214 research outputs found

    Getting More from Less in Defined Benefit Plans: Three Levers for a Low-Return World

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    As global interest rates hover near historic lows, defined benefit pension plan sponsors must grapple with the prospect of lower investment returns. This paper examines three levers that can enhance portfolio outcomes in a low-return world. The levers include: increased contributions; reduced investment costs; and increased portfolio risk. We use portfolio simulations based on a stochastic asset class forecasting model to evaluate each lever according to two criteria—its magnitude of impact and the certainty that this impact will be realized. Our analysis indicates that increased contributions have the greatest and most certain impact. Reduced costs have a more modest, but equally certain impact. Increased risk can deliver a significant impact, but with the least certainty

    Overnight Atmospheric Transport and Chemical Processing of Photochemically Aged Houston Urban and Petrochemical Industrial Plume

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    Overnight atmospheric transport and chemical evolution of photochemically aged Houston urban and petrochemical industrial plume were investigated in July 2005. We report here on the 26 July episode in which the aged plume was tagged 1.5 h before sunset with a pair of free-floating controlled meteorological balloons, which guided quasi-Lagrangian aircraft sampling in the plume as it was advected 300 km to the north over 8 h. The aged plume around sunset was well mixed within a 1600 m residual layer, and was characterized by enhanced levels of aerosol, O3, CO, olefins, acetaldehyde, total odd nitrogen compounds (NOy), and relatively small amounts (\u3c1 \u3eppbv) of NO x. The plume experienced appreciable shearing overnight due to the development of a low-altitude nocturnal jet between 300 and 500 m above mean sea level (MSL). However, the plume above 600 m MSL remained largely undiluted even after 8 h of transport due to lack of turbulent mixing above the jet. About 40-60% of the NOx present in the aged plume around sunset was found to be depleted over this 8 h period. A constrained plume modeling analysis of the quasi-Lagrangian aircraft observations suggested that by dawn this NO x was converted to nitric acid, organic nitrates, and peroxy acyl nitrates via reactions of NO3 radicals with enhanced levels of olefins and aldehydes in the plume. Sensitivity of NOx depletion to heterogeneous hydrolysis of N2O5 on aerosols was examined. These results have significant implications for the impacts of urban and industrial pollution on far downwind regions

    Efficient Dynamic Importance Sampling of Rare Events in One Dimension

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    Exploiting stochastic path integral theory, we obtain \emph{by simulation} substantial gains in efficiency for the computation of reaction rates in one-dimensional, bistable, overdamped stochastic systems. Using a well-defined measure of efficiency, we compare implementations of ``Dynamic Importance Sampling'' (DIMS) methods to unbiased simulation. The best DIMS algorithms are shown to increase efficiency by factors of approximately 20 for a 5kBT5 k_B T barrier height and 300 for 9kBT9 k_B T, compared to unbiased simulation. The gains result from close emulation of natural (unbiased), instanton-like crossing events with artificially decreased waiting times between events that are corrected for in rate calculations. The artificial crossing events are generated using the closed-form solution to the most probable crossing event described by the Onsager-Machlup action. While the best biasing methods require the second derivative of the potential (resulting from the ``Jacobian'' term in the action, which is discussed at length), algorithms employing solely the first derivative do nearly as well. We discuss the importance of one-dimensional models to larger systems, and suggest extensions to higher-dimensional systems.Comment: version to be published in Phys. Rev.

    Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

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    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

    Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

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    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

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    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

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    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

    Facing differences with an open mind: Openness to Experience, salience of intra-group differences, and performance of diverse groups.

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    This study examined how the performance of diverse teams is affected by member openness to experience and the extent to which team reward structure emphasizes intragroup differences. Fifty-eight heterogeneous four-person teams engaged in an interactive task. Teams in which reward structure converged with diversity (i.e., "faultline" teams) performed more poorly than teams in which reward structure cut across differences between group members or pointed to a "superordinate identity." High openness to experience positively influenced teams in which differences were salient (i.e., faultline and "cross-categorized" teams) but not teams with a superordinate identity. This effect was mediated by information elaboration
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