses, 1173 Aedes spp. mosquitoes collected in 2010 and 2012 were grouped in 53 pools and tested by RT nested PCR using flavivirus generic primers. Eight pools (15.09 %) were found to be PCR positive: five pools (5/53, 9.4 %) contained RNA sequences related to Ochlerotatus caspius flavivirus (OCFV), an ISF previously detected in the Iberian peninsula, two pools (2/53, 3.8 %) contained sequences related to a mosquito flavivirus detected in Aedes vexans (AeveV) in Italy and the Czech Republic, and one pool contained a DNA sequence that was too short to identify accurately. The highest OCFV prevalence (12.9 %) was observed in August 2010 in the regional unit of Thessaloniki. Similar sequences were later obtained from two Culex spp. pools collected in 2013 in the same regions. A genetic difference of 0.2-1.4 % was seen among the Greek OCFV strains, which differed by 2.2-4.1 % from the Iberian strains and by 6.2-11.1 % from the Finnish Hanko virus. The genetic distances among strains varied depending on the genome region (genes for E, NS3 and NS5 proteins), with NS3 being the most variable. The present study shows no evidence of infection of Aedes mosquitoes with known pathogenic flaviviruses, but it expands the geographic distribution of OCFV in the eastern Mediterranean area. Any implication of ISFs for public health (either directly or through interactions with other flaviviruses in the mosquitoes) remains to be elucidated. PMID:27198866

  14. Universal primers that amplify RNA from all three flavivirus subgroups

    PubMed Central

    Maher-Sturgess, Sheryl L; Forrester, Naomi L; Wayper, Paul J; Gould, Ernest A; Hall, Roy A; Barnard, Ross T; Gibbs, Mark J

    2008-01-01

    Background Species within the Flavivirus genus pose public health problems around the world. Increasing cases of Dengue and Japanese encephalitis virus in Asia, frequent outbreaks of Yellow fever virus in Africa and South America, and the ongoing spread of West Nile virus throughout the Americas, show the geographical burden of flavivirus diseases. Flavivirus infections are often indistinct from and confused with other febrile illnesses. Here we review the specificity of published primers, and describe a new universal primer pair that can detect a wide range of flaviviruses, including viruses from each of the recognised subgroups. Results Bioinformatic analysis of 257 published full-length Flavivirus genomes revealed conserved regions not previously targeted by primers. Two degenerate primers, Flav100F and Flav200R were designed from these regions and used to generate an 800 base pair cDNA product. The region amplified encoded part of the methyltransferase and most of the RNA-dependent-RNA-polymerase (NS5) coding sequence. One-step RT-PCR testing was successful using standard conditions with RNA from over 60 different flavivirus strains representing about 50 species. The cDNA from each virus isolate was sequenced then used in phylogenetic analyses and database searches to confirm the identity of the template RNA. Conclusion Comprehensive testing has revealed the broad specificity of these primers. We briefly discuss the advantages and uses of these universal primers. PMID:18218114

  15. Minimum variance geographic sampling

    NASA Technical Reports Server (NTRS)

    Terrell, G. R. (Principal Investigator)

    1980-01-01

    Resource inventories require samples with geographical scatter, sometimes not as widely spaced as would be hoped. A simple model of correlation over distances is used to create a minimum variance unbiased estimate population means. The fitting procedure is illustrated from data used to estimate Missouri corn acreage.

  16. Novel flaviviruses from mosquitoes: Mosquito-specific evolutionary lineages within the phylogenetic group of mosquito-borne flaviviruses

    PubMed Central

    Huhtamo, Eili; Cook, Shelley; Moureau, Gregory; Uzcátegui, Nathalie Y.; Sironen, Tarja; Kuivanen, Suvi; Putkuri, Niina; Kurkela, Satu; Harbach, Ralph E.; Firth, Andrew E.; Vapalahti, Olli; Gould, Ernest A.; de Lamballerie, Xavier

    2014-01-01

    Novel flaviviruses that are genetically related to pathogenic mosquito-borne flaviviruses (MBFV) have been isolated from mosquitoes in various geographical locations, including Finland. We isolated and characterized another novel virus of this group from Finnish mosquitoes collected in 2007, designated as Ilomantsi virus (ILOV). Unlike the MBFV that infect both vertebrates and mosquitoes, the MBFV-related viruses appear to be specific to mosquitoes similar to the insect-specific flaviviruses (ISFs). In this overview of MBFV-related viruses we conclude that they differ from the ISFs genetically and antigenically. Phylogenetic analyses separated the MBFV-related viruses isolated in Africa, the Middle East and South America from those isolated in Europe and Asia. Serological cross-reactions of MBFV-related viruses with other flaviviruses and their potential for vector-borne transmission require further characterization. The divergent MBFV-related viruses are probably significantly under sampled to date and provide new information on the variety, properties and evolution of vector-borne flaviviruses. PMID:25108382

  17. Molecular amplification assays for the detection of flaviviruses.

    PubMed

    Lanciotti, Robert S

    2003-01-01

    Over the past 10 years, a number of molecular amplification assays have been developed for the detection of flaviviruses. Most of these assays utilize the reverse transcriptase-polymerase chain reaction (RT-PCR) as the amplification format with detection by either agarose gel electrophoresis and ethidium bromide staining or hybridization with molecular probes. Recently, a modification of the standard RT-PCR using fluorescent-labeled oligonucleotide probes for detection (TaqMan) has been described. As a result, several assays for detecting flaviviruses have been developed using this approach. In addition, another amplification format, nucleic acid sequence based amplification (NASBA), has been developed and utilized for the detection of several flaviviruses. The various assay formats will be described and their utility discussed. PMID:14714430

  18. Population dynamics of flaviviruses revealed by molecular phylogenies.

    PubMed Central

    Zanotto, P M; Gould, E A; Gao, G F; Harvey, P H; Holmes, E C

    1996-01-01

    The phylogeny of 123 complete envelope gene sequences was reconstructed in order to understand the evolution of tick- and mosquito-borne flaviviruses. An analysis of phylogenetic tree structure reveals a continual and asymmetric branching process in the tick-borne flaviviruses, compared with an explosive radiation in the last 200 years in viruses transmitted by mosquitoes. The distinction between these two viral groups probably reflects differences in modes of dispersal, propagation, and changes in the size of host populations. The most serious implication of this work is that growing human populations are being exposed to an expanding range of increasingly diverse viral strains. PMID:8570593

  19. Visual detection of Flavivirus RNA in living cells.

    PubMed

    Miorin, Lisa; Maiuri, Paolo; Marcello, Alessandro

    2016-04-01

    Flaviviruses include a wide range of important human pathogens delivered by insects or ticks. These viruses have a positive-stranded RNA genome that is replicated in the cytoplasm of the infected cell. The viral RNA genome is the template for transcription by the virally encoded RNA polymerase and for translation of the viral proteins. Furthermore, the double-stranded RNA intermediates of viral replication are believed to trigger the innate immune response through interaction with cytoplasmic cellular sensors. Therefore, understanding the subcellular distribution and dynamics of Flavivirus RNAs is of paramount importance to understand the interaction of the virus with its cellular host, which could be of insect, tick or mammalian, including human, origin. Recent advances on the visualization of Flavivirus RNA in living cells together with the development of methods to measure the dynamic properties of viral RNA are reviewed and discussed in this essay. In particular the application of bleaching techniques such as fluorescence recovery after photobleaching (FRAP) and fluorescence loss in photobleaching (FLIP) are analysed in the context of tick-borne encephalitis virus replication. Conclusions driven by this approached are discussed in the wider context Flavivirus infection. PMID:26542763

  20. The role of viral persistence in flavivirus biology

    PubMed Central

    Mlera, Luwanika; Melik, Wessam; Bloom, Marshall E.

    2014-01-01

    In nature, vector-borne flaviviruses are persistently cycled between either the tick or mosquito vector and small mammals such as rodents, skunks, and swine. These viruses account for considerable human morbidity and mortality worldwide. Increasing and substantial evidence of viral persistence in humans, which includes the isolation of RNA by RT-PCR and infectious virus by culture, continues to be reported. Viral persistence can also be established in vitro in various human, animal, arachnid and insect cell lines in culture. Although some research has focused on the potential roles of defective virus particles, evasion of the immune response through the manipulation of autophagy and/or apoptosis, the precise mechanism of flavivirus persistence is still not well understood. We propose additional research for further understanding of how viral persistence is established in different systems. Avenues for additional studies include determining if the multifunctional flavivirus protein NS5 has a role in viral persistence, the development of relevant animal models of viral persistence as well as investigating the host responses that allow vector borne flavivirus replication without detrimental effects on infected cells. Such studies might shed more light on the viral-host relationships, and could be used to unravel the mechanisms for establishment of persistence. PMID:24737600

  1. Constancy and diversity in the flavivirus fusion peptide

    PubMed Central

    Seligman, Stephen J

    2008-01-01

    Background Flaviviruses include the mosquito-borne dengue, Japanese encephalitis, yellow fever and West Nile and the tick-borne encephalitis viruses. They are responsible for considerable world-wide morbidity and mortality. Viral entry is mediated by a conserved fusion peptide containing 16 amino acids located in domain II of the envelope protein E. Highly orchestrated conformational changes initiated by exposure to acidic pH accompany the fusion process and are important factors limiting amino acid changes in the fusion peptide that still permit fusion with host cell membranes in both arthropod and vertebrate hosts. The cell-fusing related agents, growing only in mosquitoes or insect cell lines, possess a different homologous peptide. Results Analysis of 46 named flaviviruses deposited in the Entrez Nucleotides database extended the constancy in the canonical fusion peptide sequences of mosquito-borne, tick-borne and viruses with no known vector to include more recently-sequenced viruses. The mosquito-borne signature amino acid, G104, was also found in flaviviruses with no known vector and with the cell-fusion related viruses. Despite the constancy in the canonical sequences in pathogenic flaviviruses, mutations were surprisingly frequent with a 27% prevalence of nonsynonymous mutations in yellow fever virus fusion peptide sequences, and 0 to 7.4% prevalence in the others. Six of seven yellow fever patients whose virus had fusion peptide mutations died. In the cell-fusing related agents, not enough sequences have been deposited to estimate reliably the prevalence of fusion peptide mutations. However, the canonical sequences homologous to the fusion peptide and the pattern of disulfide linkages in protein E differed significantly from the other flaviviruses. Conclusion The constancy of the canonical fusion peptide sequences in the arthropod-borne flaviviruses contrasts with the high prevalence of mutations in most individual viruses. The discrepancy may be the

  2. Flavivirus NS4A-induced autophagy protects cells against death and enhances virus replication.

    PubMed

    McLean, Jeffrey E; Wudzinska, Aleksandra; Datan, Emmanuel; Quaglino, Daniela; Zakeri, Zahra

    2011-06-24

    Flaviviruses include the most prevalent and medically challenging viruses. Persistent infection with flaviviruses of epithelial cells and hepatocytes that do not undergo cell death is common. Here, we report that, in epithelial cells, up-regulation of autophagy following flavivirus infection markedly enhances virus replication and that one flavivirus gene, NS4A, uniquely determines the up-regulation of autophagy. Dengue-2 and Modoc (a murine flavivirus) kill primary murine macrophages but protect epithelial cells and fibroblasts against death provoked by several insults. The flavivirus-induced protection derives from the up-regulation of autophagy, as up-regulation of autophagy by starvation or inactivation of mammalian target of rapamycin also protects the cells against insult, whereas inhibition of autophagy via inactivation of PI3K nullifies the protection conferred by flavivirus. Inhibition of autophagy also limits replication of both Dengue-2 and Modoc virus in epithelial cells. Expression of flavivirus NS4A is sufficient to induce PI3K-dependent autophagy and to protect cells against death; expression of other viral genes, including NS2A and NS4B, fails to protect cells against several stressors. Flavivirus NS4A protein induces autophagy in epithelial cells and thus protects them from death during infection. As autophagy is vital to flavivirus replication in these cells, NS4A is therefore also identified as a critical determinant of flavivirus replication. PMID:21511946

  3. Expectoration of Flaviviruses during sugar feeding by mosquitoes (Diptera: Culicidae).

    PubMed

    van den Hurk, Andrew F; Johnson, Petrina H; Hall-Mendelin, Sonja; Northill, Judy A; Simmons, Russell J; Jansen, Cassie C; Frances, Stephen P; Smith, Greg A; Ritchie, Scott A

    2007-09-01

    Biological transmission of arboviruses to a vertebrate host occurs when virions are expelled along with saliva during blood feeding by a hematophagous arthropod. We undertook experiments to determine whether mosquitoes expectorate flaviviruses in their saliva while sugar feeding. Batches of Culex annulirostris Skuse and Culex gelidus Theobald (Diptera: Culicidae) were orally infected with Japanese encephalitis (family Flaviviridae, genus Flavivirus, JEV), Kunjin (family Flaviviridae, genus Flavivirus, KUNV; a subtype of West Nile virus), and Murray Valley encephalitis (family Flaviviridae, genus Flavivirus, MVEV) viruses. After a 7-d extrinsic incubation, these mosquitoes were offered sucrose meals via cotton pledgets, which were removed daily and processed for viral RNA by using real-time TaqMan reverse transcriptase-polymerase chain reaction (RT-PCR) assays. JEV, MVEV, and KUNV RNA was detected in all pledgets removed from batches of Cx. gelidus on days 7-14 postexposure. In contrast, detection rates were variable for Cx. annulirostris, with KUNV detected in 0.3 M sucrose pledgets on all days postexposure, and JEV and MVEV detected on 57 and 50% of days postexposure, respectively. Higher concentrations of sucrose in the pledget did not increase virus detection rates. When individual JEV-infected Cx. gelidus were exposed to the sucrose pledget, 73% of mosquitoes expectorated virus with titers that were detectable by TaqMan RT-PCR. These results clearly show that flaviviruses are expectorated by infected mosquitoes during the process of sugar feeding on artificial pledgets. Potential applications of the method for arboviral bioassays and field surveillance are discussed. PMID:17915518

  4. Ecuador Paraiso Escondido Virus, a New Flavivirus Isolated from New World Sand Flies in Ecuador, Is the First Representative of a Novel Clade in the Genus Flavivirus

    PubMed Central

    Zapata, Sonia; Bichaud, Laurence; Moureau, Grégory; Lemey, Philippe; Firth, Andrew E.; Gritsun, Tamara S.; Gould, Ernest A.; de Lamballerie, Xavier; Depaquit, Jérôme

    2015-01-01

    ABSTRACT A new flavivirus, Ecuador Paraiso Escondido virus (EPEV), named after the village where it was discovered, was isolated from sand flies (Psathyromyia abonnenci, formerly Lutzomyia abonnenci) that are unique to the New World. This represents the first sand fly-borne flavivirus identified in the New World. EPEV exhibited a typical flavivirus genome organization. Nevertheless, the maximum pairwise amino acid sequence identity with currently recognized flaviviruses was 52.8%. Phylogenetic analysis of the complete coding sequence showed that EPEV represents a distinct clade which diverged from a lineage that was ancestral to the nonvectored flaviviruses Entebbe bat virus, Yokose virus, and Sokoluk virus and also the Aedes-associated mosquito-borne flaviviruses, which include yellow fever virus, Sepik virus, Saboya virus, and others. EPEV replicated in C6/36 mosquito cells, yielding high infectious titers, but failed to reproduce either in vertebrate cell lines (Vero, BHK, SW13, and XTC cells) or in suckling mouse brains. This surprising result, which appears to eliminate an association with vertebrate hosts in the life cycle of EPEV, is discussed in the context of the evolutionary origins of EPEV in the New World. IMPORTANCE The flaviviruses are rarely (if ever) vectored by sand fly species, at least in the Old World. We have identified the first representative of a sand fly-associated flavivirus, Ecuador Paraiso Escondido virus (EPEV), in the New World. EPEV constitutes a novel clade according to current knowledge of the flaviviruses. Phylogenetic analysis of the virus genome showed that EPEV roots the Aedes-associated mosquito-borne flaviviruses, including yellow fever virus. In light of this new discovery, the New World origin of EPEV is discussed together with that of the other flaviviruses. PMID:26355096

  5. Nuclear Material Variance Calculation

    Energy Science and Technology Software Center (ESTSC)

    1995-01-01

    MAVARIC (Materials Accounting VARIance Calculations) is a custom spreadsheet that significantly reduces the effort required to make the variance and covariance calculations needed to determine the detection sensitivity of a materials accounting system and loss of special nuclear material (SNM). The user is required to enter information into one of four data tables depending on the type of term in the materials balance (MB) equation. The four data tables correspond to input transfers, output transfers,more » and two types of inventory terms, one for nondestructive assay (NDA) measurements and one for measurements made by chemical analysis. Each data entry must contain an identification number and a short description, as well as values for the SNM concentration, the bulk mass (or solution volume), the measurement error standard deviations, and the number of measurements during an accounting period. The user must also specify the type of error model (additive or multiplicative) associated with each measurement, and possible correlations between transfer terms. Predefined spreadsheet macros are used to perform the variance and covariance calculations for each term based on the corresponding set of entries. MAVARIC has been used for sensitivity studies of chemical separation facilities, fuel processing and fabrication facilities, and gas centrifuge and laser isotope enrichment facilities.« less

  6. Salicylates Inhibit Flavivirus Replication Independently of Blocking Nuclear Factor Kappa B Activation

    PubMed Central

    Liao, Ching-Len; Lin, Yi-Ling; Wu, Bi-Ching; Tsao, Chang-Huei; Wang, Mei-Chuan; Liu, Chiu-I; Huang, Yue-Ling; Chen, Jui-Hui; Wang, Jia-Pey; Chen, Li-Kuang

    2001-01-01

    Flaviviruses comprise a positive-sense RNA genome that replicates exclusively in the cytoplasm of infected cells. Whether flaviviruses require an activated nuclear factor(s) to complete their life cycle and trigger apoptosis in infected cells remains elusive. Flavivirus infections quickly activate nuclear factor kappa B (NF-κB), and salicylates have been shown to inhibit NF-κB activation. In this study, we investigated whether salicylates suppress flavivirus replication and virus-induced apoptosis in cultured cells. In a dose-dependent inhibition, we found salicylates within a range of 1 to 5 mM not only restricted flavivirus replication but also abrogated flavivirus-triggered apoptosis. However, flavivirus replication was not affected by a specific NF-κB peptide inhibitor, SN50, and a proteosome inhibitor, lactacystin. Flaviviruses also replicated and triggered apoptosis in cells stably expressing IκBα-ΔN, a dominant-negative mutant that antagonizes NF-κB activation, as readily as in wild-type BHK-21 cells, suggesting that NF-κB activation is not essential for either flavivirus replication or flavivirus-induced apoptosis. Salicylates still diminished flavivirus replication and blocked apoptosis in the same IκBα-ΔN cells. This inhibition of flaviviruses by salicylates could be partially reversed by a specific p38 mitogen-activated protein (MAP) kinase inhibitor, SB203580. Together, these results show that the mechanism by which salicylates suppress flavivirus infection may involve p38 MAP kinase activity but is independent of blocking the NF-κB pathway. PMID:11483726

  7. Focus on flaviviruses: current and future drug targets

    PubMed Central

    Geiss, Brian J; Stahla, Hillary; Hannah, Amanda M; Gari, Harmid H; Keenan, Susan M

    2009-01-01

    Background Infection by mosquito-borne flaviviruses (family Flaviviridae) is increasing in prevalence worldwide. The vast global, social and economic impact due to the morbidity and mortality associated with the diseases caused by these viruses necessitates therapeutic intervention. There is currently no effective clinical treatment for any flaviviral infection. Therefore, there is a great need for the identification of novel inhibitors to target the virus lifecycle. Discussion In this article, we discuss structural and nonstructural viral proteins that are the focus of current target validation and drug discovery efforts. Both inhibition of essential enzymatic activities and disruption of necessary protein–protein interactions are considered. In addition, we address promising new targets for future research. Conclusion As our molecular and biochemical understanding of the flavivirus life cycle increases, the number of targets for antiviral therapeutic discovery grows and the possibility for novel drug discovery continues to strengthen. PMID:20165556

  8. Structure and Function of Flavivirus NS5 Methyltransferase

    SciTech Connect

    Zhou,Y.; Ray, D.; Zhao, Y.; Dong, H.; Ren, S.; Li, Z.; Guo, Y.; Bernard, K.; Shi, P.; Li, H.

    2007-01-01

    The plus-strand RNA genome of flavivirus contains a 5' terminal cap 1 structure (m{sup 7}GpppAmG). The flaviviruses encode one methyltransferase, located at the N-terminal portion of the NS5 protein, to catalyze both guanine N-7 and ribose 2'-OH methylations during viral cap formation. Representative flavivirus methyltransferases from dengue, yellow fever, and West Nile virus (WNV) sequentially generate GpppA {yields} m{sup 7}GpppA {yields} m{sup 7}GpppAm. The 2'-O methylation can be uncoupled from the N-7 methylation, since m{sup 7}GpppA-RNA can be readily methylated to m{sup 7}GpppAm-RNA. Despite exhibiting two distinct methylation activities, the crystal structure of WNV methyltransferase at 2.8 {angstrom} resolution showed a single binding site for S-adenosyl-L-methionine (SAM), the methyl donor. Therefore, substrate GpppA-RNA should be repositioned to accept the N-7 and 2'-O methyl groups from SAM during the sequential reactions. Electrostatic analysis of the WNV methyltransferase structure showed that, adjacent to the SAM-binding pocket, is a highly positively charged surface that could serve as an RNA binding site during cap methylations. Biochemical and mutagenesis analyses show that the N-7 and 2'-O cap methylations require distinct buffer conditions and different side chains within the K{sub 61}-D{sub 146}-K{sub 182}-E{sub 218} motif, suggesting that the two reactions use different mechanisms. In the context of complete virus, defects in both methylations are lethal to WNV; however, viruses defective solely in 2'-O methylation are attenuated and can protect mice from later wild-type WNV challenge. The results demonstrate that the N-7 methylation activity is essential for the WNV life cycle and, thus, methyltransferase represents a novel target for flavivirus therapy.

  9. Flaviviruses Are Sensitive to Inhibition of Thymidine Synthesis Pathways

    PubMed Central

    Fischer, Matthew A.; Smith, Jessica L.; Shum, David; Stein, David A.; Parkins, Christopher; Bhinder, Bhavneet; Radu, Constantin; Hirsch, Alec J.; Djaballah, Hakim; Nelson, Jay A.

    2013-01-01

    Dengue virus has emerged as a global health threat to over one-third of humankind. As a positive-strand RNA virus, dengue virus relies on the host cell metabolism for its translation, replication, and egress. Therefore, a better understanding of the host cell metabolic pathways required for dengue virus infection offers the opportunity to develop new approaches for therapeutic intervention. In a recently described screen of known drugs and bioactive molecules, we observed that methotrexate and floxuridine inhibited dengue virus infections at low micromolar concentrations. Here, we demonstrate that all serotypes of dengue virus, as well as West Nile virus, are highly sensitive to both methotrexate and floxuridine, whereas other RNA viruses (Sindbis virus and vesicular stomatitis virus) are not. Interestingly, flavivirus replication was restored by folinic acid, a thymidine precursor, in the presence of methotrexate and by thymidine in the presence of floxuridine, suggesting an unexpected role for thymidine in flavivirus replication. Since thymidine is not incorporated into RNA genomes, it is likely that increased thymidine production is indirectly involved in flavivirus replication. A possible mechanism is suggested by the finding that p53 inhibition restored dengue virus replication in the presence of floxuridine, consistent with thymidine-less stress triggering p53-mediated antiflavivirus effects in infected cells. Our data reveal thymidine synthesis pathways as new and unexpected therapeutic targets for antiflaviviral drug development. PMID:23824813

  10. Oculopathologic findings in flavivirus-infected gallinaceous birds.

    PubMed

    Gamino, V; Escribano-Romero, E; Gutiérrez-Guzmán, A V; Blázquez, A B; Saiz, J C; Höfle, U

    2014-11-01

    Using eye samples of nine 9-week-old experimentally West Nile virus (WNV)-infected red-legged partridges (Alectoris rufa), time course of lesions and WNV antigen appearance in ocular structures were examined. In addition, eye samples of 6 red-legged partridges and 3 common pheasants (Phasianus colchicus) naturally infected with Bagaza virus (BAGV) were used to study lesions and flavivirus antigen distribution in relation to apparent blindness in the former. The rapid onset of microscopic lesions and early presence of viral antigen in the eye of experimentally WNV-infected partridges, prior to the central nervous system involvement, suggested hematogenous spread of the virus into the eye. BAGV-infected partridges had a more pronunced inflammatory reaction and more widespread flavivirus antigen distribution in the retina compared with pheasants and experimentally fatally WNV-infected partridges. Our results suggest that flavivirus replication and development of lesions in ocular structures of gallinaceous game birds vary with the specific virus and host species involved. PMID:24395913

  11. Flavivirus NS1: a multifaceted enigmatic viral protein.

    PubMed

    Rastogi, Meghana; Sharma, Nikhil; Singh, Sunit Kumar

    2016-01-01

    Flaviviruses are emerging arthropod-borne viruses representing an immense global health problem. The prominent viruses of this group include dengue virus, yellow fever virus, Japanese encephalitis virus, West Nile virus tick borne encephalitis virus and Zika Virus. These are endemic in many parts of the world. They are responsible for the illness ranging from mild flu like symptoms to severe hemorrhagic, neurologic and cognitive manifestations leading to death. NS1 is a highly conserved non-structural protein among flaviviruses, which exist in diverse forms. The intracellular dimer form of NS1 plays role in genome replication, whereas, the secreted hexamer plays role in immune evasion. The secreted NS1 has been identified as a potential diagnostic marker for early detection of the infections caused by flaviviruses. In addition to the diagnostic marker, the importance of NS1 has been reported in the development of therapeutics. NS1 based subunit vaccines are at various stages of development. The structural details and diverse functions of NS1 have been discussed in detail in this review. PMID:27473856

  12. Latitude dependence of eddy variances

    NASA Technical Reports Server (NTRS)

    Bowman, Kenneth P.; Bell, Thomas L.

    1987-01-01

    The eddy variance of a meteorological field must tend to zero at high latitudes due solely to the nature of spherical polar coordinates. The zonal averaging operator defines a length scale: the circumference of the latitude circle. When the circumference of the latitude circle is greater than the correlation length of the field, the eddy variance from transient eddies is the result of differences between statistically independent regions. When the circumference is less than the correlation length, the eddy variance is computed from points that are well correlated with each other, and so is reduced. The expansion of a field into zonal Fourier components is also influenced by the use of spherical coordinates. As is well known, a phenomenon of fixed wavelength will have different zonal wavenumbers at different latitudes. Simple analytical examples of these effects are presented along with an observational example from satellite ozone data. It is found that geometrical effects can be important even in middle latitudes.

  13. Nhumirim virus, a novel flavivirus isolated from mosquitoes from the Pantanal, Brazil

    PubMed Central

    Solberg, Owen; Couto-Lima, Dinair; Kenney, Joan; Serra-Freire, Nicolau; Brault, Aaron; Nogueira, Rita; Langevin, Stanley; Komar, Nicholas

    2016-01-01

    We describe the isolation of a novel flavivirus, isolated from a pool of mosquitoes identified as Culex (Culex) chidesteri collected in 2010 in the Pantanal region of west-central Brazil. The virus is herein designated Nhumirim virus (NHUV) after the name of the ranch from which the mosquito pool was collected. Flavivirus RNA was detected by real-time RT-PCR of homogenized mosquitoes and from the corresponding C6/36 culture supernatant. Based on full-genome sequencing, the virus isolate was genetically distinct from but most closely related to Barkedji virus (BJV), a newly described flavivirus from Senegal. Phylogenetic analysis demonstrated that NHUV grouped with mosquito-borne flaviviruses forming a clade with BJV. This clade may be genetically intermediate between the Culex-borne flaviviruses amplified by birds and the insect-only flaviviruses. PMID:25252815

  14. Localization and Characterization of Flavivirus Envelope Glycoprotein Cross-Reactive Epitopes

    PubMed Central

    Crill, Wayne D.; Chang, Gwong-Jen J.

    2004-01-01

    The flavivirus E glycoprotein, the primary antigen that induces protective immunity, is essential for membrane fusion and mediates binding to cellular receptors. Human flavivirus infections stimulate virus species-specific as well as flavivirus cross-reactive immune responses. Flavivirus cross-reactive antibodies in human sera create a serious problem for serodiagnosis, especially for secondary flavivirus infections, due to the difficulty of differentiating primary from secondary cross-reactive serum antibodies. The presence of subneutralizing levels of flavivirus cross-reactive serum antibodies may result in a dramatic increase in the severity of secondary flavivirus infections via antibody-dependent enhancement. An understanding of flavivirus E-glycoprotein cross-reactive epitopes is therefore critical for improving public health responses to these serious diseases. We identified six E-glycoprotein residues that are incorporated into three distinct flavivirus cross-reactive epitopes. Two of these epitopes which are recognized by distinct monoclonal antibodies contain overlapping continuous residues located within the highly conserved fusion peptide. The third epitope consists of discontinuous residues that are structurally related to the strictly conserved tryptophan at dengue virus serotype 2 E-glycoprotein position 231. PMID:15564505

  15. Post-translational regulation and modifications of flavivirus structural proteins.

    PubMed

    Roby, Justin A; Setoh, Yin Xiang; Hall, Roy A; Khromykh, Alexander A

    2015-07-01

    Flaviviruses are a group of single-stranded, positive-sense RNA viruses that generally circulate between arthropod vectors and susceptible vertebrate hosts, producing significant human and veterinary disease burdens. Intensive research efforts have broadened our scientific understanding of the replication cycles of these viruses and have revealed several elegant and tightly co-ordinated post-translational modifications that regulate the activity of viral proteins. The three structural proteins in particular - capsid (C), pre-membrane (prM) and envelope (E) - are subjected to strict regulatory modifications as they progress from translation through virus particle assembly and egress. The timing of proteolytic cleavage events at the C-prM junction directly influences the degree of genomic RNA packaging into nascent virions. Proteolytic maturation of prM by host furin during Golgi transit facilitates rearrangement of the E proteins at the virion surface, exposing the fusion loop and thus increasing particle infectivity. Specific interactions between the prM and E proteins are also important for particle assembly, as prM acts as a chaperone, facilitating correct conformational folding of E. It is only once prM/E heterodimers form that these proteins can be secreted efficiently. The addition of branched glycans to the prM and E proteins during virion transit also plays a key role in modulating the rate of secretion, pH sensitivity and infectivity of flavivirus particles. The insights gained from research into post-translational regulation of structural proteins are beginning to be applied in the rational design of improved flavivirus vaccine candidates and make attractive targets for the development of novel therapeutics. PMID:25711963

  16. Characterization of a novel insect-specific flavivirus from Brazil: Potential for inhibition of infection of arthropod cells with medically important flaviviruses.

    DOE PAGESBeta

    Kenney, Joan L.; Solberg, Owen D.; Langevin, Stanley A.; Brault, Aaron C.

    2014-01-12

    In the past decade, there has been an upsurge in the number of newly described insect-specific flaviviruses isolated pan-globally. We recently described the isolation of a novel flavivirus (tentatively designated ‘Nhumirim virus’; NHUV) that represents an example of a unique subset of apparently insect-specific viruses that phylogenetically affiliate with dual-host mosquito-borne flaviviruses despite appearing to be limited to replication in mosquito cells. We characterized the in vitro growth potential and 3' untranslated region (UTR) sequence homology with alternative flaviviruses, and evaluated the virus’s capacity to suppress replication of representative Culex spp.-vectored pathogenic flaviviruses in mosquito cells. Only mosquito cell linesmore » were found to support NHUV replication, further reinforcing the insect-specific phenotype of this virus. Analysis of the sequence and predicted RNA secondary structures of the 3' UTR indicated NHUV to be most similar to viruses within the yellow fever serogroup and Japanese encephalitis serogroup, and viruses in the tick-borne flavivirus clade. NHUV was found to share the fewest conserved sequence elements when compared with traditional insect-specific flaviviruses. This suggests that, despite apparently being insect specific, this virus probably diverged from an ancestral mosquito-borne flavivirus. Co-infection experiments indicated that prior or concurrent infection of mosquito cells with NHUV resulted in a significant reduction in virus production of West Nile virus (WNV), St Louis encephalitis virus (SLEV) and Japanese encephalitis virus. As a result, the inhibitory effect was most effective against WNV and SLEV with over a 106-fold and 104-fold reduction in peak titres, respectively.« less

  17. Characterization of a novel insect-specific flavivirus from Brazil: Potential for inhibition of infection of arthropod cells with medically important flaviviruses.

    SciTech Connect

    Kenney, Joan L.; Solberg, Owen D.; Langevin, Stanley A.; Brault, Aaron C.

    2014-01-12

    In the past decade, there has been an upsurge in the number of newly described insect-specific flaviviruses isolated pan-globally. We recently described the isolation of a novel flavivirus (tentatively designated ‘Nhumirim virus’; NHUV) that represents an example of a unique subset of apparently insect-specific viruses that phylogenetically affiliate with dual-host mosquito-borne flaviviruses despite appearing to be limited to replication in mosquito cells. We characterized the in vitro growth potential and 3' untranslated region (UTR) sequence homology with alternative flaviviruses, and evaluated the virus’s capacity to suppress replication of representative Culex spp.-vectored pathogenic flaviviruses in mosquito cells. Only mosquito cell lines were found to support NHUV replication, further reinforcing the insect-specific phenotype of this virus. Analysis of the sequence and predicted RNA secondary structures of the 3' UTR indicated NHUV to be most similar to viruses within the yellow fever serogroup and Japanese encephalitis serogroup, and viruses in the tick-borne flavivirus clade. NHUV was found to share the fewest conserved sequence elements when compared with traditional insect-specific flaviviruses. This suggests that, despite apparently being insect specific, this virus probably diverged from an ancestral mosquito-borne flavivirus. Co-infection experiments indicated that prior or concurrent infection of mosquito cells with NHUV resulted in a significant reduction in virus production of West Nile virus (WNV), St Louis encephalitis virus (SLEV) and Japanese encephalitis virus. As a result, the inhibitory effect was most effective against WNV and SLEV with over a 106-fold and 104-fold reduction in peak titres, respectively.

  18. Characterization of a novel insect-specific flavivirus from Brazil: potential for inhibition of infection of arthropod cells with medically important flaviviruses

    PubMed Central

    Kenney, Joan L.; Solberg, Owen D.; Langevin, Stanley A.; Brault, Aaron C.

    2015-01-01

    In the past decade there has been an upsurge in the number of newly described insect-specific flaviviruses isolated pan-globally. We recently described the isolation of a novel flavivirus (tentatively designated “Nhumirim virus”; NHUV) (Pauvolid-Correa et al., in review) that represents an example of a unique subset of apparently insect-specific viruses that phylogenetically affiliate with dual-host mosquito-borne flaviviruses despite appearing to be limited to replication in mosquito cells. We characterized the in vitro growth potential, 3’ untranslated region (UTR) sequence homology with alternative flaviviruses, and evaluated the virus’s capacity to suppress replication of representative Culex spp. vectored pathogenic flaviviruses in mosquito cells. Only mosquito cell lines were found to support NHUV replication, further reinforcing the insect-specific phenotype of this virus. Analysis of the sequence and predicted RNA secondary structures of the 3’ UTR indicate NHUV to be most similar to viruses within the yellow fever serogroup, Japanese encephalitis serogroup, and viruses in the tick-borne flavivirus clade. NHUV was found to share the fewest conserved sequence elements when compared to traditional insect-specific flaviviruses. This suggests that, despite being apparently insect-specific, this virus likely diverged from an ancestral mosquito-borne flavivirus. Co-infection experiments indicated that prior or concurrent infection of mosquito cells with NHUV resulted in significant reduction in viral production of West Nile virus (WNV), St. Louis encephalitis virus (SLEV) and Japanese encephalitis virus. The inhibitory effect was most effective against WNV and SLEV with over a million-fold and 10,000-fold reduction in peak titers, respectively. PMID:25146007

  19. Serologic Evidence of Flavivirus Infections in Peridomestic Rodents in Merida, Mexico.

    PubMed

    Cigarroa-Toledo, Nohemi; Talavera-Aguilar, Lourdes G; Baak-Baak, Carlos M; García-Rejón, Julián E; Hernandez-Betancourt, Silvia; Blitvich, Bradley J; Machain-Williams, Carlos

    2016-01-01

    We conducted surveillance for flavivirus infection in peridomestic rodents in Merida, Mexico in 2011-12. We captured 161 rodents inside private residences, using Sherman traps, including 86 house mice (Mus musculus) and 75 black rats (Rattus rattus). Serum from each animal was assayed by plaque reduction neutralization test (PRNT) using two vertebrate-specific flaviviruses (Apoi and Modoc viruses) and five mosquito-borne flaviviruses (dengue 2, dengue 4, St. Louis encephalitis virus, West Nile, and yellow fever viruses). Sixty-one (37.9%) rodents had antibodies that neutralized at least one virus. Prevalences for flaviviruses were 64.0% and 15.1% for black rats and house mice, respectively. None of the PRNT90 titers exceeded 80, and often they were highest for Modoc virus. These data suggest that a subset of rodents had been infected with Modoc virus or a closely related flavivirus that was not included in the PRNT analysis. PMID:26540177

  20. Regulation of cell survival and death during Flavivirus infections

    PubMed Central

    Ghosh Roy, Sounak; Sadigh, Beata; Datan, Emmanuel; Lockshin, Richard A; Zakeri, Zahra

    2014-01-01

    Flaviviruses, ss(+) RNA viruses, include many of mankind’s most important pathogens. Their pathogenicity derives from their ability to infect many types of cells including neurons, to replicate, and eventually to kill the cells. Flaviviruses can activate tumor necrosis factor α and both intrinsic (Bax-mediated) and extrinsic pathways to apoptosis. Thus they can use many approaches for activating these pathways. Infection can lead to necrosis if viral load is extremely high or to other types of cell death if routes to apoptosis are blocked. Dengue and Japanese Encephalitis Virus can also activate autophagy. In this case the autophagy temporarily spares the infected cell, allowing a longer period of reproduction for the virus, and the autophagy further protects the cell against other stresses such as those caused by reactive oxygen species. Several of the viral proteins have been shown to induce apoptosis or autophagy on their own, independent of the presence of other viral proteins. Given the versatility of these viruses to adapt to and manipulate the metabolism, and thus to control the survival of, the infected cells, we need to understand much better how the specific viral proteins affect the pathways to apoptosis and autophagy. Only in this manner will we be able to minimize the pathology that they cause. PMID:24921001

  1. Detection of Culex flavivirus and Aedes flavivirus nucleotide sequences in mosquitoes from parks in the city of São Paulo, Brazil.

    PubMed

    Fernandes, Licia Natal; de Paula, Marcia Bicudo; Araújo, Alessandra Bergamo; Gonçalves, Elisabeth Fernandes Bertoletti; Romano, Camila Malta; Natal, Delsio; Malafronte, Rosely dos Santos; Marrelli, Mauro Toledo; Levi, José Eduardo

    2016-05-01

    The dengue viruses are widespread in Brazil and are a major public health concern. Other flaviviruses also cause diseases in humans, although on a smaller scale. The city of São Paulo is in a highly urbanized area with few green spaces apart from its parks, which are used for recreation and where potential vertebrate hosts and mosquito vectors of pathogenic Flavivirus species can be found. Although this scenario can contribute to the transmission of Flavivirus to humans, little is known about the circulation of members of this genus in these areas. In light of this, the present study sought to identify Flavivirus infection in mosquitoes (Diptera: Culicidae) collected in parks in the city of São Paulo. Seven parks in different sectors of the city were selected. Monthly mosquito collections were carried out in each park from March 2011 to February 2012 using aspiration and traps (Shannon and CD C-CO2). Nucleic acids were extracted from the mosquitoes collected and used for reverse-transcriptase and real-time polymerase chain reactions with genus-specific primers targeting a 200-nucleotide region in the Flavivirus NS5 gene. Positive samples were sequenced, and phylogenetic analyses were performed. Culex and Aedes were the most frequent genera of Culicidae collected. Culex flavivirus (CxFV)-related and Aedes flavivirus (AEFV)- related nucleotide sequences were detected in 17 pools of Culex and two pools of Aedes mosquitoes, respectively, among the 818 pools of non-engorged females analyzed. To the best of our knowledge, this is the first report of CxFV and AEFV in the city of São Paulo and Latin America, respectively. Both viruses are insect- specific flaviviruses, a group known to replicate only in mosquito cells and induce a cytopathic effect in some situations. Hence, our data suggests that CxFV and AEFV are present in Culex and Aedes mosquitoes, respectively, in parks in the city of São Paulo. Even though Flavivirus species of medical importance were not

  2. A High-Performance Multiplex Immunoassay for Serodiagnosis of Flavivirus-Associated Neurological Diseases in Horses

    PubMed Central

    Beck, Cécile; Desprès, Philippe; Paulous, Sylvie; Vanhomwegen, Jessica; Lowenski, Steeve; Nowotny, Norbert; Durand, Benoit; Garnier, Annabelle; Blaise-Boisseau, Sandra; Guitton, Edouard; Yamanaka, Takashi; Zientara, Stéphan; Lecollinet, Sylvie

    2015-01-01

    West Nile virus (WNV), Japanese encephalitis virus (JEV), and tick-borne encephalitis virus (TBEV) are flaviviruses responsible for severe neuroinvasive infections in humans and horses. The confirmation of flavivirus infections is mostly based on rapid serological tests such as enzyme-linked immunosorbent assays (ELISAs). These tests suffer from poor specificity, mainly due to antigenic cross-reactivity among flavivirus members. Robust diagnosis therefore needs to be validated through virus neutralisation tests (VNTs) which are time-consuming and require BSL3 facilities. The flavivirus envelope (E) glycoprotein ectodomain is composed of three domains (D) named DI, DII, and DIII, with EDIII containing virus-specific epitopes. In order to improve the serological differentiation of flavivirus infections, the recombinant soluble ectodomain of WNV E (WNV.sE) and EDIIIs (rEDIIIs) of WNV, JEV, and TBEV were synthesised using the Drosophila S2 expression system. Purified antigens were covalently bonded to fluorescent beads. The microspheres coupled to WNV.sE or rEDIIIs were assayed with about 300 equine immune sera from natural and experimental flavivirus infections and 172 nonimmune equine sera as negative controls. rEDIII-coupled microspheres captured specific antibodies against WNV, TBEV, or JEV in positive horse sera. This innovative multiplex immunoassay is a powerful alternative to ELISAs and VNTs for veterinary diagnosis of flavivirus-related diseases. PMID:26457301

  3. New Insights into Flavivirus Evolution, Taxonomy and Biogeographic History, Extended by Analysis of Canonical and Alternative Coding Sequences

    PubMed Central

    Moureau, Gregory; Cook, Shelley; Lemey, Philippe; Nougairede, Antoine; Forrester, Naomi L.; Khasnatinov, Maxim; Charrel, Remi N.; Firth, Andrew E.; Gould, Ernest A.; de Lamballerie, Xavier

    2015-01-01

    To generate the most diverse phylogenetic dataset for the flaviviruses to date, we determined the genomic sequences and phylogenetic relationships of 14 flaviviruses, of which 10 are primarily associated with Culex spp. mosquitoes. We analyze these data, in conjunction with a comprehensive collection of flavivirus genomes, to characterize flavivirus evolutionary and biogeographic history in unprecedented detail and breadth. Based on the presumed introduction of yellow fever virus into the Americas via the transatlantic slave trade, we extrapolated a timescale for a relevant subset of flaviviruses whose evolutionary history, shows that different Culex-spp. associated flaviviruses have been introduced from the Old World to the New World on at least five separate occasions, with 2 different sets of factors likely to have contributed to the dispersal of the different viruses. We also discuss the significance of programmed ribosomal frameshifting in a central region of the polyprotein open reading frame in some mosquito-associated flaviviruses. PMID:25719412

  4. Inverse modeling for seawater intrusion in coastal aquifers: Insights about parameter sensitivities, variances, correlations and estimation procedures derived from the Henry problem

    USGS Publications Warehouse

    Sanz, E.; Voss, C.I.

    2006-01-01

    Inverse modeling studies employing data collected from the classic Henry seawater intrusion problem give insight into several important aspects of inverse modeling of seawater intrusion problems and effective measurement strategies for estimation of parameters for seawater intrusion. Despite the simplicity of the Henry problem, it embodies the behavior of a typical seawater intrusion situation in a single aquifer. Data collected from the numerical problem solution are employed without added noise in order to focus on the aspects of inverse modeling strategies dictated by the physics of variable-density flow and solute transport during seawater intrusion. Covariances of model parameters that can be estimated are strongly dependent on the physics. The insights gained from this type of analysis may be directly applied to field problems in the presence of data errors, using standard inverse modeling approaches to deal with uncertainty in data. Covariance analysis of the Henry problem indicates that in order to generally reduce variance of parameter estimates, the ideal places to measure pressure are as far away from the coast as possible, at any depth, and the ideal places to measure concentration are near the bottom of the aquifer between the center of the transition zone and its inland fringe. These observations are located in and near high-sensitivity regions of system parameters, which may be identified in a sensitivity analysis with respect to several parameters. However, both the form of error distribution in the observations and the observation weights impact the spatial sensitivity distributions, and different choices for error distributions or weights can result in significantly different regions of high sensitivity. Thus, in order to design effective sampling networks, the error form and weights must be carefully considered. For the Henry problem, permeability and freshwater inflow can be estimated with low estimation variance from only pressure or only

  5. In vitro antiviral activity of adenosine analog NITD008 against tick-borne flaviviruses.

    PubMed

    Lo, Michael K; Shi, Pei-Yong; Chen, Yen-Liang; Flint, Mike; Spiropoulou, Christina F

    2016-06-01

    There are currently no antiviral therapies available for the tick-borne flaviviruses associated with hemorrhagic fevers: Kyasanur Forest disease virus (KFDV), both classical and the Alkhurma hemorrhagic fever virus (AHFV) subtype, and Omsk hemorrhagic fever virus (OHFV). In this brief study, we describe the in vitro antiviral activity of adenosine analog NITD008 against KFDV, AHFV, OHFV, as well as Tick-borne Encephalitis virus (TBEV). Alongside the well-established activity of NITD008 against mosquito-borne flaviviruses, our results have demonstrated the feasibility of identifying nucleoside analog inhibitors that have pan-flavivirus activity. PMID:27016316

  6. Cross-infection enhancement among African flaviviruses by immune mouse ascitic fluids.

    PubMed

    Fagbami, A H; Halstead, S B; Marchette, N J; Larsen, K

    1987-01-01

    Cross-infection enhancement of seven African flaviviruses by subneutralising concentrations of antibody in immune ascitic fluids was investigated in P388D1 cell culture. Infection by all the seven flaviviruses tested was enhanced by homologous and at least one of six heterologous immune mouse ascitic fluids (IMAF) tested. Enhancement ratios and enhancing antibody titres were higher in homologous than in heterologous enhancement. Zika, Wesselsbron, Uganda S and West Nile viruses were enhanced in culture by all the IMAF tested. Enhancement of Dakar bat and Yellow fever viruses was produced by five heterologous IMAF, but Potiskum virus was enhanced by one heterologous flavivirus antibody. The antibody to Potiskum virus was the most potent mediator of heterologous infection enhancement; all six heterologous flaviviruses were markedly enhanced by this antibody. PMID:3028713

  7. Flaviviruses in Europe: Complex Circulation Patterns and Their Consequences for the Diagnosis and Control of West Nile Disease

    PubMed Central

    Beck, Cécile; Jimenez-Clavero, Miguel Angel; Leblond, Agnès; Durand, Benoît; Nowotny, Norbert; Leparc-Goffart, Isabelle; Zientara, Stéphan; Jourdain, Elsa; Lecollinet, Sylvie

    2013-01-01

    In Europe, many flaviviruses are endemic (West Nile, Usutu, tick-borne encephalitis viruses) or occasionally imported (dengue, yellow fever viruses). Due to the temporal and geographical co-circulation of flaviviruses in Europe, flavivirus differentiation by diagnostic tests is crucial in the adaptation of surveillance and control efforts. Serological diagnosis of flavivirus infections is complicated by the antigenic similarities among the Flavivirus genus. Indeed, most flavivirus antibodies are directed against the highly immunogenic envelope protein, which contains both flavivirus cross-reactive and virus-specific epitopes. Serological assay results should thus be interpreted with care and confirmed by comparative neutralization tests using a panel of viruses known to circulate in Europe. However, antibody cross-reactivity could be advantageous in efforts to control emerging flaviviruses because it ensures partial cross-protection. In contrast, it might also facilitate subsequent diseases, through a phenomenon called antibody-dependent enhancement mainly described for dengue virus infections. Here, we review the serological methods commonly used in WNV diagnosis and surveillance in Europe. By examining past and current epidemiological situations in different European countries, we present the challenges involved in interpreting flavivirus serological tests and setting up appropriate surveillance programs; we also address the consequences of flavivirus circulation and vaccination for host immunity. PMID:24225644

  8. Posttranslational signal peptidase cleavage at the flavivirus C-prM junction in vitro.

    PubMed Central

    Stocks, C E; Lobigs, M

    1995-01-01

    We have investigated the cleavages at the flavivirus capsid-prM protein junction in vitro. When expressed in the absence of the flavivirus proteinase, capsid and prM, which are separated by an internal signal sequence, exist as a membrane-spanning precursor protein. Here we show the induction of posttranslational signal peptidase cleavage of prM by trypsin cleavage of a cytoplasmic region of this precursor protein. PMID:7494334

  9. Monte Carlo variance reduction

    NASA Technical Reports Server (NTRS)

    Byrn, N. R.

    1980-01-01

    Computer program incorporates technique that reduces variance of forward Monte Carlo method for given amount of computer time in determining radiation environment in complex organic and inorganic systems exposed to significant amounts of radiation.

  10. A COSMIC VARIANCE COOKBOOK

    SciTech Connect

    Moster, Benjamin P.; Rix, Hans-Walter; Somerville, Rachel S.; Newman, Jeffrey A. E-mail: rix@mpia.de E-mail: janewman@pitt.edu

    2011-04-20

    Deep pencil beam surveys (<1 deg{sup 2}) are of fundamental importance for studying the high-redshift universe. However, inferences about galaxy population properties (e.g., the abundance of objects) are in practice limited by 'cosmic variance'. This is the uncertainty in observational estimates of the number density of galaxies arising from the underlying large-scale density fluctuations. This source of uncertainty can be significant, especially for surveys which cover only small areas and for massive high-redshift galaxies. Cosmic variance for a given galaxy population can be determined using predictions from cold dark matter theory and the galaxy bias. In this paper, we provide tools for experiment design and interpretation. For a given survey geometry, we present the cosmic variance of dark matter as a function of mean redshift z-bar and redshift bin size {Delta}z. Using a halo occupation model to predict galaxy clustering, we derive the galaxy bias as a function of mean redshift for galaxy samples of a given stellar mass range. In the linear regime, the cosmic variance of these galaxy samples is the product of the galaxy bias and the dark matter cosmic variance. We present a simple recipe using a fitting function to compute cosmic variance as a function of the angular dimensions of the field, z-bar , {Delta}z, and stellar mass m{sub *}. We also provide tabulated values and a software tool. The accuracy of the resulting cosmic variance estimates ({delta}{sigma}{sub v}/{sigma}{sub v}) is shown to be better than 20%. We find that for GOODS at z-bar =2 and with {Delta}z = 0.5, the relative cosmic variance of galaxies with m{sub *}>10{sup 11} M{sub sun} is {approx}38%, while it is {approx}27% for GEMS and {approx}12% for COSMOS. For galaxies of m{sub *} {approx} 10{sup 10} M{sub sun}, the relative cosmic variance is {approx}19% for GOODS, {approx}13% for GEMS, and {approx}6% for COSMOS. This implies that cosmic variance is a significant source of uncertainty at z

  11. A Cosmic Variance Cookbook

    NASA Astrophysics Data System (ADS)

    Moster, Benjamin P.; Somerville, Rachel S.; Newman, Jeffrey A.; Rix, Hans-Walter

    2011-04-01

    Deep pencil beam surveys (<1 deg2) are of fundamental importance for studying the high-redshift universe. However, inferences about galaxy population properties (e.g., the abundance of objects) are in practice limited by "cosmic variance." This is the uncertainty in observational estimates of the number density of galaxies arising from the underlying large-scale density fluctuations. This source of uncertainty can be significant, especially for surveys which cover only small areas and for massive high-redshift galaxies. Cosmic variance for a given galaxy population can be determined using predictions from cold dark matter theory and the galaxy bias. In this paper, we provide tools for experiment design and interpretation. For a given survey geometry, we present the cosmic variance of dark matter as a function of mean redshift \\bar{z} and redshift bin size Δz. Using a halo occupation model to predict galaxy clustering, we derive the galaxy bias as a function of mean redshift for galaxy samples of a given stellar mass range. In the linear regime, the cosmic variance of these galaxy samples is the product of the galaxy bias and the dark matter cosmic variance. We present a simple recipe using a fitting function to compute cosmic variance as a function of the angular dimensions of the field, \\bar{z}, Δz, and stellar mass m *. We also provide tabulated values and a software tool. The accuracy of the resulting cosmic variance estimates (δσ v /σ v ) is shown to be better than 20%. We find that for GOODS at \\bar{z}=2 and with Δz = 0.5, the relative cosmic variance of galaxies with m *>1011 M sun is ~38%, while it is ~27% for GEMS and ~12% for COSMOS. For galaxies of m * ~ 1010 M sun, the relative cosmic variance is ~19% for GOODS, ~13% for GEMS, and ~6% for COSMOS. This implies that cosmic variance is a significant source of uncertainty at \\bar{z}=2 for small fields and massive galaxies, while for larger fields and intermediate mass galaxies, cosmic variance is

  12. Natural Exposure of Horses to Mosquito-Borne Flaviviruses in South-East Queensland, Australia

    PubMed Central

    Prow, Natalie A.; Tan, Cindy S. E.; Wang, Wenqi; Hobson-Peters, Jody; Kidd, Lisa; Barton, Anita; Wright, John; Hall, Roy A.; Bielefeldt-Ohmann, Helle

    2013-01-01

    In 2011 an unprecedented epidemic of equine encephalitis occurred in south-eastern (SE) Australia following heavy rainfall and severe flooding in the preceding 2–4 months. Less than 6% of the documented cases occurred in Queensland, prompting the question of pre-existing immunity in Queensland horses. A small-scale serological survey was conducted on horses residing in one of the severely flood-affected areas of SE-Queensland. Using a flavivirus-specific blocking-ELISA we found that 63% (39/62) of horses older than 3 years were positive for flavivirus antibodies, and of these 18% (7/38) had neutralizing antibodies to Murray Valley encephalitis virus (MVEV), Kunjin virus (WNVKUN) and/or Alfuy virus (ALFV). The remainder had serum-neutralizing antibodies to viruses in the Kokobera virus (KOKV) complex or antibodies to unknown/untested flaviviruses. Amongst eight yearlings one presented with clinical MVEV-encephalomyelitis, while another, clinically normal, had MVEV-neutralizing antibodies. The remaining six yearlings were flavivirus antibody negative. Of 19 foals born between August and November 2011 all were flavivirus antibody negative in January 2012. This suggests that horses in the area acquire over time active immunity to a range of flaviviruses. Nevertheless, the relatively infrequent seropositivity to MVEV, WNVKUN and ALFV (15%) suggests that factors other than pre-existing immunity may have contributed to the low incidence of arboviral disease in SE-Queensland horses during the 2011 epidemic. PMID:24048209

  13. Serological evidence for the circulation of flaviviruses in seabird populations of the western Indian Ocean.

    PubMed

    Jaeger, A; Lecollinet, S; Beck, C; Bastien, M; Le Corre, M; Dellagi, K; Pascalis, H; Boulinier, T; Lebarbenchon, C

    2016-02-01

    Birds play a central role in the epidemiology of several flaviviruses of concern for public and veterinary health. Seabirds represent the most abundant and widespread avifauna in the western Indian Ocean and may play an important role as host reservoirs and spreaders of arthropod-borne pathogens such as flaviviruses. We report the results of a serological investigation based on blood samples collected from nine seabird species from seven islands in the Indian Ocean. Using a commercial competitive enzyme-linked immunosorbent assay directed against the prototypic West Nile flavivirus, antibodies against flaviviruses were detected in the serum of 47 of the 855 seabirds tested. They were detected in bird samples from three islands and from four bird species. Seroneutralization tests on adults and chicks suggested that great frigatebirds (Fregata minor) from Europa were infected by West Nile virus during their non-breeding period, and that Usutu virus probably circulated within bird colonies on Tromelin and on Juan de Nova. Real-time polymerase chain reactions performed on bird blood samples did not yield positive results precluding the genetic characterization of flavivirus using RNA sequencing. Our findings stress the need to further investigate flavivirus infections in arthropod vectors present in seabird colonies. PMID:26194365

  14. Development of a novel protocol for generating flavivirus reporter particles.

    PubMed

    Fernández, Igor Velado; Okamoto, Natsumi; Ito, Aki; Fukuda, Miki; Someya, Azusa; Nishino, Yosii; Sasaki, Nobuya; Maeda, Akihiko

    2014-11-01

    Infection with West Nile virus (WNV), a mosquito-borne flavivirus, is a growing public and animal health concern worldwide. Prevention, diagnosis and treatment strategies for the infection are urgently required. Recently, viral reverse genetic systems have been developed and applied to clinical WNV virology. We developed a protocol for generating reporter virus particles (RVPs) of WNV with the aim of overcoming two major problems associated with conventional protocols, the difficulty in generating RVPs due to the specific skills required for handling RNAs, and the potential for environmental contamination by antibiotic-resistant genes encoded within the genome RNA of the RVPs. By using the proposed protocol, cells were established in which the RVP genome RNA is replicated constitutively and does not encode any antibiotic-resistant genes, and used as the cell supply for RVP genome RNA. Generation of the WNV RVPs requires only the simple transfection of the expression vectors for the viral structural proteins into the cells. Therefore, no RNA handling is required in this protocol. The WNV RVP yield obtained using this protocol was similar that obtained using the conventional protocol. According to these results, the newly developed protocol appears to be a good alternative for the generation of WNV RVPs, particularly for clinical applications. PMID:25116200

  15. Stability of a Tick-Borne Flavivirus in Milk.

    PubMed

    Offerdahl, Danielle K; Clancy, Niall G; Bloom, Marshall E

    2016-01-01

    The tick-borne flaviviruses (TBFV) occur worldwide and the tick-borne encephalitis virus (TBEV) members of the group often cause severe, debilitating neurological disease in humans. Although the primary route of infection is through the bite of an infected tick, alimentary infection through the consumption of TBEV-contaminated dairy products is also well-documented and is responsible for some disease in endemic areas. Experimental infection of goats, cattle, and sheep with TBEV shows that the virus can be excreted in the milk of infected animals. Additionally, the virus remains infectious after exposure to low pH levels, similar to those found in the stomach. To evaluate the survival of virus in milk, we studied the stability of the BSL-2 TBFV, Langat virus, in unpasteurized goat milk over time and after different thermal treatments. Virus was stable in milk maintained under refrigeration conditions; however, there was a marked reduction in virus titer after incubation at room temperature. High temperature, short time pasteurization protocols completely inactivated the virus. Interestingly, simulation of a typical thermal regime utilized for cheese did not completely inactivate the virus in milk. These findings stress the importance of proper milk handling and pasteurization processes in areas endemic for TBEV. PMID:27243000

  16. Antiviral effects of an iminosugar derivative on flavivirus infections.

    PubMed

    Wu, Shu-Fen; Lee, Chyan-Jang; Liao, Ching-Len; Dwek, Raymond A; Zitzmann, Nicole; Lin, Yi-Ling

    2002-04-01

    Endoplasmic reticulum (ER) alpha-glucosidase inhibitors, which block the trimming step of N-linked glycosylation, have been shown to eliminate the production of several ER-budding viruses. Here we investigated the effects of one such inhibitor, N-nonyl-deoxynojirimycin (NN-DNJ), a 9-carbon alkyl iminosugar derivative, on infection by Japanese encephalitis virus (JEV) and dengue virus serotype 2 (DEN-2). In the presence of NN-DNJ, JEV and DEN-2 infections were suppressed in a dose-dependent manner. This inhibitory effect appeared to influence DEN-2 infection more than JEV infection, since lower concentrations of NN-DNJ substantially blocked DEN-2 replication. Secretion of the flaviviral glycoproteins E and NS1 was greatly reduced, and levels of DEN-2 viral RNA replication measured by fluorogenic reverse transcription-PCR were also decreased, by NN-DNJ. Notably, the viral glycoproteins, prM, E, and NS1 were found to associate transiently with the ER chaperone calnexin, and this interaction was affected by NN-DNJ, suggesting a potential role of calnexin in the folding of flaviviral glycoproteins. Additionally, in a mouse model of lethal challenge by JEV infection, oral delivery of NN-DNJ reduced the mortality rate. These findings show that NN-DNJ has an antiviral effect on flavivirus infection, likely through interference with virus replication at the posttranslational modification level, occurring mainly in the ER. PMID:11907199

  17. Stability of a Tick-Borne Flavivirus in Milk

    PubMed Central

    Offerdahl, Danielle K.; Clancy, Niall G.; Bloom, Marshall E.

    2016-01-01

    The tick-borne flaviviruses (TBFV) occur worldwide and the tick-borne encephalitis virus (TBEV) members of the group often cause severe, debilitating neurological disease in humans. Although the primary route of infection is through the bite of an infected tick, alimentary infection through the consumption of TBEV-contaminated dairy products is also well-documented and is responsible for some disease in endemic areas. Experimental infection of goats, cattle, and sheep with TBEV shows that the virus can be excreted in the milk of infected animals. Additionally, the virus remains infectious after exposure to low pH levels, similar to those found in the stomach. To evaluate the survival of virus in milk, we studied the stability of the BSL-2 TBFV, Langat virus, in unpasteurized goat milk over time and after different thermal treatments. Virus was stable in milk maintained under refrigeration conditions; however, there was a marked reduction in virus titer after incubation at room temperature. High temperature, short time pasteurization protocols completely inactivated the virus. Interestingly, simulation of a typical thermal regime utilized for cheese did not completely inactivate the virus in milk. These findings stress the importance of proper milk handling and pasteurization processes in areas endemic for TBEV. PMID:27243000

  18. Nuclear Localization of Flavivirus RNA Synthesis in Infected Cells

    PubMed Central

    Uchil, Pradeep Devappa; Kumar, Anil V. A.; Satchidanandam, Vijaya

    2006-01-01

    Flaviviral replication is believed to be exclusively cytoplasmic, occurring within virus-induced membrane-bound replication complexes in the host cytoplasm. Here we show that a significant proportion (20%) of the total RNA-dependent RNA polymerase (RdRp) activity from cells infected with West Nile virus, Japanese encephalitis virus (JEV), and dengue virus is resident within the nucleus. Consistent with this, the major replicase proteins NS3 and NS5 of JEV also localized within the nucleus. NS5 was found distributed throughout the nucleoplasm, but NS3 was present at sites of active flaviviral RNA synthesis, colocalizing with NS5, and visible as distinct foci along the inner periphery of the nucleus by confocal and immunoelectron microscopy. Both these viral replicase proteins were also present in the nuclear matrix, colocalizing with the peripheral lamina, and revealed a well-entrenched nuclear location for the viral replication complex. In keeping with this observation, antibodies to either NS3 or NS5 coimmunoprecipitated the other protein from isolated nuclei along with newly synthesized viral RNA. Taken together these data suggest an absolute requirement for both of the replicase proteins for nucleus-localized synthesis of flavivirus RNA. Thus, we conclusively demonstrate for the first time that the host cell nucleus functions as an additional site for the presence of functionally active flaviviral replicase complex. PMID:16699025

  19. Getting around cosmic variance

    SciTech Connect

    Kamionkowski, M.; Loeb, A.

    1997-10-01

    Cosmic microwave background (CMB) anisotropies probe the primordial density field at the edge of the observable Universe. There is a limiting precision ({open_quotes}cosmic variance{close_quotes}) with which anisotropies can determine the amplitude of primordial mass fluctuations. This arises because the surface of last scatter (SLS) probes only a finite two-dimensional slice of the Universe. Probing other SLS{close_quote}s observed from different locations in the Universe would reduce the cosmic variance. In particular, the polarization of CMB photons scattered by the electron gas in a cluster of galaxies provides a measurement of the CMB quadrupole moment seen by the cluster. Therefore, CMB polarization measurements toward many clusters would probe the anisotropy on a variety of SLS{close_quote}s within the observable Universe, and hence reduce the cosmic-variance uncertainty. {copyright} {ital 1997} {ital The American Physical Society}

  20. Insect-specific flaviviruses, a worldwide widespread group of viruses only detected in insects.

    PubMed

    Calzolari, Mattia; Zé-Zé, Líbia; Vázquez, Ana; Sánchez Seco, Mari Paz; Amaro, Fátima; Dottori, Michele

    2016-06-01

    Several flaviviruses are important pathogens for humans and animals (Dengue viruses, Japanese encephalitis virus, Yellow-fever virus, Tick-borne encephalitis virus, West Nile virus). In recent years, numerous novel and related flaviviruses without known pathogenic capacity have been isolated worldwide in the natural mosquito population. However, phylogenetic studies have shown that genomic sequences of these viruses diverge from other flaviviruses. Moreover, these viruses seem to be exclusive of insects (they do not seem to grow on vertebrate cell lines), and were already defined as mosquito-only flaviviruses or insect-specific flaviviruses. At least eleven of these viruses were isolated worldwide, and sequences ascribable to other eleven putative viruses were detected in several mosquito species. A large part of the cycle of these viruses is not well known, and their persistence in the environment is poorly understood. These viruses are detected in a wide variety of distinct mosquito species and also in sandflies and chironomids worldwide; a single virus, or the genetic material ascribable to a virus, was detected in several mosquito species in different countries, often in different continents. Furthermore, some of these viruses are carried by invasive mosquitoes, and do not seem to have a depressive action on their fitness. The global distribution and the continuous detection of new viruses in this group point out the likely underestimation of their number, and raise interesting issues about their possible interactions with the pathogenic flaviviruses, and their influence on the bionomics of arthropod hosts. Some enigmatic features, as their integration in the mosquito genome, the recognition of their genetic material in DNA forms in field-collected mosquitoes, or the detection of the same virus in both mosquitoes and sandflies, indicate that the cycle of these viruses has unknown characteristics that could be of use to reach a deeper understanding of the cycle

  1. Variance Anisotropy in Kinetic Plasmas

    NASA Astrophysics Data System (ADS)

    Parashar, Tulasi N.; Oughton, Sean; Matthaeus, William H.; Wan, Minping

    2016-06-01

    Solar wind fluctuations admit well-documented anisotropies of the variance matrix, or polarization, related to the mean magnetic field direction. Typically, one finds a ratio of perpendicular variance to parallel variance of the order of 9:1 for the magnetic field. Here we study the question of whether a kinetic plasma spontaneously generates and sustains parallel variances when initiated with only perpendicular variance. We find that parallel variance grows and saturates at about 5% of the perpendicular variance in a few nonlinear times irrespective of the Reynolds number. For sufficiently large systems (Reynolds numbers) the variance approaches values consistent with the solar wind observations.

  2. Conversations across Meaning Variance

    ERIC Educational Resources Information Center

    Cordero, Alberto

    2013-01-01

    Progressive interpretations of scientific theories have long been denounced as naive, because of the inescapability of meaning variance. The charge reportedly applies to recent realist moves that focus on theory-parts rather than whole theories. This paper considers the question of what "theory-parts" of epistemic significance (if any) relevantly…

  3. Naive Analysis of Variance

    ERIC Educational Resources Information Center

    Braun, W. John

    2012-01-01

    The Analysis of Variance is often taught in introductory statistics courses, but it is not clear that students really understand the method. This is because the derivation of the test statistic and p-value requires a relatively sophisticated mathematical background which may not be well-remembered or understood. Thus, the essential concept behind…

  4. A CRISPR screen defines a signal peptide processing pathway required by flaviviruses.

    PubMed

    Zhang, Rong; Miner, Jonathan J; Gorman, Matthew J; Rausch, Keiko; Ramage, Holly; White, James P; Zuiani, Adam; Zhang, Ping; Fernandez, Estefania; Zhang, Qiang; Dowd, Kimberly A; Pierson, Theodore C; Cherry, Sara; Diamond, Michael S

    2016-07-01

    Flaviviruses infect hundreds of millions of people annually, and no antiviral therapy is available. We performed a genome-wide CRISPR/Cas9-based screen to identify host genes that, when edited, resulted in reduced flavivirus infection. Here, we validated nine human genes required for flavivirus infectivity, and these were associated with endoplasmic reticulum functions including translocation, protein degradation, and N-linked glycosylation. In particular, a subset of endoplasmic reticulum-associated signal peptidase complex (SPCS) proteins was necessary for proper cleavage of the flavivirus structural proteins (prM and E) and secretion of viral particles. Loss of SPCS1 expression resulted in markedly reduced yield of all Flaviviridae family members tested (West Nile, Dengue, Zika, yellow fever, Japanese encephalitis, and hepatitis C viruses), but had little impact on alphavirus, bunyavirus, or rhabdovirus infection or the surface expression or secretion of diverse host proteins. We found that SPCS1 dependence could be bypassed by replacing the native prM protein leader sequences with a class I major histocompatibility complex (MHC) antigen leader sequence. Thus, SPCS1, either directly or indirectly via its interactions with unknown host proteins, preferentially promotes the processing of specific protein cargo, and Flaviviridae have a unique dependence on this signal peptide processing pathway. SPCS1 and other signal processing pathway members could represent pharmacological targets for inhibiting infection by the expanding number of flaviviruses of medical concern. PMID:27383988

  5. Duck egg-drop syndrome caused by BYD virus, a new Tembusu-related flavivirus.

    PubMed

    Su, Jingliang; Li, Shuang; Hu, Xudong; Yu, Xiuling; Wang, Yongyue; Liu, Peipei; Lu, Xishan; Zhang, Guozhong; Hu, Xueying; Liu, Di; Li, Xiaoxia; Su, Wenliang; Lu, Hao; Mok, Ngai Shing; Wang, Peiyi; Wang, Ming; Tian, Kegong; Gao, George F

    2011-01-01

    Since April 2010, a severe outbreak of duck viral infection, with egg drop, feed uptake decline and ovary-oviduct disease, has spread around the major duck-producing regions in China. A new virus, named BYD virus, was isolated in different areas, and a similar disease was reproduced in healthy egg-producing ducks, infecting with the isolated virus. The virus was re-isolated from the affected ducks and replicated well in primary duck embryo fibroblasts and Vero cells, causing the cytopathic effect. The virus was identified as an enveloped positive-stranded RNA virus with a size of approximately 55 nm in diameter. Genomic sequencing of the isolated virus revealed that it is closely related to Tembusu virus (a mosquito-borne Ntaya group flavivirus), with 87-91% nucleotide identity of the partial E (envelope) proteins to that of Tembusu virus and 72% of the entire genome coding sequence with Bagaza virus, the most closely related flavivirus with an entirely sequenced genome. Collectively our systematic studies fulfill Koch's postulates, and therefore, the causative agent of the duck egg drop syndrome occurring in China is a new flavivirus. Flavivirus is an emerging and re-emerging zoonotic pathogen and BYD virus that causes severe egg-drop, could be disastrous for the duck industry. More importantly its public health concerns should also be evaluated, and its epidemiology should be closely watched due to the zoonotic nature of flaviviruses. PMID:21455312

  6. Structures of the Zika Virus Envelope Protein and Its Complex with a Flavivirus Broadly Protective Antibody.

    PubMed

    Dai, Lianpan; Song, Jian; Lu, Xishan; Deng, Yong-Qiang; Musyoki, Abednego Moki; Cheng, Huijun; Zhang, Yanfang; Yuan, Yuan; Song, Hao; Haywood, Joel; Xiao, Haixia; Yan, Jinghua; Shi, Yi; Qin, Cheng-Feng; Qi, Jianxun; Gao, George F

    2016-05-11

    Zika virus (ZIKV), a mosquito-borne flavivirus, is a current global public health concern. The flavivirus envelope (E) glycoprotein is responsible for virus entry and represents a major target of neutralizing antibodies for other flaviviruses. Here, we report the structures of ZIKV E protein at 2.0 Å and in complex with a flavivirus broadly neutralizing murine antibody 2A10G6 at 3.0 Å. ZIKV-E resembles all the known flavivirus E structures but contains a unique, positively charged patch adjacent to the fusion loop region of the juxtaposed monomer, which may influence host attachment. The ZIKV-E-2A10G6 complex structure reveals antibody recognition of a highly conserved fusion loop. 2A10G6 binds to ZIKV-E with high affinity in vitro and neutralizes currently circulating ZIKV strains in vitro and in mice. The E protein fusion loop epitope represents a potential candidate for therapeutic antibodies against ZIKV. PMID:27158114

  7. Inhibitors of tick-borne flavivirus reproduction from structure-based virtual screening.

    PubMed

    Osolodkin, Dmitry I; Kozlovskaya, Liubov I; Dueva, Evgenia V; Dotsenko, Victor V; Rogova, Yulia V; Frolov, Konstantin A; Krivokolysko, Sergey G; Romanova, Ekaterina G; Morozov, Alexey S; Karganova, Galina G; Palyulin, Vladimir A; Pentkovski, Vladimir M; Zefirov, Nikolay S

    2013-09-12

    Flaviviruses form a large family of enveloped viruses affecting millions of people over the world. To date, no specific therapy was suggested for the infected people, making the treatment exclusively symptomatic. Several attempts were performed earlier for the design of fusion inhibitors for mosquito-borne flaviviruses, whereas for the tick-borne flaviviruses such design had not been performed. We have constructed homology models of envelope glycoproteins of tick-transmitted flaviviruses with the detergent binding pocket in the open state. Molecular docking of substituted 1,4-dihydropyridines and pyrido[2,1-b][1,3,5]thiadiazines was made against these models, and 89 hits were selected for the in vitro experimental evaluation. Seventeen compounds showed significant inhibition against tick-borne encephalitis virus, Powassan virus, or Omsk hemorrhagic fever virus in the 50% plaque reduction test in PEK cells. These compounds identified through rational design are the first ones possessing reproduction inhibition activity against tick-borne flaviviruses. PMID:24900762

  8. Duck Egg-Drop Syndrome Caused by BYD Virus, a New Tembusu-Related Flavivirus

    PubMed Central

    Yu, Xiuling; Wang, Yongyue; Liu, Peipei; Lu, Xishan; Zhang, Guozhong; Hu, Xueying; Liu, Di; Li, Xiaoxia; Su, Wenliang; Lu, Hao; Mok, Ngai Shing; Wang, Peiyi; Wang, Ming; Tian, Kegong; Gao, George F.

    2011-01-01

    Since April 2010, a severe outbreak of duck viral infection, with egg drop, feed uptake decline and ovary-oviduct disease, has spread around the major duck-producing regions in China. A new virus, named BYD virus, was isolated in different areas, and a similar disease was reproduced in healthy egg-producing ducks, infecting with the isolated virus. The virus was re-isolated from the affected ducks and replicated well in primary duck embryo fibroblasts and Vero cells, causing the cytopathic effect. The virus was identified as an enveloped positive-stranded RNA virus with a size of approximately 55 nm in diameter. Genomic sequencing of the isolated virus revealed that it is closely related to Tembusu virus (a mosquito-borne Ntaya group flavivirus), with 87–91% nucleotide identity of the partial E (envelope) proteins to that of Tembusu virus and 72% of the entire genome coding sequence with Bagaza virus, the most closely related flavivirus with an entirely sequenced genome. Collectively our systematic studies fulfill Koch's postulates, and therefore, the causative agent of the duck egg drop syndrome occurring in China is a new flavivirus. Flavivirus is an emerging and re-emerging zoonotic pathogen and BYD virus that causes severe egg-drop, could be disastrous for the duck industry. More importantly its public health concerns should also be evaluated, and its epidemiology should be closely watched due to the zoonotic nature of flaviviruses. PMID:21455312

  9. Spectral Ambiguity of Allan Variance

    NASA Technical Reports Server (NTRS)

    Greenhall, C. A.

    1996-01-01

    We study the extent to which knowledge of Allan variance and other finite-difference variances determines the spectrum of a random process. The variance of first differences is known to determine the spectrum. We show that, in general, the Allan variance does not. A complete description of the ambiguity is given.

  10. Production and characterization of vaccines based on flaviviruses defective in replication

    SciTech Connect

    Mason, Peter W.; Shustov, Alexandr V.; Frolov, Ilya . E-mail: ivfrolov@utmb.edu

    2006-08-01

    To develop new vaccine candidates for flavivirus infections, we have engineered two flaviviruses, yellow fever virus (YFV) and West Nile virus (WNV), that are deficient in replication. These defective pseudoinfectious viruses (PIVs) lack a functional copy of the capsid (C) gene in their genomes and are incapable of causing spreading infection upon infection of cells both in vivo and in vitro. However, they produce extracellular E protein in form of secreted subviral particles (SVPs) that are known to be an effective immunogen. PIVs can be efficiently propagated in trans-complementing cell lines making high levels of C or all three viral structural proteins. PIVs derived from YFV and WNV, demonstrated very high safety and immunization produced high levels of neutralizing antibodies and protective immune response. Such defective flaviviruses can be produced in large scale under low biocontainment conditions and should be useful for diagnostic or vaccine applications.

  11. Flaviviruses, an expanding threat in public health: focus on dengue, West Nile, and Japanese encephalitis virus.

    PubMed

    Daep, Carlo Amorin; Muñoz-Jordán, Jorge L; Eugenin, Eliseo Alberto

    2014-12-01

    The flaviviruses dengue, West Nile, and Japanese encephalitis represent three major mosquito-borne viruses worldwide. These pathogens impact the lives of millions of individuals and potentially could affect non-endemic areas already colonized by mosquito vectors. Unintentional transport of infected vectors (Aedes and Culex spp.), traveling within endemic areas, rapid adaptation of the insects into new geographic locations, climate change, and lack of medical surveillance have greatly contributed to the increase in flaviviral infections worldwide. The mechanisms by which flaviviruses alter the immune and the central nervous system have only recently been examined despite the alarming number of infections, related deaths, and increasing global distribution. In this review, we will discuss the expansion of the geographic areas affected by flaviviruses, the potential threats to previously unaffected countries, the mechanisms of pathogenesis, and the potential therapeutic interventions to limit the devastating consequences of these viruses. PMID:25287260

  12. Structure of Dengue Virus: Implications for Flavivirus Organization, Maturation, and Fusion

    PubMed Central

    Kuhn, Richard J.; Zhang, Wei; Rossmann, Michael G.; Pletnev, Sergei V.; Corver, Jeroen; Lenches, Edith; Jones, Christopher T.; Mukhopadhyay, Suchetana; Chipman, Paul R.; Strauss, Ellen G.; Baker, Timothy S.; Strauss, James H.

    2014-01-01

    Summary The first structure of a flavivirus has been determined by using a comThe first structure of a flavivirus has been determined by using a combination of cryoelectron microscopy and fitting of the known structure of glycoprotein E into the electron density map. The virus core, within a lipid bilayer, has a less-ordered structure than the external, icosahedral scaffold of 90 glycoprotein E dimers. The three E monomers per icosahedral asymmetric unit do not have quasiequivalent symmetric environments. Difference maps indicate the location of the small membrane protein M relative to the overlaying scaffold of E dimers. The structure suggests that flaviviruses, and by analogy also alphaviruses, employ a fusion mechanism in which the distal β barrels of domain II of the glycoprotein E are inserted into the cellular membrane. PMID:11893341

  13. Flaviviruses, an expanding threat in public health: focus on Dengue, West Nile, and Japanese encephalitis virus

    PubMed Central

    Daep, Carlo Amorin; Muñoz-Jordán, Jorge L.; Eugenin, Eliseo Alberto

    2014-01-01

    The flaviviruses Dengue, West Nile, and Japanese encephalitis represent three major mosquito-borne viruses worldwide. These pathogens impact the lives of millions of individuals and potentially could affect non-endemic areas already colonized by mosquito vectors. Unintentional transport of infected vectors (Aedes and Culex sp), traveling within endemic areas, rapid adaptation of the insects into new geographic locations, climate change, and lack of medical surveillance have greatly contributed to the increase in flaviviral infections worldwide. The mechanisms by which flaviviruses alter the immune and the central nervous system have only recently been examined despite the alarming number of infections, related deaths, and increasing global distribution. In this review, we will discuss the expansion of the geographic areas affected by flaviviruses, the potential threats to previously unaffected countries, the mechanisms of pathogenesis, and the potential therapeutic interventions to limit the devastating consequences of these viruses. PMID:25287260

  14. Biclustering with heterogeneous variance.

    PubMed

    Chen, Guanhua; Sullivan, Patrick F; Kosorok, Michael R

    2013-07-23

    In cancer research, as in all of medicine, it is important to classify patients into etiologically and therapeutically relevant subtypes to improve diagnosis and treatment. One way to do this is to use clustering methods to find subgroups of homogeneous individuals based on genetic profiles together with heuristic clinical analysis. A notable drawback of existing clustering methods is that they ignore the possibility that the variance of gene expression profile measurements can be heterogeneous across subgroups, and methods that do not consider heterogeneity of variance can lead to inaccurate subgroup prediction. Research has shown that hypervariability is a common feature among cancer subtypes. In this paper, we present a statistical approach that can capture both mean and variance structure in genetic data. We demonstrate the strength of our method in both synthetic data and in two cancer data sets. In particular, our method confirms the hypervariability of methylation level in cancer patients, and it detects clearer subgroup patterns in lung cancer data. PMID:23836637

  15. Use of envelope domain III protein for detection and differentiation of flaviviruses in the Free State Province, South Africa.

    PubMed

    Mathengtheng, Lehlohonolo; Burt, Felicity J

    2014-04-01

    The presence of the mosquito-borne flavivirus species West Nile virus (WNV) and Wesselsbron virus (WESSV) in southern Africa is well established; however, their true prevalence remains unknown. To date, the presence of tick-borne flaviviruses has not been confirmed in this region. Serological assays using reagents that can be handled in a biosafety level 2 or lower facility were developed and evaluated for the detection and differentiation of tick- and mosquito-borne flaviviruses in the Free State province of South Africa. A total of 2393 serum samples from a variety of species including humans, cattle, and sheep were tested using Kunjin virus (KUNV) cell lysate antigen for the detection of anti-flavivirus antibodies in an indirect immunoglobulin G (IgG) enzyme-linked immonosorbent assay (ELISA). To further differentiate positive reactors on the KUNV assay for antibodies against tick- or mosquito-borne flaviviruses, recombinant envelope domain III (r-EDIII) proteins of Langat virus (LGTV), WNV, and WESSV were expressed in a bacterial expression system and used in ELISA. A total of 722 samples were positive using the KUNV assay, of which 71, 457, and 431 were positive using the r-LGTVEDIII, r-WNVEDIII, and r-WESSVEDIII assays, respectively. A total of 70 samples were reactive using the KUNV assay but not using any of the other assays, suggesting that there are possibly other flaviviruses circulating in the Free State province for which specific r-EDIII assays were not available. Collectively, the results suggest a strong presence of flaviviruses co-circulating in the Free State province with an abundance of mosquito-borne flaviviruses. There is evidence suggesting the presence of tick-borne flaviviruses, but it has yet to be confirmed. The EDIII protein is a useful tool that can be used in the detection and differentiation of flaviviruses in resource-limited laboratories, but virus neutralization assays are suggested for accurate confirmation of results. PMID

  16. Comparison of Flavivirus Universal Primer Pairs and Development of a Rapid, Highly Sensitive Heminested Reverse Transcription-PCR Assay for Detection of Flaviviruses Targeted to a Conserved Region of the NS5 Gene Sequences

    PubMed Central

    Scaramozzino, Natale; Crance, Jean-Marc; Jouan, Alain; DeBriel, Dominique A.; Stoll, Françoise; Garin, Daniel

    2001-01-01

    Arthropod-transmitted flaviviruses are responsible for considerable morbidity and mortality, causing severe encephalitic, hemorrhagic, and febrile illnesses in humans. Because there are no specific clinical symptoms for infection by a determined virus and because different arboviruses could be present in the same area, a genus diagnosis by PCR would be a useful first-line diagnostic method. The six published Flavivirus genus primer pairs localized in the NS1, NS3, NS5, and 3′ NC regions were evaluated in terms of specificity and sensitivity with flaviviruses (including the main viruses pathogenic for humans) at a titer of 105 50% tissue culture infectious doses (TCID50s) ml−1 with a common identification step by agarose gel electrophoresis. Only one NS5 primer pair allowed the detection of all tested flaviviruses with the sensitivity limit of 105 TCID50s ml−1. Using a heminested PCR with new primers designed in the same region after an alignment of 30 different flaviviruses, the sensitivity of reverse transcription-PCR was improved and allowed the detection of about 200 infectious doses ml−1 with all of the tick- and mosquito-borne flaviviruses tested. It was confirmed that the sequenced amplified products in the NS5 region allowed predictability of flavivirus species by dendrogram, including the New York 99 West Nile strain. This technique was successfully performed with a cerebrospinal fluid sample from a patient hospitalized with West Nile virus encephalitis. PMID:11326014

  17. Minimum variance beamformer weights revisited.

    PubMed

    Moiseev, Alexander; Doesburg, Sam M; Grunau, Ruth E; Ribary, Urs

    2015-10-15

    Adaptive minimum variance beamformers are widely used analysis tools in MEG and EEG. When the target brain activity presents in the form of spatially localized responses, the procedure usually involves two steps. First, positions and orientations of the sources of interest are determined. Second, the filter weights are calculated and source time courses reconstructed. This last step is the object of the current study. Despite different approaches utilized at the source localization stage, basic expressions for the weights have the same form, dictated by the minimum variance condition. These classic expressions involve covariance matrix of the measured field, which includes contributions from both the sources of interest and the noise background. We show analytically that the same weights can alternatively be obtained, if the full field covariance is replaced with that of the noise, provided the beamformer points to the true sources precisely. In practice, however, a certain mismatch is always inevitable. We show that such mismatch results in partial suppression of the true sources if the traditional weights are used. To avoid this effect, the "alternative" weights based on properly estimated noise covariance should be applied at the second, source time course reconstruction step. We demonstrate mathematically and using simulated and real data that in many situations the alternative weights provide significantly better time course reconstruction quality than the traditional ones. In particular, they a) improve source-level SNR and yield more accurately reconstructed waveforms; b) provide more accurate estimates of inter-source correlations; and c) reduce the adverse influence of the source correlations on the performance of single-source beamformers, which are used most often. Importantly, the alternative weights come at no additional computational cost, as the structure of the expressions remains the same. PMID:26143207

  18. Structure and functionality in flavivirus NS-proteins: perspectives for drug design.

    PubMed

    Bollati, Michela; Alvarez, Karin; Assenberg, René; Baronti, Cécile; Canard, Bruno; Cook, Shelley; Coutard, Bruno; Decroly, Etienne; de Lamballerie, Xavier; Gould, Ernest A; Grard, Gilda; Grimes, Jonathan M; Hilgenfeld, Rolf; Jansson, Anna M; Malet, Hélène; Mancini, Erika J; Mastrangelo, Eloise; Mattevi, Andrea; Milani, Mario; Moureau, Grégory; Neyts, Johan; Owens, Raymond J; Ren, Jingshan; Selisko, Barbara; Speroni, Silvia; Steuber, Holger; Stuart, David I; Unge, Torsten; Bolognesi, Martino

    2010-08-01

    Flaviviridae are small enveloped viruses hosting a positive-sense single-stranded RNA genome. Besides yellow fever virus, a landmark case in the history of virology, members of the Flavivirus genus, such as West Nile virus and dengue virus, are increasingly gaining attention due to their re-emergence and incidence in different areas of the world. Additional environmental and demographic considerations suggest that novel or known flaviviruses will continue to emerge in the future. Nevertheless, up to few years ago flaviviruses were considered low interest candidates for drug design. At the start of the European Union VIZIER Project, in 2004, just two crystal structures of protein domains from the flaviviral replication machinery were known. Such pioneering studies, however, indicated the flaviviral replication complex as a promising target for the development of antiviral compounds. Here we review structural and functional aspects emerging from the characterization of two main components (NS3 and NS5 proteins) of the flavivirus replication complex. Most of the reviewed results were achieved within the European Union VIZIER Project, and cover topics that span from viral genomics to structural biology and inhibition mechanisms. The ultimate aim of the reported approaches is to shed light on the design and development of antiviral drug leads. PMID:19945487

  19. Functional non-coding RNAs derived from the flavivirus 3' untranslated region.

    PubMed

    Clarke, B D; Roby, J A; Slonchak, A; Khromykh, A A

    2015-08-01

    Flaviviruses are single-stranded positive sense RNA enveloped viruses. The flavivirus genus includes important human pathogens such as dengue virus (DENV), West Nile virus (WNV), yellow fever virus (YFV), Japanese encephalitis virus (JEV), tick-borne encephalitis virus (TBEV), and Murray Valley encephalitis virus (MVEV). In addition to the viral proteins and viral genomic RNA, flaviviruses produce at least two functional non-coding RNAs derived from the 3' untranslated region (3'UTR), the subgenomic flavivirus RNA (sfRNA) and a putative WNV miRNA (KUN-miR-1). In this review we summarize published data from studies with WNV, YFV, DENV, JEV, and MVEV on sfRNA production following incomplete degradation of the viral genomic RNA by the cellular 5'-3' exoribonuclease 1 (XRN1), RNA structural elements involved in stalling XRN1 to generate sfRNA, and functions of sfRNA in modulating cellular mRNA decay and RNAi pathways as well as in modulating anti-viral type I interferon response. In addition, we also summarize data on the mechanisms of biogenesis of 3'UTR-derived KUN-miR-1 and its function in WNV replication in mosquito host, along with recent findings on a discovery of a second potential flaviviral miRNA vsRNA5, derived from the 3'UTR of DENV. This review thus summarizes the known mechanisms of generation and the functions of flaviviral 3'UTR-derived non-coding RNAs. PMID:25660582

  20. Dual miRNA Targeting Restricts Host Range and Attenuates Neurovirulence of Flaviviruses

    PubMed Central

    Tsetsarkin, Konstantin A.; Liu, Guangping; Kenney, Heather; Bustos-Arriaga, Jose; Hanson, Christopher T.; Whitehead, Stephen S.; Pletnev, Alexander G.

    2015-01-01

    Mosquito-borne flaviviruses are among the most significant arboviral pathogens worldwide. Vaccinations and mosquito population control programs remain the most reliable means for flavivirus disease prevention, and live attenuated viruses remain one of the most attractive flavivirus vaccine platforms. Some live attenuated viruses are capable of infecting principle mosquito vectors, as demonstrated in the laboratory, which in combination with their intrinsic genetic instability could potentially lead to a vaccine virus reversion back to wild-type in nature, followed by introduction and dissemination of potentially dangerous viral strains into new geographic locations. To mitigate this risk we developed a microRNA-targeting approach that selectively restricts replication of flavivirus in the mosquito host. Introduction of sequences complementary to a mosquito-specific mir-184 and mir-275 miRNAs individually or in combination into the 3’NCR and/or ORF region resulted in selective restriction of dengue type 4 virus (DEN4) replication in mosquito cell lines and adult Aedes mosquitos. Moreover a combined targeting of DEN4 genome with mosquito-specific and vertebrate CNS-specific mir-124 miRNA can silence viral replication in two evolutionally distant biological systems: mosquitoes and mouse brains. Thus, this approach can reinforce the safety of newly developed or existing vaccines for use in humans and could provide an additional level of biosafety for laboratories using viruses with altered pathogenic or transmissibility characteristics. PMID:25906260

  1. Structure and functionality in flavivirus NS-proteins: Perspectives for drug design

    PubMed Central

    Bollati, Michela; Alvarez, Karin; Assenberg, René; Baronti, Cécile; Canard, Bruno; Cook, Shelley; Coutard, Bruno; Decroly, Etienne; de Lamballerie, Xavier; Gould, Ernest A.; Grard, Gilda; Grimes, Jonathan M.; Hilgenfeld, Rolf; Jansson, Anna M.; Malet, Hélène; Mancini, Erika J.; Mastrangelo, Eloise; Mattevi, Andrea; Milani, Mario; Moureau, Grégory; Neyts, Johan; Owens, Raymond J.; Ren, Jingshan; Selisko, Barbara; Speroni, Silvia; Steuber, Holger; Stuart, David I.; Unge, Torsten; Bolognesi, Martino

    2010-01-01

    Flaviviridae are small enveloped viruses hosting a positive-sense single-stranded RNA genome. Besides yellow fever virus, a landmark case in the history of virology, members of the Flavivirus genus, such as West Nile virus and dengue virus, are increasingly gaining attention due to their re-emergence and incidence in different areas of the world. Additional environmental and demographic considerations suggest that novel or known flaviviruses will continue to emerge in the future. Nevertheless, up to few years ago flaviviruses were considered low interest candidates for drug design. At the start of the European Union VIZIER Project, in 2004, just two crystal structures of protein domains from the flaviviral replication machinery were known. Such pioneering studies, however, indicated the flaviviral replication complex as a promising target for the development of antiviral compounds. Here we review structural and functional aspects emerging from the characterization of two main components (NS3 and NS5 proteins) of the flavivirus replication complex. Most of the reviewed results were achieved within the European Union VIZIER Project, and cover topics that span from viral genomics to structural biology and inhibition mechanisms. The ultimate aim of the reported approaches is to shed light on the design and development of antiviral drug leads. PMID:19945487

  2. Flavivirus NS1 protein in infected host sera enhances viral acquisition by mosquitoes.

    PubMed

    Liu, Jianying; Liu, Yang; Nie, Kaixiao; Du, Senyan; Qiu, Jingjun; Pang, Xiaojing; Wang, Penghua; Cheng, Gong

    2016-01-01

    The arbovirus life cycle involves viral transfer between a vertebrate host and an arthropod vector, and acquisition of virus from an infected mammalian host by a vector is an essential step in this process. Here, we report that flavivirus nonstructural protein-1 (NS1), which is abundantly secreted into the serum of an infected host, plays a critical role in flavivirus acquisition by mosquitoes. The presence of dengue virus (DENV) and Japanese encephalitis virus NS1s in the blood of infected interferon-α and γ receptor-deficient mice (AG6) facilitated virus acquisition by their native mosquito vectors because the protein enabled the virus to overcome the immune barrier of the mosquito midgut. Active immunization of AG6 mice with a modified DENV NS1 reduced DENV acquisition by mosquitoes and protected mice against a lethal DENV challenge, suggesting that immunization with NS1 could reduce the number of virus-carrying mosquitoes as well as the incidence of flaviviral diseases. Our study demonstrates that flaviviruses utilize NS1 proteins produced during their vertebrate phases to enhance their acquisition by vectors, which might be a result of flavivirus evolution to adapt to multiple host environments. PMID:27562253

  3. Stress responses in flavivirus-infected cells: activation of unfolded protein response and autophagy

    PubMed Central

    Blázquez, Ana-Belén; Escribano-Romero, Estela; Merino-Ramos, Teresa; Saiz, Juan-Carlos; Martín-Acebes, Miguel A.

    2014-01-01

    The Flavivirus is a genus of RNA viruses that includes multiple long known human, animal, and zoonotic pathogens such as Dengue virus, yellow fever virus, West Nile virus, or Japanese encephalitis virus, as well as other less known viruses that represent potential threats for human and animal health such as Usutu or Zika viruses. Flavivirus replication is based on endoplasmic reticulum-derived structures. Membrane remodeling and accumulation of viral factors induce endoplasmic reticulum stress that results in activation of a cellular signaling response termed unfolded protein response (UPR), which can be modulated by the viruses for their own benefit. Concomitant with the activation of the UPR, an upregulation of the autophagic pathway in cells infected with different flaviviruses has also been described. This review addresses the current knowledge of the relationship between endoplasmic reticulum stress, UPR, and autophagy in flavivirus-infected cells and the growing evidences for an involvement of these cellular pathways in the replication and pathogenesis of these viruses. PMID:24917859

  4. Spectral variance of aeroacoustic data

    NASA Technical Reports Server (NTRS)

    Rao, K. V.; Preisser, J. S.

    1981-01-01

    An asymptotic technique for estimating the variance of power spectra is applied to aircraft flyover noise data. The results are compared with directly estimated variances and they are in reasonable agreement. The basic time series need not be Gaussian for asymptotic theory to apply. The asymptotic variance formulae can be useful tools both in the design and analysis phase of experiments of this type.

  5. Construction and characterization of recombinant flaviviruses bearing insertions between E and NS1 genes

    PubMed Central

    Bonaldo, Myrna C; Mello, Samanta M; Trindade, Gisela F; Rangel, Aymara A; Duarte, Adriana S; Oliveira, Prisciliana J; Freire, Marcos S; Kubelka, Claire F; Galler, Ricardo

    2007-01-01

    Background The yellow fever virus, a member of the genus Flavivirus, is an arthropod-borne pathogen causing severe disease in humans. The attenuated yellow fever 17D virus strain has been used for human vaccination for 70 years and has several characteristics that are desirable for the development of new, live attenuated vaccines. We described here a methodology to construct a viable, and immunogenic recombinant yellow fever 17D virus expressing a green fluorescent protein variant (EGFP). This approach took into account the presence of functional motifs and amino acid sequence conservation flanking the E and NS1 intergenic region to duplicate and fuse them to the exogenous gene and thereby allow the correct processing of the viral polyprotein precursor. Results YF 17D EGFP recombinant virus was grew in Vero cells and reached a peak titer of approximately 6.45 ± 0.4 log10 PFU/mL at 96 hours post-infection. Immunoprecipitation and confocal laser scanning microscopy demonstrated the expression of the EGFP, which was retained in the endoplasmic reticulum and not secreted from infected cells. The association with the ER compartment did not interfere with YF assembly, since the recombinant virus was fully competent to replicate and exit the cell. This virus was genetically stable up to the tenth serial passage in Vero cells. The recombinant virus was capable to elicit a neutralizing antibody response to YF and antibodies to EGFP as evidenced by an ELISA test. The applicability of this cloning strategy to clone gene foreign sequences in other flavivirus genomes was demonstrated by the construction of a chimeric recombinant YF 17D/DEN4 virus. Conclusion This system is likely to be useful for a broader live attenuated YF 17D virus-based vaccine development for human diseases. Moreover, insertion of foreign genes into the flavivirus genome may also allow in vivo studies on flavivirus cell and tissue tropism as well as cellular processes related to flavivirus infection. PMID

  6. Noncoding flavivirus RNA displays RNA interference suppressor activity in insect and Mammalian cells.

    PubMed

    Schnettler, Esther; Sterken, Mark G; Leung, Jason Y; Metz, Stefan W; Geertsema, Corinne; Goldbach, Rob W; Vlak, Just M; Kohl, Alain; Khromykh, Alexander A; Pijlman, Gorben P

    2012-12-01

    West Nile virus (WNV) and dengue virus (DENV) are highly pathogenic, mosquito-borne flaviviruses (family Flaviviridae) that cause severe disease and death in humans. WNV and DENV actively replicate in mosquitoes and human hosts and thus encounter different host immune responses. RNA interference (RNAi) is the predominant antiviral response against invading RNA viruses in insects and plants. As a countermeasure, plant and insect RNA viruses encode RNA silencing suppressor (RSS) proteins to block the generation/activity of small interfering RNA (siRNA). Enhanced flavivirus replication in mosquitoes depleted for RNAi factors suggests an important biological role for RNAi in restricting virus replication, but it has remained unclear whether or not flaviviruses counteract RNAi via expression of an RSS. First, we established that flaviviral RNA replication suppressed siRNA-induced gene silencing in WNV and DENV replicon-expressing cells. Next, we showed that none of the WNV encoded proteins displayed RSS activity in mammalian and insect cells and in plants by using robust RNAi suppressor assays. In contrast, we found that the 3'-untranslated region-derived RNA molecule known as subgenomic flavivirus RNA (sfRNA) efficiently suppressed siRNA- and miRNA-induced RNAi pathways in both mammalian and insect cells. We also showed that WNV sfRNA inhibits in vitro cleavage of double-stranded RNA by Dicer. The results of the present study suggest a novel role for sfRNA, i.e., as a nucleic acid-based regulator of RNAi pathways, a strategy that may be conserved among flaviviruses. PMID:23035235

  7. Noncoding Flavivirus RNA Displays RNA Interference Suppressor Activity in Insect and Mammalian Cells

    PubMed Central

    Schnettler, Esther; Sterken, Mark G.; Leung, Jason Y.; Metz, Stefan W.; Geertsema, Corinne; Goldbach, Rob W.; Vlak, Just M.; Kohl, Alain

    2012-01-01

    West Nile virus (WNV) and dengue virus (DENV) are highly pathogenic, mosquito-borne flaviviruses (family Flaviviridae) that cause severe disease and death in humans. WNV and DENV actively replicate in mosquitoes and human hosts and thus encounter different host immune responses. RNA interference (RNAi) is the predominant antiviral response against invading RNA viruses in insects and plants. As a countermeasure, plant and insect RNA viruses encode RNA silencing suppressor (RSS) proteins to block the generation/activity of small interfering RNA (siRNA). Enhanced flavivirus replication in mosquitoes depleted for RNAi factors suggests an important biological role for RNAi in restricting virus replication, but it has remained unclear whether or not flaviviruses counteract RNAi via expression of an RSS. First, we established that flaviviral RNA replication suppressed siRNA-induced gene silencing in WNV and DENV replicon-expressing cells. Next, we showed that none of the WNV encoded proteins displayed RSS activity in mammalian and insect cells and in plants by using robust RNAi suppressor assays. In contrast, we found that the 3′-untranslated region-derived RNA molecule known as subgenomic flavivirus RNA (sfRNA) efficiently suppressed siRNA- and miRNA-induced RNAi pathways in both mammalian and insect cells. We also showed that WNV sfRNA inhibits in vitro cleavage of double-stranded RNA by Dicer. The results of the present study suggest a novel role for sfRNA, i.e., as a nucleic acid-based regulator of RNAi pathways, a strategy that may be conserved among flaviviruses. PMID:23035235

  8. Decomposition of Variance for Spatial Cox Processes

    PubMed Central

    Jalilian, Abdollah; Guan, Yongtao; Waagepetersen, Rasmus

    2012-01-01

    Spatial Cox point processes is a natural framework for quantifying the various sources of variation governing the spatial distribution of rain forest trees. We introduce a general criterion for variance decomposition for spatial Cox processes and apply it to specific Cox process models with additive or log linear random intensity functions. We moreover consider a new and flexible class of pair correlation function models given in terms of normal variance mixture covariance functions. The proposed methodology is applied to point pattern data sets of locations of tropical rain forest trees. PMID:23599558

  9. Cosmology without cosmic variance

    SciTech Connect

    Bernstein, Gary M.; Cai, Yan -Chuan

    2011-10-01

    The growth of structures in the Universe is described by a function G that is predicted by the combination of the expansion history of the Universe and the laws of gravity within it. We examine the improvements in constraints on G that are available from the combination of a large-scale galaxy redshift survey with a weak gravitational lensing survey of background sources. We describe a new combination of such observations that in principle this yields a measure of the growth rate that is free of sample variance, i.e. the uncertainty in G can be reduced without bound by increasing the number of redshifts obtained within a finite survey volume. The addition of background weak lensing data to a redshift survey increases information on G by an amount equivalent to a 10-fold increase in the volume of a standard redshift-space distortion measurement - if the lensing signal can be measured to sub-per cent accuracy. This argues that a combined lensing and redshift survey over a common low-redshift volume of the Universe is a more powerful test of general relativity than an isolated redshift survey over larger volume at high redshift, especially as surveys begin to cover most of the available sky.

  10. Cosmology without cosmic variance

    DOE PAGESBeta

    Bernstein, Gary M.; Cai, Yan -Chuan

    2011-10-01

    The growth of structures in the Universe is described by a function G that is predicted by the combination of the expansion history of the Universe and the laws of gravity within it. We examine the improvements in constraints on G that are available from the combination of a large-scale galaxy redshift survey with a weak gravitational lensing survey of background sources. We describe a new combination of such observations that in principle this yields a measure of the growth rate that is free of sample variance, i.e. the uncertainty in G can be reduced without bound by increasing themore » number of redshifts obtained within a finite survey volume. The addition of background weak lensing data to a redshift survey increases information on G by an amount equivalent to a 10-fold increase in the volume of a standard redshift-space distortion measurement - if the lensing signal can be measured to sub-per cent accuracy. This argues that a combined lensing and redshift survey over a common low-redshift volume of the Universe is a more powerful test of general relativity than an isolated redshift survey over larger volume at high redshift, especially as surveys begin to cover most of the available sky.« less

  11. Variances and Covariances of Kendall's Tau and Their Estimation.

    ERIC Educational Resources Information Center

    Cliff, Norman; Charlin, Ventura

    1991-01-01

    Variance formulas of H. E. Daniels and M. G. Kendall (1947) are generalized to allow for the presence of ties and variance of the sample tau correlation. Applications of these generalized formulas are discussed and illustrated using data from a 1965 study of contraceptive use in 15 developing countries. (SLD)

  12. A Computer Program to Determine Reliability Using Analysis of Variance

    ERIC Educational Resources Information Center

    Burns, Edward

    1976-01-01

    A computer program, written in Fortran IV, is described which assesses reliability by using analysis of variance. It produces a complete analysis of variance table in addition to reliability coefficients for unadjusted and adjusted data as well as the intraclass correlation for m subjects and n items. (Author)

  13. Blood meal analysis, flavivirus screening, and influence of meteorological variables on the dynamics of potential mosquito vectors of West Nile virus in northern Italy.

    PubMed

    Roiz, David; Vazquez, Ana; Rosà, Roberto; Muñoz, Joaquin; Arnoldi, Daniele; Rosso, Fausta; Figuerola, Jordi; Tenorio, Antonio; Rizzoli, Annapaola

    2012-06-01

    An extended area of northern Italy has experienced several West Nile virus (WNV) outbreaks and the emergence of Usutu virus (USUV) during previous years. Our aim was to study some of the factors that could explain disease patterns in the Trentino region, where circulation was detected in human sera and sentinel chickens, but no human or equine cases were reported. We collected Culex species (Diptera: Culicidae) in peridomestic environments. The collected specimens were analyzed for feeding behavior, the influence of temperature and rainfall on the abundance of mosquitoes, and the occurrence of flaviviruses. Analysis of blood meals showed that Culex pipiens fed mainly on blackbirds (Turdus merula) and house sparrows (Passer domesticus), while Culex hortensis fed strictly on lizards. The abundance of Cx. pipiens females correlated positively with mean temperature and negatively with rainfall (one to four weeks before capture). This negative relationship could be due to the direct effect of the flushing of habitats together with an indirect effect of oviposition repellency. The mean weekly temperature influenced the abundance of Cx. hortensis. No flaviviruses were detected in the analyzed Culex mosquitoes. These data suggest a silent cycle at low enzootic transmission levels in the area. Furthermore, we present the first contribution to understanding the transmission role of Cx. pipiens mosquitoes in Italy by identifying vertebrate hosts to species level. PMID:22548533

  14. Budget variance analysis using RVUs.

    PubMed

    Berlin, M F; Budzynski, M R

    1998-01-01

    This article details the use of the variance analysis as management tool to evaluate the financial health of the practice. A common financial tool for administrators has been a simple calculation measuring the difference between actual financials vs. budget financials. Standard cost accounting provides a methodology known as variance analysis to better understand the actual vs. budgeted financial streams. The standard variance analysis has been modified by applying relative value units (RVUs) as standards for the practice. PMID:10387247

  15. Evidence for ribosomal frameshifting and a novel overlapping gene in the genomes of insect-specific flaviviruses

    SciTech Connect

    Firth, Andrew E.; Blitvich, Bradley J.; Wills, Norma M.; Miller, Cathy L.; Atkins, John F.

    2010-03-30

    Flaviviruses have a positive-sense, single-stranded RNA genome of approx11 kb, encoding a large polyprotein that is cleaved to produce approx10 mature proteins. Cell fusing agent virus, Kamiti River virus, Culex flavivirus and several recently discovered flaviviruses have no known vertebrate host and apparently infect only insects. We present compelling bioinformatic evidence for a 253-295 codon overlapping gene (designated fifo) conserved throughout these insect-specific flaviviruses and immunofluorescent detection of its product. Fifo overlaps the NS2A/NS2B coding sequence in the - 1/+ 2 reading frame and is most likely expressed as a trans-frame fusion protein via ribosomal frameshifting at a conserved GGAUUUY slippery heptanucleotide with 3'-adjacent RNA secondary structure (which stimulates efficient frameshifting in vitro). The discovery bears striking parallels to the recently discovered ribosomal frameshifting site in the NS2A coding sequence of the Japanese encephalitis serogroup of flaviviruses and suggests that programmed ribosomal frameshifting may be more widespread in flaviviruses than currently realized.

  16. A game of numbers: the stoichiometry of antibody-mediated neutralization of flavivirus infection

    PubMed Central

    Pierson, Theodore C.; Diamond, Michael S.

    2016-01-01

    The humoral response contributes to the protection against viral pathogens. Although antibodies have the potential to inhibit viral infections via several mechanisms, an ability to neutralize viruses directly may be particularly important. Neutralizing antibody titers are commonly used as predictors of protection from infection, especially in the context of vaccine responses and immunity. Despite the simplicity of the concept, how antibody binding results in virus inactivation is incompletely understood despite decades of research. Flaviviruses have been an attractive system in which to seek a structural and quantitative understanding of how antibody interactions with virions modulate infection because of the contribution of antibodies to both protection and pathogenesis. This review will present a stoichiometric model of antibody-mediated neutralization of flaviviruses and discuss how these concepts can inform the development of vaccines and antibody-based therapeutics. PMID:25595803

  17. Zoonotic encephalitides caused by arboviruses: transmission and epidemiology of alphaviruses and flaviviruses.

    PubMed

    Go, Yun Young; Balasuriya, Udeni B R; Lee, Chong-Kyo

    2014-01-01

    In this review, we mainly focus on zoonotic encephalitides caused by arthropod-borne viruses (arboviruses) of the families Flaviviridae (genus Flavivirus) and Togaviridae (genus Alphavirus) that are important in both humans and domestic animals. Specifically, we will focus on alphaviruses (Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus) and flaviviruses (Japanese encephalitis virus and West Nile virus). Most of these viruses were originally found in tropical regions such as Africa and South America or in some regions in Asia. However, they have dispersed widely and currently cause diseases around the world. Global warming, increasing urbanization and population size in tropical regions, faster transportation and rapid spread of arthropod vectors contribute in continuous spreading of arboviruses into new geographic areas causing reemerging or resurging diseases. Most of the reemerging arboviruses also have emerged as zoonotic disease agents and created major public health issues and disease epidemics. PMID:24427764

  18. Flavivirus infection from mosquitoes in vitro reveals cell entry at the plasma membrane

    SciTech Connect

    Vancini, Ricardo; Kramer, Laura D.; Ribeiro, Mariana; Hernandez, Raquel; Brown, Dennis

    2013-01-20

    Dengue and West Nile viruses are enveloped RNA viruses that belong to genus Flavivirus (family Flaviviridae) and are considered important mosquito-borne viral pathogenic agents worldwide. A potential target for intervention strategies is the virus cell entry mechanism. Previous studies of flavivirus entry have focused on the effects of biochemical and molecular inhibitors on viral entry leading to controversial conclusions suggesting that the process is dependent upon endocytosis and low pH mediated membrane fusion. In this study we analyzed the early events in the infection process by means of electron microscopy and immuno-gold labeling of viral particles during cell entry, and used as a new approach for infecting cells with viruses obtained directly from mosquitoes. The results show that Dengue and West Nile viruses may infect cells by a mechanism that involves direct penetration of the host cell plasma membrane as proposed for alphaviruses.

  19. Rapid Evolutionary Dynamics of Structural Disorder as a Potential Driving Force for Biological Divergence in Flaviviruses

    PubMed Central

    Ortiz, Juan F.; MacDonald, Madolyn L.; Masterson, Patrick; Uversky, Vladimir N.; Siltberg-Liberles, Jessica

    2013-01-01

    Protein structure is commonly regarded to be conserved and to dictate function. Most proteins rely on conformational flexibility to some degree. Are regions that convey conformational flexibility conserved over evolutionary time? Can changes in conformational flexibility alter protein function? Here, the evolutionary dynamics of structurally ordered and disordered (flexible) regions are investigated genome-wide in flaviviruses, revealing that the amount and location of structural disorder fluctuates highly among related proteins. Some regions are prone to shift between structured and flexible states. Increased evolutionary dynamics of structural disorder is observed for some lineages but not in others. Lineage-specific transitions of this kind could alter the conformational ensemble accessible to the same protein in different species, causing a functional change, even if the predominant function remains conserved. Thus, rapid evolutionary dynamics of structural disorder is a potential driving force for phenotypic divergence among flaviviruses. PMID:23418179

  20. Detection and quantification of flavivirus NS5 methyl-transferase activities.

    PubMed

    Lim, Siew Pheng; Bodenreider, Christophe; Shi, Pei-Yong

    2013-01-01

    Flavivirus NS5 is the most conserved protein amongst the flavivirus proteins and is an essential enzyme for viral mRNA capping and replication. It encodes a methyl-transferase (MTase) domain at its N-terminal region which carries out sequential N7 and 2'-O methylation, resulting in the formation of the cap1 structure on its viral RNA genome. Two key methods have been established to measure these activities in vitro: thin-layer chromatography (TLC) and scintillation proximity assays (SPA). TLC offers the advantage of direct visualization of the amounts and types of cap structures formed whilst the SPA assay is more sensitive and quantitative. It is also amenable to high-throughput compound screening. The drawback of both assays is the need for radioisotope usage. We further describe the adaptation of a nonradioactive immune-competitive fluorescence polarization assay for detection of dengue virus MTase activity. PMID:23821274

  1. Zoonotic encephalitides caused by arboviruses: transmission and epidemiology of alphaviruses and flaviviruses

    PubMed Central

    Balasuriya, Udeni B. R.; Lee, Chong-kyo

    2014-01-01

    In this review, we mainly focus on zoonotic encephalitides caused by arthropod-borne viruses (arboviruses) of the families Flaviviridae (genus Flavivirus) and Togaviridae (genus Alphavirus) that are important in both humans and domestic animals. Specifically, we will focus on alphaviruses (Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus) and flaviviruses (Japanese encephalitis virus and West Nile virus). Most of these viruses were originally found in tropical regions such as Africa and South America or in some regions in Asia. However, they have dispersed widely and currently cause diseases around the world. Global warming, increasing urbanization and population size in tropical regions, faster transportation and rapid spread of arthropod vectors contribute in continuous spreading of arboviruses into new geographic areas causing reemerging or resurging diseases. Most of the reemerging arboviruses also have emerged as zoonotic disease agents and created major public health issues and disease epidemics. PMID:24427764

  2. Nonstructural Proteins Are Preferential Positive Selection Targets in Zika Virus and Related Flaviviruses.

    PubMed

    Sironi, Manuela; Forni, Diego; Clerici, Mario; Cagliani, Rachele

    2016-09-01

    The Flavivirus genus comprises several human pathogens such as dengue virus (DENV), Japanese encephalitis virus (JEV), and Zika virus (ZIKV). Although ZIKV usually causes mild symptoms, growing evidence is linking it to congenital birth defects and to increased risk of Guillain-Barré syndrome. ZIKV encodes a polyprotein that is processed to produce three structural and seven nonstructural (NS) proteins. We investigated the evolution of the viral polyprotein in ZIKV and in related flaviviruses (DENV, Spondweni virus, and Kedougou virus). After accounting for saturation issues, alignment uncertainties, and recombination, we found evidence of episodic positive selection on the branch that separates DENV from the other flaviviruses. NS1 emerged as the major selection target, and selected sites were located in immune epitopes or in functionally important protein regions. Three of these sites are located in an NS1 region that interacts with structural proteins and is essential for virion biogenesis. Analysis of the more recent evolutionary history of ZIKV lineages indicated that positive selection acted on NS5 and NS4B, this latter representing the preferential target. All selected sites were located in the N-terminal portion of NS4B, which inhibits interferon response. One of the positively selected sites (26M/I/T/V) in ZIKV also represents a selection target in sylvatic DENV2 isolates, and a nearby residue evolves adaptively in JEV. Two additional positively selected sites are within a protein region that interacts with host (e.g. STING) and viral (i.e. NS1, NS4A) proteins. Notably, mutations in the NS4B region of other flaviviruses modulate neurovirulence and/or neuroinvasiveness. These results suggest that the positively selected sites we identified modulate viral replication and contribute to immune evasion. These sites should be prioritized in future experimental studies. However, analyses herein detected no selective events associated to the spread of the Asian

  3. Culex Flavivirus and West Nile Virus Mosquito Coinfection and Positive Ecological Association in Chicago, United States

    PubMed Central

    Newman, Christina M.; Cerutti, Francesco; Anderson, Tavis K.; Hamer, Gabriel L.; Walker, Edward D.; Kitron, Uriel D.; Ruiz, Marilyn O.; Brawn, Jeffery D.

    2011-01-01

    Abstract Culex flavivirus (CxFV) is an insect-specific flavivirus globally distributed in mosquitoes of the genus Culex. CxFV was positively associated with West Nile virus (WNV) infection in a case–control study of 268 mosquito pools from an endemic focus of WNV transmission in Chicago, United States. Specifically, WNV-positive Culex mosquito pools were four times more likely also to be infected with CxFV than were spatiotemporally matched WNV-negative pools. In addition, mosquito pools from residential sites characterized by dense housing and impermeable surfaces were more likely to be infected with CxFV than were pools from nearby urban green spaces. Further, 6/15 (40%) WNV-positive individual mosquitoes were also CxFV positive, demonstrating that both viruses can coinfect mosquitoes in nature. Phylogenetic analysis of CxFV from Chicago demonstrated a pattern similar to WNV, consisting of low global viral diversity and lack of geographic clustering. These results illustrate a positive ecological association between CxFV and WNV, and that coinfection of individual mosquitoes can occur naturally in areas of high flaviviral transmission. These conclusions represent a challenge to the hypothesis of super-infection exclusion in the CxFV/WNV system, whereby an established infection with one virus may interfere with secondary viral infection with a similar virus. This study suggests that infection with insect-specific flaviviruses such as CxFV may not exclude secondary infection with genetically distinct flaviviruses such as WNV, and that both viruses can naturally coinfect mosquitoes that are epidemic bridge vectors of WNV to humans. PMID:21254845

  4. Physico-chemical requirements and kinetics of membrane fusion of flavivirus-like particles.

    PubMed

    Espósito, Danillo L A; Nguyen, Jennifer B; DeWitt, David C; Rhoades, Elizabeth; Modis, Yorgo

    2015-07-01

    Flaviviruses deliver their RNA genome into the host-cell cytoplasm by fusing their lipid envelope with a cellular membrane. Expression of the flavivirus pre-membrane and envelope glycoprotein genes in the absence of other viral genes results in the spontaneous assembly and secretion of virus-like particles (VLPs) with membrane fusion activity. Here, we examined the physico-chemical requirements for membrane fusion of VLPs from West Nile and Japanese encephalitis viruses. In a bulk fusion assay, optimal hemifusion (or lipid mixing) efficiencies were observed at 37 °C. Fusion efficiency increased with decreasing pH; half-maximal hemifusion was attained at pH 5.6. The anionic lipids bis(monoacylglycero)phosphate and phosphatidylinositol-3-phosphate, when present in the target membrane, significantly enhanced fusion efficiency, consistent with the emerging model that flaviviruses fuse with intermediate-to-late endosomal compartments, where these lipids are most abundant. In a single-particle fusion assay, VLPs catalysed membrane hemifusion, tracked as lipid mixing with the cellular membrane, on a timescale of 7-20 s after acidification. Lipid mixing kinetics suggest that hemifusion is a kinetically complex, multistep process. PMID:25740960

  5. Serological Investigations of Flavivirus Prevalence in Khammouane Province, Lao People's Democratic Republic, 2007–2008

    PubMed Central

    Hiscox, Alexandra; Winter, Christian H.; Vongphrachanh, Phengta; Sisouk, Thongchanh; Somoulay, Virasack; Phompida, Samlane; Kaul, Surinder; Sananikhom, Pany; Yen, Nguyen Thi; Paul, Richard E.; Brey, Paul; Bryant, Juliet E.

    2010-01-01

    A large-scale cross-sectional seroprevalence study of dengue (DEN) and Japanese encephalitis (JE) was conducted in Khammouane province, Lao PDR, as part of the initial baseline health impact assessment of the Nam Theun 2 hydroelectric dam construction project. Health surveys were performed between May 2007 and February 2008 with serum samples collected from healthy individuals involved in the resettlement program of 16 villages (total surveyed population 4,369). Hemagglutination inhibition assay using flavivirus antigens (DENV1, DENV3, and JEV) performed on 1,708 plasma specimens revealed 30.4% (519) cross-reactive positives, and 10% (172) and 1.3% (22) positives to JEV or DENV, respectively. Entomological surveys conducted during the rainy season of 2008 indicated the presence of competent flavivirus vectors (Culex vishnui group and Aedes albopictus), although Aedes aegypti was not found. Continued surveillance and investigation is warranted to assess the clinical disease burden of flaviviruses in this area that is undergoing rapid ecological and demographic change. PMID:21036856

  6. Viral Membrane Fusion and Nucleocapsid Delivery into the Cytoplasm are Distinct Events in Some Flaviviruses

    PubMed Central

    Nour, Adel M.; Li, Yue; Wolenski, Joseph; Modis, Yorgo

    2013-01-01

    Flaviviruses deliver their genome into the cell by fusing the viral lipid membrane to an endosomal membrane. The sequence and kinetics of the steps required for nucleocapsid delivery into the cytoplasm remain unclear. Here we dissect the cell entry pathway of virions and virus-like particles from two flaviviruses using single-particle tracking in live cells, a biochemical membrane fusion assay and virus infectivity assays. We show that the virus particles fuse with a small endosomal compartment in which the nucleocapsid remains trapped for several minutes. Endosomal maturation inhibitors inhibit infectivity but not membrane fusion. We propose a flavivirus cell entry mechanism in which the virus particles fuse preferentially with small endosomal carrier vesicles and depend on back-fusion of the vesicles with the late endosomal membrane to deliver the nucleocapsid into the cytoplasm. Virus entry modulates intracellular calcium release and phosphatidylinositol-3-phosphate kinase signaling. Moreover, the broadly cross-reactive therapeutic antibody scFv11 binds to virus-like particles and inhibits fusion. PMID:24039574

  7. Vector Competence in West African Aedes aegypti Is Flavivirus Species and Genotype Dependent

    PubMed Central

    Dickson, Laura B.; Sanchez-Vargas, Irma; Sylla, Massamba; Fleming, Karen; Black, William C.

    2014-01-01

    Background Vector competence of Aedes aegypti mosquitoes is a quantitative genetic trait that varies among geographic locations and among different flavivirus species and genotypes within species. The subspecies Ae. aegypti formosus, found mostly in sub-Saharan Africa, is considered to be refractory to both dengue (DENV) and yellow fever viruses (YFV) compared to the more globally distributed Ae. aegypti aegypti. Within Senegal, vector competence varies with collection site and DENV-2 viral isolate, but knowledge about the interaction of West African Ae. aegypti with different flaviviruses is lacking. The current study utilizes low passage isolates of dengue-2 (DENV-2-75505 sylvatic genotype) and yellow fever (YFV BA-55 -West African Genotype I, or YFV DAK 1279-West African Genotype II) from West Africa and field derived Ae. aegypti collected throughout Senegal to determine whether vector competence is flavivirus or virus genotype dependent. Methodology/Principal Findings Eight collections of 20–30 mosquitoes from different sites were fed a bloodmeal containing either DENV-2 or either isolate of YFV. Midgut and disseminated infection phenotypes were determined 14 days post infection. Collections varied significantly in the rate and intensity of midgut and disseminated infection among the three viruses. Conclusions/Significance Overall, vector competence was dependent upon both viral and vector strains. Importantly, contrary to previous studies, sylvatic collections of Ae. aegypti showed high levels of disseminated infection for local isolates of both DENV-2 and YFV. PMID:25275366

  8. Physico-chemical requirements and kinetics of membrane fusion of flavivirus-like particles

    PubMed Central

    Espósito, Danillo L. A.; Nguyen, Jennifer B.; DeWitt, David C.; Rhoades, Elizabeth

    2015-01-01

    Flaviviruses deliver their RNA genome into the host-cell cytoplasm by fusing their lipid envelope with a cellular membrane. Expression of the flavivirus pre-membrane and envelope glycoprotein genes in the absence of other viral genes results in the spontaneous assembly and secretion of virus-like particles (VLPs) with membrane fusion activity. Here, we examined the physico-chemical requirements for membrane fusion of VLPs from West Nile and Japanese encephalitis viruses. In a bulk fusion assay, optimal hemifusion (or lipid mixing) efficiencies were observed at 37 °C. Fusion efficiency increased with decreasing pH; half-maximal hemifusion was attained at pH 5.6. The anionic lipids bis(monoacylglycero)phosphate and phosphatidylinositol-3-phosphate, when present in the target membrane, significantly enhanced fusion efficiency, consistent with the emerging model that flaviviruses fuse with intermediate-to-late endosomal compartments, where these lipids are most abundant. In a single-particle fusion assay, VLPs catalysed membrane hemifusion, tracked as lipid mixing with the cellular membrane, on a timescale of 7–20 s after acidification. Lipid mixing kinetics suggest that hemifusion is a kinetically complex, multistep process. PMID:25740960

  9. Unique Requirement for ESCRT Factors in Flavivirus Particle Formation on the Endoplasmic Reticulum.

    PubMed

    Tabata, Keisuke; Arimoto, Masaru; Arakawa, Masashi; Nara, Atsuki; Saito, Kazunobu; Omori, Hiroko; Arai, Arisa; Ishikawa, Tomohiro; Konishi, Eiji; Suzuki, Ryosuke; Matsuura, Yoshiharu; Morita, Eiji

    2016-08-30

    Flavivirus infection induces endoplasmic reticulum (ER) membrane rearrangements to generate a compartment for replication of the viral genome and assembly of viral particles. Using quantitative mass spectrometry, we identified several ESCRT (endosomal sorting complex required for transport) proteins that are recruited to sites of virus replication on the ER. Systematic small interfering RNA (siRNA) screening revealed that release of both dengue virus and Japanese encephalitis virus was dramatically decreased by single depletion of TSG101 or co-depletion of specific combinations of ESCRT-III proteins, resulting in ≥1,000-fold titer reductions. By contrast, release was unaffected by depletion of some core ESCRTs, including VPS4. Reintroduction of ESCRT proteins to siRNA-depleted cells revealed interactions among ESCRT proteins that are crucial for flavivirus budding. Electron-microscopy studies revealed that the CHMP2 and CHMP4 proteins function directly in membrane deformation at the ER. Thus, a unique and specific subset of ESCRT contributes to ER membrane biogenesis during flavivirus infection. PMID:27545892

  10. 3',5'Di-O-trityluridine inhibits in vitro flavivirus replication.

    PubMed

    De Burghgraeve, Tine; Selisko, Barbara; Kaptein, Suzanne; Chatelain, Grégory; Leyssen, Pieter; Debing, Yannick; Jacobs, Michael; Van Aerschot, Arthur; Canard, Bruno; Neyts, Johan

    2013-05-01

    The dengue fever virus (DENV) and the yellow fever virus (YFV) are members of the genus flavivirus in the family Flaviviridae. An estimated 50-100 million cases of DENV infections occur each year and approximately half a million patients require hospitalization. There is no vaccine or effective antiviral treatment available. There is an urgent need for potent and safe inhibitors of DENV replication; ideally such compounds should have broad-spectrum activity against flaviviruses. We here report on the in vitro activity of 3',5'di-O-trityluridine on flavivirus replication. The compound results in a dose-dependent inhibition of (i) DENV- and YFV-induced cytopathic effect (CPE) (EC₅₀ values in the low micromolar range for the 4 DENV serotypes), (ii) RNA replication (DENV-2 EC₅₀=1.5 μM; YFV-17D EC₅₀=0.83 μM) and (iii) viral antigen production. Antiviral activity was also demonstrated in DENV subgenomic replicons (which do not encode the structural viral proteins) (EC₅₀=2.3 μM), indicating that the compound inhibits intracellular events of the viral replication cycle. Preliminary data indicate that the molecule may inhibit the viral RNA-dependent RNA polymerase. PMID:23470860

  11. Dominance Genetic Variance for Traits Under Directional Selection in Drosophila serrata

    PubMed Central

    Sztepanacz, Jacqueline L.; Blows, Mark W.

    2015-01-01

    In contrast to our growing understanding of patterns of additive genetic variance in single- and multi-trait combinations, the relative contribution of nonadditive genetic variance, particularly dominance variance, to multivariate phenotypes is largely unknown. While mechanisms for the evolution of dominance genetic variance have been, and to some degree remain, subject to debate, the pervasiveness of dominance is widely recognized and may play a key role in several evolutionary processes. Theoretical and empirical evidence suggests that the contribution of dominance variance to phenotypic variance may increase with the correlation between a trait and fitness; however, direct tests of this hypothesis are few. Using a multigenerational breeding design in an unmanipulated population of Drosophila serrata, we estimated additive and dominance genetic covariance matrices for multivariate wing-shape phenotypes, together with a comprehensive measure of fitness, to determine whether there is an association between directional selection and dominance variance. Fitness, a trait unequivocally under directional selection, had no detectable additive genetic variance, but significant dominance genetic variance contributing 32% of the phenotypic variance. For single and multivariate morphological traits, however, no relationship was observed between trait–fitness correlations and dominance variance. A similar proportion of additive and dominance variance was found to contribute to phenotypic variance for single traits, and double the amount of additive compared to dominance variance was found for the multivariate trait combination under directional selection. These data suggest that for many fitness components a positive association between directional selection and dominance genetic variance may not be expected. PMID:25783700

  12. Dominance genetic variance for traits under directional selection in Drosophila serrata.

    PubMed

    Sztepanacz, Jacqueline L; Blows, Mark W

    2015-05-01

    In contrast to our growing understanding of patterns of additive genetic variance in single- and multi-trait combinations, the relative contribution of nonadditive genetic variance, particularly dominance variance, to multivariate phenotypes is largely unknown. While mechanisms for the evolution of dominance genetic variance have been, and to some degree remain, subject to debate, the pervasiveness of dominance is widely recognized and may play a key role in several evolutionary processes. Theoretical and empirical evidence suggests that the contribution of dominance variance to phenotypic variance may increase with the correlation between a trait and fitness; however, direct tests of this hypothesis are few. Using a multigenerational breeding design in an unmanipulated population of Drosophila serrata, we estimated additive and dominance genetic covariance matrices for multivariate wing-shape phenotypes, together with a comprehensive measure of fitness, to determine whether there is an association between directional selection and dominance variance. Fitness, a trait unequivocally under directional selection, had no detectable additive genetic variance, but significant dominance genetic variance contributing 32% of the phenotypic variance. For single and multivariate morphological traits, however, no relationship was observed between trait-fitness correlations and dominance variance. A similar proportion of additive and dominance variance was found to contribute to phenotypic variance for single traits, and double the amount of additive compared to dominance variance was found for the multivariate trait combination under directional selection. These data suggest that for many fitness components a positive association between directional selection and dominance genetic variance may not be expected. PMID:25783700

  13. Tissue-specific transcription profile of cytokine and chemokine genes associated with flavivirus control and non-lethal neuropathogenesis in rabbits.

    PubMed

    Suen, Willy W; Uddin, Muhammad Jasim; Prow, Natalie A; Bowen, Richard A; Hall, Roy A; Bielefeldt-Ohmann, Helle

    2016-07-01

    We previously showed that New Zealand White (NZWRs) and cottontail rabbits (CTRs) are a suitable model for studying immune mechanisms behind virus control and non-lethal neuropathogenesis associated with West Nile virus (WNV) and Murray Valley encephalitis virus (MVEV) infections. In the current study, we observed that MVEV infection induced high IFNα, TNFα, IL6, and CXCL10 transcript levels in the brains of weanling NZWRs, unlike infection with the less virulent WNVNSW2011. These transcript levels also correlated with encephalitis severity. Widespread STAT1 protein expression in brain with moderate neuropathology suggests that IFN-I signaling is crucial for limiting neural infection and mediating non-lethal neuropathogenesis. Unlike NZWRs, CTRs limit neuroinvasion without upregulation of many cytokine/chemokine transcripts, suggesting a species-dependent virus control mechanism. However, the common IFNγ, TNFα and IL6 transcript upregulation in specific lymphoid organs suggest some conserved elements in the response against flaviviruses, unique to all rabbits. PMID:27061052

  14. Saturation of number variance in embedded random-matrix ensembles

    NASA Astrophysics Data System (ADS)

    Prakash, Ravi; Pandey, Akhilesh

    2016-05-01

    We study fluctuation properties of embedded random matrix ensembles of noninteracting particles. For ensemble of two noninteracting particle systems, we find that unlike the spectra of classical random matrices, correlation functions are nonstationary. In the locally stationary region of spectra, we study the number variance and the spacing distributions. The spacing distributions follow the Poisson statistics, which is a key behavior of uncorrelated spectra. The number variance varies linearly as in the Poisson case for short correlation lengths but a kind of regularization occurs for large correlation lengths, and the number variance approaches saturation values. These results are known in the study of integrable systems but are being demonstrated for the first time in random matrix theory. We conjecture that the interacting particle cases, which exhibit the characteristics of classical random matrices for short correlation lengths, will also show saturation effects for large correlation lengths.

  15. A Broadly Flavivirus Cross-Neutralizing Monoclonal Antibody that Recognizes a Novel Epitope within the Fusion Loop of E Protein

    PubMed Central

    Jiang, Tao; Wang, Hua-Jing; Yang, Hai-ou; Tan, Weng-Long; Liu, Ran; Yu, Man; Ge, Bao-Xue; Zhu, Qing-Yu; Qin, E-De; Guo, Ya-Jun; Qin, Cheng-Feng

    2011-01-01

    Flaviviruses are a group of human pathogenic, enveloped RNA viruses that includes dengue (DENV), yellow fever (YFV), West Nile (WNV), and Japanese encephalitis (JEV) viruses. Cross-reactive antibodies against Flavivirus have been described, but most of them are generally weakly neutralizing. In this study, a novel monoclonal antibody, designated mAb 2A10G6, was determined to have broad cross-reactivity with DENV 1–4, YFV, WNV, JEV, and TBEV. Phage-display biopanning and structure modeling mapped 2A10G6 to a new epitope within the highly conserved flavivirus fusion loop peptide, the 98DRXW101 motif. Moreover, in vitro and in vivo experiments demonstrated that 2A10G6 potently neutralizes DENV 1–4, YFV, and WNV and confers protection from lethal challenge with DENV 1–4 and WNV in murine model. Furthermore, functional studies revealed that 2A10G6 blocks infection at a step after viral attachment. These results define a novel broadly flavivirus cross-reactive mAb with highly neutralizing activity that can be further developed as a therapeutic agent against severe flavivirus infections in humans. PMID:21264311

  16. The Impact of Prior Flavivirus Infections on the Development of Type 2 Diabetes Among the Indigenous Australians.

    PubMed

    Sorenson, Alanna; Owens, Leigh; Caltabiano, Marie; Cadet-James, Yvonne; Hall, Roy; Govan, Brenda; Clancy, Paula

    2016-08-01

    It is estimated that 5% of Australians over the age of 18 have diabetes, with the number of new cases increasing every year. Type 2 diabetes (T2D) also represents a significant disease burden in the Australian indigenous population, where prevalence is three times greater than that of non-indigenous Australians. Prevalence of T2D has been found to be higher in rural and remote indigenous Australian populations compared with urban indigenous Australian populations. Several studies have also found that body mass index and waist circumference are not appropriate for the prediction of T2D risk in indigenous Australians. Regional and remote areas of Australia are endemic for a variety of mosquito-borne flaviviruses. Studies that have investigated seroprevalence of flaviviruses in remote aboriginal communities have found high proportions of seroconversion. The family Flaviviridae comprises several genera of viruses with non-segmented single-stranded positive sense RNA genomes, and includes the flaviviruses and hepaciviruses. Hepatitis C virus (HCV) has been shown to be associated with insulin resistance and subsequent development of T2D. Flaviviruses and HCV possess conserved proteins and subgenomic RNA structures that may play similar roles in the development of insulin resistance. Although dietary and lifestyle factors are associated with increased risk of developing T2D, the impact of infectious diseases such as arboviruses has not been assessed. Flaviviruses circulating in indigenous Australian communities may play a significant role in inducing glucose intolerance and exacerbating T2D. PMID:27001762

  17. Differential salivary gland transcript expression profile in Ixodes scapularis nymphs upon feeding or flavivirus infection

    PubMed Central

    McNally, Kristin L.; Mitzel, Dana N.; Anderson, Jennifer M.; Ribeiro, José M. C.; Valenzuela, Jesus G.; Myers, Timothy G.; Godinez, Alvaro; Wolfinbarger, James B.; Best, Sonja M.; Bloom, Marshall E.

    2011-01-01

    Ixodid ticks are vectors of human diseases such as Lyme disease, babesiosis, anaplasmosis, and tick-borne encephalitis. These diseases cause significant morbidity and mortality worldwide and are transmitted to humans during tick feeding. The tick-host-pathogen interface is a complex environment where host responses are modulated by the molecules in tick saliva to enable the acquisition of a blood meal. Disruption of host responses at the site of the tick bite may also provide an advantage for pathogens to survive and replicate. Thus, the molecules in tick saliva not only aid the tick in securing a nutrient-rich blood meal, but can also enhance the transmission and acquisition of pathogens. To investigate the effect of feeding and flavivirus infection on the salivary gland transcript expression profile in ticks, a first-generation microarray was developed using ESTs from a cDNA library derived from Ixodes scapularis salivary glands. When the salivary gland transcript profile in ticks feeding over the course of 3 days was compared to that in unfed ticks, a dramatic increase in transcripts related to metabolism was observed. Specifically, 578 transcripts were up-regulated compared to 151 down-regulated transcripts in fed ticks. When specific time points post attachment were analyzed, a temporal pattern of gene expression was observed. When Langat virus-infected ticks were compared to mock-infected ticks, transcript expression changes were observed at all 3 days of feeding. Differentially regulated transcripts include putative secreted proteins, lipocalins, Kunitz domain-containing proteins, anti-microbial peptides, and transcripts of unknown function. These studies identify salivary gland transcripts that are differentially regulated during feeding or in the context of flavivirus infection in Ixodes scapularis nymphs, a medically important disease vector. Further analysis of these transcripts may identify salivary factors that affect the transmission or replication of

  18. Differential salivary gland transcript expression profile in Ixodes scapularis nymphs upon feeding or flavivirus infection.

    PubMed

    McNally, Kristin L; Mitzel, Dana N; Anderson, Jennifer M; Ribeiro, José M C; Valenzuela, Jesus G; Myers, Timothy G; Godinez, Alvaro; Wolfinbarger, James B; Best, Sonja M; Bloom, Marshall E

    2012-02-01

    Ixodid ticks are vectors of human diseases such as Lyme disease, babesiosis, anaplasmosis, and tick-borne encephalitis. These diseases cause significant morbidity and mortality worldwide and are transmitted to humans during tick feeding. The tick-host-pathogen interface is a complex environment where host responses are modulated by the molecules in tick saliva to enable the acquisition of a blood meal. Disruption of host responses at the site of the tick bite may also provide an advantage for pathogens to survive and replicate. Thus, the molecules in tick saliva not only aid the tick in securing a nutrient-rich blood meal, but can also enhance the transmission and acquisition of pathogens. To investigate the effect of feeding and flavivirus infection on the salivary gland transcript expression profile in ticks, a first-generation microarray was developed using ESTs from a cDNA library derived from Ixodes scapularis salivary glands. When the salivary gland transcript profile in ticks feeding over the course of 3 days was compared to that in unfed ticks, a dramatic increase in transcripts related to metabolism was observed. Specifically, 578 transcripts were up-regulated compared to 151 down-regulated transcripts in response to feeding. When specific time points post attachment were analyzed, a temporal pattern of gene expression was observed. When Langat virus-infected ticks were compared to mock-infected ticks, transcript expression changes were observed at all 3 days of feeding. Differentially regulated transcripts include putative secreted proteins, lipocalins, Kunitz domain-containing proteins, anti-microbial peptides, and transcripts of unknown function. These studies identify salivary gland transcripts that are differentially regulated during feeding or in the context of flavivirus infection in Ixodes scapularis nymphs, a medically important disease vector. Further analysis of these transcripts may identify salivary factors that affect the transmission or

  19. Immunization with Immune Complexes Modulates the Fine Specificity of Antibody Responses to a Flavivirus Antigen

    PubMed Central

    Tsouchnikas, Georgios; Zlatkovic, Juergen; Jarmer, Johanna; Strauß, Judith; Vratskikh, Oksana; Kundi, Michael; Stiasny, Karin

    2015-01-01

    ABSTRACT The antibody response to proteins may be modulated by the presence of preexisting antigen-specific antibodies and the formation of immune complexes (ICs). Effects such as a general increase or decrease of the response as well as epitope-specific phenomena have been described. In this study, we investigated influences of IC immunization on the fine specificity of antibody responses in a structurally well-defined system, using the envelope (E) protein of tick-borne encephalitis (TBE) virus as an immunogen. TBE virus occurs in Europe and Asia and—together with the yellow fever, dengue, West Nile, and Japanese encephalitis viruses—represents one of the major human-pathogenic flaviviruses. Mice were immunized with a dimeric soluble form of E (sE) alone or in complex with monoclonal antibodies specific for each of the three domains of E, and the antibody response induced by these ICs was compared to that seen after immunization with sE alone. Immunoassays using recombinant domains and domain combinations of TBE virus sE as well as the distantly related West Nile virus sE allowed the dissection and quantification of antibody subsets present in postimmunization sera, thus generating fine-specificity patterns of the polyclonal responses. There were substantially different responses with two of the ICs, and the differences could be mechanistically related to (i) epitope shielding and (ii) antibody-mediated structural changes leading to dissociation of the sE dimer. The phenomena described may also be relevant for polyclonal responses upon secondary infections and/or booster immunizations and may affect antibody responses in an individual-specific way. IMPORTANCE Infections with flaviviruses such as yellow fever, dengue, Japanese encephalitis, West Nile, and tick-borne encephalitis (TBE) viruses pose substantial public health problems in different parts of the world. Antibodies to viral envelope protein E induced by natural infection or vaccination were shown to

  20. Anti‐flavivirus Activity of Different Tritylated Pyrimidine and Purine Nucleoside Analogues

    PubMed Central

    Serpi, Michaela; Slusarczyk, Magdalena; Ferrari, Valentina; Pertusati, Fabrizio; Meneghesso, Silvia; Derudas, Marco; Farleigh, Laura; Zanetta, Paola; Bugert, Joachim

    2016-01-01

    Abstract A series of tritylated and dimethoxytritylated analogues of selected pyrimidine and purine nucleosides were synthesized and evaluated for their in vitro inhibitory activity against two important members of the genus Flavivirus in the Flaviviridae family, the yellow fever (YFV) and dengue viruses (DENV). Among all compounds tested, the 5′‐O‐tritylated and the 5′‐O‐dimethoxytritylated 5‐fluorouridine derivatives exerted potency against YFV. Interestingly in the series of purine analogues, the 5′O, N‐bis‐tritylated fludarabine derivative revealed strong inhibitory activity against DENV at μm concentrations, however significantly weaker potency against YFV. PMID:27551659

  1. Zika virus NS1 structure reveals diversity of electrostatic surfaces among flaviviruses.

    PubMed

    Song, Hao; Qi, Jianxun; Haywood, Joel; Shi, Yi; Gao, George F

    2016-05-01

    The association of Zika virus (ZIKV) infections with microcephaly has resulted in an ongoing public-health emergency. Here we report the crystal structure of a C-terminal fragment of ZIKV nonstructural protein 1 (NS1), a major host-interaction molecule that functions in flaviviral replication, pathogenesis and immune evasion. Comparison with West Nile and dengue virus NS1 structures reveals conserved features but diverse electrostatic characteristics at host-interaction interfaces, thus possibly implying different modes of flavivirus pathogenesis. PMID:27088990

  2. Anti-flavivirus Activity of Different Tritylated Pyrimidine and Purine Nucleoside Analogues.

    PubMed

    McGuigan, Christopher; Serpi, Michaela; Slusarczyk, Magdalena; Ferrari, Valentina; Pertusati, Fabrizio; Meneghesso, Silvia; Derudas, Marco; Farleigh, Laura; Zanetta, Paola; Bugert, Joachim

    2016-06-01

    A series of tritylated and dimethoxytritylated analogues of selected pyrimidine and purine nucleosides were synthesized and evaluated for their in vitro inhibitory activity against two important members of the genus Flavivirus in the Flaviviridae family, the yellow fever (YFV) and dengue viruses (DENV). Among all compounds tested, the 5'-O-tritylated and the 5'-O-dimethoxytritylated 5-fluorouridine derivatives exerted potency against YFV. Interestingly in the series of purine analogues, the 5'O, N-bis-tritylated fludarabine derivative revealed strong inhibitory activity against DENV at μm concentrations, however significantly weaker potency against YFV. PMID:27551659

  3. Identification and characterization of a novel tick-borne flavivirus subtype in goats (Capra hircus) in Spain.

    PubMed

    Mansfield, Karen L; Morales, Ana Balseiro; Johnson, Nicholas; Ayllón, Nieves; Höfle, Ursula; Alberdi, Pilar; Fernández de Mera, Isabel G; Marín, Juan Francisco García; Gortázar, Christian; de la Fuente, José; Fooks, Anthony R

    2015-07-01

    In 2011, a neurological disease was reported in a herd of goats (Capra hircus) in Asturias, Spain. Initial sequencing identified the causative agent as louping ill virus (LIV). Subsequently, with the application of whole genome sequencing and phylogenetic analysis, empirical data demonstrates that the LIV-like virus detected is significantly divergent from LIV and Spanish sheep encephalitis virus (SSEV). This virus encoded an amino acid sequence motif at the site of a previously identified marker for differentiating tick-borne flaviviruses that was shared with a virus previously isolated in Ireland in 1968. The significance of these observations reflects the diversity of tick-borne flaviviruses in Europe. These data also contribute to our knowledge of the evolution of tick-borne flaviviruses and could reflect the movement of viruses throughout Europe. Based on these observations, the proposed name for this virus is Spanish goat encephalitis virus (SGEV), to distinguish it from SSEV. PMID:25701823

  4. Preparation of pure, high titer, pseudoinfectious Flavivirus particles by hollow fiber tangential flow filtration and anion exchange chromatography.

    PubMed

    Mundle, Sophia T; Giel-Moloney, Maryann; Kleanthous, Harry; Pugachev, Konstantin V; Anderson, Stephen F

    2015-08-20

    Purification of enveloped viruses such as live flavivirus vaccine candidates poses a challenge as one must retain viral infectivity to preserve immunogenicity. Here we describe a laboratory-scale purification procedure for two replication defective (single-cycle) flavivirus variants for use in a pre-clinical setting. The two step purification scheme based on hollow fiber tangential flow filtration (TFF) followed by anion exchange chromatography using convective interaction media (CIM(®)) monoliths results in a ∼60% recovery of infectious virus titer and can be used to prepare nearly homogenous, highly purified vaccine viruses with titers as high as 1×10(9) focus forming units per mL. Flavivirus virions prepared by this method are 2 and 3 orders of magnitude more pure with respect to dsDNA and BHK host cell proteins, respectively, as compared to the raw feed stream. PMID:25498209

  5. Bicluster Pattern of Codon Context Usages between Flavivirus and Vector Mosquito Aedes aegypti: Relevance to Infection and Transcriptional Response of Mosquito Genes

    PubMed Central

    Behura, Susanta K.; Severson, David W.

    2014-01-01

    The mosquito Aedes aegypti is the primary vector of dengue virus (DENV) infection in most of the subtropical and tropical countries. Besides DENV, yellow fever virus (YFV) is also transmitted by A. aegypti. Susceptibility of A. aegypti to West Nile virus (WNV) has also been confirmed. Although studies have indicated correlation of codon bias between flaviviridae and their animal/insect hosts, it is not clear if codon sequences have any relation to susceptibility of A. aegypti to DENV, YFV and WNV. In the current study, usages of codon context sequences (codon pairs for neighboring amino acids) of the vector (A. aegypti) genome as well as the flaviviral genomes are investigated. We used bioinformatics methods to quantify codon context bias in a genome-wide manner of A. aegypti as well as DENV, WNV and YFV sequences. Mutual information statistics was applied to perform bicluster analysis of codon context bias between vector and flaviviral sequences. Functional relevance of the bicluster pattern was inferred from published microarray data. Our study shows that codon context bias of DENV, WNV and YFV sequences varies in a bicluster manner with that of specific sets of genes of A. aegypti. Many of these mosquito genes are known to be differentially expressed in response to flaviviral infection suggesting that codon context sequences of A. aegypti and the flaviviruses may play a role in the susceptible interaction between flaviviruses and this mosquito. The bias inusages of codon context sequences likely has a functional association with susceptibility of A. aegypti to flaviviral infection. The results from this study will allow us to conduct hypothesis driven tests to examine the role of codon contexts bias in evolution of vector-virus interactions at the molecular level. PMID:24838953

  6. Characterizing the Conformational Landscape of Flavivirus Fusion Peptides via Simulation and Experiment

    NASA Astrophysics Data System (ADS)

    Marzinek, Jan K.; Lakshminarayanan, Rajamani; Goh, Eunice; Huber, Roland G.; Panzade, Sadhana; Verma, Chandra; Bond, Peter J.

    2016-01-01

    Conformational changes in the envelope proteins of flaviviruses help to expose the highly conserved fusion peptide (FP), a region which is critical to membrane fusion and host cell infection, and which represents a significant target for antiviral drugs and antibodies. In principle, extended timescale atomic-resolution simulations may be used to characterize the dynamics of such peptides. However, the resultant accuracy is critically dependent upon both the underlying force field and sufficient conformational sampling. In the present study, we report a comprehensive comparison of three simulation methods and four force fields comprising a total of more than 40 μs of sampling. Additionally, we describe the conformational landscape of the FP fold across all flavivirus family members. All investigated methods sampled conformations close to available X-ray structures, but exhibited differently populated ensembles. The best force field / sampling combination was sufficiently accurate to predict that the solvated peptide fold is less ordered than in the crystallographic state, which was subsequently confirmed via circular dichroism and spectrofluorometric measurements. Finally, the conformational landscape of a mutant incapable of membrane fusion was significantly shallower than wild-type variants, suggesting that dynamics should be considered when therapeutically targeting FP epitopes.

  7. Characterizing the Conformational Landscape of Flavivirus Fusion Peptides via Simulation and Experiment

    PubMed Central

    Marzinek, Jan K.; Lakshminarayanan, Rajamani; Goh, Eunice; Huber, Roland G.; Panzade, Sadhana; Verma, Chandra; Bond, Peter J.

    2016-01-01

    Conformational changes in the envelope proteins of flaviviruses help to expose the highly conserved fusion peptide (FP), a region which is critical to membrane fusion and host cell infection, and which represents a significant target for antiviral drugs and antibodies. In principle, extended timescale atomic-resolution simulations may be used to characterize the dynamics of such peptides. However, the resultant accuracy is critically dependent upon both the underlying force field and sufficient conformational sampling. In the present study, we report a comprehensive comparison of three simulation methods and four force fields comprising a total of more than 40 μs of sampling. Additionally, we describe the conformational landscape of the FP fold across all flavivirus family members. All investigated methods sampled conformations close to available X-ray structures, but exhibited differently populated ensembles. The best force field / sampling combination was sufficiently accurate to predict that the solvated peptide fold is less ordered than in the crystallographic state, which was subsequently confirmed via circular dichroism and spectrofluorometric measurements. Finally, the conformational landscape of a mutant incapable of membrane fusion was significantly shallower than wild-type variants, suggesting that dynamics should be considered when therapeutically targeting FP epitopes. PMID:26785994

  8. Preliminary characterization of (nucleoside-2′-O-)-methyltransferase crystals from Meaban and Yokose flaviviruses

    SciTech Connect

    Mastrangelo, Eloise; Bollati, Michela; Milani, Mario; Lamballeire, Xavier de; Brisbare, Nadege; Dalle, Karen; Lantez, Violaine; Egloff, Marie-Pierre; Coutard, Bruno; Canard, Bruno; Gould, Ernest; Forrester, Naomi; Bolognesi, Martino

    2006-08-01

    Two methyltransferases from flaviviruses (Meaban and Yokose viruses) have been overexpressed and crystallized. Diffraction data and characterization of the two crystal forms are presented, together with a preliminary molecular-replacement solution for both enzymes. Viral methyltranferases (MTase) are involved in the third step of the mRNA-capping process, transferring a methyl group from S-adenosyl-l-methionine (SAM) to the capped mRNA. MTases are classified into two groups: (guanine-N7)-methyltransferases (N7MTases), which add a methyl group onto the N7 atom of guanine, and (nucleoside-2′-O-)-methyltransferases (2′OMTases), which add a methyl group to a ribose hydroxyl. The MTases of two flaviviruses, Meaban and Yokose viruses, have been overexpressed, purified and crystallized in complex with SAM. Characterization of the crystals together with details of preliminary X-ray diffraction data collection (at 2.8 and 2.7 Å resolution, respectively) are reported here. The sequence homology relative to Dengue virus 2′OMTase and the structural conservation of specific residues in the putative active sites suggest that both enzymes belong to the 2′OMTase subgroup.

  9. The Variance Reaction Time Model

    ERIC Educational Resources Information Center

    Sikstrom, Sverker

    2004-01-01

    The variance reaction time model (VRTM) is proposed to account for various recognition data on reaction time, the mirror effect, receiver-operating-characteristic (ROC) curves, etc. The model is based on simple and plausible assumptions within a neural network: VRTM is a two layer neural network where one layer represents items and one layer…

  10. Analysis of Variance: Variably Complex

    ERIC Educational Resources Information Center

    Drummond, Gordon B.; Vowler, Sarah L.

    2012-01-01

    These authors have previously described how to use the "t" test to compare two groups. In this article, they describe the use of a different test, analysis of variance (ANOVA) to compare more than two groups. ANOVA is a test of group differences: do at least two of the means differ from each other? ANOVA assumes (1) normal distribution of…

  11. Variance of a Few Observations

    ERIC Educational Resources Information Center

    Joarder, Anwar H.

    2009-01-01

    This article demonstrates that the variance of three or four observations can be expressed in terms of the range and the first order differences of the observations. A more general result, which holds for any number of observations, is also stated.

  12. Motion Detection Using Mean Normalized Temporal Variance

    SciTech Connect

    Chan, C W

    2003-08-04

    Scene-Based Wave Front Sensing uses the correlation between successive wavelets to determine the phase aberrations which cause the blurring of digital images. Adaptive Optics technology uses that information to control deformable mirrors to correct for the phase aberrations making the image clearer. The correlation between temporal subimages gives tip-tilt information. If these images do not have identical image content, tip-tilt estimations may be incorrect. Motion detection is necessary to help avoid errors initiated by dynamic subimage content. With a finely limited number of pixels per subaperature, most conventional motion detection algorithms fall apart on our subimages. Despite this fact, motion detection based on the normalized variance of individual pixels proved to be effective.

  13. 10 CFR 851.31 - Variance process.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Variance process. 851.31 Section 851.31 Energy DEPARTMENT OF ENERGY WORKER SAFETY AND HEALTH PROGRAM Variances § 851.31 Variance process. (a) Application. Contractors desiring a variance from a safety and health standard, or portion thereof, may submit a...

  14. 13 CFR 307.22 - Variances.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Variances. 307.22 Section 307.22....22 Variances. EDA may approve variances to the requirements contained in this subpart, provided such variances: (a) Are consistent with the goals of the Economic Adjustment Assistance program and with an...

  15. 29 CFR 1920.2 - Variances.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 7 2010-07-01 2010-07-01 false Variances. 1920.2 Section 1920.2 Labor Regulations Relating...' COMPENSATION ACT § 1920.2 Variances. (a) Variances from standards in parts 1915 through 1918 of this chapter may be granted in the same circumstances in which variances may be granted under sections 6(b)...

  16. Characterisation of divergent flavivirus NS3 and NS5 protein sequences detected in Rhipicephalus microplus ticks from Brazil

    PubMed Central

    Maruyama, Sandra Regina; Castro-Jorge, Luiza Antunes; Ribeiro, José Marcos Chaves; Gardinassi, Luiz Gustavo; Garcia, Gustavo Rocha; Brandão, Lucinda Giampietro; Rodrigues, Aline Rezende; Okada, Marcos Ituo; Abrão, Emiliana Pereira; Ferreira, Beatriz Rossetti; da Fonseca, Benedito Antonio Lopes; de Miranda-Santos, Isabel Kinney Ferreira

    2013-01-01

    Transcripts similar to those that encode the nonstructural (NS) proteins NS3 and NS5 from flaviviruses were found in a salivary gland (SG) complementary DNA (cDNA) library from the cattle tick Rhipicephalus microplus. Tick extracts were cultured with cells to enable the isolation of viruses capable of replicating in cultured invertebrate and vertebrate cells. Deep sequencing of the viral RNA isolated from culture supernatants provided the complete coding sequences for the NS3 and NS5 proteins and their molecular characterisation confirmed similarity with the NS3 and NS5 sequences from other flaviviruses. Despite this similarity, phylogenetic analyses revealed that this potentially novel virus may be a highly divergent member of the genus Flavivirus. Interestingly, we detected the divergent NS3 and NS5 sequences in ticks collected from several dairy farms widely distributed throughout three regions of Brazil. This is the first report of flavivirus-like transcripts in R. microplus ticks. This novel virus is a potential arbovirus because it replicated in arthropod and mammalian cells; furthermore, it was detected in a cDNA library from tick SGs and therefore may be present in tick saliva. It is important to determine whether and by what means this potential virus is transmissible and to monitor the virus as a potential emerging tick-borne zoonotic pathogen. PMID:24626302

  17. Serological Evidence of Widespread Circulation of West Nile Virus and Other Flaviviruses in Equines of the Pantanal, Brazil

    PubMed Central

    Pauvolid-Corrêa, Alex; Campos, Zilca; Juliano, Raquel; Velez, Jason; Nogueira, Rita Maria Ribeiro; Komar, Nicholas

    2014-01-01

    A recent study reported neutralizing antibodies to West Nile virus (WNV) in horses from four ranches of southern Pantanal. To extend that study, a serosurvey for WNV and 11 Brazilian flaviviruses was conducted with 760 equines, 238 sheep and 61 caimans from 17 local cattle ranches. Among the tested equines, 32 were collected from a ranch where a neurologic disorder outbreak had been recently reported. The sera were initially screened by using a blocking ELISA and then titrated by 90% plaque-reduction neutralization test (PRNT90) for 12 flaviviruses. Employing the criterion of 4-fold greater titer, 78 (10.3%) equines were seropositive for Ilheus virus, 59 (7.8%) for Saint Louis encephalitis virus, 24 (3.2%) for WNV, two (0.3%) for Cacipacore virus and one (0.1%) for Rocio virus. No serological evidence was found linking the neurological disease that affected local equines to WNV. All caimans and sheep were negative by blocking ELISA for flaviviruses. There were no seropositive equines for Bussuquara, Iguape, Yellow fever and all four Dengue virus serotypes. The detection of WNV-seropositive equines in ten ranches and ILHV and SLEV-seropositive equines in fourteen ranches of two different sub-regions of Pantanal is strong evidence of widespread circulation of these flaviviruses in the region. PMID:24551266

  18. Variance decomposition in stochastic simulators

    SciTech Connect

    Le Maître, O. P.; Knio, O. M.; Moraes, A.

    2015-06-28

    This work aims at the development of a mathematical and computational approach that enables quantification of the inherent sources of stochasticity and of the corresponding sensitivities in stochastic simulations of chemical reaction networks. The approach is based on reformulating the system dynamics as being generated by independent standardized Poisson processes. This reformulation affords a straightforward identification of individual realizations for the stochastic dynamics of each reaction channel, and consequently a quantitative characterization of the inherent sources of stochasticity in the system. By relying on the Sobol-Hoeffding decomposition, the reformulation enables us to perform an orthogonal decomposition of the solution variance. Thus, by judiciously exploiting the inherent stochasticity of the system, one is able to quantify the variance-based sensitivities associated with individual reaction channels, as well as the importance of channel interactions. Implementation of the algorithms is illustrated in light of simulations of simplified systems, including the birth-death, Schlögl, and Michaelis-Menten models.

  19. Variance decomposition in stochastic simulators

    NASA Astrophysics Data System (ADS)

    Le Maître, O. P.; Knio, O. M.; Moraes, A.

    2015-06-01

    This work aims at the development of a mathematical and computational approach that enables quantification of the inherent sources of stochasticity and of the corresponding sensitivities in stochastic simulations of chemical reaction networks. The approach is based on reformulating the system dynamics as being generated by independent standardized Poisson processes. This reformulation affords a straightforward identification of individual realizations for the stochastic dynamics of each reaction channel, and consequently a quantitative characterization of the inherent sources of stochasticity in the system. By relying on the Sobol-Hoeffding decomposition, the reformulation enables us to perform an orthogonal decomposition of the solution variance. Thus, by judiciously exploiting the inherent stochasticity of the system, one is able to quantify the variance-based sensitivities associated with individual reaction channels, as well as the importance of channel interactions. Implementation of the algorithms is illustrated in light of simulations of simplified systems, including the birth-death, Schlögl, and Michaelis-Menten models.

  20. Estimating the Modified Allan Variance

    NASA Technical Reports Server (NTRS)

    Greenhall, Charles

    1995-01-01

    The third-difference approach to modified Allan variance (MVAR) leads to a tractable formula for a measure of MVAR estimator confidence, the equivalent degrees of freedom (edf), in the presence of power-law phase noise. The effect of estimation stride on edf is tabulated. A simple approximation for edf is given, and its errors are tabulated. A theorem allowing conservative estimates of edf in the presence of compound noise processes is given.

  1. Neutrino mass without cosmic variance

    NASA Astrophysics Data System (ADS)

    LoVerde, Marilena

    2016-05-01

    Measuring the absolute scale of the neutrino masses is one of the most exciting opportunities available with near-term cosmological data sets. Two quantities that are sensitive to neutrino mass, scale-dependent halo bias b (k ) and the linear growth parameter f (k ) inferred from redshift-space distortions, can be measured without cosmic variance. Unlike the amplitude of the matter power spectrum, which always has a finite error, the error on b (k ) and f (k ) continues to decrease as the number density of tracers increases. This paper presents forecasts for statistics of galaxy and lensing fields that are sensitive to neutrino mass via b (k ) and f (k ). The constraints on neutrino mass from the auto- and cross-power spectra of spectroscopic and photometric galaxy samples are weakened by scale-dependent bias unless a very high density of tracers is available. In the high-density limit, using multiple tracers allows cosmic variance to be beaten, and the forecasted errors on neutrino mass shrink dramatically. In practice, beating the cosmic-variance errors on neutrino mass with b (k ) will be a challenge, but this signal is nevertheless a new probe of neutrino effects on structure formation that is interesting in its own right.

  2. Detection of RNA from a Novel West Nile-like Virus and High Prevalence of an Insect-specific Flavivirus in Mosquitoes in the Yucatan Peninsula of Mexico

    PubMed Central

    Farfan-Ale, Jose A.; Loroño-Pino, Maria A.; Garcia-Rejon, Julian E.; Hovav, Einat; Powers, Ann M.; Lin, Ming; Dorman, Karin S.; Platt, Kenneth B.; Bartholomay, Lyric C.; Soto, Victor; Beaty, Barry J.; Lanciotti, Robert S.; Blitvich, Bradley J.

    2009-01-01

    As part of our ongoing surveillance efforts for West Nile virus (WNV) in the Yucatan Peninsula of Mexico, 96,687 mosquitoes collected from January through December 2007 were assayed by virus isolation in mammalian cells. Three mosquito pools caused cytopathic effect. Two isolates were orthobunyaviruses (Cache Valley virus and Kairi virus) and the identity of the third infectious agent was not determined. A subset of mosquitoes was also tested by reverse transcription–polymerase chain reaction (RT-PCR) using WNV-, flavivirus-, alphavirus-, and orthobunyavirus-specific primers. A total of 7,009 Culex quinquefasciatus in 210 pools were analyzed. Flavivirus RNA was detected in 146 (70%) pools, and all PCR products were sequenced. The nucleotide sequence of one PCR product was most closely related (71–73% identity) with homologous regions of several other flaviviruses, including WNV, St. Louis encephalitis virus, and Ilheus virus. These data suggest that a novel flavivirus (tentatively named T’Ho virus) is present in Mexico. The other 145 PCR products correspond to Culex flavivirus, an insect-specific flavivirus first isolated in Japan in 2003. Culex flavivirus was isolated in mosquito cells from approximately one in four homogenates tested. The genomic sequence of one isolate was determined. Surprisingly, heterogeneous sequences were identified at the distal end of the 5′ untranslated region. PMID:19141845

  3. The Influence of Therapist Variance on the Dependability of Therapists' Alliance Scores: A Brief Comment on "The Dependability of Alliance Assessments: The Alliance-Outcome Correlation Is Larger than You Think" (Crits-Christoph et al., 2011)

    ERIC Educational Resources Information Center

    Baldwin, Scott A.; Imel, Zac E.; Atkins, David C.

    2012-01-01

    Objective: Crits-Christoph, Connolly Gibbons, Hamilton, Ring-Kurtz, and Gallop (2011) used generalizability theory to critique the measurement of the therapeutic alliance in psychotherapy research, showing that the dependability of alliance scores may be quite low, which in turn can lead to attenuated alliance-outcome correlation estimates. Method…

  4. An Expansion of the Trait-State-Occasion Model: Accounting for Shared Method Variance

    ERIC Educational Resources Information Center

    LaGrange, Beth; Cole, David A.

    2008-01-01

    This article examines 4 approaches for explaining shared method variance, each applied to a longitudinal trait-state-occasion (TSO) model. Many approaches have been developed to account for shared method variance in multitrait-multimethod (MTMM) data. Some of these MTMM approaches (correlated method, orthogonal method, correlated method minus one,…

  5. The structural basis of pathogenic subgenomic flavivirus RNA (sfRNA) production.

    PubMed

    Chapman, Erich G; Costantino, David A; Rabe, Jennifer L; Moon, Stephanie L; Wilusz, Jeffrey; Nix, Jay C; Kieft, Jeffrey S

    2014-04-18

    Flaviviruses are emerging human pathogens and worldwide health threats. During infection, pathogenic subgenomic flaviviral RNAs (sfRNAs) are produced by resisting degradation by the 5'→3' host cell exonuclease Xrn1 through an unknown RNA structure-based mechanism. Here, we present the crystal structure of a complete Xrn1-resistant flaviviral RNA, which contains interwoven pseudoknots within a compact structure that depends on highly conserved nucleotides. The RNA's three-dimensional topology creates a ringlike conformation, with the 5' end of the resistant structure passing through the ring from one side of the fold to the other. Disruption of this structure prevents formation of sfRNA during flaviviral infection. Thus, sfRNA formation results from an RNA fold that interacts directly with Xrn1, presenting the enzyme with a structure that confounds its helicase activity. PMID:24744377

  6. The structural basis of pathogenic subgenomic flavivirus RNA (sfRNA) production

    PubMed Central

    Chapman, Erich G.; Costantino, David A.; Rabe, Jennifer L.; Moon, Stephanie L.; Wilusz, Jeffrey; Nix, Jay C.; Kieft, Jeffrey S.

