Measured and predicted pressure distributions on the AFTI/F-111 mission adaptive wing

Flight tests have been conducted using an F-111 aircraft modified with a mission adaptive wing (MAW). The MAW has variable-camber leading and trailing edge surfaces that can change the wing camber in flight, while preserving smooth upper surface contours. This paper contains wing surface pressure measurements obtained during flight tests at Dryden Flight Research Facility of NASA Ames Research Center. Upper and lower surface steady pressure distributions were measured along four streamwise rows of static pressure orifices on the right wing for a leading-edge sweep angle of 26 deg. The airplane, wing, instrumentation, and test conditions are discussed. Steady pressure results are presented for selected wing camber deflections flown at subsonic Mach numbers up to 0.90 and an angle-of-attack range of 5 to 12 deg. The Reynolds number was 26 million, based on the mean aerodynamic chord. The MAW flight data are compared to MAW wind tunnel data, transonic aircraft technology (TACT) flight data, and predicted pressure distributions. The results provide a unique database for a smooth, variable-camber, advanced supercritical wing

Joint analysis of stressors and ecosystem services to enhance restoration effectiveness

With increasing pressure placed on natural systems by growing human populations, both scientists and resource managers need a better understanding of the relationships between cumulative stress from human activities and valued ecosystem services. Societies often seek to mitigate threats to these services through large-scale, costly restoration projects, such as the over one billion dollar Great Lakes Restoration Initiative currently underway. To help inform these efforts, we merged high-resolution spatial analyses of environmental stressors with mapping of ecosystem services for all five Great Lakes. Cumulative ecosystem stress is highest in near-shore habitats, but also extends offshore in Lakes Erie, Ontario, and Michigan. Variation in cumulative stress is driven largely by spatial concordance among multiple stressors, indicating the importance of considering all stressors when planning restoration activities. In addition, highly stressed areas reflect numerous different combinations of stressors rather than a single suite of problems, suggesting that a detailed understanding of the stressors needing alleviation could improve restoration planning. We also find that many important areas for fisheries and recreation are subject to high stress, indicating that ecosystem degradation could be threatening key services. Current restoration efforts have targeted high-stress sites almost exclusively, but generally without knowledge of the full range of stressors affecting these locations or differences among sites in service provisioning. Our results demonstrate that joint spatial analysis of stressors and ecosystem services can provide a critical foundation for maximizing social and ecological benefits from restoration investments. www.pnas.org/lookup/suppl/doi:10.1073/pnas.1213841110/-/DCSupplementa

Beliefs and Communication Practices Regarding Cognitive Functioning Among Consumers and Primary Care Providers in the United States, 2009

IntroductionLimited research has examined primary care providers’ communication with patients about maintaining cognitive functioning. Our study’s objective was to compare the perceptions of consumers and primary care providers related to beliefs and communication practices about lifestyle behaviors beneficial for overall health and for maintaining cognitive functioning.MethodsIn 2009, we submitted 10 questions to Porter Novelli’s HealthStyles survey and 6 questions to their DocStyles survey. We compared consumers’ (n = 4,728) and providers’ (n = 1,250) beliefs, practices, and information sources related to maintaining health and cognitive functioning. We made comparisons using nonparametric statistics.ResultsApproximately 76% of consumers considered their health to be good or very good; 73.4% were concerned or very concerned about the possibility that their memory may worsen with age. Women were significantly more concerned than men, and white consumers were more concerned than black and Hispanic consumers. Consumers reported they believed that intellectual stimulation (86.6%), physical activity (82.6%), and healthful diet (82.5%) prevented or delayed cognitive impairment. Providers reported advising patients to reduce cognitive impairment risk through physical activity (85.9%), intellectual stimulation (80.3%), and social involvement (67.4%). Few consumers (7.8%) reported receiving this information from providers but reported learning about strategies to maintain memory, primarily from television (50.1%), magazines (44.1%), and newspapers (33.7%).ConclusionProviders reported advising patients about how to reduce risks of cognitive impairment. Consumers reported receiving this information from other sources. Findings suggest a need to examine and assess media messages and to better understand patient–provider communication about cognitive functioning

Rating impacts in a multi‐stressor world: a quantitative assessment of 50 stressors affecting the Great Lakes

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/116318/1/eap2015253717.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

Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH -Mutant Molecular Profiles

Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDH mutant subtype. More broadly, we found that IDH mutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance