Dynamic strain propagation in nanoparticulate zirconia refractory

Residual and intrinsic strains in granular materials have been studied extensively. However, understanding the dynamic strains that cause these resultant residual strains is key to developing better strain-resistant materials. This investigation demonstrates a method for characterizing dynamic strain propagation in granular materials. The specimen is a zirconia-based refractory composed of sol–gel-derived zirconia nanoparticles in a potassium silicate glass binder.In situsynchrotron X-ray powder diffraction in flat-plate geometry is used to characterize the sample structure on timescales of the order of 1 ms. A 125 W CO2laser is used to strain the sample with a 25 ms pulse length. To compensate for the poor flux on this timescale, a pump–probe method is repeated 1000 times and the resulting data are subsequently re-binned to improve statistics. A Gaussian weighting function is also used to introduce better contrast between strained and unstrained frames.TOPAS Academicis used for fitting with a Le Bail model in `batch mode'. Lattice parameters and sample height are refined during fitting, along with a Lorentzian line width for extracting microstrain broadening. Microstrains, ∊, in the range of 1.01 &lt; ∊ &lt; 1.46% are reported on a 1 ms timescale.</jats:p

A Bioinformatics Approach for Determining Sample Identity from Different Lanes of High-Throughput Sequencing Data

The ability to generate whole genome data is rapidly becoming commoditized. For example, a mammalian sized genome (∼3Gb) can now be sequenced using approximately ten lanes on an Illumina HiSeq 2000. Since lanes from different runs are often combined, verifying that each lane in a genome's build is from the same sample is an important quality control. We sought to address this issue in a post hoc bioinformatic manner, instead of using upstream sample or “barcode” modifications. We rely on the inherent small differences between any two individuals to show that genotype concordance rates can be effectively used to test if any two lanes of HiSeq 2000 data are from the same sample. As proof of principle, we use recent data from three different human samples generated on this platform. We show that the distributions of concordance rates are non-overlapping when comparing lanes from the same sample versus lanes from different samples. Our method proves to be robust even when different numbers of reads are analyzed. Finally, we provide a straightforward method for determining the gender of any given sample. Our results suggest that examining the concordance of detected genotypes from lanes purported to be from the same sample is a relatively simple approach for confirming that combined lanes of data are of the same identity and quality

The Legacy of ERA, Privatization and the Policy Ratchet

This article explores the ways in which the neo-liberal impetus toward the privatization of state schooling signalled in the Education Reform Act 1988 (ERA) has become embedded in the English school system. Four main points are made. First, that ERA itself was of huge strategic rather than substantive importance as far as privatization is concerned. Second, by tracing the lineage of privatization from ERA onwards a 'ratchet' effect of small and incremental policy moves can be identified, which have disseminated, embedded and naturalized privatization within public sector provision. Third, that while privatization has been taken up and taken much further by New Labour than it had been by the Conservatives there are differences between the two sets of governments in the role of privatization in education policy and the role of the state. Fourth, the participation of private providers in the planning and delivery of state services has put the private sector at the very heart of policy. At points the article draws upon interviews conducted with private sector providers. © 2008 Sage Publications

Negative compressibility in platinum sulfide using density-functional theory

Copyright © 2010 The American Physical SocietyThe structural and dynamic properties of the mineral Cooperite (PtS) are investigated using density-functional theory. The results show that a competition with the less symmetric but more compact PdS structure leads to a phase transition when the pressure is increased. However, before the phase transition, PtS displays a rare anomalous elastic behavior by expanding along its long axis under hydrostatic pressure. We report the elastic constants of PtS and interpret this negative linear compressibility in the context of a displacive phase transition. We also show that the real structure of PtS is less symmetric than originally determined by experiment

BoostMe accurately predicts DNA methylation values in whole-genome bisulfite sequencing of multiple human tissues

Abstract Background Bisulfite sequencing is widely employed to study the role of DNA methylation in disease; however, the data suffer from biases due to coverage depth variability. Imputation of methylation values at low-coverage sites may mitigate these biases while also identifying important genomic features associated with predictive power. Results Here we describe BoostMe, a method for imputing low-quality DNA methylation estimates within whole-genome bisulfite sequencing (WGBS) data. BoostMe uses a gradient boosting algorithm, XGBoost, and leverages information from multiple samples for prediction. We find that BoostMe outperforms existing algorithms in speed and accuracy when applied to WGBS of human tissues. Furthermore, we show that imputation improves concordance between WGBS and the MethylationEPIC array at low WGBS depth, suggesting improved WGBS accuracy after imputation. Conclusions Our findings support the use of BoostMe as a preprocessing step for WGBS analysis.https://deepblue.lib.umich.edu/bitstream/2027.42/143848/1/12864_2018_Article_4766.pd

Azole Antifungal Agents To Treat the Human Pathogens Acanthamoeba castellanii and Acanthamoeba polyphaga through Inhibition of Sterol 14α-Demethylase (CYP51)