    2014-01-01

    Flaviviruses are emerging human pathogens and worldwide health threats. During infection, a pathogenic, subgenomic flaviviral RNAs (sfRNAs) are produced by resisting degradation by the 5’→3’ host cell exonuclease Xrn1 through an unknown RNA structure-based mechanism. Here, we present the crystal structure of a complete Xrn1-resistant flaviviral RNA, which contains interwoven pseudoknots within a compact structure that depends on highly-conserved nucleotides. The RNA’s three-dimensional topology creates a ring-like conformation with the 5’ end of the resistant structure passing through the ring from one side of the fold to the other. Disruption of this structure prevents formation of sfRNA during flaviviral infection. Thus, sfRNA formation results from an RNA fold that interacts directly with Xrn1, presenting the enzyme with a structure that confounds its helicase activity. PMID:24744377

  7. The Flavivirus Precursor Membrane-Envelope Protein Complex: Structure and Maturation

    SciTech Connect

    Li, Long; Lok, Shee-Mei; Yu, I-Mei; Zhang, Ying; Kuhn, Richard J.; Chen, Jue; Rossmann, Michael G.

    2008-09-17

    Many viruses go through a maturation step in the final stages of assembly before being transmitted to another host. The maturation process of flaviviruses is directed by the proteolytic cleavage of the precursor membrane protein (prM), turning inert virus into infectious particles. We have determined the 2.2 angstrom resolution crystal structure of a recombinant protein in which the dengue virus prM is linked to the envelope glycoprotein E. The structure represents the prM-E heterodimer and fits well into the cryo-electron microscopy density of immature virus at neutral pH. The pr peptide {beta}-barrel structure covers the fusion loop in E, preventing fusion with host cell membranes. The structure provides a basis for identifying the stages of its pH-directed conformational metamorphosis during maturation, ending with release of pr when budding from the host.

  8. The Structural Dynamics of the Flavivirus Fusion Peptide–Membrane Interaction

    PubMed Central

    Souza, Theo L. F.; Sousa, Ivanildo P.; Bianconi, M. Lucia; Bernardi, Rafael C.; Pascutti, Pedro G.; Silva, Jerson L.; Gomes, Andre M. O.; Oliveira, Andréa C.

    2012-01-01

    Membrane fusion is a crucial step in flavivirus infections and a potential target for antiviral strategies. Lipids and proteins play cooperative roles in the fusion process, which is triggered by the acidic pH inside the endosome. This acidic environment induces many changes in glycoprotein conformation and allows the action of a highly conserved hydrophobic sequence, the fusion peptide (FP). Despite the large volume of information available on the virus-triggered fusion process, little is known regarding the mechanisms behind flavivirus–cell membrane fusion. Here, we evaluated the contribution of a natural single amino acid difference on two flavivirus FPs, FLAG (98DRGWGNGCGLFGK110) and FLAH (98DRGWGNHCGLFGK110), and investigated the role of the charge of the target membrane on the fusion process. We used an in silico approach to simulate the interaction of the FPs with a lipid bilayer in a complementary way and used spectroscopic approaches to collect conformation information. We found that both peptides interact with neutral and anionic micelles, and molecular dynamics (MD) simulations showed the interaction of the FPs with the lipid bilayer. The participation of the indole ring of Trp appeared to be important for the anchoring of both peptides in the membrane model, as indicated by MD simulations and spectroscopic analyses. Mild differences between FLAG and FLAH were observed according to the pH and the charge of the target membrane model. The MD simulations of the membrane showed that both peptides adopted a bend structure, and an interaction between the aromatic residues was strongly suggested, which was also observed by circular dichroism in the presence of micelles. As the FPs of viral fusion proteins play a key role in the mechanism of viral fusion, understanding the interactions between peptides and membranes is crucial for medical science and biology and may contribute to the design of new antiviral drugs. PMID:23094066

  9. Flaviviruses as a Cause of Undifferentiated Fever in Sindh Province, Pakistan: A Preliminary Report

    PubMed Central

    Khan, Erum; Farooqi, Joveria Q.; Barr, Kelli L.; Prakoso, Dhani; Nasir, Amna; Kanji, Akbar; Shakoor, Sadia; Malik, Faisal Riaz; Hasan, Rumina; Lednicky, John A.; Long, Maureen T.

    2016-01-01

    Arboviral diseases are expanding worldwide, yet global surveillance is often limited due to diplomatic and cultural barriers between nations. With human encroachment into new habitats, mosquito-borne viruses are also invading new areas. The actual prevalence of expanding arboviruses is unknown in Pakistan due to inappropriate diagnosis and poor testing for arboviral diseases. The primary objective of this study was to document evidence of flavivirus infections as the cause of undifferentiated fever in Pakistan. Through a cooperative effort between the USA and Pakistan, patient exposure to dengue virus (DENV), West Nile virus (WNV), and Japanese encephalitis virus (JEV) was examined in Sindh Province for the first time in decades. Initial results from the 2015 arbovirus season consisting of a cross-sectional study of 467 patients in 5 sites, DENV NS1 antigen was identified in 63 of the screened subjects, WNV IgM antibodies in 16 patients, and JEV IgM antibodies in 32 patients. In addition, a number of practical findings were made including (1) in silico optimization of RT-PCR primers for flavivirus strains circulating in the Middle East, (2) shipping and storage of RT-PCR master mix and other reagents at ambient temperature, (3) Smart phone applications for the collection of data in areas with limited infrastructure, and (4) fast and reliable shipping for transport of reagents and specimens to and from the Middle East. Furthermore, this work is producing a group of highly trained local scientists and medical professionals disseminating modern scientific methods and more accurate diagnostic procedures to the community. PMID:26909342

  10. Flaviviruses as a Cause of Undifferentiated Fever in Sindh Province, Pakistan: A Preliminary Report.

    PubMed

    Khan, Erum; Farooqi, Joveria Q; Barr, Kelli L; Prakoso, Dhani; Nasir, Amna; Kanji, Akbar; Shakoor, Sadia; Malik, Faisal Riaz; Hasan, Rumina; Lednicky, John A; Long, Maureen T

    2016-01-01

    Arboviral diseases are expanding worldwide, yet global surveillance is often limited due to diplomatic and cultural barriers between nations. With human encroachment into new habitats, mosquito-borne viruses are also invading new areas. The actual prevalence of expanding arboviruses is unknown in Pakistan due to inappropriate diagnosis and poor testing for arboviral diseases. The primary objective of this study was to document evidence of flavivirus infections as the cause of undifferentiated fever in Pakistan. Through a cooperative effort between the USA and Pakistan, patient exposure to dengue virus (DENV), West Nile virus (WNV), and Japanese encephalitis virus (JEV) was examined in Sindh Province for the first time in decades. Initial results from the 2015 arbovirus season consisting of a cross-sectional study of 467 patients in 5 sites, DENV NS1 antigen was identified in 63 of the screened subjects, WNV IgM antibodies in 16 patients, and JEV IgM antibodies in 32 patients. In addition, a number of practical findings were made including (1) in silico optimization of RT-PCR primers for flavivirus strains circulating in the Middle East, (2) shipping and storage of RT-PCR master mix and other reagents at ambient temperature, (3) Smart phone applications for the collection of data in areas with limited infrastructure, and (4) fast and reliable shipping for transport of reagents and specimens to and from the Middle East. Furthermore, this work is producing a group of highly trained local scientists and medical professionals disseminating modern scientific methods and more accurate diagnostic procedures to the community. PMID:26909342

  11. A Wavelet Perspective on the Allan Variance.

    PubMed

    Percival, Donald B

    2016-04-01

    The origins of the Allan variance trace back 50 years ago to two seminal papers, one by Allan (1966) and the other by Barnes (1966). Since then, the Allan variance has played a leading role in the characterization of high-performance time and frequency standards. Wavelets first arose in the early 1980s in the geophysical literature, and the discrete wavelet transform (DWT) became prominent in the late 1980s in the signal processing literature. Flandrin (1992) briefly documented a connection between the Allan variance and a wavelet transform based upon the Haar wavelet. Percival and Guttorp (1994) noted that one popular estimator of the Allan variance-the maximal overlap estimator-can be interpreted in terms of a version of the DWT now widely referred to as the maximal overlap DWT (MODWT). In particular, when the MODWT is based on the Haar wavelet, the variance of the resulting wavelet coefficients-the wavelet variance-is identical to the Allan variance when the latter is multiplied by one-half. The theory behind the wavelet variance can thus deepen our understanding of the Allan variance. In this paper, we review basic wavelet variance theory with an emphasis on the Haar-based wavelet variance and its connection to the Allan variance. We then note that estimation theory for the wavelet variance offers a means of constructing asymptotically correct confidence intervals (CIs) for the Allan variance without reverting to the common practice of specifying a power-law noise type a priori. We also review recent work on specialized estimators of the wavelet variance that are of interest when some observations are missing (gappy data) or in the presence of contamination (rogue observations or outliers). It is a simple matter to adapt these estimators to become estimators of the Allan variance. Finally we note that wavelet variances based upon wavelets other than the Haar offer interesting generalizations of the Allan variance. PMID:26529757

  12. Estimating the Modified Allan Variance

    NASA Technical Reports Server (NTRS)

    Greenhall, Charles

    1995-01-01

    A paper at the 1992 FCS showed how to express the modified Allan variance (mvar) in terms of the third difference of the cumulative sum of time residuals. Although this reformulated definition was presented merely as a computational trick for simplifying the calculation of mvar estimates, it has since turned out to be a powerful theoretical tool for deriving the statistical quality of those estimates in terms of their equivalent degrees of freedom (edf), defined for an estimator V by edf V = 2(EV)2/(var V). Confidence intervals for mvar can then be constructed from levels of the appropriate 2 distribution.

  13. Variance decomposition in stochastic simulators.

    PubMed

    Le Maître, O P; Knio, O M; Moraes, A

    2015-06-28

    This work aims at the development of a mathematical and computational approach that enables quantification of the inherent sources of stochasticity and of the corresponding sensitivities in stochastic simulations of chemical reaction networks. The approach is based on reformulating the system dynamics as being generated by independent standardized Poisson processes. This reformulation affords a straightforward identification of individual realizations for the stochastic dynamics of each reaction channel, and consequently a quantitative characterization of the inherent sources of stochasticity in the system. By relying on the Sobol-Hoeffding decomposition, the reformulation enables us to perform an orthogonal decomposition of the solution variance. Thus, by judiciously exploiting the inherent stochasticity of the system, one is able to quantify the variance-based sensitivities associated with individual reaction channels, as well as the importance of channel interactions. Implementation of the algorithms is illustrated in light of simulations of simplified systems, including the birth-death, Schlögl, and Michaelis-Menten models. PMID:26133418

  14. Explaining Common Variance Shared by Early Numeracy and Literacy

    ERIC Educational Resources Information Center

    Davidse, N. J.; De Jong, M. T.; Bus, A. G.

    2014-01-01

    How can it be explained that early literacy and numeracy share variance? We specifically tested whether the correlation between four early literacy skills (rhyming, letter knowledge, emergent writing, and orthographic knowledge) and simple sums (non-symbolic and story condition) reduced after taking into account preschool attention control,…

  15. Strength of Relationship in Multivariate Analysis of Variance.

    ERIC Educational Resources Information Center

    Smith, I. Leon

    Methods for the calculation of eta coefficient, or correlation ratio, squared have recently been presented for examining the strength of relationship in univariate analysis of variance. This paper extends them to the multivariate case in which the effects of independent variables may be examined in relation to two or more dependent variables, and…

  16. Variance in Math Achievement Attributable to Visual Cognitive Constructs

    ERIC Educational Resources Information Center

    Oehlert, Jeremy J.

    2012-01-01

    Previous research has reported positive correlations between math achievement and the cognitive constructs of spatial visualization, working memory, and general intelligence; however, no single study has assessed variance in math achievement attributable to all three constructs, examined in combination. The current study fills this gap in the…

  17. Variance analysis. Part I, Extending flexible budget variance analysis to acuity.

    PubMed

    Finkler, S A

    1991-01-01

    The author reviews the concepts of flexible budget variance analysis, including the price, quantity, and volume variances generated by that technique. He also introduces the concept of acuity variance and provides direction on how such a variance measure can be calculated. Part II in this two-part series on variance analysis will look at how personal computers can be useful in the variance analysis process. PMID:1870002

  18. 40 CFR 52.2183 - Variance provision.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) South Dakota § 52.2183 Variance provision. The revisions to the variance provisions in Chapter 74:26:01:31.01 of the South Dakota Air...

  19. 40 CFR 52.2183 - Variance provision.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) South Dakota § 52.2183 Variance provision. The revisions to the variance provisions in Chapter 74:26:01:31.01 of the South Dakota Air...

  20. 40 CFR 52.2183 - Variance provision.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) South Dakota § 52.2183 Variance provision. The revisions to the variance provisions in Chapter 74:26:01:31.01 of the South Dakota Air...

  1. Cyclostationary analysis with logarithmic variance stabilisation

    NASA Astrophysics Data System (ADS)

    Borghesani, Pietro; Shahriar, Md Rifat

    2016-03-01

    Second order cyclostationary (CS2) components in vibration or acoustic emission signals are typical symptoms of a wide variety of faults in rotating and alternating mechanical systems. The square envelope spectrum (SES), obtained via Hilbert transform of the original signal, is at the basis of the most common indicators used for detection of CS2 components. It has been shown that the SES is equivalent to an autocorrelation of the signal's discrete Fourier transform, and that CS2 components are a cause of high correlations in the frequency domain of the signal, thus resulting in peaks in the SES. Statistical tests have been proposed to determine if peaks in the SES are likely to belong to a normal variability in the signal or if they are proper symptoms of CS2 components. Despite the need for automated fault recognition and the theoretical soundness of these tests, this approach to machine diagnostics has been mostly neglected in industrial applications. In fact, in a series of experimental applications, even with proper pre-whitening steps, it has been found that healthy machines might produce high spectral correlations and therefore result in a highly biased SES distribution which might cause a series of false positives. In this paper a new envelope spectrum is defined, with the theoretical intent of rendering the hypothesis test variance-free. This newly proposed indicator will prove unbiased in case of multiple CS2 sources of spectral correlation, thus reducing the risk of false alarms.

  2. Speed Variance and Its Influence on Accidents.

    ERIC Educational Resources Information Center

    Garber, Nicholas J.; Gadirau, Ravi

    A study was conducted to investigate the traffic engineering factors that influence speed variance and to determine to what extent speed variance affects accident rates. Detailed analyses were carried out to relate speed variance with posted speed limit, design speeds, and other traffic variables. The major factor identified was the difference…

  3. 21 CFR 1010.4 - Variances.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Variances. 1010.4 Section 1010.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) RADIOLOGICAL HEALTH PERFORMANCE STANDARDS FOR ELECTRONIC PRODUCTS: GENERAL General Provisions § 1010.4 Variances. (a) Criteria for variances. (1) Upon application by...

  4. 40 CFR 52.2183 - Variance provision.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 4 2010-07-01 2010-07-01 false Variance provision. 52.2183 Section 52...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) South Dakota § 52.2183 Variance provision. The revisions to the variance provisions in Chapter 74:26:01:31.01 of the South Dakota Air...

  5. 40 CFR 142.41 - Variance request.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Variance request. 142.41 Section 142...) NATIONAL PRIMARY DRINKING WATER REGULATIONS IMPLEMENTATION Variances Issued by the Administrator Under Section 1415(a) of the Act § 142.41 Variance request. A supplier of water may request the granting of...

  6. 10 CFR 851.31 - Variance process.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Variance process. 851.31 Section 851.31 Energy DEPARTMENT OF ENERGY WORKER SAFETY AND HEALTH PROGRAM Variances § 851.31 Variance process. (a) Application..., practices, means, methods, operations, or processes used or proposed to be used by the contractor; and...

  7. 10 CFR 851.31 - Variance process.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Variance process. 851.31 Section 851.31 Energy DEPARTMENT OF ENERGY WORKER SAFETY AND HEALTH PROGRAM Variances § 851.31 Variance process. (a) Application..., practices, means, methods, operations, or processes used or proposed to be used by the contractor; and...

  8. 10 CFR 851.31 - Variance process.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Variance process. 851.31 Section 851.31 Energy DEPARTMENT OF ENERGY WORKER SAFETY AND HEALTH PROGRAM Variances § 851.31 Variance process. (a) Application..., practices, means, methods, operations, or processes used or proposed to be used by the contractor; and...

  9. 10 CFR 851.31 - Variance process.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Variance process. 851.31 Section 851.31 Energy DEPARTMENT OF ENERGY WORKER SAFETY AND HEALTH PROGRAM Variances § 851.31 Variance process. (a) Application..., practices, means, methods, operations, or processes used or proposed to be used by the contractor; and...

  10. 40 CFR 52.2183 - Variance provision.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 4 2011-07-01 2011-07-01 false Variance provision. 52.2183 Section 52.2183 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) South Dakota § 52.2183 Variance provision. The revisions to the variance provisions...

  11. Experimental Transmission of Karshi (Mammalian Tick-Borne Flavivirus Group) Virus by Ornithodoros Ticks >2,900 Days after Initial Virus Exposure Supports the Role of Soft Ticks as a Long-Term Maintenance Mechanism for Certain Flaviviruses

    PubMed Central

    Turell, Michael J.

    2015-01-01

    Background Members of the mammalian tick-borne flavivirus group, including tick-borne encephalitis virus, are responsible for at least 10,000 clinical cases of tick-borne encephalitis each year. To attempt to explain the long-term maintenance of members of this group, we followed Ornithodoros parkeri, O. sonrai, and O. tartakovskyi for >2,900 days after they had been exposed to Karshi virus, a member of the mammalian tick-borne flavivirus group. Methodology/Principal Findings Ticks were exposed to Karshi virus either by allowing them to feed on viremic suckling mice or by intracoelomic inoculation. The ticks were then allowed to feed individually on suckling mice after various periods of extrinsic incubation to determine their ability to transmit virus by bite and to determine how long the ticks would remain infectious. The ticks remained efficient vectors of Karshi virus, even when tested >2,900 d after their initial exposure to virus, including those ticks exposed to Karshi virus either orally or by inoculation. Conclusions/Significance Ornithodoros spp. ticks were able to transmit Karshi virus for >2,900 days (nearly 8 years) after a single exposure to a viremic mouse. Therefore, these ticks may serve as a long-term maintenance mechanism for Karshi virus and potentially other members of the mammalian tick-borne flavivirus group. PMID:26285211

  12. Review: A neglected Flavivirus: an update on Zika virus in 2016 and the future direction of research.

    PubMed

    Bharucha, Tehmina; Breuer, Judith

    2016-06-01

    The 2015-16 global emergence of Zika virus infection (ZIKV) and its link with Guillain-Barré Syndrome and microcephaly, at the tail-end of the Ebola epidemic, has provoked unease throughout the international community. The World Health Organisation declared ZIKV a public health emergency on 1st February 2016, but until the 31st March 2016 maintained that there was insufficient evidence that ZIKV was independently responsible for any serious complications. Our current understanding of this arthropod-borne flavivirus is still at an early stage. The first reported human infections were 60 years ago, and until the first outbreak in Micronesia in 2007, there were only 14 documented cases. Nonetheless, there are parallels that we can draw from our understanding of other related arbo-flaviviruses, such as dengue, Japanese encephalitis and West Nile viruses. This article provides a focussed review of the literature on ZIKV to date, with perspectives on the direction of future research. PMID:27029817

  13. Flavivirus premembrane protein cleavage and spike heterodimer secretion require the function of the viral proteinase NS3.

    PubMed Central

    Lobigs, M

    1993-01-01

    Flavivirus protein biosynthesis involves the proteolytic processing of a single polyprotein precursor by host- and virus-encoded proteinases. In this study, the requirement for the proteolytic function of the viral proteinase NS3 for correct processing of a polyprotein segment encompassing the Murray Valley encephalitis virus structural proteins is shown. The NS3-mediated cleavage in the structural polyprotein region presumably releases the capsid protein from its membrane anchor and triggers the appearance of the premembrane (prM) protein. This suggests that cleavage of prM by signal peptidase in the lumen of the endoplasmic reticulum is under control of a cytoplasmic cleavage catalyzed by a viral proteinase. The function of the viral proteinase is also essential for secretion of flaviviral spike proteins when expressed from cDNA via vaccinia virus recombinants or in COS cell transfections. This has important implications for the design of flavivirus subunit vaccines. Images Fig. 1 Fig. 2 Fig. 3 PMID:8392191

  14. The many faces of the flavivirus NS1 protein offer a multitude of options for inhibitor design.

    PubMed

    Watterson, Daniel; Modhiran, Naphak; Young, Paul R

    2016-06-01

    The flavivirus non-structural protein, NS1, is an unusual viral gene product. Despite the recent unveiling of its atomic structure (Akey et al., 2014), and a growing list of host molecules with which it has been found associated, the primary function of NS1 remains elusive. It assumes many diverse roles including direct participation in the flaviviral replication complex and virion maturation. In its secreted form it is a hexameric lipoparticle that is involved in systemic immune and endothelial cell modulation. In this review we highlight recent advances in elucidating the molecular mechanisms underpinning NS1 function and present the current state of play and some future prospects for NS1 targeted antiviral strategies. This article forms part of a symposium on flavivirus drug discovery in Antiviral Research. PMID:26944216

  15. Rapid detection of newly isolated Tembusu-related Flavivirus by reverse-transcription loop-mediated isothermal amplification assay

    PubMed Central

    2011-01-01

    Background From April 2010 to January 2011, a severe new viral disease had devastated most duck-farming regions in China. This disease affected not only laying ducks but also meat ducks, causing huge economic losses for the poultry industry. The objective of this study is to develop a one-step reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for the detection of the new virus related to Tembusu-related Flavivirus. Results The RT-LAMP assay is very simple and rapid, and the amplification can be completed within 50 min under isothermal conditions at 63°C by a set of 6 primers targeting the E gene based on the sequences analysis of the newly isolated viruses and other closely related Flavivirus.The monitoring of gene amplification can also be visualized by using SYBR green I fluorescent dye. In addition, the RT-LAMP assay for newly isolated Tembusu-related Flavivirus showed higher sensitivity with an RNA detection-limit of 2 copies/μL compared with 190 copies/μL of the conventional RT-PCR method. The specificity was identified without cross reaction to other common avian pathogens. By screening a panel of clinical samples this method was more feasible in clinical settings and there was higher positive coincidence rate than conventional RT-PCR and virus isolation. Conclusion The RT-LAMP assay for newly isolated Tembusu-related Flavivirus is a valuable tool for the rapid and real-time detection not only in well-equipped laboratories but also in general conditions. PMID:22185513

  16. FLAVIdB: A data mining system for knowledge discovery in flaviviruses with direct applications in immunology and vaccinology

    PubMed Central

    Olsen, Lars Rønn; Zhang, Guang Lan; Reinherz, Ellis L.; Brusic, Vladimir

    2013-01-01

    Background The flavivirus genus is unusually large, comprising more than 70 species, of which more than half are known human pathogens. It includes a set of clinically relevant infectious agents such as dengue, West Nile, yellow fever, and Japanese encephalitis viruses. Although these pathogens have been studied extensively, safe and efficient vaccines lack for the majority of the flaviviruses. Results We have assembled a database that combines antigenic data of flaviviruses, specialized analysis tools, and workflows for automated complex analyses focusing on applications in immunology and vaccinology. FLAVIdB contains 12,858 entries of flavivirus antigen sequences, 184 verified T-cell epitopes, 201 verified B-cell epitopes, and 4 representative molecular structures of the dengue virus envelope protein. FLAVIdB was assembled by collection, annotation, and integration of data from GenBank, GenPept, UniProt, IEDB, and PDB. The data were subject to extensive quality control (redundancy elimination, error detection, and vocabulary consolidation). Further annotation of selected functionally relevant features was performed by organizing information extracted from the literature. The database was incorporated into a web-accessible data mining system, combining specialized data analysis tools for integrated analysis of relevant data categories (protein sequences, macromolecular structures, and immune epitopes). The data mining system includes tools for variability and conservation analysis, T-cell epitope prediction, and characterization of neutralizing components of B-cell epitopes. FLAVIdB is accessible at cvc.dfci.harvard.edu/flavi/ Conclusion FLAVIdB represents a new generation of databases in which data and tools are integrated into a data mining infrastructures specifically designed to aid rational vaccine design by discovery of vaccine targets. PMID:25544857

  17. The pathogenesis of 3 neurotropic flaviviruses in a mouse model depends on the route of neuroinvasion after viremia.

    PubMed

    Nagata, Noriyo; Iwata-Yoshikawa, Naoko; Hayasaka, Daisuke; Sato, Yuko; Kojima, Asato; Kariwa, Hiroaki; Takashima, Ikuo; Takasaki, Tomohiko; Kurane, Ichiro; Sata, Tetsutaro; Hasegawa, Hideki

    2015-03-01

    Neurotropic flavivirus infection of humans results in viremia subsequently; in some cases, it causes meningitis encephalomyelitis, although the pathways from viremia to central nervous system (CNS) invasion are uncertain. Here, we intravenously infected BALB/c mice with 3 neurotropic flaviviruses, then examined the clinical manifestations and histopathologic changes. The Sofjin strain of tick-borne encephalitis virus-infected mice exhibited dose-dependent survival. The animals showed distention of the small intestine caused by peripheral neuritis because of infection of the myenteric plexus. Histopathologically, the strongly neurotropic Sofjin strain invaded the CNS of viremic mice via the autonomic nerves running from the plexus. The JaTH-160 strain of Japanese encephalitis virus was isolated from the lymph nodes during the preclinical phase of viral encephalitis. Therefore, this strain might infect the CNS via a hematogenous pathway, including through lymphoid tissues. The NY99-6922 strain of the West Nile virus caused clinical signs suggestive of intestinal, lymphoid, and/or neurologic involvement; the infected mice had prolonged viremia, suggesting that NY99-6922 may mainly use the hematogenous pathway; however, there was also histopathologic evidence of involvement of the autonomic nervous system pathway. In conclusion, the three neurotropic flaviviruses showed different pathogenesis, which were dependent upon overlapping but distinct pathways to CNS invasion after viremia. PMID:25668565

  18. Variance in the reproductive success of dominant male mountain gorillas.

    PubMed

    Robbins, Andrew M; Gray, Maryke; Uwingeli, Prosper; Mburanumwe, Innocent; Kagoda, Edwin; Robbins, Martha M

    2014-10-01

    Using 30 years of demographic data from 15 groups, this study estimates how harem size, female fertility, and offspring survival may contribute to variance in the siring rates of dominant male mountain gorillas throughout the Virunga Volcano Region. As predicted for polygynous species, differences in harem size were the greatest source of variance in the siring rate, whereas differences in female fertility and offspring survival were relatively minor. Harem size was positively correlated with offspring survival, even after removing all known and suspected cases of infanticide, so the correlation does not seem to reflect differences in the ability of males to protect their offspring. Harem size was not significantly correlated with female fertility, which is consistent with the hypothesis that mountain gorillas have minimal feeding competition. Harem size, offspring survival, and siring rates were not significantly correlated with the proportion of dominant tenures that occurred in multimale groups versus one-male groups; even though infanticide is less likely when those tenures end in multimale groups than one-male groups. In contrast with the relatively small contribution of offspring survival to variance in the siring rates of this study, offspring survival is a major source of variance in the male reproductive success of western gorillas, which have greater predation risks and significantly higher rates of infanticide. If differences in offspring protection are less important among male mountain gorillas than western gorillas, then the relative importance of other factors may be greater for mountain gorillas. Thus, our study illustrates how variance in male reproductive success and its components can differ between closely related species. PMID:24818867

  19. Practice reduces task relevant variance modulation and forms nominal trajectory

    NASA Astrophysics Data System (ADS)

    Osu, Rieko; Morishige, Ken-Ichi; Nakanishi, Jun; Miyamoto, Hiroyuki; Kawato, Mitsuo

    2015-12-01

    Humans are capable of achieving complex tasks with redundant degrees of freedom. Much attention has been paid to task relevant variance modulation as an indication of online feedback control strategies to cope with motor variability. Meanwhile, it has been discussed that the brain learns internal models of environments to realize feedforward control with nominal trajectories. Here we examined trajectory variance in both spatial and temporal domains to elucidate the relative contribution of these control schemas. We asked subjects to learn reaching movements with multiple via-points, and found that hand trajectories converged to stereotyped trajectories with the reduction of task relevant variance modulation as learning proceeded. Furthermore, variance reduction was not always associated with task constraints but was highly correlated with the velocity profile. A model assuming noise both on the nominal trajectory and motor command was able to reproduce the observed variance modulation, supporting an expression of nominal trajectories in the brain. The learning-related decrease in task-relevant modulation revealed a reduction in the influence of optimal feedback around the task constraints. After practice, the major part of computation seems to be taken over by the feedforward controller around the nominal trajectory with feedback added only when it becomes necessary.

  20. Practice reduces task relevant variance modulation and forms nominal trajectory.

    PubMed

    Osu, Rieko; Morishige, Ken-ichi; Nakanishi, Jun; Miyamoto, Hiroyuki; Kawato, Mitsuo

    2015-01-01

    Humans are capable of achieving complex tasks with redundant degrees of freedom. Much attention has been paid to task relevant variance modulation as an indication of online feedback control strategies to cope with motor variability. Meanwhile, it has been discussed that the brain learns internal models of environments to realize feedforward control with nominal trajectories. Here we examined trajectory variance in both spatial and temporal domains to elucidate the relative contribution of these control schemas. We asked subjects to learn reaching movements with multiple via-points, and found that hand trajectories converged to stereotyped trajectories with the reduction of task relevant variance modulation as learning proceeded. Furthermore, variance reduction was not always associated with task constraints but was highly correlated with the velocity profile. A model assuming noise both on the nominal trajectory and motor command was able to reproduce the observed variance modulation, supporting an expression of nominal trajectories in the brain. The learning-related decrease in task-relevant modulation revealed a reduction in the influence of optimal feedback around the task constraints. After practice, the major part of computation seems to be taken over by the feedforward controller around the nominal trajectory with feedback added only when it becomes necessary. PMID:26639942

  1. Increased spatial variance accompanies reorganization of two continental shelf ecosystems.

    PubMed

    Litzow, Michael A; Urban, J Daniel; Laurel, Benjamin J

    2008-09-01

    Phase transitions between alternate stable states in marine ecosystems lead to disruptive changes in ecosystem services, especially fisheries productivity. We used trawl survey data spanning phase transitions in the North Pacific (Gulf of Alaska) and the North Atlantic (Scotian Shelf) to test for increases in ecosystem variability that might provide early warning of such transitions. In both time series, elevated spatial variability in a measure of community composition (ratio of cod [Gadus sp.] abundance to prey abundance) accompanied transitions between ecosystem states, and variability was negatively correlated with distance from the ecosystem transition point. In the Gulf of Alaska, where the phase transition was apparently the result of a sudden perturbation (climate regime shift), variance increased one year before the transition in mean state occurred. On the Scotian Shelf, where ecosystem reorganization was the result of persistent overfishing, a significant increase in variance occurred three years before the transition in mean state was detected. However, we could not reject the alternate explanation that increased variance may also have simply been inherent to the final stable state in that ecosystem. Increased variance has been previously observed around transition points in models, but rarely in real ecosystems, and our results demonstrate the possible management value in tracking the variance of key parameters in exploited ecosystems. PMID:18767612

  2. Practice reduces task relevant variance modulation and forms nominal trajectory

    PubMed Central

    Osu, Rieko; Morishige, Ken-ichi; Nakanishi, Jun; Miyamoto, Hiroyuki; Kawato, Mitsuo

    2015-01-01

    Humans are capable of achieving complex tasks with redundant degrees of freedom. Much attention has been paid to task relevant variance modulation as an indication of online feedback control strategies to cope with motor variability. Meanwhile, it has been discussed that the brain learns internal models of environments to realize feedforward control with nominal trajectories. Here we examined trajectory variance in both spatial and temporal domains to elucidate the relative contribution of these control schemas. We asked subjects to learn reaching movements with multiple via-points, and found that hand trajectories converged to stereotyped trajectories with the reduction of task relevant variance modulation as learning proceeded. Furthermore, variance reduction was not always associated with task constraints but was highly correlated with the velocity profile. A model assuming noise both on the nominal trajectory and motor command was able to reproduce the observed variance modulation, supporting an expression of nominal trajectories in the brain. The learning-related decrease in task-relevant modulation revealed a reduction in the influence of optimal feedback around the task constraints. After practice, the major part of computation seems to be taken over by the feedforward controller around the nominal trajectory with feedback added only when it becomes necessary. PMID:26639942

  3. The Composition of West Nile Virus Lipid Envelope Unveils a Role of Sphingolipid Metabolism in Flavivirus Biogenesis

    PubMed Central

    Martín-Acebes, Miguel A.; Merino-Ramos, Teresa; Blázquez, Ana-Belén; Casas, Josefina; Escribano-Romero, Estela

    2014-01-01

    ABSTRACT West Nile virus (WNV) is an emerging zoonotic mosquito-borne flavivirus responsible for outbreaks of febrile illness and meningoencephalitis. The replication of WNV takes place on virus-modified membranes from the endoplasmic reticulum of the host cell, and virions acquire their envelope by budding into this organelle. Consistent with this view, the cellular biology of this pathogen is intimately linked to modifications of the intracellular membranes, and the requirement for specific lipids, such as cholesterol and fatty acids, has been documented. In this study, we evaluated the impact of WNV infection on two important components of cellular membranes, glycerophospholipids and sphingolipids, by mass spectrometry of infected cells. A significant increase in the content of several glycerophospholipids (phosphatidylcholine, plasmalogens, and lysophospholipids) and sphingolipids (ceramide, dihydroceramide, and sphingomyelin) was noticed in WNV-infected cells, suggesting that these lipids have functional roles during WNV infection. Furthermore, the analysis of the lipid envelope of WNV virions and recombinant virus-like particles revealed that their envelopes had a unique composition. The envelopes were enriched in sphingolipids (sphingomyelin) and showed reduced levels of phosphatidylcholine, similar to sphingolipid-enriched lipid microdomains. Inhibition of neutral sphingomyelinase (which catalyzes the hydrolysis of sphingomyelin into ceramide) by either pharmacological approaches or small interfering RNA-mediated silencing reduced the release of flavivirus virions as well as virus-like particles, suggesting a role of sphingomyelin-to-ceramide conversion in flavivirus budding and confirming the importance of sphingolipids in the biogenesis of WNV. IMPORTANCE West Nile virus (WNV) is a neurotropic flavivirus spread by mosquitoes that can infect multiple vertebrate hosts, including humans. There is no specific vaccine or therapy against this pathogen licensed

  4. Defining Hsp70 Subnetworks in Dengue Virus Replication Reveals Key Vulnerability in Flavivirus Infection.

    PubMed

    Taguwa, Shuhei; Maringer, Kevin; Li, Xiaokai; Bernal-Rubio, Dabeiba; Rauch, Jennifer N; Gestwicki, Jason E; Andino, Raul; Fernandez-Sesma, Ana; Frydman, Judith

    2015-11-19

    Viral protein homeostasis depends entirely on the machinery of the infected cell. Accordingly, viruses can illuminate the interplay between cellular proteostasis components and their distinct substrates. Here, we define how the Hsp70 chaperone network mediates the dengue virus life cycle. Cytosolic Hsp70 isoforms are required at distinct steps of the viral cycle, including entry, RNA replication, and virion biogenesis. Hsp70 function at each step is specified by nine distinct DNAJ cofactors. Of these, DnaJB11 relocalizes to virus-induced replication complexes to promote RNA synthesis, while DnaJB6 associates with capsid protein and facilitates virion biogenesis. Importantly, an allosteric Hsp70 inhibitor, JG40, potently blocks infection of different dengue serotypes in human primary blood cells without eliciting viral resistance or exerting toxicity to the host cells. JG40 also blocks replication of other medically-important flaviviruses including yellow fever, West Nile and Japanese encephalitis viruses. Thus, targeting host Hsp70 subnetworks provides a path for broad-spectrum antivirals. PMID:26582131

  5. Patterns of Flavivirus Seroprevalence in the Human Population of Northern Laos.

    PubMed

    Conlan, James V; Vongxay, Khamphouth; Khamlome, Boualam; Jarman, Richard G; Gibbons, Robert V; Fenwick, Stanley G; Thompson, R C A; Blacksell, Stuart D

    2015-11-01

    A total of 1,136 samples from 289 households in four provinces in northern Laos were subjected to Japanese encephalitis virus (JEV) and dengue virus hemagglutination inhibition (DENV HI). Overall, antibodies to JEV were detected by HI in 620 (54.6%) of 1,136 people; of which 217 (19.1%) had HI activity against JEV only. Antibodies to DENV4 were detected by HI in 526 (46.3%) of 1,136 people; of which 124 (10.9%) had HI activity against DENV4 only. Antibodies to DENV1-3 were detected by HI in 296 (26.1%), 274 (24.1%), and 283 (24.9) of 1,136 people, respectively; of which 7, 1, and 0, respectively, had HI activity against DENV1-3 only. JEV was the most prevalent Flavivirus in Oudomxay, Luangprabang, and Huaphan provinces and DENV4 was the most prevalent in Xiengkhouang province. Seroprevalence for JEV increased with increasing age and wealth and was higher in villages where rice was cultivated in paddy fields and highest for people of Lao-Tai ethnicity. PMID:26304925

  6. Patterns of Flavivirus Seroprevalence in the Human Population of Northern Laos

    PubMed Central

    Conlan, James V.; Vongxay, Khamphouth; Khamlome, Boualam; Jarman, Richard G.; Gibbons, Robert V.; Fenwick, Stanley G.; Thompson, R. C. A.; Blacksell, Stuart D.

    2015-01-01

    A total of 1,136 samples from 289 households in four provinces in northern Laos were subjected to Japanese encephalitis virus (JEV) and dengue virus hemagglutination inhibition (DENV HI). Overall, antibodies to JEV were detected by HI in 620 (54.6%) of 1,136 people; of which 217 (19.1%) had HI activity against JEV only. Antibodies to DENV4 were detected by HI in 526 (46.3%) of 1,136 people; of which 124 (10.9%) had HI activity against DENV4 only. Antibodies to DENV1–3 were detected by HI in 296 (26.1%), 274 (24.1%), and 283 (24.9) of 1,136 people, respectively; of which 7, 1, and 0, respectively, had HI activity against DENV1–3 only. JEV was the most prevalent Flavivirus in Oudomxay, Luangprabang, and Huaphan provinces and DENV4 was the most prevalent in Xiengkhouang province. Seroprevalence for JEV increased with increasing age and wealth and was higher in villages where rice was cultivated in paddy fields and highest for people of Lao-Tai ethnicity. PMID:26304925

  7. Structural Differences Observed in Arboviruses of the Alphavirus and Flavivirus Genera

    PubMed Central

    Hernandez, Raquel; Brown, Dennis T.; Paredes, Angel

    2014-01-01

    Arthropod borne viruses have developed a complex life cycle adapted to alternate between insect and vertebrate hosts. These arthropod-borne viruses belong mainly to the families Togaviridae, Flaviviridae, and Bunyaviridae. This group of viruses contains many pathogens that cause febrile, hemorrhagic, and encephalitic disease or arthritic symptoms which can be persistent. It has been appreciated for many years that these viruses were evolutionarily adapted to function in the highly divergent cellular environments of both insect and mammalian phyla. These viruses are hybrid in nature, containing viral-encoded RNA and proteins which are glycosylated by the host and encapsulate viral nucleocapsids in the context of a host-derived membrane. From a structural perspective, these virus particles are macromolecular machines adapted in design to assemble into a packaging and delivery system for the virus genome and, only when associated with the conditions appropriate for a productive infection, to disassemble and deliver the RNA cargo. It was initially assumed that the structures of the virus from both hosts were equivalent. New evidence that alphaviruses and flaviviruses can exist in more than one conformation postenvelopment will be discussed in this review. The data are limited but should refocus the field of structural biology on the metastable nature of these viruses. PMID:25309597

  8. Antagonism of the complement component C4 by flavivirus nonstructural protein NS1

    PubMed Central

    Avirutnan, Panisadee; Fuchs, Anja; Hauhart, Richard E.; Somnuke, Pawit; Youn, Soonjeon

    2010-01-01

    The complement system plays an essential protective role in the initial defense against many microorganisms. Flavivirus NS1 is a secreted nonstructural glycoprotein that accumulates in blood, is displayed on the surface of infected cells, and has been hypothesized to have immune evasion functions. Herein, we demonstrate that dengue virus (DENV), West Nile virus (WNV), and yellow fever virus (YFV) NS1 attenuate classical and lectin pathway activation by directly interacting with C4. Binding of NS1 to C4 reduced C4b deposition and C3 convertase (C4b2a) activity. Although NS1 bound C4b, it lacked intrinsic cofactor activity to degrade C4b, and did not block C3 convertase formation or accelerate decay of the C3 and C5 convertases. Instead, NS1 enhanced C4 cleavage by recruiting and activating the complement-specific protease C1s. By binding C1s and C4 in a complex, NS1 promotes efficient degradation of C4 to C4b. Through this mechanism, NS1 protects DENV from complement-dependent neutralization in solution. These studies define a novel immune evasion mechanism for restricting complement control of microbial infection. PMID:20308361

  9. Small Variance in Growth Rate in Annual Plants has Large Effects on Genetic Drift

    Technology Transfer Automated Retrieval System (TEKTRAN)

    When plant size is strongly correlated with plant reproduction, variance in growth rates results in a lognormal distribution of seed production within a population. Fecundity variance affects effective population size (Ne), which reflects the ability of a population to maintain beneficial mutations ...

  10. Consistent Small-Sample Variances for Six Gamma-Family Measures of Ordinal Association

    ERIC Educational Resources Information Center

    Woods, Carol M.

    2009-01-01

    Gamma-family measures are bivariate ordinal correlation measures that form a family because they all reduce to Goodman and Kruskal's gamma in the absence of ties (1954). For several gamma-family indices, more than one variance estimator has been introduced. In previous research, the "consistent" variance estimator described by Cliff and colleagues…

  11. Insect-Specific Flaviviruses: A Systematic Review of Their Discovery, Host Range, Mode of Transmission, Superinfection Exclusion Potential and Genomic Organization

    PubMed Central

    Blitvich, Bradley J.; Firth, Andrew E.

    2015-01-01

    There has been a dramatic increase in the number of insect-specific flaviviruses (ISFs) discovered in the last decade. Historically, these viruses have generated limited interest due to their inability to infect vertebrate cells. This viewpoint has changed in recent years because some ISFs have been shown to enhance or suppress the replication of medically important flaviviruses in co-infected mosquito cells. Additionally, comparative studies between ISFs and medically important flaviviruses can provide a unique perspective as to why some flaviviruses possess the ability to infect and cause devastating disease in humans while others do not. ISFs have been isolated exclusively from mosquitoes in nature but the detection of ISF-like sequences in sandflies and chironomids indicates that they may also infect other dipterans. ISFs can be divided into two distinct phylogenetic groups. The first group currently consists of approximately 12 viruses and includes cell fusing agent virus, Kamiti River virus and Culex flavivirus. These viruses are phylogenetically distinct from all other known flaviviruses. The second group, which is apparently not monophyletic, currently consists of nine viruses and includes Chaoyang virus, Nounané virus and Lammi virus. These viruses phylogenetically affiliate with mosquito/vertebrate flaviviruses despite their apparent insect-restricted phenotype. This article provides a review of the discovery, host range, mode of transmission, superinfection exclusion ability and genomic organization of ISFs. This article also attempts to clarify the ISF nomenclature because some of these viruses have been assigned more than one name due to their simultaneous discoveries by independent research groups. PMID:25866904

  12. Simulation testing of unbiasedness of variance estimators

    USGS Publications Warehouse

    Link, W.A.

    1993-01-01

    In this article I address the evaluation of estimators of variance for parameter estimates. Given an unbiased estimator X of a parameter 0, and an estimator V of the variance of X, how does one test (via simulation) whether V is an unbiased estimator of the variance of X? The derivation of the test statistic illustrates the need for care in substituting consistent estimators for unknown parameters.

  13. 40 CFR 59.106 - Variance.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... VOLATILE ORGANIC COMPOUND EMISSION STANDARDS FOR CONSUMER AND COMMERCIAL PRODUCTS National Volatile Organic Compound Emission Standards for Automobile Refinish Coatings § 59.106 Variance. (a) Any regulated...

  14. 40 CFR 59.106 - Variance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... VOLATILE ORGANIC COMPOUND EMISSION STANDARDS FOR CONSUMER AND COMMERCIAL PRODUCTS National Volatile Organic Compound Emission Standards for Automobile Refinish Coatings § 59.106 Variance. (a) Any regulated...

  15. 40 CFR 59.106 - Variance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... VOLATILE ORGANIC COMPOUND EMISSION STANDARDS FOR CONSUMER AND COMMERCIAL PRODUCTS National Volatile Organic Compound Emission Standards for Automobile Refinish Coatings § 59.106 Variance. (a) Any regulated...

  16. 40 CFR 59.106 - Variance.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... VOLATILE ORGANIC COMPOUND EMISSION STANDARDS FOR CONSUMER AND COMMERCIAL PRODUCTS National Volatile Organic Compound Emission Standards for Automobile Refinish Coatings § 59.106 Variance. (a) Any regulated...

  17. 40 CFR 59.106 - Variance.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... VOLATILE ORGANIC COMPOUND EMISSION STANDARDS FOR CONSUMER AND COMMERCIAL PRODUCTS National Volatile Organic Compound Emission Standards for Automobile Refinish Coatings § 59.106 Variance. (a) Any regulated...

  18. Encoding of natural sounds by variance of the cortical local field potential.

    PubMed

    Ding, Nai; Simon, Jonathan Z; Shamma, Shihab A; David, Stephen V

    2016-06-01

    Neural encoding of sensory stimuli is typically studied by averaging neural signals across repetitions of the same stimulus. However, recent work has suggested that the variance of neural activity across repeated trials can also depend on sensory inputs. Here we characterize how intertrial variance of the local field potential (LFP) in primary auditory cortex of awake ferrets is affected by continuous natural sound stimuli. We find that natural sounds often suppress the intertrial variance of low-frequency LFP (<16 Hz). However, the amount of the variance reduction is not significantly correlated with the amplitude of the mean response at the same recording site. Moreover, the variance changes occur with longer latency than the mean response. Although the dynamics of the mean response and intertrial variance differ, spectro-temporal receptive field analysis reveals that changes in LFP variance have frequency tuning similar to multiunit activity at the same recording site, suggesting a local origin for changes in LFP variance. In summary, the spectral tuning of LFP intertrial variance and the absence of a correlation with the amplitude of the mean evoked LFP suggest substantial heterogeneity in the interaction between spontaneous and stimulus-driven activity across local neural populations in auditory cortex. PMID:26912594

  19. The mean and variance of phylogenetic diversity under rarefaction.

    PubMed

    Nipperess, David A; Matsen, Frederick A

    2013-06-01

    Phylogenetic diversity (PD) depends on sampling depth, which complicates the comparison of PD between samples of different depth. One approach to dealing with differing sample depth for a given diversity statistic is to rarefy, which means to take a random subset of a given size of the original sample. Exact analytical formulae for the mean and variance of species richness under rarefaction have existed for some time but no such solution exists for PD.We have derived exact formulae for the mean and variance of PD under rarefaction. We confirm that these formulae are correct by comparing exact solution mean and variance to that calculated by repeated random (Monte Carlo) subsampling of a dataset of stem counts of woody shrubs of Toohey Forest, Queensland, Australia. We also demonstrate the application of the method using two examples: identifying hotspots of mammalian diversity in Australasian ecoregions, and characterising the human vaginal microbiome.There is a very high degree of correspondence between the analytical and random subsampling methods for calculating mean and variance of PD under rarefaction, although the Monte Carlo method requires a large number of random draws to converge on the exact solution for the variance.Rarefaction of mammalian PD of ecoregions in Australasia to a common standard of 25 species reveals very different rank orderings of ecoregions, indicating quite different hotspots of diversity than those obtained for unrarefied PD. The application of these methods to the vaginal microbiome shows that a classical score used to quantify bacterial vaginosis is correlated with the shape of the rarefaction curve.The analytical formulae for the mean and variance of PD under rarefaction are both exact and more efficient than repeated subsampling. Rarefaction of PD allows for many applications where comparisons of samples of different depth is required. PMID:23833701

  20. Molecular Archaeology of Flaviviridae Untranslated Regions: Duplicated RNA Structures in the Replication Enhancer of Flaviviruses and Pestiviruses Emerged via Convergent Evolution

    PubMed Central

    Gritsun, Dmitri J.; Jones, Ian M.; Gould, Ernest A.; Gritsun, Tamara S.

    2014-01-01

    RNA secondary structures in the 3′untranslated regions (3′UTR) of the viruses of the family Flaviviridae, previously identified as essential (promoters) or beneficial (enhancers) for replication, have been analysed. Duplicated enhancer elements are revealed as a global feature in the evolution of the 3′UTR of distantly related viruses within the genera Flavivirus and Pestivirus. For the flaviviruses, duplicated structures occur in the 3′UTR of all four distantly related ecological virus subgroups (tick-borne, mosquito-borne, no known vector and insect-specific flaviviruses (ISFV). RNA structural differences distinguish tick-borne flaviviruses with discrete pathogenetic characteristics. For Aedes- and Culex-associated ISFV, secondary RNA structures with different conformations display numerous short ssRNA direct repeats, exposed as loops and bulges. Long quadruplicate regions comprise almost the entire 3′UTR of Culex-associated ISFV. Extended duplicated sequence and associated RNA structures were also discovered in the 3′UTR of pestiviruses. In both the Flavivirus and Pestivirus genera, duplicated RNA structures were localized to the enhancer regions of the 3′UTR suggesting an adaptive role predominantly in wild-type viruses. We propose sequence reiteration might act as a scaffold for dimerization of proteins involved in assembly of viral replicase complexes. Numerous nucleotide repeats exposed as loops/bulges might also interfere with host immune responses acting as a molecular sponge to sequester key host proteins or microRNAs. PMID:24647143

  1. 20 CFR 654.402 - Variances.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Variances. 654.402 Section 654.402 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR SPECIAL RESPONSIBILITIES OF THE EMPLOYMENT SERVICE SYSTEM Housing for Agricultural Workers Purpose and Applicability § 654.402 Variances. (a) An employer may apply for a...

  2. 20 CFR 654.402 - Variances.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Variances. 654.402 Section 654.402 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR SPECIAL RESPONSIBILITIES OF THE EMPLOYMENT SERVICE SYSTEM Housing for Agricultural Workers Purpose and Applicability § 654.402 Variances....

  3. 40 CFR 142.41 - Variance request.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... nature and duration of variance requested. (b) Relevant analytical results of water quality sampling of... relevant to ability to comply. (3) Analytical results of raw water quality relevant to the variance request... request made under § 142.40(b), a statement that the system will perform monitoring and other...

  4. 40 CFR 142.41 - Variance request.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... nature and duration of variance requested. (b) Relevant analytical results of water quality sampling of... relevant to ability to comply. (3) Analytical results of raw water quality relevant to the variance request... request made under § 142.40(b), a statement that the system will perform monitoring and other...

  5. 40 CFR 142.41 - Variance request.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... nature and duration of variance requested. (b) Relevant analytical results of water quality sampling of... relevant to ability to comply. (3) Analytical results of raw water quality relevant to the variance request... request made under § 142.40(b), a statement that the system will perform monitoring and other...

  6. 21 CFR 1010.4 - Variances.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Variances. 1010.4 Section 1010.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) RADIOLOGICAL HEALTH... and Radiological Health, Food and Drug Administration, may grant a variance from one or...

  7. 21 CFR 1010.4 - Variances.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Variances. 1010.4 Section 1010.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) RADIOLOGICAL HEALTH... and Radiological Health, Food and Drug Administration, may grant a variance from one or...

  8. 21 CFR 1010.4 - Variances.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Variances. 1010.4 Section 1010.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) RADIOLOGICAL HEALTH... and Radiological Health, Food and Drug Administration, may grant a variance from one or...

  9. On Some Representations of Sample Variance

    ERIC Educational Resources Information Center

    Joarder, Anwar H.

    2002-01-01

    The usual formula for variance depending on rounding off the sample mean lacks precision, especially when computer programs are used for the calculation. The well-known simplification of the total sums of squares does not always give benefit. Since the variance of two observations is easily calculated without the use of a sample mean, and the…

  10. 10 CFR 1021.343 - Variances.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Procedures § 1021.343 Variances. (a) Emergency actions. DOE may take an action without observing all provisions of this part or the CEQ Regulations, in accordance with 40 CFR 1506.11, in emergency situations... 10 Energy 4 2010-01-01 2010-01-01 false Variances. 1021.343 Section 1021.343 Energy DEPARTMENT...

  11. 18 CFR 1304.408 - Variances.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 2 2010-04-01 2010-04-01 false Variances. 1304.408 Section 1304.408 Conservation of Power and Water Resources TENNESSEE VALLEY AUTHORITY APPROVAL OF... § 1304.408 Variances. The Vice President or the designee thereof is authorized, following...

  12. Nonlinear Epigenetic Variance: Review and Simulations

    ERIC Educational Resources Information Center

    Kan, Kees-Jan; Ploeger, Annemie; Raijmakers, Maartje E. J.; Dolan, Conor V.; van Der Maas, Han L. J.

    2010-01-01

    We present a review of empirical evidence that suggests that a substantial portion of phenotypic variance is due to nonlinear (epigenetic) processes during ontogenesis. The role of such processes as a source of phenotypic variance in human behaviour genetic studies is not fully appreciated. In addition to our review, we present simulation studies…

  13. Comparative Neuropathogenesis and Neurovirulence of Attenuated Flaviviruses in Nonhuman Primates▿ †

    PubMed Central

    Maximova, Olga A.; Ward, Jerrold M.; Asher, David M.; St. Claire, Marisa; Finneyfrock, Brad W.; Speicher, James M.; Murphy, Brian R.; Pletnev, Alexander G.

