Secular Changes in Eta Carinae's Wind 1998-2011

Stellar wind-emission features in the spectrum of eta Carinae have decreased by factors of 1.5-3 relative to the continuum within the last 10 years. We investigate a large data set from several instruments (STIS, GMOS, UVES) obtained between 1998 and 2011 and we analyze the progression of spectral changes in the direct view of the star, in the reflected polar-on spectra at FOS4, and at the Weigelt knots. We find that the spectral changes occurred gradually on a time scale of about 10 years and that they are dependent on the viewing angle. The line strengths declined most in our direct view of the star. About a decade ago, broad stellar wind-emission features were much stronger in our line-of-sight view of the star than at FOS4. After the 2009 event, the wind-emission line strengths are now very similar at both locations. High-excitation He I and N II absorption lines in direct view of the star strengthened gradually. The terminal velocity of Balmer P Cyg absorption lines now appears to be less latitude-dependent and the absorption strength may have weakened at FOS4. Latitude-dependent alterations in the mass-loss rate and the ionization structure of eta Carinae's wind are likely explanations for the observed spectral changes.Comment: 42 pages, 12 figures, 2 table

Clinical and Echocardiographic Findings in an Aged Population of Cavalier King Charles Spaniels

Myxomatous mitral valve disease (MMVD) is the most common cardiac disease in dogs. It varies from dogs without clinical signs to those developing left-sided congestive heart failure, leading to death. Cavalier King Charles Spaniels (CKCSs) are particularly susceptible to MMVD. We hypothesised that within the elderly CKCS population, there is a sub-cohort of MMVD-affected dogs that do not have cardiac remodelling. The objectives of the present study were (i) to determine the prevalence and the degree of cardiac remodelling associated with MMVD; and (ii) assess the effect of age, gender, and body weight on echocardiographic status in a population of aged CKCSs. A total of 126 CKCSs ≥ 8 years old were prospectively included. They all had a physical and echocardiographic examination. A systolic murmur was detected in 89% of dogs; the presence of clinical signs was reported in 19% of them; and echocardiographic evidence of MMVD was described in 100%. Despite the high prevalence, 44.4% of the dogs were clear of echocardiographic signs of cardiac remodelling. Age was significantly associated with the presence and severity of cardiac remodelling and mitral valve prolapse. Our results showed that a proportion of elderly CKCS with confirmed MMVD did not undergo advanced stages of this pathology.This research was funded by the British CKCS Breed Club and The Roslin Institute, University of Edinburgh

Mid-Cycle Changes in Eta Carinae

In late 2006, ground-based photometry of $\eta$ Car plus the Homunculus showed an unexpected decrease in its integrated apparent brightness, an apparent reversal of its long-term brightening. Subsequent HST/WFPC2 photometry of the central star in the near-UV showed that this was not a simple reversal. This multi-wavelength photometry did not support increased extinction by dust as the explanation for the decrease in brightness. A spectrum obtained with GMOS on the Gemini-South telescope, revealed subtle changes mid-way in $\eta$ Car's 5.5 yr spectroscopic cycle 0when compared with HST/STIS spectra at the same phase in the cycle. At mid-cycle the secondary star is 20--30 AU from the primary. We suggest that the spectroscopic changes are consistent with fluctuations in the density and velocity of the primary star's wind, unrelated to the 5.5 yr cycle but possibly related to its latitude-dependent morphology. We also discuss subtle effects that must be taken into account when comparing ground-based and HST/STIS spectra.Comment: 34 pages, 9 Figure

Critical Differences and Clues in Eta Car's 2009 Event

We monitored Eta Carinae with HST WFPC2 and Gemini GMOS throughout the 2009 spectroscopic event, which was expected to differ from its predecessor in 2003 (Davidson et al. 2005). Here we report major observed differences between events, and their implications. Some of these results were quite unexpected. (1) The UV brightness minimum was much deeper in 2009. This suggests that physical conditions in the early stages of an event depend on different parameters than the "normal" inter-event wind. Extra mass ejection from the primary star is one possible cause. (2) The expected He II 4687 brightness maximum was followed several weeks later by another. We explain why this fact, and the timing of the 4687 maxima, strongly support a "shock breakup" hypothesis for X-ray and 4687 behavior as proposed 5-10 years ago. (3) We observed a polar view of the star via light reflected by dust in the Homunculus nebula. Surprisingly, at that location the variations of emission-line brightness and Doppler velocities closely resembled a direct view of the star; which should not have been true for any phenomena related to the orbit. This result casts very serious doubt on all the proposed velocity interpretations that depend on the secondary star's orbital motion. (4) Latitude-dependent variations of H I, He I and Fe II features reveal aspects of wind behavior during the event. In addition, we discuss implications of the observations for several crucial unsolved problems.Comment: 45 pages, 9 figures, submitted to Ap

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

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 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

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

Impact of Host Genes and Strand Selection on miRNA and miRNA* Expression

Dysregulation of miRNAs expression plays a critical role in the pathogenesis of genetic, multifactorial disorders and in human cancers. We exploited sequence, genomic and expression information to investigate two main aspects of post-transcriptional regulation in miRNA biogenesis, namely strand selection regulation and expression relationships between intragenic miRNAs and host genes. We considered miRNAs expression profiles, measured in five sizeable microarray datasets, including samples from different normal cell types and tissues, as well as different tumours and disease states. First, the study of expression profiles of “sister” miRNA pairs (miRNA/miRNA*, 5′ and 3′ strands of the same hairpin precursor) showed that the strand selection is highly regulated since it shows tissue-/cell-/condition-specific modulation. We used information about the direction and the strength of the strand selection bias to perform an unsupervised cluster analysis for the sample classification evidencing that is able to distinguish among different tissues, and sometimes between normal and malignant cells. Then, considering a minimum expression threshold, in few miRNA pairs only one mature miRNA is always present in all considered cell types, whereas the majority of pairs were concurrently expressed in some cell types and alternatively in others. In a significant fraction of concurrently expressed pairs, the major and the minor forms found at comparable levels may contribute to post-transcriptional gene silencing, possibly in a coordinate way. In the second part of the study, the behaved tendency to co-expression of intragenic miRNAs and their “host” mRNA genes was confuted by expression profiles examination, suggesting that the expression profile of a given host gene can hardly be a good estimator of co-transcribed miRNA(s) for post-transcriptional regulatory networks inference. Our results point out the regulatory importance of post-transcriptional phases of miRNAs biogenesis, reinforcing the role of such layer of miRNA biogenesis in miRNA-based regulation of cell activities