263 research outputs found
Robots, drugs, reality and education: how the future will change how we think
Emerging technologies for learning report - Article exploring various future trends and their potential impact on educatio
THE DETERMINATION OF COPPER IN SEA WATER USING FLOW INJECTION WITH CHEMILUMINESCENCE DETECTION
This thesis describes the design, optimisation and shipboard deployment of a flow
injection - chemiluminescence (FI-CL) technique for the determination of labile Cu(II) and
total copper (by UV irradiation) in seawater. The operational parameters of the FI manifold
in a UHP water sample matrix and the 1,10-phenanthroline CL reaction were rigorously
optimised. Interferences to the CL reaction were investigated and the good analytical
figures of merit obtained presented. The FI-CL method was modified for the
determination of ultra trace levels of Cu(II) in seawater by the incorporation of a new
design of micro-column containing 8-hydroxyquinoline (8HQ) resin for in-line matrix
separation and preconcentration. Reagent clean-up techniques, blank procedures and a
standard addition protocol are detailed. The optimised method is selective for Cu(II) in the
linear range 0.1 - 50 nM, with precision of <4% (n=4) for a typical seawater analysis, and a
limit of detection (3s) of 25 pM for a loading time of 90 s.
The FI-CL analyser was fully automated and then validated by field deployment on
the Tamar Estuary, during which its robustness, reliability and stand alone capability were
demonstrated. Good accuracy was achieved for a seawater CRM analysed onboard. The
near real time Cu data obtained was in good agreement with a comparative voltammetric
method.
The FI-CL method was further validated by field deployment on the Atlantic
Meridional Transect (AMT 9) during which Cu(II) (filtered, acidified (pH 2) HNO3) in the
surface waters (<250 m) of the North and South Atlantic (50°N to 50 °S) was mapped.
Spatial variation in Cu(II) concentrations was observed (<0.7 to 6.1 nM) through the
contrasting biogeochemical provinces encountered that representated coastal, upwelling
and oligotrophic regions. Copper (II) enrichments were imposed on a trend of decreasing
Cu(Il) concentrations away from European coastal waters (>2.5 nM) to open ocean gyres
(< 1 nM). Away from strong input mechanisms, upper water column Cu(II) concentrations
were ca. 1.5 nM, being dominated by long range aerosol input mechanisms. Input sources
are fingerprinted via correlation with nutrients and hydrographic data, whilst the dominant
sinks are active biological uptake and particle reactivity. Cu(II) vertical distributions
through the upper mixed layer display strong relationships with chlorophyll α particularly
in remote oceanic regimes.
An in-line UA photo-oxidation system was constructed and optimised for the
digestion of organically complexed Cu to enable near real time determination of total Cu in
seawater by FI-CL. It achieved very efficient digestion of DOM (96.3 %) using a short
irradiation time (600 s), with good recovery of Cu. Robustness, reproducibilty of
irradiation, effective operational life and safety were considerably improved compared to
existing systems. DOM rich Tamar Estuary and Celtic Sea samples were in good agreement
with Cu(II) results from conventional batch UV digestion and voltammetric detection.Plymouth Marine Laborator
Close-Range Photogrammetric Measurement of Static Deflections for an Aeroelastic Supercritical Wing
Close range photogrammetric measurements were made for the lower wing surface of a full span aspect ratio 10.3 aeroelastic supercritical research wing. The measurements were made during wind tunnel tests for quasi-steady pressure distributions on the wing. The tests were conducted in the NASA Langley Transonic Dynamics Tunnel at Mach numbers up to 0.90 and dynamic pressures up to 300 pounds per square foot. Deflection data were obtained for 57 locations on the wing lower surface using dual non-metric cameras. Representative data are presented as graphical overview to show variations and trends of spar deflection with test variables. Comparative data are presented for photogrammetric and cathetometric results of measurements for the wing tip deflections. A tabulation of the basic measurements is presented in a supplement to this report
Evaluation of the Cambridge House Playdagogy Programme: final research report (strand 1)
Evaluation of the Cambridge House Playdagogy Programme: final research report (strand 1
Carboxy terminal tail of polycystin-1 regulates localization of TSC2 to repress mTOR.
