Data Acquisition & Management: TU1206 COST Sub-Urban WG2 Report

City authorities and other stakeholders in urban environments produce and have access to a greater density of data than is often the case in lesser populated areas, however, it is often very difficult to collate all relevant information together in a useful and easily communicated manner. With such a wide spectrum of stakeholder groups, each with specialist requirements and differing levels of knowledge, it is extremely challenging to provide effective communication tools that disseminate geoscience data and models as useable information. Information about the subsurface needs to be made available in ways which are appropriate to each type of consumer, from a geotechnical engineer carrying out a site investigation to a member of the public wanting to know if their house is at risk of flooding. Arguably the biggest challenges facing those who attempt to understand urban subsurface environments is developing a reliable and affordable strategy for data acquisition, storage, management and communication. Relationships between geological properties and human processes need to be better understood, this requires a greater understanding of interdisciplinary relationships. Geological Survey Organisations (GSOs), and other public bodies, need to incorporate data from external, sometimes commercial, sources in order to see the whole picture and despite advances in technology which have resulted in more data being made available in digital formats, there remains a large body of analogue data sources which are expensive to digitize. Financial constraints on public authorities and the increasing volumes and variability of data generated means that the current labour intensive processes for acquiring subsurface data are unsustainable. In order to minimize manual processing it is necessary for newly acquired data to be captured and communicated between stakeholders using standardized digital formats that support automated processing

Observing GRBs with the LOFT Wide Field Monitor

LOFT (Large Observatory For X-ray Timing) is one of the four candidate missions currently under assessment study for the M3 mission in ESAs Cosmic Vision program to be launched in 2024. LOFT will carry two instruments with prime sensitivity in the 2-30 keV range: a 10 m2 class large area detector (LAD) with a <1° collimated field of view and a wide field monitor (WFM) instrument. The WFM is based on the coded mask principle, and 5 camera units will provide coverage of more than 1/3 of the sky. The prime goal of the WFM is to detect transient sources to be observed by the LAD. With its wide field of view and good energy resolution of <500 eV, the WFM will be an excellent instrument for detecting and studying GRBs and X-ray flashes. The WFM will be able to detect ~150 gamma ray bursts per year, and a burst alert system will enable the distribution of ~100 GRB positions per year with a ~1 arcmin location accuracy within 30 s of the burst

Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.

We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease

Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ glycosaminoglycan synthesis ) involved in growth . Our results demonstrate that sufficiently large sample sizes can uncover rare and low - frequency variants of moderate to large effect associated with polygenic human phenotypes , and that these variants implicate relevant genes and pathways