How Can Viral Dynamics Models Inform Endpoint Measures in Clinical Trials of Therapies for Acute Viral Infections?

Acute viral infections pose many practical challenges for the accurate assessment of the impact of novel therapies on viral growth and decay. Using the example of influenza A, we illustrate how the measurement of infection-related quantities that determine the dynamics of viral load within the human host, can inform investigators on the course and severity of infection and the efficacy of a novel treatment. We estimated the values of key infection-related quantities that determine the course of natural infection from viral load data, using Markov Chain Monte Carlo methods. The data were placebo group viral load measurements collected during volunteer challenge studies, conducted by Roche, as part of the oseltamivir trials. We calculated the values of the quantities for each patient and the correlations between the quantities, symptom severity and body temperature. The greatest variation among individuals occurred in the viral load peak and area under the viral load curve. Total symptom severity correlated positively with the basic reproductive number. The most sensitive endpoint for therapeutic trials with the goal to cure patients is the duration of infection. We suggest laboratory experiments to obtain more precise estimates of virological quantities that can supplement clinical endpoint measurements

Dependence of the superconducting critical temperature on the number of layers in homologous series of high-Tc cuprates

We study a model of $n$-layer high-temperature cuprates of homologous series like HgBa_2Ca_(n-1)Cu_nO_(2+2n+\delta) to explain the dependence of the critical temperature Tc(n) on the number $n$ of Cu-O planes in the elementary cell. Focusing on the description of the high-temperature superconducting system in terms of the collective phase variables, we have considered a semi-microscopic anisotropic three-dimensional vector XY model of stacked copper-oxide layers with adjustable parameters representing microscopic in-plane and out-of-plane phase stiffnesses. The model captures the layered composition along c-axis of homologous series and goes beyond the phenomenological Lawrence-Doniach model for layered superconductors. Implementing the spherical closure relation for vector variables we have solved the phase XY model exactly with the help of transfer matrix method and calculated Tc(n) for arbitrary block size $n$, elucidating the role of the c-axis anisotropy and its influence on the critical temperature. Furthermore, we accommodate inhomogeneous charge distribution among planes characterized by the charge imbalance coefficient $R$ being the function of number of layers $n$. By making a physically justified assumption regarding the doping dependence of the microscopic phase stiffnesses, we have calculated the values of parameter $R$ as a function of block size $n$ in good agreement with the nuclear magnetic resonance data of carrier distribution in multilayered high-Tc cuprates.Comment: 15 pages, 10 figures. Submitted to Physical Review

The genome sequence and effector complement of the flax rust pathogen Melampsora lini

Rust fungi cause serious yield reductions on crops, including wheat, barley, soybean, coffee, and represent real threats to global food security. Of these fungi, the flax rust pathogen Melampsora lini has been developed most extensively over the past 80 years as a model to understand the molecular mechanisms that underpin pathogenesis. During infection, M. lini secretes virulence effectors to promote disease. The number of these effectors, their function and their degree of conservation across rust fungal species is unknown. To assess this, we sequenced and assembled de novo the genome of M. lini isolate CH5 into 21,130 scaffolds spanning 189 Mbp (scaffold N50 of 31 kbp). Global analysis of the DNA sequence revealed that repetitive elements, primarily retrotransposons, make up at least 45% of the genome. Using ab initio predictions, transcriptome data and homology searches, we identified 16,271 putative protein-coding genes. An analysis pipeline was then implemented to predict the effector complement of M. lini and compare it to that of the poplar rust, wheat stem rust and wheat stripe rust pathogens to identify conserved and species-specific effector candidates. Previous knowledge of four cloned M. lini avirulence effector proteins and two basidiomycete effectors was used to optimize parameters of the effector prediction pipeline. Markov clustering based on sequence similarity was performed to group effector candidates from all four rust pathogens. Clusters containing at least one member from M. lini were further analyzed and prioritized based on features including expression in isolated haustoria and infected leaf tissue and conservation across rust species. Herein, we describe 200 of 940 clusters that ranked highest on our priority list, representing 725 flax rust candidate effectors. Our findings on this important model rust species provide insight into how effectors of rust fungi are conserved across species and how they may act to promote infection on their hosts.This work was funded by a grant from the CSIRO Transformational Biology Capability Platform to Adnane Nemri. Claire Anderson was supported by an ARC Discovery Grant (DP120104044) awarded to David A. Jones and Peter N. Dodds

