Computability and Tiling Problems

In this thesis we will present and discuss various results pertaining to tiling problems and mathematical logic, specifically computability theory. We focus on Wang prototiles, as defined in [32]. We begin by studying Domino Problems, and do not restrict ourselves to the usual problems concerning finite sets of prototiles. We first consider two domino problems: whether a given set of prototiles S has total planar tilings, which we denote TILE, or whether it has infinite connected but not necessarily total tilings, WTILE (short for ‘weakly tile’). We show that both TILE ≡m ILL ≡m WTILE, and thereby both TILE and WTILE are Σ11-complete. We also show that the opposite problems, ¬TILE and SNT (short for ‘Strongly Not Tile’) are such that ¬TILE ≡m WELL ≡m SNT and so both ¬TILE and SNT are both Π11-complete. Next we give some consideration to the problem of whether a given (infinite) set of prototiles is periodic or aperiodic. We study the sets PTile of periodic tilings, and ATile of aperiodic tilings. We then show that both of these sets are complete for the class of problems of the form (Σ1 1 ∧Π1 1). We also present results for finite versions of these tiling problems. We then move on to consider the Weihrauch reducibility for a general total tiling principle CT as well as weaker principles of tiling, and show that there exist Weihrauch equivalences to closed choice on Baire space, Cωω. We also show that all Domino Problems that tile some infinite connected region are Weihrauch reducible to Cωω. Finally, we give a prototile set of 15 prototiles that can encode any Elementary CellularAutomaton(ECA). We make use of an unusual tileset, based on hexagons and lozenges that we have not seen in the literature before, in order to achieve this

Chemical Safety Assessment Using Read-Across: Assessing the Use of Novel Testing Methods to Strengthen the Evidence Base for Decision Making

Background: Safety assessment for repeated dose toxicity is one of the largest challenges in the process to replace animal testing. This is also one of the proof of concept ambitions of SEURAT-1, the largest ever European Union research initiative on alternative testing, co-funded by the European Commission and Cosmetics Europe. This review is based on the discussion and outcome of a workshop organized on initiative of the SEURAT-1 consortium joined by a group of international experts with complementary knowledge to further develop traditional read-across and include new approach data. Objectives: The aim of the suggested strategy for chemical read-across is to show how a traditional read-across based on structural similarities between source and target substance can be strengthened with additional evidence from new approach data—for example, information from in vitro molecular screening, “-omics” assays and computational models—to reach regulatory acceptance. Methods: We identified four read-across scenarios that cover typical human health assessment situations. For each such decision context, we suggested several chemical groups as examples to prove when read-across between group members is possible, considering both chemical and biological similarities. Conclusions: We agreed to carry out the complete read-across exercise for at least one chemical category per read-across scenario in the context of SEURAT-1, and the results of this exercise will be completed and presented by the end of the research initiative in December 2015

Archaeobotany in Australia and New Guinea: practice, potential and prospects

Archaeobotany is the study of plant remains from archaeological contexts. Despite Australasian research being at the forefront of several methodological innovations over the last three decades, archaebotany is now a relatively peripheral concern to most archaeological projects in Australia and New Guinea. In this paper, many practicing archaeobotanists working in these regions argue for a more central role for archaeobotany in standard archaeological practice. An overview of archaeobotanical techniques and applications is presented, the potential for archaeobotany to address key historical research questions is indicated, and initiatives designed to promote archaeobotany and improve current practices are outlined

Archaeobotany in Australia and New Guinea: practice, potential and prospects

Archaeobotany is the study of plant remains from archaeological contexts. Despite Australasian research being at the forefront of several methodological innovations over the last three decades, archaebotany is now a relatively peripheral concern to most archaeological projects in Australia and New Guinea. In this paper, many practicing archaeobotanists working in these regions argue for a more central role for archaeobotany in standard archaeological practice. An overview of archaeobotanical techniques and applications is presented, the potential for archaeobotany to address key historical research questions is indicated, and initiatives designed to promote archaeobotany and improve current practices are outlined

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

Comprehensive molecular characterization of gastric adenocarcinoma

Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein–Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also knownasPD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies