2016 Pipeline Report HIV and TB

HIV and TB: Drugs, Diagnostics, Vaccines, Preventive Technologies, Research Toward a Cure, and Immune-Based and Gene Therapies in Developmen

Supermassive Black Holes in Active Galactic Nuclei. II. Calibration of the M-sigma Relationship for AGNs

We calibrate reverberation-based black hole masses in active galactic nuclei (AGNs) by using the correlation between black hole mass, M, and bulge/spheroid stellar velocity dispersion, sigma. We use new measurements of sigma for 6 AGNs and published velocity dispersions for 10 others, in conjunction with improved reverberation mapping results, to determine the scaling factor required to bring reverberation-based black hole masses into agreement with the quiescent galaxy M-sigma relationship. The scatter in the AGN black hole masses is found to be less than a factor of 3. The current observational uncertainties preclude use of the scaling factor to discriminate between broad-line region models.Comment: 16 pages, including 3 figures. Accepted for publication in Ap

Workshop report: “Towards a Cure: HIV Reservoirs and Strategies to Control Them”

On 16 and 17 July 2010, immediately prior to the XVIII International AIDS Conference in Vienna, Austria, the International AIDS Society held a workshop on the important topic of moving beyond antiretroviral therapy and addressing HIV persistence. “Towards a Cure: HIV Reservoirs and Strategies to Control Them” was chaired by Nobel laureate Françoise Barré-Sinoussi and co-sponsored by the French National Agency for Research on AIDS and Viral Hepatitis, Bundesministerium für Wissenschaft und Forschung, the National Institutes of Health, Sidaction and the Treatment Action Group. This article gives an overview of the findings presented at the workshop; complete abstracts are included in this supplement to the Journal of the International AIDS Society

Winston Churchill's "crazy broadcast": party, nation, and the 1945 Gestapo speech

Copyright © 2010 by The North American Conference on British Studies. Published version reproduced with permission of the publisher.Article doesn't contain an abstract

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

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

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