Formal Foundations for the Specification of Software Architecture

This investigation establishes a formal foundation for software architecture that allows for the specification of large, non-trivial software systems using well founded, consistency preserving construction techniques. Two fundamental problems were addressed: how to define and express architectures formally using the concept of theories, and how architecture theories can be practically applied in specification construction. The initial stages of this investigation sought to establish a formal, mathematical relationship between functional specifications of behavior and specifications defining system structure. Experimental results lead to the conclusion that architectures defining the structure of functional operations can be defined using functional logic, but more complex architectures require a separate process logic. A process logic based on Hoare\u27s Communicating Sequential Processes (CSP) was selected for representing and reasoning about system structure and was used in the definition of a process-based specification development system. Specifically, CSP was used to define a category of process-based specifications and specification morphisms. This allowed well-founded specification construction techniques such as specification morphisms, colimits, and interpretations to be applied to the construction of consistent software architecture. Architecture theories expressed in terms of functional and process-based specifications were defined, and translations between these architecture theories were investigated. A feasibility analysis on an image processing application demonstrated that architecture theories can be used to develop specifications for large, non-trivial applications. (KAR) P. 2

Pluralism about Knowledge

In this paper I consider the prospects for pluralism about knowledge, that is, the view that there is a plurality of knowledge relations. After a brief overview of some views that entail a sort of pluralism about knowledge, I focus on a particular kind of knowledge pluralism I call standards pluralism. Put roughly, standards pluralism is the view that one never knows anything simpliciter. Rather, one knows by this-or-that epistemic standard. Because there is a plurality of epistemic standards, there is a plurality of knowledge relations. In §1 I argue that one can construct an impressive case for standards pluralism. In §2 I clarify the relationship between standards pluralism, epistemic contextualism and epistemic relativism. In §3 I argue that standards pluralism faces a serious objection. The gist of the objection is that standards pluralism is incompatible with plausible claims about the normative role of knowledge. In §4 I finish by sketching the form that a standards pluralist response to this objection might take

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

Collage Vol. II

JUDY COCHRAN: Editorial, 4-5 ROBERTA CHAPMEN: Photo, 6 ANITRA CHUGHTAI (Translations): Haikus, 7 CHARLES O\u27KEEFE: Photo, 8 MARK VANDERLINDE-ABERNATHY, ALYSSA LANDRY (Translator): Memories of a Spider (Les souvenirs d\u27une araignee), 9 MARK VANDERLINE-ABERNATHY, AMY NORSKOG (Translator): Tomato Fields (Champ de tomates), 10 SARAH BISHOP, HEFEDH ZANINA (Translator): Dear John (Cher John), 11 RYAN BUTZ (Translator): Basho\u27s Haiku, Issa\u27s Haiku, 12-13 JENNIFER HUMBERT, FADOUA EL BOUAMRAOUI (Translator): Pressed Lips (Levres Serrees), 15 ADELE REEVES (Translator): Contemporary song by Mr. Children, 16-17 BRODY PAGEL, GRACE DUGAR (Translator): The Lizard King (Le Roi Lezard), 18 JIMMY PIPKIN (Translator): In Love with You, 19 MOLLY ROSCOE: Saturday Night at Rusty\u27s (Samedi Soir a Rusty\u27s), 20 CHARLES O\u27KEEFE: Photo, 21 MATT MESSMER (Translator): Waseda University School Song, 22-23 TIMOTHY COOPER: Wenn du grosh bist… (When you\u27re Tall…), 24 DAVID HARMAN: Der Dunkle Stern (The Dark Star), 25 ANN TOWNSEND, JUDY COCHRAN (Translator): From a Window (D\u27une Fenetre), 26-27 SARA CAHILL: El sauce lloron (The Weeping Willow), 28-32 CHARLES O\u27KEEFE: Photo, 30 JENNIFER HUMBERT, MATT BISHOP: Past, Present (passe, present), 33 CAROL GENEYA KAPLAN, FADOUA EL BOUAMRAOUI (Translator): Une Autre Femme (Another Woman), 34-35 CHARLES O\u27KEEFE: Photo, 36 ANN TOWNSEND, JUDY COCHRAN (Translator): The Mowers (Les Faucheurs), 37 PRISCILLA PATON: Photo, 38 GONZALO TUESTA: La Grande Dame De Paris (The Great Lady of Paris), 39 SARAH PILLERDORF (Translator): Japanese Cartoons by Tezuka Osamu, 41-45 DANIELLE GERKEN: Schuhe der Heimat (Boots of Home), 47 CURTIS PLOWGIAN: Le peste de la langue francaise, 48-52 PRISCILLA PATON: Photo, 50 ZANE HOUSEHOLDER: Vive la Republique! (Film), 54 JENNIFER ZIMMER: EL tenis y las frustraciones (Tennis and Frustrations), La tumba de Ben (Ben\u27s Grave), 56-57 AUTUMN LOTZE: Times Square in the rain, 58-59 CHARLES O\u27KEEFE: Photo, 60 STEPHEN M. JULKA: Colors of the Earth, 61 THOMAS BRESSOUD: Java, 62 ERIC NELSON: World, 63 SARAH CLAPP (Translator): At a long day\u27s end (Natsume Soseki), A friend has come and is now leaving, Eating persimmons (Masaoka Shiki), 64 CHARLES O\u27KEEFE: Photo, 65 JOHN BURZYNSKI, MEGAN FETTER (Translator): Home is where the heart is, 66 RICHARD BANAHAN: Photo, 67 KIM FREEMAN: Baltimore, 68 JACOB RIDRIGUEZ-NOBLE: Home (Heimat), 69 SUZANNE KENNEDY: Oft verberge ich mich (Oft I hide myself), 70 RICHARD BANAHAN: Photo, 7

