Logic and the basis of ethics : a critical evaluation with respect to the naturalistic fallacy : a thesis presented in partial fulfilment of the requirements for the degree of Master of Arts in Philosophy at Massey University, Palmerston North, New Zealand

Arthur Prior (1914-1969) was a New Zealand philosopher who worked primarily on Logic and is often referred to as the father of tense logic. In 1949, while lecturing at Canterbury University in Christchurch, New Zealand, Prior published Logic and the Basis of Ethics, in which he developed a historical background of the 'issue' as he called it of describing character and conduct by using ethical predicates. Prior believed that when one attempts to describe character and conduct using terms such as 'good' and 'bad' one will likely resort to giving a definition of those terms to support their use in a situation, and then one will be guilty of fallacious reasoning since those terms are indefinable. Prior makes reference to almost fifty philosophers and others over the course of about one hundred pages, but spends more time on G. E. Moore and Ralph Cudworth than many of the others he covers. In this thesis I will critically evaluate Prior's arguments in Logic and the Basis of Ethics, in particular those that relate to Moore, Cudworth, and the naturalistic fallacy. There is a long-standing debate about the naturalistic fallacy because while some argue that it is obviously a fallacy, others argue that it is not a fallacy at all, thus the aim in this thesis will be to consider whether Prior's arguments regarding the naturalistic fallacy are confused and to illustrate the nature of the scholarly controversy

A pan-cancer proteomic perspective on The Cancer Genome Atlas.

Protein levels and function are poorly predicted by genomic and transcriptomic analysis of patient tumours. Therefore, direct study of the functional proteome has the potential to provide a wealth of information that complements and extends genomic, epigenomic and transcriptomic analysis in The Cancer Genome Atlas (TCGA) projects. Here we use reverse-phase protein arrays to analyse 3,467 patient samples from 11 TCGA 'Pan-Cancer' diseases, using 181 high-quality antibodies that target 128 total proteins and 53 post-translationally modified proteins. The resultant proteomic data are integrated with genomic and transcriptomic analyses of the same samples to identify commonalities, differences, emergent pathways and network biology within and across tumour lineages. In addition, tissue-specific signals are reduced computationally to enhance biomarker and target discovery spanning multiple tumour lineages. This integrative analysis, with an emphasis on pathways and potentially actionable proteins, provides a framework for determining the prognostic, predictive and therapeutic relevance of the functional proteome

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 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

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

THE WELFARE AND ETHICS OF RESEARCH INVOLVING WILD ANIMALS: A PRIMER

ABSTRACT 1. Wild animals are used in scientific research in a wide variety of contexts both in situ and ex situ. Guidelines for best practice, where they exist, are not always clearly linked to animal welfare and may instead have their origins in practicality. This is complicated by a lack of clarity about indicators of welfare for wild animals, and to what extent a researcher should intervene in cases of compromised welfare. 2. This Primer highlights and discusses the broad topic of wild animal welfare and the ethics of using wild animals in scientific research, both in the wild and in controlled conditions. Throughout, we discuss issues associated with the capture, handling, housing and experimental approaches for species occupying varied habitats, in both vertebrates and invertebrates (principally insects, crustaceans and molluscs). 3. We highlight where data on the impacts of wild animal research are lacking and provide suggestive guidance to help direct, prepare and mitigate potential welfare issues, including the consideration of end-points and the ethical framework around euthanasia. 4. We conclude with a series of recommendations for researchers to implement from the design stage of any study that uses animals, right through to publication, and discuss the role of journals in promoting better reporting of wild animal studies, ultimately to the benefit of wild animal welfare

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