Exile Vol. XL No. 1

38th Year Title Page by Carrie Horner \u2797 i Epigraph by Ezra Pound ii Table of Contents iii-iv Vertigo by Lisa Stillman \u2795 1 Departing Flight by Morgan Roper \u2794 2 Untitled by Lizzie Loud \u2795 3 Marietta by Craig McDonough \u2794 4 Interlaken by Kira A . Pollack \u2794 5 Why Nature Surprises Us by Josh Endicott \u2796 6-7 Untitled by Colin Mack \u2794 7 My Father by Matt Wanat \u2795 8 Legs In The Dust by Alison Stevens \u2795 9-11 Untitled by Lilly Streett \u2794 12 of cigarettes, saltwater and death... by Tricia B. Swearingen \u2794 13 Serendipity by Lizzie Lout \u2795 14 Untitled by Lilly Streett \u2794 15 Summer by Allison Lemieux \u2795 16 And the Rain Fell by Jeremy Aufrance \u2795 17-18 Main Street by Elise Gargarella \u2795 19 Füssen by Morgan Roper \u2794 20 Lightning on the Snow by Matt Wanat \u2795 21 A discussion of 12 year-old murders, of course by Jeremy Aufrance \u2795 22 Get your hands off my hat by Jamie Oliver \u2794 23 The Hero by Sara Sterling Ely \u2796 24-26 Punker Dave by Trevett Allen \u2795 27 still looking for the perfect line by ryan shafer \u2794 28-29 Untitled by Lizzie Loud \u2795 30 Civil War by Katherine Anne Campo \u2794 31 Disposable belief by ryan shafer \u2794 32-33 Schizophrenic Sylvia by Maria Mohiuddin \u2795 34 Excerpts from Revolutions, a novel by Marcu McLaughlin \u2794 35-36 Untitled by Keith Chapman \u2795 37 The Survivors by Kira A. Pollack \u2794 38 Days of Prophecy by Trey Dunham \u2794 39 Untitled by Carrie Horner \u2797 40 What to do by Christopher Harnish \u2794 41 Familiar Stranger by Lisa Stillman \u2795 42-46 Untitled by John Salter \u2797 47 On Meeting Emma by Allison Lemieux \u2795 48 Nude Figure by James Oliver \u2794 49 Tathagata by Leslie Dana Wells \u2794 50 On Fences and My Dogs by Christopher Harnish \u2794 51 Editorial Board 52 Cover, Kira Pollack \u2794 -iv Editorial decision is shared equally among the Editorial Board. -5

Exile Vol. XL No. 2

38th Year Title Page by Carrie Horner \u2797 i Epigraph by Ezra Pound ii Table of Contents iii-iv Remembering Sundays by Allison Lemieux \u2795 1 Untitled by James Oliver \u2794 2 \u2778 Beige Chevy Malibu by Craig J. McDonough \u2794 3-4 Brushtown Road by Lelei Jennings \u2795 5 In Memoriam: River Phoenix, 1970-93 by Kirstin Rogers \u2794 6 Untitled by Kira Pollack \u2794 7 Checkmate by Kevin Nix \u2794 8 Anywhere in Ohio by Jen Hanysh \u2795 9 Untitled by Nicky Taylor \u2794 10 Under Your Influence by Katherine Anne Campo \u2794 11 Tulips by Tricia B. Swearingen \u2794 12 Untitled by Keith Chapman \u2795 12 December Storm by Erin Lott \u2796 13-19 On Meeting Phil Levine After a Reading at Denison University April 6, 1993 by Christopher Harnish \u2794 20 The 422 Bypass by Joel Husenits \u2795 21 Untitled by Ken Tyburski \u2794 22 Shakespeare\u27s Foreskin by Carey Christie \u2795 23 The Thaw by Chris Iven \u2794 24 The Rockbridge County Fair by Morgan Roper \u2794 25 Let it Drop Through by Carey Christie \u2795 26-27 Aladdin\u27s by Paul Rinkes \u2794 28-29 Untitled by Aileen Jones \u2794 30 The Tango by Hope Layne Morgan \u2794 31 Icarus by Carey Christine \u2795 32-33 fad by Jeremy Aufrance \u2795 34 Untitled by James Oliver \u2794 35 Desert Villanelle by Christopher Harnish \u2794 36 The Skull by Nicky Taylor \u2794 37 Rodeo Bar by Carl Jeffrey Boon \u2796 38 I, Mordred by Carey Christie \u2795 39-43 Between Centuries by Leslie Dana Wells \u2794 44-45 Untitled by Carrie Horner \u2797 45 Untitled by Alex Emmons \u2796 46 Coleridge\u27s Curse by Allison Lemieux \u2795 47 Untitled by Jenny Baker \u2794 48 five by Jeremy Aufrance \u2795 49 Untitled by James Oliver \u2794 50 Lobster Boy by Kirstin Rogers \u2794 51 Fire on the Mountain by Christopher Harnish \u2794 52-53 Yosemite by Morgan Roper \u2794 54 Untitled by Carrie Horner \u2797 54 Untitled by Ken Tyburski \u2794 55 Sleepless Nights Fades to Credits by Allison Lemieux \u2794 56 Dancing Days by Julie McDonald \u2794 57 Immobile by Adrienne Fair \u2796 58-59 Untitled by Kira Pollack \u2794 60 Dorm Fire by Lisa Marie Antonille \u2795 Untitled by Carrie Horner \u2797 61 The Book by Matt Wanat \u2795 62-63 Distance by Carl Jeffrey Boon \u2796 64 Untitled by Jenny Baker \u2794 65 Cover by Ken Tyburski \u2794 Editorial decision is shared equally among the Editorial Board. -6

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

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

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

Discovery and Preclinical Pharmacology of INE963, a Potent and Fast-Acting Blood-Stage Antimalarial with a High Barrier to Resistance and Potential for Single-Dose Cures in Uncomplicated Malaria.

A series of 5-aryl-2-amino-imidazothiadiazole (ITD) derivatives were identified by a phenotype-based high-throughput screening using a blood stage Plasmodium falciparum (Pf) growth inhibition assay. A lead optimization program focused on improving antiplasmodium potency, selectivity against human kinases, and absorption, distribution, metabolism, excretion, and toxicity properties and extended pharmacological profiles culminated in the identification of INE963 (1), which demonstrates potent cellular activity against Pf 3D7 (EC50 = 0.006 μM) and achieves artemisinin-like kill kinetics in vitro with a parasite clearance time of \u3c24 h. A single dose of 30 mg/kg is fully curative in the Pf-humanized severe combined immunodeficient mouse model. INE963 (1) also exhibits a high barrier to resistance in drug selection studies and a long half-life (T1/2) across species. These properties suggest the significant potential for INE963 (1) to provide a curative therapy for uncomplicated malaria with short dosing regimens. For these reasons, INE963 (1) was progressed through GLP toxicology studies and is now undergoing Ph1 clinical trials

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead