Viral antibody dynamics in a chiropteran host

1. Bats host many viruses that are significant for human and domestic animal health, but the dynamics of these infections in their natural reservoir hosts remain poorly elucidated.<p></p> 2. In these, and other, systems, there is evidence that seasonal life-cycle events drive infection dynamics, directly impacting the risk of exposure to spillover hosts. Understanding these dynamics improves our ability to predict zoonotic spillover from the reservoir hosts.<p></p> 3. To this end, we followed henipavirus antibody levels of >100 individual E. helvum in a closed, captive, breeding population over a 30-month period, using a powerful novel antibody quantitation method.<p></p> 4. We demonstrate the presence of maternal antibodies in this system and accurately determine their longevity. We also present evidence of population-level persistence of viral infection and demonstrate periods of increased horizontal virus transmission associated with the pregnancy/lactation period.<p></p> 5.The novel findings of infection persistence and the effect of pregnancy on viral transmission, as well as an accurate quantitation of chiropteran maternal antiviral antibody half-life, provide fundamental baseline data for the continued study of viral infections in these important reservoir hosts

Binary black hole initial data for numerical general relativity based on post-Newtonian data

With the goal of taking a step toward the construction of astrophysically realistic initial data for numerical simulations of black holes, we for the first time derive a family of fully general relativistic initial data based on post-2-Newtonian expansions of the 3-metric and extrinsic curvature without spin. It is expected that such initial data provide a direct connection with the early inspiral phase of the binary system. We discuss a straightforward numerical implementation, which is based on a generalized puncture method. Furthermore, we suggest a method to address some of the inherent ambiguity in mapping post-Newtonian data onto a solution of the general relativistic constraints.Comment: 13 pages, 8 figures, RevTex

Mode coupling in the nonlinear response of black holes

We study the properties of the outgoing gravitational wave produced when a non-spinning black hole is excited by an ingoing gravitational wave. Simulations using a numerical code for solving Einstein's equations allow the study to be extended from the linearized approximation, where the system is treated as a perturbed Schwarzschild black hole, to the fully nonlinear regime. Several nonlinear features are found which bear importance to the data analysis of gravitational waves. When compared to the results obtained in the linearized approximation, we observe large phase shifts, a stronger than linear generation of gravitational wave output and considerable generation of radiation in polarization states which are not found in the linearized approximation. In terms of a spherical harmonic decomposition, the nonlinear properties of the harmonic amplitudes have simple scaling properties which offer an economical way to catalog the details of the waves produced in such black hole processes.Comment: 17 pages, 20 figures, abstract and introduction re-writte

How should we evaluate and use evidence to improve population oral health?

Generating and implementing evidence-based policy is an important aim for many publicly funded health systems. In dentistry, this is based on the assumption that evidence-based health care increases the efficiency and effectiveness of interventions to improve oral health at a population level. This article argues that a linear logic model that links the generation of research evidence with its use is overly simplistic. It also challenges an uncritical interpretation of the evidence-based paradigm and explores approaches to the evaluation of complex interventions and how they can be embedded into policy and practice to improve oral health at a population level

Connecting Numerical Relativity and Data Analysis of Gravitational Wave Detectors

Gravitational waves deliver information in exquisite detail about astrophysical phenomena, among them the collision of two black holes, a system completely invisible to the eyes of electromagnetic telescopes. Models that predict gravitational wave signals from likely sources are crucial for the success of this endeavor. Modeling binary black hole sources of gravitational radiation requires solving the Eintein equations of General Relativity using powerful computer hardware and sophisticated numerical algorithms. This proceeding presents where we are in understanding ground-based gravitational waves resulting from the merger of black holes and the implications of these sources for the advent of gravitational-wave astronomy.Comment: Appeared in the Proceedings of 2014 Sant Cugat Forum on Astrophysics. Astrophysics and Space Science Proceedings, ed. C.Sopuerta (Berlin: Springer-Verlag

Self-similar Approximants of the Permeability in Heterogeneous Porous Media from Moment Equation Expansions

We use a mathematical technique, the self-similar functional renormalization, to construct formulas for the average conductivity that apply for large heterogeneity, based on perturbative expansions in powers of a small parameter, usually the log-variance $\sigma_Y^2$ of the local conductivity. Using perturbation expansions up to third order and fourth order in $\sigma_Y^2$ obtained from the moment equation approach, we construct the general functional dependence of the transport variables in the regime where $\sigma_Y^2$ is of order 1 and larger than 1. Comparison with available numerical simulations give encouraging results and show that the proposed method provides significant improvements over available expansions.Comment: Latex, 14 pages + 5 ps figure

Study of a Swiss dopa-responsive dystonia family with a deletion in GCH1: redefining DYT14 as DYT5.

