253 research outputs found

    Novel use of a Franklin split lens for cycling with hemianopia

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    Purpose: Optical rehabilitation for hemianopia includes the prescription of partial aperture prismatic lenses. Fresnel lenses for this purpose have poor optical quality, while bonded lenses have poor cosmesis and can only be made in glass, creating a potential hazard. Here we present an alternative lens type, which does not reduce contrast sensitivity and which can be made in plastic materials. / Methods: A rotated Franklin split lens was prescribed for the right eye only to provide a full aperture prismatic lens without using a Fresnel prism or bonded lenses. Using different refractive indices in each lens provided a minimal transition in thickness and an acceptable cosmetic appearance. This lens was prescribed to a 34-year-old woman with homonymous right hemianopia. Her contemporaneous comments are presented. / Results: The rotated Franklin split lens provided 18Δ over the temporal edge of the lens. The wearer noticed chromatic aberration with this lens, but was able to cycle comfortably when wearing the lens without any reduction in contrast. / Conclusions: A rotated Franklin split lens can be used for the optical rehabilitation of hemianopia. In this case study, cycling was possible with this lens

    Low-cost leaky feeder communication for mines rescue

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    This is the author accepted manuscript. The final version is available from Taylor and Francis via the DOI in this recordA low-cost, low-weight leaky feeder system is proposed for mines rescue communication, for use when the mine’s permanent communication infrastructure has been compromised by an incident. Unlike the leaky feeders that are permanently installed in some transport tunnels and mines, which are very expensive, bulky and heavy, the system described here relies on the fact that some ordinary coaxial cables leak signal unintentionally. Experimental evaluation of the two main types of low-cost coaxial cable identified a suitable cable and an optimal frequency of 27MHz. Longer range tests characterised the real world underground performance of a system. A range of around a kilometre is achievable but this could be increased substantially by using in-line amplifiers. In comparison to low frequency guidewire systems that have previously been produced for mines rescue use, the method outlined here does not force rescuers to clip handsets to the cable, thereby allowing them much more freedom of movement.Research Fund for Coal and Stee

    Modelling flooding due to runoff from spoil heaps during heavy rainfall

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    This is the final version. Available from Taylor & Francis via the DOI in this record. Flash floods generated by runoff from abandoned spoil heaps have posed great risks to neighbouring areas but there has been little study on the process, so it is difficult to evaluate the effectiveness of runoff retention or detention measures. These events are likely to become more frequent in a future climate change scenario. To provide a means by which interested parties can study such events, including methods of mitigation, a computer modelling approach is proposed using free open-source software. Unlike conventional tools that solve the shallow water equations, the software tool uses a cellular automata approach to reduce the computational overhead. It is also easy to use so it is suitable for use by practitioners who are not hydrology experts. The method is illustrated by modelling a historical flood in the UK involving spoil heap runoff. Good correlation was observed between the characteristics of the actual and simulated flood event.Research Fund for Coal and SteelEngineering and Physical Sciences Research Counci

    Frozen Mode Regime in an Optical Waveguide With Distributed Bragg Reflector

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    We introduce a glide symmetric optical waveguide exhibiting a stationary inflection point (SIP) in the Bloch wavenumber dispersion relation. An SIP is a third order exceptional point of degeneracy (EPD) where three Bloch eigenmodes coalesce to form a so-called frozen mode with vanishing group velocity and diverging amplitude. We show that the incorporation of chirped distributed Bragg reflectors and distributed coupling between waveguides in the periodic structure facilitates the SIP formation and greatly enhances the characteristics of the frozen mode regime. We confirm the existence of an SIP in two ways: by observing the flatness of the dispersion diagram and also by using a coalescence parameter describing the separation of the three eigenvectors collapsing on each other. We find that in the absence of losses, both the quality factor and the group delay at the SIP grow with the cubic power of the cavity length. The frozen mode regime can be very attractive for light amplification and lasing, in optical delay lines, sensors, and modulators.Comment: 11 pages, 14 figure

    Design of a Modified Coupled Resonators Optical Waveguide Supporting a Frozen Mode

