Ghost-tree: creating hybrid-gene phylogenetic trees for diversity analyses.

BackgroundFungi play critical roles in many ecosystems, cause serious diseases in plants and animals, and pose significant threats to human health and structural integrity problems in built environments. While most fungal diversity remains unknown, the development of PCR primers for the internal transcribed spacer (ITS) combined with next-generation sequencing has substantially improved our ability to profile fungal microbial diversity. Although the high sequence variability in the ITS region facilitates more accurate species identification, it also makes multiple sequence alignment and phylogenetic analysis unreliable across evolutionarily distant fungi because the sequences are hard to align accurately. To address this issue, we created ghost-tree, a bioinformatics tool that integrates sequence data from two genetic markers into a single phylogenetic tree that can be used for diversity analyses. Our approach starts with a "foundation" phylogeny based on one genetic marker whose sequences can be aligned across organisms spanning divergent taxonomic groups (e.g., fungal families). Then, "extension" phylogenies are built for more closely related organisms (e.g., fungal species or strains) using a second more rapidly evolving genetic marker. These smaller phylogenies are then grafted onto the foundation tree by mapping taxonomic names such that each corresponding foundation-tree tip would branch into its new "extension tree" child.ResultsWe applied ghost-tree to graft fungal extension phylogenies derived from ITS sequences onto a foundation phylogeny derived from fungal 18S sequences. Our analysis of simulated and real fungal ITS data sets found that phylogenetic distances between fungal communities computed using ghost-tree phylogenies explained significantly more variance than non-phylogenetic distances. The phylogenetic metrics also improved our ability to distinguish small differences (effect sizes) between microbial communities, though results were similar to non-phylogenetic methods for larger effect sizes.ConclusionsThe Silva/UNITE-based ghost tree presented here can be easily integrated into existing fungal analysis pipelines to enhance the resolution of fungal community differences and improve understanding of these communities in built environments. The ghost-tree software package can also be used to develop phylogenetic trees for other marker gene sets that afford different taxonomic resolution, or for bridging genome trees with amplicon trees.Availabilityghost-tree is pip-installable. All source code, documentation, and test code are available under the BSD license at https://github.com/JTFouquier/ghost-tree

Spatial and Temporal Trends in Travel for COVID-19 Vaccinations

Highlights : Disparities in distances people traveled for vaccinations by demographics exist. Males and White people traveled longer distances for vaccination appointments. Travel distances of over 10 miles for vaccination likely required motorized transportation. Introduction: Understanding spatial and temporal trends in travel for COVID-19 vaccinations by key demographic characteristics (i.e., gender, race, age) is important for ensuring equitable access to and increasing distribution efficiency of vaccines and other health services. The aim of this study is to examine trends in travel distance for COVID-19 vaccinations over the course of the vaccination rollout in North Carolina. Methods: Data were collected using electronic medical records of individuals who had first- or single-dose COVID-19 vaccination appointments through UNC Health between December 15, 2020, and August 31, 2021 (N = 204,718). Travel distances to appointments were calculated using the Euclidean distance from individuals’ home ZIP code centroids to clinic addresses. Descriptive statistics and multivariable regression models with individuals’ home ZIP codes incorporated as fixed effects were used to examine differences in travel distances by gender, race, and age. Results: Males and White individuals traveled significantly farther for vaccination appointments throughout the vaccination rollout. On average, females traveled 14. 4 miles, 3.5% shorter distances than males; Black individuals traveled 13.6 miles, 10.0% shorter distances than White individuals; and people aged 65 and older traveled 14.5 miles, 2.6% longer distances than younger people living in the same ZIP code. Conclusions: Controlling for socioeconomic status and spatial proximity to vaccination clinics at the ZIP code level, males and White individuals traveled longer distances for vaccination appointments, demonstrating more ability to travel for vaccinations. Results indicate a need to consider differential ability to travel to vaccinations by key demographic characteristics in COVID-19 vaccination programs and future mass health service delivery efforts

Interoperable human behavior models for simulations

Modern simulations and games have limited capabilities for simulated characters to interact with each other and with humans in rich, meaningful ways. Although significant achievements have been made in developing human behavior models (HBMs) that are able to control a single simulated entity (or a single group of simulated entities), a limiting factor is the inability of HBMs developed by different groups to interact with each other. We present an architecture and multi-level message framework for enabling HBMs to communicate with each other about their actions and their intents, and describe the results of our crowd control demonstration system which applied it to allow three distinct HBMs to interoperate within a single training-oriented simulation. Our hope is that this will encourage the development of standards for interoperability among HBMs which will lead to the development of richer training and analysis simulations.Postprint (author’s final draft

Cell-specific discrimination of desmosterol and desmosterol mimetics confers selective regulation of LXR and SREBP in macrophages.

Activation of liver X receptors (LXRs) with synthetic agonists promotes reverse cholesterol transport and protects against atherosclerosis in mouse models. Most synthetic LXR agonists also cause marked hypertriglyceridemia by inducing the expression of sterol regulatory element-binding protein (SREBP)1c and downstream genes that drive fatty acid biosynthesis. Recent studies demonstrated that desmosterol, an intermediate in the cholesterol biosynthetic pathway that suppresses SREBP processing by binding to SCAP, also binds and activates LXRs and is the most abundant LXR ligand in macrophage foam cells. Here we explore the potential of increasing endogenous desmosterol production or mimicking its activity as a means of inducing LXR activity while simultaneously suppressing SREBP1c-induced hypertriglyceridemia. Unexpectedly, while desmosterol strongly activated LXR target genes and suppressed SREBP pathways in mouse and human macrophages, it had almost no activity in mouse or human hepatocytes in vitro. We further demonstrate that sterol-based selective modulators of LXRs have biochemical and transcriptional properties predicted of desmosterol mimetics and selectively regulate LXR function in macrophages in vitro and in vivo. These studies thereby reveal cell-specific discrimination of endogenous and synthetic regulators of LXRs and SREBPs, providing a molecular basis for dissociation of LXR functions in macrophages from those in the liver that lead to hypertriglyceridemia

Power spectrum for the small-scale Universe

The first objects to arise in a cold dark matter universe present a daunting challenge for models of structure formation. In the ultra small-scale limit, CDM structures form nearly simultaneously across a wide range of scales. Hierarchical clustering no longer provides a guiding principle for theoretical analyses and the computation time required to carry out credible simulations becomes prohibitively high. To gain insight into this problem, we perform high-resolution (N=720^3 - 1584^3) simulations of an Einstein-de Sitter cosmology where the initial power spectrum is P(k) propto k^n, with -2.5 < n < -1. Self-similar scaling is established for n=-1 and n=-2 more convincingly than in previous, lower-resolution simulations and for the first time, self-similar scaling is established for an n=-2.25 simulation. However, finite box-size effects induce departures from self-similar scaling in our n=-2.5 simulation. We compare our results with the predictions for the power spectrum from (one-loop) perturbation theory and demonstrate that the renormalization group approach suggested by McDonald improves perturbation theory's ability to predict the power spectrum in the quasilinear regime. In the nonlinear regime, our power spectra differ significantly from the widely used fitting formulae of Peacock & Dodds and Smith et al. and a new fitting formula is presented. Implications of our results for the stable clustering hypothesis vs. halo model debate are discussed. Our power spectra are inconsistent with predictions of the stable clustering hypothesis in the high-k limit and lend credence to the halo model. Nevertheless, the fitting formula advocated in this paper is purely empirical and not derived from a specific formulation of the halo model.Comment: 30 pages including 10 figures; accepted for publication in MNRA

Clinical Correlates of Benefit From Radium‐223 Therapy in Metastatic Castration Resistant Prostate Cancer

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136309/1/pros23286.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136309/2/pros23286_am.pd

Spatial and Temporal Trends in Travel for COVID-19 Vaccinations

Introduction: Understanding spatial and temporal trends in travel for COVID-19 vaccinations by key demographic characteristics (i.e., gender, race, age) is important for ensuring equitable access to and increasing distribution efficiency of vaccines and other health services. The aim of this study is to examine trends in travel distance for COVID-19 vaccinations over the course of the vaccination rollout in North Carolina. Methods: Data were collected using electronic medical records of individuals who had first- or single-dose COVID-19 vaccination appointments through UNC Health between December 15, 2020, and August 31, 2021 (N = 204,718). Travel distances to appointments were calculated using the Euclidean distance from individuals’ home ZIP code centroids to clinic addresses. Descriptive statistics and multivariable regression models with individuals’ home ZIP codes incorporated as fixed effects were used to examine differences in travel distances by gender, race, and age. Results: Males and White individuals traveled significantly farther for vaccination appointments throughout the vaccination rollout. On average, females traveled 14. 4 miles, 3.5% shorter distances than males; Black individuals traveled 13.6 miles, 10.0% shorter distances than White individuals; and people aged 65 and older traveled 14.5 miles, 2.6% longer distances than younger people living in the same ZIP code. Conclusions: Controlling for socioeconomic status and spatial proximity to vaccination clinics at the ZIP code level, males and White individuals traveled longer distances for vaccination appointments, demonstrating more ability to travel for vaccinations. Results indicate a need to consider differential ability to travel to vaccinations by key demographic characteristics in COVID-19 vaccination programs and future mass health service delivery efforts

DUSTiNGS III: Distribution of Intermediate-Age and Old Stellar Populations in Disks and Outer Extremities of Dwarf Galaxies

We have traced the spatial distributions of intermediate-age and old stars in nine dwarf galaxies in the distant parts of the Local Group, using multi-epoch 3.6 and 4.5 micron data from the DUST in Nearby Galaxies with Spitzer (DUSTiNGS) survey. Using complementary optical imaging from the Hubble Space Telescope, we identify the tip of the red giant branch (TRGB) in the 3.6 micron photometry, separating thermally-pulsating asymptotic giant branch (TP-AGB) stars from the larger red giant branch (RGB) populations. Unlike the constant TRGB in the I-band, at 3.6 micron the TRGB magnitude varies by ~0.7 mag, making it unreliable as a distance indicator. The intermediate-age and old stars are well mixed in two-thirds of the sample with no evidence of a gradient in the ratio of the intermediate-age to old stellar populations outside the central ~1-2'. Variable AGB stars are detected in the outer extremities of the galaxies, indicating that chemical enrichment from these dust-producing stars may occur in the outer regions of galaxies with some frequency. Theories of structure formation in dwarf galaxies must account for the lack of radial gradients in intermediate-age populations and the presence of these stars in the outer extremities of dwarfs. Finally, we identify unique features in individual galaxies, such as extended tidal features in Sex A and Sag DIG and a central concentration of AGB stars in the inner regions of NGC 185 and NGC 147.Comment: 27 pages, 21 figures, 6 table