Spitzer Secondary Eclipses of the Dense, Modestly-irradiated, Giant Exoplanet HAT-P-20b Using Pixel-Level Decorrelation

HAT-P-20b is a giant exoplanet that orbits a metal-rich star. The planet itself has a high total density, suggesting that it may also have a high metallicity in its atmosphere. We analyze two eclipses of the planet in each of the 3.6- and 4.5 micron bands of Warm Spitzer. These data exhibit intra-pixel detector sensitivity fluctuations that were resistant to traditional decorrelation methods. We have developed a simple, powerful, and radically different method to correct the intra-pixel effect for Warm Spitzer data, which we call pixel-level decorrelation (PLD). PLD corrects the intra-pixel effect very effectively, but without explicitly using - or even measuring - the fluctuations in the apparent position of the stellar image. We illustrate and validate PLD using synthetic and real data, and comparing the results to previous analyses. PLD can significantly reduce or eliminate red noise in Spitzer secondary eclipse photometry, even for eclipses that have proven to be intractable using other methods. Our successful PLD analysis of four HAT-P-20b eclipses shows a best-fit blackbody temperature of 1134 +/-29K, indicating inefficient longitudinal transfer of heat, but lacking evidence for strong molecular absorption. We find sufficient evidence for variability in the 4.5 micron band that the eclipses should be monitored at that wavelength by Spitzer, and this planet should be a high priority for JWST spectroscopy. All four eclipses occur about 35 minutes after orbital phase 0.5, indicating a slightly eccentric orbit. A joint fit of the eclipse and transit times with extant RV data yields e(cos{omega}) = 0.01352 (+0.00054, -0.00057), and establishes the small eccentricity of the orbit to high statistical confidence. Given the existence of a bound stellar companion, HAT-P-20b is another excellent candidate for orbital evolution via Kozai migration or other three-body mechanism.Comment: version published in ApJ, minor text and figure revision

The Science Advantage of a Redder Filter for WFIRST

WFIRST will be capable of providing Hubble-quality imaging performance over several thousand square degrees of the sky. The wide-area, high spatial resolution survey data from WFIRST will be unsurpassed for many decades into the future. With the current baseline design, the WFIRST filter complement will extend from the bluest wavelength allowed by the optical design to a reddest filter (F184W) that has a red cutoff at 2.0 microns. In this white paper, we outline some of the science advantages for adding a K_s filter with a 2.15 micron central wavelength in order to extend the wavelength coverage for WFIRST as far to the red as the possible given the thermal performance of the observatory and the sensitivity of the detectors

The Science Case for an Extended Spitzer Mission

Although the final observations of the Spitzer Warm Mission are currently scheduled for March 2019, it can continue operations through the end of the decade with no loss of photometric precision. As we will show, there is a strong science case for extending the current Warm Mission to December 2020. Spitzer has already made major impacts in the fields of exoplanets (including microlensing events), characterizing near Earth objects, enhancing our knowledge of nearby stars and brown dwarfs, understanding the properties and structure of our Milky Way galaxy, and deep wide-field extragalactic surveys to study galaxy birth and evolution. By extending Spitzer through 2020, it can continue to make ground-breaking discoveries in those fields, and provide crucial support to the NASA flagship missions JWST and WFIRST, as well as the upcoming TESS mission, and it will complement ground-based observations by LSST and the new large telescopes of the next decade. This scientific program addresses NASA's Science Mission Directive's objectives in astrophysics, which include discovering how the universe works, exploring how it began and evolved, and searching for life on planets around other stars.Comment: 75 pages. See page 3 for Table of Contents and page 4 for Executive Summar

The Science Advantage of a Redder Filter for WFIRST

WFIRST will be capable of providing Hubble-quality imaging performance over several thousand square degrees of the sky. The wide-area, high spatial resolution survey data from WFIRST will be unsurpassed for many decades into the future. With the current baseline design, the WFIRST filter complement will extend from the bluest wavelength allowed by the optical design to a reddest filter (F184W) that has a red cutoff at 2.0 microns. In this white paper, we outline some of the science advantages for adding a K_s filter with a 2.15 micron central wavelength in order to extend the wavelength coverage for WFIRST as far to the red as the possible given the thermal performance of the observatory and the sensitivity of the detectors

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

Microneedle Array Design Determines the Induction of Protective Memory CD8+ T Cell Responses Induced by a Recombinant Live Malaria Vaccine in Mice

BACKGROUND: Vaccine delivery into the skin has received renewed interest due to ease of access to the immune system and microvasculature, however the stratum corneum (SC), must be breached for successful vaccination. This has been achieved by removing the SC by abrasion or scarification or by delivering the vaccine intradermally (ID) with traditional needle-and-syringes or with long microneedle devices. Microneedle patch-based transdermal vaccine studies have predominantly focused on antibody induction by inactivated or subunit vaccines. Here, our principal aim is to determine if the design of a microneedle patch affects the CD8(+) T cell responses to a malaria antigen induced by a live vaccine. METHODOLOGY AND FINDINGS: Recombinant modified vaccinia virus Ankara (MVA) expressing a malaria antigen was percutaneously administered to mice using a range of silicon microneedle patches, termed ImmuPatch, that differed in microneedle height, density, patch area and total pore volume. We demonstrate that microneedle arrays that have small total pore volumes induce a significantly greater proportion of central memory T cells that vigorously expand to secondary immunization. Microneedle-mediated vaccine priming induced significantly greater T cell immunity post-boost and equivalent protection against malaria challenge compared to ID vaccination. Notably, unlike ID administration, ImmuPatch-mediated vaccination did not induce inflammatory responses at the site of immunization or in draining lymph nodes. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that the design of microneedle patches significantly influences the magnitude and memory of vaccine-induced CD8(+) T cell responses and can be optimised for the induction of desired immune responses. Furthermore, ImmuPatch-mediated delivery may be of benefit to reducing unwanted vaccine reactogenicity. In addition to the advantages of low cost and lack of pain, the development of optimised microneedle array designs for the induction of T cell responses by live vaccines aids the development of solutions to current obstacles of immunization programmes