275 research outputs found

    Development of a floating tidal energy system suitable for use in shallow water

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    A proposal is made for the use of a traditional streamwaterwheel suspended between two floating catamaranNPL series demi-hulls as means of generating electricalpower. Two prototype devices, of lengths 1.6m and 4.5m,have been developed, constructed and tested. It was foundthat the concept is sound although greater investment isrequired with regards to the materials and bothhydrodynamic and aerodynamic design of the waterwheelto ensure an economically viable system. The workpresented concentrates on practical aspects associated withdesign, construction and trial testing in Southampton waterof the 4.5m prototype. The relatively low cost, ease ofdeployment, and the fact that conventional boat mooringsystems are effective, combine to make this an attractivealternative energy solution for remote communities

    Thiol-Reactive PODS-Bearing Bifunctional Chelators for the Development of EGFR-Targeting [<sup>18</sup>F]AlF-Affibody Conjugates.

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    Site-selective bioconjugation of cysteine-containing peptides and proteins is currently achieved via a maleimide-thiol reaction (Michael addition). When maleimide-functionalized chelators are used and the resulting bioconjugates are subsequently radiolabeled, instability has been observed both during radiosynthesis and post-injection in vivo, reducing radiochemical yield and negatively impacting performance. Recently, a phenyloxadiazolyl methylsulfone derivative (PODS) was proposed as an alternative to maleimide for the site-selective conjugation and radiolabeling of proteins, demonstrating improved in vitro stability and in vivo performance. Therefore, we have synthesized two novel PODS-bearing bifunctional chelators (NOTA-PODS and NODAGA-PODS) and attached them to the EGFR-targeting affibody molecule ZEGFR:03115. After radiolabeling with the aluminum fluoride complex ([18F]AlF), both conjugates showed good stability in murine serum. When injected in high EGFR-expressing tumor-bearing mice, [18F]AlF-NOTA-PODS-ZEGFR:03115 and [18F]AlF-NODAGA-PODS-ZEGFR:03115 showed similar pharmacokinetics and a specific tumor uptake of 14.1 ± 5.3% and 16.7 ± 4.5% ID/g at 1 h post-injection, respectively. The current results are encouraging for using PODS as an alternative to maleimide-based thiol-selective bioconjugation reactions

    ¹⁸F-meta-fluorobenzylguanidine (¹⁸F-mFBG) to monitor changes in norepinephrine transporter expression in response to therapeutic intervention in neuroblastoma models

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    argeted radiotherapy with {13}^1I-mIBG, a substrate of the human norepinephrine transporter (NET-1), shows promising responses in heavily pre-treated neuroblastoma (NB) patients. Combinatorial approaches that enhance {13}^1I-mIBG tumour uptake are of substantial clinical interest but biomarkers of response are needed. Here, we investigate the potential of {18}^F-mFBG, a positron emission tomography (PET) analogue of the {123}^I-mIBG radiotracer, to quantify NET-1 expression levels in mouse models of NB following treatment with AZD2014, a dual mTOR inhibitor. The response to AZD2014 treatment was evaluated in MYCN amplified NB cell lines (Kelly and SK-N-BE(2)C) by Western blot (WB) and immunohistochemistry. PET quantification of {18}^F-mFBG uptake post-treatment in vivo was performed, and data correlated with NET-1 protein levels measured ex vivo. Following 72 h AZD2014 treatment, in vitro WB analysis indicated decreased mTOR signalling and enhanced NET-1 expression in both cell lines, and {18}^F-mFBG revealed a concentration-dependent increase in NET-1 function. AZD2014 treatment failed however to inhibit mTOR signalling in vivo and did not significantly modulate intratumoural NET-1 activity. Image analysis of {18}^F-mFBG PET data showed correlation to tumour NET-1 protein expression, while further studies are needed to elucidate whether NET-1 upregulation induced by blocking mTOR might be a useful adjunct to {131}^I-mIBG therapy

    The Qt distribution of the Breit current hemisphere in DIS as a probe of small-x broadening effects

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    We study the distribution 1/sigma dsigma/dQt, where Qt is the modulus of the transverse momentum vector, obtained by summing over all hadrons, in the current hemisphere of the DIS Breit frame. We resum the large logarithms in the small Qt region, to next-to--leading logarithmic accuracy, including the non-global logarithms involved. We point out that this observable is simply related to the Drell-Yan vector boson and predicted Higgs Qt spectra at hadron colliders. Comparing our predictions to existing HERA data thus ought to be a valuable source of information on the role or absence of small-x (BFKL) effects, neglected in conventional resummations of such quantities.Comment: 16 pages, 3 figures, uses JHEP3.cl

