934 research outputs found

    Invisible cyclists? Disabled people and cycle planning–A case study of London

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    This paper reports on analysis of over 50 London transport and cycling strategy documents. Both image and text were analysed, in exploring representations of disabled people, particularly as cyclists or potential cyclists. It remains unusual for disabled people's cycling to be considered within broader transport strategy documents; instead they are overwhelmingly conceptualised as public transport users and pedestrians. By contrast it was more usual for cycling strategies to at least mention disabled people as cyclists or potential cyclists. However, discussion of policies that might increase disabled people's participation in cycling was often limited to general aspirations or references to leisure cycling clubs and training. Few images in cycling strategies (and even less so transport strategies) showed non-standard cycles of the kind used by some disabled cyclists. Disabled people's cycling (and barriers to cycling) needs further research and a policy approach that targets social and structural exclusion from cycling, not only individual ability and attitudes. More thought needs to be given to a range of types of disability and how these might affect cycling needs

    Adjacent mutations in the gating loop of Kir6.2 produce neonatal diabetes and hyperinsulinism

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    K(ATP) channels regulate insulin secretion from pancreatic beta-cells. Loss- and gain-of-function mutations in the genes encoding the Kir6.2 and SUR1 subunits of this channel cause hyperinsulinism of infancy and neonatal diabetes, respectively. We report two novel mutations in the gating loop of Kir6.2 which cause neonatal diabetes with developmental delay (T293N) and hyperinsulinism (T294M). These mutations increase (T293N) or decrease (T294M) whole-cell K(ATP) currents, accounting for the different clinical phenotypes. The T293N mutation increases the intrinsic channel open probability (Po((0))), thereby indirectly decreasing channel inhibition by ATP and increasing whole-cell currents. T294M channels exhibit a dramatically reduced Po((0)) in the homozygous but not in the pseudo-heterozygous state. Unlike wild-type channels, hetT294M channels were activated by MgADP in the absence but not in the presence of MgATP; however, they are activated by MgGDP in both the absence and presence of MgGTP. These mutations demonstrate the importance of the gating loop of Kir channels in regulating Po((0)) and further suggest that Mg-nucleotide interaction with SUR1 may reduce ATP inhibition at Kir6.2.We thank the Wellcome Trust (076436/Z/05/Z and 081188/A/06/Z), the Royal Society and the European Union (EuroDia, SHM‐CT‐2006‐518513 and EDICT, 201924) for support. FMA is a Royal Society Research Professor. Brittany Zadek was supported by an OXION studentship and Sarah Flanagan by a Sir Graham Wilkins Research Fellowship

    Disturbance distance: quantifying forests' vulnerability to disturbance under current and future conditions

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    Disturbances, both natural and anthropogenic, are critical determinants of forest structure, function, and distribution. The vulnerability of forests to potential changes in disturbance rates remains largely unknown. Here, we developed a framework for quantifying and mapping the vulnerability of forests to changes in disturbance rates. By comparing recent estimates of observed forest disturbance rates over a sample of contiguous US forests to modeled rates of disturbance resulting in forest loss, a novel index of vulnerability, Disturbance Distance, was produced. Sample results indicate that 20% of current US forestland could be lost if disturbance rates were to double, with southwestern forests showing highest vulnerability. Under a future climate scenario, the majority of US forests showed capabilities of withstanding higher rates of disturbance then under the current climate scenario, which may buffer some impacts of intensified forest disturbanceinfo:eu-repo/semantics/publishedVersio

    Epifania, recriação e ressentimento: fragmentos narrativos sobre a experiĂȘncia da viagem na imigração italiana no Brasil

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    L'expĂ©rience du voyage dans le processus de l'immigration marque le premier contact avec l'inconnu. L'aventure de la traversĂ©e de l'ocĂ©an signifie par consĂ©quent l'abandon du seul monde tangible. Le nouveau monde va se dĂ©voiler Ă  l'Ă©migrant au fur et Ă  mesure que le navire avance en mer, en un mĂ©lange de reprĂ©sentations produites avant le dĂ©part et de nouvelles “idĂ©es-images” que l'expĂ©rience elle-mĂȘme du voyage contribue Ă  Ă©laborer en continu. Au cours de ce processus, la lecture de "Sull'Oceano" d’Edmondo De Amicis permet une immersion dans ce monde fragmentaire d'images et des rĂ©cits que l'Ă©migrant va produire. Il tente par ce biais de comprendre sa propre expĂ©rience et son existence, en un monde entrecroisĂ© de diffĂ©rentes expressions de la sensibilitĂ©. LĂȘ nouveau monde se rĂ©vĂšle, souvenir tout Ă  la fois d’une terre que l’on a abandonnĂ©e et recrĂ©ation d'une reprĂ©sentation pacificatrice

    Continued glacial retreat linked to changing macronutrient supply along the West Antarctic Peninsula

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    At the West Antarctic Peninsula (WAP), continued atmospheric and oceanic warming is causing significant physical and biogeochemical changes to glaciers and the marine environment. We compare sediment sources and drivers of macronutrient distributions at two bays along the WAP during austral summer 2020, using radioactive radium and stable oxygen isotopes to trace sedimentary influences and quantify different freshwater inputs. In the Ryder Bay, where the Sheldon Glacier is marine-terminating, radium activities at the sediment-water interface indicate considerable benthic mixing. Using radium isotope activity gradients to resolve radium and macronutrient fluxes, we find buoyant meltwater proximal to the glacier drives vigorous mixing of sediment and entrainment of macronutrient deep waters, on the order of 2.0 × 105 mol d−1 for nitrate. Conversely, in the Marian Cove, where the Fourcade Glacier terminates on land, low salinities and oxygen isotopes indicate a meltwater-rich surface layer <1 m thick and rich in sediment, and strong vertical mixing to the seafloor. A continued shift to land-terminating glaciers along the WAP may have a significant impact upon nutrient and sediment supply to the euphotic zone, with impacts upon primary productivity and carbon uptake efficiency. The future of primary production, carbon uptake, and food web dynamics is therefore linked to glacier retreat dynamics in the many fjords along the WAP