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    We design a three-way silicon optical waveguide with the Bloch dispersion relation supporting a stationary inflection point (SIP). The SIP is a third order exceptional point of degeneracy (EPD) where three Bloch modes coalesce forming the frozen mode with greatly enhanced amplitude. The proposed design consists of a coupled resonators optical waveguide (CROW) coupled to a parallel straight waveguide. At any given frequency, this structure supports three pairs of reciprocal Bloch eigenmodes, propagating and/or evanescent. In addition to full-wave simulations, we also employ a so-called ''hybrid model'' that uses transfer matrices obtained from full-wave simulations of sub-blocks of the unit cell. This allows us to account for radiation losses and enables a design procedure based on minimizing the eigenmodes' coalescence parameter. The proposed finite-length CROW displays almost unitary transfer function at the SIP frequency, implying a nearly perfect conversion of the input light into the frozen mode. The group delay and the effective quality factor at the SIP frequency show an N3N^{3} scaling, where NN is the number of unit cells in the cavity. The frozen mode in the CROW can be utilized in various applications like sensors, lasers and optical delay lines.Comment: 14 pages, 17 figure

    The degradation of p53 and its major E3 ligase Mdm2 is differentially dependent on the proteasomal ubiquitin receptor S5a.

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    p53 and its major E3 ligase Mdm2 are both ubiquitinated and targeted to the proteasome for degradation. Despite the importance of this in regulating the p53 pathway, little is known about the mechanisms of proteasomal recognition of ubiquitinated p53 and Mdm2. In this study, we show that knockdown of the proteasomal ubiquitin receptor S5a/PSMD4/Rpn10 inhibits p53 protein degradation and results in the accumulation of ubiquitinated p53. Overexpression of a dominant-negative deletion of S5a lacking its ubiquitin-interacting motifs (UIM)s, but which can be incorporated into the proteasome, also causes the stabilization of p53. Furthermore, small-interferring RNA (siRNA) rescue experiments confirm that the UIMs of S5a are required for the maintenance of low p53 levels. These observations indicate that S5a participates in the recognition of ubiquitinated p53 by the proteasome. In contrast, targeting S5a has no effect on the rate of degradation of Mdm2, indicating that proteasomal recognition of Mdm2 can be mediated by an S5a-independent pathway. S5a knockdown results in an increase in the transcriptional activity of p53. The selective stabilization of p53 and not Mdm2 provides a mechanism for p53 activation. Depletion of S5a causes a p53-dependent decrease in cell proliferation, demonstrating that p53 can have a dominant role in the response to targeting S5a. This study provides evidence for alternative pathways of proteasomal recognition of p53 and Mdm2. Differences in recognition by the proteasome could provide a means to modulate the relative stability of p53 and Mdm2 in response to cellular signals. In addition, they could be exploited for p53-activating therapies. This work shows that the degradation of proteins by the proteasome can be selectively dependent on S5a in human cells, and that this selectivity can extend to an E3 ubiquitin ligase and its substrate

    Antenatal vaccination against Group B streptococcus: attitudes of pregnant women and healthcare professionals in the UK towards participation in clinical trials and routine implementation

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    Introduction : Maternal vaccination is increasingly part of antenatal care in the UK and worldwide. Trials of Group B streptococcus (GBS) vaccines are ongoing. This study investigated the attitudes of pregnant women and healthcare profe ssionals towards antenatal vaccination, both in routine care and a clinical trial setting. Material and methods : Survey of 269 pregnant women, 273 midwives/obstetricians and 97 neonatal doctors across seven sites in the UK assessing attitudes towards antenatal vaccinations, knowledge of GBS, a hypothetical GBS vaccine and participation in clinical vaccine trials. Results : Sixty -eight percent of pregnant women intended to receive a vaccine during their current pregnancy (183/269) and 43% (of all respondents, 115/269) reported they would be very/fairly likely to accept a vaccine against GBS despite only 29% (55/269) knowing what GBS was. This increased to 69% after additional information about GBS was provided. Twenty -four percent of pregnant women reported they would be likely to take part in a clinical trial of an unlicensed GBS vaccine. Fifty -nine percent of maternity professionals and 74% of neonatologists would be likely to recommend participation in a GBS vaccine trial to women , with the vast majority (>99%) willing to be involved in such a study . Incentives to take part cited by pregnant women included extra antenatal scans and the opportunity to be tested for GBS. Conclusion : Pregnant women and healthcare professionals were open to the idea of an antenatal GBS vaccine and involvement in clinical trials of such a vaccine. Education and support from midwives would be key to successful implementation

    Alcohol-related brain damage in humans

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    Chronic excessive alcohol intoxications evoke cumulative damage to tissues and organs. We examined prefrontal cortex (Brodmann’s area (BA) 9) from 20 human alcoholics and 20 age, gender, and postmortem delay matched control subjects. H & E staining and light microscopy of prefrontal cortex tissue revealed a reduction in the levels of cytoskeleton surrounding the nuclei of cortical and subcortical neurons, and a disruption of subcortical neuron patterning in alcoholic subjects. BA 9 tissue homogenisation and one dimensional polyacrylamide gel electrophoresis (PAGE) proteomics of cytosolic proteins identified dramatic reductions in the protein levels of spectrin β II, and α- and β-tubulins in alcoholics, and these were validated and quantitated by Western blotting. We detected a significant increase in α-tubulin acetylation in alcoholics, a non-significant increase in isoaspartate protein damage, but a significant increase in protein isoaspartyl methyltransferase protein levels, the enzyme that triggers isoaspartate damage repair in vivo. There was also a significant reduction in proteasome activity in alcoholics. One dimensional PAGE of membrane-enriched fractions detected a reduction in β-spectrin protein levels, and a significant increase in transmembranous α3 (catalytic) subunit of the Na+,K+-ATPase in alcoholic subjects. However, control subjects retained stable oligomeric forms of α-subunit that were diminished in alcoholics. In alcoholics, significant loss of cytosolic α- and β-tubulins were also seen in caudate nucleus, hippocampus and cerebellum, but to different levels, indicative of brain regional susceptibility to alcohol-related damage. Collectively, these protein changes provide a molecular basis for some of the neuronal and behavioural abnormalities attributed to alcoholics

    Problematic mobile phone use and smartphone addiction across generations: the roles of psychopathological symptoms and smartphone use

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    Contemporary technological advances have led to a significant increase in using mobile technologies. Recent research has pointed to potential problems as a consequence of mobile overuse, including addiction, financial problems, dangerous use (i.e. whilst driving) and prohibited use (i.e. use in forbidden areas). The aim of this study is to extend previous findings regarding the predictive power of psychopathological symptoms (depression, anxiety and stress), mobile phone use (i.e. calls, SMS, time spent on the phone, as well as the engagement in specific smartphone activities) across Generations X and Y on problematic mobile phone use in a sample of 273 adults. Findings revealed prohibited use and dependence were predicted by calls/day, time on the phone and using social media. Only for dependent mobile phone use (rather than prohibited), stress appeared as significant. Using social media and anxiety significantly predicted belonging to Generation Y, with calls per day predicted belonging to Generation X. This finding suggests Generation Y are more likely to use asynchronous social media-based communication, whereas Generation X engage more in synchronous communication. The findings have implications for prevention and awareness-raising efforts of possibly problematic mobile phone use for educators, parents and individuals, particularly including dependence and prohibited use

    Crystal Structure of TDRD3 and Methyl-Arginine Binding Characterization of TDRD3, SMN and SPF30

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    SMN (Survival motor neuron protein) was characterized as a dimethyl-arginine binding protein over ten years ago. TDRD3 (Tudor domain-containing protein 3) and SPF30 (Splicing factor 30 kDa) were found to bind to various methyl-arginine proteins including Sm proteins as well later on. Recently, TDRD3 was shown to be a transcriptional coactivator, and its transcriptional activity is dependent on its ability to bind arginine-methylated histone marks. In this study, we systematically characterized the binding specificity and affinity of the Tudor domains of these three proteins quantitatively. Our results show that TDRD3 preferentially recognizes asymmetrical dimethylated arginine mark, and SMN is a very promiscuous effector molecule, which recognizes different arginine containing sequence motifs and preferentially binds symmetrical dimethylated arginine. SPF30 is the weakest methyl-arginine binder, which only binds the GAR motif sequences in our library. In addition, we also reported high-resolution crystal structures of the Tudor domain of TDRD3 in complex with two small molecules, which occupy the aromatic cage of TDRD3
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