Sedimentological characterization of Antarctic moraines using UAVs and Structure-from-Motion photogrammetry

In glacial environments particle-size analysis of moraines provides insights into clast origin, transport history, depositional mechanism and processes of reworking. Traditional methods for grain-size classification are labour-intensive, physically intrusive and are limited to patch-scale (1m2) observation. We develop emerging, high-resolution ground- and unmanned aerial vehicle-based ‘Structure-from-Motion’ (UAV-SfM) photogrammetry to recover grain-size information across an moraine surface in the Heritage Range, Antarctica. SfM data products were benchmarked against equivalent datasets acquired using terrestrial laser scanning, and were found to be accurate to within 1.7 and 50mm for patch- and site-scale modelling, respectively. Grain-size distributions were obtained through digital grain classification, or ‘photo-sieving’, of patch-scale SfM orthoimagery. Photo-sieved distributions were accurate to <2mm compared to control distributions derived from dry sieving. A relationship between patch-scale median grain size and the standard deviation of local surface elevations was applied to a site-scale UAV-SfM model to facilitate upscaling and the production of a spatially continuous map of the median grain size across a 0.3 km2 area of moraine. This highly automated workflow for site scale sedimentological characterization eliminates much of the subjectivity associated with traditional methods and forms a sound basis for subsequent glaciological process interpretation and analysis

Eating Paradise: Food as Coloniality and Leisure

Sandals Resorts’ Gourmet Discovery Dining programme continues the company’s practice of marketing difference by combining tourism with the commodification of food from non-Western cultures (Dodman and Rhiney 2008). The article draws on bell hooks’ (1992) concept of ‘eating the other’ and the analysis undertakes an interdisciplinary approach that combines visual analysis with Anibal Quijano’s (2007) concept of modernity/coloniality. The discussion explores the trends of global multiculturalism that have been adopted by Sandals in a hybridized cut and mix approach to selling a packaged ideal of the Caribbean. The visual techniques devised to create a culinary holiday package are overlaid onto a manufactured and homogenised or McDonaldized (Ritzer and Liska 1997) Caribbean that provides insight into the way in which global neoliberal multiculturalism is framed by ongoing colonial relations after formal colonial rule has ended in the Caribbean region

Sedimentological characterisation of Antarctic moraines using UAVs and Structure-from-Motion photogrammetry

In glacial environments particle-size analysis of moraines provides insights into clast origin, transport history, depositional mechanism and processes of reworking. Traditional methods for grain-size classification are labour-intensive, physically intrusive and are limited to patch-scale (1m2) observation. We develop emerging, high-resolution ground- and unmanned aerial vehicle-based ‘Structure-from-Motion’ (UAV-SfM) photogrammetry to recover grain-size information across an moraine surface in the Heritage Range, Antarctica. SfM data products were benchmarked against equivalent datasets acquired using terrestrial laser scanning, and were found to be accurate to within 1.7 and 50mm for patch- and site-scale modelling, respectively. Grain-size distributions were obtained through digital grain classification, or ‘photo-sieving’, of patch-scale SfM orthoimagery. Photo-sieved distributions were accurate to <2mm compared to control distributions derived from dry sieving. A relationship between patch-scale median grain size and the standard deviation of local surface elevations was applied to a site-scale UAV-SfM model to facilitate upscaling and the production of a spatially continuous map of the median grain size across a 0.3 km2 area of moraine. This highly automated workflow for site scale sedimentological characterization eliminates much of the subjectivity associated with traditional methods and forms a sound basis for subsequent glaciological process interpretation and analysis

Single-cell paired-end genome sequencing reveals structural variation per cell cycle

The nature and pace of genome mutation is largely unknown. Because standard methods sequence DNA from populations of cells, the genetic composition of individual cells is lost, de novo mutations in cells are concealed within the bulk signal and per cell cycle mutation rates and mechanisms remain elusive. Although single-cell genome analyses could resolve these problems, such analyses are error-prone because of whole-genome amplification (WGA) artefacts and are limited in the types of DNA mutation that can be discerned. We developed methods for paired-end sequence analysis of single-cell WGA products that enable (i) detecting multiple classes of DNA mutation, (ii) distinguishing DNA copy number changes from allelic WGA-amplification artefacts by the discovery of matching aberrantly mapping read pairs among the surfeit of paired-end WGA and mapping artefacts and (iii) delineating the break points and architecture of structural variants. By applying the methods, we capture DNA copy number changes acquired over one cell cycle in breast cancer cells and in blastomeres derived from a human zygote after in vitro fertilization. Furthermore, we were able to discover and fine-map a heritable inter-chromosomal rearrangement t(1;16)(p36;p12) by sequencing a single blastomere. The methods will expedite applications in basic genome research and provide a stepping stone to novel approaches for clinical genetic diagnosis

The Scottish Early Rheumatoid Arthritis (SERA) Study:an inception cohort and biobank

Background: The Scottish Early Rheumatoid Arthritis (SERA) study is an inception cohort of rheumatoid (RA) and undifferentiated arthritis (UA) patients that aims to provide a contemporary description of phenotype and outcome and facilitate discovery of phenotypic and prognostic biomarkers Methods: Demographic and clinical outcome data are collected from newly diagnosed RA/UA patients every 6 months from around Scotland. Health service utilization data is acquired from Information Services Division, NHS National Services Scotland. Plain radiographs of hands and feet are collected at baseline and 12 months. Additional samples of whole blood, plasma, serum and filtered urine are collected at baseline, 6 and 12 months Results: Results are available for 1073 patients; at baseline, 76 % were classified as RA and 24 % as UA. Median time from onset to first review was 163 days (IQR97-323). Methotrexate was first-line DMARD for 75 % patients. Disease activity, functional ability and health-related quality of life improved significantly between baseline and 24 months, however the proportion in any employment fell (51 to 38 %, p = 0.0005). 24 % patients reported symptoms of anxiety and/or depression at baseline. 35/391 (9 %) patients exhibited rapid radiographic progression after 12 months. The SERA Biobank has accrued 60,612 samples Conclusions: In routine care, newly diagnosed RA/UA patients experience significant improvements in disease activity, functional ability and health-related quality of life but have high rates of psychiatric symptoms and declining employment rates. The co-existence of a multi-domain description of phenotype and a comprehensive biobank will facilitate multi-platform translational research to identify predictive markers of phenotype and prognosis