Decreased sex ratio following maternal exposure to polychlorinated biphenyls from contaminated Great Lakes sport-caught fish: a retrospective cohort study.

BACKGROUND: Fish from the Great Lakes are contaminated with polychlorinated biphenyls, which have been found to have several adverse reproductive effects. Several environmental contaminants have been found to alter the sex ratio of offspring at birth, but the evidence of such an effect of polychlorinated biphenyls has been inconsistent. METHODS: We examined parental serum polychlorinated biphenyl concentration in relation to the sex ratio of 173 children of mothers and 208 children of fathers from the Great Lakes region of the United States between 1970 and 1995. We calculated odds ratios for a male child using logistic regression and generalized estimating equations with adjustment for the year of birth of the child, maternal and paternal age, the mother's parity at the child's birth, and whether the child had an older brother. RESULTS: The adjusted odds ratio for having a male child among mothers in the highest quintile of serum polychlorinated biphenyl concentration was 0.18 (95% CI: 0.06–0.59) compared to mothers in the lowest quintile. Treating exposure as a continuous variable, the adjusted odds ratio for having a male child was 0.54 per unit increase in the natural log of maternal serum polychlorinated biphenyl concentration (95% CI: 0.33–0.89). There was little evidence of an association with paternal exposure. We found no association between either maternal or paternal serum dichlorodiphenyl-dichloroethene concentration and the sex ratio. CONCLUSIONS: These findings suggest that maternal exposure to polychlorinated biphenyls may decrease the sex ratio of offspring. These data add to the growing body of evidence that exposure to particular chemicals can alter the sex ratio at birth

The influence of an eddy in the success rates and distributions of passively advected or actively swimming biological organisms crossing the continental slope

Author Posting. © American Meteorological Society, 2020. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 50(7), (2020): 1839-1852, https://doi.org/10.1175/JPO-D-19-0209.1.The Lagrangian characteristics of the surface flow field arising when an idealized, anticyclonic, mesoscale, isolated deep-ocean eddy collides with continental slope and shelf topography are explored. In addition to fluid parcel trajectories, we consider the trajectories of biological organisms that are able to navigate and swim, and for which shallow water is a destination. Of particular interest is the movement of organisms initially located in the offshore eddy, the manner in which the eddy influences the ability of the organisms to reach the shelf break, and the spatial and temporal distributions of organisms that do so. For nonswimmers or very slow swimmers, the organisms arrive at the shelf break in distinct pulses, with different pulses occurring at different locations along the shelf break. This phenomenon is closely related to the episodic formation of trailing vortices that are formed after the eddy collides with the continental slope, turns, and travels parallel to the coast. Analysis based on finite-time Lyapunov exponents reveals initial locations of all successful trajectories reaching the shoreline, and provides maps of the transport pathways showing that much of the cross-shelf-break transport occurs in the lee of the eddy as it moves parallel to the shore. The same analysis shows that the onshore transport is interrupted after a trailing vortex detaches. As the swimming speeds are increased, the organisms are influenced less by the eddy and tend to show up en mass and in a single pulse.IR and LP were supported by National Science Foundation (NSF) Grant OCE-1558806. DC was supported by NSF U.S. National Science Foundation’s Physical Oceanography program through Grants OCE-1059632 and OCE-1433953 as well as the Academic Programs Office, Woods Hole Oceanographic Institution. We acknowledge high-performance computing support from Yellowstone (http://n2t.net/ark:/85065/d7wd3xhc) provided by NCAR’s Computational and Information Systems Laboratory, sponsored by the National Science Foundation

Probabilistic movement modeling for intention inference in human-robot interaction.

