Peculiar Hydrogen-deficient Carbon Stars: Strontium-Rich Stars and the s-Process

Context: R Coronae Borealis (RCB) variables and their non-variable counterparts, the dustless Hydrogen-Deficient Carbon (dLHdC) stars have been known to exhibit enhanced s-processed material on their surfaces, especially Sr, Y, and Ba. No comprehensive work has been done to explore the s-process in these types of stars, however one particular RCB star, U Aqr, has been under scrutiny for its extraordinary Sr enhancement. Aims: We aim to identify RCB and dLHdC stars that have significantly enhanced Sr abundances, such as U Aqr, and use stellar evolution models to begin to estimate the type of neutron exposure that occurs in a typical HdC star. Methods: We compare the strength of the Sr II 4077 $\AA$ spectral line to Ca II H to identify the new subclass of Sr-rich HdCs. We additionally use the structural and abundance information from existing RCB MESA models to calculate the neutron exposure parameter, $\tau$ Results: We identify six stars in the Sr-rich class. Two are RCBs, and four are dLHdCs. We additionally find that the preferred RCB MESA model has a neutron exposure $\tau$ ~ 0.1 mb$^{-1}$, which is lower than the estimated $\tau$ between 0.15 and 0.6 mb$^{-1}$ for the Sr-rich star U Aqr found in the literature. We find trends in the neutron exposure corresponding to He-burning shell temperature, metallicity, and assumed s-processing site. Conclusions: We have found a sub-class of 6 HdCs known as the Sr-rich class, which tend to lie in the halo, outside the typical distribution of RCBs and dLHdCs. We find that dLHdC stars are more likely to be Sr-rich than RCBs, with an occurrence rate of ~13\% for dLHdCs and ~2\% for RCBs. This is one of the first potential spectroscopic differences between RCBs and dLHdCs, along with dLHdCs having stronger surface abundances of $^{18}$O.Comment: 8 pages, submitted to A&

Modeling R Coronae Borealis Stars: Effects of He-Burning Shell Temperature and Metallicity

The R Coronae Borealis (RCB) stars are extremely hydrogen-deficient carbon stars which produce large amounts of dust, causing sudden deep declines in brightness. They are believed to be formed primarily through white dwarf mergers. In this paper, we use MESA to investigate how post-merger objects with a range of initial He-burning shell temperatures from 2.1 - 5.4 *10^8 K with solar and subsolar metallicities evolve into RCB stars. The most successful model of these has subsolar metallicity and an initial temperature near 3 *10^8 K. We find a strong dependence on initial He-burning shell temperature for surface abundances of elements involved in the CNO cycle, as well as differences in effective temperature and radius of RCBs. Elements involved in nucleosynthesis present around 1 dex diminished surface abundances in the 10% solar metallicity models, with the exception of carbon and lithium which are discussed in detail. Models with subsolar metallicities also exhibit longer lifetimes than their solar counterparts. Additionally, we find that convective mixing of the burned material occurs only in the first few years of post-merger evolution, after which the surface abundances are constant during and after the RCB phase, providing evidence for why these stars show a strong enhancement of partial He-burning products.Comment: 13 pages, 12 figures, accepted to MNRAS on August 15, 202

R Coronae Borealis Star Evolution: Simulating 3D Merger Events to 1D Stellar Evolution Including Large Scale Nucleosynthesis

R Coronae Borealis (RCB) stars are rare hydrogen-deficient carbon-rich variable supergiants thought to be the result of dynamically unstable white dwarf mergers. We attempt to model RCBs through all the relevant timescales by simulating a merger event in Octo-tiger, a 3D adaptive mesh refinement (AMR) hydrodynamics code and mapping the post-merger object into MESA, a 1D stellar evolution code. We then post-process the nucleosynthesis on a much larger nuclear reaction network to study the enhancement of s-process elements. We present models that match observations or previous studies in most surface abundances, isotopic ratios, early evolution and lifetimes. We also observe similar mixing behavior as previous modeling attempts which result in the partial He-burning products visible on the surface in observations. However, we do note that our sub-solar models lack any enhancement in s-process elements, which we attribute to a lack of hydrogen in the envelope. We also find that the Oxygen-16/Oxygen-18 isotopic ratio is very sensitive to initial hydrogen abundance and increases outside of the acceptable range with a hydrogen mass fraction greater than $10^{-4}$.Comment: 18 pages, 17 figures, 1 table. To be published in The Astrophysical Journa

