Increased Severity of HSV-1 Keratitis and Mortality in Mice Lacking The 2–5A-Dependent RNase L Gene

Purpose: The2′,5′-oligoadenylate-dependent RNase L gene functions in the interferon-inducible RNA decay pathway known as the 2–5A system. The purpose of this study was to determine whether the absence of this gene affects the pathogenesis of herpes simplex virus type 1 (HSV-1) ocular infection in the mouse. Methods: HSV-1 (strain McKrae) was applied bilaterally to unscarified corneas of RNase L–null mice and congenic controls. To evaluate the severity of herpetic keratitis, slit lamp examinations (SLE) were performed every other day for 14 days. To study corneal histology and apoptosis, HSV-1–inoculated RNase-L-null and congenic control mice, as well as mock-inoculated mice (apoptosis negative control), were killed at 6 and 18 hours postinoculation (PI). Uninoculated mice that underwent corneal scarification (apoptosis positive control) were killed 2 hours after scarification. Eyes were dissected and the corneas processed for light and transmission electron microscopy and the TUNEL assay. Results: In comparison with the congenic control mice, RNase L–null mice showed significantly more severe herpetic keratitis (PI day 8, SLE score, mean ± SEM: 3.27 ± 0.10 vs. 2.34 ± 0.06; P \u3c 0.001) and significantly higher mortality (PI day 14, 70% vs. 20%; P \u3c 0.001). Few apoptotic cells were seen in HSV-1–infected RNase L–null mice, although DNA fragmentation consistent with apoptosis was detected in the corneas of congenic control mice 6 and 18 hours after HSV-1 inoculation and in uninfected mice with scarified corneas. Signs of apoptosis were not present in the mock-infected corneas. Electron microscopic evidence of keratocytic apoptosis was detected only in the uninfected scarified corneas and the HSV-1–infected congenic control corneas. Conclusions: The increased severity of ocular disease and increased mortality in the RNase L–null mice provides evidence, for the first time, that the 2–5A system contributes to protection during ocular herpetic infection. The reduced frequency of apoptosis in these mice suggests that one possible mechanism for this protective effect could be the induction of apoptosis in corneal cells as a means of reducing the spread of infectious virus

Allele Size Miscalling due to the Pull-Up Effect Influencing Size Standard Calibration in Capillary Electrophoresis: A Case Study Using HEX Fluorescent Dye in Microsatellites

Microsatellites are important genetic markers and have been broadly employed in many genetic studies. Currently, polymorphisms in microsatellites are often detected by an automated system of capillary electrophoresis with fluorescent dyes. In this situation, different dye combinations may cause pull-up/bleed-through problems, which introduce noise signals from one dye channel into another, causing genotyping errors. Here, we report the detection of such a problem at two microsatellite loci that used the HEX dye. Using three datasets, we tested for noise effects in four allele-scoring programmes: Genemapper, Genemarker, Gelquest and Fragman. We found that, because some allele sizes were identical or close to the size of one of the internal size standards, all four programmes gave allele size calling errors due to wrongly identifying pull-up signals as the internal size standard. In addition, because allele miscalling in this study was caused by the fluorescent dye that the microsatellites used introducing noise of the same colour as the internal size standard used, the pull-up correction function in Genemapper, Genemarker and Fragman failed to deal with this. Considering that pull-up peak scoring errors can occur with any dye colour, the phenomenon is not limited to the current HEX dye. Using different software and visual scoring of each result will allow accurate sizing of microsatellite alleles

Role of dimensional crossover on spin-orbit torque efficiency in magnetic insulator thin films

Magnetic insulators (MIs) attract tremendous interest for spintronic applications due to low Gilbert damping and absence of Ohmic loss. Magnetic order of MIs can be manipulated and even switched by spin-orbit torques (SOTs) generated through spin Hall effect and Rashba-Edelstein effect in heavy metal/MI bilayers. SOTs on MIs are more intriguing than magnetic metals since SOTs cannot be transferred to MIs through direct injection of electron spins. Understanding of SOTs on MIs remains elusive, especially how SOTs scale with the film thickness. Here, we observe the critical role of dimensionality on the SOT efficiency by systematically studying the MI layer thickness dependent SOT efficiency in tungsten/thulium iron garnet (W/TmIG) bilayers. We first show that the TmIG thin film evolves from two-dimensional to three-dimensional magnetic phase transitions as the thickness increases, due to the suppression of long-wavelength thermal fluctuation. Then, we report the significant enhancement of the measured SOT efficiency as the thickness increases. We attribute this effect to the increase of the magnetic moment density in concert with the suppression of thermal fluctuations. At last, we demonstrate the current-induced SOT switching in the W/TmIG bilayers with a TmIG thickness up to 15 nm. The switching current density is comparable with those of heavy metal/ferromagnetic metal cases. Our findings shed light on the understanding of SOTs in MIs, which is important for the future development of ultrathin MI-based low-power spintronics

Application of the Aquifer Impact Model to support decisions at a CO2 sequestration site

The National Risk Assessment Partnership (NRAP) has developed a suite of tools to assess and manage risk at CO sequestration sites. The NRAP tool suite includes the Aquifer Impact Model (AIM), which evaluates the potential for groundwater impacts from leaks of CO and brine through abandoned wellbores. There are two aquifer reduced-order models (ROMs) included with the AIM tool, a confined alluvium aquifer, and an unconfined carbonate aquifer. The models accept aquifer parameters as a range of variable inputs so they may have broad applicability. The generic aquifer models may be used at the early stages of site selection, when site-specific data is not available. Guidelines have been developed for determining when the generic ROMs might be applicable to a new site. This paper considers the application of the AIM to predicting the impact of CO or brine leakage were it to occur at the Illinois Basin Decatur Project (IBDP). Results of the model sensitivity analysis can help guide characterization efforts; the hydraulic parameters and leakage source term magnitude are more sensitive than clay fraction or cation exchange capacity. Sand permeability was the only hydraulic parameter measured at the IBDP site. More information on the other hydraulic parameters could reduce uncertainty in risk estimates. Some non-adjustable parameters are significantly different for the ROM than for the observations at the IBDP site. The generic ROMs could be made more useful to a wider range of sites if the initial conditions and no-impact threshold values were adjustable parameters. © 2017 Society of Chemical Industry and John Wiley & Sons, Ltd. 2 2

Statistical Analysis of the Consistency of HRV Analysis Using BCG or Pulse Wave Signals

Ballistocardiography (BCG) is considered a good alternative to HRV analysis with its non-contact and unobtrusive acquisition characteristics. However, consensus about its validity has not yet been established. In this study, 50 healthy subjects (26.2 ± 5.5 years old, 22 females, 28 males) were invited. Comprehensive statistical analysis, including Coefficients of Variation (CV), Lin’s Concordance Correlation Coefficient (LCCC), and Bland-Altman analysis (BA ratio), were utilized to analyze the consistency of BCG and ECG signals in HRV analysis. If the methods gave different answers, the worst case was taken as the result. Measures of consistency such as Mean, SDNN, LF gave good agreement (the absolute value of CV difference 0.99, BA ratio 0.95, BA ratio < 0.2), while RMSSD, HF, LF/HF indicated poor agreement (the absolute value of CV difference ≥ 5% or LCCC ≤ 0.95 or BA ratio ≥ 0.2). Additionally, the R-R intervals were compared with P-P intervals extracted from the pulse wave (PW). Except for pNN50, which exhibited poor agreement in this comparison, the performances of the HRV indices estimated from the PW and the BCG signals were similar

Learning Shape Priors for Robust Cardiac MR Segmentation from Multi-view Images

© 2019, Springer Nature Switzerland AG. Cardiac MR image segmentation is essential for the morphological and functional analysis of the heart. Inspired by how experienced clinicians assess the cardiac morphology and function across multiple standard views (i.e. long- and short-axis views), we propose a novel approach which learns anatomical shape priors across different 2D standard views and leverages these priors to segment the left ventricular (LV) myocardium from short-axis MR image stacks. The proposed segmentation method has the advantage of being a 2D network but at the same time incorporates spatial context from multiple, complementary views that span a 3D space. Our method achieves accurate and robust segmentation of the myocardium across different short-axis slices (from apex to base), outperforming baseline models (e.g. 2D U-Net, 3D U-Net) while achieving higher data efficiency. Compared to the 2D U-Net, the proposed method reduces the mean Hausdorff distance (mm) from 3.24 to 2.49 on the apical slices, from 2.34 to 2.09 on the middle slices and from 3.62 to 2.76 on the basal slices on the test set, when only 10% of the training data was used

Identifying metabolites by integrating metabolome databases with mass spectrometry cheminformatics.

