37 research outputs found
EVR-CB-001: An evolving, progenitor, white dwarf compact binary discovered with the Evryscope
We present EVR-CB-001, the discovery of a compact binary with an extremely
low mass () helium core white dwarf progenitor (pre-He
WD) and an unseen low mass () helium white dwarf (He
WD) companion. He WDs are thought to evolve from the remnant helium-rich core
of a main-sequence star stripped during the giant phase by a close companion.
Low mass He WDs are exotic objects (only about .2 of WDs are thought to be
less than .3 ), and are expected to be found in compact binaries.
Pre-He WDs are even rarer, and occupy the intermediate phase after the core is
stripped, but before the star becomes a fully degenerate WD and with a larger
radius () than a typical WD. The primary component of
EVR-CB-001 (the pre-He WD) was originally thought to be a hot subdwarf (sdB)
star from its blue color and under-luminous magnitude, characteristic of sdBs.
The mass, temperature (), and surface gravity
() solutions from this work are lower than values for
typical hot subdwarfs. The primary is likely to be a post-RGB, pre-He WD
contracting into a He WD, and at a stage that places it nearest to sdBs on
color-magnitude and - diagrams. EVR-CB-001 is expected to
evolve into a fully double degenerate, compact system that should spin down and
potentially evolve into a single hot subdwarf star. Single hot subdwarfs are
observed, but progenitor systems have been elusive.Comment: 14 pages, 11 figures. Published in The Astrophysical Journa
Proguanil plus sulfamethoxazole is not causally prophylactic in the Macaca mulatta - Plasmodium cynomolgi model
New drugs for causal prophylaxis of malaria are needed. A proguanil/sulfamethoxazole combination was investigated using a rhesus monkey model (Macaca mulatta infected with Plasmodium cynomolgi) to determine whether causal prophylaxis could be achieved. When a five-day regimen of proguanil (40 mg/kg/day) combined with sulfamethoxazole (100 mg/kg/day) was used, infection of all animals (6 of 6) was observed, with an extended prepatent period (median 40 days). Two control animals became infected on days 9 and 23 following sporozoite inoculation. Plasma concentrations indicated that proguanil and sulfamethoxazole were adequately absorbed and metabolized to cycloguanil and N-4-acetylsulfamethoxazole, respectively. Analysis of liver biopsy specimens demonstrated that the drugs were present two days following sporozoite inoculation but were not detectable one week later. Proguanil plus sulfamethoxazole does not eliminate exoerythrocytic-stage parasites in the rhesus monkey-P. cynomolgi model
I Spy Transits and Pulsations: Empirical Variability in White Dwarfs Using Gaia and the Zwicky Transient Facility
We present a novel method to detect variable astrophysical objects and
transient phenomena using anomalous excess scatter in repeated measurements
from public catalogs of Gaia DR2 and Zwicky Transient Facility (ZTF) DR3
photometry. We first provide a generalized, all-sky proxy for variability using
only Gaia DR2 photometry, calibrated to white dwarf stars. To ensure more
robust candidate detection, we further employ a method combining Gaia with ZTF
photometry and alerts. To demonstrate the efficacy, we apply this latter
technique to a sample of roughly white dwarfs within 200 pc centered
on the ZZ Ceti instability strip, where hydrogen-atmosphere white dwarfs are
known to pulsate. Through inspecting the top samples ranked by these
methods, we demonstrate that both the Gaia-only and ZTF-informed techniques are
highly effective at identifying known and new variable white dwarfs, which we
verify using follow-up, high-speed photometry. We confirm variability in all 33
out of 33 () observed white dwarfs within our top highest-ranked
candidates, both inside and outside the ZZ Ceti instability strip. In addition
to dozens of new pulsating white dwarfs, we also identify five white dwarfs
highly likely to show transiting planetary debris; if confirmed, these systems
would more than triple the number of white dwarfs known to host transiting
debris.Comment: 30 pages, 14 figures, revised and accepted to ApJ on March 11, 202
Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context
Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts
Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas
This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing
molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin
Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas
Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN
Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images
Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images
of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL
maps are derived through computational staining using a convolutional neural network trained to
classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and
correlation with overall survival. TIL map structural patterns were grouped using standard
histopathological parameters. These patterns are enriched in particular T cell subpopulations
derived from molecular measures. TIL densities and spatial structure were differentially enriched
among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial
infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic
patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for
the TCGA image archives with insights into the tumor-immune microenvironment
Development of the PSYCHS: Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS
Aim: To harmonize two ascertainment and severity rating instruments commonly used for the clinical high risk syndrome for psychosis (CHR-P): the Structured Interview for Psychosis-risk Syndromes (SIPS) and the Comprehensive Assessment of At-Risk Mental States (CAARMS). Methods: The initial workshop is described in the companion report from Addington et al. After the workshop, lead experts for each instrument continued harmonizing attenuated positive symptoms and criteria for psychosis and CHR-P through an intensive series of joint videoconferences. Results: Full harmonization was achieved for attenuated positive symptom ratings and psychosis criteria, and modest harmonization for CHR-P criteria. The semi-structured interview, named Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS (PSYCHS), generates CHR-P criteria and severity scores for both CAARMS and SIPS. Conclusions: Using the PSYCHS for CHR-P ascertainment, conversion determination, and attenuated positive symptom severity rating will help in comparing findings across studies and in meta-analyses