600 research outputs found

    HIV-TRACE (Transmission Cluster Engine):A tool for large scale molecular epidemiology of HIV-1 and other rapidly evolving pathogens

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    In modern applications of molecular epidemiology, genetic sequence data are routinely used to identify clusters of transmission in rapidly evolving pathogens, most notably HIV-1. Traditional 'shoe-leather' epidemiology infers transmission clusters by tracing chains of partners sharing epidemiological connections (e.g., sexual contact). Here, we present a computational tool for identifying a molecular transmission analog of such clusters: HIV-TRACE (TRAnsmission Cluster Engine). HIV-TRACE implements an approach inspired by traditional epidemiology, by identifying chains of partners whose viral genetic relatedness imply direct or indirect epidemiological connections. Molecular transmission clusters are constructed using codon-aware pairwise alignment to a reference sequence followed by pairwise genetic distance estimation among all sequences. This approach is computationally tractable and is capable of identifying HIV-1 transmission clusters in large surveillance databases comprising tens or hundreds of thousands of sequences in near real time, that is, on the order of minutes to hours. HIV-TRACE is available at www.hivtrace.org and from www.github.com/veg/hivtrace, along with the accompanying result visualization module from www.github.com/veg/hivtrace-viz. Importantly, the approach underlying HIV-TRACE is not limited to the study of HIV-1 and can be applied to study outbreaks and epidemics of other rapidly evolving pathogens

    Ordering of droplets and light scattering in polymer dispersed liquid crystal films

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    We study the effects of droplet ordering in initial optical transmittance through polymer dispersed liquid crystal (PDLC) films prepared in the presence of an electrical field. The experimental data are interpreted by using a theoretical approach to light scattering in PDLC films that explicitly relates optical transmittance and the order parameters characterizing both the orientational structures inside bipolar droplets and orientational distribution of the droplets. The theory relies on the Rayleigh-Gans approximation and uses the Percus-Yevick approximation to take into account the effects due to droplet positional correlations.Comment: revtex4, 18 pages, 8 figure

    INTERLAYER COUPLING AND THE METAL-INSULATOR TRANSITION IN Pr-SUBSTITUTED Bi(2)Sr(2)CaCu(2)O(8+y)

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    Substitution of rare-earth ions for Ca in Bi2Sr2CaCu2O8+y is known to cause a metal-insulator transition. Using resonant photoemission we study how this chemical substitution affects the electronic structure of the material. For the partial Cu-density of states at E_F and in the region of the valence band we observe no significant difference between a pure superconducting sample and an insulating sample with 60% Pr for Ca. This suggests that the states responsible for superconductivity are predomi- nately O-states. The partial Pr-4f density of states was extracted utilizing the Super- Koster-Kronig Pr 4d-4f resonance. It consists of a single peak at 1.36eV binding energy. The peak shows a strongly assymetric Doniach-Sunjic line- shape indicating the presence of a continuum of electronic states with sharp cut off at E_F even in this insulating sample. This finding excludes a bandgap in the insulating sample and supports the existance of a mobility gap caused by spatial localization of the carriers. The presence of such carriers at the Pr-site, between the CuO_2 planes shows that the electronic structure is not purely 2-dimensional but that there is a finite interlayer coupling. The resonance enhancement of the photoemission cross section, at the Pr-4d threshold, was studied for the Pr-4f and for Cu-states. Both the Pr-4f and the Cu-states show a Fano-like resonance. This resonance of Cu-states with Pr-states is another indication of coupling between the the Pr-states and those in the CuO_2 plane. Because of the statistical distribution of the Pr-ions this coupling leads to a non-periodic potential for the states in the CuO_2 plane which can lead to localization and thus to the observed metal-insulator transition.Comment: Gziped uuencoded postscript file including 7 figures Scheduled for publication in Physical Review B, May 1, 1995

    Effect of Finite Impurity Mass on the Anderson Orthogonality Catastrophe in One Dimension

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    A one-dimensional tight-binding Hamiltonian describes the evolution of a single impurity interacting locally with NN electrons. The impurity spectral function has a power-law singularity A(ω)ωω01+βA(\omega)\propto\mid\omega-\omega_0\mid^{-1+\beta} with the same exponent β\beta that characterizes the logarithmic decay of the quasiparticle weight ZZ with the number of electrons NN, ZNβZ\propto N^{-\beta}. The exponent β\beta is computed by (1) perturbation theory in the interaction strength and (2) numerical evaluations with exact results for small systems and variational results for larger systems. A nonanalytical behavior of β\beta is observed in the limit of infinite impurity mass. For large interaction strength, the exponent depends strongly on the mass of the impurity in contrast to the perturbative result.Comment: 26 pages, RevTeX, 7 figures included, to be published in Phys. Rev.