    Consistency of Field-Based Measures of Neuromuscular Control Using Force Plate Diagnostics in Elite Male Youth Soccer Players

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    Consistency of field-based measures of neuromuscular control using force-plate diagnostics in elite male youth soccer players. J Strength Cond Res 30(12): 3304–3311, 2016—Deficits in neuromuscular control during movement patterns such as landing are suggested pathomechanics that underlie sport-related injury. A common mode of assessment is measurement of landing forces during jumping tasks; however, these measures have been used less frequently in male youth soccer players, and reliability data are sparse. The aim of this study was to examine the reliability of a field-based neuromuscular control screening battery using force-plate diagnostics in this cohort. Twenty-six pre–peak height velocity (PHV) and 25 post-PHV elite male youth soccer players completed a drop vertical jump (DVJ), single-leg 75% horizontal hop and stick (75%HOP), and single-leg countermovement jump (SLCMJ). Measures of peak landing vertical ground reaction force (pVGRF), time to stabilization, time to pVGRF, and pVGRF asymmetry were recorded. A test-retest design was used, and reliability statistics included change in mean, intraclass correlation coefficient, and coefficient of variation (CV). No significant differences in mean score were reported for any of the assessed variables between test sessions. In both groups, pVGRF and asymmetry during the 75%HOP and SLCMJ demonstrated largely acceptable reliability (CV ≀ 10%). Greater variability was evident in DVJ pVGRF and all other assessed variables, across the 3 protocols (CV range = 13.8–49.7%). Intraclass correlation coefficient values ranged from small to large and were generally higher in the post-PHV players. The results of this study suggest that pVGRF and asymmetry can be reliably assessed using a 75%HOP and SLCMJ in this cohort. These measures could be used to support a screening battery for elite male youth soccer players and for test-retest comparison

    Analysis of transcription factors key for mouse pancreatic development establishes NKX2-2 and MNX1 mutations as causes of neonatal diabetes in man

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    notes: PMCID: PMC3887257This is a freely-available open access publication. Please cite the published version which is available via the DOI link in this record.Understanding transcriptional regulation of pancreatic development is required to advance current efforts in developing beta cell replacement therapies for patients with diabetes. Current knowledge of key transcriptional regulators has predominantly come from mouse studies, with rare, naturally occurring mutations establishing their relevance in man. This study used a combination of homozygosity analysis and Sanger sequencing in 37 consanguineous patients with permanent neonatal diabetes to search for homozygous mutations in 29 transcription factor genes important for murine pancreatic development. We identified homozygous mutations in 7 different genes in 11 unrelated patients and show that NKX2-2 and MNX1 are etiological genes for neonatal diabetes, thus confirming their key role in development of the human pancreas. The similar phenotype of the patients with recessive mutations and mice with inactivation of a transcription factor gene support there being common steps critical for pancreatic development and validate the use of rodent models for beta cell development.Wellcome TrustDiabetes UKEuropean Community’s Seventh Framework Programme (FP7/2007-2013

    Upper limits on the strength of periodic gravitational waves from PSR J1939+2134

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    The first science run of the LIGO and GEO gravitational wave detectors presented the opportunity to test methods of searching for gravitational waves from known pulsars. Here we present new direct upper limits on the strength of waves from the pulsar PSR J1939+2134 using two independent analysis methods, one in the frequency domain using frequentist statistics and one in the time domain using Bayesian inference. Both methods show that the strain amplitude at Earth from this pulsar is less than a few times 10−2210^{-22}.Comment: 7 pages, 1 figure, to appear in the Proceedings of the 5th Edoardo Amaldi Conference on Gravitational Waves, Tirrenia, Pisa, Italy, 6-11 July 200

    Improving the sensitivity to gravitational-wave sources by modifying the input-output optics of advanced interferometers

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    We study frequency dependent (FD) input-output schemes for signal-recycling interferometers, the baseline design of Advanced LIGO and the current configuration of GEO 600. Complementary to a recent proposal by Harms et al. to use FD input squeezing and ordinary homodyne detection, we explore a scheme which uses ordinary squeezed vacuum, but FD readout. Both schemes, which are sub-optimal among all possible input-output schemes, provide a global noise suppression by the power squeeze factor, while being realizable by using detuned Fabry-Perot cavities as input/output filters. At high frequencies, the two schemes are shown to be equivalent, while at low frequencies our scheme gives better performance than that of Harms et al., and is nearly fully optimal. We then study the sensitivity improvement achievable by these schemes in Advanced LIGO era (with 30-m filter cavities and current estimates of filter-mirror losses and thermal noise), for neutron star binary inspirals, and for narrowband GW sources such as low-mass X-ray binaries and known radio pulsars. Optical losses are shown to be a major obstacle for the actual implementation of these techniques in Advanced LIGO. On time scales of third-generation interferometers, like EURO/LIGO-III (~2012), with kilometer-scale filter cavities, a signal-recycling interferometer with the FD readout scheme explored in this paper can have performances comparable to existing proposals. [abridged]Comment: Figs. 9 and 12 corrected; Appendix added for narrowband data analysi
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