Short-term genome stability of serial Clostridium difficile ribotype 027 isolates in an experimental gut model and recurrent human disease

Copyright: © 2013 Eyre et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedClostridium difficile whole genome sequencing has the potential to identify related isolates, even among otherwise indistinguishable strains, but interpretation depends on understanding genomic variation within isolates and individuals.Serial isolates from two scenarios were whole genome sequenced. Firstly, 62 isolates from 29 timepoints from three in vitro gut models, inoculated with a NAP1/027 strain. Secondly, 122 isolates from 44 patients (2–8 samples/patient) with mostly recurrent/on-going symptomatic NAP-1/027 C. difficile infection. Reference-based mapping was used to identify single nucleotide variants (SNVs).Across three gut model inductions, two with antibiotic treatment, total 137 days, only two new SNVs became established. Pre-existing minority SNVs became dominant in two models. Several SNVs were detected, only present in the minority of colonies at one/two timepoints. The median (inter-quartile range) [range] time between patients’ first and last samples was 60 (29.5–118.5) [0–561] days. Within-patient C. difficile evolution was 0.45 SNVs/called genome/year (95%CI 0.00–1.28) and within-host diversity was 0.28 SNVs/called genome (0.05–0.53). 26/28 gut model and patient SNVs were non-synonymous, affecting a range of gene targets.The consistency of whole genome sequencing data from gut model C. difficile isolates, and the high stability of genomic sequences in isolates from patients, supports the use of whole genome sequencing in detailed transmission investigations.Peer reviewe

Transmission efficiency and noise, vibration and harshness refinement of differential hypoid gear pairs

This article presents a combined multi-body dynamics and lubricated contact mechanics model of vehicular differential hypoid gear pairs, demonstrating the transient nature of transmission efficiency and noise, vibration and harshness performance under various driving conditions. The contact of differential hypoid gears is subjected to mixed thermo-elastohydrodynamic regime of lubrication. The coefficient of friction is obtained using an analytical approach for non-Newtonian lubricant shear and supplemented by boundary interactions for thin films. Additionally, road data and aerodynamic effects are used in the form of resisting torque applied to the output side of the gear pair. Sinusoidal engine torque variation is also included to represent engine order torsional input resident on the pinion gear. Analysis results are presented for New European Driving Cycle transience from low-speed city driving condition in second gear to steady-state cruising in fourth gear for a light truck. It is shown that the New European Driving Cycle captures the transmission efficiency characteristics of the differential hypoid gear pair under worst case scenario, with its underlying implications for fuel efficiency and emissions. However, it fails to address the other key attribute, being the noise, vibration and harshness performance. In the case of hypoid gears, the resultant noise, vibration and harshness characteristics can be particularly annoying. It is concluded that broader transient manoeuvres encompassing New European Driving Cycle are required for assessment, in order to obtain a balanced approach for transmission efficiency and noise, vibration and harshness performance. This approach is undertaken in this article, which is not hitherto reported in the literature

Can explicit convection improve modelled dust in summertime West Africa?