Intention inference can be an essential step toward efficient humanrobot interaction. For this purpose, we propose the Intention-Driven Dynamics Model (IDDM) to probabilistically model the generative process of movements that are directed by the intention. The IDDM allows to infer the intention from observed movements using Bayes ’ theorem. The IDDM simultaneously finds a latent state representation of noisy and highdimensional observations, and models the intention-driven dynamics in the latent states. As most robotics applications are subject to real-time constraints, we develop an efficient online algorithm that allows for real-time intention inference. Two human-robot interaction scenarios, i.e., target prediction for robot table tennis and action recognition for interactive humanoid robots, are used to evaluate the performance of our inference algorithm. In both intention inference tasks, the proposed algorithm achieves substantial improvements over support vector machines and Gaussian processes.

Quiver Structure of Heterotic Moduli

We analyse the vector bundle moduli arising from generic heterotic compactifications from the point of view of quiver representations. Phenomena such as stability walls, crossing between chambers of supersymmetry, splitting of non-Abelian bundles and dynamic generation of D-terms are succinctly encoded into finite quivers. By studying the Poincar\'e polynomial of the quiver moduli space using the Reineke formula, we can learn about such useful concepts as Donaldson-Thomas invariants, instanton transitions and supersymmetry breaking.Comment: 38 pages, 5 figures, 1 tabl

Transverse optical plasmons in layered superconductors

We discuss the possible existance of transverse optical plasma modes in superlattices consisting of Josephson coupled superconducting layers. These modes appear as resonances in the current-current correlation function, as opposed to the usual plasmons which are poles in the density-density channel. We consider both bilayer superlattices, and single layer lattices with a spread of interlayer Josephson couplings. We show that our model is in quantitative agreement with the recent experimental observation by a number of groups of a peak at the Josephson plasma frequency in the optical conductivity of La$_{1.85}$Sr$_{0.15}$CuO$_4$Comment: Proceedings of LT21, in press, 4 pages, Latex with LTpaper.sty and epsfig.sty, 2 postscript figure

Spatially resolved spectroscopy of Cassiopeia A with MECS on board BeppoSAX

We have performed the first detailed spatially resolved spectroscopy of Cas A in the 1.6-10 keV energy range, using data taken with the MECS spectrometer on board the BeppoSAX Observatory. We performed a spatial deconvolution of the data and eventually generated a set of spectra, covering a region of about 3 arcmin radius around the centre of Cas A. The results obtained by fitting these spectra using a non-equilibrium ionisation plasma model and a power law, are: (i) a single thermal component is sufficient to fit all the spectra; (ii) kT is rather uniformly distributed with a minimum in the east and a maximum in the west, and no evidence is found for high kT expected from the interaction of the main shock with the ISM; (iii) from the distribution of the values of the ionisation parameter n_et we infer the presence of two distinct components: the first (a) in the range 1-10 cm^(-3), the second (b) with values ten times higher; if we associate component a to the CSM and component b to the ejecta, the mass ratio M(a)/M(b)<= 1/10 indicates a progenitor star that lost only a small fraction of the envelope during its pre-SN life. In this hypothesis the distribution of component b across the remnant suggests that the explosion was not spherically symmetric; (iv) the distribution of abundances indicates that we are detecting a CSM component with almost solar composition, and an ejecta component enriched in heavier elements. Abundances found for alpha-elements are consistent with the current view that Cas A was produced by the explosion of a massive star.Comment: 16 pages, 9 PostScript figures, 4 tables, Accepted for publication on Astronomy & Astrophysics (submitted July 12, 2000; accepted December 20, 2000