    Random-effects substitution models for phylogenetics via scalable gradient approximations

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    Phylogenetic and discrete-trait evolutionary inference depend heavily on an appropriate characterization of the underlying character substitution process. In this paper, we present random-effects substitution models that extend common continuous-time Markov chain models into a richer class of processes capable of capturing a wider variety of substitution dynamics. As these random-effects substitution models often require many more parameters than their usual counterparts, inference can be both statistically and computationally challenging. Thus, we also propose an efficient approach to compute an approximation to the gradient of the data likelihood with respect to all unknown substitution model parameters. We demonstrate that this approximate gradient enables scaling of sampling-based inference, namely Bayesian inference via Hamiltonian Monte Carlo, under random-effects substitution models across large trees and state-spaces. Applied to a dataset of 583 SARS-CoV-2 sequences, an HKY model with random-effects shows strong signals of nonreversibility in the substitution process, and posterior predictive model checks clearly show that it is a more adequate model than a reversible model. When analyzing the pattern of phylogeographic spread of 1441 influenza A virus (H3N2) sequences between 14 regions, a random-effects phylogeographic substitution model infers that air travel volume adequately predicts almost all dispersal rates. A random-effects state-dependent substitution model reveals no evidence for an effect of arboreality on the swimming mode in the tree frog subfamily Hylinae. Simulations reveal that random-effects substitution models can accommodate both negligible and radical departures from the underlying base substitution model. We show that our gradient-based inference approach is over an order of magnitude more time efficient than conventional approaches

    Superconductivity in Fullerides

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    Experimental studies of superconductivity properties of fullerides are briefly reviewed. Theoretical calculations of the electron-phonon coupling, in particular for the intramolecular phonons, are discussed extensively. The calculations are compared with coupling constants deduced from a number of different experimental techniques. It is discussed why the A_3 C_60 are not Mott-Hubbard insulators, in spite of the large Coulomb interaction. Estimates of the Coulomb pseudopotential μ\mu^*, describing the effect of the Coulomb repulsion on the superconductivity, as well as possible electronic mechanisms for the superconductivity are reviewed. The calculation of various properties within the Migdal-Eliashberg theory and attempts to go beyond this theory are described.Comment: 33 pages, latex2e, revtex using rmp style, 15 figures, submitted to Review of Modern Physics, more information at http://radix2.mpi-stuttgart.mpg.de/fullerene/fullerene.htm

    Production, characterization, and antigen specificity of recombinant 62-71-3, a candidate monoclonal antibody for rabies prophylaxis in humans

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    Rabies kills many people throughout the developing world every year. The murine monoclonal antibody (mAb) 62-71-3 was recently identified for its potential application in rabies postexposure prophylaxis (PEP). The purpose here was to establish a plant-based production system for a chimeric mouse-human version of mAb 62-71-3, to characterize the recombinant antibody and investigate at a molecular level its interaction with rabies virus glycoprotein. Chimeric 62-71-3 was successfully expressed in Nicotiana benthamiana. Glycosylation was analyzed by mass spectroscopy; functionality was confirmed by antigen ELISA, as well as rabies and pseudotype virus neutralization. Epitope characterization was performed using pseudotype virus expressing mutagenized rabies glycoproteins. Purified mAb demonstrated potent viral neutralization at 500 IU/mg. A critical role for antigenic site I of the glycoprotein, as well as for two specific amino acid residues (K226 and G229) within site I, was identified with regard to mAb 62-71-3 neutralization. Pseudotype viruses expressing glycoprotein from lyssaviruses known not to be neutralized by this antibody were the controls. The results provide the molecular rationale for developing 62-71-3 mAb for rabies PEP; they also establish the basis for developing an inexpensive plant-based antibody product to benefit low-income families in developing countries.—Both, L., van Dolleweerd, C., Wright, E., Banyard, A. C., Bulmer-Thomas, B., Selden, D., Altmann, F., Fooks, A. R., Ma, J. K.-C. Production, characterization, and antigen specificity of recombinant 62-71-3, a candidate monoclonal antibody for rabies prophylaxis in humans

    Electronic states and phases of KxC60 from photoemission and X-ray absorption spectroscopy

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    HIGH-resolution photoemission and soft X-ray absorption spectroscopies have provided valuable information on the electronic structure near the Fermi energy in the superconducting copper oxide compounds 1-4, helping to constrain the possible mechanisms of superconductivity. Here we describe the application of these techniques to K(x)C60, found recently to be superconducting below 19.3 K for x almost-equal-to 3 (refs 5-7). The photoemission and absorption spectra as a function of x can be fitted by a linear combination of data from just three phases, C60, K3C60, and K6C60, indicating that there is phase separation in our samples. The photoemission spectra clearly show a well defined Fermi edge in the K3C60 phase with a density of states of 5.2 x 10(-3) electrons eV-1 angstrom-3 and an occupied-band width of 1.2 eV, suggesting that this phase may be a weakly coupled BCS-like (conventional) superconductor. The C1s absorption spectra show large non-rigid-band shifts between the three phases with half and complete filling, in the K3C60 and K6C60 phases respectively, of the conduction band formed from the lowest unoccupied molecular orbital of C60. These observations clearly demonstrate that the conduction band has C 2p character. The non-rigid-band shift coupled with the anomalous occupied-band width implies that there is significant mixing of the electronic states of K and C60 in the superconducting phase
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