Maunakea Spectroscopic Explorer Advancing from Conceptual Design

The Maunakea Spectroscopic Explorer (MSE) project has completed its Conceptual Design Phase. This paper is a status report of the MSE project regarding its technical and programmatic progress. The technical status includes its conceptual design and system performance, and highlights findings and recommendations from the System and various subsystems design reviews. The programmatic status includes the project organization and management plan for the Preliminary Design Phase. In addition, this paper provides the latest information related to the permitting process for Maunakea construction.Comment: 15 pages; Proceedings of SPIE Astronomical Telescopes + Instrumentation 2018; Ground-based and Airborne Telescopes VI

Uniflow: a collapsible prostatic stent to treat the symptoms of benign prostatic hyperplasia

BPH is a widespread problem that currently does not have any highly effective and cheap solutions. We propose a solution involving a collapsible and durable stent for insertion in to the urethra to aid in urination by opening the urethra only when needed

Predominant Asymmetrical Stem Cell Fate Outcome Limits the Rate of Niche Succession in Human Colonic Crypts.

Stem cell (SC) dynamics within the human colorectal crypt SC niche remain poorly understood, with previous studies proposing divergent hypotheses on the predominant mode of SC self-renewal and the rate of SC replacement. Here we use age-related mitochondrial oxidative phosphorylation (OXPHOS) defects to trace clonal lineages within human colorectal crypts across the adult life-course. By resolving the frequency and size distribution of OXPHOS-deficient clones, quantitative analysis shows that, in common with mouse, long-term maintenance of the colonic epithelial crypt relies on stochastic SC loss and replacement mediated by competition for limited niche access. We find that the colonic crypt is maintained by ~5 effective SCs. However, with a SC loss/replacement rate estimated to be slower than once per year, our results indicate that the vast majority of individual SC divisions result in asymmetric fate outcome. These findings provide a quantitative platform to detect and study deviations from human colorectal crypt SC niche homeostasis during the process of colorectal carcinogenesis.Wellcome Trus

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

Evidence for a Grooming Claw in a North American Adapiform Primate: Implications for Anthropoid Origins

Among fossil primates, the Eocene adapiforms have been suggested as the closest relatives of living anthropoids (monkeys, apes, and humans). Central to this argument is the form of the second pedal digit. Extant strepsirrhines and tarsiers possess a grooming claw on this digit, while most anthropoids have a nail. While controversial, the possible presence of a nail in certain European adapiforms has been considered evidence for anthropoid affinities. Skeletons preserved well enough to test this idea have been lacking for North American adapiforms. Here, we document and quantitatively analyze, for the first time, a dentally associated skeleton of Notharctus tenebrosus from the early Eocene of Wyoming that preserves the complete bones of digit II in semi-articulation. Utilizing twelve shape variables, we compare the distal phalanges of Notharctus tenebrosus to those of extant primates that bear nails (n = 21), tegulae (n = 4), and grooming claws (n = 10), and those of non-primates that bear claws (n = 7). Quantitative analyses demonstrate that Notharctus tenebrosus possessed a grooming claw with a surprisingly well-developed apical tuft on its second pedal digit. The presence of a wide apical tuft on the pedal digit II of Notharctus tenebrosus may reflect intermediate morphology between a typical grooming claw and a nail, which is consistent with the recent hypothesis that loss of a grooming claw occurred in a clade containing adapiforms (e.g. Darwinius masillae) and anthropoids. However, a cladistic analysis including newly documented morphologies and thorough representation of characters acknowledged to have states constituting strepsirrhine, haplorhine, and anthropoid synapomorphies groups Notharctus tenebrosus and Darwinius masillae with extant strepsirrhines rather than haplorhines suggesting that the form of pedal digit II reflects substantial homoplasy during the course of early primate evolution