On the Nose

A 67-year-old man presented with a 3-day history of chest tightness, wheezing, coughing, and dyspnea. He had a history of asthma but had not had major exacerbations for 20 years. He did not have fever, sputum production, hemoptysis, orthopnea, or edema

Equatorial winds on Saturn and the stratospheric oscillation

The zonal jets on the giant planets have been thought to be stable in time. A decline in the velocity of Saturn’s equatorial jet has been identified, on the basis of a comparison of cloud-tracking data across two decades, but the differences in cloud speeds have since been suggested to stem from changes in cloud altitude in combination with vertical wind shear, rather than from temporal changes in wind strength at a given height. Here, we combine observations of cloud tracks and of atmospheric temperatures taken by two instruments on the Cassini spacecraft to reveal a significant temporal variation in the strength of the high-altitude equatorial jet on Saturn. Specifically, we find that wind speeds at atmospheric pressure levels of 60 mbar, corresponding to Saturn’s tropopause, increased by about 20 m s^(−1) between 2004 and 2008, whereas the wind speed has been essentially constant over time in the southern equatorial troposphere. The observations further reveal that the equatorial jet intensified by about 60 m s^(−1) between 2005 and 2008 in the stratosphere, that is, at pressure levels of 1–5 mbar. Because the wind acceleration is weaker near the tropopause than higher up, in the stratosphere, we conclude that the semi-annual equatorial oscillation of Saturn’s middle atmosphere is also damped as it propagates downwards

Saturn's emitted power

Long-term (2004–2009) on-orbit observations by Cassini Composite Infrared Spectrometer are analyzed to precisely measure Saturn's emitted power and its meridional distribution. Our evaluations suggest that the average global emitted power is 4.952 ± 0.035 W m^(−2) during the period of 2004–2009. The corresponding effective temperature is 96.67 ± 0.17 K. The emitted power is 16.6% higher in the Southern Hemisphere than in the Northern Hemisphere. From 2005 to 2009, the global mean emitted power and effective temperature decreased by ~2% and ~0.5%, respectively. Our study further reveals the interannual variability of emitted power and effective temperature between the epoch of Voyager (~1 Saturn year ago) and the current epoch of Cassini, suggesting changes in the cloud opacity from year to year on Saturn. The seasonal and interannual variability of emitted power implies that the energy balance and internal heat are also varying

Integrated RNA and DNA sequencing reveals early drivers of metastatic breast cancer

Breast cancer metastasis remains a clinical challenge, even within a single patient across multiple sites of the disease. Genome-wide comparisons of both the DNA and gene expression of primary tumors and metastases in multiple patients could help elucidate the underlying mechanisms that cause breast cancer metastasis. To address this issue, we performed DNA exome and RNA sequencing of matched primary tumors and multiple metastases from 16 patients, totaling 83 distinct specimens. We identified tumor-specific drivers by integrating known protein-protein network information with RNA expression and somatic DNA alterations and found that genetic drivers were predominantly established in the primary tumor and maintained through metastatic spreading. In addition, our analyses revealed that most genetic drivers were DNA copy number changes, the TP53 mutation was a recurrent founding mutation regardless of subtype, and that multiclonal seeding of metastases was frequent and occurred in multiple subtypes. Genetic drivers unique to metastasis were identified as somatic mutations in the estrogen and androgen receptor genes. These results highlight the complexity of metastatic spreading, be it monoclonal or multiclonal, and suggest that most metastatic drivers are established in the primary tumor, despite the substantial heterogeneity seen in the metastases

Dynamics of Saturn's South Polar Vortex

The camera onboard the Cassini spacecraft has allowed us to observe many of Saturn's cloud features. We present observations of Saturn's south polar vortex (SPV) showing that it shares some properties with terrestrial hurricanes: cyclonic circulation, warm central region (the eye) surrounded by a ring of high clouds (the eye wall), and convective clouds outside the eye. The polar location and the absence of an ocean are major differences. It also shares properties with the polar vortices on Venus, such as polar location, cyclonic circulation, warm center, and long lifetime, but the Venus vortices have cold collars and are not associated with convective clouds. The SPV's combination of properties is unique among vortices in the solar system

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