OBJECTIVE: To report the study of a multigenerational Swiss family with dopa-responsive dystonia (DRD). METHODS: Clinical investigation was made of available family members, including historical and chart reviews. Subject examinations were video recorded. Genetic analysis included a genome-wide linkage study with microsatellite markers (STR), GTP cyclohydrolase I (GCH1) gene sequencing, and dosage analysis. RESULTS: We evaluated 32 individuals, of whom 6 were clinically diagnosed with DRD, with childhood-onset progressive foot dystonia, later generalizing, followed by parkinsonism in the two older patients. The response to levodopa was very good. Two additional patients had late onset dopa-responsive parkinsonism. Three other subjects had DRD symptoms on historical grounds. We found suggestive linkage to the previously reported DYT14 locus, which excluded GCH1. However, further study with more stringent criteria for disease status attribution showed linkage to a larger region, which included GCH1. No mutation was found in GCH1 by gene sequencing but dosage methods identified a novel heterozygous deletion of exons 3 to 6 of GCH1. The mutation was found in seven subjects. One of the patients with dystonia represented a phenocopy. CONCLUSIONS: This study rules out the previously reported DYT14 locus as a cause of disease, as a novel multiexonic deletion was identified in GCH1. This work highlights the necessity of an accurate clinical diagnosis in linkage studies as well as the need for appropriate allele frequencies, penetrance, and phenocopy estimates. Comprehensive sequencing and dosage analysis of known genes is recommended prior to genome-wide linkage analysis

Lysosomal and phagocytic activity is increased in astrocytes during disease progression in the SOD1 G93A mouse model of amyotrophic lateral sclerosis

Astrocytes are key players in the progression of amyotrophic lateral sclerosis (ALS). Previously, gene expression profiling of astrocytes from the pre-symptomatic stage of the SOD1G93A model of ALS has revealed reduced lactate metabolism and altered trophic support. Here, we have performed microarray analysis of symptomatic and late-stage disease astrocytes isolated by laser capture microdissection (LCM) from the lumbar spinal cord of the SOD1G93A mouse to complete the picture of astrocyte behavior throughout the disease course. Astrocytes at symptomatic and late-stage disease show a distinct up-regulation of transcripts defining a reactive phenotype, such as those involved in the lysosome and phagocytic pathways. Functional analysis of hexosaminidase B enzyme activity in the spinal cord and of astrocyte phagocytic ability has demonstrated a significant increase in lysosomal enzyme activity and phagocytic activity in SOD1G93A vs. littermate controls, validating the findings of the microarray study. In addition to the increased reactivity seen at both stages, astrocytes from late-stage disease showed decreased expression of many transcripts involved in cholesterol homeostasis. Staining for the master regulator of cholesterol synthesis, SREBP2, has revealed an increased localization to the cytoplasm of astrocytes and motor neurons in late-stage SOD1G93A spinal cord, indicating that down-regulation of transcripts may be due to an excess of cholesterol in the CNS during late-stage disease possibly due to phagocytosis of neuronal debris. Our data reveal that SOD1G93A astrocytes are characterized more by a loss of supportive function than a toxic phenotype during ALS disease progression and future studies should focus upon restorative therapies

Circular orbits of corotating binary black holes: comparison between analytical and numerical results

We compare recent numerical results, obtained within a ``helical Killing vector'' (HKV) approach, on circular orbits of corotating binary black holes to the analytical predictions made by the effective one body (EOB) method (which has been recently extended to the case of spinning bodies). On the scale of the differences between the results obtained by different numerical methods, we find good agreement between numerical data and analytical predictions for several invariant functions describing the dynamical properties of circular orbits. This agreement is robust against the post-Newtonian accuracy used for the analytical estimates, as well as under choices of resummation method for the EOB ``effective potential'', and gets better as one uses a higher post-Newtonian accuracy. These findings open the way to a significant ``merging'' of analytical and numerical methods, i.e. to matching an EOB-based analytical description of the (early and late) inspiral, up to the beginning of the plunge, to a numerical description of the plunge and merger. We illustrate also the ``flexibility'' of the EOB approach, i.e. the possibility of determining some ``best fit'' values for the analytical parameters by comparison with numerical data.Comment: Minor revisions, accepted for publication in Phys. Rev. D, 19 pages, 6 figure