Evaluation of a Dynamic Weather-Avoidance Rerouting Tool in Adjacent-Center Arrival Metering

Dynamic Reroutes for Arrivals in Weather (DRAW) is a NASA-developed decision-support tool for Traffic Management Coordinators (TMCs) at the Federal Aviation Administration's Air Route Traffic Control Centers ("Centers"). DRAW proposes weather-avoidance reroutes for en route arrival flights subject to metering restrictions when transitioning into a busy terminal airspace. The prior DRAW study demonstrated that TMCs' use of DRAW promotes earlier reroutes of arrivals, and reduces the number of routes conflicting with weather in the Center. The present paper focuses on how DRAW benefits metering delivery accuracy when schedule freeze horizon distance was altered. A human-in-the-loop simulation was conducted at NASA Ames Research Center in October-November 2018, where retired TMCs and controllers performed simulated metering operations for southeast arrivals through the Atlanta and Jacksonville Centers to the Hartsfield-Jackson Atlanta International Airport during convective weather periods. Results demonstrated that DRAW use reduced the frequency of manual adjustments of Scheduled Times of Arrival and lowered TMC workload. DRAW use also made the metering accuracy, the number of reroute amendments after the freeze horizon, and the en route sector controller workload more robust to the effect of different freeze horizon distance

Chemical abundances and ages of the bulge stars in APOGEE high-velocity peaks

A cold high-velocity (HV, $\sim$ 200 km/s) peak was first reported in several Galactic bulge fields based on the APOGEE commissioning observations. Both the existence and the nature of the high-velocity peak are still under debate. Here we revisit this feature with the latest APOGEE DR13 data. We find that most of the low latitude bulge fields display a skewed Gaussian distribution with a HV shoulder. However, only 3 out of 53 fields show distinct high-velocity peaks around 200 km/s. The velocity distribution can be well described by Gauss-Hermite polynomials, except the three fields showing clear HV peaks. We find that the correlation between the skewness parameter ($h_{3}$) and the mean velocity ($\bar{v}$), instead of a distinctive HV peak, is a strong indicator of the bar. It was recently suggested that the HV peak is composed of preferentially young stars. We choose three fields showing clear HV peaks to test this hypothesis using the metallicity, [$\alpha$/M] and [C/N] as age proxies. We find that both young and old stars show HV features. The similarity between the chemical abundances of stars in the HV peaks and the main component indicates that they are not systematically different in terms of chemical abundance or age. In contrast, there are clear differences in chemical space between stars in the Sagittarius dwarf and the bulge stars. The strong HV peaks off-plane are still to be explained properly, and could be different in nature.Comment: 13 pages, 10 figures, published in ApJ. Updated to match the final ApJ published version. Minor revisions to the text and Figure

APOGEE Chemical Abundances of the Sagittarius Dwarf Galaxy

The Apache Point Observatory Galactic Evolution Experiment (APOGEE) provides the opportunity to measure elemental abundances for C, N, O, Na, Mg, Al, Si, P, K, Ca, V, Cr, Mn, Fe, Co, and Ni in vast numbers of stars. We analyze the chemical abundance patterns of these elements for 158 red giant stars belonging to the Sagittarius dwarf galaxy (Sgr). This is the largest sample of Sgr stars with detailed chemical abundances and the first time C, N, P, K, V, Cr, Co, and Ni have been studied at high-resolution in this galaxy. We find that the Sgr stars with [Fe/H] $\gtrsim$ -0.8 are deficient in all elemental abundance ratios (expressed as [X/Fe]) relative to the Milky Way, suggesting that Sgr stars observed today were formed from gas that was less enriched by Type II SNe than stars formed in the Milky Way. By examining the relative deficiencies of the hydrostatic (O, Na, Mg, and Al) and explosive (Si, P, K, and Mn) elements, our analysis supports the argument that previous generations of Sgr stars were formed with a top-light IMF, one lacking the most massive stars that would normally pollute the ISM with the hydrostatic elements. We use a simple chemical evolution model, flexCE to further backup our claim and conclude that recent stellar generations of Fornax and the LMC could also have formed according to a top-light IMF.Comment: 14 pages, 12 figures, accepted for publication in Ap

Cross-National Differences in Victimization : Disentangling the Impact of Composition and Context

Varying rates of criminal victimization across countries are assumed to be the outcome of countrylevel structural constraints that determine the supply ofmotivated o¡enders, as well as the differential composition within countries of suitable targets and capable guardianship. However, previous empirical tests of these ‘compositional’ and ‘contextual’ explanations of cross-national di¡erences have been performed upon macro-level crime data due to the unavailability of comparable individual-level data across countries. This limitation has had two important consequences for cross-national crime research. First, micro-/meso-level mechanisms underlying cross-national differences cannot be truly inferred from macro-level data. Secondly, the e¡ects of contextual measures (e.g. income inequality) on crime are uncontrolled for compositional heterogeneity. In this paper, these limitations are overcome by analysing individual-level victimization data across 18 countries from the International CrimeVictims Survey. Results from multi-level analyses on theft and violent victimization indicate that the national level of income inequality is positively related to risk, independent of compositional (i.e. micro- and meso-level) di¡erences. Furthermore, crossnational variation in victimization rates is not only shaped by di¡erences in national context, but also by varying composition. More speci¢cally, countries had higher crime rates the more they consisted of urban residents and regions with lowaverage social cohesion.

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

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

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

Two groups of red giants with distinct chemical abundances in the bulge globular cluster NGC 6553 through the eyes of APOGEE

Multiple populations revealed in globular clusters (GCs) are important windows to the formation and evolution of these stellar systems. The metal-rich GCs in the Galactic bulge are an indispensable part of this picture, but the high optical extinction in this region has prevented extensive research. In this work, we use the high-resolution near-infrared (NIR) spectroscopic data from Apache Point Observatory Galactic Evolution Experiment (APOGEE) to study the chemical abundances of NGC 6553, which is one of the most metal-rich bulge GCs. We identify 10 red giants as cluster members using their positions, radial velocities, iron abundances, and NIR photometry. Our sample stars show a mean radial velocity of −0.14 ± 5.47 km s−1, and a mean [Fe/H] of −0.15 ± 0.05. We clearly separate two populations of stars in C and N in this GC for the first time. NGC 6553 is the most metal-rich GC where the multiple stellar population phenomenon is found until now. Substantial chemical variations are also found in Na, O, and Al. However, the two populations show similar Si, Ca, and iron-peak element abundances. Therefore, we infer that the CNO, NeNa, and MgAl cycles have been activated, but the MgAl cycle is too weak to show its effect on Mg. Type Ia and Type II supernovae do not seem to have significantly polluted the second generation stars. Comparing with other GC studies, NGC 6553 shows similar chemical variations as other relatively metal-rich GCs. We also confront current GC formation theories with our results, and suggest possible avenues for improvement in the models

MD-2 is required for disulfide HMGB1-dependent TLR4 signaling

Innate immune receptors for pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) orchestrate inflammatory responses to infection and injury. Secreted by activated immune cells or passively released by damaged cells, HMGB1 is subjected to redox modification that distinctly influences its extracellular functions. Previously, it was unknown how the TLR4 signalosome distinguished between HMGB1 isoforms. Here we demonstrate that the extracellular TLR4 adaptor, myeloid differentiation factor 2 (MD-2), binds specifically to the cytokine-inducing disulfide isoform of HMGB1, to the exclusion of other isoforms. Using MD-2–deficient mice, as well as MD-2 silencing in macrophages, we show a requirement for HMGB1-dependent TLR4 signaling. By screening HMGB1 peptide libraries, we identified a tetramer (FSSE, designated P5779) as a specific MD-2 antagonist preventing MD-2–HMGB1 interaction and TLR4 signaling. P5779 does not interfere with lipopolysaccharide-induced cytokine/chemokine production, thus preserving PAMP-mediated TLR4–MD-2 responses. Furthermore, P5779 can protect mice against hepatic ischemia/reperfusion injury, chemical toxicity, and sepsis. These findings reveal a novel mechanism by which innate systems selectively recognize specific HMGB1 isoforms. The results may direct toward strategies aimed at attenuating DAMP-mediated inflammation while preserving antimicrobial immune responsiveness