Introduction: looking beyond the walls

In its consideration of the remarkable extent and variety of non-university researchers, this book takes a broader view of ‘knowledge’ and ‘research’ than in the many hot debates about today’s knowledge society, ‘learning age’, or organisation of research. It goes beyond the commonly held image of ‘knowledge’ as something produced and owned by the full-time experts to take a look at those engaged in active knowledge building outside the university walls

\u3ci\u3eMylanodon rosei\u3c/i\u3e, a New Metacheiromyid (Mammalia: Palaeanodonta) from the Late Tiffanian (Late Paleocene) of Northwestern Wyoming

Mylanodon rosei is a new genus and species of late Paleocene metacheiromyid palaeanodont from a new late Tiffanian locality, Y2K Quarry, in the Clarks Fork Basin, Wyoming. The type is an adult dentary with P4 and a molariform double-rooted M1. This provides the first evidence that molariform teeth were retained in early Metacheiromyidae. A second specimen is a juvenile dentary with a partial P3 and an unerupted P4. This is the first juvenile dentition known for a Paleocene metacheiromyid. The new specimens enable determination of dental homologies. Reduction of teeth in early metacheiromyids took place from back to front, opening the characteristic posterior diastema. Both Mylanodon and Propalaeanodon, a slightly older metacheiromyid, are intermediate morphologically and temporally between the older Tiffanian epoicotheriid Amelotabes and the younger Clarkforkian and Wasatchian metacheiromyid Palaeanodon. Propalaeanodon has a single-rooted M1, a derived characteristic not found in Mylanodon, suggesting that two lineages are involved and Propalaeanodon was not ancestral to Mylanodon

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

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

Social, emotional, and behavioral functioning of secondary school students with low academic and language performance: perspectives from students, teachers, and parents

Adolescence is a time of transition when young people with language difficulties are at increased risk of experiencing social, emotional, and behavioral difficulties (SEBD). Most studies of social, emotional, and behavioral functioning (SEBF) in individuals with language difficulties focus on children with a clinical diagnosis of language impairment. This study explores SEBF in a nonclinical group of 12-year-old students with low educational and language performance from their own perspectives and those of their parents and teachers

Bigger, Faster, Better? Rhetorics and Practices of Large-Scale Research in Contemporary Bioscience

publication-status: Publishedtypes: ArticleEditorial for Special Issu

The Biological Records Centre: a pioneer of citizen science

People have been recording wildlife for centuries and the resulting datasets lead to important scientific research. The Biological Records Centre (BRC), established in 1964, is a national focus for terrestrial and freshwater species recording in the United Kingdom (UK). BRC works with the voluntary recording community (i.e. a mutualistic symbiosis) through support of national recording schemes (i.e. ‘citizen science’, but unlike most citizen science it is volunteer led) and adds value to the data through analysis and reporting. Biological recording represents a diverse range of activities, involving an estimated 70 000 people annually in the UK, from expert volunteers undertaking systematic monitoring to mass participation recording. It is an invaluable monitoring tool because the datasets are long term, have large geographic extent and are taxonomically diverse (85 taxonomic groups). It supports a diverse range of outputs, e.g. atlases showing national distributions (12 127 species from over 40 taxonomic groups) and quantified trends (1636 species). BRC pioneers the use of technology for data capture (online portals and smartphone apps) and verification (including automated verification) through customisable, inter-operable database systems to facilitate efficient data flow. We are confident that biological recording has a bright future with benefits for people, science, and nature