Draft genome sequence of the Streptococcus pneumoniae Avery strain A66

We have used HiSeq 2000 technology to generate a draft genome sequence of Streptococcus pneumoniae strain A66. This is a common study strain used in investigations of pneumococcal bacterium-host interactions and was used in the seminal genetic studies of Avery et al

CMOS programmable analog memory-cell array using floating-gate circuits

Journal ArticleThe complexity of analog VLSI systems is often limited by the number of pins on a chip rather than by the die area. Currently, many analog parameters and biases are stored off-chip. Moving parameter storage on-chip could save pins and allow us to create complex programmable analog systems. In this paper, we present a design for an on-chip nonvolatile analog memory cell that can be configured in addressable arrays and programmed easily. We use floating-gate MOS transistors to store charge, and we use the processes of tunneling and hot-electron injection to program values. We have fabricated two versions of this design: one with an nFET injection mechanism and one with a pFET injection mechanism. With these designs, we achieve greater than 13-bit output precision with a 39-dB power-supply rejection ratio and no crosstalk between memory cells

Estimating the frequency of trains approaching red signals: A case study for improving the understanding of SPAD risk

This paper describes a novel technique for estimating the frequency with which trains approach signals showing a red aspect. This knowledge is potentially important for understanding the likelihood of a signal being passed at danger (SPAD) at individual signals and also for normalisation of SPAD data, both locally and nationally, for trending and benchmarking. The industry currently uses estimates for the number of red aspect approaches based on driver surveys which are considered to have significant shortcomings. Data for this analysis is sourced from publicly available live feeds provided by Network Rail which give information on train movements and signal states. The development of the analysis model and supporting software are described and some sample results from case studies are presented. An initial study of seven signalling areas showed that approximately 3.3% of all signal approaches are to red signals. However, it also highlighted that there is a large variation in the red approach rates between signalling areas and between individual signals. SPAD risk assessment at individual signals may be significantly enhanced by the ability to estimate red approach rates for individual signals using the techniques described

Genomic Analysis of Companion Rabbit Staphylococcus aureus.

In addition to being an important human pathogen, Staphylococcus aureus is able to cause a variety of infections in numerous other host species. While the S. aureus strains causing infection in several of these hosts have been well characterised, this is not the case for companion rabbits (Oryctolagus cuniculus), where little data are available on S. aureus strains from this host. To address this deficiency we have performed antimicrobial susceptibility testing and genome sequencing on a collection of S. aureus isolates from companion rabbits. The findings show a diverse S. aureus population is able to cause infection in this host, and while antimicrobial resistance was uncommon, the isolates possess a range of known and putative virulence factors consistent with a diverse clinical presentation in companion rabbits including severe abscesses. We additionally show that companion rabbit isolates carry polymorphisms within dltB as described as underlying host-adaption of S. aureus to farmed rabbits. The availability of S. aureus genome sequences from companion rabbits provides an important aid to understanding the pathogenesis of disease in this host and in the clinical management and surveillance of these infections.This project was supported by internal funding from the School of Biological, Biomedical and Environmental Sciences, University of Hull (GKP), a Medical Research Council (MRC) Partnership Grant (G1001787/1) (MAH and JP), and the Wellcome Trust, Grant number 098051 (JP).This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.pone.015145

Characterization of Redlen CZT detectors for hard x-ray astronomy

We present the results of ongoing characterization of Cadmium Zinc Telluride (CZT) semiconductors produced by Redlen Technologies. In particular we hope to determine their viability for future X-ray astronomy missions such as the High Energy X-ray Probe (HEX-P). The fully fabricated hybrid detectors consist of CZT crystals with a collecting area of 2 cm × 2 cm and thickness of 3 mm mounted on a custom pixelated ASIC originally designed for the Nuclear Spectroscopic Telescope Array (NuSTAR) mission, which launched in 2012. We present the results of inter-pixel conductance and leakage current tests as well as spectral characterization using an 241Am source. Although further calibration and testing is necessary to determine the capabilities of these detectors, preliminary results indicate that Redlen CZT will be able to achieve spectral resolution and noise levels comparable to those of the CZT detectors currently in use aboard NuSTAR

Does testosterone mediate the relationship between vitamin D and prostate cancer progression? A systematic review and meta-analysis