Autosomal dominant polycystic kidney disease (ADPKD) is a commonly inherited renal disorder caused by defects in the PKD1 or PKD2 genes. ADPKD is associated with significant morbidity, and is a major underlying cause of end-stage renal failure (ESRF). Commonly, treatment options are limited to the management of hypertension, cardiovascular risk factors, dialysis, and transplantation when ESRF develops, although several new pharmacotherapies, including rapamycin, have shown early promise in animal and human studies. Evidence implicates polycystin-1 (PC-1), the gene product of the PKD1 gene, in regulation of the mTOR pathway. Here we demonstrate a mechanism by which the intracellular, carboxy-terminal tail of polycystin-1 (CP1) regulates mTOR signaling by altering the subcellular localization of the tuberous sclerosis complex 2 (TSC2) tumor suppressor, a gatekeeper for mTOR activity. Phosphorylation of TSC2 at S939 by AKT causes partitioning of TSC2 away from the membrane, its GAP target Rheb, and its activating partner TSC1 to the cytosol via 14-3-3 protein binding. We found that TSC2 and a C-terminal polycystin-1 peptide (CP1) directly interact and that a membrane-tethered CP1 protects TSC2 from AKT phosphorylation at S939, retaining TSC2 at the membrane to inhibit the mTOR pathway. CP1 decreased binding of 14-3-3 proteins to TSC2 and increased the interaction between TSC2 and its activating partner TSC1. Interestingly, while membrane tethering of CP1 was required to activate TSC2 and repress mTOR, the ability of CP1 to inhibit mTOR signaling did not require primary cilia and was independent of AMPK activation. These data identify a unique mechanism for modulation of TSC2 repression of mTOR signaling via membrane retention of this tumor suppressor, and identify PC-1 as a regulator of this downstream component of the PI3K signaling cascade
A coupled compressible flow and geomechanics model for dynamic fracture aperture during carbon sequestration in coal
This paper presents the development of a discrete fracture model of fully coupled compressible fluid flow, adsorption and geomechanics to investigate the dynamic behaviour of fractures in coal. The model is applied in the study of geological carbon dioxide sequestration and differs from the dual porosity model developed in our previous work, with fractures now represented explicitly using lower‐dimensional interface elements. The model consists of the fracture‐matrix fluid transport model, the matrix deformation model and the stress‐strain model for fracture deformation. A sequential implicit numerical method based on Galerkin finite element is employed to numerically solve the coupled governing equations, and verification is completed using published solutions as benchmarks. To explore the dynamic behaviour of fractures for understanding the process of carbon sequestration in coal, the model is used to investigate the effects of gas injection pressure and composition, adsorption and matrix permeability on the dynamic behaviour of fractures. The numerical results indicate that injecting nonadsorbing gas causes a monotonic increase in fracture aperture; however, the evolution of fracture aperture due to gas adsorption is complex due to the swelling‐induced transition from local swelling to macro swelling. The change of fracture aperture is mainly controlled by the normal stress acting on the fracture surface. The fracture aperture initially increases for smaller matrix permeability and then declines after reaching a maximum value. When the local swelling becomes global, fracture aperture starts to rebound. However, when the matrix permeability is larger, the fracture aperture decreases before recovering to a higher value and remaining constant. Gas mixtures containing more carbon dioxide lead to larger closure of fracture aperture compared with those containing more nitrogen
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European ADPKD Forum multidisciplinary position statement on autosomal dominant polycystic kidney disease care: European ADPKD Forum and Multispecialist Roundtable participants.
Autosomal dominant polycystic kidney disease (ADPKD) is a chronic, progressive condition characterized by the development and growth of cysts in the kidneys and other organs and by additional systemic manifestations. Individuals with ADPKD should have access to lifelong, multidisciplinary, specialist and patient-centred care involving: (i) a holistic and comprehensive assessment of the manifestations, complications, prognosis and impact of the disease (in physical, psychological and social terms) on the patient and their family; (ii) access to treatment to relieve symptoms, manage complications, preserve kidney function, lower the risk of cardiovascular disease and maintain quality of life; and (iii) information and support to help patients and their families act as fully informed and active partners in care, i.e. to maintain self-management approaches, deal with the impact of the condition and participate in decision-making regarding healthcare policies, services and research. Building on discussions at an international roundtable of specialists and patient advocates involved in ADPKD care, this article sets out (i) the principles for a patient-centred, holistic approach to the organization and delivery of ADPKD care in practice, with a focus on multispecialist collaboration and shared-decision making, and (ii) the rationale and knowledge base for a route map for ADPKD care intended to help patients navigate the services available to them and to help stakeholders and decision-makers take practical steps to ensure that all patients with ADPKD can access the comprehensive multispecialist care to which they are entitled. Further multispecialty collaboration is encouraged to design and implement these services, and to work with patient organizations to promote awareness building, education and research
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von Hippel-Lindau Disease: an Update
Funder: University of CambridgeAbstract: Purpose of Review: In this review, we discuss the key molecular and clinical developments in VHL disease that have the potential to impact on the natural history of the disease and improve patient outcomes. Recent Findings: Identifiable mutations in VHL underlie most cases of VHL and define clear genotype-phenotype correlations. Detailed clinical and molecular characterisation has allowed the implementation of lifelong screening programmes that have improved clinical outcomes. Functional characterisation of the VHL protein complex has revealed its role in oxygen sensing and the mechanisms of tumourigenesis that are now being exploited to develop novel therapies for VHL and renal cancer. Summary: The molecular and cellular landscape of VHL-associated tumours is revealing new opportunities to modify the natural history of the disease and develop therapies. Drugs are now entering clinical trials and combined with improved clinical and molecular diagnosis, and lifelong surveillance programmes, further progress towards reducing the morbidity and mortality associated with VHL disease is anticipated
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