Revealing a brain network endophenotype in families with idiopathic generalised epilepsy

Idiopathic generalised epilepsy (IGE) has a genetic basis. The mechanism of seizure expression is not fully known, but is assumed to involve large-scale brain networks. We hypothesised that abnormal brain network properties would be detected using EEG in patients with IGE, and would be manifest as a familial endophenotype in their unaffected first-degree relatives. We studied 117 participants: 35 patients with IGE, 42 unaffected first-degree relatives, and 40 normal controls, using scalp EEG. Graph theory was used to describe brain network topology in five frequency bands for each subject. Frequency bands were chosen based on a published Spectral Factor Analysis study which demonstrated these bands to be optimally robust and independent. Groups were compared, using Bonferroni correction to account for nonindependent measures and multiple groups. Degree distribution variance was greater in patients and relatives than controls in the 6-9 Hz band (p = 0.0005, p = 0.0009 respectively). Mean degree was greater in patients than healthy controls in the 6-9 Hz band (p = 0.0064). Clustering coefficient was higher in patients and relatives than controls in the 6-9 Hz band (p = 0.0025, p = 0.0013). Characteristic path length did not differ between groups. No differences were found between patients and unaffected relatives. These findings suggest brain network topology differs between patients with IGE and normal controls, and that some of these network measures show similar deviations in patients and in unaffected relatives who do not have epilepsy. This suggests brain network topology may be an inherited endophenotype of IGE, present in unaffected relatives who do not have epilepsy, as well as in affected patients. We propose that abnormal brain network topology may be an endophenotype of IGE, though not in itself sufficient to cause epilepsy

The Magnitude of Global Marine Species Diversity

Background: The question of how many marine species exist is important because it provides a metric for how much we do and do not know about life in the oceans. We have compiled the first register of the marine species of the world and used this baseline to estimate how many more species, partitioned among all major eukaryotic groups, may be discovered. Results: There are ∼226,000 eukaryotic marine species described. More species were described in the past decade (∼20,000) than in any previous one. The number of authors describing new species has been increasing at a faster rate than the number of new species described in the past six decades. We report that there are ∼170,000 synonyms, that 58,000–72,000 species are collected but not yet described, and that 482,000–741,000 more species have yet to be sampled. Molecular methods may add tens of thousands of cryptic species. Thus, there may be 0.7–1.0 million marine species. Past rates of description of new species indicate there may be 0.5 ± 0.2 million marine species. On average 37% (median 31%) of species in over 100 recent field studies around the world might be new to science. Conclusions: Currently, between one-third and two-thirds of marine species may be undescribed, and previous estimates of there being well over one million marine species appear highly unlikely. More species than ever before are being described annually by an increasing number of authors. If the current trend continues, most species will be discovered this century