    2008-01-01

    Based on previous preclinical evaluation in mice and monkeys, the chimeric TBEV/DEN4Δ30 virus, carrying the prM and E protein genes from a highly virulent Far Eastern strain of tick-borne encephalitis virus (TBEV) on the backbone of a nonneuroinvasive dengue type 4 virus (DEN4), has been identified as a promising live attenuated virus vaccine candidate against disease caused by TBEV. However, prior to use of this vaccine candidate in humans, its neurovirulence in nonhuman primates needed to be evaluated. In the present study, we compared the neuropathogeneses of the chimeric TBEV/DEN4Δ30 virus; Langat virus (LGTV), a former live TBEV vaccine; and yellow fever 17D virus vaccine (YF 17D) in rhesus monkeys inoculated intracerebrally. TBEV/DEN4Δ30 and YF 17D demonstrated remarkably similar spatiotemporal profiles of virus replication and virus-associated histopathology in the central nervous system (CNS) that were high in cerebral hemispheres but progressively decreased toward the spinal cord. In contrast, the neurovirulence of LGTV exhibited the reverse profile, progressing from the site of inoculation toward the cerebellum and spinal cord. Analysis of the spatiotemporal distribution of viral antigens in the CNS of monkeys revealed a prominent neurotropism associated with all three attenuated viruses. Nevertheless, TBEV/DEN4Δ30 virus exhibited higher neurovirulence in monkeys than either LGTV or YF 17D, suggesting insufficient attenuation. These results provide insight into the neuropathogenesis associated with attenuated flaviviruses that may guide the design of safe vaccines. PMID:18353947

  14. End-point disease investigation for virus strains of intermediate virulence as illustrated by flavivirus infections.

    PubMed

    Suen, Willy W; Prow, Natalie A; Setoh, Yin X; Hall, Roy A; Bielefeldt-Ohmann, Helle

    2016-02-01

    Viruses of intermediate virulence are defined as isolates causing an intermediate morbidity/mortality rate in a specific animal model system, involving specific host and inoculation parameters (e.g. dose and route). Therefore, variable disease phenotype may exist between animals that develop severe disease or die and those that are asymptomatic or survive after infection with these isolates. There may also be variability amongst animals within each of these subsets. Such potential variability may confound the use of time-point sacrifice experiments to investigate pathogenesis of this subset of virus strains, as uniformity in disease outcome is a fundamental assumption for time-course sacrifice experiments. In the current study, we examined the disease phenotype, neuropathology, neural infection and glial cell activity in moribund/dead and surviving Swiss white (CD-1) mice after intraperitoneal infection with various Australian flaviviruses, including West Nile virus (WNV) strains of intermediate virulence (WNVNSW2011 and WNVNSW2012), and highly virulent Murray Valley encephalitis virus (MVEV) isolates. We identified notable intragroup variation in the end-point disease in mice infected with either WNVNSW strain, but to a lesser extent in mice infected with MVEV strains. The variable outcomes associated with WNVNSW infection suggest that pathogenesis investigations using time-point sacrifice of WNVNSW-infected mice may not be the best approach, as the assumption of uniformity in outcomes is violated. Our study has therefore highlighted a previously unacknowledged challenge to investigating pathogenesis of virus isolates of intermediate virulence. We have also set a precedent for routine examination of the disease phenotype in moribund/dead and surviving mice during survival challenge experiments. PMID:26614392

  15. Limonoids from Melia azedarach Fruits as Inhibitors of Flaviviruses and Mycobacterium tubercolosis

    PubMed Central

    Sanna, Giuseppina; Madeddu, Silvia; Giliberti, Gabriele; Ntalli, Nikoletta G.; Cottiglia, Filippo; De Logu, Alessandro; Agus, Emanuela; Caboni, Pierluigi

    2015-01-01

    The biological diversity of nature is the source of a wide range of bioactive molecules. The natural products, either as pure compounds or as standardized plant extracts, have been a successful source of inspiration for the development of new drugs. The present work was carried out to investigate the cytotoxicity, antiviral and antimycobacterial activity of the methanol extract and of four identified limonoids from the fruits of Melia azedarach (Meliaceae). The extract and purified limonoids were tested in cell-based assays for antiviral activity against representatives of ssRNA, dsRNA and dsDNA viruses and against Mycobacterium tuberculosis. Very interestingly, 3-α-tigloyl-melianol and melianone showed a potent antiviral activity (EC50 in the range of 3–11μM) against three important human pathogens, belonging to Flaviviridae family, West Nile virus, Dengue virus and Yellow Fever virus. Mode of action studies demonstrated that title compounds were inhibitors of West Nile virus only when added during the infection, acting as inhibitors of the entry or of a very early event of life cycle. Furthermore, 3-α-tigloyl-melianol and methyl kulonate showed interesting antimycobacterial activity (with MIC values of 29 and 70 μM respectively). The limonoids are typically lipophilic compounds present in the fruits of Melia azeradach. They are known as cytotoxic compounds against different cancer cell lines, while their potential as antiviral and antibacterial was poorly investigated. Our studies show that they may serve as a good starting point for the development of novel drugs for the treatment of infections by Flaviviruses and Mycobacterium tuberculosis, for which there is a continued need. PMID:26485025

  16. Development of a Model System for Tick-Borne Flavivirus Persistence in HEK 293T Cells

    PubMed Central

    Mlera, Luwanika; Offerdahl, Danielle K.; Martens, Craig; Porcella, Stephen F.; Melik, Wessam

    2015-01-01

    ABSTRACT We devised a model system to study persistent infection by the tick-borne flavivirus Langat virus (LGTV) in 293T cells. Infection with a molecularly cloned LGTV strain produced an acute lytic crisis that left few surviving cells. The culture was repopulated by cells that were ~90% positive for LGTV E protein, thus initiating a persistent infection that was maintained for at least 35 weeks without additional lytic crises. Staining of cells for viral proteins and ultrastructural analysis revealed only minor differences from the acute phase of infection. Infectious LGTV decreased markedly over the study period, but the number of viral genomes remained relatively constant, suggesting the development of defective interfering particles (DIPs). Viral genome changes were investigated by RNA deep sequencing. At the initiation of persistent infection, levels of DIPs were below the limit of detection at a coverage depth of 11,288-fold, implying that DIPs are not required for initiation of persistence. However, after 15 passages, DIPs constituted approximately 34% of the total LGTV population (coverage of 1,293-fold). Furthermore, at this point, one specific DIP population predominated in which nucleotides 1058 to 2881 had been deleted. This defective genome specified an intact polyprotein that coded for a truncated fusion protein containing 28 N-terminal residues of E and 134 C-terminal residues of NS1. Such a fusion protein has not previously been described, and a possible function in persistent infection is uncertain. DIPs are not required for the initiation of persistent LGTV infection but may play a role in the maintenance of viral persistence. PMID:26045539

  17. Portfolio optimization with mean-variance model

    NASA Astrophysics Data System (ADS)

    Hoe, Lam Weng; Siew, Lam Weng

    2016-06-01

    Investors wish to achieve the target rate of return at the minimum level of risk in their investment. Portfolio optimization is an investment strategy that can be used to minimize the portfolio risk and can achieve the target rate of return. The mean-variance model has been proposed in portfolio optimization. The mean-variance model is an optimization model that aims to minimize the portfolio risk which is the portfolio variance. The objective of this study is to construct the optimal portfolio using the mean-variance model. The data of this study consists of weekly returns of 20 component stocks of FTSE Bursa Malaysia Kuala Lumpur Composite Index (FBMKLCI). The results of this study show that the portfolio composition of the stocks is different. Moreover, investors can get the return at minimum level of risk with the constructed optimal mean-variance portfolio.

  18. Heterogeneity of variances for carcass traits by percentage Brahman inheritance.

    PubMed

    Crews, D H; Franke, D E

    1998-07-01

    considered as a source of heterogeneity of variance. Genetic covariances estimated from the model accounting for heterogeneous variances resulted in genetic correlations of or near unity. These results suggest that different genetic values be considered for genetic evaluation of carcass yield and shear force traits from steers with different degrees of Brahman inheritance. PMID:9690635

  19. Development of multiplex real-time reverse transcriptase PCR assays for detecting eight medically important flaviviruses in mosquitoes.

    PubMed

    Chao, Day-Yu; Davis, Brent S; Chang, Gwong-Jen J

    2007-02-01

    A multiplex real-time reverse transcriptase PCR has been developed for the rapid detection and identification of eight medically important flaviviruses from laboratory-reared, virus-infected mosquito pools. The method used involves the gene-specific amplification of yellow fever virus (YFV), Japanese encephalitis virus (JEV), West Nile virus (WNV), St. Louis encephalitis virus (SLEV), and dengue virus (DENV) serotypes 1 to 4 (DENV-1 to DENV-4, respectively) by use of the flavivirus consensus amplimers located at the RNA-dependent RNA polymerase domain of nonstructural protein 5. Virus-specific amplicons were detected by four newly characterized TaqMan fluorogenic probes (probes specific for YFV, JEV, WNV, and SLEV) and four previously published probes specific for DENV-1 to -4 (L. J. Chien, T. L. Liao, P. Y. Shu, J. H. Huang, D. J. Gubler, and G. J. Chang, J. Clin. Microbiol. 44:1295-1304, 2006). This assay had a specificity of 100% and various sensitivities of at least 3.5 PFU/ml for YFV, 2.0 PFU/ml for JEV, 10.0 PFU/ml for WNV, and 10.0 PFU/ml for SLEV. Additionally, we have developed an in vitro transcription system to generate RNase-resistant RNA templates for each of these eight viruses. These templates can be incorporated into the assay as RNA copy number controls and/or as external controls for RNA-spiked mosquito pools for quality assurance purposes. Although further study with mosquitoes collected in the field is needed, the incorporation of this assay into mosquito surveillance could be used as an early-warning system for the detection of medically important flaviviruses, particularly when the cocirculation of multiple viruses in the same region is suspected. PMID:17108075

  20. Exploring of Primate Models of Tick-Borne Flaviviruses Infection for Evaluation of Vaccines and Drugs Efficacy

    PubMed Central

    Pripuzova, Natalia S.; Gmyl, Larissa V.; Romanova, Lidiya Iu.; Tereshkina, Natalia V.; Rogova, Yulia V.; Terekhina, Liubov L.; Kozlovskaya, Liubov I.; Vorovitch, Mikhail F.; Grishina, Karina G.; Timofeev, Andrey V.; Karganova, Galina G.

    2013-01-01

    Tick-borne encephalitis virus (TBEV) is one of the most prevalent and medically important tick-borne arboviruses in Eurasia. There are overlapping foci of two flaviviruses: TBEV and Omsk hemorrhagic fever virus (OHFV) in Russia. Inactivated vaccines exist only against TBE. There are no antiviral drugs for treatment of both diseases. Optimal animal models are necessary to study efficacy of novel vaccines and treatment preparations against TBE and relative flaviviruses. The models for TBE and OHF using subcutaneous inoculation were tested in Cercopithecus aethiops and Macaca fascicularis monkeys with or without prior immunization with inactivated TBE vaccine. No visible clinical signs or severe pathomorphological lesions were observed in any monkey infected with TBEV or OHFV. C. aethiops challenged with OHFV showed massive hemolytic syndrome and thrombocytopenia. Infectious virus or viral RNA was revealed in visceral organs and CNS of C. aethiops infected with both viruses; however, viremia was low. Inactivated TBE vaccines induced high antibody titers against both viruses and expressed booster after challenge. The protective efficacy against TBE was shown by the absence of virus in spleen, lymph nodes and CNS of immunized animals after challenge. Despite the absence of expressed hemolytic syndrome in immunized C. aethiops TBE vaccine did not prevent the reproduction of OHFV in CNS and visceral organs. Subcutaneous inoculation of M. fascicularis with two TBEV strains led to a febrile disease with well expressed viremia, fever, and virus reproduction in spleen, lymph nodes and CNS. The optimal terms for estimation of the viral titers in CNS were defined as 8–16 days post infection. We characterized two animal models similar to humans in their susceptibility to tick-borne flaviviruses and found the most optimal scheme for evaluation of efficacy of preventive and therapeutic preparations. We also identified M. fascicularis to be more susceptible to TBEV than C

  1. Module organization and variance in protein-protein interaction networks

    PubMed Central

    Lin, Chun-Yu; Lee, Tsai-Ling; Chiu, Yi-Yuan; Lin, Yi-Wei; Lo, Yu-Shu; Lin, Chih-Ta; Yang, Jinn-Moon

    2015-01-01

    A module is a group of closely related proteins that act in concert to perform specific biological functions through protein–protein interactions (PPIs) that occur in time and space. However, the underlying module organization and variance remain unclear. In this study, we collected module templates to infer respective module families, including 58,041 homologous modules in 1,678 species, and PPI families using searches of complete genomic database. We then derived PPI evolution scores and interface evolution scores to describe the module elements, including core and ring components. Functions of core components were highly correlated with those of essential genes. In comparison with ring components, core proteins/PPIs were conserved across multiple species. Subsequently, protein/module variance of PPI networks confirmed that core components form dynamic network hubs and play key roles in various biological functions. Based on the analyses of gene essentiality, module variance, and gene co-expression, we summarize the observations of module organization and variance as follows: 1) a module consists of core and ring components; 2) core components perform major biological functions and collaborate with ring components to execute certain functions in some cases; 3) core components are more conserved and essential during organizational changes in different biological states or conditions. PMID:25797237

  2. Portfolio optimization using median-variance approach

    NASA Astrophysics Data System (ADS)

    Wan Mohd, Wan Rosanisah; Mohamad, Daud; Mohamed, Zulkifli

    2013-04-01

    Optimization models have been applied in many decision-making problems particularly in portfolio selection. Since the introduction of Markowitz's theory of portfolio selection, various approaches based on mathematical programming have been introduced such as mean-variance, mean-absolute deviation, mean-variance-skewness and conditional value-at-risk (CVaR) mainly to maximize return and minimize risk. However most of the approaches assume that the distribution of data is normal and this is not generally true. As an alternative, in this paper, we employ the median-variance approach to improve the portfolio optimization. This approach has successfully catered both types of normal and non-normal distribution of data. With this actual representation, we analyze and compare the rate of return and risk between the mean-variance and the median-variance based portfolio which consist of 30 stocks from Bursa Malaysia. The results in this study show that the median-variance approach is capable to produce a lower risk for each return earning as compared to the mean-variance approach.

  3. 40 CFR 59.206 - Variances.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... VOLATILE ORGANIC COMPOUND EMISSION STANDARDS FOR CONSUMER AND COMMERCIAL PRODUCTS National Volatile Organic Compound Emission Standards for Consumer Products § 59.206 Variances. (a) Any regulated entity who...

  4. 40 CFR 59.206 - Variances.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... VOLATILE ORGANIC COMPOUND EMISSION STANDARDS FOR CONSUMER AND COMMERCIAL PRODUCTS National Volatile Organic Compound Emission Standards for Consumer Products § 59.206 Variances. (a) Any regulated entity who...

  5. 40 CFR 59.206 - Variances.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... VOLATILE ORGANIC COMPOUND EMISSION STANDARDS FOR CONSUMER AND COMMERCIAL PRODUCTS National Volatile Organic Compound Emission Standards for Consumer Products § 59.206 Variances. (a) Any regulated entity who...

  6. 40 CFR 59.206 - Variances.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... VOLATILE ORGANIC COMPOUND EMISSION STANDARDS FOR CONSUMER AND COMMERCIAL PRODUCTS National Volatile Organic Compound Emission Standards for Consumer Products § 59.206 Variances. (a) Any regulated entity who...

  7. 40 CFR 59.206 - Variances.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... VOLATILE ORGANIC COMPOUND EMISSION STANDARDS FOR CONSUMER AND COMMERCIAL PRODUCTS National Volatile Organic Compound Emission Standards for Consumer Products § 59.206 Variances. (a) Any regulated entity who...

  8. Reducing variance in batch partitioning measurements

    SciTech Connect

    Mariner, Paul E.

    2010-08-11

    The partitioning experiment is commonly performed with little or no attention to reducing measurement variance. Batch test procedures such as those used to measure K{sub d} values (e.g., ASTM D 4646 and EPA402 -R-99-004A) do not explain how to evaluate measurement uncertainty nor how to minimize measurement variance. In fact, ASTM D 4646 prescribes a sorbent:water ratio that prevents variance minimization. Consequently, the variance of a set of partitioning measurements can be extreme and even absurd. Such data sets, which are commonplace, hamper probabilistic modeling efforts. An error-savvy design requires adjustment of the solution:sorbent ratio so that approximately half of the sorbate partitions to the sorbent. Results of Monte Carlo simulations indicate that this simple step can markedly improve the precision and statistical characterization of partitioning uncertainty.

  9. Variance anisotropy in compressible 3-D MHD

    NASA Astrophysics Data System (ADS)

    Oughton, S.; Matthaeus, W. H.; Wan, Minping; Parashar, Tulasi

    2016-06-01

    We employ spectral method numerical simulations to examine the dynamical development of anisotropy of the variance, or polarization, of the magnetic and velocity field in compressible magnetohydrodynamic (MHD) turbulence. Both variance anisotropy and spectral anisotropy emerge under influence of a large-scale mean magnetic field B0; these are distinct effects, although sometimes related. Here we examine the appearance of variance parallel to B0, when starting from a highly anisotropic state. The discussion is based on a turbulence theoretic approach rather than a wave perspective. We find that parallel variance emerges over several characteristic nonlinear times, often attaining a quasi-steady level that depends on plasma beta. Consistency with solar wind observations seems to occur when the initial state is dominated by quasi-two-dimensional fluctuations.

  10. Another Line for the Analysis of Variance

    ERIC Educational Resources Information Center

    Brown, Bruce L.; Harshbarger, Thad R.

    1976-01-01

    A test is developed for hypotheses about the grand mean in the analysis of variance, using the known relationship between the t distribution and the F distribution with 1 df (degree of freedom) for the numerator. (Author/RC)

  11. Nonorthogonal Analysis of Variance Programs: An Evaluation.

    ERIC Educational Resources Information Center

    Hosking, James D.; Hamer, Robert M.

    1979-01-01

    Six computer programs for four methods of nonorthogonal analysis of variance are compared for capabilities, accuracy, cost, transportability, quality of documentation, associated computational capabilities, and ease of use: OSIRIS; SAS; SPSS; MANOVA; BMDP2V; and MULTIVARIANCE. (CTM)

  12. Comparative Analysis Between Flaviviruses Reveals Specific Neural Stem Cell Tropism for Zika Virus in the Mouse Developing Neocortex.

    PubMed

    Brault, Jean-Baptiste; Khou, Cécile; Basset, Justine; Coquand, Laure; Fraisier, Vincent; Frenkiel, Marie-Pascale; Goud, Bruno; Manuguerra, Jean-Claude; Pardigon, Nathalie; Baffet, Alexandre D

    2016-08-01

    The recent Zika outbreak in South America and French Polynesia was associated with an epidemic of microcephaly, a disease characterized by a reduced size of the cerebral cortex. Other members of the Flavivirus genus, including West Nile virus (WNV), can cause encephalitis but were not demonstrated to cause microcephaly. It remains unclear whether Zika virus (ZIKV) and other flaviviruses may infect different cell populations in the developing neocortex and lead to distinct developmental defects. Here, we describe an assay to infect mouse E15 embryonic brain slices with ZIKV, WNV and dengue virus serotype 4 (DENV-4). We show that this tissue is able to support viral replication of ZIKV and WNV, but not DENV-4. Cell fate analysis reveals a remarkable tropism of ZIKV infection for neural stem cells. Closely related WNV displays a very different tropism of infection, with a bias towards neurons. We further show that ZIKV infection, but not WNV infection, impairs cell cycle progression of neural stem cells. Both viruses inhibited apoptosis at early stages of infection. This work establishes a powerful comparative approach to identify ZIKV-specific alterations in the developing neocortex and reveals specific preferential infection of neural stem cells by ZIKV. PMID:27453325

  13. Response variance in functional maps: neural darwinism revisited.

    PubMed

    Takahashi, Hirokazu; Yokota, Ryo; Kanzaki, Ryohei

    2013-01-01

    The mechanisms by which functional maps and map plasticity contribute to cortical computation remain controversial. Recent studies have revisited the theory of neural Darwinism to interpret the learning-induced map plasticity and neuronal heterogeneity observed in the cortex. Here, we hypothesize that the Darwinian principle provides a substrate to explain the relationship between neuron heterogeneity and cortical functional maps. We demonstrate in the rat auditory cortex that the degree of response variance is closely correlated with the size of its representational area. Further, we show that the response variance within a given population is altered through training. These results suggest that larger representational areas may help to accommodate heterogeneous populations of neurons. Thus, functional maps and map plasticity are likely to play essential roles in Darwinian computation, serving as effective, but not absolutely necessary, structures to generate diverse response properties within a neural population. PMID:23874733

  14. Variational bayesian method of estimating variance components.

    PubMed

    Arakawa, Aisaku; Taniguchi, Masaaki; Hayashi, Takeshi; Mikawa, Satoshi

    2016-07-01

    We developed a Bayesian analysis approach by using a variational inference method, a so-called variational Bayesian method, to determine the posterior distributions of variance components. This variational Bayesian method and an alternative Bayesian method using Gibbs sampling were compared in estimating genetic and residual variance components from both simulated data and publically available real pig data. In the simulated data set, we observed strong bias toward overestimation of genetic variance for the variational Bayesian method in the case of low heritability and low population size, and less bias was detected with larger population sizes in both methods examined. The differences in the estimates of variance components between the variational Bayesian and the Gibbs sampling were not found in the real pig data. However, the posterior distributions of the variance components obtained with the variational Bayesian method had shorter tails than those obtained with the Gibbs sampling. Consequently, the posterior standard deviations of the genetic and residual variances of the variational Bayesian method were lower than those of the method using Gibbs sampling. The computing time required was much shorter with the variational Bayesian method than with the method using Gibbs sampling. PMID:26877207

  15. A variance-decomposition approach to investigating multiscale habitat associations

    USGS Publications Warehouse

    Lawler, J.J.; Edwards, T.C., Jr.

    2006-01-01

    The recognition of the importance of spatial scale in ecology has led many researchers to take multiscale approaches to studying habitat associations. However, few of the studies that investigate habitat associations at multiple spatial scales have considered the potential effects of cross-scale correlations in measured habitat variables. When cross-scale correlations in such studies are strong, conclusions drawn about the relative strength of habitat associations at different spatial scales may be inaccurate. Here we adapt and demonstrate an analytical technique based on variance decomposition for quantifying the influence of cross-scale correlations on multiscale habitat associations. We used the technique to quantify the variation in nest-site locations of Red-naped Sapsuckers (Sphyrapicus nuchalis) and Northern Flickers (Colaptes auratus) associated with habitat descriptors at three spatial scales. We demonstrate how the method can be used to identify components of variation that are associated only with factors at a single spatial scale as well as shared components of variation that represent cross-scale correlations. Despite the fact that no explanatory variables in our models were highly correlated (r < 0.60), we found that shared components of variation reflecting cross-scale correlations accounted for roughly half of the deviance explained by the models. These results highlight the importance of both conducting habitat analyses at multiple spatial scales and of quantifying the effects of cross-scale correlations in such analyses. Given the limits of conventional analytical techniques, we recommend alternative methods, such as the variance-decomposition technique demonstrated here, for analyzing habitat associations at multiple spatial scales. ?? The Cooper Ornithological Society 2006.

  16. Inferred changes in El Niño-Southern Oscillation variance over the past six centuries

    NASA Astrophysics Data System (ADS)

    McGregor, S.; Timmermann, A.; England, M. H.; Elison Timm, O.; Wittenberg, A. T.

    2013-10-01

    It is vital to understand how the El Niño-Southern Oscillation (ENSO) has responded to past changes in natural and anthropogenic forcings, in order to better understand and predict its response to future greenhouse warming. To date, however, the instrumental record is too brief to fully characterize natural ENSO variability, while large discrepancies exist amongst paleo-proxy reconstructions of ENSO. These paleo-proxy reconstructions have typically attempted to reconstruct ENSO's temporal evolution, rather than the variance of these temporal changes. Here a new approach is developed that synthesizes the variance changes from various proxy data sets to provide a unified and updated estimate of past ENSO variance. The method is tested using surrogate data from two coupled general circulation model (CGCM) simulations. It is shown that in the presence of dating uncertainties, synthesizing variance information provides a more robust estimate of ENSO variance than synthesizing the raw data and then identifying its running variance. We also examine whether good temporal correspondence between proxy data and instrumental ENSO records implies a good representation of ENSO variance. In the climate modeling framework we show that a significant improvement in reconstructing ENSO variance changes is found when combining information from diverse ENSO-teleconnected source regions, rather than by relying on a single well-correlated location. This suggests that ENSO variance estimates derived from a single site should be viewed with caution. Finally, synthesizing existing ENSO reconstructions to arrive at a better estimate of past ENSO variance changes, we find robust evidence that the ENSO variance for any 30 yr period during the interval 1590-1880 was considerably lower than that observed during 1979-2009.

  17. Inferred changes in El Niño-Southern Oscillation variance over the past six centuries

    NASA Astrophysics Data System (ADS)

    McGregor, S.; Timmermann, A.; England, M. H.; Elison Timm, O.; Wittenberg, A. T.

    2013-05-01

    It is vital to understand how the El Niño-Southern Oscillation (ENSO) has responded to past changes in natural and anthropogenic forcings, in order to better understand and predict its response to future greenhouse warming. To date, however, the instrumental record is too brief to fully characterize natural ENSO variability, while large discrepancies exist amongst paleo-proxy reconstructions of ENSO. These paleo-proxy reconstructions have typically attempted to reconstruct the full temporal variability of ENSO, rather than focusing simply on its variance. Here a new approach is developed that synthesizes the information on common low frequency variance changes from various proxy datasets to obtain estimates of ENSO variance. The method is tested using surrogate data from two coupled general circulation model (CGCM) simulations. It is shown that in the presence of dating uncertainties, synthesizing variance information provides a more robust estimate of ENSO variance than synthesizing the raw data than identifying its running variance. We also examine whether good temporal correspondence between proxy data and instrumental ENSO records implies a good representation of ENSO variance. A significant improvement in reconstructing ENSO variance changes is found when combining several proxies from diverse ENSO-teleconnected source regions, rather than by relying on a single well-correlated location, suggesting that ENSO variance estimates provided derived from a single site should be viewed with caution. Finally, identifying the common variance signal in a series of existing proxy based reconstructions of ENSO variability over the last 600 yr we find that the common ENSO variance over the period 1600-1900 was considerably lower than during 1979-2009.

  18. Discrimination of frequency variance for tonal sequencesa)

    PubMed Central

    Byrne, Andrew J.; Viemeister, Neal F.; Stellmack, Mark A.

    2014-01-01

    Real-world auditory stimuli are highly variable across occurrences and sources. The present study examined the sensitivity of human listeners to differences in global stimulus variability. In a two-interval, forced-choice task, variance discrimination was measured using sequences of five 100-ms tone pulses. The frequency of each pulse was sampled randomly from a distribution that was Gaussian in logarithmic frequency. In the non-signal interval, the sampled distribution had a variance of σSTAN2, while in the signal interval, the variance of the sequence was σSIG2 (with σSIG2 > σSTAN2). The listener's task was to choose the interval with the larger variance. To constrain possible decision strategies, the mean frequency of the sampling distribution of each interval was randomly chosen for each presentation. Psychometric functions were measured for various values of σSTAN2. Although the performance was remarkably similar across listeners, overall performance was poorer than that of an ideal observer (IO) which perfectly compares interval variances. However, like the IO, Weber's Law behavior was observed, with a constant ratio of (σSIG2-σSTAN2) to σSTAN2 yielding similar performance. A model which degraded the IO with a frequency-resolution noise and a computational noise provided a reasonable fit to the real data. PMID:25480064

  19. Cosmic variance of the galaxy cluster weak lensing signal

    NASA Astrophysics Data System (ADS)

    Gruen, D.; Seitz, S.; Becker, M. R.; Friedrich, O.; Mana, A.

    2015-06-01

    Intrinsic variations of the projected density profiles of clusters of galaxies at fixed mass are a source of uncertainty for cluster weak lensing. We present a semi-analytical model to account for this effect, based on a combination of variations in halo concentration, ellipticity and orientation, and the presence of correlated haloes. We calibrate the parameters of our model at the 10 per cent level to match the empirical cosmic variance of cluster profiles at M_{200m}≈ 10^{14}ldots 10^{15} h^{-1}{ M_{⊙}}, z = 0.25…0.5 in a cosmological simulation. We show that weak lensing measurements of clusters significantly underestimate mass uncertainties if intrinsic profile variations are ignored, and that our model can be used to provide correct mass likelihoods. Effects on the achievable accuracy of weak lensing cluster mass measurements are particularly strong for the most massive clusters and deep observations (with ≈20 per cent uncertainty from cosmic variance alone at M_{200m}≈ 10^{15} h^{-1}{ M_{⊙}} and z = 0.25), but significant also under typical ground-based conditions. We show that neglecting intrinsic profile variations leads to biases in the mass-observable relation constrained with weak lensing, both for intrinsic scatter and overall scale (the latter at the 15 per cent level). These biases are in excess of the statistical errors of upcoming surveys and can be avoided if the cosmic variance of cluster profiles is accounted for.

  20. Cross-bispectrum computation and variance estimation

    NASA Technical Reports Server (NTRS)

    Lii, K. S.; Helland, K. N.

    1981-01-01

    A method for the estimation of cross-bispectra of discrete real time series is developed. The asymptotic variance properties of the bispectrum are reviewed, and a method for the direct estimation of bispectral variance is given. The symmetry properties are described which minimize the computations necessary to obtain a complete estimate of the cross-bispectrum in the right-half-plane. A procedure is given for computing the cross-bispectrum by subdividing the domain into rectangular averaging regions which help reduce the variance of the estimates and allow easy application of the symmetry relationships to minimize the computational effort. As an example of the procedure, the cross-bispectrum of a numerically generated, exponentially distributed time series is computed and compared with theory.

  1. Inhomogeneity-induced variance of cosmological parameters

    NASA Astrophysics Data System (ADS)

    Wiegand, A.; Schwarz, D. J.

    2012-02-01

    Context. Modern cosmology relies on the assumption of large-scale isotropy and homogeneity of the Universe. However, locally the Universe is inhomogeneous and anisotropic. This raises the question of how local measurements (at the ~102 Mpc scale) can be used to determine the global cosmological parameters (defined at the ~104 Mpc scale)? Aims: We connect the questions of cosmological backreaction, cosmic averaging and the estimation of cosmological parameters and show how they relate to the problem of cosmic variance. Methods: We used Buchert's averaging formalism and determined a set of locally averaged cosmological parameters in the context of the flat Λ cold dark matter model. We calculated their ensemble means (i.e. their global value) and variances (i.e. their cosmic variance). We applied our results to typical survey geometries and focused on the study of the effects of local fluctuations of the curvature parameter. Results: We show that in the context of standard cosmology at large scales (larger than the homogeneity scale and in the linear regime), the question of cosmological backreaction and averaging can be reformulated as the question of cosmic variance. The cosmic variance is found to be highest in the curvature parameter. We propose to use the observed variance of cosmological parameters to measure the growth factor. Conclusions: Cosmological backreaction and averaging are real effects that have been measured already for a long time, e.g. by the fluctuations of the matter density contrast averaged over spheres of a certain radius. Backreaction and averaging effects from scales in the linear regime, as considered in this work, are shown to be important for the precise measurement of cosmological parameters.

  2. Integrating Variances into an Analytical Database

    NASA Technical Reports Server (NTRS)

    Sanchez, Carlos

    2010-01-01

    For this project, I enrolled in numerous SATERN courses that taught the basics of database programming. These include: Basic Access 2007 Forms, Introduction to Database Systems, Overview of Database Design, and others. My main job was to create an analytical database that can handle many stored forms and make it easy to interpret and organize. Additionally, I helped improve an existing database and populate it with information. These databases were designed to be used with data from Safety Variances and DCR forms. The research consisted of analyzing the database and comparing the data to find out which entries were repeated the most. If an entry happened to be repeated several times in the database, that would mean that the rule or requirement targeted by that variance has been bypassed many times already and so the requirement may not really be needed, but rather should be changed to allow the variance's conditions permanently. This project did not only restrict itself to the design and development of the database system, but also worked on exporting the data from the database to a different format (e.g. Excel or Word) so it could be analyzed in a simpler fashion. Thanks to the change in format, the data was organized in a spreadsheet that made it possible to sort the data by categories or types and helped speed up searches. Once my work with the database was done, the records of variances could be arranged so that they were displayed in numerical order, or one could search for a specific document targeted by the variances and restrict the search to only include variances that modified a specific requirement. A great part that contributed to my learning was SATERN, NASA's resource for education. Thanks to the SATERN online courses I took over the summer, I was able to learn many new things about computers and databases and also go more in depth into topics I already knew about.

  3. Wave propagation analysis using the variance matrix.

    PubMed

    Sharma, Richa; Ivan, J Solomon; Narayanamurthy, C S

    2014-10-01

    The propagation of a coherent laser wave-field through a pseudo-random phase plate is studied using the variance matrix estimated from Shack-Hartmann wavefront sensor data. The uncertainty principle is used as a tool in discriminating the data obtained from the Shack-Hartmann wavefront sensor. Quantities of physical interest such as the twist parameter, and the symplectic eigenvalues, are estimated from the wavefront sensor measurements. A distance measure between two variance matrices is introduced and used to estimate the spatial asymmetry of a wave-field in the experiment. The estimated quantities are then used to compare a distorted wave-field with its undistorted counterpart. PMID:25401243

  4. Variance in binary stellar population synthesis

    NASA Astrophysics Data System (ADS)

    Breivik, Katelyn; Larson, Shane L.

    2016-03-01

    In the years preceding LISA, Milky Way compact binary population simulations can be used to inform the science capabilities of the mission. Galactic population simulation efforts generally focus on high fidelity models that require extensive computational power to produce a single simulated population for each model. Each simulated population represents an incomplete sample of the functions governing compact binary evolution, thus introducing variance from one simulation to another. We present a rapid Monte Carlo population simulation technique that can simulate thousands of populations in less than a week, thus allowing a full exploration of the variance associated with a binary stellar evolution model.

  5. Variance Reduction Using Nonreversible Langevin Samplers

    NASA Astrophysics Data System (ADS)

    Duncan, A. B.; Lelièvre, T.; Pavliotis, G. A.

    2016-05-01

    A standard approach to computing expectations with respect to a given target measure is to introduce an overdamped Langevin equation which is reversible with respect to the target distribution, and to approximate the expectation by a time-averaging estimator. As has been noted in recent papers [30, 37, 61, 72], introducing an appropriately chosen nonreversible component to the dynamics is beneficial, both in terms of reducing the asymptotic variance and of speeding up convergence to the target distribution. In this paper we present a detailed study of the dependence of the asymptotic variance on the deviation from reversibility. Our theoretical findings are supported by numerical simulations.

  6. A Simple Algorithm for Approximating Confidence on the Modified Allan Variance and the Time Variance

    NASA Technical Reports Server (NTRS)

    Weiss, Marc A.; Greenhall, Charles A.

    1996-01-01

    An approximating algorithm for computing equvalent degrees of freedom of the Modified Allan Variance and its square root, the Modified Allan Deviation (MVAR and MDEV), and the Time Variance and Time Deviation (TVAR and TDEV) is presented, along with an algorithm for approximating the inverse chi-square distribution.

  7. Gravity Wave Variance in LIMS Temperatures. Part II: Comparison with the Zonal-Mean Momentum Balance.

    NASA Astrophysics Data System (ADS)

    Fetzer, Eric J.; Gille, John C.

    1996-02-01

    Zonal-mean gravity wave variance in the Limb Infrared Monitor of the Stratosphere (LIMS) temperature data is seen to correlate strongly with the residual term in the LIMS zonal-mean momentum budget throughout much of the observed mesosphere. This momentum residual is attributed to gravity wave momentum transport at scales that cannot be directly sampled by the LIMS instrument Correlation is highest in the vicinity of the fall and winter mesospheric jets, where both gravity wave variance and momentum residual reach their largest values. Correlation is also high in the Southern Hemisphere subtropical mesophere, where gravity wave variance and the momentum residual have broad temporal maxima during the easterly acceleration of the stratopause semi-annual oscillation (SAO). This subtropical correlation has important implications for the SAO eastward acceleration, which several studies suggest is forced by gravity wave momentum flux divergence. Correlation between gravity wave variance and inferred gravity wave momentum flux divergence is unexpected because variance is dominated by large scales and long periods (inertio-gravity waves), while both theoretical arguments and ground-based observations indicate that momentum transport is dominated by periods under 1 h. The results of this study suggest a broadband gravity wave field experiencing forcing and loss processes, which are largely independent of frequency.

  8. Revisiting the Clinal Concept of Evolution and Dispersal for the Tick-Borne Flaviviruses by Using Phylogenetic and Biogeographic Analyses

    PubMed Central

    Heinze, D. M.; Gould, E. A.

    2012-01-01

    Tick-borne flaviviruses (TBF) are widely dispersed across Africa, Europe, Asia, Oceania, and North America, and some present a significant threat to human health. Seminal studies on tick-borne encephalitis viruses (TBEV), based on partial envelope gene sequences, predicted a westward clinal pattern of evolution and dispersal across northern Eurasia, terminating in the British Isles. We tested this hypothesis using all available full-length open reading frame (ORF) TBF sequences. Phylogenetic analysis was consistent with current reports. However, linear and nonlinear regression analysis of genetic versus geographic distance combined with BEAST analysis identified two separate clines, suggesting that TBEV spread both east and west from a central point. In addition, BEAST analysis suggested that TBF emerged and dispersed more than 16,000 years ago, significantly earlier than previously predicted. Thus, climatic and ecological changes may have played a greater role in TBF dispersal than humans. PMID:22674986

  9. Perturbation in the Conserved Methyltransferase-Polymerase Interface of Flavivirus NS5 Differentially Affects Polymerase Initiation and Elongation

    PubMed Central

    Wu, Jiqin; Lu, Guoliang; Zhang, Bo

    2014-01-01

    ABSTRACT The flavivirus NS5 is a natural fusion of a methyltransferase (MTase) and an RNA-dependent RNA polymerase (RdRP). Analogous to DNA-dependent RNA polymerases, the NS5 polymerase initiates RNA synthesis through a de novo mechanism and then makes a transition to a processive elongation phase. However, whether and how the MTase affects polymerase activities through intramolecular interactions remain elusive. By solving the crystal structure of the Japanese encephalitis virus (JEV) NS5, we recently identified an MTase-RdRP interface containing a set of six hydrophobic residues highly conserved among flaviviruses. To dissect the functional relevance of this interface, we made a series of JEV NS5 constructs with mutations of these hydrophobic residues and/or with the N-terminal first 261 residues and other residues up to the first 303 residues deleted. Compared to the wild-type (WT) NS5, full-length NS5 variants exhibited consistent up- or downregulation of the initiation activities in two types of polymerase assays. Five representative full-length NS5 constructs were then tested in an elongation assay, from which the apparent single-nucleotide incorporation rate constant was estimated. Interestingly, two constructs exhibited different elongation kinetics from the WT NS5, with an effect rather opposite to what was observed at initiation. Moreover, constructs with MTase and/or the linker region (residues 266 to 275) removed still retained polymerase activities, albeit at overall lower levels. However, further removal of the N-terminal extension (residues 276 to 303) abolished regular template-directed synthesis. Together, our data showed that the MTase-RdRP interface is relevant in both polymerase initiation and elongation, likely with different regulation mechanisms in these two major phases of RNA synthesis. IMPORTANCE The flavivirus NS5 is very unique in having a methyltransferase (MTase) placed on the immediate N terminus of its RNA-dependent RNA polymerase

  10. Shake, rattle, and roll: Impact of the dynamics of flavivirus particles on their interactions with the host

    PubMed Central

    Kuhn, Richard J.; Dowd, Kimberly A.; Post, Carol Beth; Pierson, Theodore C.

    2016-01-01

    Remarkable progress in structural biology has equipped virologists with insight into structures of viral proteins and virions at increasingly high resolution. Structural information has been used extensively to address fundamental questions about virtually all aspects of how viruses replicate in cells, interact with the host, and in the design of antiviral compounds. However, many critical aspects of virology exist outside the snapshots captured by traditional methods used to generate high-resolution structures. Like all proteins, viral proteins are not static structures. The conformational flexibility and dynamics of proteins play a significant role in protein-protein interactions, and in the structure and biology of virus particles. This review will discuss the implications of the dynamics of viral proteins on the biology, antigenicity, and immunogenicity of flaviviruses. PMID:25835729

  11. The zoonotic flaviviruses of southern, south-eastern and eastern Asia, and Australasia: the potential for emergent viruses.

    PubMed

    Mackenzie, J S; Williams, D T

    2009-08-01

    The genus Flaviviridae comprises about 70 members, of which about 30 are found in southern, south-eastern and eastern Asia and Australasia. These include major pathogens such as Japanese encephalitis (JE), West Nile (WN), Murray Valley encephalitis (MVE), tick-borne encephalitis, Kyasanur Forest disease virus, and the dengue viruses. Other members are known to be associated with mild febrile disease in humans, or with no known disease. In addition, novel flaviviruses continue to be discovered, as demonstrated recently by New Mapoon virus in Australia, Sitiawan virus in Malaysia, and ThCAr virus in Thailand. About 19 of these viruses are mosquito-borne, six are tick-borne, and four have no known vector and represent isolates from rodents or bats. Evidence from phylogenetic studies suggest that JE, MVE and Alfuy viruses probably emerged in the Malaya-Indonesian region from an African progenitor virus, possibly a virus related to Usutu virus. WN virus, however, is believed to have emerged in Africa, and then dispersed through avian migration. Evidence suggests that there are at least seven genetic lineages of WN virus, of which lineage 1b spread to Australasia as Kunjin virus, lineages 1a and 5 spread to India, and lineage 6 spread to Malaysia. Indeed, flaviviruses have a propensity to spread and emerge in new geographic areas, and they represent a potential source for new disease emergence. Many of the factors associated with disease emergence are present in the region, such as changes in land use and deforestation, increasing population movement, urbanization, and increasing trade. Furthermore, because of their ecology and dependence on climate, there is a strong likelihood that global warming may significantly increase the potential for disease emergence and/or spread. PMID:19486319

  12. Videotape Project in Child Variance. Final Report.

    ERIC Educational Resources Information Center

    Morse, William C.; Smith, Judith M.

    The design, production, dissemination, and evaluation of a series of videotaped training packages designed to enable teachers, parents, and paraprofessionals to interpret child variance in light of personal and alternative perspectives of behavior are discussed. The goal of each package is to highlight unique contributions of different theoretical…

  13. Testing Variances in Psychological and Educational Research.

    ERIC Educational Resources Information Center

    Ramsey, Philip H.

    1994-01-01

    A review of the literature indicates that the two best procedures for testing variances are one that was proposed by O'Brien (1981) and another that was proposed by Brown and Forsythe (1974). An examination of these procedures for a variety of populations confirms their robustness and indicates how optimal power can usually be obtained. (SLD)

  14. 10 CFR 1022.16 - Variances.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... such an action) DOE shall document the emergency actions in accordance with NEPA procedures at 10 CFR... ENERGY (GENERAL PROVISIONS) COMPLIANCE WITH FLOODPLAIN AND WETLAND ENVIRONMENTAL REVIEW REQUIREMENTS Procedures for Floodplain and Wetland Reviews § 1022.16 Variances. (a) Emergency actions. DOE may...

  15. 10 CFR 1022.16 - Variances.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... such an action) DOE shall document the emergency actions in accordance with NEPA procedures at 10 CFR... ENERGY (GENERAL PROVISIONS) COMPLIANCE WITH FLOODPLAIN AND WETLAND ENVIRONMENTAL REVIEW REQUIREMENTS Procedures for Floodplain and Wetland Reviews § 1022.16 Variances. (a) Emergency actions. DOE may...

  16. 10 CFR 1022.16 - Variances.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... such an action) DOE shall document the emergency actions in accordance with NEPA procedures at 10 CFR... ENERGY (GENERAL PROVISIONS) COMPLIANCE WITH FLOODPLAIN AND WETLAND ENVIRONMENTAL REVIEW REQUIREMENTS Procedures for Floodplain and Wetland Reviews § 1022.16 Variances. (a) Emergency actions. DOE may...

  17. 10 CFR 1022.16 - Variances.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... such an action) DOE shall document the emergency actions in accordance with NEPA procedures at 10 CFR... ENERGY (GENERAL PROVISIONS) COMPLIANCE WITH FLOODPLAIN AND WETLAND ENVIRONMENTAL REVIEW REQUIREMENTS Procedures for Floodplain and Wetland Reviews § 1022.16 Variances. (a) Emergency actions. DOE may...

  18. 10 CFR 1022.16 - Variances.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... such an action) DOE shall document the emergency actions in accordance with NEPA procedures at 10 CFR... ENERGY (GENERAL PROVISIONS) COMPLIANCE WITH FLOODPLAIN AND WETLAND ENVIRONMENTAL REVIEW REQUIREMENTS Procedures for Floodplain and Wetland Reviews § 1022.16 Variances. (a) Emergency actions. DOE may...

  19. Variance Reduction for a Discrete Velocity Gas

    NASA Astrophysics Data System (ADS)

    Morris, A. B.; Varghese, P. L.; Goldstein, D. B.

    2011-05-01

    We extend a variance reduction technique developed by Baker and Hadjiconstantinou [1] to a discrete velocity gas. In our previous work, the collision integral was evaluated by importance sampling of collision partners [2]. Significant computational effort may be wasted by evaluating the collision integral in regions where the flow is in equilibrium. In the current approach, substantial computational savings are obtained by only solving for the deviations from equilibrium. In the near continuum regime, the deviations from equilibrium are small and low noise evaluation of the collision integral can be achieved with very coarse statistical sampling. Spatially homogenous relaxation of the Bobylev-Krook-Wu distribution [3,4], was used as a test case to verify that the method predicts the correct evolution of a highly non-equilibrium distribution to equilibrium. When variance reduction is not used, the noise causes the entropy to undershoot, but the method with variance reduction matches the analytic curve for the same number of collisions. We then extend the work to travelling shock waves and compare the accuracy and computational savings of the variance reduction method to DSMC over Mach numbers ranging from 1.2 to 10.

  20. Multiple Comparison Procedures when Population Variances Differ.

    ERIC Educational Resources Information Center

    Olejnik, Stephen; Lee, JaeShin

    A review of the literature on multiple comparison procedures suggests several alternative approaches for comparing means when population variances differ. These include: (1) the approach of P. A. Games and J. F. Howell (1976); (2) C. W. Dunnett's C confidence interval (1980); and (3) Dunnett's T3 solution (1980). These procedures control the…

  1. Variance Anisotropy of Solar Wind fluctuations

    NASA Astrophysics Data System (ADS)

    Oughton, S.; Matthaeus, W. H.; Wan, M.; Osman, K.

    2013-12-01

    Solar wind observations at MHD scales indicate that the energy associated with velocity and magnetic field fluctuations transverse to the mean magnetic field is typically much larger than that associated with parallel fluctuations [eg, 1]. This is often referred to as variance anisotropy. Various explanations for it have been suggested, including that the fluctuations are predominantly shear Alfven waves [1] and that turbulent dynamics leads to such states [eg, 2]. Here we investigate the origin and strength of such variance anisotropies, using spectral method simulations of the compressible (polytropic) 3D MHD equations. We report on results from runs with initial conditions that are either (i) broadband turbulence or (ii) fluctuations polarized in the same sense as shear Alfven waves. The dependence of the variance anisotropy on the plasma beta and Mach number is examined [3], along with the timescale for any variance anisotropy to develop. Implications for solar wind fluctuations will be discussed. References: [1] Belcher, J. W. and Davis Jr., L. (1971), J. Geophys. Res., 76, 3534. [2] Matthaeus, W. H., Ghosh, S., Oughton, S. and Roberts, D. A. (1996), J. Geophys. Res., 101, 7619. [3] Smith, C. W., B. J. Vasquez and K. Hamilton (2006), J. Geophys. Res., 111, A09111.

  2. Comparing the Variances of Two Dependent Groups.

    ERIC Educational Resources Information Center

    Wilcox, Rand R.

    1990-01-01

    Recently, C. E. McCulloch (1987) suggested a modification of the Morgan-Pitman test for comparing the variances of two dependent groups. This paper demonstrates that there are situations where the procedure is not robust. A subsample approach, similar to the Box-Scheffe test, and the Sandvik-Olsson procedure are also assessed. (TJH)

  3. Formative Use of Intuitive Analysis of Variance

    ERIC Educational Resources Information Center

    Trumpower, David L.

    2013-01-01

    Students' informal inferential reasoning (IIR) is often inconsistent with the normative logic underlying formal statistical methods such as Analysis of Variance (ANOVA), even after instruction. In two experiments reported here, student's IIR was assessed using an intuitive ANOVA task at the beginning and end of a statistics course. In…

  4. 78 FR 14122 - Revocation of Permanent Variances

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-04

    ... OSHA's scaffolds standards for construction (77 FR 46948). Today's notice revoking the variances takes... Safety and Health Act of 1970 (OSH Act; 29 U.S.C. 651, 655) in 1971 (see 36 FR 7340). Paragraphs (a)(4..., construction, and use of scaffolds (61 FR 46026). In the preamble to the final rule, OSHA stated that it...

  5. 7 CFR 205.290 - Temporary variances.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 3 2011-01-01 2011-01-01 false Temporary variances. 205.290 Section 205.290 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) ORGANIC FOODS PRODUCTION ACT PROVISIONS NATIONAL ORGANIC PROGRAM...

  6. 18 CFR 1304.408 - Variances.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 2 2012-04-01 2012-04-01 false Variances. 1304.408 Section 1304.408 Conservation of Power and Water Resources TENNESSEE VALLEY AUTHORITY APPROVAL OF CONSTRUCTION IN THE TENNESSEE RIVER SYSTEM AND REGULATION OF STRUCTURES AND OTHER ALTERATIONS...

  7. 18 CFR 1304.408 - Variances.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 2 2011-04-01 2011-04-01 false Variances. 1304.408 Section 1304.408 Conservation of Power and Water Resources TENNESSEE VALLEY AUTHORITY APPROVAL OF CONSTRUCTION IN THE TENNESSEE RIVER SYSTEM AND REGULATION OF STRUCTURES AND OTHER ALTERATIONS...

  8. How well can we estimate error variance of satellite precipitation data around the world?

    NASA Astrophysics Data System (ADS)

    Gebregiorgis, Abebe S.; Hossain, Faisal

    2015-03-01

    Providing error information associated with existing satellite precipitation estimates is crucial to advancing applications in hydrologic modeling. In this study, we present a method of estimating the square difference prediction of satellite precipitation (hereafter used synonymously with "error variance") using regression model for three satellite precipitation products (3B42RT, CMORPH, and PERSIANN-CCS) using easily available geophysical features and satellite precipitation rate. Building on a suite of recent studies that have developed the error variance models, the goal of this work is to explore how well the method works around the world in diverse geophysical settings. Topography, climate, and seasons are considered as the governing factors to segregate the satellite precipitation uncertainty and fit a nonlinear regression equation as a function of satellite precipitation rate. The error variance models were tested on USA, Asia, Middle East, and Mediterranean region. Rain-gauge based precipitation product was used to validate the error variance of satellite precipitation products. The regression approach yielded good performance skill with high correlation between simulated and observed error variances. The correlation ranged from 0.46 to 0.98 during the independent validation period. In most cases (~ 85% of the scenarios), the correlation was higher than 0.72. The error variance models also captured the spatial distribution of observed error variance adequately for all study regions while producing unbiased residual error. The approach is promising for regions where missed precipitation is not a common occurrence in satellite precipitation estimation. Our study attests that transferability of model estimators (which help to estimate the error variance) from one region to another is practically possible by leveraging the similarity in geophysical features. Therefore, the quantitative picture of satellite precipitation error over ungauged regions can be

  9. R package MVR for Joint Adaptive Mean-Variance Regularization and Variance Stabilization

    PubMed Central

    Dazard, Jean-Eudes; Xu, Hua; Rao, J. Sunil

    2015-01-01

    We present an implementation in the R language for statistical computing of our recent non-parametric joint adaptive mean-variance regularization and variance stabilization procedure. The method is specifically suited for handling difficult problems posed by high-dimensional multivariate datasets (p ≫ n paradigm), such as in ‘omics’-type data, among which are that the variance is often a function of the mean, variable-specific estimators of variances are not reliable, and tests statistics have low powers due to a lack of degrees of freedom. The implementation offers a complete set of features including: (i) normalization and/or variance stabilization function, (ii) computation of mean-variance-regularized t and F statistics, (iii) generation of diverse diagnostic plots, (iv) synthetic and real ‘omics’ test datasets, (v) computationally efficient implementation, using C interfacing, and an option for parallel computing, (vi) manual and documentation on how to setup a cluster. To make each feature as user-friendly as possible, only one subroutine per functionality is to be handled by the end-user. It is available as an R package, called MVR (‘Mean-Variance Regularization’), downloadable from the CRAN. PMID:26819572

  10. Variance of the Quantum Dwell Time for a Nonrelativistic Particle

    NASA Technical Reports Server (NTRS)

    Hahne, Gerhard

    2012-01-01

    Munoz, Seidel, and Muga [Phys. Rev. A 79, 012108 (2009)], following an earlier proposal by Pollak and Miller [Phys. Rev. Lett. 53, 115 (1984)] in the context of a theory of a collinear chemical reaction, showed that suitable moments of a two-flux correlation function could be manipulated to yield expressions for the mean quantum dwell time and mean square quantum dwell time for a structureless particle scattering from a time-independent potential energy field between two parallel lines in a two-dimensional spacetime. The present work proposes a generalization to a charged, nonrelativistic particle scattering from a transient, spatially confined electromagnetic vector potential in four-dimensional spacetime. The geometry of the spacetime domain is that of the slab between a pair of parallel planes, in particular those defined by constant values of the third (z) spatial coordinate. The mean Nth power, N = 1, 2, 3, . . ., of the quantum dwell time in the slab is given by an expression involving an N-flux-correlation function. All these means are shown to be nonnegative. The N = 1 formula reduces to an S-matrix result published previously [G. E. Hahne, J. Phys. A 36, 7149 (2003)]; an explicit formula for N = 2, and of the variance of the dwell time in terms of the S-matrix, is worked out. A formula representing an incommensurability principle between variances of the output-minus-input flux of a pair of dynamical variables (such as the particle s time flux and others) is derived.

  11. Family effects on early survival and variance in long-term reproductive success of female cheetahs.

    PubMed

    Pettorelli, Nathalie; Durant, Sarah M

    2007-09-01

    1. While it is generally accepted that the survival of offspring within families may be correlated, the extent of correlation has been largely untested. Furthermore, the impact of such correlation on the estimated variance in females' reproductive success has rarely been quantified. 2. Here we use an exceptional data set from a long-term study of individually recognized cheetahs from the Serengeti National Park in Tanzania to formally quantify family effects in carnivores. 3. We show (i) that cubs from the same litter exhibit more similar fates than unrelated cubs when it comes to first-year survival; and (ii) that the observed variance of the long-term reproductive success of females is twice the variance expected under the assumption of complete independence of fates between cubs. 4. We suggest that family effects are likely to be widespread in vertebrates with average litter sizes > 1, and could have important consequences for population dynamics and population viability analyses. PMID:17714269

  12. 42 CFR 456.525 - Request for renewal of variance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Request for renewal of variance. 456.525 Section..., and Variances for Hospitals and Mental Hospitals Ur Plan: Remote Facility Variances from Time Requirements § 456.525 Request for renewal of variance. (a) The agency must submit a request for renewal of...

  13. 10 CFR 851.32 - Action on variance requests.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Action on variance requests. 851.32 Section 851.32 Energy DEPARTMENT OF ENERGY WORKER SAFETY AND HEALTH PROGRAM Variances § 851.32 Action on variance requests. (a... approval of a variance application, the Chief Health, Safety and Security Officer must forward to the...

  14. 41 CFR 50-204.1a - Variances.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 41 Public Contracts and Property Management 1 2010-07-01 2010-07-01 true Variances. 50-204.1a... and Application § 50-204.1a Variances. (a) Variances from standards in this part may be granted in the same circumstances in which variances may be granted under sections 6(b)(6)(A) or 6(d) of the...

  15. 21 CFR 898.14 - Exemptions and variances.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Exemptions and variances. 898.14 Section 898.14... variances. (a) A request for an exemption or variance shall be submitted in the form of a petition under... with the device; and (4) Other information justifying the exemption or variance. (b) An exemption...

  16. 10 CFR 851.30 - Consideration of variances.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Consideration of variances. 851.30 Section 851.30 Energy DEPARTMENT OF ENERGY WORKER SAFETY AND HEALTH PROGRAM Variances § 851.30 Consideration of variances. (a) Variances shall be granted by the Under Secretary after considering the recommendation of the Chief...

  17. 42 CFR 456.521 - Conditions for granting variance requests.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Conditions for granting variance requests. 456.521..., and Variances for Hospitals and Mental Hospitals Ur Plan: Remote Facility Variances from Time Requirements § 456.521 Conditions for granting variance requests. (a) Except as described under paragraph...