Herein, we have investigated the amebicidal activities of the pharmaceutical triazole CYP51 inhibitors fluconazole, itraconazole, and voriconazole against Acanthamoeba castellanii and Acanthamoeba polyphaga and assess their potential as therapeutic agents against Acanthamoeba infections in humans. Amebicidal activities of the triazoles were assessed by in vitro minimum inhibition concentration (MIC) determinations using trophozoites of A. castellanii and A. polyphaga. In addition, triazole effectiveness was assessed by ligand binding studies and inhibition of CYP51 activity of purified A. castellanii CYP51 (AcCYP51) that was heterologously expressed in Escherichia coli. Itraconazole and voriconazole bound tightly to AcCYP51 (dissociation constant [Kd] of 10 and 13 nM), whereas fluconazole bound weakly (Kd of 2,137 nM). Both itraconazole and voriconazole were confirmed to be strong inhibitors of AcCYP51 activity (50% inhibitory concentrations [IC50] of 0.23 and 0.39 μM), whereas inhibition by fluconazole was weak (IC50, 30 μM). However, itraconazole was 8- to 16-fold less effective (MIC, 16 mg/liter) at inhibiting A. polyphaga and A. castellanii cell proliferation than voriconazole (MIC, 1 to 2 mg/liter), while fluconazole did not inhibit Acanthamoeba cell division (MIC, >64 mg/liter) in vitro. Voriconazole was an effective inhibitor of trophozoite proliferation for A. castellanii and A. polyphaga; therefore, it should be evaluated in trials versus itraconazole for controlling Acanthamoeba infections

The place of strategic environmental assessment in the privatised electricity industry

The private sector has given relatively little attention to the emergence of strategic environmental assessment (SEA); even recently privatised utilities, where SEA might be deemed particularly appropriate, and whose activities are likely to fall within the scope of the European Union SEA Directive, have shown less interest than might be expected. However, the global trend towards the privatisation of state-owned enterprises makes the adaptation of SEA towards these industries all the more pressing. This paper addresses the place that SEA might take within the electricity sector, taking the privatised UK electricity industry as an example. Particular challenges are posed by the radical restructuring of the industry, designed to introduce competitive behaviour, making the development of comprehensive SEA processes problematic, and requiring SEA to be placed in the context of corporate environmental policy and objectives.</p

Single-cell ATAC-Seq in human pancreatic islets and deep learning upscaling of rare cells reveals cell-specific type 2 diabetes regulatory signatures

Objective: Type 2 diabetes (T2D) is a complex disease characterized by pancreatic islet dysfunction, insulin resistance, and disruption of blood glucose levels. Genome-wide association studies (GWAS) have identified > 400 independent signals that encode genetic predisposition. More than 90% of associated single-nucleotide polymorphisms (SNPs) localize to non-coding regions and are enriched in chromatin-defined islet enhancer elements, indicating a strong transcriptional regulatory component to disease susceptibility. Pancreatic islets are a mixture of cell types that express distinct hormonal programs, so each cell type may contribute differentially to the underlying regulatory processes that modulate T2D-associated transcriptional circuits. Existing chromatin profiling methods such as ATAC-seq and DNase-seq, applied to islets in bulk, produce aggregate profiles that mask important cellular and regulatory heterogeneity. Methods: We present genome-wide single-cell chromatin accessibility profiles in >1,600 cells derived from a human pancreatic islet sample using single-cell combinatorial indexing ATAC-seq (sci-ATAC-seq). We also developed a deep learning model based on U-Net architecture to accurately predict open chromatin peak calls in rare cell populations. Results: We show that sci-ATAC-seq profiles allow us to deconvolve alpha, beta, and delta cell populations and identify cell-type-specific regulatory signatures underlying T2D. Particularly, T2D GWAS SNPs are significantly enriched in beta cell-specific and across cell-type shared islet open chromatin, but not in alpha or delta cell-specific open chromatin. We also demonstrate, using less abundant delta cells, that deep learning models can improve signal recovery and feature reconstruction of rarer cell populations. Finally, we use co-accessibility measures to nominate the cell-specific target genes at 104 non-coding T2D GWAS signals. Conclusions: Collectively, we identify the islet cell type of action across genetic signals of T2D predisposition and provide higher-resolution mechanistic insights into genetically encoded risk pathways. Published by Elsevier GmbH.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

De Jure Determinants of New Firm Formation: How the Pillars of Constitutions Influence Entrepreneurship

This paper provides empirical evidence supporting the view that constitutions may influence the organization of economic activities. Dealing with the issue of the institutional determinants of entrepreneurship, it shows that some of the provisions contained in national constitutions are positively and significantly associated to a standard measure of entrepreneurial dynamics, namely the rate of new business density. Using a novel dataset containing the characteristics of the constitutions enacted in the world and a sample of 115 countries, the paper finds that provisions about the right to conduct/establish a business, the right to strike, consumer protection, protection of trademarks, and education promote higher rates of new firm formation