Polygenic in vivo validation of cancer mutations using transposons

The in vivo validation of cancer mutations and genes identified in cancer genomics is resource-intensive because of the low throughput of animal experiments. We describe a mouse model that allows multiple cancer mutations to be validated in each animal line. Animal lines are generated with multiple candidate cancer mutations using transposons. The candidate cancer genes are tagged and randomly expressed in somatic cells, allowing easy identification of the cancer genes involved in the generated tumours. This system presents a useful, generalised and efficient means for animal validation of cancer genes.Link_to_subscribed_fulltex

The genetic heterogeneity and mutational burden of engineered melanomas in zebrafish models.

BACKGROUND: Melanoma is the most deadly form of skin cancer. Expression of oncogenic BRAF or NRAS, which are frequently mutated in human melanomas, promote the formation of nevi but are not sufficient for tumorigenesis. Even with germline mutated p53, these engineered melanomas present with variable onset and pathology, implicating additional somatic mutations in a multi-hit tumorigenic process. RESULTS: To decipher the genetics of these melanomas, we sequence the protein coding exons of 53 primary melanomas generated from several BRAF(V600E) or NRAS(Q61K) driven transgenic zebrafish lines. We find that engineered zebrafish melanomas show an overall low mutation burden, which has a strong, inverse association with the number of initiating germline drivers. Although tumors reveal distinct mutation spectrums, they show mostly C > T transitions without UV light exposure, and enrichment of mutations in melanogenesis, p53 and MAPK signaling. Importantly, a recurrent amplification occurring with pre-configured drivers BRAF(V600E) and p53-/- suggests a novel path of BRAF cooperativity through the protein kinase A pathway. CONCLUSION: This is the first analysis of a melanoma mutational landscape in the absence of UV light, where tumors manifest with remarkably low mutation burden and high heterogeneity. Genotype specific amplification of protein kinase A in cooperation with BRAF and p53 mutation suggests the involvement of melanogenesis in these tumors. This work is important for defining the spectrum of events in BRAF or NRAS driven melanoma in the absence of UV light, and for informed exploitation of models such as transgenic zebrafish to better understand mechanisms leading to human melanoma formation

Mutational processes molding the genomes of 21 breast cancers.

All cancers carry somatic mutations. The patterns of mutation in cancer genomes reflect the DNA damage and repair processes to which cancer cells and their precursors have been exposed. To explore these mechanisms further, we generated catalogs of somatic mutation from 21 breast cancers and applied mathematical methods to extract mutational signatures of the underlying processes. Multiple distinct single- and double-nucleotide substitution signatures were discernible. Cancers with BRCA1 or BRCA2 mutations exhibited a characteristic combination of substitution mutation signatures and a distinctive profile of deletions. Complex relationships between somatic mutation prevalence and transcription were detected. A remarkable phenomenon of localized hypermutation, termed "kataegis," was observed. Regions of kataegis differed between cancers but usually colocalized with somatic rearrangements. Base substitutions in these regions were almost exclusively of cytosine at TpC dinucleotides. The mechanisms underlying most of these mutational signatures are unknown. However, a role for the APOBEC family of cytidine deaminases is proposed

Mutational processes molding the genomes of 21 breast cancers

All cancers carry somatic mutations. The patterns of mutation in cancer genomes reflect the DNA damage and repair processes to which cancer cells and their precursors have been exposed. To explore these mechanisms further, we generated catalogs of somatic mutation from 21 breast cancers and applied mathematical methods to extract mutational signatures of the underlying processes. Multiple distinct single- and double-nucleotide substitution signatures were discernible. Cancers with BRCA1 or BRCA2 mutations exhibited a characteristic combination of substitution mutation signatures and a distinctive profile of deletions. Complex relationships between somatic mutation prevalence and transcription were detected. A remarkable phenomenon of localized hypermutation, termed "kataegis," was observed. Regions of kataegis differed between cancers but usually colocalized with somatic rearrangements. Base substitutions in these regions were almost exclusively of cytosine at TpC dinucleotides. The mechanisms underlying most of these mutational signatures are unknown. However, a role for the APOBEC family of cytidine deaminases is proposed

The life history of 21 breast cancers.

Cancer evolves dynamically as clonal expansions supersede one another driven by shifting selective pressures, mutational processes, and disrupted cancer genes. These processes mark the genome, such that a cancer's life history is encrypted in the somatic mutations present. We developed algorithms to decipher this narrative and applied them to 21 breast cancers. Mutational processes evolve across a cancer's lifespan, with many emerging late but contributing extensive genetic variation. Subclonal diversification is prominent, and most mutations are found in just a fraction of tumor cells. Every tumor has a dominant subclonal lineage, representing more than 50% of tumor cells. Minimal expansion of these subclones occurs until many hundreds to thousands of mutations have accumulated, implying the existence of long-lived, quiescent cell lineages capable of substantial proliferation upon acquisition of enabling genomic changes. Expansion of the dominant subclone to an appreciable mass may therefore represent the final rate-limiting step in a breast cancer's development, triggering diagnosis