  18. Estimates of variances due to direct and maternal effects for growth traits of Romanov sheep.

    PubMed

    María, G A; Boldman, K G; Van Vleck, L D

    1993-04-01

    Records of growth traits of 2,086 Romanov lambs were used to estimate variance components for an animal model and genetic correlations between growth traits. Traits analyzed were birth weight (BWT), weaning weight (WW), 90-d weight (W90), and daily gain for the periods birth to weaning (DG1) and weaning to 90 d (DG2). Weaning was at approximately 40 d. Variance components were estimated using restricted maximum likelihood with an animal model including fixed effects for year x season, sex, rearing type, and litter size and random effects for the direct genetic effect of the animal (with relative variance h2), the maternal genetic effect (with relative variance m2), the permanent environmental effect (with relative variance c2), and random residual effect. Genetic correlations were estimated for a model with the same fixed effects and only additive genetic effects. Estimates of the variances of random effects, h2, m2, and c2, respectively, as a proportion of phenotypic variance were .04, .22, .10 (BWT); .34, .25, .0 (WW); .09, .01, .07 (W90); .26, .17, .02 (DG1); and .15, .01, .03 (DG2). Estimates of genetic correlations were .12 (BWT with WW); .24 (BWT with W90); .48 (WW with W90); .69 (DG1 with DG2); -.01 (BWT with DG1); .05 (BWT with DG2); .59 (WW with DG1); .47 (WW with DG2); .67 (W90 with DG1); and .98 (W90 with DG2). Results suggest that selection should be effective for WW, DG1, and DG2 but less effective for BWT and W90. An important maternal effect was observed for BWT, WW, and DG1. The estimates of genetic correlations showed no genetic antagonisms among the traits. PMID:8478286

  19. The latitude dependence of the variance of zonally averaged quantities. [in polar meteorology with attention to geometrical effects of earth

    NASA Technical Reports Server (NTRS)

    North, G. R.; Bell, T. L.; Cahalan, R. F.; Moeng, F. J.

    1982-01-01

    Geometric characteristics of the spherical earth are shown to be responsible for the increase of variance with latitude of zonally averaged meteorological statistics. An analytic model is constructed to display the effect of a spherical geometry on zonal averages, employing a sphere labeled with radial unit vectors in a real, stochastic field expanded in complex spherical harmonics. The variance of a zonally averaged field is found to be expressible in terms of the spectrum of the vector field of the spherical harmonics. A maximum variance is then located at the poles, and the ratio of the variance to the zonally averaged grid-point variance, weighted by the cosine of the latitude, yields the zonal correlation typical of the latitude. An example is provided for the 500 mb level in the Northern Hemisphere compared to 15 years of data. Variance is determined to increase north of 60 deg latitude.

  20. Heritable environmental variance causes nonlinear relationships between traits: application to birth weight and stillbirth of pigs.

    PubMed

    Mulder, Herman A; Hill, William G; Knol, Egbert F

    2015-04-01

    There is recent evidence from laboratory experiments and analysis of livestock populations that not only the phenotype itself, but also its environmental variance, is under genetic control. Little is known about the relationships between the environmental variance of one trait and mean levels of other traits, however. A genetic covariance between these is expected to lead to nonlinearity between them, for example between birth weight and survival of piglets, where animals of extreme weights have lower survival. The objectives were to derive this nonlinear relationship analytically using multiple regression and apply it to data on piglet birth weight and survival. This study provides a framework to study such nonlinear relationships caused by genetic covariance of environmental variance of one trait and the mean of the other. It is shown that positions of phenotypic and genetic optima may differ and that genetic relationships are likely to be more curvilinear than phenotypic relationships, dependent mainly on the environmental correlation between these traits. Genetic correlations may change if the population means change relative to the optimal phenotypes. Data of piglet birth weight and survival show that the presence of nonlinearity can be partly explained by the genetic covariance between environmental variance of birth weight and survival. The framework developed can be used to assess effects of artificial and natural selection on means and variances of traits and the statistical method presented can be used to estimate trade-offs between environmental variance of one trait and mean levels of others. PMID:25631318

  1. Heritable Environmental Variance Causes Nonlinear Relationships Between Traits: Application to Birth Weight and Stillbirth of Pigs

    PubMed Central

    Mulder, Herman A.; Hill, William G.; Knol, Egbert F.

    2015-01-01

    There is recent evidence from laboratory experiments and analysis of livestock populations that not only the phenotype itself, but also its environmental variance, is under genetic control. Little is known about the relationships between the environmental variance of one trait and mean levels of other traits, however. A genetic covariance between these is expected to lead to nonlinearity between them, for example between birth weight and survival of piglets, where animals of extreme weights have lower survival. The objectives were to derive this nonlinear relationship analytically using multiple regression and apply it to data on piglet birth weight and survival. This study provides a framework to study such nonlinear relationships caused by genetic covariance of environmental variance of one trait and the mean of the other. It is shown that positions of phenotypic and genetic optima may differ and that genetic relationships are likely to be more curvilinear than phenotypic relationships, dependent mainly on the environmental correlation between these traits. Genetic correlations may change if the population means change relative to the optimal phenotypes. Data of piglet birth weight and survival show that the presence of nonlinearity can be partly explained by the genetic covariance between environmental variance of birth weight and survival. The framework developed can be used to assess effects of artificial and natural selection on means and variances of traits and the statistical method presented can be used to estimate trade-offs between environmental variance of one trait and mean levels of others. PMID:25631318

  2. Analysis of variance of microarray data.

    PubMed

    Ayroles, Julien F; Gibson, Greg

    2006-01-01

    Analysis of variance (ANOVA) is an approach used to identify differentially expressed genes in complex experimental designs. It is based on testing for the significance of the magnitude of effect of two or more treatments taking into account the variance within and between treatment classes. ANOVA is a highly flexible analytical approach that allows investigators to simultaneously assess the contributions of multiple factors to gene expression variation, including technical (dye, batch) effects and biological (sex, genotype, drug, time) ones, as well as interactions between factors. This chapter provides an overview of the theory of linear mixture modeling and the sequence of steps involved in fitting gene-specific models and discusses essential features of experimental design. Commercial and open-source software for performing ANOVA is widely available. PMID:16939792

  3. PHD filtering with localised target number variance

    NASA Astrophysics Data System (ADS)

    Delande, Emmanuel; Houssineau, Jérémie; Clark, Daniel

    2013-05-01

    Mahler's Probability Hypothesis Density (PHD filter), proposed in 2000, addresses the challenges of the multipletarget detection and tracking problem by propagating a mean density of the targets in any region of the state space. However, when retrieving some local evidence on the target presence becomes a critical component of a larger process - e.g. for sensor management purposes - the local target number is insufficient unless some confidence on the estimation of the number of targets can be provided as well. In this paper, we propose a first implementation of a PHD filter that also includes an estimation of localised variance in the target number following each update step; we then illustrate the advantage of the PHD filter + variance on simulated data from a multiple-target scenario.

  4. Applications of non-parametric statistics and analysis of variance on sample variances

    NASA Technical Reports Server (NTRS)

    Myers, R. H.

    1981-01-01

    Nonparametric methods that are available for NASA-type applications are discussed. An attempt will be made here to survey what can be used, to attempt recommendations as to when each would be applicable, and to compare the methods, when possible, with the usual normal-theory procedures that are avavilable for the Gaussion analog. It is important here to point out the hypotheses that are being tested, the assumptions that are being made, and limitations of the nonparametric procedures. The appropriateness of doing analysis of variance on sample variances are also discussed and studied. This procedure is followed in several NASA simulation projects. On the surface this would appear to be reasonably sound procedure. However, difficulties involved center around the normality problem and the basic homogeneous variance assumption that is mase in usual analysis of variance problems. These difficulties discussed and guidelines given for using the methods.

  5. Systems Engineering Programmatic Estimation Using Technology Variance

    NASA Technical Reports Server (NTRS)

    Mog, Robert A.

    2000-01-01

    Unique and innovative system programmatic estimation is conducted using the variance of the packaged technologies. Covariance analysis is performed on the subsystems and components comprising the system of interest. Technological "return" and "variation" parameters are estimated. These parameters are combined with the model error to arrive at a measure of system development stability. The resulting estimates provide valuable information concerning the potential cost growth of the system under development.

  6. Systems Engineering Programmatic Estimation Using Technology Variance

    NASA Technical Reports Server (NTRS)

    Mog, Robert A.

    2000-01-01

    Unique and innovative system programmatic estimation is conducted using the variance of the packaged technologies. Covariance analysis is performed oil the subsystems and components comprising the system of interest. Technological "returns" and "variation" parameters, are estimated. These parameters are combined with the model error to arrive at a measure of system development stability. The resulting estimates provide valuable information concerning the potential cost growth of the system under development.

  7. Analysis of variance based on fuzzy observations

    NASA Astrophysics Data System (ADS)

    Nourbakhsh, M.; Mashinchi, M.; Parchami, A.

    2013-04-01

    Analysis of variance (ANOVA) is an important method in exploratory and confirmatory data analysis. The simplest type of ANOVA is one-way ANOVA for comparison among means of several populations. In this article, we extend one-way ANOVA to a case where observed data are fuzzy observations rather than real numbers. Two real-data examples are given to show the performance of this method.

  8. The Theory of Variances in Equilibrium Reconstruction

    SciTech Connect

    Zakharov, Leonid E.; Lewandowski, Jerome; Foley, Elizabeth L.; Levinton, Fred M.; Yuh, Howard Y.; Drozdov, Vladimir; McDonald, Darren

    2008-01-14

    The theory of variances of equilibrium reconstruction is presented. It complements existing practices with information regarding what kind of plasma profiles can be reconstructed, how accurately, and what remains beyond the abilities of diagnostic systems. The σ-curves, introduced by the present theory, give a quantitative assessment of quality of effectiveness of diagnostic systems in constraining equilibrium reconstructions. The theory also suggests a method for aligning the accuracy of measurements of different physical nature.

  9. Minimum variance and variance of outgoing quality limit MDS-1(c1, c2) plans

    NASA Astrophysics Data System (ADS)

    Raju, C.; Vidya, R.

    2016-06-01

    In this article, the outgoing quality (OQ) and total inspection (TI) of multiple deferred state sampling plans MDS-1(c1,c2) are studied. It is assumed that the inspection is rejection rectification. Procedures for designing MDS-1(c1,c2) sampling plans with minimum variance of OQ and TI are developed. A procedure for obtaining a plan for a designated upper limit for the variance of the OQ (VOQL) is outlined.

  10. Hypothesis exploration with visualization of variance

    PubMed Central

    2014-01-01

    Background The Consortium for Neuropsychiatric Phenomics (CNP) at UCLA was an investigation into the biological bases of traits such as memory and response inhibition phenotypes—to explore whether they are linked to syndromes including ADHD, Bipolar disorder, and Schizophrenia. An aim of the consortium was in moving from traditional categorical approaches for psychiatric syndromes towards more quantitative approaches based on large-scale analysis of the space of human variation. It represented an application of phenomics—wide-scale, systematic study of phenotypes—to neuropsychiatry research. Results This paper reports on a system for exploration of hypotheses in data obtained from the LA2K, LA3C, and LA5C studies in CNP. ViVA is a system for exploratory data analysis using novel mathematical models and methods for visualization of variance. An example of these methods is called VISOVA, a combination of visualization and analysis of variance, with the flavor of exploration associated with ANOVA in biomedical hypothesis generation. It permits visual identification of phenotype profiles—patterns of values across phenotypes—that characterize groups. Visualization enables screening and refinement of hypotheses about variance structure of sets of phenotypes. Conclusions The ViVA system was designed for exploration of neuropsychiatric hypotheses by interdisciplinary teams. Automated visualization in ViVA supports ‘natural selection’ on a pool of hypotheses, and permits deeper understanding of the statistical architecture of the data. Large-scale perspective of this kind could lead to better neuropsychiatric diagnostics. PMID:25097666

  11. Directional variance analysis of annual rings

    NASA Astrophysics Data System (ADS)

    Kumpulainen, P.; Marjanen, K.

    2010-07-01

    The wood quality measurement methods are of increasing importance in the wood industry. The goal is to produce more high quality products with higher marketing value than is produced today. One of the key factors for increasing the market value is to provide better measurements for increased information to support the decisions made later in the product chain. Strength and stiffness are important properties of the wood. They are related to mean annual ring width and its deviation. These indicators can be estimated from images taken from the log ends by two-dimensional power spectrum analysis. The spectrum analysis has been used successfully for images of pine. However, the annual rings in birch, for example are less distinguishable and the basic spectrum analysis method does not give reliable results. A novel method for local log end variance analysis based on Radon-transform is proposed. The directions and the positions of the annual rings can be estimated from local minimum and maximum variance estimates. Applying the spectrum analysis on the maximum local variance estimate instead of the original image produces more reliable estimate of the annual ring width. The proposed method is not limited to log end analysis only. It is usable in other two-dimensional random signal and texture analysis tasks.

  12. Variance component estimates for alternative litter size traits in swine.

    PubMed

    Putz, A M; Tiezzi, F; Maltecca, C; Gray, K A; Knauer, M T

    2015-11-01

    Litter size at d 5 (LS5) has been shown to be an effective trait to increase total number born (TNB) while simultaneously decreasing preweaning mortality. The objective of this study was to determine the optimal litter size day for selection (i.e., other than d 5). Traits included TNB, number born alive (NBA), litter size at d 2, 5, 10, 30 (LS2, LS5, LS10, LS30, respectively), litter size at weaning (LSW), number weaned (NW), piglet mortality at d 30 (MortD30), and average piglet birth weight (BirthWt). Litter size traits were assigned to biological litters and treated as a trait of the sow. In contrast, NW was the number of piglets weaned by the nurse dam. Bivariate animal models included farm, year-season, and parity as fixed effects. Number born alive was fit as a covariate for BirthWt. Random effects included additive genetics and the permanent environment of the sow. Variance components were plotted for TNB, NBA, and LS2 to LS30 using univariate animal models to determine how variances changed over time. Additive genetic variance was minimized at d 7 in Large White and at d 14 in Landrace pigs. Total phenotypic variance for litter size traits decreased over the first 10 d and then stabilized. Heritability estimates increased between TNB and LS30. Genetic correlations between TNB, NBA, and LS2 to LS29 with LS30 plateaued within the first 10 d. A genetic correlation with LS30 of 0.95 was reached at d 4 for Large White and at d 8 for Landrace pigs. Heritability estimates ranged from 0.07 to 0.13 for litter size traits and MortD30. Birth weight had an h of 0.24 and 0.26 for Large White and Landrace pigs, respectively. Genetic correlations among LS30, LSW, and NW ranged from 0.97 to 1.00. In the Large White breed, genetic correlations between MortD30 with TNB and LS30 were 0.23 and -0.64, respectively. These correlations were 0.10 and -0.61 in the Landrace breed. A high genetic correlation of 0.98 and 0.97 was observed between LS10 and NW for Large White and

  13. Changes in the Proteome of Langat-Infected Ixodes scapularis ISE6 Cells: Metabolic Pathways Associated with Flavivirus Infection

    PubMed Central

    Grabowski, Jeffrey M.; Perera, Rushika; Roumani, Ali M.; Hedrick, Victoria E.; Inerowicz, Halina D.; Hill, Catherine A.; Kuhn, Richard J.

    2016-01-01

    Background Ticks (Family Ixodidae) transmit a variety of disease causing agents to humans and animals. The tick-borne flaviviruses (TBFs; family Flaviviridae) are a complex of viruses, many of which cause encephalitis and hemorrhagic fever, and represent global threats to human health and biosecurity. Pathogenesis has been well studied in human and animal disease models. Equivalent analyses of tick-flavivirus interactions are limited and represent an area of study that could reveal novel approaches for TBF control. Methodology/Principal Findings High resolution LC-MS/MS was used to analyze the proteome of Ixodes scapularis (Lyme disease tick) embryonic ISE6 cells following infection with Langat virus (LGTV) and identify proteins associated with viral infection and replication. Maximal LGTV infection of cells and determination of peak release of infectious virus, was observed at 36 hours post infection (hpi). Proteins were extracted from ISE6 cells treated with LGTV and non-infectious (UV inactivated) LGTV at 36 hpi and analyzed by mass spectrometry. The Omics Discovery Pipeline (ODP) identified thousands of MS peaks. Protein homology searches against the I. scapularis IscaW1 genome assembly identified a total of 486 proteins that were subsequently assigned to putative functional pathways using searches against the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. 266 proteins were differentially expressed following LGTV infection relative to non-infected (mock) cells. Of these, 68 proteins exhibited increased expression and 198 proteins had decreased expression. The majority of the former were classified in the KEGG pathways: “translation”, “amino acid metabolism”, and “protein folding/sorting/degradation”. Finally, Trichostatin A and Oligomycin A increased and decreased LGTV replication in vitro in ISE6 cells, respectively. Conclusions/Significance Proteomic analyses revealed ISE6 proteins that were differentially expressed at the peak of LGTV

  14. First isolation of Aedes flavivirus in the Western Hemisphere and evidence of vertical transmission in the mosquito Aedes (Stegomyia) albopictus (Diptera: Culicidae)

    SciTech Connect

    Haddow, Andrew D.; Guzman, Hilda; Popov, Vsevolod L.; Wood, Thomas G.; Widen, Steven G.; Haddow, Alastair D.; Tesh, Robert B.; Weaver, Scott C.

    2013-06-05

    We report here the first evidence of vertical transmission of Aedes flavivirus (AEFV) and its first isolation in the Western Hemisphere. AEFV strain SPFLD-MO-2011-MP6 was isolated in C6/36 cells from a pool of male Aedes albopictus mosquitoes that were reared to adults from larvae collected in southwest Missouri, USA, in 2011. Electron micrographs of the virus showed virions of approximately 45 nm in diameter with morphological characteristics associated with flaviviruses. The genomic sequence demonstrated that AEFV-SPFLD-MO-2011-MP6 shares a high degree of nucleotide and amino acid sequence identity with the AEFV Narita-21 strain, isolated in Japan in 2003. Intracerebral inoculation of newborn mice with the virus failed to produce observable illness or death and the virus did not replicate in vertebrate cells, consistent with a lack of vertebrate host range. - Highlights: ► The first report of Aedes flavivirus (AEFV) in the Western Hemisphere. ► The first evidence of vertical transmission of AEFV in mosquitoes. ► The first electron micrograph of AEFV. ► The first attempt to infect animals with AEFV.

  15. Meta-analysis of All Immune Epitope Data in the Flavivirus Genus: Inventory of Current Immune Epitope Data Status in the Context of Virus Immunity and Immunopathology

    PubMed Central

    Greenbaum, Jason; Blythe, Martin; Peters, Bjoern; Sette, Alessandro

    2010-01-01

    Abstract A meta-analysis was performed in order to inventory the immune epitope data related to viruses in the genus Flavivirus. Nearly 2000 epitopes were captured from over 130 individual Flavivirus-related references identified from PubMed and reported as of September 2009. This report includes all epitope structures and associated immune reactivity from the past and current literature, including: the epitope distribution among pathogens and related strains, the epitope distribution among different pathogen antigens, the number of epitopes defined in human and animal models of disease, the relationship between epitopes identified in different disease states following natural (or experimental) infection, and data from studies focused on candidate vaccines. We found that the majority of epitopes were defined for dengue virus (DENV) and West Nile virus (WNV). The prominence of DENV and WNV data in the epitope literature is likely a reflection of their overall worldwide impact on human disease, and the lack of vaccines. Conversely, the relatively smaller number of epitopes defined for the other viruses within the genus (yellow fever and Japanese encephalitis virus) most likely reflects the presence of established prophylaxis and/or their more modest impact on morbidity and mortality globally. Through this work we hope to provide useful data to those working in the area of Flavivirus research. PMID:20565291

  16. Minimum variance brain source localization for short data sequences.

    PubMed

    Ravan, Maryam; Reilly, James P; Hasey, Gary

    2014-02-01

    In the electroencephalogram (EEG) or magnetoencephalogram (MEG) context, brain source localization methods that rely on estimating second-order statistics often fail when the number of samples of the recorded data sequences is small in comparison to the number of electrodes. This condition is particularly relevant when measuring evoked potentials. Due to the correlated background EEG/MEG signal, an adaptive approach to localization is desirable. Previous work has addressed these issues by reducing the adaptive degrees of freedom (DoFs). This reduction results in decreased resolution and accuracy of the estimated source configuration. This paper develops and tests a new multistage adaptive processing technique based on the minimum variance beamformer for brain source localization that has been previously used in the radar statistical signal processing context. This processing, referred to as the fast fully adaptive (FFA) approach, can significantly reduce the required sample support, while still preserving all available DoFs. To demonstrate the performance of the FFA approach in the limited data scenario, simulation and experimental results are compared with two previous beamforming approaches; i.e., the fully adaptive minimum variance beamforming method and the beamspace beamforming method. Both simulation and experimental results demonstrate that the FFA method can localize all types of brain activity more accurately than the other approaches with limited data. PMID:24108457

  17. Visual SLAM Using Variance Grid Maps

    NASA Technical Reports Server (NTRS)

    Howard, Andrew B.; Marks, Tim K.

    2011-01-01

    An algorithm denoted Gamma-SLAM performs further processing, in real time, of preprocessed digitized images acquired by a stereoscopic pair of electronic cameras aboard an off-road robotic ground vehicle to build accurate maps of the terrain and determine the location of the vehicle with respect to the maps. Part of the name of the algorithm reflects the fact that the process of building the maps and determining the location with respect to them is denoted simultaneous localization and mapping (SLAM). Most prior real-time SLAM algorithms have been limited in applicability to (1) systems equipped with scanning laser range finders as the primary sensors in (2) indoor environments (or relatively simply structured outdoor environments). The few prior vision-based SLAM algorithms have been feature-based and not suitable for real-time applications and, hence, not suitable for autonomous navigation on irregularly structured terrain. The Gamma-SLAM algorithm incorporates two key innovations: Visual odometry (in contradistinction to wheel odometry) is used to estimate the motion of the vehicle. An elevation variance map (in contradistinction to an occupancy or an elevation map) is used to represent the terrain. The Gamma-SLAM algorithm makes use of a Rao-Blackwellized particle filter (RBPF) from Bayesian estimation theory for maintaining a distribution over poses and maps. The core idea of the RBPF approach is that the SLAM problem can be factored into two parts: (1) finding the distribution over robot trajectories, and (2) finding the map conditioned on any given trajectory. The factorization involves the use of a particle filter in which each particle encodes both a possible trajectory and a map conditioned on that trajectory. The base estimate of the trajectory is derived from visual odometry, and the map conditioned on that trajectory is a Cartesian grid of elevation variances. In comparison with traditional occupancy or elevation grid maps, the grid elevation variance

  18. Preliminary findings on Bagaza virus (Flavivirus: Flaviviridae) growth kinetics, transmission potential & transovarial transmission in three species of mosquitoes

    PubMed Central

    Sudeep, A.B.; Bondre, V.P.; Mavale, M.S.; Ghodke, Y.S.; George, R.P.; Aher, R.V.; Gokhale, M.D.

    2013-01-01

    Background & objectives: Bagaza virus (BAGV), a flavivirus synonymous with Israel turkey meningoencephalitis virus, has been found to circulate in India. BAGV has recently been held responsible for inducing febrile illness in humans and causing unusually high mortality to wild birds in Spain. A study was therefore, undertaken to determine its replication kinetics in certain mosquitoes and to determine vector competence and potential of the mosquitoes to transmit BAGV experimentally. Methods: Aedes aegypti, Culex tritaeniorhynchus and Cx quinquefasciatus mosquitoes were inoculated with BAGV; samples were harvested every day and titrated in BHK-21 cell line. Vector competence and experimental transmission were determined by examining the saliva of infected mosquitoes for virus and induction of sickness in suckling mice, respectively. Results: Cx. tritaeniorhynchus and Ae. aegypti mosquitoes yielded 5 log10 and 4.67 log10 TCID50/ml of virus on day 3 post-infection (PI), respectively while Cx. quinquefasciatus yielded a titre of 4 log10 TCID50/ml on day 4 PI. BAGV was detected in saliva of all the infected mosquitoes demonstrating their vector competence. Experimental transmission of BAGV to infant mice as well as transovarial transmission was demonstrated by Cx. tritaeniorhynchus but not by Ae. aegypti and Cx. quinquefasciatus mosquitoes. Interpretation & conclusions: Replication of BAGV to high titres and dissemination to saliva in three most prevalent mosquitoes in India is of immense public health importance. Though no major outbreak involving man has been reported yet, BAGV has a potential to cause outbreaks in future. PMID:24056604

  19. [The Alkhurma virus (family Flaviviridae, genus Flavivirus): an emerging pathogen responsible for hemorrhage fever in the Middle East].

    PubMed

    Charrel, R N; de Lamballerie, X

    2003-01-01

    To date tick-borne flaviviruses causing hemorrhagic fevers in humans have been isolated in Siberia (Omsk hemorrhagic fever virus), India (Kyasanur Forest disease virus), and Saudi Arabia (Akhurma virus). Because of their potential use as biological weapons for bioterrorism, these 3 viruses require level 4 biosafety handling facilities and have been listed as hypervirulent pathogens by the Center for Disease Control and Prevention. Alkhurma virus was isolated in 1995 from patients with hemorrhagic fever in Saudi Arabia. Current evidence suggests that transmission to humans can occur either transcutaneously either by contamination of a skin wound with the blood of an infected vertebrate or bites of an infected tick or orally by drinking unpasteurized contaminated milk. To date a total of 24 symptomatic human cases have been recorded with a mortality rate at 25% (6/24). Pauci-symptomatic or asymptomatic cases are likely but epidemiologic data are currently unavailable. The complete coding sequence of the prototype strain of Alkhurma virus was determined and published in 2001 based on international research project involving investigators from France, Great Britain, and Saudi Arabia. Phylogenetic studies demonstrate that closest known relative of Alkhurma virus is Kyasanur Forest disease virus and that both viruses share a common ancestor. Genetic analysis of several human strains sequentially isolated over a 5-year period showed a very low diversity. This finding has important potential implications for diagnosis and vaccination. PMID:14579470

  20. Genetic Determinants of Sindbis Virus Mosquito Infection Are Associated with a Highly Conserved Alphavirus and Flavivirus Envelope Sequence▿

    PubMed Central

    Pierro, Dennis J.; Powers, Erik L.; Olson, Ken E.

    2008-01-01

    Wild-type Sindbis virus (SINV) strain MRE16 efficiently infects Aedes aegypti midgut epithelial cells (MEC), but laboratory-derived neurovirulent SINV strain TE/5′2J infects MEC poorly. SINV determinants for MEC infection have been localized to the E2 glycoprotein. The E2 amino acid sequences of MRE16 and TE/5′2J differ at 60 residue sites. To identify the genetic determinants of MEC infection of MRE16, the TE/5′2J virus genome was altered to contain either domain chimeras or more focused nucleotide substitutions of MRE16. The growth patterns of derived viruses in cell culture were determined, as were the midgut infection rates (MIR) in A. aegypti mosquitoes. The results showed that substitutions of MRE16 E2 aa 95 to 96 and 116 to 119 into the TE/5′2J virus increased MIR both independently and in combination with each other. In addition, a unique PPF/.GDS amino acid motif was located between these two sites that was found to be a highly conserved sequence among alphaviruses and flaviviruses but not other arboviruses. PMID:18160430

  1. Cosmic variance in inflation with two light scalars

    NASA Astrophysics Data System (ADS)

    Bonga, Béatrice; Brahma, Suddhasattwa; Deutsch, Anne-Sylvie; Shandera, Sarah

    2016-05-01

    We examine the squeezed limit of the bispectrum when a light scalar with arbitrary non-derivative self-interactions is coupled to the inflaton. We find that when the hidden sector scalar is sufficiently light (m lesssim 0.1 H), the coupling between long and short wavelength modes from the series of higher order correlation functions (from arbitrary order contact diagrams) causes the statistics of the fluctuations to vary in sub-volumes. This means that observations of primordial non-Gaussianity cannot be used to uniquely reconstruct the potential of the hidden field. However, the local bispectrum induced by mode-coupling from these diagrams always has the same squeezed limit, so the field's locally determined mass is not affected by this cosmic variance.

  2. Variance estimation for the Federal Waterfowl Harvest Surveys

    USGS Publications Warehouse

    Geissler, P.H.

    1988-01-01

    The Federal Waterfowl Harvest Surveys provide estimates of waterfowl harvest by species for flyways and states, harvests of most other migratory game bird species (by waterfowl hunters), crippling losses for ducks, geese, and coots, days hunted, and bag per hunter. The Waterfowl Hunter Questionnaire Survey separately estimates the harvest of ducks and geese using cluster samples of hunters who buy duck stamps at sample post offices. The Waterfowl Parts Collection estimates species, age, and sex ratios from parts solicited from successful hunters who responded to the Waterfowl Hunter Questionnaire Survey in previous years. These ratios are used to partition the duck and goose harvest into species, age, and sex specific harvest estimates. Annual estimates are correlated because successful hunters who respond to the Questionnaire Survey in one year may be asked to contribute to the Parts Collection for the next three years. Bootstrap variance estimates are used because covariances among years are difficult to estimate.

  3. Simulated central apnea detection using the pressure variance.

    PubMed

    Townsend, Daphne I; Holtzman, Megan; Goubran, Rafik; Frize, Monique; Knoefel, Frank

    2009-01-01

    This paper presents use of an unobtrusive pressure sensor array for simulated central apnea detection. Data was collected from seven volunteers who performed a series of regular breathing and breath holding exercises to simulate central apneas. Results of the feature extraction from the breathing signals show that breathing events may be differentiated with epoch based variance calculations. Two approaches were considered: the single sensor approach and the multisensor vote approach. The multisensor vote approach can decrease false positives and increase the value of Matthew's Correlation Coefficient. The effect of lying position on correct classification was investigated by modifying the multisensor vote approach to reduce false positives segments caused by the balistocardiogram signal and as such increase sensitivity while maintaining a low false positive rate. Intersubject classification results had low variability in both approaches. PMID:19964320

  4. Empirical data and the variance-covariance matrix for the 1969 Smithsonian Standard Earth (2)

    NASA Technical Reports Server (NTRS)

    Gaposchkin, E. M.

    1972-01-01

    The empirical data used in the 1969 Smithsonian Standard Earth (2) are presented. The variance-covariance matrix, or the normal equations, used for correlation analysis, are considered. The format and contents of the matrix, available on magnetic tape, are described and a sample printout is given.

  5. The Evolution of Human Intelligence and the Coefficient of Additive Genetic Variance in Human Brain Size

    ERIC Educational Resources Information Center

    Miller, Geoffrey F.; Penke, Lars

    2007-01-01

    Most theories of human mental evolution assume that selection favored higher intelligence and larger brains, which should have reduced genetic variance in both. However, adult human intelligence remains highly heritable, and is genetically correlated with brain size. This conflict might be resolved by estimating the coefficient of additive genetic…

  6. Estimators for variance components in structured stair nesting models

    NASA Astrophysics Data System (ADS)

    Monteiro, Sandra; Fonseca, Miguel; Carvalho, Francisco

    2016-06-01

    The purpose of this paper is to present the estimation of the components of variance in structured stair nesting models. The relationship between the canonical variance components and the original ones, will be very important in obtaining that estimators.

  7. Variance of the quantum dwell time for a nonrelativistic particle

    SciTech Connect

    Hahne, G. E.

    2013-01-15

    Munoz, Seidel, and Muga [Phys. Rev. A 79, 012108 (2009)], following an earlier proposal by Pollak and Miller [Phys. Rev. Lett. 53, 115 (1984)] in the context of a theory of a collinear chemical reaction, showed that suitable moments of a two-flux correlation function could be manipulated to yield expressions for the mean quantum dwell time and mean square quantum dwell time for a structureless particle scattering from a time-independent potential energy field between two parallel lines in a two-dimensional spacetime. The present work proposes a generalization to a charged, nonrelativistic particle scattering from a transient, spatially confined electromagnetic vector potential in four-dimensional spacetime. The geometry of the spacetime domain is that of the slab between a pair of parallel planes, in particular, those defined by constant values of the third (z) spatial coordinate. The mean Nth power, N= 1, 2, 3, Horizontal-Ellipsis , of the quantum dwell time in the slab is given by an expression involving an N-flux-correlation function. All these means are shown to be nonnegative. The N= 1 formula reduces to an S-matrix result published previously [G. E. Hahne, J. Phys. A 36, 7149 (2003)]; an explicit formula for N= 2, and of the variance of the dwell time in terms of the S-matrix, is worked out. A formula representing an incommensurability principle between variances of the output-minus-input flux of a pair of dynamical variables (such as the particle's time flux and others) is derived.

  8. Variance of the quantum dwell time for a nonrelativistic particle

    NASA Astrophysics Data System (ADS)

    Hahne, G. E.

    2013-01-01

    Muñoz, Seidel, and Muga [Phys. Rev. A 79, 012108 (2009), 10.1103/PhysRevA.79.012108], following an earlier proposal by Pollak and Miller [Phys. Rev. Lett. 53, 115 (1984), 10.1103/PhysRevLett.53.115] in the context of a theory of a collinear chemical reaction, showed that suitable moments of a two-flux correlation function could be manipulated to yield expressions for the mean quantum dwell time and mean square quantum dwell time for a structureless particle scattering from a time-independent potential energy field between two parallel lines in a two-dimensional spacetime. The present work proposes a generalization to a charged, nonrelativistic particle scattering from a transient, spatially confined electromagnetic vector potential in four-dimensional spacetime. The geometry of the spacetime domain is that of the slab between a pair of parallel planes, in particular, those defined by constant values of the third (z) spatial coordinate. The mean Nth power, N = 1, 2, 3, …, of the quantum dwell time in the slab is given by an expression involving an N-flux-correlation function. All these means are shown to be nonnegative. The N = 1 formula reduces to an S-matrix result published previously [G. E. Hahne, J. Phys. A 36, 7149 (2003), 10.1088/0305-4470/36/25/316]; an explicit formula for N = 2, and of the variance of the dwell time in terms of the S-matrix, is worked out. A formula representing an incommensurability principle between variances of the output-minus-input flux of a pair of dynamical variables (such as the particle's time flux and others) is derived.

  9. 40 CFR 124.62 - Decision on variances.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 21 2010-07-01 2010-07-01 false Decision on variances. 124.62 Section... FOR DECISIONMAKING Specific Procedures Applicable to NPDES Permits § 124.62 Decision on variances... following variances (subject to EPA objection under § 123.44 for State permits): (1) Extensions under...

  10. 40 CFR 59.509 - Can I get a variance?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 5 2010-07-01 2010-07-01 false Can I get a variance? 59.509 Section 59... Volatile Organic Compound Emission Standards for Aerosol Coatings § 59.509 Can I get a variance? (a) Any... its reasonable control may apply in writing to the Administrator for a temporary variance....

  11. 36 CFR 27.4 - Variances and exceptions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Variances and exceptions. 27... CAPE COD NATIONAL SEASHORE; ZONING STANDARDS § 27.4 Variances and exceptions. (a) Zoning bylaws may provide for variances and exceptions. (b) Bylaws adopted pursuant to these standards shall...

  12. 20 CFR 901.40 - Proof; variance; amendment of pleadings.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Proof; variance; amendment of pleadings. 901... Suspension or Termination of Enrollment § 901.40 Proof; variance; amendment of pleadings. In the case of a variance between the allegations in a pleading and the evidence adduced in support of the pleading,...

  13. 31 CFR 10.67 - Proof; variance; amendment of pleadings.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Proof; variance; amendment of... BEFORE THE INTERNAL REVENUE SERVICE Rules Applicable to Disciplinary Proceedings § 10.67 Proof; variance; amendment of pleadings. In the case of a variance between the allegations in pleadings and the...

  14. 7 CFR 718.105 - Tolerances, variances, and adjustments.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 7 2010-01-01 2010-01-01 false Tolerances, variances, and adjustments. 718.105... APPLICABLE TO MULTIPLE PROGRAMS Determination of Acreage and Compliance § 718.105 Tolerances, variances, and... marketing quota crop allotment. (d) An administrative variance is applicable to all allotment crop...

  15. 40 CFR 52.1390 - Missoula variance provision.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 4 2010-07-01 2010-07-01 false Missoula variance provision. 52.1390... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Montana § 52.1390 Missoula variance provision. The Missoula City-County Air Pollution Control Program's Chapter X, Variances, which was...

  16. 29 CFR 1905.5 - Effect of variances.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 5 2010-07-01 2010-07-01 false Effect of variances. 1905.5 Section 1905.5 Labor... RULES OF PRACTICE FOR VARIANCES, LIMITATIONS, VARIATIONS, TOLERANCES, AND EXEMPTIONS UNDER THE WILLIAMS-STEIGER OCCUPATIONAL SAFETY AND HEALTH ACT OF 1970 General § 1905.5 Effect of variances. All...

  17. 40 CFR 190.11 - Variances for unusual operations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Variances for unusual operations. 190... Standards for the Uranium Fuel Cycle § 190.11 Variances for unusual operations. The standards specified in § 190.10 may be exceeded if: (a) The regulatory agency has granted a variance based upon...

  18. 40 CFR 124.64 - Appeals of variances.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 21 2010-07-01 2010-07-01 false Appeals of variances. 124.64 Section... FOR DECISIONMAKING Specific Procedures Applicable to NPDES Permits § 124.64 Appeals of variances. (a) When a State issues a permit on which EPA has made a variance decision, separate appeals of the...

  19. 31 CFR 8.59 - Proof; variance; amendment of pleadings.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Proof; variance; amendment of... BEFORE THE BUREAU OF ALCOHOL, TOBACCO AND FIREARMS Disciplinary Proceedings § 8.59 Proof; variance; amendment of pleadings. In the case of a variance between the allegations in a pleading, the...

  20. 36 CFR 30.5 - Variances, exceptions, and use permits.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Variances, exceptions, and... UNIT § 30.5 Variances, exceptions, and use permits. (a) Zoning ordinances or amendments thereto, for... Recreation Area may provide for the granting of variances and exceptions. (b) Zoning ordinances or...

  1. 40 CFR 141.4 - Variances and exemptions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 23 2014-07-01 2014-07-01 false Variances and exemptions. 141.4 Section 141.4 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS General § 141.4 Variances and exemptions. (a) Variances or exemptions from certain provisions...

  2. 29 CFR 1905.5 - Effect of variances.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 5 2014-07-01 2014-07-01 false Effect of variances. 1905.5 Section 1905.5 Labor...-STEIGER OCCUPATIONAL SAFETY AND HEALTH ACT OF 1970 General § 1905.5 Effect of variances. All variances granted pursuant to this part shall have only future effect. In his discretion, the Assistant...

  3. A quantitative model of the relationship between phenotypic variance and heterozygosity at marker loci under partial selfing.

    PubMed Central

    David, P

    1999-01-01

    Negative relationships between allozyme heterozygosity and morphological variance have often been observed and interpreted as evidence for increased developmental stability in heterozygotes. However, inbreeding can also generate such relationships by decreasing heterozygosity at neutral loci and redistributing genetic variance at the same time. I here provide a quantitative genetic model of this process by analogy with heterozygosity-fitness relationships. Inbreeding generates negative heterozygosity-variance relationships irrespective of the genetic architecture of the trait. This holds for fitness traits as well as neutral traits, the effect being stronger for fitness traits under directional dominance or overdominance. The order of magnitude of heterozygosity-variance regressions is compatible with empirical data even with very low inbreeding. Although developmental stability effects cannot be excluded, inbreeding is a parsimonious explanation that should be seriously considered to explain correlations between heterozygosity and both mean and variance of phenotypes in natural populations. PMID:10545474

  4. The Parabolic Variance (PVAR): A Wavelet Variance Based on the Least-Square Fit.

    PubMed

    Vernotte, Francois; Lenczner, Michel; Bourgeois, Pierre-Yves; Rubiola, Enrico

    2016-04-01

    This paper introduces the parabolic variance (PVAR), a wavelet variance similar to the Allan variance (AVAR), based on the linear regression (LR) of phase data. The companion article arXiv:1506.05009 [physics.ins-det] details the Ω frequency counter, which implements the LR estimate. The PVAR combines the advantages of AVAR and modified AVAR (MVAR). PVAR is good for long-term analysis because the wavelet spans over 2τ, the same as the AVAR wavelet, and good for short-term analysis because the response to white and flicker PM is 1/τ(3) and 1/τ(2), the same as the MVAR. After setting the theoretical framework, we study the degrees of freedom and the confidence interval for the most common noise types. Then, we focus on the detection of a weak noise process at the transition-or corner-where a faster process rolls off. This new perspective raises the question of which variance detects the weak process with the shortest data record. Our simulations show that PVAR is a fortunate tradeoff. PVAR is superior to MVAR in all cases, exhibits the best ability to divide between fast noise phenomena (up to flicker FM), and is almost as good as AVAR for the detection of random walk and drift. PMID:26571523

  5. Dynamics of mean-variance-skewness of cumulative crop yield impact temporal yield variance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Production risk associated with cropping systems influences farmers’ decisions to adopt a new management practice or a production system. Cumulative yield (CY), temporal yield variance (TYV) and coefficient of variation (CV) were used to assess the risk associated with adopting combinations of new m...

  6. The variance of the adjusted Rand index.

    PubMed

    Steinley, Douglas; Brusco, Michael J; Hubert, Lawrence

    2016-06-01

    For 30 years, the adjusted Rand index has been the preferred method for comparing 2 partitions (e.g., clusterings) of a set of observations. Although the index is widely used, little is known about its variability. Herein, the variance of the adjusted Rand index (Hubert & Arabie, 1985) is provided and its properties are explored. It is shown that a normal approximation is appropriate across a wide range of sample sizes and varying numbers of clusters. Further, it is shown that confidence intervals based on the normal distribution have desirable levels of coverage and accuracy. Finally, the first power analysis evaluating the ability to detect differences between 2, different adjusted Rand indices is provided. (PsycINFO Database Record PMID:26881693

  7. Calculating bone-lead measurement variance.

    PubMed Central

    Todd, A C

    2000-01-01

    The technique of (109)Cd-based X-ray fluorescence (XRF) measurements of lead in bone is well established. A paper by some XRF researchers [Gordon CL, et al. The Reproducibility of (109)Cd-based X-ray Fluorescence Measurements of Bone Lead. Environ Health Perspect 102:690-694 (1994)] presented the currently practiced method for calculating the variance of an in vivo measurement once a calibration line has been established. This paper corrects typographical errors in the method published by those authors; presents a crude estimate of the measurement error that can be acquired without computational peak fitting programs; and draws attention to the measurement error attributable to covariance, an important feature in the construct of the currently accepted method that is flawed under certain circumstances. PMID:10811562

  8. Variance-based interaction index measuring heteroscedasticity

    NASA Astrophysics Data System (ADS)

    Ito, Keiichi; Couckuyt, Ivo; Poles, Silvia; Dhaene, Tom

    2016-06-01

    This work is motivated by the need to deal with models with high-dimensional input spaces of real variables. One way to tackle high-dimensional problems is to identify interaction or non-interaction among input parameters. We propose a new variance-based sensitivity interaction index that can detect and quantify interactions among the input variables of mathematical functions and computer simulations. The computation is very similar to first-order sensitivity indices by Sobol'. The proposed interaction index can quantify the relative importance of input variables in interaction. Furthermore, detection of non-interaction for screening can be done with as low as 4 n + 2 function evaluations, where n is the number of input variables. Using the interaction indices based on heteroscedasticity, the original function may be decomposed into a set of lower dimensional functions which may then be analyzed separately.

  9. Characterizing nonconstant instrumental variance in emerging miniaturized analytical techniques.

    PubMed

    Noblitt, Scott D; Berg, Kathleen E; Cate, David M; Henry, Charles S

    2016-04-01

    Measurement variance is a crucial aspect of quantitative chemical analysis. Variance directly affects important analytical figures of merit, including detection limit, quantitation limit, and confidence intervals. Most reported analyses for emerging analytical techniques implicitly assume constant variance (homoskedasticity) by using unweighted regression calibrations. Despite the assumption of constant variance, it is known that most instruments exhibit heteroskedasticity, where variance changes with signal intensity. Ignoring nonconstant variance results in suboptimal calibrations, invalid uncertainty estimates, and incorrect detection limits. Three techniques where homoskedasticity is often assumed were covered in this work to evaluate if heteroskedasticity had a significant quantitative impact-naked-eye, distance-based detection using paper-based analytical devices (PADs), cathodic stripping voltammetry (CSV) with disposable carbon-ink electrode devices, and microchip electrophoresis (MCE) with conductivity detection. Despite these techniques representing a wide range of chemistries and precision, heteroskedastic behavior was confirmed for each. The general variance forms were analyzed, and recommendations for accounting for nonconstant variance discussed. Monte Carlo simulations of instrument responses were performed to quantify the benefits of weighted regression, and the sensitivity to uncertainty in the variance function was tested. Results show that heteroskedasticity should be considered during development of new techniques; even moderate uncertainty (30%) in the variance function still results in weighted regression outperforming unweighted regressions. We recommend utilizing the power model of variance because it is easy to apply, requires little additional experimentation, and produces higher-precision results and more reliable uncertainty estimates than assuming homoskedasticity. PMID:26995641

  10. Transcriptome Analysis Reveals a Signature Profile for Tick-Borne Flavivirus Persistence in HEK 293T Cells

    PubMed Central

    Lam, Jennifer; Offerdahl, Danielle K.; Martens, Craig; Sturdevant, Daniel; Turner, Charles V.; Porcella, Stephen F.; Bloom, Marshall E.

    2016-01-01

    ABSTRACT Tick-borne flaviviruses (TBFVs) cause febrile illnesses, which may progress to severe encephalitis and/or death in humans globally. Most people who recover from severe acute disease suffer from debilitating neurological sequelae, which may be due to viral persistence, infection-induced neurological cell damage, host response, or some combination of these. Acute TBFV infection of human embryonic kidney (HEK) 293T cells in vitro results in the death of >95% of infected cells by day 5. However, replacing cell growth medium allows surviving cells to repopulate and become persistently infected for extended periods of time. The mechanisms responsible for initiation and maintenance of viral persistence remain vague. We subjected the HEK 293T cell transcriptome to deep sequencing to identify genes differentially expressed during acute infection and persistent infection. A total of 451 genes showed unique significant differential expression levels in persistently infected cells relative to the acute phase of infection. Ingenuity Pathway Analysis results suggested that the expression of prosurvival oncogenes AKT2 and ERBB2 was upregulated in persistently infected cells, whereas proapoptotic genes, such as Bad and the beta interferon 1 (IFN-β1) gene, were downregulated. Genes encoding antiviral cytokines such as the CCL5, tumor necrosis factor alpha (TNF-α), and CXCL10 genes were upregulated during the acute phase, but the same genes were relatively quiescent in persistently infected cells. Exogenous induction of apoptosis demonstrated that persistently infected cells were resistant to apoptosis in a dose-dependent manner. In summary, the differential transcriptome profiles of acute-phase compared to persistently infected HEK 293T cells demonstrated an evasion of apoptosis, which may be critical for a chronic TBFV infection state. These results provide a basis for further study of the mechanisms of TBFV persistence. PMID:27222466

  11. On discrete stochastic processes with long-lasting time dependence in the variance

    NASA Astrophysics Data System (ADS)

    Queirós, S. M. D.

    2008-11-01

    In this manuscript, we analytically and numerically study statistical properties of an heteroskedastic process based on the celebrated ARCH generator of random variables whose variance is defined by a memory of qm-exponencial, form (eqm=1 x=ex). Specifically, we inspect the self-correlation function of squared random variables as well as the kurtosis. In addition, by numerical procedures, we infer the stationary probability density function of both of the heteroskedastic random variables and the variance, the multiscaling properties, the first-passage times distribution, and the dependence degree. Finally, we introduce an asymmetric variance version of the model that enables us to reproduce the so-called leverage effect in financial markets.

  12. Explanatory Variance in Maximal Oxygen Uptake

    PubMed Central

    Robert McComb, Jacalyn J.; Roh, Daesung; Williams, James S.

    2006-01-01

    The purpose of this study was to develop a prediction equation that could be used to estimate maximal oxygen uptake (VO2max) from a submaximal water running protocol. Thirty-two volunteers (n =19 males, n = 13 females), ages 18 - 24 years, underwent the following testing procedures: (a) a 7-site skin fold assessment; (b) a land VO2max running treadmill test; and (c) a 6 min water running test. For the water running submaximal protocol, the participants were fitted with an Aqua Jogger Classic Uni-Sex Belt and a Polar Heart Rate Monitor; the participants’ head, shoulders, hips and feet were vertically aligned, using a modified running/bicycle motion. A regression model was used to predict VO2max. The criterion variable, VO2max, was measured using open-circuit calorimetry utilizing the Bruce Treadmill Protocol. Predictor variables included in the model were percent body fat (% BF), height, weight, gender, and heart rate following a 6 min water running protocol. Percent body fat accounted for 76% (r = -0.87, SEE = 3.27) of the variance in VO2max. No other variables significantly contributed to the explained variance in VO2max. The equation for the estimation of VO2max is as follows: VO2max ml.kg-1·min-1 = 56.14 - 0.92 (% BF). Key Points Body Fat is an important predictor of VO2 max. Individuals with low skill level in water running may shorten their stride length to avoid the onset of fatigue at higher work-loads, therefore, the net oxygen cost of the exercise cannot be controlled in inexperienced individuals in water running at fatiguing workloads. Experiments using water running protocols to predict VO2max should use individuals trained in the mechanics of water running. A submaximal water running protocol is needed in the research literature for individuals trained in the mechanics of water running, given the popularity of water running rehabilitative exercise programs and training programs. PMID:24260003

  13. Successful propagation of flavivirus infectious cDNAs by a novel method to reduce the cryptic bacterial promoter activity of virus genomes.

    PubMed

    Pu, Szu-Yuan; Wu, Ren-Huang; Yang, Chi-Chen; Jao, Tzu-Ming; Tsai, Ming-Han; Wang, Jing-Chyi; Lin, Hui-Mei; Chao, Yu-Sheng; Yueh, Andrew

    2011-03-01

    Reverse genetics is a powerful tool to study single-stranded RNA viruses. Despite tremendous efforts having been made to improve the methodology for constructing flavivirus cDNAs, the cause of toxicity of flavivirus cDNAs in bacteria remains unknown. Here we performed mutational analysis studies to identify Escherichia coli promoter (ECP) sequences within nucleotides (nt) 1 to 3000 of the dengue virus type 2 (DENV2) and Japanese encephalitis virus (JEV) genomes. Eight and four active ECPs were demonstrated within nt 1 to 3000 of the DENV2 and JEV genomes, respectively, using fusion constructs containing DENV2 or JEV segments and empty vector reporter gene Renilla luciferase. Full-length DENV2 and JEV cDNAs were obtained by inserting mutations reducing their ECP activity in bacteria without altering amino acid sequences. A severe cytopathic effect occurred when BHK21 cells were transfected with in vitro-transcribed RNAs from either a DENV2 cDNA clone with multiple silent mutations within the prM-E-NS1 region of dengue genome or a JEV cDNA clone with an A-to-C mutation at nt 90 of the JEV genome. The virions derived from the DENV2 or JEV cDNA clone exhibited infectivities similar to those of their parental viruses in C6/36 and BHK21 cells. A cis-acting element essential for virus replication was revealed by introducing silent mutations into the central portion (nt 160 to 243) of the core gene of DENV2 infectious cDNA or a subgenomic DENV2 replicon clone. This novel strategy of constructing DENV2 and JEV infectious clones could be applied to other flaviviruses or pathogenic RNA viruses to facilitate research in virology, viral pathogenesis, and vaccine development. PMID:21228244

  14. Seasonal variation of potential flavivirus vectors in an urban biological reserve in northeastern Brazil.

    PubMed

    Medeiros, Arlinete S; Marcondes, Carlos B; De Azevedo, Paulo R M; Jerônimo, Selma M B; e Silva, Virginia P Macedo; Ximenes, Maria de Fátima Freire de Melo

    2009-11-01

    Although yellow fever (YF) has not been reported on the eastern coast of Brazil since 1942, there was a reemergence of dengue fever in Brazil in 1987 due to the reintroduction of Aedes aegypti (L.). To assess areas of potential risk for transmission of vector-borne diseases, a surveillance system was placed in a large Atlantic Forest reserve in Natal, Rio Grande do Norte, Brazil, where in 2004 unexplained epizootics were reported among marmosets. The etiologic agent causing the mortality in marmosets has not been identified. Wyeomyia bourrouli Lutz, Haemagogus leucocelaenus Dyar & Shannon, Ae. aegypti, Aedes albopictus (Skuse), Ochlerotatus scapularis Rondani, Ochlerotatus serratus Theobald, Ochlerotatus taeniorhynchus Wiedemann, Culex quinquefasciatus Say, and Limatus durhami Theobald were collected in the park and in the proximity of the households adjacent to the park. Seasonal abundance fluctuation was significant for Ae. aegypti, Ae. albopictus, Ochlerotatus scapularis (Rondani), and Hg. leucocelaenus. Eggs of Ae. aegypti, Ae. albopictus, and Hg. leucocelaenus were more frequently found at the conclusion of the rainy season. A significant negative correlation between the number ofAe. albopictus collected and temperature was observed (r = -0.50), i.e., for each 10C increase in temperature, the number of specimens collected decreased eight-fold. The findings reported herein reinforce the need for a sustainable arboviral surveillance program in this area to decrease the potential risk of emergence of vector borne diseases as YF. PMID:19960696

  15. Automatic variance analysis of multistage care pathways.

    PubMed

    Li, Xiang; Liu, Haifeng; Zhang, Shilei; Mei, Jing; Xie, Guotong; Yu, Yiqin; Li, Jing; Lakshmanan, Geetika T

    2014-01-01

    A care pathway (CP) is a standardized process that consists of multiple care stages, clinical activities and their relations, aimed at ensuring and enhancing the quality of care. However, actual care may deviate from the planned CP, and analysis of these deviations can help clinicians refine the CP and reduce medical errors. In this paper, we propose a CP variance analysis method to automatically identify the deviations between actual patient traces in electronic medical records (EMR) and a multistage CP. As the care stage information is usually unavailable in EMR, we first align every trace with the CP using a hidden Markov model. From the aligned traces, we report three types of deviations for every care stage: additional activities, absent activities and violated constraints, which are identified by using the techniques of temporal logic and binomial tests. The method has been applied to a CP for the management of congestive heart failure and real world EMR, providing meaningful evidence for the further improvement of care quality. PMID:25160280

  16. Transmission dynamics of an insect-specific flavivirus in a naturally infected Culex pipiens laboratory colony and effects of co-infection on vector competence for West Nile virus

    PubMed Central

    Bolling, Bethany G.; Olea-Popelka, Francisco J.; Eisen, Lars; Moore, Chester G.; Blair, Carol D.

    2012-01-01

    We established a laboratory colony of Culex pipiens mosquitoes from eggs collected in Colorado and discovered that mosquitoes in the colony are naturally infected with Culex flavivirus (CxFV), an insect-specific flavivirus. In this study we examined transmission dynamics of CxFV and effects of persistent CxFV infection on vector competence for West Nile virus (WNV). We found that vertical transmission is the primary mechanism for persistence of CxFV in Cx. pipiens, with venereal transmission potentially playing a minor role. Vector competence experiments indicated possible early suppression of WNV replication by persistent CxFV infection in Cx. pipiens. This is the first description of insect-specific flavivirus transmission dynamics in a naturally infected mosquito colony and the observation of delayed dissemination of superinfecting WNV suggests that the presence of CxFV may impact the intensity of enzootic transmission of WNV and the risk of human exposure to this important pathogen. PMID:22425062

  17. Estimating the encounter rate variance in distance sampling

    USGS Publications Warehouse

    Fewster, R.M.; Buckland, S.T.; Burnham, K.P.; Borchers, D.L.; Jupp, P.E.; Laake, J.L.; Thomas, L.

