Chandra Observations of the Dwarf Nova WX Hyi in Quiescence

We report Chandra observations of the dwarf nova WX Hyi in quiescence. The X-ray spectrum displays strong and narrow emission lines of N, O, Mg, Ne, Si, S and Fe. The various ionization states implied by the lines suggest that the emission is produced within a flow spanning a wide temperature range, from T ~ 10^6 K to T >~ 10^8 K. Line diagnostics indicate that most of the radiation originates from a very dense region, with n ~ 10^{13}-10^{14} cm^{-3}. The Chandra data allow the first tests of specific models proposed in the literature for the X-ray emission in quiescent dwarf novae. We have computed the spectra for a set of models ranging from hot boundary layers, to hot settling flows solutions, to X-ray emitting coronae. WX Hyi differs from other dwarf novae observed at minimum in having much stronger low temperature lines, which prove difficult to fit with existing models, and possibly a very strong, broad O VII line, perhaps produced in a wind moving at a few x 10^3 km/s. The accretion rate inferred from the X-rays is lower than the value inferred from the UV. The presence of high-velocity mass ejection could account for this discrepancy while at the same time explaining the presence of the broad O VII line. If this interpretation is correct, it would provide the first detection of a wind from a dwarf nova in quiescence.Comment: accepted to ApJ; 19 pages, 3 figures, 1 tabl

Early life metal dysregulation in amyotrophic lateral sclerosis

ObjectiveDeficiencies and excess of essential elements and toxic metals are implicated in amyotrophic lateral sclerosis (ALS), but the age when metal dysregulation appears remains unknown. This study aims to determine whether metal uptake is dysregulated during childhood in individuals eventually diagnosed with ALS.MethodsLaser ablation- inductively coupled plasma- mass spectrometry was used to obtain time series data of metal uptake using biomarkers in teeth from autopsies or dental extractions of ALS (n = 36) and control (n = 31) participants. Covariate data included sex, smoking, occupational exposures, and ALS family history. Case- control differences were identified in temporal profiles of metal uptake for individual metals using distributed lag models. Weighted quantile sum (WQS) regression was used for metals mixture analyses. Similar analyses were performed on an ALS mouse model to further verify the relevance of dysregulation of metals in ALS.ResultsMetal levels were higher in cases than in controls: 1.49 times for chromium (1.11- 1.82; at 15 years), 1.82 times for manganese (1.34- 2.46; at birth), 1.65 times for nickel (1.22- 2.01; at 8 years), 2.46 times for tin (1.65- 3.30; at 2 years), and 2.46 times for zinc (1.49- 3.67; at 6 years). Co- exposure to 11 elements indicated that childhood metal dysregulation was associated with ALS. The mixture contribution of metals to disease outcome was likewise apparent in tooth biomarkers of an ALS mouse model, and differences in metal distribution were evident in ALS mouse brains compared to brains from littermate controls.InterpretationOverall, our study reveals direct evidence that altered metal uptake during specific early life time windows is associated with adult- onset ALS.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155978/1/acn351006_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155978/2/acn351006.pd

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

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies

Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good

Juxtaposing BTE and ATE – on the role of the European insurance industry in funding civil litigation

One of the ways in which legal services are financed, and indeed shaped, is through private insurance arrangement. Two contrasting types of legal expenses insurance contracts (LEI) seem to dominate in Europe: before the event (BTE) and after the event (ATE) legal expenses insurance. Notwithstanding institutional differences between different legal systems, BTE and ATE insurance arrangements may be instrumental if government policy is geared towards strengthening a market-oriented system of financing access to justice for individuals and business. At the same time, emphasizing the role of a private industry as a keeper of the gates to justice raises issues of accountability and transparency, not readily reconcilable with demands of competition. Moreover, multiple actors (clients, lawyers, courts, insurers) are involved, causing behavioural dynamics which are not easily predicted or influenced. Against this background, this paper looks into BTE and ATE arrangements by analysing the particularities of BTE and ATE arrangements currently available in some European jurisdictions and by painting a picture of their respective markets and legal contexts. This allows for some reflection on the performance of BTE and ATE providers as both financiers and keepers. Two issues emerge from the analysis that are worthy of some further reflection. Firstly, there is the problematic long-term sustainability of some ATE products. Secondly, the challenges faced by policymakers that would like to nudge consumers into voluntarily taking out BTE LEI