    On the Strong Scalability of Maritime CFD

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    Since 2004, supercomputer growth hasbeen constrained by energy efficiency rather than raw hardware speeds. Tomaintain exponential growth of overall computing power, a massive growth inparallelization is under way. To keep up with these changes, computationalfluid dynamics (CFD) must improve its strong scalability – its ability tohandle lower cells-per-core ratios and achieve finer-grain parallelization. Amaritime-focused, unstructured, finite-volume code (ReFRESCO) is used toinvestigate the scalability problems for incompressible, viscous CFD using two classicaltest-cases. Existing research suggests that the linear equation-system solveris the main bottleneck to incompressible codes, due to the stiff Poisson pressure equation. Here, these results are expandedby analysing the reasons for this poor scalability. In particular, a number ofalternative linear solvers and preconditioners are tested to determine if thescalability problem can be circumvented, including GMRES, Pipelined-GMRES,Flexible-GMRES and BCGS. Conventional block-wise preconditioners are tested,along with multi-grid preconditioners and smoothers in various configurations.Memory-bandwidth constraints and global communication patterns are found to bethe main bottleneck, and no state-of-the-art solution techniques which solve thestrong-scalability problem satisfactorily could be found. There is significantincentive for more research and development in this area

    Chaotic multigrid methods for the solution of elliptic equations

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    Supercomputer power has been doubling approximately every 14 months for several decades, increasing the capabilities of scientific modelling at a similar rate. However, to utilize these machines effectively for applications such as computational fluid dynamics, improvements to strong scalability are required. Here, the particular focus is on semi-implicit, viscous-flow CFD, where the largest bottleneck to strong scalability is the parallel solution of the linear pressure-correction equation — an elliptic Poisson equation. State-of-the-art linear solvers, such as Krylov subspace or multigrid methods, provide excellent numerical performance for elliptic equations, but do not scale efficiently due to frequent synchronization between processes. Complete desynchronization is possible for basic, Jacobi-like solvers using the theory of ‘chaotic relaxations’. These non-deterministic, chaotic solvers scale superbly, as demonstrated herein, but lack the numerical performance to converge elliptic equations — even with the relatively lax convergence requirements of the example CFD application. However, these chaotic principles can also be applied to multigrid solvers. In this paper, a ‘chaotic-cycle’ algebraic multigrid method is described and implemented as an open-source library. It is tested on a model Poisson equation, and also within the context of CFD. Two CFD test cases are used: the canonical lid-driven cavity flow and the flow simulation of a ship (KVLCC2). The chaotic-cycle multigrid shows good scalability and numerical performance compared to classical V-, W- and F-cycles. On 2048 cores the chaotic-cycle multigrid solver performs up to faster than Flexible-GMRES and faster than classical V-cycle multigrid. Further improvements to chaotic-cycle multigrid can be made, relating to coarse-grid communications and desynchronized residual computations. It is expected that the chaotic-cycle multigrid could be applied to other scientific fields, wherever a scalable elliptic-equation solver is required

    Geographically touring the eastern bloc: British geography, travel cultures and the Cold War

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    This paper considers the role of travel in the generation of geographical knowledge of the eastern bloc by British geographers. Based on oral history and surveys of published work, the paper examines the roles of three kinds of travel experience: individual private travels, tours via state tourist agencies, and tours by academic delegations. Examples are drawn from across the eastern bloc, including the USSR, Poland, Romania, East Germany and Albania. The relationship between travel and publication is addressed, notably within textbooks, and in the Geographical Magazine. The study argues for the extension of accounts of cultures of geographical travel, and seeks to supplement the existing historiography of Cold War geography

    Global and regional trends in particulate air pollution and attributable health burden over the past 50 years

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    Long-term exposure to ambient particulate matter (PM2.5, mass of particles with an aerodynamic dry diameter of < 2.5 μm) is a major risk factor to the global burden of disease. Previous studies have focussed on present day or future health burdens attributed to ambient PM2.5. Few studies have estimated changes in PM2.5 and attributable health burdens over the last few decades, a period where air quality has changed rapidly. Here we used the HadGEM3-UKCA coupled chemistry-climate model, integrated exposure-response relationships, demographic and background disease data to provide the first estimate of the changes in global and regional ambient PM2.5 concentrations and attributable health burdens over the period 1960 to 2009. Over this period, global mean population-weighted PM2.5 concentrations increased by 38%, dominated by increases in China and India. Global attributable deaths increased by 89% to 124% over the period 1960 to 2009, dominated by large increases in China and India. Population growth and ageing contributed mostly to the increases in attributable deaths in China and India, highlighting the importance of demographic trends. In contrast, decreasing PM2.5 concentrations and background disease dominated the reduction in attributable health burden in Europe and the United States. Our results shed light on how future projected trends in demographics and uncertainty in the exposure–response relationship may provide challenges for future air quality policy in Asia
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