PURPOSE: Observational studies and randomized controlled trials (RCTs) have shown an association between vitamin D levels and prostate cancer progression. However, evidence of direct causality is sparse and studies have not examined biological mechanisms, which can provide information on plausibility and strengthen the evidence for causality. METHODS: We used the World Cancer Research Fund International/University of Bristol two-stage framework for mechanistic systematic reviews. In stage one, both text mining of published literature and expert opinion identified testosterone as a plausible biological mechanism. In stage two, we performed a systematic review and meta-analysis to assess the evidence from both human and animal studies examining the effect of vitamin D on testosterone, and testosterone on advanced prostate cancer (diagnostic Gleason score of ≥ 8, development of metastasis) or prostate cancer-specific mortality. RESULTS: A meta-analysis of ten human RCTs showed evidence of an effect of vitamin D on total testosterone (standardised mean difference (SMD) = 0.133, 95% CI =  − 0.003–0.269, I(2) = 0.0%, p = 0.056). Five human RCTs showed evidence of an effect of vitamin D on free testosterone (SMD = 0.173, 95% CI =  − 0.104–0.450, I(2) = 52.4%, p = 0.220). Three human cohort studies of testosterone on advanced prostate cancer or prostate cancer-specific mortality provided inconsistent results. In one study, higher levels of calculated free testosterone were positively associated with advanced prostate cancer or prostate cancer-specific mortality. In contrast, higher levels of dihydrotestosterone were associated with lowering prostate cancer-specific mortality in another study. No animal studies met the study eligibility criteria. CONCLUSION: There is some evidence that vitamin D increases levels of total and free testosterone, although the effect of testosterone levels within the normal range on prostate cancer progression is unclear. The role of testosterone as a mechanism between vitamin D and prostate cancer progression remains inconclusive. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10552-022-01591-w

The XMM Cluster Survey: Evidence for energy injection at high redshift from evolution of the X-ray luminosity-temperature relation

We measure the evolution of the X-ray luminosity-temperature (L_X-T) relation since z~1.5 using a sample of 211 serendipitously detected galaxy clusters with spectroscopic redshifts drawn from the XMM Cluster Survey first data release (XCS-DR1). This is the first study spanning this redshift range using a single, large, homogeneous cluster sample. Using an orthogonal regression technique, we find no evidence for evolution in the slope or intrinsic scatter of the relation since z~1.5, finding both to be consistent with previous measurements at z~0.1. However, the normalisation is seen to evolve negatively with respect to the self-similar expectation: we find E(z)^{-1} L_X = 10^{44.67 +/- 0.09} (T/5)^{3.04 +/- 0.16} (1+z)^{-1.5 +/- 0.5}, which is within 2 sigma of the zero evolution case. We see milder, but still negative, evolution with respect to self-similar when using a bisector regression technique. We compare our results to numerical simulations, where we fit simulated cluster samples using the same methods used on the XCS data. Our data favour models in which the majority of the excess entropy required to explain the slope of the L_X-T relation is injected at high redshift. Simulations in which AGN feedback is implemented using prescriptions from current semi-analytic galaxy formation models predict positive evolution of the normalisation, and differ from our data at more than 5 sigma. This suggests that more efficient feedback at high redshift may be needed in these models.Comment: Accepted for publication in MNRAS; 12 pages, 6 figures; added references to match published versio

Old Drugs To Treat Resistant Bugs: Methicillin-Resistant Staphylococcus aureus Isolates with mecC Are Susceptible to a Combination of Penicillin and Clavulanic Acid.

β-Lactam resistance in methicillin-resistant Staphylococcus aureus (MRSA) is mediated by the expression of an alternative penicillin-binding protein 2a (PBP2a) (encoded by mecA) with a low affinity for β-lactam antibiotics. Recently, a novel variant of mecA, known as mecC, was identified in MRSA isolates from both humans and animals. In this study, we demonstrate that mecC-encoded PBP2c does not mediate resistance to penicillin. Rather, broad-spectrum β-lactam resistance in MRSA strains carrying mecC (mecC-MRSA strains) is mediated by a combination of both PBP2c and the distinct β-lactamase encoded by the blaZ gene of strain LGA251 (blaZLGA251), which is part of mecC-encoding staphylococcal cassette chromosome mec (SCCmec) type XI. We further demonstrate that mecC-MRSA strains are susceptible to the combination of penicillin and the β-lactam inhibitor clavulanic acid in vitro and that the same combination is effective in vivo for the treatment of experimental mecC-MRSA infection in wax moth larvae. Thus, we demonstrate how the distinct biological differences between mecA- and mecC-encoded PBP2a and PBP2c have the potential to be exploited as a novel approach for the treatment of mecC-MRSA infections.This work was supported by a Medical Research Council (MRC) Partnership Grant (G1001787/1) held between the Department of Veterinary Medicine, University of Cambridge (M. A. H.), the School of Clinical Medicine, University of Cambridge (S. J. P.), the Moredun Research Institute (R. N. Z.) and the Wellcome Trust Sanger Institute (J. P. and S. J. P.).This is the author accepted manuscript. The final version is available from American Society for Microbiology via http://dx.doi.org/10.1128/AAC.01469-1