Modelling of human low frequency sound localization acuity demonstrates dominance of spatial variation of interaural time difference and suggests uniform just-noticeable differences in interaural time difference.

Sound source localization is critical to animal survival and for identification of auditory objects. We investigated the acuity with which humans localize low frequency, pure tone sounds using timing differences between the ears. These small differences in time, known as interaural time differences or ITDs, are identified in a manner that allows localization acuity of around 1° at the midline. Acuity, a relative measure of localization ability, displays a non-linear variation as sound sources are positioned more laterally. All species studied localize sounds best at the midline and progressively worse as the sound is located out towards the side. To understand why sound localization displays this variation with azimuthal angle, we took a first-principles, systemic, analytical approach to model localization acuity. We calculated how ITDs vary with sound frequency, head size and sound source location for humans. This allowed us to model ITD variation for previously published experimental acuity data and determine the distribution of just-noticeable differences in ITD. Our results suggest that the best-fit model is one whereby just-noticeable differences in ITDs are identified with uniform or close to uniform sensitivity across the physiological range. We discuss how our results have several implications for neural ITD processing in different species as well as development of the auditory system

Endogenous chloride channels of insect sf9 cells. Evidence for coordinated activity of small elementary channel units

The endogenous Cl- conductance of Spodoptera frugiperda (Sf9) cells was studied 20-35 h after plating out of either uninfected cells or cells infected by a baculovirus vector carrying the cloned beta-galactosidase gene (beta-Gal cells). With the cation Tris+ in the pipette and Na+ in the bath, the reversal potential of whole-cell currents was governed by the prevailing Cl- equilibrium potential and could be fitted by the Goldman-Hodgkin-Katz equation with similar permeabilities for uninfected and beta-Gal cells. In the frequency range 0.12 < f < 300 Hz, the power density spectrum of whole-cell Cl- currents could be fitted by three Lorentzians. Independent of membrane potential, >50% of the total variance of whole-cell current fluctuations was accounted for by the low frequency Lorentzian (fc = 0.40 +/- 0.03 Hz, n = 6). Single-Cl- channels showed complex gating kinetics with long lasting (seconds) openings interrupted by similar long closures. In the open state, channels exhibited fast burst-like closures. Since the patches normally contained more than a single channel, it was not possible to measure open and closed dwell-time distributions for comparing single-Cl- channel activity with the kinetic features of whole-cell currents. However, the power density spectrum of Cl- currents of cell-attached and excised outside-out patches contained both high and low frequency Lorentzian components, with the corner frequency of the slow component (fc = 0.40 +/- 0.02 Hz, n = 4) similar to that of whole-cell current fluctuations. Chloride channels exhibited multiple conductance states with similar Goldman-Hodgkin-Katz-type rectification. Single-channel permeabilities covered the range from approximately 0.6.10(-14) cm5/s to approximately 6.10(-14) cm3/s, corresponding to a limiting conductance (gamma 150/150) of approximately 3.5 pS and approximately 35 pS, respectively. All states reversed near the same membrane potential, and they exhibited similar halide ion selectivity, P1 > PCl approximately PBr. Accordingly, Cl- current amplitudes larger than current flow through the smallest channel unit resolved seem to result from simultaneous open/shut events of two or more channel units

Determinants of health care utilisation: The case of Timor-Leste

© The Author(s) 2018. Background: Health financing and delivery reforms designed to achieve universal health coverage (UHC) need to be informed by an understanding of factors that both promote access to health care and undermine it. This study examines the level of health care utilisation in Timor-Leste and the factors that drive it. Methods: Data from a nationally representative cross-sectional survey of health care utilisation in 1712 households were used to develop multilevel models exploring how need and predisposing and enabling factors explain health care utilisation at both primary and secondary care facilities. Results: Need was found to be the key driver in seeking both primary care and hospital services. Rural households were less likely to go to hospital (odds ratio 0.7) than urban households. The poorest quintile was also less likely to use more expensive hospital services than other socio-economic groups. Conclusions: Understanding the determinants of seeking health care in Timor-Leste is of considerable policy significance, because health care is free at the point of use. Our findings indicate that the public resources for health care are subsidising the rich more than the poor. Health care reforms in Timor-Leste need to reduce the 'other' costs of health care, such as distance barriers, to address these inequities

Expedited batch processing and analysis of transposon insertions

<p>Abstract</p> <p>Background</p> <p>With advances in sequencing technology, greater and greater amounts of eukaryotic genome data are becoming available. Often, large portions of these genomes consist of transposable elements, frequently accounting for 50% or more in vertebrates. Each transposable element family may have thousands or tens of thousands of individual copies within a given genome, and therefore it can take an exorbitant amount of time and effort to process data in a meaningful fashion.</p> <p>Findings</p> <p>In order to combat this problem, we developed a set of bioinformatics techniques and programs to streamline the analysis. This includes a unique Perl script which automates the process of taking BLAST, Repeatmasker and similar data to extract and manipulate the hit sequences from the genome. This script, called Process_hits uses an object-oriented methodology to compile all hit locations from a given file for processing, organize this data into useable categories, and output it in multiple formats.</p> <p>Conclusions</p> <p>The program proved capable of handling large amounts of transposon data in an efficient fashion. It is equipped with a number of useful sub-functions, each of which is contained within its own sub-module to allow for greater expandability and as a foundation for future program design.</p