    2009-01-01

    The dominant source of variance in line transect sampling is usually the encounter rate variance. Systematic survey designs are often used to reduce the true variability among different realizations of the design, but estimating the variance is difficult and estimators typically approximate the variance by treating the design as a simple random sample of lines. We explore the properties of different encounter rate variance estimators under random and systematic designs. We show that a design-based variance estimator improves upon the model-based estimator of Buckland et al. (2001, Introduction to Distance Sampling. Oxford: Oxford University Press, p. 79) when transects are positioned at random. However, if populations exhibit strong spatial trends, both estimators can have substantial positive bias under systematic designs. We show that poststratification is effective in reducing this bias. ?? 2008, The International Biometric Society.

  18. Variance analysis. Part II, The use of computers.

    PubMed

    Finkler, S A

    1991-09-01

    This is the second in a two-part series on variance analysis. In the first article (JONA, July/August 1991), the author discussed flexible budgeting, including the calculation of price, quantity, volume, and acuity variances. In this second article, the author focuses on the use of computers by nurse managers to aid in the process of calculating, understanding, and justifying variances. PMID:1919788

  19. Functional Analysis of Variance for Association Studies

    PubMed Central

    Vsevolozhskaya, Olga A.; Zaykin, Dmitri V.; Greenwood, Mark C.; Wei, Changshuai; Lu, Qing

    2014-01-01

    While progress has been made in identifying common genetic variants associated with human diseases, for most of common complex diseases, the identified genetic variants only account for a small proportion of heritability. Challenges remain in finding additional unknown genetic variants predisposing to complex diseases. With the advance in next-generation sequencing technologies, sequencing studies have become commonplace in genetic research. The ongoing exome-sequencing and whole-genome-sequencing studies generate a massive amount of sequencing variants and allow researchers to comprehensively investigate their role in human diseases. The discovery of new disease-associated variants can be enhanced by utilizing powerful and computationally efficient statistical methods. In this paper, we propose a functional analysis of variance (FANOVA) method for testing an association of sequence variants in a genomic region with a qualitative trait. The FANOVA has a number of advantages: (1) it tests for a joint effect of gene variants, including both common and rare; (2) it fully utilizes linkage disequilibrium and genetic position information; and (3) allows for either protective or risk-increasing causal variants. Through simulations, we show that FANOVA outperform two popularly used methods – SKAT and a previously proposed method based on functional linear models (FLM), – especially if a sample size of a study is small and/or sequence variants have low to moderate effects. We conduct an empirical study by applying three methods (FANOVA, SKAT and FLM) to sequencing data from Dallas Heart Study. While SKAT and FLM respectively detected ANGPTL 4 and ANGPTL 3 associated with obesity, FANOVA was able to identify both genes associated with obesity. PMID:25244256

  20. Network Structure and Biased Variance Estimation in Respondent Driven Sampling

    PubMed Central

    Verdery, Ashton M.; Mouw, Ted; Bauldry, Shawn; Mucha, Peter J.

    2015-01-01

    This paper explores bias in the estimation of sampling variance in Respondent Driven Sampling (RDS). Prior methodological work on RDS has focused on its problematic assumptions and the biases and inefficiencies of its estimators of the population mean. Nonetheless, researchers have given only slight attention to the topic of estimating sampling variance in RDS, despite the importance of variance estimation for the construction of confidence intervals and hypothesis tests. In this paper, we show that the estimators of RDS sampling variance rely on a critical assumption that the network is First Order Markov (FOM) with respect to the dependent variable of interest. We demonstrate, through intuitive examples, mathematical generalizations, and computational experiments that current RDS variance estimators will always underestimate the population sampling variance of RDS in empirical networks that do not conform to the FOM assumption. Analysis of 215 observed university and school networks from Facebook and Add Health indicates that the FOM assumption is violated in every empirical network we analyze, and that these violations lead to substantially biased RDS estimators of sampling variance. We propose and test two alternative variance estimators that show some promise for reducing biases, but which also illustrate the limits of estimating sampling variance with only partial information on the underlying population social network. PMID:26679927

  1. Estimation of Variance Components of Quantitative Traits in Inbred Populations

    PubMed Central

    Abney, Mark; McPeek, Mary Sara; Ober, Carole

    2000-01-01

    Summary Use of variance-component estimation for mapping of quantitative-trait loci in humans is a subject of great current interest. When only trait values, not genotypic information, are considered, variance-component estimation can also be used to estimate heritability of a quantitative trait. Inbred pedigrees present special challenges for variance-component estimation. First, there are more variance components to be estimated in the inbred case, even for a relatively simple model including additive, dominance, and environmental effects. Second, more identity coefficients need to be calculated from an inbred pedigree in order to perform the estimation, and these are computationally more difficult to obtain in the inbred than in the outbred case. As a result, inbreeding effects have generally been ignored in practice. We describe here the calculation of identity coefficients and estimation of variance components of quantitative traits in large inbred pedigrees, using the example of HDL in the Hutterites. We use a multivariate normal model for the genetic effects, extending the central-limit theorem of Lange to allow for both inbreeding and dominance under the assumptions of our variance-component model. We use simulated examples to give an indication of under what conditions one has the power to detect the additional variance components and to examine their impact on variance-component estimation. We discuss the implications for mapping and heritability estimation by use of variance components in inbred populations. PMID:10677322

  2. Multiperiod Mean-Variance Portfolio Optimization via Market Cloning

    SciTech Connect

    Ankirchner, Stefan; Dermoune, Azzouz

    2011-08-15

    The problem of finding the mean variance optimal portfolio in a multiperiod model can not be solved directly by means of dynamic programming. In order to find a solution we therefore first introduce independent market clones having the same distributional properties as the original market, and we replace the portfolio mean and variance by their empirical counterparts. We then use dynamic programming to derive portfolios maximizing a weighted sum of the empirical mean and variance. By letting the number of market clones converge to infinity we are able to solve the original mean variance problem.

  3. Network Structure and Biased Variance Estimation in Respondent Driven Sampling.

    PubMed

    Verdery, Ashton M; Mouw, Ted; Bauldry, Shawn; Mucha, Peter J

    2015-01-01

    This paper explores bias in the estimation of sampling variance in Respondent Driven Sampling (RDS). Prior methodological work on RDS has focused on its problematic assumptions and the biases and inefficiencies of its estimators of the population mean. Nonetheless, researchers have given only slight attention to the topic of estimating sampling variance in RDS, despite the importance of variance estimation for the construction of confidence intervals and hypothesis tests. In this paper, we show that the estimators of RDS sampling variance rely on a critical assumption that the network is First Order Markov (FOM) with respect to the dependent variable of interest. We demonstrate, through intuitive examples, mathematical generalizations, and computational experiments that current RDS variance estimators will always underestimate the population sampling variance of RDS in empirical networks that do not conform to the FOM assumption. Analysis of 215 observed university and school networks from Facebook and Add Health indicates that the FOM assumption is violated in every empirical network we analyze, and that these violations lead to substantially biased RDS estimators of sampling variance. We propose and test two alternative variance estimators that show some promise for reducing biases, but which also illustrate the limits of estimating sampling variance with only partial information on the underlying population social network. PMID:26679927

  4. The mechanism by which P250L mutation impairs flavivirus-NS1 dimerization: an investigation based on molecular dynamics simulations.

    PubMed

    Oliveira, Edson R A; de Alencastro, Ricardo B; Horta, Bruno A C

    2016-09-01

    The flavivirus non-structural protein 1 (NS1) is a conserved glycoprotein with as yet undefined biological function. This protein dimerizes when inside infected cells or associated to cell membranes but also forms lipid-associated hexamers when secreted to the extracellular space. A single amino acid substitution (P250L) is capable of preventing the dimerization of NS1 resulting in lower virulence and slower virus replication. In this work, based on molecular dynamics simulations of the dengue-2 virus NS1 [Formula: see text]-ladder monomer as a core model, we found that this mutation can induce several conformational changes that importantly affect critical monomer-monomer interactions. Based on additional simulations, we suggest a mechanism by which a highly orchestrated sequence of events propagate the local perturbations around the mutation site towards the dimer interface. The elucidation of such a mechanism could potentially support new strategies for rational production of live-attenuated vaccines and highlights a step forward in the development of novel anti-flavivirus measures. PMID:27324799

  5. A conserved predicted pseudoknot in the NS2A-encoding sequence of West Nile and Japanese encephalitis flaviviruses suggests NS1' may derive from ribosomal frameshifting

    PubMed Central

    Firth, Andrew E; Atkins, John F

    2009-01-01

    Japanese encephalitis, West Nile, Usutu and Murray Valley encephalitis viruses form a tight subgroup within the larger Flavivirus genus. These viruses utilize a single-polyprotein expression strategy, resulting in ~10 mature proteins. Plotting the conservation at synonymous sites along the polyprotein coding sequence reveals strong conservation peaks at the very 5' end of the coding sequence, and also at the 5' end of the sequence encoding the NS2A protein. Such peaks are generally indicative of functionally important non-coding sequence elements. The second peak corresponds to a predicted stable pseudoknot structure whose biological importance is supported by compensatory mutations that preserve the structure. The pseudoknot is preceded by a conserved slippery heptanucleotide (Y CCU UUU), thus forming a classical stimulatory motif for -1 ribosomal frameshifting. We hypothesize, therefore, that the functional importance of the pseudoknot is to stimulate a portion of ribosomes to shift -1 nt into a short (45 codon), conserved, overlapping open reading frame, termed foo. Since cleavage at the NS1-NS2A boundary is known to require synthesis of NS2A in cis, the resulting transframe fusion protein is predicted to be NS1-NS2AN-term-FOO. We hypothesize that this may explain the origin of the previously identified NS1 'extension' protein in JEV-group flaviviruses, known as NS1'. PMID:19196463

  6. Variance fluctuations in nonstationary time series: a comparative study of music genres

    NASA Astrophysics Data System (ADS)

    Jennings, Heather D.; Ivanov, Plamen Ch.; De Martins, Allan M.; da Silva, P. C.; Viswanathan, G. M.

    2004-05-01

    An important problem in physics concerns the analysis of audio time series generated by transduced acoustic phenomena. Here, we develop a new method to quantify the scaling properties of the local variance of nonstationary time series. We apply this technique to analyze audio signals obtained from selected genres of music. We find quantitative differences in the correlation properties of high art music, popular music, and dance music. We discuss the relevance of these objective findings in relation to the subjective experience of music.

  7. 7 CFR 718.105 - Tolerances, variances, and adjustments.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 7 2014-01-01 2014-01-01 false Tolerances, variances, and adjustments. 718.105 Section 718.105 Agriculture Regulations of the Department of Agriculture (Continued) FARM SERVICE AGENCY... APPLICABLE TO MULTIPLE PROGRAMS Determination of Acreage and Compliance § 718.105 Tolerances, variances,...

  8. 7 CFR 718.105 - Tolerances, variances, and adjustments.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 7 2012-01-01 2012-01-01 false Tolerances, variances, and adjustments. 718.105 Section 718.105 Agriculture Regulations of the Department of Agriculture (Continued) FARM SERVICE AGENCY... APPLICABLE TO MULTIPLE PROGRAMS Determination of Acreage and Compliance § 718.105 Tolerances, variances,...

  9. 36 CFR 27.4 - Variances and exceptions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 36 Parks, Forests, and Public Property 1 2013-07-01 2013-07-01 false Variances and exceptions. 27.4 Section 27.4 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR CAPE COD NATIONAL SEASHORE; ZONING STANDARDS § 27.4 Variances and exceptions. (a) Zoning bylaws...

  10. 36 CFR 27.4 - Variances and exceptions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 36 Parks, Forests, and Public Property 1 2014-07-01 2014-07-01 false Variances and exceptions. 27.4 Section 27.4 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR CAPE COD NATIONAL SEASHORE; ZONING STANDARDS § 27.4 Variances and exceptions. (a) Zoning bylaws...

  11. 36 CFR 27.4 - Variances and exceptions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 1 2011-07-01 2011-07-01 false Variances and exceptions. 27.4 Section 27.4 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR CAPE COD NATIONAL SEASHORE; ZONING STANDARDS § 27.4 Variances and exceptions. (a) Zoning bylaws...

  12. 36 CFR 27.4 - Variances and exceptions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 36 Parks, Forests, and Public Property 1 2012-07-01 2012-07-01 false Variances and exceptions. 27.4 Section 27.4 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR CAPE COD NATIONAL SEASHORE; ZONING STANDARDS § 27.4 Variances and exceptions. (a) Zoning bylaws...

  13. Characterizing the evolution of genetic variance using genetic covariance tensors.

    PubMed

    Hine, Emma; Chenoweth, Stephen F; Rundle, Howard D; Blows, Mark W

    2009-06-12

    Determining how genetic variance changes under selection in natural populations has proved to be a very resilient problem in evolutionary genetics. In the same way that understanding the availability of genetic variance within populations requires the simultaneous consideration of genetic variance in sets of functionally related traits, determining how genetic variance changes under selection in natural populations will require ascertaining how genetic variance-covariance (G) matrices evolve. Here, we develop a geometric framework using higher-order tensors, which enables the empirical characterization of how G matrices have diverged among populations. We then show how divergence among populations in genetic covariance structure can then be associated with divergence in selection acting on those traits using key equations from evolutionary theory. Using estimates of G matrices of eight male sexually selected traits from nine geographical populations of Drosophila serrata, we show that much of the divergence in genetic variance occurred in a single trait combination, a conclusion that could not have been reached by examining variation among the individual elements of the nine G matrices. Divergence in G was primarily in the direction of the major axes of genetic variance within populations, suggesting that genetic drift may be a major cause of divergence in genetic variance among these populations. PMID:19414471

  14. 40 CFR 52.1390 - Missoula variance provision.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 4 2014-07-01 2014-07-01 false Missoula variance provision. 52.1390 Section 52.1390 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Montana § 52.1390 Missoula variance provision. The Missoula City-County...

  15. 29 CFR 1904.38 - Variances from the recordkeeping rule.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... process your variance petition. (i) The Assistant Secretary will offer your employees and their authorized... the facts or conduct that may warrant revocation of your variance; and (ii) Provide you, your employees, and authorized employee representatives with an opportunity to participate in the...

  16. Productive Failure in Learning the Concept of Variance

    ERIC Educational Resources Information Center

    Kapur, Manu

    2012-01-01

    In a study with ninth-grade mathematics students on learning the concept of variance, students experienced either direct instruction (DI) or productive failure (PF), wherein they were first asked to generate a quantitative index for variance without any guidance before receiving DI on the concept. Whereas DI students relied only on the canonical…

  17. 10 CFR 52.93 - Exemptions and variances.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... CFR 52.7, and that the special circumstances outweigh any decrease in safety that may result from the... 10 Energy 2 2010-01-01 2010-01-01 false Exemptions and variances. 52.93 Section 52.93 Energy... Combined Licenses § 52.93 Exemptions and variances. (a) Applicants for a combined license under...

  18. Determining Sample Sizes for Precise Contrast Analysis with Heterogeneous Variances

    ERIC Educational Resources Information Center

    Jan, Show-Li; Shieh, Gwowen

    2014-01-01

    The analysis of variance (ANOVA) is one of the most frequently used statistical analyses in practical applications. Accordingly, the single and multiple comparison procedures are frequently applied to assess the differences among mean effects. However, the underlying assumption of homogeneous variances may not always be tenable. This study…

  19. A Study of Variance Estimation Methods. Working Paper Series.

    ERIC Educational Resources Information Center

    Zhang, Fan; Weng, Stanley; Salvucci, Sameena; Hu, Ming-xiu

    This working paper contains reports of five studies of variance estimation methods. The first, An Empirical Study of Poststratified Estimator, by Fan Zhang uses data from the National Household Education Survey to illustrate use of poststratified estimation. The second paper, BRR Variance Estimation Using BPLX Hadamard Procedure, by Stanley Weng…

  20. 21 CFR 821.2 - Exemptions and variances.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Exemptions and variances. 821.2 Section 821.2 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES MEDICAL DEVICE TRACKING REQUIREMENTS General Provisions § 821.2 Exemptions and variances. (a) A manufacturer, importer, or distributor...

  1. 40 CFR 142.40 - Requirements for a variance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Section 142.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS IMPLEMENTATION Variances Issued by the Administrator... one or more variances to any public water system within a State that does not have primary...

  2. Relating the Hadamard Variance to MCS Kalman Filter Clock Estimation

    NASA Technical Reports Server (NTRS)

    Hutsell, Steven T.

    1996-01-01

    The Global Positioning System (GPS) Master Control Station (MCS) currently makes significant use of the Allan Variance. This two-sample variance equation has proven excellent as a handy, understandable tool, both for time domain analysis of GPS cesium frequency standards, and for fine tuning the MCS's state estimation of these atomic clocks. The Allan Variance does not explicitly converge for the nose types of alpha less than or equal to minus 3 and can be greatly affected by frequency drift. Because GPS rubidium frequency standards exhibit non-trivial aging and aging noise characteristics, the basic Allan Variance analysis must be augmented in order to (a) compensate for a dynamic frequency drift, and (b) characterize two additional noise types, specifically alpha = minus 3, and alpha = minus 4. As the GPS program progresses, we will utilize a larger percentage of rubidium frequency standards than ever before. Hence, GPS rubidium clock characterization will require more attention than ever before. The three sample variance, commonly referred to as a renormalized Hadamard Variance, is unaffected by linear frequency drift, converges for alpha is greater than minus 5, and thus has utility for modeling noise in GPS rubidium frequency standards. This paper demonstrates the potential of Hadamard Variance analysis in GPS operations, and presents an equation that relates the Hadamard Variance to the MCS's Kalman filter process noises.

  3. 40 CFR 142.43 - Disposition of a variance request.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ....43 Section 142.43 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS IMPLEMENTATION Variances Issued by the... variance may be terminated at any time upon a finding that the nature of the raw water source is such...

  4. 40 CFR 142.43 - Disposition of a variance request.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ....43 Section 142.43 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS IMPLEMENTATION Variances Issued by the... variance may be terminated at any time upon a finding that the nature of the raw water source is such...

  5. 40 CFR 142.43 - Disposition of a variance request.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ....43 Section 142.43 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS IMPLEMENTATION Variances Issued by the... variance may be terminated at any time upon a finding that the nature of the raw water source is such...

  6. 40 CFR 142.43 - Disposition of a variance request.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ....43 Section 142.43 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS IMPLEMENTATION Variances Issued by the... variance may be terminated at any time upon a finding that the nature of the raw water source is such...

  7. A correlation procedure for augmenting hydrologic data

    USGS Publications Warehouse

    Matalas, N.C.; Jacobs, Barbara

    1964-01-01

    A linear regression for a short and long sequence of hydrologic events is used to lengthen the short sequence. The lengthened sequence consists of the original observations and regressed values plus noise, where the noise is a random variable with zero mean and variance proportional to the variance of the observations for the short sequence about the line of regression. Estimates of the mean and variance for the lengthened sequence are shown to be unbiased. If the correlation coefficient, which measures the strength of the linear regression, exceeds about 0.5, then the estimates of the mean and variance based on the lengthened sequence are better estimators of the population values of the mean and variance than the estimates based on the observations for the short sequence. If noise is not added to the regressed values, the correlation coefficient must exceed about 0.8 to obtain improvement in the estimates by use of correlated values.

  8. An efficient method to evaluate energy variances for extrapolation methods

    NASA Astrophysics Data System (ADS)

    Puddu, G.

    2012-08-01

    The energy variance extrapolation method consists of relating the approximate energies in many-body calculations to the corresponding energy variances and inferring eigenvalues by extrapolating to zero variance. The method needs a fast evaluation of the energy variances. For many-body methods that expand the nuclear wavefunctions in terms of deformed Slater determinants, the best available method for the evaluation of energy variances scales with the sixth power of the number of single-particle states. We propose a new method which depends on the number of single-particle orbits and the number of particles rather than the number of single-particle states. We discuss as an example the case of 4He using the chiral N3LO interaction in a basis consisting up to 184 single-particle states.

  9. Utility functions predict variance and skewness risk preferences in monkeys

    PubMed Central

    Genest, Wilfried; Stauffer, William R.; Schultz, Wolfram

    2016-01-01

    Utility is the fundamental variable thought to underlie economic choices. In particular, utility functions are believed to reflect preferences toward risk, a key decision variable in many real-life situations. To assess the validity of utility representations, it is therefore important to examine risk preferences. In turn, this approach requires formal definitions of risk. A standard approach is to focus on the variance of reward distributions (variance-risk). In this study, we also examined a form of risk related to the skewness of reward distributions (skewness-risk). Thus, we tested the extent to which empirically derived utility functions predicted preferences for variance-risk and skewness-risk in macaques. The expected utilities calculated for various symmetrical and skewed gambles served to define formally the direction of stochastic dominance between gambles. In direct choices, the animals’ preferences followed both second-order (variance) and third-order (skewness) stochastic dominance. Specifically, for gambles with different variance but identical expected values (EVs), the monkeys preferred high-variance gambles at low EVs and low-variance gambles at high EVs; in gambles with different skewness but identical EVs and variances, the animals preferred positively over symmetrical and negatively skewed gambles in a strongly transitive fashion. Thus, the utility functions predicted the animals’ preferences for variance-risk and skewness-risk. Using these well-defined forms of risk, this study shows that monkeys’ choices conform to the internal reward valuations suggested by their utility functions. This result implies a representation of utility in monkeys that accounts for both variance-risk and skewness-risk preferences. PMID:27402743

  10. Variance After-Effects Distort Risk Perception in Humans.

    PubMed

    Payzan-LeNestour, Elise; Balleine, Bernard W; Berrada, Tony; Pearson, Joel

    2016-06-01

    In many contexts, decision-making requires an accurate representation of outcome variance-otherwise known as "risk" in economics. Conventional economic theory assumes this representation to be perfect, thereby focusing on risk preferences rather than risk perception per se [1-3] (but see [4]). However, humans often misrepresent their physical environment. Perhaps the most striking of such misrepresentations are the many well-known sensory after-effects, which most commonly involve visual properties, such as color, contrast, size, and motion. For example, viewing downward motion of a waterfall induces the anomalous biased experience of upward motion during subsequent viewing of static rocks to the side [5]. Given that after-effects are pervasive, occurring across a wide range of time horizons [6] and stimulus dimensions (including properties such as face perception [7, 8], gender [9], and numerosity [10]), and that some evidence exists that neurons show adaptation to variance in the sole visual feature of motion [11], we were interested in assessing whether after-effects distort variance perception in humans. We found that perceived variance is decreased after prolonged exposure to high variance and increased after exposure to low variance within a number of different visual representations of variance. We demonstrate these after-effects occur across very different visual representations of variance, suggesting that these effects are not sensory, but operate at a high (cognitive) level of information processing. These results suggest, therefore, that variance constitutes an independent cognitive property and that prolonged exposure to extreme variance distorts risk perception-a fundamental challenge for economic theory and practice. PMID:27161500

  11. 40 CFR 260.33 - Procedures for variances from classification as a solid waste, for variances to be classified as...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... classification as a solid waste, for variances to be classified as a boiler, or for non-waste determinations. 260... from classification as a solid waste, for variances to be classified as a boiler, or for non-waste... as boilers, or applications for non-waste determinations. (a) The applicant must apply to...

  12. 40 CFR 260.33 - Procedures for variances from classification as a solid waste, for variances to be classified as...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... classification as a solid waste, for variances to be classified as a boiler, or for non-waste determinations. 260... from classification as a solid waste, for variances to be classified as a boiler, or for non-waste... as boilers, or applications for non-waste determinations. (a) The applicant must apply to...

  13. 40 CFR 260.33 - Procedures for variances from classification as a solid waste, for variances to be classified as...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... classification as a solid waste, for variances to be classified as a boiler, or for non-waste determinations. 260... from classification as a solid waste, for variances to be classified as a boiler, or for non-waste... as boilers, or applications for non-waste determinations. (a) The applicant must apply to...

  14. 40 CFR 260.33 - Procedures for variances from classification as a solid waste, for variances to be classified as...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... classification as a solid waste, for variances to be classified as a boiler, or for non-waste determinations. 260... from classification as a solid waste, for variances to be classified as a boiler, or for non-waste... as boilers, or applications for non-waste determinations. (a) The applicant must apply to...

  15. 40 CFR 260.33 - Procedures for variances from classification as a solid waste, for variances to be classified as...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... classification as a solid waste, for variances to be classified as a boiler, or for non-waste determinations. 260... from classification as a solid waste, for variances to be classified as a boiler, or for non-waste... as boilers, or applications for non-waste determinations. (a) The applicant must apply to...

  16. Modeling variance structure of body shape traits of Lipizzan horses.

    PubMed

    Kaps, M; Curik, I; Baban, M

    2010-09-01

    Heterogeneity of variance of growth traits over age is a common issue in estimating genetic parameters and is addressed in this study by selecting appropriate variance structure models for additive genetic and environmental variances. Modeling and partitioning those variances connected with analyzing small data sets were demonstrated on Lipizzan horses. The following traits were analyzed: withers height, chest girth, and cannon bone circumference. The measurements were taken at birth, and at approximately 6, 12, 24, and 36 mo of age of 660 Lipizzan horses born in Croatia between 1948 and 2000. The corresponding pedigree file consisted of 1,458 horses. Sex, age of dam, and stud-year-season interaction were considered fixed effects; additive genetic and permanent environment effects were defined as random. Linear adjustments of age at measuring were done within measuring groups. Maternal effects were included only for measurements taken at birth and at 6 mo. Additive genetic variance structures were modeled by using uniform structures or structures based on polynomial random regression. Environmental variance structures were modeled by using one of the following models: unstructured, exponential, Gaussian, or combinations of identity or diagonal with structures based on polynomial random regression. The parameters were estimated by using REML. Comparison and fits of the models were assessed by using Akaike and Bayesian information criteria, and by checking graphically the adequacy of the shape of the overall (phenotypic) and component (additive genetic and environmental) variance functions. The best overall fit was obtained from models with unstructured error variance. Compared with the model with uniform additive genetic variance, models with structures based on random regression only slightly improved overall fit. Exponential and Gaussian models were generally not suitable because they do not accommodate adequately heterogeneity of variance. Using the unstructured

  17. Quantitative genetic variance and multivariate clines in the Ivyleaf morning glory, Ipomoea hederacea

    PubMed Central

    Stock, Amanda J.; Campitelli, Brandon E.; Stinchcombe, John R.

    2014-01-01

    Clinal variation is commonly interpreted as evidence of adaptive differentiation, although clines can also be produced by stochastic forces. Understanding whether clines are adaptive therefore requires comparing clinal variation to background patterns of genetic differentiation at presumably neutral markers. Although this approach has frequently been applied to single traits at a time, we have comparatively fewer examples of how multiple correlated traits vary clinally. Here, we characterize multivariate clines in the Ivyleaf morning glory, examining how suites of traits vary with latitude, with the goal of testing for divergence in trait means that would indicate past evolutionary responses. We couple this with analysis of genetic variance in clinally varying traits in 20 populations to test whether past evolutionary responses have depleted genetic variance, or whether genetic variance declines approaching the range margin. We find evidence of clinal differentiation in five quantitative traits, with little evidence of isolation by distance at neutral loci that would suggest non-adaptive or stochastic mechanisms. Within and across populations, the traits that contribute most to population differentiation and clinal trends in the multivariate phenotype are genetically variable as well, suggesting that a lack of genetic variance will not cause absolute evolutionary constraints. Our data are broadly consistent theoretical predictions of polygenic clines in response to shallow environmental gradients. Ecologically, our results are consistent with past findings of natural selection on flowering phenology, presumably due to season-length variation across the range. PMID:25002704

  18. Toward a more robust variance-based global sensitivity analysis of model outputs

    SciTech Connect

    Tong, C

    2007-10-15

    Global sensitivity analysis (GSA) measures the variation of a model output as a function of the variations of the model inputs given their ranges. In this paper we consider variance-based GSA methods that do not rely on certain assumptions about the model structure such as linearity or monotonicity. These variance-based methods decompose the output variance into terms of increasing dimensionality called 'sensitivity indices', first introduced by Sobol' [25]. Sobol' developed a method of estimating these sensitivity indices using Monte Carlo simulations. McKay [13] proposed an efficient method using replicated Latin hypercube sampling to compute the 'correlation ratios' or 'main effects', which have been shown to be equivalent to Sobol's first-order sensitivity indices. Practical issues with using these variance estimators are how to choose adequate sample sizes and how to assess the accuracy of the results. This paper proposes a modified McKay main effect method featuring an adaptive procedure for accuracy assessment and improvement. We also extend our adaptive technique to the computation of second-order sensitivity indices. Details of the proposed adaptive procedure as wells as numerical results are included in this paper.

  19. Monochromaticity of orientation maps in v1 implies minimum variance for hypercolumn size.

    PubMed

    Afgoustidis, Alexandre

    2015-01-01

    In the primary visual cortex of many mammals, the processing of sensory information involves recognizing stimuli orientations. The repartition of preferred orientations of neurons in some areas is remarkable: a repetitive, non-periodic, layout. This repetitive pattern is understood to be fundamental for basic non-local aspects of vision, like the perception of contours, but important questions remain about its development and function. We focus here on Gaussian Random Fields, which provide a good description of the initial stage of orientation map development and, in spite of shortcomings we will recall, a computable framework for discussing general principles underlying the geometry of mature maps. We discuss the relationship between the notion of column spacing and the structure of correlation spectra; we prove formulas for the mean value and variance of column spacing, and we use numerical analysis of exact analytic formulae to study the variance. Referring to studies by Wolf, Geisel, Kaschube, Schnabel, and coworkers, we also show that spectral thinness is not an essential ingredient to obtain a pinwheel density of π, whereas it appears as a signature of Euclidean symmetry. The minimum variance property associated to thin spectra could be useful for information processing, provide optimal modularity for V1 hypercolumns, and be a first step toward a mathematical definition of hypercolumns. A measurement of this property in real maps is in principle possible, and comparison with the results in our paper could help establish the role of our minimum variance hypothesis in the development process. PMID:25859421

  20. Quantitative genetic variance and multivariate clines in the Ivyleaf morning glory, Ipomoea hederacea.

    PubMed

    Stock, Amanda J; Campitelli, Brandon E; Stinchcombe, John R

    2014-08-19

    Clinal variation is commonly interpreted as evidence of adaptive differentiation, although clines can also be produced by stochastic forces. Understanding whether clines are adaptive therefore requires comparing clinal variation to background patterns of genetic differentiation at presumably neutral markers. Although this approach has frequently been applied to single traits at a time, we have comparatively fewer examples of how multiple correlated traits vary clinally. Here, we characterize multivariate clines in the Ivyleaf morning glory, examining how suites of traits vary with latitude, with the goal of testing for divergence in trait means that would indicate past evolutionary responses. We couple this with analysis of genetic variance in clinally varying traits in 20 populations to test whether past evolutionary responses have depleted genetic variance, or whether genetic variance declines approaching the range margin. We find evidence of clinal differentiation in five quantitative traits, with little evidence of isolation by distance at neutral loci that would suggest non-adaptive or stochastic mechanisms. Within and across populations, the traits that contribute most to population differentiation and clinal trends in the multivariate phenotype are genetically variable as well, suggesting that a lack of genetic variance will not cause absolute evolutionary constraints. Our data are broadly consistent theoretical predictions of polygenic clines in response to shallow environmental gradients. Ecologically, our results are consistent with past findings of natural selection on flowering phenology, presumably due to season-length variation across the range. PMID:25002704

  1. Variance predicts salience in central sensory processing.

    PubMed

    Hermundstad, Ann M; Briguglio, John J; Conte, Mary M; Victor, Jonathan D; Balasubramanian, Vijay; Tkačik, Gašper

    2014-01-01

    Information processing in the sensory periphery is shaped by natural stimulus statistics. In the periphery, a transmission bottleneck constrains performance; thus efficient coding implies that natural signal components with a predictably wider range should be compressed. In a different regime--when sampling limitations constrain performance--efficient coding implies that more resources should be allocated to informative features that are more variable. We propose that this regime is relevant for sensory cortex when it extracts complex features from limited numbers of sensory samples. To test this prediction, we use central visual processing as a model: we show that visual sensitivity for local multi-point spatial correlations, described by dozens of independently-measured parameters, can be quantitatively predicted from the structure of natural images. This suggests that efficient coding applies centrally, where it extends to higher-order sensory features and operates in a regime in which sensitivity increases with feature variability. PMID:25396297

  2. Lack of identification of Flaviviruses in oral and cloacal swabs from long- and short-distance migratory birds in Trentino-Alto Adige (North-eastern Italy)

    PubMed Central

    2013-01-01

    Background West Nile virus (WNV) and Usutu virus (USUV), both belonging to the genus Flavivirus, are emerging in Italy as important human and animal pathogens. Migratory birds are involved in the spread of Flaviviruses over long distances, particularly from Africa to Europe. Once introduced, these viruses can be further be dispersed by short-distance migratory and resident bird species. Thus far, there is still a considerable knowledge gap on the role played by different bird species in the ecology and transmission mechanisms of these viruses. The Region of Trentino-Alto Adige (north-eastern Italy) is located on the migratory route of many of the short- and long-distance migratory birds that cross the Alps, connecting northern Europe and western Asia with southern Europe and Africa. Until now, only a silent circulation of WNV and USUV within the territory of the Province of Trento has been confirmed by serological screening, whilst no cases of infected humans or animals have so far been reported. However, continuous spillover events of both viruses have been reported in neighbouring Regions. The aim of this study was to monitor the circulation of WNV and USUV in Trentino-Alto Adige, in order to detect if active virus shedding occurs in migratory birds captured during their seasonal movements and to evaluate the role that different bird species could play in the spreading of these viruses. Methods We carried out a biomolecular survey on oral and cloacal swabs collected from migratory birds during seasonal migrations. Birds belonging to 18 transaharian and 21 intrapaleartic species were examined during spring (n = 176) and autumn (n = 146), and were tested using a generic nested-PCR. Results All samples tested negative for Flaviviruses. The possible causes of unapparent shedding, along with ecological and epidemiological implications are discussed. Conclusions The lack of detection of active virus shedding in these bird species does not exclude the

  3. Meta-analysis of ratios of sample variances.

    PubMed

    Prendergast, Luke A; Staudte, Robert G

    2016-05-20

    When conducting a meta-analysis of standardized mean differences (SMDs), it is common to use Cohen's d, or its variants, that require equal variances in the two arms of each study. While interpretation of these SMDs is simple, this alone should not be used as a justification for assuming equal variances. Until now, researchers have either used an F-test for each individual study or perhaps even conveniently ignored such tools altogether. In this paper, we propose a meta-analysis of ratios of sample variances to assess whether the equality of variances assumptions is justified prior to a meta-analysis of SMDs. Quantile-quantile plots, an omnibus test for equal variances or an overall meta-estimate of the ratio of variances can all be used to formally justify the use of less common methods when evidence of unequal variances is found. The methods in this paper are simple to implement and the validity of the approaches are reinforced by simulation studies and an application to a real data set. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27062644

  4. A note on preliminary tests of equality of variances.

    PubMed

    Zimmerman, Donald W

    2004-05-01

    Preliminary tests of equality of variances used before a test of location are no longer widely recommended by statisticians, although they persist in some textbooks and software packages. The present study extends the findings of previous studies and provides further reasons for discontinuing the use of preliminary tests. The study found Type I error rates of a two-stage procedure, consisting of a preliminary Levene test on samples of different sizes with unequal variances, followed by either a Student pooled-variances t test or a Welch separate-variances t test. Simulations disclosed that the twostage procedure fails to protect the significance level and usually makes the situation worse. Earlier studies have shown that preliminary tests often adversely affect the size of the test, and also that the Welch test is superior to the t test when variances are unequal. The present simulations reveal that changes in Type I error rates are greater when sample sizes are smaller, when the difference in variances is slight rather than extreme, and when the significance level is more stringent. Furthermore, the validity of the Welch test deteriorates if it is used only on those occasions where a preliminary test indicates it is needed. Optimum protection is assured by using a separate-variances test unconditionally whenever sample sizes are unequal. PMID:15171807

  5. Variance Estimation for Myocardial Blood Flow by Dynamic PET.

    PubMed

    Moody, Jonathan B; Murthy, Venkatesh L; Lee, Benjamin C; Corbett, James R; Ficaro, Edward P

    2015-11-01

    The estimation of myocardial blood flow (MBF) by (13)N-ammonia or (82)Rb dynamic PET typically relies on an empirically determined generalized Renkin-Crone equation to relate the kinetic parameter K1 to MBF. Because the Renkin-Crone equation defines MBF as an implicit function of K1, the MBF variance cannot be determined using standard error propagation techniques. To overcome this limitation, we derived novel analytical approximations that provide first- and second-order estimates of MBF variance in terms of the mean and variance of K1 and the Renkin-Crone parameters. The accuracy of the analytical expressions was validated by comparison with Monte Carlo simulations, and MBF variance was evaluated in clinical (82)Rb dynamic PET scans. For both (82)Rb and (13)N-ammonia, good agreement was observed between both (first- and second-order) analytical variance expressions and Monte Carlo simulations, with moderately better agreement for second-order estimates. The contribution of the Renkin-Crone relation to overall MBF uncertainty was found to be as high as 68% for (82)Rb and 35% for (13)N-ammonia. For clinical (82)Rb PET data, the conventional practice of neglecting the statistical uncertainty in the Renkin-Crone parameters resulted in underestimation of the coefficient of variation of global MBF and coronary flow reserve by 14-49%. Knowledge of MBF variance is essential for assessing the precision and reliability of MBF estimates. The form and statistical uncertainty in the empirical Renkin-Crone relation can make substantial contributions to the variance of MBF. The novel analytical variance expressions derived in this work enable direct estimation of MBF variance which includes this previously neglected contribution. PMID:25974932

  6. Global Gravity Wave Variances from Aura MLS: Characteristics and Interpretation

    NASA Technical Reports Server (NTRS)

    Wu, Dong L.; Eckermann, Stephen D.

    2008-01-01

    The gravity wave (GW)-resolving capabilities of 118-GHz saturated thermal radiances acquired throughout the stratosphere by the Microwave Limb Sounder (MLS) on the Aura satellite are investigated and initial results presented. Because the saturated (optically thick) radiances resolve GW perturbations from a given altitude at different horizontal locations, variances are evaluated at 12 pressure altitudes between 21 and 51 km using the 40 saturated radiances found at the bottom of each limb scan. Forward modeling simulations show that these variances are controlled mostly by GWs with vertical wavelengths z 5 km and horizontal along-track wavelengths of y 100-200 km. The tilted cigar-shaped three-dimensional weighting functions yield highly selective responses to GWs of high intrinsic frequency that propagate toward the instrument. The latter property is used to infer the net meridional component of GW propagation by differencing the variances acquired from ascending (A) and descending (D) orbits. Because of improved vertical resolution and sensitivity, Aura MLS GW variances are 5?8 times larger than those from the Upper Atmosphere Research Satellite (UARS) MLS. Like UARS MLS variances, monthly-mean Aura MLS variances in January and July 2005 are enhanced when local background wind speeds are large, due largely to GW visibility effects. Zonal asymmetries in variance maps reveal enhanced GW activity at high latitudes due to forcing by flow over major mountain ranges and at tropical and subtropical latitudes due to enhanced deep convective generation as inferred from contemporaneous MLS cloud-ice data. At 21-28-km altitude (heights not measured by the UARS MLS), GW variance in the tropics is systematically enhanced and shows clear variations with the phase of the quasi-biennial oscillation, in general agreement with GW temperature variances derived from radiosonde, rocketsonde, and limb-scan vertical profiles.

  7. Mesoscale Gravity Wave Variances from AMSU-A Radiances

    NASA Technical Reports Server (NTRS)

    Wu, Dong L.

    2004-01-01

    A variance analysis technique is developed here to extract gravity wave (GW) induced temperature fluctuations from NOAA AMSU-A (Advanced Microwave Sounding Unit-A) radiance measurements. By carefully removing the instrument/measurement noise, the algorithm can produce reliable GW variances with the minimum detectable value as small as 0.1 K2. Preliminary analyses with AMSU-A data show GW variance maps in the stratosphere have very similar distributions to those found with the UARS MLS (Upper Atmosphere Research Satellite Microwave Limb Sounder). However, the AMSU-A offers better horizontal and temporal resolution for observing regional GW variability, such as activity over sub-Antarctic islands.

  8. Variance predicts salience in central sensory processing

    PubMed Central

    Hermundstad, Ann M; Briguglio, John J; Conte, Mary M; Victor, Jonathan D; Balasubramanian, Vijay; Tkačik, Gašper

    2014-01-01

    Information processing in the sensory periphery is shaped by natural stimulus statistics. In the periphery, a transmission bottleneck constrains performance; thus efficient coding implies that natural signal components with a predictably wider range should be compressed. In a different regime—when sampling limitations constrain performance—efficient coding implies that more resources should be allocated to informative features that are more variable. We propose that this regime is relevant for sensory cortex when it extracts complex features from limited numbers of sensory samples. To test this prediction, we use central visual processing as a model: we show that visual sensitivity for local multi-point spatial correlations, described by dozens of independently-measured parameters, can be quantitatively predicted from the structure of natural images. This suggests that efficient coding applies centrally, where it extends to higher-order sensory features and operates in a regime in which sensitivity increases with feature variability. DOI: http://dx.doi.org/10.7554/eLife.03722.001 PMID:25396297

  9. Very low levels of direct additive genetic variance in fitness and fitness components in a red squirrel population

    PubMed Central

    McFarlane, S Eryn; Gorrell, Jamieson C; Coltman, David W; Humphries, Murray M; Boutin, Stan; McAdam, Andrew G

    2014-01-01

    A trait must genetically correlate with fitness in order to evolve in response to natural selection, but theory suggests that strong directional selection should erode additive genetic variance in fitness and limit future evolutionary potential. Balancing selection has been proposed as a mechanism that could maintain genetic variance if fitness components trade off with one another and has been invoked to account for empirical observations of higher levels of additive genetic variance in fitness components than would be expected from mutation–selection balance. Here, we used a long-term study of an individually marked population of North American red squirrels (Tamiasciurus hudsonicus) to look for evidence of (1) additive genetic variance in lifetime reproductive success and (2) fitness trade-offs between fitness components, such as male and female fitness or fitness in high- and low-resource environments. “Animal model” analyses of a multigenerational pedigree revealed modest maternal effects on fitness, but very low levels of additive genetic variance in lifetime reproductive success overall as well as fitness measures within each sex and environment. It therefore appears that there are very low levels of direct genetic variance in fitness and fitness components in red squirrels to facilitate contemporary adaptation in this population. PMID:24963372

  10. The Effects of Spontaneous Mutation on Quantitative Traits. I. Variances and Covariances of Life History Traits

    PubMed Central

    Houle, D.; Hughes, K. A.; Hoffmaster, D. K.; Ihara, J.; Assimacopoulos, S.; Canada, D.; Charlesworth, B.

    1994-01-01

    We have accumulated spontaneous mutations in the absence of natural selection in Drosophila melanogaster by backcrossing 200 heterozygous replicates of a single high fitness second chromosome to a balancer stock for 44 generations. At generations 33 and 44 of accumulation, we extracted samples of chromosomes and assayed their homozygous performance for female fecundity early and late in adult life, male and female longevity, male mating ability early and late in adult life, productivity (a measure of fecundity times viability) and body weight. The variance among lines increased significantly for all traits except male mating ability and weight. The rate of increase in variance was similar to that found in previous studies of egg-to-adult viability, when calculated relative to trait means. The mutational correlations among traits were all strongly positive. Many correlations were significantly different from 0, while none was significantly different from 1. These data suggest that the mutation-accumulation hypothesis is not a sufficient explanation for the evolution of senescence in D. melanogaster. Mutation-selection balance does seem adequate to explain a substantial proportion of the additive genetic variance for fecundity and longevity. PMID:7851773

  11. Automatic treatment of the variance estimation bias in TRIPOLI-4 criticality calculations

    SciTech Connect

    Dumonteil, E.; Malvagi, F.

    2012-07-01

    The central limit (CLT) theorem States conditions under which the mean of a sufficiently large number of independent random variables, each with finite mean and variance, will be approximately normally distributed. The use of Monte Carlo transport codes, such as Tripoli4, relies on those conditions. While these are verified in protection applications (the cycles provide independent measurements of fluxes and related quantities), the hypothesis of independent estimates/cycles is broken in criticality mode. Indeed the power iteration technique used in this mode couples a generation to its progeny. Often, after what is called 'source convergence' this coupling almost disappears (the solution is closed to equilibrium) but for loosely coupled systems, such as for PWR or large nuclear cores, the equilibrium is never found, or at least may take time to reach, and the variance estimation such as allowed by the CLT is under-evaluated. In this paper we first propose, by the mean of two different methods, to evaluate the typical correlation length, as measured in cycles number, and then use this information to diagnose correlation problems and to provide an improved variance estimation. Those two methods are based on Fourier spectral decomposition and on the lag k autocorrelation calculation. A theoretical modeling of the autocorrelation function, based on Gauss-Markov stochastic processes, will also be presented. Tests will be performed with Tripoli4 on a PWR pin cell. (authors)

  12. A Practical Methodology for Quantifying Random and Systematic Components of Unexplained Variance in a Wind Tunnel

    NASA Technical Reports Server (NTRS)

    Deloach, Richard; Obara, Clifford J.; Goodman, Wesley L.

    2012-01-01

    This paper documents a check standard wind tunnel test conducted in the Langley 0.3-Meter Transonic Cryogenic Tunnel (0.3M TCT) that was designed and analyzed using the Modern Design of Experiments (MDOE). The test designed to partition the unexplained variance of typical wind tunnel data samples into two constituent components, one attributable to ordinary random error, and one attributable to systematic error induced by covariate effects. Covariate effects in wind tunnel testing are discussed, with examples. The impact of systematic (non-random) unexplained variance on the statistical independence of sequential measurements is reviewed. The corresponding correlation among experimental errors is discussed, as is the impact of such correlation on experimental results generally. The specific experiment documented herein was organized as a formal test for the presence of unexplained variance in representative samples of wind tunnel data, in order to quantify the frequency with which such systematic error was detected, and its magnitude relative to ordinary random error. Levels of systematic and random error reported here are representative of those quantified in other facilities, as cited in the references.

  13. Accounting for Variance in Hyperspectral Data Coming from Limitations of the Imaging System

    NASA Astrophysics Data System (ADS)

    Shurygin, B.; Shestakova, M.; Nikolenko, A.; Badasen, E.; Strakhov, P.

    2016-06-01

    Over the course of the past few years, a number of methods was developed to incorporate hyperspectral imaging specifics into generic data mining techniques, traditionally used for hyperspectral data processing. Projection pursuit methods embody the largest class of methods empoyed for hyperspectral image data reduction, however, they all have certain drawbacks making them either hard to use or inefficient. It has been shown that hyperspectral image (HSI) statistics tend to display "heavy tails" (Manolakis2003)(Theiler2005), rendering most of the projection pursuit methods hard to use. Taking into consideration the magnitude of described deviations of observed data PDFs from normal distribution, it is apparent that a priori knowledge of variance in data caused by the imaging system is to be employed in order to efficiently classify objects on HSIs (Kerr, 2015), especially in cases of wildly varying SNR. A number of attempts to describe this variance and compensating techniques has been made (Aiazzi2006), however, new data quality standards are not yet set and accounting for the detector response is made under large set of assumptions. Current paper addresses the issue of hyperspectral image classification in the context of different variance sources based on the knowledge of calibration curves (both spectral and radiometric) obtained for each pixel of imaging camera. A camera produced by ZAO NPO Lepton (Russia) was calibrated and used to obtain a test image. A priori known values of SNR and spectral channel cross-correlation were incorporated into calculating test statistics used in dimensionality reduction and feature extraction. Expectation-Maximization classification algorithm modification for non-Gaussian model as described by (Veracini2010) was further employed. The impact of calibration data coarsening by ignoring non-uniformities on false alarm rate was studied. Case study shows both regions of scene-dominated variance and sensor-dominated variance, leading

  14. Some variance reduction methods for numerical stochastic homogenization.

    PubMed

    Blanc, X; Le Bris, C; Legoll, F

    2016-04-28

    We give an overview of a series of recent studies devoted to variance reduction techniques for numerical stochastic homogenization. Numerical homogenization requires that a set of problems is solved at the microscale, the so-called corrector problems. In a random environment, these problems are stochastic and therefore need to be repeatedly solved, for several configurations of the medium considered. An empirical average over all configurations is then performed using the Monte Carlo approach, so as to approximate the effective coefficients necessary to determine the macroscopic behaviour. Variance severely affects the accuracy and the cost of such computations. Variance reduction approaches, borrowed from other contexts in the engineering sciences, can be useful. Some of these variance reduction techniques are presented, studied and tested here. PMID:27002065

  15. RISK ANALYSIS, ANALYSIS OF VARIANCE: GETTING MORE FROM OUR DATA

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Analysis of variance (ANOVA) and regression are common statistical techniques used to analyze agronomic experimental data and determine significant differences among yields due to treatments or other experimental factors. Risk analysis provides an alternate and complimentary examination of the same...

  16. 40 CFR 142.42 - Consideration of a variance request.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... contaminant level required by the national primary drinking water regulations because of the nature of the raw... effectiveness of treatment methods for the contaminant for which the variance is requested. (2) Cost and...

  17. 40 CFR 141.4 - Variances and exemptions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... subparts H, P, S, T, W, and Y of this part. ... total coliforms and E. coli and variances from any of the treatment technique requirements of subpart H... Section 141.4 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER...

  18. Modern diet and metabolic variance – a recipe for disaster?

    PubMed Central

    2014-01-01

    Objective Recently, a positive correlation between alanine transaminase activity and body mass was established among healthy young individuals of normal weight. Here we explore further this relationship and propose a physiological rationale for this link. Design Cross-sectional statistical analysis of adiposity across large samples of adults differing by age, diet and lifestyle. Subjects 46,684 19–20 years old Swiss male conscripts and published data on 1000 Eskimos, 518 Toronto residents and 97,000 North American Adventists. Measurements Serum concentrations of the alanine transaminase, post-prandial glucose levels, cholesterol, body height and weight, blood pressure and routine blood analysis (thrombocytes and leukocytes) for Swiss conscripts. Adiposity measures and dietary information for other groups were also obtained. Results Stepwise multiple regression after correction for random errors of physiological tests showed that 28% of the total variance in body mass is associated with ALT concentrations. This relationship remained significant when only metabolically healthy (as defined by the American Heart Association) Swiss conscripts were selected. The data indicated that high protein only or high carbohydrate only diets are associated with lower levels of obesity than a diet combining proteins and carbohydrates. Conclusion Elevated levels of alanine transaminase, and likely other transaminases, may result in overactivity of the alanine cycle that produces pyruvate from protein. When a mixed meal of protein, carbohydrate and fat is consumed, carbohydrates and fats are digested faster and metabolised to satisfy body’s energetic needs while slower digested protein is ultimately converted to malonyl CoA and stored as fat. Chronicity of this sequence is proposed to cause accumulation of somatic fat stores and thus obesity. PMID:24502225

  19. Low complex subspace minimum variance beamformer for medical ultrasound imaging.

    PubMed

    Deylami, Ali Mohades; Asl, Babak Mohammadzadeh

    2016-03-01

    Minimum variance (MV) beamformer enhances the resolution and contrast in the medical ultrasound imaging at the expense of higher computational complexity with respect to the non-adaptive delay-and-sum beamformer. The major complexity arises from the estimation of the L×L array covariance matrix using spatial averaging, which is required to more accurate estimation of the covariance matrix of correlated signals, and inversion of it, which is required for calculating the MV weight vector which are as high as O(L(2)) and O(L(3)), respectively. Reducing the number of array elements decreases the computational complexity but degrades the imaging resolution. In this paper, we propose a subspace MV beamformer which preserves the advantages of the MV beamformer with lower complexity. The subspace MV neglects some rows of the array covariance matrix instead of reducing the array size. If we keep η rows of the array covariance matrix which leads to a thin non-square matrix, the weight vector of the subspace beamformer can be achieved in the same way as the MV obtains its weight vector with lower complexity as high as O(η(2)L). More calculations would be saved because an η×L covariance matrix must be estimated instead of a L×L. We simulated a wire targets phantom and a cyst phantom to evaluate the performance of the proposed beamformer. The results indicate that we can keep about 16 from 43 rows of the array covariance matrix which reduces the order of complexity to 14% while the image resolution is still comparable to that of the standard MV beamformer. We also applied the proposed method to an experimental RF data and showed that the subspace MV beamformer performs like the standard MV with lower computational complexity. PMID:26678788

  20. Potential for Co-Infection of a Mosquito-Specific Flavivirus, Nhumirim Virus, to Block West Nile Virus Transmission in Mosquitoes.

    PubMed

    Goenaga, Silvina; Kenney, Joan L; Duggal, Nisha K; Delorey, Mark; Ebel, Gregory D; Zhang, Bo; Levis, Silvana C; Enria, Delia A; Brault, Aaron C

    2015-11-01

    Nhumirim virus (NHUV) is an insect-specific virus that phylogenetically affiliates with dual-host mosquito-borne flaviviruses. Previous in vitro co-infection experiments demonstrated prior or concurrent infection of Aedes albopictus C6/36 mosquito cells with NHUV resulted in a 10,000-fold reduction in viral production of West Nile virus (WNV). This interference between WNV and NHUV was observed herein in an additional Ae. albopictus mosquito cell line, C7-10. A WNV 2K peptide (V9M) mutant capable of superinfection with a pre-established WNV infection demonstrated a comparable level of interference from NHUV as the parental WNV strain in C6/36 and C7-10 cells. Culex quinquefasciatus and Culex pipiens mosquitoes intrathoracically inoculated with NHUV and WNV, or solely with WNV as a control, were allowed to extrinsically incubate the viruses up to nine and 14 days, respectively, and transmissibility and replication of WNV was determined. The proportion of Cx. quinquefasciatus mosquitoes capable of transmitting WNV was significantly lower for the WNV/NHUV group than the WNV control at seven and nine days post inoculation (dpi), while no differences were observed in the Cx. pipiens inoculation group. By dpi nine, a 40% reduction in transmissibility in mosquitoes from the dual inoculation group was observed compared to the WNV-only control. These data indicate the potential that infection of some Culex spp. vectors with NHUV could serve as a barrier for efficient transmissibility of flaviviruses associated with human disease. PMID:26569286

  1. Potential for Co-Infection of a Mosquito-Specific Flavivirus, Nhumirim Virus, to Block West Nile Virus Transmission in Mosquitoes

    PubMed Central

    Goenaga, Silvina; Kenney, Joan L.; Duggal, Nisha K.; Delorey, Mark; Ebel, Gregory D.; Zhang, Bo; Levis, Silvana C.; Enria, Delia A.; Brault, Aaron C.

    2015-01-01

    Nhumirim virus (NHUV) is an insect-specific virus that phylogenetically affiliates with dual-host mosquito-borne flaviviruses. Previous in vitro co-infection experiments demonstrated prior or concurrent infection of Aedes albopictus C6/36 mosquito cells with NHUV resulted in a 10,000-fold reduction in viral production of West Nile virus (WNV). This interference between WNV and NHUV was observed herein in an additional Ae. albopictus mosquito cell line, C7-10. A WNV 2K peptide (V9M) mutant capable of superinfection with a pre-established WNV infection demonstrated a comparable level of interference from NHUV as the parental WNV strain in C6/36 and C7-10 cells. Culex quinquefasciatus and Culex pipiens mosquitoes intrathoracically inoculated with NHUV and WNV, or solely with WNV as a control, were allowed to extrinsically incubate the viruses up to nine and 14 days, respectively, and transmissibility and replication of WNV was determined. The proportion of Cx. quinquefasciatus mosquitoes capable of transmitting WNV was significantly lower for the WNV/NHUV group than the WNV control at seven and nine days post inoculation (dpi), while no differences were observed in the Cx. pipiens inoculation group. By dpi nine, a 40% reduction in transmissibility in mosquitoes from the dual inoculation group was observed compared to the WNV-only control. These data indicate the potential that infection of some Culex spp. vectors with NHUV could serve as a barrier for efficient transmissibility of flaviviruses associated with human disease. PMID:26569286

  2. Prevalence of antibodies to alphaviruses and flaviviruses in free-ranging game animals and nonhuman primates in the greater Congo basin.

