708 research outputs found

    3D geological models and their hydrogeological applications : supporting urban development : a case study in Glasgow-Clyde, UK

    Get PDF
    Urban planners and developers in some parts of the United Kingdom can now access geodata in an easy-to-retrieve and understandable format. 3D attributed geological framework models and associated GIS outputs, developed by the British Geological Survey (BGS), provide a predictive tool for planning site investigations for some of the UK's largest regeneration projects in the Thames and Clyde River catchments. Using the 3D models, planners can get a 3D preview of properties of the subsurface using virtual cross-section and borehole tools in visualisation software, allowing critical decisions to be made before any expensive site investigation takes place, and potentially saving time and money. 3D models can integrate artificial and superficial deposits and bedrock geology, and can be used for recognition of major resources (such as water, thermal and sand and gravel), for example in buried valleys, groundwater modelling and assessing impacts of underground mining. A preliminary groundwater recharge and flow model for a pilot area in Glasgow has been developed using the 3D geological models as a framework. This paper focuses on the River Clyde and the Glasgow conurbation, and the BGS's Clyde Urban Super-Project (CUSP) in particular, which supports major regeneration projects in and around the City of Glasgow in the West of Scotland

    A Novel Signaling Network Essential for Regulating Pseudomonas aeruginosa Biofilm Development

    Get PDF
    The important human pathogen Pseudomonas aeruginosa has been linked to numerous biofilm-related chronic infections. Here, we demonstrate that biofilm formation following the transition to the surface attached lifestyle is regulated by three previously undescribed two-component systems: BfiSR (PA4196-4197) harboring an RpoD-like domain, an OmpR-like BfmSR (PA4101-4102), and MifSR (PA5511-5512) belonging to the family of NtrC-like transcriptional regulators. These two-component systems become sequentially phosphorylated during biofilm formation. Inactivation of bfiS, bfmR, and mifR arrested biofilm formation at the transition to the irreversible attachment, maturation-1 and -2 stages, respectively, as indicated by analyses of biofilm architecture, and protein and phosphoprotein patterns. Moreover, discontinuation of bfiS, bfmR, and mifR expression in established biofilms resulted in the collapse of biofilms to an earlier developmental stage, indicating a requirement for these regulatory systems for the development and maintenance of normal biofilm architecture. Interestingly, inactivation did not affect planktonic growth, motility, polysaccharide production, or initial attachment. Further, we demonstrate the interdependency of this two-component systems network with GacS (PA0928), which was found to play a dual role in biofilm formation. This work describes a novel signal transduction network regulating committed biofilm developmental steps following attachment, in which phosphorelays and two sigma factor-dependent response regulators appear to be key components of the regulatory machinery that coordinates gene expression during P. aeruginosa biofilm development in response to environmental cues

    Finishing the euchromatic sequence of the human genome

    Get PDF
    The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

    Search for top squark production in fully hadronic final states in proton-proton collisions at root s=13 TeV

    Get PDF
    A search for production of the supersymmetric partners of the top quark, top squarks, is presented. The search is based on proton-proton collision events containing multiple jets, no leptons, and large transverse momentum imbalance. The data were collected with the CMS detector at the CERN LHC at a center-of-mass energy of 13 TeV, and correspond to an integrated luminosity of 137 fb(-1). The targeted signal production scenarios are direct and gluino-mediated top squark production, including scenarios in which the top squark and neutralino masses are nearly degenerate. The search utilizes novel algorithms based on deep neural networks that identify hadronically decaying top quarks and W bosons, which are expected in many of the targeted signal models. No statistically significant excess of events is observed relative to the expectation from the standard model, and limits on the top squark production cross section are obtained in the context of simplified supersymmetric models for various production and decay modes. Exclusion limits as high as 1310 GeVare established at the 95% confidence level on the mass of the top squark for direct top squark production models, and as high as 2260 GeV on the mass of the gluino for gluino-mediated top squark production models. These results represent a significant improvement over the results of previous searches for supersymmetry by CMS in the same final state.Peer reviewe

    Observation of tW production in the single-lepton channel in pp collisions at root s=13 TeV

    Get PDF
    A measurement of the cross section of the associated production of a single top quark and a W boson in final states with a muon or electron and jets in proton-proton collisions at root s = 13 TeV is presented. The data correspond to an integrated luminosity of 36 fb(-1) collected with the CMS detector at the CERN LHC in 2016. A boosted decision tree is used to separate the tW signal from the dominant t (t) over bar background, whilst the subleading W+jets and multijet backgrounds are constrained using data-based estimates. This result is the first observation of the tW process in final states containing a muon or electron and jets, with a significance exceeding 5 standard deviations. The cross section is determined to be 89 +/- 4 (stat) +/- 12 (syst) pb, consistent with the standard model.Peer reviewe

    Making geological data accessible to non-geoscientists : a 3D model case history from Glasgow, U.K.