Novel metabolites distinct from canonical pathways can be identified through the integration of three cheminformatics tools: BinVestigate, which queries the BinBase gas chromatography-mass spectrometry (GC-MS) metabolome database to match unknowns with biological metadata across over 110,000 samples; MS-DIAL 2.0, a software tool for chromatographic deconvolution of high-resolution GC-MS or liquid chromatography-mass spectrometry (LC-MS); and MS-FINDER 2.0, a structure-elucidation program that uses a combination of 14 metabolome databases in addition to an enzyme promiscuity library. We showcase our workflow by annotating N-methyl-uridine monophosphate (UMP), lysomonogalactosyl-monopalmitin, N-methylalanine, and two propofol derivatives

Is telomere length socially patterned? Evidence from the West of Scotland Twenty-07 study

Lower socioeconomic status (SES) is strongly associated with an increased risk of morbidity and premature mortality, but it is not known if the same is true for telomere length, a marker often used to assess biological ageing. The West of Scotland Twenty-07 Study was used to investigate this and consists of three cohorts aged approximately 35 (N = 775), 55 (N = 866) and 75 years (N = 544) at the time of telomere length measurement. Four sets of measurements of SES were investigated: those collected contemporaneously with telomere length assessment, educational markers, SES in childhood and SES over the preceding twenty years. We found mixed evidence for an association between SES and telomere length. In 35-year-olds, many of the education and childhood SES measures were associated with telomere length, i.e. those in poorer circumstances had shorter telomeres, as was intergenerational social mobility, but not accumulated disadvantage. A crude estimate showed that, at the same chronological age, social renters, for example, were nine years (biologically) older than home owners. No consistent associations were apparent in those aged 55 or 75. There is evidence of an association between SES and telomere length, but only in younger adults and most strongly using education and childhood SES measures. These results may reflect that childhood is a sensitive period for telomere attrition. The cohort differences are possibly the result of survival bias suppressing the SES-telomere association; cohort effects with regard different experiences of SES; or telomere possibly being a less effective marker of biological ageing at older ages

Synthesis and Application of Carbon–Iron Oxide Microspheres’ Black Pigments in Electrophoretic Displays

Carbon–iron oxide microspheres’ black pigments (CIOMBs) had been prepared via ultrasonic spray pyrolysis of aqueous solutions containing ferrous chloride and glucose. Due to the presence of carbon, CIOMBs not only exhibited remarkably acid resistance, but also could be well dispersed in both polar solvents and nonpolar solvent. Finally, dispersions of hollow CIOMBs in tetrachloroethylene had successfully been applied in electrophoretic displays

PPAR? Downregulation by TGF in Fibroblast and Impaired Expression and Function in Systemic Sclerosis: A Novel Mechanism for Progressive Fibrogenesis

The nuclear orphan receptor peroxisome proliferator-activated receptor-gamma (PPAR-γ) is expressed in multiple cell types in addition to adipocytes. Upon its activation by natural ligands such as fatty acids and eicosanoids, or by synthetic agonists such as rosiglitazone, PPAR-γ regulates adipogenesis, glucose uptake and inflammatory responses. Recent studies establish a novel role for PPAR-γ signaling as an endogenous mechanism for regulating transforming growth factor-ß (TGF-ß)- dependent fibrogenesis. Here, we sought to characterize PPAR-γ function in the prototypic fibrosing disorder systemic sclerosis (SSc), and delineate the factors governing PPAR-γ expression. We report that PPAR-γ levels were markedly diminished in skin and lung biopsies from patients with SSc, and in fibroblasts explanted from the lesional skin. In normal fibroblasts, treatment with TGF-ß resulted in a time- and dose-dependent down-regulation of PPAR-γ expression. Inhibition occurred at the transcriptional level and was mediated via canonical Smad signal transduction. Genome-wide expression profiling of SSc skin biopsies revealed a marked attenuation of PPAR-γ levels and transcriptional activity in a subset of patients with diffuse cutaneous SSc, which was correlated with the presence of a ''TGF-ß responsive gene signature'' in these biopsies. Together, these results demonstrate that the expression and function of PPAR-γ are impaired in SSc, and reveal the existence of a reciprocal inhibitory cross-talk between TGF-ß activation and PPAR-γ signaling in the context of fibrogenesis. In light of the potent anti-fibrotic effects attributed to PPAR-γ, these observations lead us to propose that excessive TGF-ß activity in SSc accounts for impaired PPAR-γ function, which in turn contributes to unchecked fibroblast activation and progressive fibrosis. © 2010 Wei et al