Global and regional models have large systematic errors in their modelled dust fields over West Africa. It is well established that cold-pool outflows from moist convection (haboobs) can raise over 50% of the dust over parts of the Sahara and Sahel in summer, but parameterised moist convection tends to give a very poor representation of this in models. Here, we test the hypothesis that an explicit representation of convection in the Met Office Unified Model (UM) improves haboob winds and so may reduce errors in modelled dust fields. The results show that despite varying both grid spacing and the representation of convection there are only minor changes in dust aerosol optical depth (AOD) and dust mass loading fields between simulations. In all simulations there is an AOD deficit over the observed central Saharan dust maximum and a high bias in AOD along the west coast: both features are consistent with many climate (CMIP5) models. Cold-pool outflows are present in the explicit simulations and do raise dust. Consistent with this, there is an improved diurnal cycle in dust-generating winds with a seasonal peak in evening winds at locations with moist convection that is absent in simulations with parameterised convection. However, the explicit convection does not change the AOD field in the UM significantly for several reasons. Firstly, the increased windiness in the evening from haboobs is approximately balanced by a reduction in morning winds associated with the breakdown of the nocturnal low-level jet (LLJ). Secondly, although explicit convection increases the frequency of the strongest winds, they are still weaker than observed, especially close to the observed summertime Saharan dust maximum: this results from the fact that, although large mesoscale convective systems (and resultant cold pools) are generated, they have a lower frequency than observed and haboob winds are too weak. Finally, major impacts of the haboobs on winds occur over the Sahel, where, although dust uplift is known to occur in reality, uplift in the simulations is limited by a seasonally constant bare-soil fraction in the model, together with soil moisture and clay fractions which are too restrictive of dust emission in seasonally varying vegetated regions. For future studies, the results demonstrate (1) the improvements in behaviour produced by the explicit representation of convection, (2) the value of simultaneously evaluating both dust and winds and (3) the need to develop parameterisations of the land surface alongside those of dust-generating winds

Electron-beam propagation in a two-dimensional electron gas

A quantum mechanical model based on a Green's function approach has been used to calculate the transmission probability of electrons traversing a two-dimensional electron gas injected and detected via mode-selective quantum point contacts. Two-dimensional scattering potentials, back-scattering, and temperature effects were included in order to compare the calculated results with experimentally observed interference patterns. The results yield detailed information about the distribution, size, and the energetic height of the scattering potentials.Comment: 7 pages, 6 figure

The cyclin-dependent kinase inhibitor p57(Kip2) is epigenetically regulated in carboplatin resistance and results in collateral sensitivity to the CDK inhibitor seliciclib in ovarian cancer

Carboplatin remains a first-line agent in the management of epithelial ovarian cancer (EOC). Unfortunately, platinum-resistant disease ultimately occurs in most patients. Using a novel EOC cell line with acquired resistance to carboplatin: PEO1CarbR, genome-wide micro-array profiling identified the cyclin-dependent kinase inhibitor p57(Kip2) as specifically downregulated in carboplatin resistance. Presently, we describe confirmation of these preliminary data with a variety of approaches

Green Plants in the Red: A Baseline Global Assessment for the IUCN Sampled Red List Index for Plants

Plants provide fundamental support systems for life on Earth and are the basis for all terrestrial ecosystems; a decline in plant diversity will be detrimental to all other groups of organisms including humans. Decline in plant diversity has been hard to quantify, due to the huge numbers of known and yet to be discovered species and the lack of an adequate baseline assessment of extinction risk against which to track changes. The biodiversity of many remote parts of the world remains poorly known, and the rate of new assessments of extinction risk for individual plant species approximates the rate at which new plant species are described. Thus the question ‘How threatened are plants?’ is still very difficult to answer accurately. While completing assessments for each species of plant remains a distant prospect, by assessing a randomly selected sample of species the Sampled Red List Index for Plants gives, for the first time, an accurate view of how threatened plants are across the world. It represents the first key phase of ongoing efforts to monitor the status of the world’s plants. More than 20% of plant species assessed are threatened with extinction, and the habitat with the most threatened species is overwhelmingly tropical rain forest, where the greatest threat to plants is anthropogenic habitat conversion, for arable and livestock agriculture, and harvesting of natural resources. Gymnosperms (e.g. conifers and cycads) are the most threatened group, while a third of plant species included in this study have yet to receive an assessment or are so poorly known that we cannot yet ascertain whether they are threatened or not. This study provides a baseline assessment from which trends in the status of plant biodiversity can be measured and periodically reassessed

The impact of sequencing depth on the inferred taxonomic composition and AMR gene content of metagenomic samples