    Get PDF
    The British Geological Survey’s 3D geological framework modelling of the entire Glasgow conurbation and surrounding River Clyde catchment, has been undertaken as part of the Clyde-Urban Super-Project (CUSP) and in partnership with Glasgow City Council and other local and regulatory authorities. The 3D modelling covers an area of complex glacial superficial deposits, overlain by heterogeneous anthropogenic deposits that reflect Glasgow’s industrial heritage, over coal-bearing Palaeozoic bedrock succession deformed by multiple faulting episodes. As such, the geology poses significant interpretive challenges for planners, regulators and engineers. The depth dimension of conventional geological maps is very hard for non-geologists to appreciate. As a result, decision makers rarely take full account of geoscience issues in planning and development; nor do they fully exploit potential subsurface assets. With the advances of 3D hardware and software, it is now possible to combine disparate geoscience data types for a wide range applications and scenarios and to display these data effectively, and in ways that non-geologists can easily understand and use to inform their decisions. Using several 3D modelling packages, but primarily GSI3D and GOCAD® workflows in tandem, we have created 3D models designed to ‘nest’ within each other. Lower resolution regional models (c.1:50,000-scale equivalent) therefore provide the context for higher resolution (1:10,000-scale equivalent), and ultimately site-specific, models. The geological framework models have been attributed with a wide range of parameters such as permeability, aquifer productivity and various engineering properties. They have also been exported to flow modelling packages to model time-series processes such as recharge and flow of groundwater and will be used to model migration of contaminant plumes and carbon dioxide. Man-made objects, such as tunnels and mine workings have been embedded as 3D objects and placed into the 3D geological framework so their relationships to faults and other geological structures can be examined. The models are already assisting in the design and layout of new subsurface infrastructure such as buried utilities, tunnels, and underground storage, as part of Glasgow’s regeneration and redevelopment. They will also help to accurately quantify resources and enable their sustainable exploitation (e.g. aggregates, coal). In particular, the models provide an excellent basis for assessing the sustainable extraction of heat, using ground source heat pumps, from mine waters in Glasgow’s extensive network of abandoned mines. 3D modelling is therefore placing geoscience data and knowledge at the heart of the decision making process. With these data in forms that are interoperable with existing 3D models of surface infrastructure, the vision of an integrated 3 dimensional surfaces and subsurface approach to future city-scale planning is becoming achievable

    Towards attributed, parameterised and fully integrated urban 3D geoscience models and related GIS datasets in the UK

    Get PDF
    Urban regeneration in the UK tackles deprivation stemming from industrial decline. These long-term projects (up to 25 years) are some of Europe’s largest. They implement land recycling, sustainable development and effective management of land and water resources. Those engaged in regeneration and large-scale construction (e.g. Olympic Games 2012 in London) need accessible and readily understood environmental geoscience information. The British Geological Survey (BGS) increasingly meets these needs with interactive, bespoke, 3D attributed geologic models, constructed with GSI3D and other software, and related GIS datasets. Close partnerships with decision-makers, including environmental regulators, help ensure effective data use. For example, in the Clyde Corridor, Scotland’s national regeneration priority, BGS works with Glasgow City Council, delivering 3D models of surficial deposits and bedrock in an urban area undermined for coal and ironstone, and masked by variably contaminated anthropogenic deposits. Comprehensive geochemical datasets are also produced. The models incorporate engineering data, and provide a platform for groundwater recharge and flow models, developed using ZOOM object-oriented software, which will be parameterized with data from a groundwater monitoring network under development. This will facilitate monitoring of groundwater quality and levels during regeneration, and aid assessment of: large-scale remediation of chromium waste; point-source groundwater recharge associated with sustainable urban drainage, a growing part of metropolitan drainage strategy; and the potential for and sustainability of ground source heat from extensive minewaters and aquifers beneath Glasgow

    Biochemical and behavioral effects of PDE10A inhibitors: Relationship to target site occupancy

    No full text
    Phosphodiesterase 10A (PDE10A) inhibitors increase the functionality of striatal medium spiny neurons and produce antipsychotic-like effects in rodents by blocking PDE10A mediated hydrolysis of cAMP and/or cGMP. In the current study, we characterized a radiolabeled PDE10A inhibitor, [3H]BMS-843496, and developed an ex vivo PDE10 binding autoradiographic assay to explore the relationship between PDE10 binding site occupancy and the observed biochemical and behavioral effects of PDE10 inhibitors in mice. [3H]BMS-843496 is a potent PDE10A inhibitor with a binding affinity (KD) of 0.15 nM and a functional selectivity of \u3e100-fold over other PDE subtypes tested. Specific [3H]BMS-843496 binding sites were dominant in the basal ganglia, especially the striatum, with low to moderate binding in the cortical and hippocampal areas, of the mouse and monkey brain. Systemic administration of PDE10 inhibitors produced a dose- and plasma/brain concentration-dependent increase in PDE10A occupancy measured in the striatum. PDE10A occupancy was positively correlated with striatal pCREB expression levels. PDE10A occupancy was also correlated with antipsychotic-like effects measured using the conditioned avoidance response model; a minimum of ∼40% occupancy was typically required to achieve efficacy. In contrast, a clear relationship between PDE10A occupancy and catalepsy scores, a potential extrapyramidal symptom readout in rodent, was not evident
    corecore