Identity and Oppression: Differential Responses to an In-Between Status

Oppression operates at various levels, with varying degrees of negativity, and groups respond in markedly different ways. In this paper, the in-between status of the colored South African group is used to illustrate issues of identity and oppression under the Apartheid system—and differing ways in which oppression was experienced and used. The colored group had many social advantages over Blacks, but were also used to oppress that group. Habituation, accommodation, and relative advantage were identified as dynamics within the broader context of power and privilege that contributed to cultural and psychological marginality and status ambivalence of the coloreds. These processes must be understood within the historical, social, and political context of the community. What is evident from the data is that groups and individuals can take up various positions along a continuum of oppressor—oppressed, depending upon the contexts, time, and social and legal relationships involved in their interactions

Truncation of the Inner Accretion Disk around a Black Hole at Low Luminosity

Most black hole binaries show large changes in X-ray luminosity caused primarily by variations in mass accretion rate. An important question for understanding black hole accretion and jet production is whether the inner edge of the accretion disk recedes at low accretion rate. Measurements of the location of the inner edge (Rin) can be made using iron emission lines that arise due to fluorescence of iron in the disk, and these indicate that Rin is very close to the black hole at high and moderate luminosities (near 1% of the Eddington luminosity, Ledd). Here, we report on X-ray observations of the black hole GX 339-4 in the hard state by Suzaku and the Rossi X-ray Timing Explorer (RXTE) that extend iron line studies to 0.14% Ledd and show that Rin increases by a factor of >27 over the value found when GX 339-4 was bright. The exact value of Rin depends on the inclination of the inner disk (i), and we derive 90% confidence limits of Rin > 35 Rg at i = 0 degrees and Rin > 175 Rg at i = 30 degrees. This provides direct evidence that the inner portion of the disk is not present at low luminosity, allowing for the possibility that the inner disk is replaced by advection- or magnetically-dominated accretion flows.Comment: Accepted for ApJ Letters, 5 pages, 4 figure

Preeclampsia and Fetal Growth: Influence of Infant Sex

In response to in utero insults, male vs. female infants have greater disadvantages in pregnancy outcome. We asked if this differential impact of fetal sex might extend to fetal growth in utero during preeclampsia. We first investigated the influence of relevant variables in normotensive pregnancy. We evaluated whether the impact of maternal pre-pregnancy body mass index (BMI), smoking and socioeconomic status were modified by sex and/or race in singleton offspring of 8,801 primiparous normotensive women enrolled in the Collaborative Perinatal Project. The mean head-to-chest circumference (HCC) decreased more or each 1kg/m2 increase in pre-pregnancy BMI, while mean birthweight and ponderal index (PI) increased more for each 1kg/m2 increase in pre-pregnancy BMI among term females vs. males (p=0.07, p<0.01 and p=0.08, interaction respectively). We then investigated whether the relationship between preeclampsia and fetal growth was modified by sex in offspring of 516 preeclamptic and 8801 normotensive primiparous women. Male vs. female preterm offspring of preeclamptic mothers had greater reductions in mean birthweight, head and chest circumferences (p=0.05, p=0.02, p=0.01; interaction respectively). The influence of preeclampsia on growth of term offspring was more modest, and the influence of sex was opposite that in preterm infants.Next we investigated placentas from 735 preeclamptic and 21,185 normotensive primiparous and multiparous women, to determine which dimensions of placental growth are reduced in preeclamptic pregnancies. We then investigated if the relationship between these measures and birthweight was constant between offspring of normotensive and preeclamptic women, as well as across infant sex. We found that the smaller but not the larger placental diameter was an independent predictor of preeclampsia ((smaller diameter <15cm OR 1.27 95% CI 1.01, 1.59) and larger diameter <18 cm (OR 1.18 95% CI 0.90, 1.54)). We also found higher rates of increase in birth weight at lower placental weight and placental diameters in offspring of preeclamptic vs. normotensive women (all p<0.05, interaction). Additionally, we found that among the offspring of preeclamptic women, female offspring with smaller diameters above 20cm, had a reduction in birth weight while males did not (p=0.02, interaction). This work yields meaningful public health findings by providing evidence that influences upon fetal and placental growth are different by infant sex. Studies of mechanisms affecting fetal growth should investigate interactions with fetal sex. We hope studies of the involved biological pathways will direct future research to reduce rates of growth restriction and later life chronic diseases

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