Radiation effects in glasses used for immobilization of high-level waste and plutonium disposition

This paper is a comprehensive review of the state-of-knowledge in the field of radiation effects in glasses that are to be used for the immobilization of high-level nuclear waste and plutonium disposition. The current status and issues in the area of radiation damage processes, defect generation, microstructure development, theoretical methods and experimental methods ase reviewed. Questions of fundamental and technological interest that offer opportunities for research are identified

Understanding the dynamics of Toll-like Receptor 5 response to flagellin and its regulation by estradiol

© 2017 The Author(s). Toll-like receptors (TLRs) are major players of the innate immune system. Once activated, they trigger a signalling cascade that leads to NF-ΰ B translocation from the cytoplasm to the nucleus. Single cell analysis shows that NF-ΰ B signalling dynamics are a critical determinant of transcriptional regulation. Moreover, the outcome of innate immune response is also affected by the cross-talk between TLRs and estrogen signalling. Here, we characterized the dynamics of TLR5 signalling, responsible for the recognition of flagellated bacteria, and those changes induced by estradiol in its signalling at the single cell level. TLR5 activation in MCF7 cells induced a single and sustained NF-k B translocation into the nucleus that resulted in high NF-k B transcription activity. The overall magnitude of NF-k B transcription activity was not influenced by the duration of the stimulus. No significant changes are observed in the dynamics of NF-k B translocation to the nucleus when MCF7 cells are incubated with estradiol. However, estradiol significantly decreased NF-k B transcriptional activity while increasing TLR5-mediated AP-1 transcription. The effect of estradiol on transcriptional activity was dependent on the estrogen receptor activated. This fine tuning seems to occur mainly in the nucleus at the transcription level rather than affecting the translocation of the NF-k B transcription factor

Wilsonian Approach to Fluid/Gravity Duality

The problem of gravitational fluctuations confined inside a finite cutoff at radius $r=r_c$ outside the horizon in a general class of black hole geometries is considered. Consistent boundary conditions at both the cutoff surface and the horizon are found and the resulting modes analyzed. For general cutoff $r_c$ the dispersion relation is shown at long wavelengths to be that of a linearized Navier-Stokes fluid living on the cutoff surface. A cutoff-dependent line-integral formula for the diffusion constant $D(r_c)$ is derived. The dependence on $r_c$ is interpreted as renormalization group (RG) flow in the fluid. Taking the cutoff to infinity in an asymptotically AdS context, the formula for $D(\infty)$ reproduces as a special case well-known results derived using AdS/CFT. Taking the cutoff to the horizon, the effective speed of sound goes to infinity, the fluid becomes incompressible and the Navier-Stokes dispersion relation becomes exact. The resulting universal formula for the diffusion constant $D(horizon)$ reproduces old results from the membrane paradigm. Hence the old membrane paradigm results and new AdS/CFT results are related by RG flow. RG flow-invariance of the viscosity to entropy ratio $\eta /s$ is shown to follow from the first law of thermodynamics together with isentropy of radial evolution in classical gravity. The ratio is expected to run when quantum gravitational corrections are included.Comment: 34 pages, harvmac, clarified boundary conditio

Determinants of muscle carnosine content

The main determinant of muscle carnosine (M-Carn) content is undoubtedly species, with, for example, aerobically trained female vegetarian athletes [with circa 13 mmol/kg dry muscle (dm)] having just 1/10th of that found in trained thoroughbred horses. Muscle fibre type is another key determinant, as type II fibres have a higher M-Carn or muscle histidine containing dipeptide (M-HCD) content than type I fibres. In vegetarians, M-Carn is limited by hepatic synthesis of β-alanine, whereas in omnivores this is augmented by the hydrolysis of dietary supplied HCD’s resulting in muscle levels two or more times higher. β-alanine supplementation will increase M-Carn. The same increase in M-Carn occurs with administration of an equal molar quantity of carnosine as an alternative source of β-alanine. Following the cessation of supplementation, M-Carn returns to pre-supplementation levels, with an estimated t1/2 of 5–9 weeks. Higher than normal M-Carn contents have been noted in some chronically weight-trained subjects, but it is unclear if this is due to the training per se, or secondary to changes in muscle fibre composition, an increase in β-alanine intake or even anabolic steroid use. There is no measureable loss of M-Carn with acute exercise, although exercise-induced muscle damage may result in raised plasma concentrations in equines. Animal studies indicate effects of gender and age, but human studies lack sufficient control of the effects of diet and changes in muscle fibre composition

Species-level functional profiling of metagenomes and metatranscriptomes.

Functional profiles of microbial communities are typically generated using comprehensive metagenomic or metatranscriptomic sequence read searches, which are time-consuming, prone to spurious mapping, and often limited to community-level quantification. We developed HUMAnN2, a tiered search strategy that enables fast, accurate, and species-resolved functional profiling of host-associated and environmental communities. HUMAnN2 identifies a community's known species, aligns reads to their pangenomes, performs translated search on unclassified reads, and finally quantifies gene families and pathways. Relative to pure translated search, HUMAnN2 is faster and produces more accurate gene family profiles. We applied HUMAnN2 to study clinal variation in marine metabolism, ecological contribution patterns among human microbiome pathways, variation in species' genomic versus transcriptional contributions, and strain profiling. Further, we introduce 'contributional diversity' to explain patterns of ecological assembly across different microbial community types