A Spectral Classification System for Hydrogen-deficient Carbon Stars

Stellar spectral classification, and especially the Yerkes system, has been highly useful in the study of stars. While there is a currently accepted classification system for carbon stars, the subset of Hydrogen-deficient Carbon (HdC) stars has not been well described by such a system, due in part to their rarity and their variability. Here we present a new system for the classification of HdCs based on their spectra, which is made wholly on their observable appearance. We use a combination of dimensionality reduction and clustering algorithms with human classification to create such a system. We classify over half of the known sample of HdC stars using this, and roughly calibrate the temperatures of each class using their colors. Additionally, we express trends in the occurrence of certain spectral peculiarities such as the presence of Hydrogen and Lithium lines. We also present three previously unpublished spectra, and report the discovery of three new Galactic dustless HdC (dLHdC) stars and additionally discuss one especially unique star that appears to border between the hottest HdCs and the coolest Extreme Helium (EHe) stars.Comment: 30 pages, 18 figures, submitted to MNRA

The Age of the Galactic Stellar Halo from Gaia White Dwarfs

We use 156 044 white dwarf candidates with $\geq5\sigma$ significant parallax measurements from the Gaia mission to measure the velocity dispersion of the Galactic disc; $(\sigma_U,\sigma_V,\sigma_W) = (30.8, 23.9, 20.0)$ km s$^{-1}$. We identify 142 objects that are inconsistent with disc membership at the $>5\sigma$ level. This is the largest sample of field halo white dwarfs identified to date. We perform a detailed model atmosphere analysis using optical and near-infrared photometry and parallaxes to constrain the mass and cooling age of each white dwarf. The white dwarf cooling ages of our targets range from 7 Myr for J1657+2056 to 10.3 Gyr for J1049-7400. The latter provides a firm lower limit of 10.3 Gyr for the age of the inner halo based on the well-understood physics of white dwarfs. Including the pre-white dwarf evolutionary lifetimes, and limiting our sample to the recently formed white dwarfs with cooling ages of $<500$ Myr, we estimate an age of $10.9 \pm 0.4$ Gyr (internal errors only) for the Galactic inner halo. The coolest white dwarfs in our sample also give similar results. For example, J1049-7400 has a total age of 10.9-11.1 Gyr. Our age measurements are consistent with other measurements of the age of the inner halo, including the white dwarf based measurements of the globular clusters M4, NGC 6397, and 47 Tuc.Comment: MNRAS, in pres

Pulmonary Metagenomic Sequencing Suggests Missed Infections in Immunocompromised Children

This article is made available for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing.BACKGROUND: Despite improved diagnostics, pulmonary pathogens in immunocompromised children frequently evade detection, leading to significant mortality. Therefore, we aimed to develop a highly sensitive metagenomic next-generation sequencing (mNGS) assay capable of evaluating the pulmonary microbiome and identifying diverse pathogens in the lungs of immunocompromised children. METHODS: We collected 41 lower respiratory specimens from 34 immunocompromised children undergoing evaluation for pulmonary disease at 3 children's hospitals from 2014-2016. Samples underwent mechanical homogenization, parallel RNA/DNA extraction, and metagenomic sequencing. Sequencing reads were aligned to the National Center for Biotechnology Information nucleotide reference database to determine taxonomic identities. Statistical outliers were determined based on abundance within each sample and relative to other samples in the cohort. RESULTS: We identified a rich cross-domain pulmonary microbiome that contained bacteria, fungi, RNA viruses, and DNA viruses in each patient. Potentially pathogenic bacteria were ubiquitous among samples but could be distinguished as possible causes of disease by parsing for outlier organisms. Samples with bacterial outliers had significantly depressed alpha-diversity (median, 0.61; interquartile range [IQR], 0.33-0.72 vs median, 0.96; IQR, 0.94-0.96; P < .001). Potential pathogens were detected in half of samples previously negative by clinical diagnostics, demonstrating increased sensitivity for missed pulmonary pathogens (P < .001). CONCLUSIONS: An optimized mNGS assay for pulmonary microbes demonstrates significant inoculation of the lower airways of immunocompromised children with diverse bacteria, fungi, and viruses. Potential pathogens can be identified based on absolute and relative abundance. Ongoing investigation is needed to determine the pathogenic significance of outlier microbes in the lungs of immunocompromised children with pulmonary disease

Prophylaxis of chemotherapy-induced febrile neutropenia with granulocyte colony-stimulating factors: where are we now?

Updated international guidelines published in 2006 have broadened the scope for the use of granulocyte colony-stimulating factor (G-CSF) in supporting delivery of myelosuppressive chemotherapy. G-CSF prophylaxis is now recommended when the overall risk of febrile neutropenia (FN) due to regimen and individual patient factors is ≥20%, for supporting dose-dense and dose-intense chemotherapy and to help maintain dose density where dose reductions have been shown to compromise outcomes. Indeed, there is now a large body of evidence for the efficacy of G-CSFs in supporting dose-dense chemotherapy. Predictive tools that can help target those patients who are most at risk of FN are now becoming available. Recent analyses have shown that, by reducing the risk of FN and chemotherapy dose delays and reductions, G-CSF prophylaxis can potentially enhance survival benefits in patients receiving chemotherapy in curative settings. Accumulating data from ‘real-world’ clinical practice settings indicate that patients often receive abbreviated courses of daily G-CSF and consequently obtain a reduced level of FN protection. A single dose of PEGylated G-CSF (pegfilgrastim) may provide a more effective, as well as a more convenient, alternative to daily G-CSF. Prospective studies are needed to validate the importance of delivering the full dose intensity of standard chemotherapy regimens, with G-CSF support where appropriate, across a range of settings. These studies should also incorporate prospective evaluation of risk stratification for neutropenia and its complications

Temporal and tissue-specific variability of SMN protein levels in mouse models of spinal muscular atrophy

textabstractSpinal muscular atrophy (SMA) is a progressive motor neuron disease caused by deleterious variants in SMN1 that lead to a marked decrease in survival motor neuron (SMN) protein expression. Humans have a second SMN gene (SMN2) that is almost identical to SMN1. However, due to alternative splicing the majority of SMN2 messenger ribonucleic acid (mRNA) is translated into a truncated, unstable protein that is quickly degraded. Because the presence of SMN2 provides a unique opportunity for therapy development in SMA patients, the mechanisms that regulate SMN2 splicing and mRNA expression have been elucidated in great detail. In contrast, how much SMN protein is produced at different developmental time points and in different tissues remains under-characterized. In this study, we addressed this issue by determining SMN protein expression levels at three developmental time points across six different mouse tissues and in two distinct mouse models of SMA ('severe' Taiwanese and 'intermediate' Smn2B/mice). We found that, in healthy control mice, SMN protein expression was significantly influenced by both age and tissue type.When comparing mouse models of SMA, we found that, despite being transcribed from genetically different alleles, control SMN levels were relatively similar. In contrast, the degree of SMN depletion between tissues in SMA varied substantially over time and between the two models. These findings offer an explanation for the differential vulnerability of tissues and organs observed in SMA and further our understanding of the systemic and temporal requirements for SMN with direct relevance for developing effective therapies for SMA

Extensive Evolutionary Changes in Regulatory Element Activity during Human Origins Are Associated with Altered Gene Expression and Positive Selection

Understanding the molecular basis for phenotypic differences between humans and other primates remains an outstanding challenge. Mutations in non-coding regulatory DNA that alter gene expression have been hypothesized as a key driver of these phenotypic differences. This has been supported by differential gene expression analyses in general, but not by the identification of specific regulatory elements responsible for changes in transcription and phenotype. To identify the genetic source of regulatory differences, we mapped DNaseI hypersensitive (DHS) sites, which mark all types of active gene regulatory elements, genome-wide in the same cell type isolated from human, chimpanzee, and macaque. Most DHS sites were conserved among all three species, as expected based on their central role in regulating transcription. However, we found evidence that several hundred DHS sites were gained or lost on the lineages leading to modern human and chimpanzee. Species-specific DHS site gains are enriched near differentially expressed genes, are positively correlated with increased transcription, show evidence of branch-specific positive selection, and overlap with active chromatin marks. Species-specific sequence differences in transcription factor motifs found within these DHS sites are linked with species-specific changes in chromatin accessibility. Together, these indicate that the regulatory elements identified here are genetic contributors to transcriptional and phenotypic differences among primate species

Type 2 Diabetes Variants Disrupt Function of SLC16A11 through Two Distinct Mechanisms

Type 2 diabetes (T2D) affects Latinos at twice the rate seen in populations of European descent. We recently identified a risk haplotype spanning SLC16A11 that explains ∼20% of the increased T2D prevalence in Mexico. Here, through genetic fine-mapping, we define a set of tightly linked variants likely to contain the causal allele(s). We show that variants on the T2D-associated haplotype have two distinct effects: (1) decreasing SLC16A11 expression in liver and (2) disrupting a key interaction with basigin, thereby reducing cell-surface localization. Both independent mechanisms reduce SLC16A11 function and suggest SLC16A11 is the causal gene at this locus. To gain insight into how SLC16A11 disruption impacts T2D risk, we demonstrate that SLC16A11 is a proton-coupled monocarboxylate transporter and that genetic perturbation of SLC16A11 induces changes in fatty acid and lipid metabolism that are associated with increased T2D risk. Our findings suggest that increasing SLC16A11 function could be therapeutically beneficial for T2D. Video Abstract [Figure presented] Keywords: type 2 diabetes (T2D); genetics; disease mechanism; SLC16A11; MCT11; solute carrier (SLC); monocarboxylates; fatty acid metabolism; lipid metabolism; precision medicin