WFPC2 Observations of Compact Star Cluster Nuclei in Low Luminosity Spiral Galaxies

We have used the Wide Field Planetary Camera 2 aboard the Hubble Space Telescope to image the compact star cluster nuclei of the nearby, late-type, low-luminosity spiral galaxies NGC 4395, NGC 4242, and ESO 359-029. We also analyze archival WFPC2 observations of the compact star cluster nucleus of M33. A comparative analysis of the structural and photometric properties of these four nuclei is presented. All of the nuclei are very compact, with luminosity densities increasing at small radii to the resolution limit of our data. NGC 4395 contains a Seyfert 1 nucleus with a distinct bipolar structure and bright associated filaments which are likely due to [OIII] emission. The M33 nucleus has a complex structure, with elongated isophotes and possible signatures of weak activity, including a jet-like component. The other two nuclei are not known to be active, but share similar physical size scales and luminosities to the M33 and NGC 4395 nuclei. The circumnuclear environments of all four of our program galaxies are extremely diffuse, have only low-to-moderate star formation, and appear to be devoid of large quantities of dust. The central gravitational potentials of the galaxies are also quite shallow, making the origin of these types of `naked' nuclei problematic.Comment: to appear in the July 1999 Astronomical Journal; 38 pages (Latex), 5 tables (postscript), 21 figures (gif); postscript versions of the figures may be obtained via anonymous ftp at ftp://ftp.cv.nrao.edu/NRAO-staff/lmatthew/lanl-nucle

Alabama Veterans Rural Health Initiative: A Preliminary Evaluation of Unmet Health Care Needs

The Alabama Veterans Rural Health Initiative aims to better understand the health care needs, health status, and barriers to care for rural veterans. Following extensive community outreach, Veteran Community Outreach Health Workers assessed 203 veterans residing in rural counties of Alabama who either: 1) had never enrolled in VA health services, or 2) had not used those services in at least two years. While 71.4 percent of participants reported having utilized non-VHA primary care within the past year, 33.5 percent reported an inability or delay in obtaining needed health care for one or more services: primary care, specialty care, mental health care, addictions treatment, dental care, or prescription medication. The most commonly cited barrier was cost. Among all participants, 56 percent screened positive for at least one Axis I mental disorder. Rurally residing, non-VHA utilizing veterans appear to have fairly good access to primary care, but need dental care, prescription medication, and mental health care

Recommendations for selecting drug-drug interactions for clinical decision support

To recommend principles for including drug-drug interactions (DDIs) in clinical decision support

Database resources of the National Center for Biotechnology Information

In addition to maintaining the GenBank(R) nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides data retrieval systems and computational resources for the analysis of data in GenBank and other biological data made available through NCBI's website. NCBI resources include Entrez, Entrez Programming Utilities, PubMed, PubMed Central, Entrez Gene, the NCBI Taxonomy Browser, BLAST, BLAST Link (BLink), Electronic PCR, OrfFinder, Spidey, RefSeq, UniGene, HomoloGene, ProtEST, dbMHC, dbSNP, Cancer Chromosomes, Entrez Genomes and related tools, the Map Viewer, Model Maker, Evidence Viewer, Clusters of Orthologous Groups (COGs), Retroviral Genotyping Tools, HIV-1/Human Protein Interaction Database, SAGEmap, Gene Expression Omnibus (GEO), Online Mendelian Inheritance in Man (OMIM), the Molecular Modeling Database (MMDB), the Conserved Domain Database (CDD) and the Conserved Domain Architecture Retrieval Tool (CDART). Augmenting many of the Web applications are custom implementations of the BLAST program optimized to search specialized datasets. All of the resources can be accessed through the NCBI home page at http://www.ncbi.nlm.nih.gov

Broad-Scale Recombination Patterns Underlying Proper Disjunction in Humans

Although recombination is essential to the successful completion of human meiosis, it remains unclear how tightly the process is regulated and over what scale. To assess the nature and stringency of constraints on human recombination, we examined crossover patterns in transmissions to viable, non-trisomic offspring, using dense genotyping data collected in a large set of pedigrees. Our analysis supports a requirement for one chiasma per chromosome rather than per arm to ensure proper disjunction, with additional chiasmata occurring in proportion to physical length. The requirement is not absolute, however, as chromosome 21 seems to be frequently transmitted properly in the absence of a chiasma in females, a finding that raises the possibility of a back-up mechanism aiding in its correct segregation. We also found a set of double crossovers in surprisingly close proximity, as expected from a second pathway that is not subject to crossover interference. These findings point to multiple mechanisms that shape the distribution of crossovers, influencing proper disjunction in humans

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