    PubMed

    Kading, Rebekah C; Borland, Erin M; Cranfield, Mike; Powers, Ann M

    2013-07-01

    Vector-borne and zoonotic pathogens have comprised a significant proportion of the emerging infectious diseases in humans in recent decades. The role of many wildlife species as reservoirs for arthropod-borne viral pathogens is poorly understood. We investigated the exposure history of various African wildlife species from the Congo basin to mosquito-borne flaviviruses and alphaviruses by testing archived serum samples. Sera from 24 African forest buffalo (Syncerus caffer nanus), 34 African elephants (Loxodonta africana), 40 duikers (Cephalophus and Philantomba spp.), 25 mandrills (Mandrillus sphinx), 32 mountain gorillas (Gorilla beringei beringei), five Grauer's gorillas (Gorilla beringei graueri), two L'Hoest's monkeys (Cercopithecus lhoesti), two golden monkeys (Cercopithecus kandti), and three chimpanzees (Pan troglodytes) sampled between 1991 and 2009 were tested for antibodies against chikungunya virus (CHIKV), o'nyong-nyong virus (ONNV), West Nile virus (WNV), dengue 2 virus (DENV-2), and yellow fever virus (YFV) by plaque reduction neutralization test. Specific neutralizing antibodies against ONNV were found in African forest buffalo in the Democratic Republic of the Congo (DRC) and Gabon, duikers in the DRC, and mandrills in Gabon, providing novel evidence of enzootic circulation of ONNV in these countries. African forest buffalo in the DRC and Gabon also demonstrated evidence of exposure to CHIKV, WNV, and DENV-2, while mandrills in Gabon were antibody positive for CHIKV, DENV-2, WNV, and YFV. All of the elephants tested had a strong neutralizing antibody response to WNV. We also document results from a survey of gorillas for arboviruses, of which 4/32 (13%) had antibody to an alphavirus or flavivirus. Overall, our results demonstrate a high prevalence of neutralizing antibodies against multiple arboviruses in wildlife in equatorial Africa. PMID:23778608

  3. Markers for trans-Golgi Membranes and the Intermediate Compartment Localize to Induced Membranes with Distinct Replication Functions in Flavivirus-Infected Cells†

    PubMed Central

    Mackenzie, Jason M.; Jones, Malcolm K.; Westaway, Edwin G.

    1999-01-01

    Replication of the flavivirus Kunjin virus is associated with virus-induced membrane structures within the cytoplasm of infected cells; these membranes appear as packets of vesicles associated with the sites of viral RNA synthesis and as convoluted membranes (CM) and paracrystalline arrays (PC) containing the components of the virus-specified protease (E. G. Westaway, J. M. Mackenzie, M. T. Kenney, M. K. Jones, and A. A. Khromykh, J. Virol. 71:6650–6661, 1997). To determine the cellular origins of these membrane structures, we compared the immunolabelling patterns of several cell markers in relation to these sites by immunofluorescence and immunoelectron microscopy. A marker for the trans-Golgi membranes and the trans-Golgi network, 1,4-galactosyltransferase (GalT), was redistributed to large foci in the cytoplasm of Kunjin virus-infected cells, partially coincident with immunofluorescent foci associated with the putative sites of viral RNA synthesis. As determined by immunoelectron microscopy, the induced vesicle packets contained GalT, whereas the CM and PC contained a specific protein marker for the intermediate compartment (ERGIC53). A further indicator of the role of cellular organelles in their biogenesis was the observation that the Golgi apparatus-disrupting agent brefeldin A prevented further development of immunofluorescent foci of induced membranes if added before the end of the latent period but that once formed, these membrane foci were resistant to brefeldin A dispersion. Reticulum membranes emanating from the induced CM and PC were also labelled with the rough endoplasmic reticulum marker anti-protein disulfide isomerase and were obviously redistributed during infection. This is the first report identifying trans-Golgi membranes and the intermediate compartment as the apparent sources of the flavivirus-induced membranes involved in events of replication. PMID:10516064

  4. A multicomb variance reduction scheme for Monte Carlo semiconductor simulators

    SciTech Connect

    Gray, M.G.; Booth, T.E.; Kwan, T.J.T.; Snell, C.M.

    1998-04-01

    The authors adapt a multicomb variance reduction technique used in neutral particle transport to Monte Carlo microelectronic device modeling. They implement the method in a two-dimensional (2-D) MOSFET device simulator and demonstrate its effectiveness in the study of hot electron effects. The simulations show that the statistical variance of hot electrons is significantly reduced with minimal computational cost. The method is efficient, versatile, and easy to implement in existing device simulators.

  5. Design impact and significance of non-stationarity of variance in extreme rainfall

    NASA Astrophysics Data System (ADS)

    Saji, M. Al; O'Sullivan, J. J.; O'Connor, A.

    2015-06-01

    Stationarity in hydro-meteorological records is often investigated through an assessment of the mean value of the tested parameter. This is arguably insufficient for capturing fully the non-stationarity signal, and parameter variance is an equally important indicator. This study applied the Mann-Kendall linear and Mann-Whitney-Wilcoxon step change trend detection techniques to investigate the changes in the mean and variance of annual maximum daily rainfalls at eight stations in Dublin, Ireland, where long and high quality daily rainfall records were available. The eight stations are located in a geographically similar and spatially compact region (< 950 km2) and their rainfalls were shown to be well correlated. Results indicate that while significant positive step changes were observed in mean annual maximum daily rainfalls (1961 and 1997) at only two of the eight stations, a significant and consistent shift in the variance was observed at all eight stations during the 1980's. This period saw a widely noted positive shift in the winter North Atlantic Oscillation that greatly influences rainfall patterns in Northern Europe. Design estimates were obtained from a frequency analysis of annual maximum daily rainfalls (AM series) using the Generalised Extreme Value distribution, identified through application of the Modified Anderson Darling Goodness of Fit criterion. To evaluate the impact of the observed non-stationarity in variance on rainfall design estimates, two sets of depth-frequency relationships at each station for return periods from 5 to 100-years were constructed. The first was constructed with bootstrapped confidence intervals based on the full AM series assuming stationarity and the second was based on a partial AM series commencing in the year that followed the observed shift in variance. Confidence intervals distinguish climate signals from natural variability. Increases in design daily rainfall estimates obtained from the depth-frequency relationship

  6. Non-destructive X-ray Computed Tomography (XCT) Analysis of Sediment Variance in Marine Cores

    NASA Astrophysics Data System (ADS)

    Oti, E.; Polyak, L. V.; Dipre, G.; Sawyer, D.; Cook, A.

    2015-12-01

    where, and to what extent, the burrow tubes deviate from the sediment matrix. Future research will correlate changes in variance due to bioturbation to other features indicating ocean temperatures and nutrient flux, such as foraminifera counts and oxygen isotope data.

  7. Measurement of Ulnar Variance in a Regional Subset of Indian Population—A Pilot Study of 30 Subjects

    PubMed Central

    Jalan, Divesh; Elhence, Abhay

    2015-01-01

    Background The variation of level of distal articulating surface of ulna with respect to distal articulating surface of radius is known as ulnar variance (UV). Positive and negative UV has been implicated in various wrist and hand pathologies. Aim To measure ulnar variance in a regional subset of Indian population and to compare two techniques of measurement of ulnar variance viz. method of perpendiculars and modification of the concentric circles method. Materials and Methods UV was measured in a regional subset of Indian population comprising of 30 subjects. The mean age of patients was 35.9 years. There were 16 males and 14 females in the study group. Antero-posterior (AP) X-rays of wrist in neutral position were taken and UV was measured using method of perpendiculars and the modified circle method. Results The mean UV using method of perpendiculars (UVA) was 0.387 mm and using modified circle method (UVB) was 0.507mm. A higher predominance of positive UV in this regional subset of Indian population was observed. There was no correlation between UV with respect to age and sex. No statistically significant difference was observed between the two methods of measurement utilized in the study. Conclusion The documentation of a negative and positive ulnar variance will help in prophylactic and timely intervention for various wrist pathologies, if required. However, a larger sample size with a longer follow up is required to suggest a correlation of ulnar variance with clinically symptomatic disease. PMID:26500970

  8. Variance and bias computations for improved modal identification using ERA/DC

    NASA Technical Reports Server (NTRS)

    Longman, Richard W.; Lew, Jiann-Shiun; Tseng, Dong-Huei; Juang, Jer-Nan

    1991-01-01

    Variance and bias confidence criteria were recently developed for the eigensystem realization algorithm (ERA) identification technique. These criteria are extended for the modified version of ERA based on data correlation, ERA/DC, and also for the Q-Markov cover algorithm. The importance and usefulness of the variance and bias information are demonstrated in numerical studies. The criteria are shown to be very effective not only by indicating the accuracy of the identification results, especially in terms of confidence intervals, but also by helping the ERA user to obtain better results by seeing the effect of changing the sample time, adjusting the Hankel matrix dimension, choosing how many singular values to retain, deciding the model order, etc.

  9. Degree variances of the earth's potential, topography and its isostatic compensation

    NASA Technical Reports Server (NTRS)

    Rapp, R. H.

    1982-01-01

    A spherical harmonic expansion of the earth's gravitational potential and equivalent rock topography to degree and order 180 is described. The potential implied by the topography considered as uncompensated and with isostatic compensation has been computed. Good agreement with the observed potential field is found when the depth of compensation in the Airy theory is assumed to be 50 km. At the higher degrees the correlation coefficient between the potential expansion and the equivalent rock topography is about 0.5. The Lachapelle equations for the topographic isostatic potential were tested using 1 x 1 deg equivalent rock topography. The degree variances agree at the lower degrees but at degree 36 the Lachapelle results using 5 deg data underestimate the potential degree variances by about one-third.

  10. Quantitative Genetic Analysis of Temperature Regulation in MUS MUSCULUS. I. Partitioning of Variance

    PubMed Central

    Lacy, Robert C.; Lynch, Carol Becker

    1979-01-01

    Heritabilities (from parent-offspring regression) and intraclass correlations of full sibs for a variety of traits were estimated from 225 litters of a heterogeneous stock (HS/Ibg) of laboratory mice. Initial variance partitioning suggested different adaptive functions for physiological, morphological and behavioral adjustments with respect to their thermoregulatory significance. Metabolic heat-production mechanisms appear to have reached their genetic limits, with little additive genetic variance remaining. This study provided no genetic evidence that body size has a close directional association with fitness in cold environments, since heritability estimates for weight gain and adult weight were similar and high, whether or not the animals were exposed to cold. Behavioral heat conservation mechanisms also displayed considerable amounts of genetic variability. However, due to strong evidence from numerous other studies that behavior serves an important adaptive role for temperature regulation in small mammals, we suggest that fluctuating selection pressures may have acted to maintain heritable variation in these traits. PMID:17248909

  11. On variance estimate for covariate adjustment by propensity score analysis.

    PubMed

    Zou, Baiming; Zou, Fei; Shuster, Jonathan J; Tighe, Patrick J; Koch, Gary G; Zhou, Haibo

    2016-09-10

    Propensity score (PS) methods have been used extensively to adjust for confounding factors in the statistical analysis of observational data in comparative effectiveness research. There are four major PS-based adjustment approaches: PS matching, PS stratification, covariate adjustment by PS, and PS-based inverse probability weighting. Though covariate adjustment by PS is one of the most frequently used PS-based methods in clinical research, the conventional variance estimation of the treatment effects estimate under covariate adjustment by PS is biased. As Stampf et al. have shown, this bias in variance estimation is likely to lead to invalid statistical inference and could result in erroneous public health conclusions (e.g., food and drug safety and adverse events surveillance). To address this issue, we propose a two-stage analytic procedure to develop a valid variance estimator for the covariate adjustment by PS analysis strategy. We also carry out a simple empirical bootstrap resampling scheme. Both proposed procedures are implemented in an R function for public use. Extensive simulation results demonstrate the bias in the conventional variance estimator and show that both proposed variance estimators offer valid estimates for the true variance, and they are robust to complex confounding structures. The proposed methods are illustrated for a post-surgery pain study. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26999553

  12. Analytic variance estimates of Swank and Fano factors

    SciTech Connect

    Gutierrez, Benjamin; Badano, Aldo; Samuelson, Frank

    2014-07-15

    Purpose: Variance estimates for detector energy resolution metrics can be used as stopping criteria in Monte Carlo simulations for the purpose of ensuring a small uncertainty of those metrics and for the design of variance reduction techniques. Methods: The authors derive an estimate for the variance of two energy resolution metrics, the Swank factor and the Fano factor, in terms of statistical moments that can be accumulated without significant computational overhead. The authors examine the accuracy of these two estimators and demonstrate how the estimates of the coefficient of variation of the Swank and Fano factors behave with data from a Monte Carlo simulation of an indirect x-ray imaging detector. Results: The authors' analyses suggest that the accuracy of their variance estimators is appropriate for estimating the actual variances of the Swank and Fano factors for a variety of distributions of detector outputs. Conclusions: The variance estimators derived in this work provide a computationally convenient way to estimate the error or coefficient of variation of the Swank and Fano factors during Monte Carlo simulations of radiation imaging systems.

  13. Variance estimation for systematic designs in spatial surveys.

    PubMed

    Fewster, R M

    2011-12-01

    In spatial surveys for estimating the density of objects in a survey region, systematic designs will generally yield lower variance than random designs. However, estimating the systematic variance is well known to be a difficult problem. Existing methods tend to overestimate the variance, so although the variance is genuinely reduced, it is over-reported, and the gain from the more efficient design is lost. The current approaches to estimating a systematic variance for spatial surveys are to approximate the systematic design by a random design, or approximate it by a stratified design. Previous work has shown that approximation by a random design can perform very poorly, while approximation by a stratified design is an improvement but can still be severely biased in some situations. We develop a new estimator based on modeling the encounter process over space. The new "striplet" estimator has negligible bias and excellent precision in a wide range of simulation scenarios, including strip-sampling, distance-sampling, and quadrat-sampling surveys, and including populations that are highly trended or have strong aggregation of objects. We apply the new estimator to survey data for the spotted hyena (Crocuta crocuta) in the Serengeti National Park, Tanzania, and find that the reported coefficient of variation for estimated density is 20% using approximation by a random design, 17% using approximation by a stratified design, and 11% using the new striplet estimator. This large reduction in reported variance is verified by simulation. PMID:21534940

  14. Genetic selection for increased mean and reduced variance of twinning rate in Belclare ewes.

    PubMed

    Cottle, D J; Gilmour, A R; Pabiou, T; Amer, P R; Fahey, A G

    2016-04-01

    It is sometimes possible to breed for more uniform individuals by selecting animals with a greater tendency to be less variable, that is, those with a smaller environmental variance. This approach has been applied to reproduction traits in various animal species. We have evaluated fecundity in the Irish Belclare sheep breed by analyses of flocks with differing average litter size (number of lambs per ewe per year, NLB) and have estimated the genetic variance in environmental variance of lambing traits using double hierarchical generalized linear models (DHGLM). The data set comprised of 9470 litter size records from 4407 ewes collected in 56 flocks. The percentage of pedigreed lambing ewes with singles, twins and triplets was 30, 54 and 14%, respectively, in 2013 and has been relatively constant for the last 15 years. The variance of NLB increases with the mean in this data; the correlation of mean and standard deviation across sires is 0.50. The breeding goal is to increase the mean NLB without unduly increasing the incidence of triplets and higher litter sizes. The heritability estimates for lambing traits were NLB, 0.09; triplet occurrence (TRI) 0.07; and twin occurrence (TWN), 0.02. The highest and lowest twinning flocks differed by 23% (75% versus 52%) in the proportion of ewes lambing twins. Fitting bivariate sire models to NLB and the residual from the NLB model using a double hierarchical generalized linear model (DHGLM) model found a strong genetic correlation (0.88 ± 0.07) between the sire effect for the magnitude of the residual (VE ) and sire effects for NLB, confirming the general observation that increased average litter size is associated with increased variability in litter size. We propose a threshold model that may help breeders with low litter size increase the percentage of twin bearers without unduly increasing the percentage of ewes bearing triplets in Belclare sheep. PMID:26081782

  15. Shared genetic variance between obesity and white matter integrity in Mexican Americans

    PubMed Central

    Spieker, Elena A.; Kochunov, Peter; Rowland, Laura M.; Sprooten, Emma; Winkler, Anderson M.; Olvera, Rene L.; Almasy, Laura; Duggirala, Ravi; Fox, Peter T.; Blangero, John; Glahn, David C.; Curran, Joanne E.

    2015-01-01

    Obesity is a chronic metabolic disorder that may also lead to reduced white matter integrity, potentially due to shared genetic risk factors. Genetic correlation analyses were conducted in a large cohort of Mexican American families in San Antonio (N = 761, 58% females, ages 18–81 years; 41.3 ± 14.5) from the Genetics of Brain Structure and Function Study. Shared genetic variance was calculated between measures of adiposity [(body mass index (BMI; kg/m2) and waist circumference (WC; in)] and whole-brain and regional measurements of cerebral white matter integrity (fractional anisotropy). Whole-brain average and regional fractional anisotropy values for 10 major white matter tracts were calculated from high angular resolution diffusion tensor imaging data (DTI; 1.7 × 1.7 × 3 mm; 55 directions). Additive genetic factors explained intersubject variance in BMI (heritability, h2 = 0.58), WC (h2 = 0.57), and FA (h2 = 0.49). FA shared significant portions of genetic variance with BMI in the genu (ρG = −0.25), body (ρG = −0.30), and splenium (ρG = −0.26) of the corpus callosum, internal capsule (ρG = −0.29), and thalamic radiation (ρG = −0.31) (all p's = 0.043). The strongest evidence of shared variance was between BMI/WC and FA in the superior fronto-occipital fasciculus (ρG = −0.39, p = 0.020; ρG = −0.39, p = 0.030), which highlights region-specific variation in neural correlates of obesity. This may suggest that increase in obesity and reduced white matter integrity share common genetic risk factors. PMID:25763009

  16. Genetic variances and covariances of aerobic metabolic rates in laboratory mice

    PubMed Central

    Wone, Bernard; Sears, Michael W.; Labocha, Marta K.; Donovan, Edward R.; Hayes, Jack P.

    2009-01-01

    The genetic variances and covariances of traits must be known to predict how they may respond to selection and how covariances among them might affect their evolutionary trajectories. We used the animal model to estimate the genetic variances and covariances of basal metabolic rate (BMR) and maximal metabolic rate (MMR) in a genetically heterogeneous stock of laboratory mice. Narrow-sense heritability (h2) was approximately 0.38 ± 0.08 for body mass, 0.26 ± 0.08 for whole-animal BMR, 0.24 ± 0.07 for whole-animal MMR, 0.19 ± 0.07 for mass-independent BMR, and 0.16 ± 0.06 for mass-independent MMR. All h2 estimates were significantly different from zero. The phenotypic correlation of whole animal BMR and MMR was 0.56 ± 0.02, and the corresponding genetic correlation was 0.79 ± 0.12. The phenotypic correlation of mass-independent BMR and MMR was 0.13 ± 0.03, and the corresponding genetic correlation was 0.72 ± 0.03. The genetic correlations of metabolic rates were significantly different from zero, but not significantly different from one. A key assumption of the aerobic capacity model for the evolution of endothermy is that BMR and MMR are linked. The estimated genetic correlation between BMR and MMR is consistent with that assumption, but the genetic correlation is not so high as to preclude independent evolution of BMR and MMR. PMID:19656796

  17. Detecting Pulsars with Interstellar Scintillation in Variance Images

    NASA Astrophysics Data System (ADS)

    Dai, S.; Johnston, S.; Bell, M. E.; Coles, W. A.; Hobbs, G.; Ekers, R. D.; Lenc, E.

    2016-08-01

    Pulsars are the only cosmic radio sources known to be sufficiently compact to show diffractive interstellar scintillations. Images of the variance of radio signals in both time and frequency can be used to detect pulsars in large-scale continuum surveys using the next generation of synthesis radio telescopes. This technique allows a search over the full field of view while avoiding the need for expensive pixel-by-pixel high time resolution searches. We investigate the sensitivity of detecting pulsars in variance images. We show that variance images are most sensitive to pulsars whose scintillation time-scales and bandwidths are close to the subintegration time and channel bandwidth. Therefore, in order to maximise the detection of pulsars for a given radio continuum survey, it is essential to retain a high time and frequency resolution, allowing us to make variance images sensitive to pulsars with different scintillation properties. We demonstrate the technique with Murchision Widefield Array data and show that variance images can indeed lead to the detection of pulsars by distinguishing them from other radio sources.

  18. Application of variance components estimation to calibrate geoid error models.

    PubMed

    Guo, Dong-Mei; Xu, Hou-Ze

    2015-01-01

    The method of using Global Positioning System-leveling data to obtain orthometric heights has been well studied. A simple formulation for the weighted least squares problem has been presented in an earlier work. This formulation allows one directly employing the errors-in-variables models which completely descript the covariance matrices of the observables. However, an important question that what accuracy level can be achieved has not yet to be satisfactorily solved by this traditional formulation. One of the main reasons for this is the incorrectness of the stochastic models in the adjustment, which in turn allows improving the stochastic models of measurement noises. Therefore the issue of determining the stochastic modeling of observables in the combined adjustment with heterogeneous height types will be a main focus point in this paper. Firstly, the well-known method of variance component estimation is employed to calibrate the errors of heterogeneous height data in a combined least square adjustment of ellipsoidal, orthometric and gravimetric geoid. Specifically, the iterative algorithms of minimum norm quadratic unbiased estimation are used to estimate the variance components for each of heterogeneous observations. Secondly, two different statistical models are presented to illustrate the theory. The first method directly uses the errors-in-variables as a priori covariance matrices and the second method analyzes the biases of variance components and then proposes bias-corrected variance component estimators. Several numerical test results show the capability and effectiveness of the variance components estimation procedure in combined adjustment for calibrating geoid error model. PMID:26306296

  19. Analysis of Variance Components for Genetic Markers with Unphased Genotypes

    PubMed Central

    Wang, Tao

    2016-01-01

    An ANOVA type general multi-allele (GMA) model was proposed in Wang (2014) on analysis of variance components for quantitative trait loci or genetic markers with phased or unphased genotypes. In this study, by applying the GMA model, we further examine estimation of the genetic variance components for genetic markers with unphased genotypes based on a random sample from a study population. In one locus and two loci cases, we first derive the least square estimates (LSE) of model parameters in fitting the GMA model. Then we construct estimators of the genetic variance components for one marker locus in a Hardy-Weinberg disequilibrium population and two marker loci in an equilibrium population. Meanwhile, we explore the difference between the classical general linear model (GLM) and GMA based approaches in association analysis of genetic markers with quantitative traits. We show that the GMA model can retain the same partition on the genetic variance components as the traditional Fisher's ANOVA model, while the GLM cannot. We clarify that the standard F-statistics based on the partial reductions in sums of squares from GLM for testing the fixed allelic effects could be inadequate for testing the existence of the variance component when allelic interactions are present. We point out that the GMA model can reduce the confounding between the allelic effects and allelic interactions at least for independent alleles. As a result, the GMA model could be more beneficial than GLM for detecting allelic interactions. PMID:27468297

  20. Allocation of experimental resources to minimize the variance of genotype mean chip color and tuber composition

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Breeders select superior genotypes despite the environment affecting phenotypic variance. Minimal variance of genotype means facilitates the statistical identification of superior genotypes. The variance components calculated from three datasets describing tuber composition and fried chip color were...

  1. An Overlooked Consequence of Dietary Mixing: A Varied Diet Reduces Interindividual Variance in Fitness.

    PubMed

    Senior, Alistair M; Nakagawa, Shinichi; Lihoreau, Mathieu; Simpson, Stephen J; Raubenheimer, David

    2015-11-01

    The determinants of diet breadth are of interest to nutritionists, ecologists, and evolutionary biologists. A recent synthesis addressing this issue found conflicting evidence for the relationship between diet breadth and mean individual fitness. Specifically, it found that while, on average, a mixed diet does increase mean fitness, in some instances, a single food provides equal (or higher) fitness than a mixed diet. Critical to ecological and evolutionary considerations of diet, however, is not only mean fitness but also variance in fitness. We combine contemporary meta-analytic methods with models of nutritional geometry to evaluate how diet affects between-individual variance in fitness within generalist consumers from a range of trophic levels. As predicted by nutritional geometry, we found that between-individual variance in fitness-related traits is higher on single-food than mixed diets. The effect was strong for longevity traits (57% higher) and reproductive traits (37%) and present but weaker for size-related traits (10%). Further, the effect became stronger as the number of available foods increased. The availability of multiple foods likely allows individuals with differing nutritional optima to customize intake, each maximizing their own fitness. Importantly, these findings may suggest that selection on traits correlated with nutritional requirements is weak in heterogeneous nutritional environments. PMID:26655777

  2. Physicochemical factors affecting the spatial variance of monomethylmercury in artificial reservoirs.

    PubMed

    Noh, Seam; Kim, Chan-Kook; Lee, Jong-Hyeon; Kim, Younghee; Choi, Kyunghee; Han, Seunghee

    2016-01-01

    The aim of this study was to identify how hydrologic factors (e.g., rainfall, maximum depth, reservoir and catchment area, and water residence time) and water chemistry factors (e.g., conductivity, pH, suspended particulate matter, chlorophyll-a, dissolved organic carbon, and sulfate) interact to affect the spatial variance in monomethylmercury (MMHg) concentration in nine artificial reservoirs. We hypothesized that the MMHg concentration of reservoir water would be higher in eutrophic than in oligotrophic reservoirs because increased dissolved organic matter and sulfate in eutrophic reservoirs can promote in situ production of MMHg. Multiple tools, including Pearson correlation, a self-organizing map, and principal component analysis, were applied in the statistical modeling of Hg species. The results showed that rainfall amount and hydraulic residence time best explained the variance of dissolved Hg and dissolved MMHg in reservoir water. High precipitation events and residence time may mobilize Hg and MMHg in the catchment and reservoir sediment, respectively. On the contrary, algal biomass was a key predictor of the variance of the percentage fraction of unfiltered MMHg over unfiltered Hg (%MMHg). The creation of suboxic conditions and the supply of sulfate subsequent to the algal decomposition seemed to support enhanced %MMHg in the bloom reservoirs. Thus, the nutrient supply should be carefully managed to limit increases in the %MMHg/Hg of temperate reservoirs. PMID:26552526

  3. MAGNETIC VARIANCES AND PITCH-ANGLE SCATTERING TIMES UPSTREAM OF INTERPLANETARY SHOCKS

    SciTech Connect

    Perri, Silvia; Zimbardo, Gaetano E-mail: gaetano.zimbardo@fis.unical.it

    2012-07-20

    Recent observations of power-law time profiles of energetic particles accelerated at interplanetary shocks have shown the possibility of anomalous, superdiffusive transport for energetic particles throughout the heliosphere. Those findings call for an accurate investigation of the magnetic field fluctuation properties at the resonance frequencies upstream of the shock's fronts. Normalized magnetic field variances, indeed, play a crucial role in the determination of the pitch-angle scattering times and then of the transport regime. The present analysis investigates the time behavior of the normalized variances of the magnetic field fluctuations, measured by the Ulysses spacecraft upstream of corotating interaction region (CIR) shocks, for those events which exhibit superdiffusion for energetic electrons. We find a quasi-constant value for the normalized magnetic field variances from about 10 hr to 100 hr from the shock front. This rules out the presence of a varying diffusion coefficient and confirms the possibility of superdiffusion for energetic electrons. A statistical analysis of the scattering times obtained from the magnetic fluctuations upstream of the CIR events has also been performed; the resulting power-law distributions of scattering times imply long range correlations and weak pitch-angle scattering, and the power-law slopes are in qualitative agreement with superdiffusive processes described by a Levy random walk.

  4. Modeling subgrid scale mixture fraction variance in LES of evaporating spray

    SciTech Connect

    Pera, Cecile; Reveillon, Julien; Vervisch, Luc; Domingo, Pascale

    2006-09-15

    Simulations of a dilute spray evaporating in spatially decaying homogeneous turbulence are performed. An Eulerian description of the flow is adopted, while the behavior of the discrete liquid phase is captured using Lagrangian modeling. Time and length scales of the continuous carrier phase are fully simulated; and by varying the properties of the modeled spray, a database of spray carrier phase direct numerical simulation (CP-DNS) is obtained. The CP-DNS is then filtered on a coarse grid to conduct a priori tests of subgrid scale (SGS) closures. The objective is to provide methods for approximating the level of SGS mixture fraction variance in large eddy simulation (LES) of fuel spray turbulent combustion. Direct estimation of the variance from the scales resolved in LES is first discussed. Then, the solving of a balance equation to get the variance is addressed, with closures for the scalar dissipation rate and the correlation between vapor source and mixture fraction. From the results, a procedure to couple spray evaporation with SGS turbulent combustion modeling emerges. (author)

  5. A model and variance reduction method for computing statistical outputs of stochastic elliptic partial differential equations

    SciTech Connect

    Vidal-Codina, F.; Nguyen, N.C.; Giles, M.B.; Peraire, J.

    2015-09-15

    We present a model and variance reduction method for the fast and reliable computation of statistical outputs of stochastic elliptic partial differential equations. Our method consists of three main ingredients: (1) the hybridizable discontinuous Galerkin (HDG) discretization of elliptic partial differential equations (PDEs), which allows us to obtain high-order accurate solutions of the governing PDE; (2) the reduced basis method for a new HDG discretization of the underlying PDE to enable real-time solution of the parameterized PDE in the presence of stochastic parameters; and (3) a multilevel variance reduction method that exploits the statistical correlation among the different reduced basis approximations and the high-fidelity HDG discretization to accelerate the convergence of the Monte Carlo simulations. The multilevel variance reduction method provides efficient computation of the statistical outputs by shifting most of the computational burden from the high-fidelity HDG approximation to the reduced basis approximations. Furthermore, we develop a posteriori error estimates for our approximations of the statistical outputs. Based on these error estimates, we propose an algorithm for optimally choosing both the dimensions of the reduced basis approximations and the sizes of Monte Carlo samples to achieve a given error tolerance. We provide numerical examples to demonstrate the performance of the proposed method.

  6. Monte Carlo variance reduction approaches for non-Boltzmann tallies

    SciTech Connect

    Booth, T.E.

    1992-12-01

    Quantities that depend on the collective effects of groups of particles cannot be obtained from the standard Boltzmann transport equation. Monte Carlo estimates of these quantities are called non-Boltzmann tallies and have become increasingly important recently. Standard Monte Carlo variance reduction techniques were designed for tallies based on individual particles rather than groups of particles. Experience with non-Boltzmann tallies and analog Monte Carlo has demonstrated the severe limitations of analog Monte Carlo for many non-Boltzmann tallies. In fact, many calculations absolutely require variance reduction methods to achieve practical computation times. Three different approaches to variance reduction for non-Boltzmann tallies are described and shown to be unbiased. The advantages and disadvantages of each of the approaches are discussed.

  7. Impact of Damping Uncertainty on SEA Model Response Variance

    NASA Technical Reports Server (NTRS)

    Schiller, Noah; Cabell, Randolph; Grosveld, Ferdinand

    2010-01-01

    Statistical Energy Analysis (SEA) is commonly used to predict high-frequency vibroacoustic levels. This statistical approach provides the mean response over an ensemble of random subsystems that share the same gross system properties such as density, size, and damping. Recently, techniques have been developed to predict the ensemble variance as well as the mean response. However these techniques do not account for uncertainties in the system properties. In the present paper uncertainty in the damping loss factor is propagated through SEA to obtain more realistic prediction bounds that account for both ensemble and damping variance. The analysis is performed on a floor-equipped cylindrical test article that resembles an aircraft fuselage. Realistic bounds on the damping loss factor are determined from measurements acquired on the sidewall of the test article. The analysis demonstrates that uncertainties in damping have the potential to significantly impact the mean and variance of the predicted response.

  8. Minimum variance lower bound estimation and realization for desired structures.

    PubMed

    Alipouri, Yousef; Poshtan, Javad

    2014-05-01

    The Minimum Variance Lower Bound (MVLB) represents the best achievable controller capability in a variance sense. Estimation and realization of MVLB for nonlinear systems confront some difficulties. Hence, almost all methods introduced so far estimate MVLB for a certain structure (e.g., NARMAX) or controller (e.g. PID). In this paper, MVLB for desired structures (not restricted to a certain type) is studied. The situation when the model is not in hand, is not accurate, or is not invertible has been considered. Moreover, in order to realize minimum variance controllers for nonlinear structures, a recursive model-free MVC design is utilized. Finally, a simulation study has been used to clarify the effectiveness of the proposed control scheme. PMID:24642244

  9. Enhancing area of review capabilities: Implementing a variance program

    SciTech Connect

    De Leon, F.

    1995-12-01

    The Railroad Commission of Texas (RRC) has regulated oil-field injection well operations since issuing its first injection permit in 1938. The Environmental Protection Agency (EPA) granted the RRC primary enforcement responsibility for the Class H Underground Injection Control (UIC) Program in April 1982. At that time, the added level of groundwater protection afforded by an Area of Review (AOR) on previously permitted Class H wells was not deemed necessary or cost effective. A proposed EPA rule change will require AORs to be performed on all pre-primacy Class II wells unless a variance can be justified. A variance methodology has been developed by researchers at the University of Missouri-Rolla in conjunction with the American Petroleum Institute (API). This paper will outline the RRC approach to implementing the AOR variance methodology. The RRC`s UIC program tracks 49,256 pre-primacy wells. Approximately 25,598 of these wells have active permits and will be subject to the proposed AOR requirements. The potential workload of performing AORs or granting variances for this many wells makes the development of a Geographic Information System (GIS) imperative. The RRC has recently completed a digitized map of the entire state and has spotted 890,000 of an estimated 1.2 million wells. Integrating this digital state map into a GIS will allow the RRC to tie its many data systems together. Once in place, this integrated data system will be used to evaluate AOR variances for pre-primacy wells on a field-wide basis. It will also reduce the regulatory cost of permitting by allowing the RRC staff to perform AORs or grant variances for the approximately 3,000 new and amended permit applications requiring AORs each year.

  10. The dynamic Allan Variance IV: characterization of atomic clock anomalies.

    PubMed

    Galleani, Lorenzo; Tavella, Patrizia

    2015-05-01

    The number of applications where precise clocks play a key role is steadily increasing, satellite navigation being the main example. Precise clock anomalies are hence critical events, and their characterization is a fundamental problem. When an anomaly occurs, the clock stability changes with time, and this variation can be characterized with the dynamic Allan variance (DAVAR). We obtain the DAVAR for a series of common clock anomalies, namely, a sinusoidal term, a phase jump, a frequency jump, and a sudden change in the clock noise variance. These anomalies are particularly common in space clocks. Our analytic results clarify how the clock stability changes during these anomalies. PMID:25965674

  11. Sensor/Actuator Selection for the Constrained Variance Control Problem

    NASA Technical Reports Server (NTRS)

    Delorenzo, M. L.; Skelton, R. E.

    1985-01-01

    The problem of designing a linear controller for systems subject to inequality variance constraints is considered. A quadratic penalty function approach is used to yield a linear controller. Both the weights in the quadratic penalty function and the locations of sensors and actuators are selected by successive approximations to obtain an optimal design which satisfies the input/output variance constraints. The method is applied to NASA's 64 meter Hoop-Column Space Antenna for satellite communications. In addition the solution for the control law, the main feature of these results is the systematic determination of actuator design requirements which allow the given input/output performance constraints to be satisfied.

  12. Variance in trace constituents following the final stratospheric warming

    NASA Technical Reports Server (NTRS)

    Hess, Peter

    1990-01-01

    Concentration variations with time in trace stratospheric constituents N2O, CF2Cl2, CFCl3, and CH4 were investigated using samples collected aboard balloons flown over southern France during the summer months of 1977-1979. Data are analyzed using a tracer transport model, and the mechanisms behind the modeled tracer variance are examined. An analysis of the N2O profiles for the month of June showed that a large fraction of the variance reported by Ehhalt et al. (1983) is on an interannual time scale.

  13. A multi-variance analysis in the time domain

    NASA Technical Reports Server (NTRS)

    Walter, Todd

    1993-01-01

    Recently a new technique for characterizing the noise processes affecting oscillators was introduced. This technique minimizes the difference between the estimates of several different variances and their values as predicted by the standard power law model of noise. The method outlined makes two significant advancements: it uses exclusively time domain variances so that deterministic parameters such as linear frequency drift may be estimated, and it correctly fits the estimates using the chi-square distribution. These changes permit a more accurate fitting at long time intervals where there is the least information. This technique was applied to both simulated and real data with excellent results.

  14. Signal Variance in Gamma Ray Detectors - A Review

    SciTech Connect

    Devanathan, Ram; Corrales, Louis R.; Gao, Fei; Weber, William J.

    2006-09-06

    Signal variance in gamma ray detector materials is reviewed with an emphasis on intrinsic variance. Phenomenological models of electron cascades are examined and the Fano factor (F) is discussed in detail. In semiconductors F is much smaller than unity and charge carrier production is nearly proportional to energy. Based on a fit to a number of semiconductors and insulators, a new relationship between the average energy for electron-hole pair production and band-gap energy is proposed. In scintillators, the resolution is governed mainly by photoelectron statistics and proportionality of light yield with respect to energy.

  15. Models of Postural Control: Shared Variance in Joint and COM Motions

    PubMed Central

    Kilby, Melissa C.; Molenaar, Peter C. M.; Newell, Karl M.

    2015-01-01

    This paper investigated the organization of the postural control system in human upright stance. To this aim the shared variance between joint and 3D total body center of mass (COM) motions was analyzed using multivariate canonical correlation analysis (CCA). The CCA was performed as a function of established models of postural control that varied in their joint degrees of freedom (DOF), namely, an inverted pendulum ankle model (2DOF), ankle-hip model (4DOF), ankle-knee-hip model (5DOF), and ankle-knee-hip-neck model (7DOF). Healthy young adults performed various postural tasks (two-leg and one-leg quiet stances, voluntary AP and ML sway) on a foam and rigid surface of support. Based on CCA model selection procedures, the amount of shared variance between joint and 3D COM motions and the cross-loading patterns we provide direct evidence of the contribution of multi-DOF postural control mechanisms to human balance. The direct model fitting of CCA showed that incrementing the DOFs in the model through to 7DOF was associated with progressively enhanced shared variance with COM motion. In the 7DOF model, the first canonical function revealed more active involvement of all joints during more challenging one leg stances and dynamic posture tasks. Furthermore, the shared variance was enhanced during the dynamic posture conditions, consistent with a reduction of dimension. This set of outcomes shows directly the degeneracy of multivariate joint regulation in postural control that is influenced by stance and surface of support conditions. PMID:25973896

  16. Models of Postural Control: Shared Variance in Joint and COM Motions.

    PubMed

    Kilby, Melissa C; Molenaar, Peter C M; Newell, Karl M

    2015-01-01

    This paper investigated the organization of the postural control system in human upright stance. To this aim the shared variance between joint and 3D total body center of mass (COM) motions was analyzed using multivariate canonical correlation analysis (CCA). The CCA was performed as a function of established models of postural control that varied in their joint degrees of freedom (DOF), namely, an inverted pendulum ankle model (2DOF), ankle-hip model (4DOF), ankle-knee-hip model (5DOF), and ankle-knee-hip-neck model (7DOF). Healthy young adults performed various postural tasks (two-leg and one-leg quiet stances, voluntary AP and ML sway) on a foam and rigid surface of support. Based on CCA model selection procedures, the amount of shared variance between joint and 3D COM motions and the cross-loading patterns we provide direct evidence of the contribution of multi-DOF postural control mechanisms to human balance. The direct model fitting of CCA showed that incrementing the DOFs in the model through to 7DOF was associated with progressively enhanced shared variance with COM motion. In the 7DOF model, the first canonical function revealed more active involvement of all joints during more challenging one leg stances and dynamic posture tasks. Furthermore, the shared variance was enhanced during the dynamic posture conditions, consistent with a reduction of dimension. This set of outcomes shows directly the degeneracy of multivariate joint regulation in postural control that is influenced by stance and surface of support conditions. PMID:25973896

  17. Upregulation of signalase processing and induction of prM-E secretion by the flavivirus NS2B-NS3 protease: roles of protease components.

    PubMed Central

    Yamshchikov, V F; Trent, D W; Compans, R W

    1997-01-01

    Recently, we have shown that the ability of the flavivirus NS2B-NS3 protease complex to promote efficient signalase processing of the C-prM precursor, as well as secretion of prM and E, does not appear to depend strictly on cleavage of the precursor at its Lys-Arg-Gly dibasic site by the protease. We suggested that the association of the protease with the precursor via NS2B may be sufficient by itself for the above effects. To study the proposed association in more detail, we have developed an assay in which processing at the C-prM dibasic cleavage site is abolished by Lys-->Gly conversion. We constructed deletion mutants and chimeras of the West Nile (WN) flavivirus NS2B protein and expressed them in the context of [5'-C-->NS3(243)] containing either wild-type C-prM or its cleavage site mutant. All NS2B variants were able to form active protease complexes. Deletion of the carboxy-terminal cluster of hydrophobic amino acids in NS2B had no apparent effect on the formation of prM and prM-E secretion for the cassettes containing either wild-type or mutated C-prM precursor. Deletion of the amino-terminal hydrophobic cluster in NS2B did not affect prM-E secretion for the cassettes with wild-type C-prM but abrogated prM-E secretion for the cassettes with the mutated dibasic cleavage site in C-prM. Similarly, the NS2B-NS3(178) protease of Japanese encephalitis (JE) virus, when substituted for the WN virus NS2B-NS3(243) protease, was able to promote prM-E secretion for the cassette with the wild-type C-prM precursor but not with the mutated one. Replacement of the deleted amino-terminal hydrophobic cluster in the WN virus NS2B protein with an analogous JE virus sequence restored the ability of the protease to promote prM-E secretion. On the basis of these observations, roles of individual protease components in upregulation of C-prM signalase processing are discussed. PMID:9151825

  18. The eukaryotic translation initiation factor 3 subunit L protein interacts with Flavivirus NS5 and may modulate yellow fever virus replication

    PubMed Central

    2013-01-01

    Background Yellow fever virus (YFV) belongs to the Flavivirus genus and causes an important disease. An alarming resurgence of viral circulation and the expansion of YFV-endemic zones have been detected in Africa and South America in recent years. NS5 is a viral protein that contains methyltransferase and RNA-dependent RNA polymerase (RdRp) domains, which are essential for viral replication, and the interactions between NS5 and cellular proteins have been studied to better understand viral replication. The aim of this study was to characterize the interaction of the NS5 protein with eukaryotic translation initiation factor 3 subunit L (eIF3L) and to evaluate the role of eIF3L in yellow fever replication. Methods To identify interactions of YFV NS5 with cellular proteins, we performed a two-hybrid screen using the YFV NS5 RdRp domain as bait with a human cDNA library, and RNApol deletion mutants were generated and analyzed using the two-hybrid system for mapping the interactions. The RNApol region involved was segmented into three fragments and analyzed using an eIF3L-expressing yeast strain. To map the NS5 residues that are critical for the interactions, we performed site-direct mutagenesis in segment 3 of the interaction domain (ID) and confirmed the interaction using in vitro assays and in vivo coimmunoprecipitation. The significance of eIF3L for YFV replication was investigated using eIF3L overexpression and RNA interference. Results In this work, we describe and characterize the interaction of NS5 with the translation factor eIF3L. The interaction between NS5 and eIF3L was confirmed using in vitro binding and in vivo coimmunoprecipitation assays. This interaction occurs at a region (the interaction domain of the RNApol domain) that is conserved in several flaviviruses and that is, therefore, likely to be relevant to the genus. eIF3L overexpression and plaque reduction assays showed a slight effect on YFV replication, indicating that the interaction of eIF3L

  19. Limitations of the complement-fixation test for distinguishing naturally acquired from vaccine-induced yellow fever infection in flavivirus-hyperendemic areas.

    PubMed

    Monath, T P; Craven, R B; Muth, D J; Trautt, C J; Calisher, C H; Fitzgerald, S A

    1980-07-01

    On the basis of previous studies, it has long been stated that 17D yellow fever (YF) vaccine generally does not induce complement-fixing (CF) antibodies, and that the presence of CF antibodies could be used in epidemiological studies to distinguish individuals infected with wild YF virus from vaccinated persons. In January 1979, seroepidemiological investigations were conducted during a YF epidemic in The Gambia, West Africa. Since a mass vaccination campaign was also in progress, it was important to confirm that the CF test could be used for serodiagnosis and determination of the incidence of natural YF infections. The serological responses of 58 individuals who received 17D YF vaccine were studied. The vaccinees fell into three gorups: 1) those with prevaccination YF neutralizing (N) antibodies; 2) immunological virgins without prevaccination YF-N antibody or hemagglutination-inhibiting (HI) antibodies to heterologous flaviviruses (Zika, West Nile, dengue 1, Uganda S, Spondweni, or Ntaya; and 3) those without prevaccination YF-N antibodies but with heterologous flaviviral HI antibodies. Vaccination of persons without prior flaviviral immunological experience resulted in monotypic YF HI and/or N antibody seroconversions, but no CF antibody response. The presence of prevaccination YF N antibodies blocked serological response to the vaccine in a high proportion of the cases; however, 24% of vaccinees in this group had a marked rise in log2 YF CF antibody titer (mean increase of 3.9). Thirteen (46%) of 28 persons without prevaccination YF N, but with heterologous flaviviral HI antibodies demonstrated YF CF antibody seroconversion or increase in titer following vaccination; in this group the mean increase in log2/ YF CF antibody titer was 2.1. The CF antibody response was generally broadly cross-reactive; but in a few individuals, the YF CF antibody response was homotypic. Nine different patterns of HI and CF homologous and heterologous antibody responses were defined

  20. Comparison of Turbulent Thermal Diffusivity and Scalar Variance Models

    NASA Technical Reports Server (NTRS)

    Yoder, Dennis A.

    2016-01-01

    In this study, several variable turbulent Prandtl number formulations are examined for boundary layers, pipe flow, and axisymmetric jets. The model formulations include simple algebraic relations between the thermal diffusivity and turbulent viscosity as well as more complex models that solve transport equations for the thermal variance and its dissipation rate. Results are compared with available data for wall heat transfer and profile measurements of mean temperature, the root-mean-square (RMS) fluctuating temperature, turbulent heat flux and turbulent Prandtl number. For wall-bounded problems, the algebraic models are found to best predict the rise in turbulent Prandtl number near the wall as well as the log-layer temperature profile, while the thermal variance models provide a good representation of the RMS temperature fluctuations. In jet flows, the algebraic models provide no benefit over a constant turbulent Prandtl number approach. Application of the thermal variance models finds that some significantly overpredict the temperature variance in the plume and most underpredict the thermal growth rate of the jet. The models yield very similar fluctuating temperature intensities in jets from straight pipes and smooth contraction nozzles, in contrast to data that indicate the latter should have noticeably higher values. For the particular low subsonic heated jet cases examined, changes in the turbulent Prandtl number had no effect on the centerline velocity decay.

  1. Intuitive Analysis of Variance-- A Formative Assessment Approach

    ERIC Educational Resources Information Center

    Trumpower, David

    2013-01-01

    This article describes an assessment activity that can show students how much they intuitively understand about statistics, but also alert them to common misunderstandings. How the activity can be used formatively to help improve students' conceptual understanding of analysis of variance is discussed. (Contains 1 figure and 1 table.)

  2. Automated variance reduction for Monte Carlo shielding analyses with MCNP

    NASA Astrophysics Data System (ADS)

    Radulescu, Georgeta

    Variance reduction techniques are employed in Monte Carlo analyses to increase the number of particles in the space phase of interest and thereby lower the variance of statistical estimation. Variance reduction parameters are required to perform Monte Carlo calculations. It is well known that adjoint solutions, even approximate ones, are excellent biasing functions that can significantly increase the efficiency of a Monte Carlo calculation. In this study, an automated method of generating Monte Carlo variance reduction parameters, and of implementing the source energy biasing and the weight window technique in MCNP shielding calculations has been developed. The method is based on the approach used in the SAS4 module of the SCALE code system, which derives the biasing parameters from an adjoint one-dimensional Discrete Ordinates calculation. Unlike SAS4 that determines the radial and axial dose rates of a spent fuel cask in separate calculations, the present method provides energy and spatial biasing parameters for the entire system that optimize the simulation of particle transport towards all external surfaces of a spent fuel cask. The energy and spatial biasing parameters are synthesized from the adjoint fluxes of three one-dimensional Discrete Ordinates adjoint calculations. Additionally, the present method accommodates multiple source regions, such as the photon sources in light-water reactor spent nuclear fuel assemblies, in one calculation. With this automated method, detailed and accurate dose rate maps for photons, neutrons, and secondary photons outside spent fuel casks or other containers can be efficiently determined with minimal efforts.

  3. Infinite variance in fermion quantum Monte Carlo calculations

    NASA Astrophysics Data System (ADS)

    Shi, Hao; Zhang, Shiwei

    2016-03-01

    For important classes of many-fermion problems, quantum Monte Carlo (QMC) methods allow exact calculations of ground-state and finite-temperature properties without the sign problem. The list spans condensed matter, nuclear physics, and high-energy physics, including the half-filled repulsive Hubbard model, the spin-balanced atomic Fermi gas, and lattice quantum chromodynamics calculations at zero density with Wilson Fermions, and is growing rapidly as a number of problems have been discovered recently to be free of the sign problem. In these situations, QMC calculations are relied on to provide definitive answers. Their results are instrumental to our ability to understand and compute properties in fundamental models important to multiple subareas in quantum physics. It is shown, however, that the most commonly employed algorithms in such situations have an infinite variance problem. A diverging variance causes the estimated Monte Carlo statistical error bar to be incorrect, which can render the results of the calculation unreliable or meaningless. We discuss how to identify the infinite variance problem. An approach is then proposed to solve the problem. The solution does not require major modifications to standard algorithms, adding a "bridge link" to the imaginary-time path integral. The general idea is applicable to a variety of situations where the infinite variance problem may be present. Illustrative results are presented for the ground state of the Hubbard model at half-filling.

  4. Unbiased Estimates of Variance Components with Bootstrap Procedures

    ERIC Educational Resources Information Center

    Brennan, Robert L.

    2007-01-01

    This article provides general procedures for obtaining unbiased estimates of variance components for any random-model balanced design under any bootstrap sampling plan, with the focus on designs of the type typically used in generalizability theory. The results reported here are particularly helpful when the bootstrap is used to estimate standard…

  5. Caution on the Use of Variance Ratios: A Comment.

    ERIC Educational Resources Information Center

    Shaffer, Juliet Popper

    1992-01-01

    Several metanalytic studies of group variability use variance ratios as measures of effect size. Problems with this approach are discussed, including limitations of using means and medians of ratios. Mean logarithms and the geometric mean are not adversely affected by the arbitrary choice of numerator. (SLD)

  6. Variance-based uncertainty relations for incompatible observables

    NASA Astrophysics Data System (ADS)

    Chen, Bin; Cao, Ning-Ping; Fei, Shao-Ming; Long, Gui-Lu

    2016-06-01

    We formulate uncertainty relations for arbitrary finite number of incompatible observables. Based on the sum of variances of the observables, both Heisenberg-type and Schrödinger-type uncertainty relations are provided. These new lower bounds are stronger in most of the cases than the ones derived from some existing inequalities. Detailed examples are presented.

  7. 40 CFR 190.11 - Variances for unusual operations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Variances for unusual operations. 190.11 Section 190.11 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS ENVIRONMENTAL RADIATION PROTECTION STANDARDS FOR NUCLEAR POWER OPERATIONS...

  8. 29 CFR 1904.38 - Variances from the recordkeeping rule.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 5 2011-07-01 2011-07-01 false Variances from the recordkeeping rule. 1904.38 Section 1904.38 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR RECORDING AND REPORTING OCCUPATIONAL INJURIES AND ILLNESSES Other OSHA Injury and...

  9. 29 CFR 1904.38 - Variances from the recordkeeping rule.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 5 2013-07-01 2013-07-01 false Variances from the recordkeeping rule. 1904.38 Section 1904.38 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR RECORDING AND REPORTING OCCUPATIONAL INJURIES AND ILLNESSES Other OSHA Injury and...

  10. 29 CFR 1904.38 - Variances from the recordkeeping rule.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 5 2014-07-01 2014-07-01 false Variances from the recordkeeping rule. 1904.38 Section 1904.38 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR RECORDING AND REPORTING OCCUPATIONAL INJURIES AND ILLNESSES Other OSHA Injury and...

  11. 29 CFR 1904.38 - Variances from the recordkeeping rule.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 5 2012-07-01 2012-07-01 false Variances from the recordkeeping rule. 1904.38 Section 1904.38 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR RECORDING AND REPORTING OCCUPATIONAL INJURIES AND ILLNESSES Other OSHA Injury and...

  12. Analysis of Variance: What Is Your Statistical Software Actually Doing?

    ERIC Educational Resources Information Center

    Li, Jian; Lomax, Richard G.

    2011-01-01

    Users assume statistical software packages produce accurate results. In this article, the authors systematically examined Statistical Package for the Social Sciences (SPSS) and Statistical Analysis System (SAS) for 3 analysis of variance (ANOVA) designs, mixed-effects ANOVA, fixed-effects analysis of covariance (ANCOVA), and nested ANOVA. For each…

  13. 44 CFR 60.6 - Variances and exceptions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... environmental document will be prepared, will be made in accordance with the procedures set out in 44 CFR part... HOMELAND SECURITY INSURANCE AND HAZARD MITIGATION National Flood Insurance Program CRITERIA FOR LAND MANAGEMENT AND USE Requirements for Flood Plain Management Regulations § 60.6 Variances and exceptions....

  14. 76 FR 78698 - Proposed Revocation of Permanent Variances

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-19

    ... several conditions that served as an alternative means of compliance to the falling-object-protection and... specified by these variances. Therefore, OSHA believes the alternative means of compliance granted by the.... 651, 655) in 1971 (see 36 FR 7340). Paragraphs (a)(4) and (a)(5) of Sec. 1926.451 required...

  15. Numbers Of Degrees Of Freedom Of Allan-Variance Estimators

    NASA Technical Reports Server (NTRS)

    Greenhall, Charles A.

    1992-01-01

    Report discusses formulas for estimation of Allan variances. Presents algorithms for closed-form approximations of numbers of degrees of freedom characterizing results obtained when various estimators applied to five power-law components of classical mathematical model of clock noise.

  16. Partitioning the Variance in Scores on Classroom Environment Instruments

    ERIC Educational Resources Information Center

    Dorman, Jeffrey P.

    2009-01-01

    This paper reports the partitioning of variance in scale scores from the use of three classroom environment instruments. Data sets from the administration of the What Is Happening In this Class (WIHIC) to 4,146 students, the Questionnaire on Teacher Interaction (QTI) to 2,167 students and the Catholic School Classroom Environment Questionnaire…

  17. 40 CFR 142.43 - Disposition of a variance request.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...) Compliance (including increments of progress) by the public water system with each contaminant level... control measures as the Administrator may require for each contaminant covered by the variance. (d) The... the Administrator. (f) The proposed schedule for implementation of additional interim control...

  18. 21 CFR 821.2 - Exemptions and variances.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES MEDICAL DEVICE TRACKING REQUIREMENTS General Provisions § 821.2 Exemptions and variances. (a) A...(s) of the device; (2) The reasons that compliance with the tracking requirements of this part...

  19. 21 CFR 821.2 - Exemptions and variances.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES MEDICAL DEVICE TRACKING REQUIREMENTS General Provisions § 821.2 Exemptions and variances. (a) A...(s) of the device; (2) The reasons that compliance with the tracking requirements of this part...

  20. 21 CFR 821.2 - Exemptions and variances.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES MEDICAL DEVICE TRACKING REQUIREMENTS General Provisions § 821.2 Exemptions and variances. (a) A...(s) of the device; (2) The reasons that compliance with the tracking requirements of this part...