Gene expression analysis of livers from female B6C3F1 mice exposed to carcinogenic and non-carcinogenic doses of furan, with or without bromodeoxyuridine (BrdU) treatment

AbstractStandard methodology for identifying chemical carcinogens is both time-consuming and resource intensive. Researchers are actively investigating how new technologies can be used to identify chemical carcinogens in a more rapid and cost-effective manner. Here we performed a toxicogenomic case study of the liver carcinogen furan. Full study and mode of action details were previously published in the Journal of Toxicology and Applied Pharmacology. Female B6C3F1 mice were sub-chronically treated with two non-carcinogenic (1 and 2mg/kg bw) and two carcinogenic (4 and 8mg/kg bw) doses of furan for 21days. Half of the mice in each dose group were also treated with 0.02% bromodeoxyuridine (BrdU) for five days prior to sacrifice [13]. Agilent gene expression microarrays were used to measure changes in liver gene and long non-coding RNA expression (published in Toxicological Sciences). Here we describe the experimental and quality control details for the microarray data. We also provide the R code used to analyze the raw data files, produce fold change and false discovery rate (FDR) adjusted p values for each gene, and construct hierarchical clustering between datasets

Measures for the Assessment of Pain in Adults

Peer reviewedPublisher PD

Metal Abundances of Intermediate-Redshift AGN: Evidence for a Population of Lower-Metallicty Seyfert 2 Galaxies at z = 0.3-0.4

We derive oxygen abundances for two samples of Seyfert 2 (Sy2) active galactic nuclei (AGN) selected from the KPNO International Spectroscopic Survey (KISS). The two samples from KISS include 17 intermediate-redshift (0.29 < z < 0.42) Sy2s detected via their [O III] lines, and 35 low-redshift (z < 0.1), Halpha-detected Sy2s. The primary goal of this work is to explore whether the metallicity distribution of these two samples changes with redshift. To determine the oxygen abundances of the KISS galaxies, we use Cloudy to create a large number of photoionization model grids by varying the temperature of the accretion disk, the ratio of X-ray to UV continuum light, the ionization parameter, the hydrogen density, and the metallicity of the narrow-line region clouds. We link the results of these models to the observed [O III]/H-beta and [N II]/H-alpha emission-line ratios of the KISS sample on the BPT diagram, interpolating across the model grids to derive metallicity. The two redshift samples overlap substantially in terms of derived metal abundances, but we find that some of the intermediate-redshift Sy2 galaxies possess lower abundances than their local universe counterparts. Our analysis provides evidence for modest levels of chemical evolution (0.18 +/- 0.06 dex) over 3-4 Gyrs of look-back time. We compare our results to other AGN abundance derivation methods from the literature.Comment: 17 pages, 12 figures; accepted for publication in the Astrophysical Journa

Efficient Graph Reconstruction and Representation Using Augmented Persistence Diagrams

Persistent homology is a tool that can be employed to summarize the shape of data by quantifying homological features. When the data is an object in $\mathbb{R}^d$, the (augmented) persistent homology transform ((A)PHT) is a family of persistence diagrams, parameterized by directions in the ambient space. A recent advance in understanding the PHT used the framework of reconstruction in order to find finite a set of directions to faithfully represent the shape, a result that is of both theoretical and practical interest. In this paper, we improve upon this result and present an improved algorithm for graph -- and, more generally one-skeleton -- reconstruction. The improvement comes in reconstructing the edges, where we use a radial binary (multi-)search. The binary search employed takes advantage of the fact that the edges can be ordered radially with respect to a reference plane, a feature unique to graphs.Comment: This work originally appeared in the 2022 proceedings of the Canadian Conference on Computational Geometry (CCCG). We have updated the proof of Theorem 2 in Appendix A for clarity and correctness. We have also corrected and clarified Section 3.2, as previously, it used slightly stricter general position assumptions than those given in Assumption

A Faithful Discretization of the Augmented Persistent Homology Transform

The persistent homology transform (PHT) represents a shape with a multiset of persistence diagrams parameterized by the sphere of directions in the ambient space. In this work, we describe a finite set of diagrams that discretize the PHT such that it faithfully represents the underlying shape. We provide a discretization that is exponential in the dimension of the shape (making it Furthermore, we provide an output-sensitive algorithm; that is, the algorithm reports the discretization in time proportional to the size of the discretization. Finally, our approach relies only on knowing the heights and dimensions of topological events, meaning that it can be adapted to provide discretizations of other dimension-returning topological transforms, including the Betti curve transform

Interplay of Staphylococcal and Host Proteases Promotes Skin Barrier Disruption in Netherton Syndrome.

Netherton syndrome (NS) is a monogenic skin disease resulting from loss of function of lymphoepithelial Kazal-type-related protease inhibitor (LEKTI-1). In this study we examine if bacteria residing on the skin are influenced by the loss of LEKTI-1 and if interaction between this human gene and resident bacteria contributes to skin disease. Shotgun sequencing of the skin microbiome demonstrates that lesional skin of NS subjects is dominated by Staphylococcus aureus (S. aureus) and Staphylococcus epidermidis (S. epidermidis). Isolates of either species from NS subjects are able to induce skin inflammation and barrier damage on mice. These microbes promote skin inflammation in the setting of LEKTI-1 deficiency due to excess proteolytic activity promoted by S. aureus phenol-soluble modulin α as well as increased bacterial proteases staphopain A and B from S. aureus or EcpA from S. epidermidis. These findings demonstrate the critical need for maintaining homeostasis of host and microbial proteases to prevent a human skin disease

Examining the Effect of Physician Language on Physician Impressions

Previous research provides evidence that stigma can be perpetuated through language with consequences for well-being and quality of care. For example, providers who use stigmatizing language transmit bias toward patients with implications for care provided by other healthcare professionals. The current work extends upon this research by investigating perceptions of physicians who use stigmatizing or humanizing language. The current work sought to document the negative consequences of providers’ indelicate language on impressions of the provider, thereby motivating thoughtful language choices. To this end, the current work experimentally manipulated the language (stigmatizing, identity-first and destigmatizing, person-first) that hypothetical providers used to describe individuals with substance use disorder and examined participants’ judgments of the providers (likeability and positive behavioral intentions). We predicted that the provider using stigmatizing, identity-first language would elicit more negative responses than the provider using destigmatizing, person-first language. However, the results provided no support for this hypothesis; instead, we observed only an effect of the vignette content: participants had more positive perceptions of the physician who spoke first, compared to the physician who spoke second. Although the current work did not observe significant effects of language, past work indicates the importance of empathy, warmth, and respect from providers for patient well-being and outcome. We suggest directions for improving upon the current study, as well as possible topics for future research that may aid in understanding these important antecedents of inclusive and successful patient-physician interactions