Shotgun metagenomics is increasingly used to characterise microbial communities, particularly for the investigation of antimicrobial resistance (AMR) in different animal and environmental contexts. There are many different approaches for inferring the taxonomic composition and AMR gene content of complex community samples from shotgun metagenomic data, but there has been little work establishing the optimum sequencing depth, data processing and analysis methods for these samples. In this study we used shotgun metagenomics and sequencing of cultured isolates from the same samples to address these issues. We sampled three potential environmental AMR gene reservoirs (pig caeca, river sediment, effluent) and sequenced samples with shotgun metagenomics at high depth (~ 200 million reads per sample). Alongside this, we cultured single-colony isolates of Enterobacteriaceae from the same samples and used hybrid sequencing (short- and long-reads) to create high- quality assemblies for comparison to the metagenomic data. To automate data processing, we developed an open- source software pipeline, ‘ResPipe’

A “Learning Revolution”? Investigating Pedagogic Practices around Interactive Whiteboards in British Primary Classrooms

Interactive whiteboards have been rapidly introduced into all primary schools under UK Government initiatives. These large, touch-sensitive screens, which control a computer connected to a digital projector, seem to be the first type of educational technology particularly suited for whole-class teaching and learning. Strong claims are made for their value by manufacturers and policy makers, but there has been little research on how, if at all, they influence established pedagogic practices, communicative processes and educational goals. This study has been designed to examine this issue, using observations in primary (elementary) school classrooms. It is funded by the UK Economic and Social Research Council and builds on the authors’ previous research on ICT in educational dialogues and collaborative activities

Purcell enhancement of a single silicon carbide color center with coherent spin control

Silicon carbide has recently been developed as a platform for optically addressable spin defects. In particular, the neutral divacancy in the 4H polytype displays an optically addressable spin-1 ground state and near-infrared optical emission. Here, we present the Purcell enhancement of a single neutral divacancy coupled to a photonic crystal cavity. We utilize a combination of nanolithographic techniques and a dopant-selective photoelectrochemical etch to produce suspended cavities with quality factors exceeding 5,000. Subsequent coupling to a single divacancy leads to a Purcell factor of ~50, which manifests as increased photoluminescence into the zero-phonon line and a shortened excited-state lifetime. Additionally, we measure coherent control of the divacancy ground state spin inside the cavity nanostructure and demonstrate extended coherence through dynamical decoupling. This spin-cavity system represents an advance towards scalable long-distance entanglement protocols using silicon carbide that require the interference of indistinguishable photons from spatially separated single qubits.Comment: 13 pages, 4 figure

Binary Galaxies in the Local Supercluster and Its Neighborhood

We report a catalog of 509 pairs identified among 10403 nearby galaxies with line-of-sight velocities V_LG < 3500 km/s.We selected binary systems in accordance with two criteria (bounding and temporal), which require the physical pair of galaxies to have negative total energy and its components to be located inside the zero-velocity surface. We assume that individual galaxy masses are proportional to their total K-band luminosities, M = L_K x 6M/L. The catalog gives the magnitudes and morphological types of galaxies and also the projected (orbital) masses and pair isolation indices. The component line-of-sight velocity differences and projected distances of the binary systems considered have power-law distributions with the median values of 35 km/s and 123 kpc, respectively. The median mass-to-K-band luminosity ratio is equal to 11 M/L, and its uncertainty is mostly due to the errors of measured velocities. Our sample of binary systems has a typical density contrast of d ro/ro_c ~ 500 and a median crossing time of about 3.5 Gyr. We point out the substantial fraction of binary systems consisting of late-type dwarf galaxies, where the luminosities of both components are lower than that of the Small Magellanic Cloud. The median projected distance for 41 such pairs is only 30 kpc, and the median difference of their line-of-sight velocities is equal to 14 km/s which is smaller than the typical error for radial-velocity (30 km/s). This specific population of gas-rich dwarf binary galaxies such as I Zw 18 may be at the stage immediately before merging of its components. Such objects, which are usually lost in flux-limited (and not distance-limited) samples deserve a thorough study in the HI radio line with high spatial and velocity resolution.Comment: published in Astrophysical Bulletin, 2008, Vol. 63, No. 4, pp. 299-34