56 research outputs found

    Investigating the foot-and-mouth disease virus 3A protein

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    Foot-and-Mouth Disease Virus (FMDV) is a globally important pathogen responsible for causing Foot-and-Mouth Disease (FMD) in wildlife and domestic livestock species and has significant economic impacts. FMD is difficult to control due to its highly infectious nature, wide diversity of host species and the existence of multiple serotypes; therefore, understanding the processes of FMDV infection and viral RNA replication are key to the development of improved diagnostics and vaccines. This thesis investigates the potential roles of the FMDV 3A non-structural protein using a combination of sub-genomic replicons, recombinant viruses and proteomics techniques. The picornavirus 3A protein has previously been linked with roles in replication complex formation, virulence and determining viral host range. This thesis presents findings showing that a naturally occurring deletion in 3A had differing effects on replication in cells lines derived from different natural hosts thereby supporting the conclusion that 3A has an important role in viral host range. Proteomic (immunoprecipitation and mass spectroscopy) investigations were carried out to identify potential cellular interaction partners of FMDV 3A, and the impact on infection and replication of reducing expression of two selected cellular proteins Rab7L1 and TBC1D20 was investigated. The 3A protein of FMDV was shown to include a conserved FFAT motif (which bind the ER resident protein VAP) in its N terminal domain. A role for this motif was also investigated with the results suggesting that the 3A FFAT motif is important for efficient viral replication. Finally, the potential role of 3A to act as the donor of 3B during replication was investigated. Key findings from experiments using FMDV replicons and recombinant viruses showed that full-length P3 and the processing intermediate 3ABBB are not required for viral RNA replication suggesting that the preferred donor of 3B for uridylation is likely a 3BC containing precursor protein

    The Oldest Stars in the Galaxy – Searching for Metal-Poor Stars in the Galactic Bulge

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    The nature of the first generations of stars that formed after the Big Bang is one of the major topics in contemporary astrophysics and cosmology. Such stars formed out of gas that was relatively free of elements heavier than helium, during a time before generations of supernovae had polluted the environment. Previous hunts have found many of these ‘old’ stars in the Galactic halo. However, not all parts of the Milky Way evolved at the same rate. Cosmological models of galaxy formation have drawn the conclusion that, due to the "inside-out" formation of galaxies like the Milky Way, the oldest stars should today preferentially reside close to the centre of the Galaxy – in or near the Galactic bulge. This thesis documents the initial results of the EMBLA Survey, the first successful search for ancient and metal-poor stars in the bulge of the Milky Way. By utilising the metallicity indicator provided by SkyMapper photometry, we were able to search through more than five million bulge stars, looking for those rare objects with extremely low iron abundances. The AAOmega spectrograph on the AAT gave us the opportunity to obtain intermediate- spectroscopy of approximately 350 stars simultaneously; during 24 nights of observing spread over three years, we observed more than 14,000 candidate metal-poor stars to spectroscopically confirm the photometric metallicity estimates. We found that 49% of the stars observed with the AAT had metallicities below [Fe/H]= 1.0, and around 1,000 stars with [Fe/H]< 2.0. This is a remarkable achievement given that previous searches had only found a total of 21 stars with metallicities that low. Thirty-seven of the most metal-poor stars were then observed with high-resolution spectro- scopy using 8 m telescopes like Magellan and the Very Large Telescope (VLT), to determine their detailed chemical compositions. As part of the Gaia-ESO Survey, four stars were observed in 2012 on the VLT, with metallicities of 2.72[Fe/H] 2.48. We then observed a further ten stars with the MIKE spectrograph at Magellan in 2012, and in 2014 we observed a final 23 targets. We have found the first EMP stars in the bulge; nine of our stars have [Fe/H]< 3.0, and one has [Fe/H]= 4.0. We compared the abundances found in our sample with stars of the same metallicities found in the Galactic halo, and found in general similar trends. Unexpectedly, however, we only found one carbon-enhanced metal-poor (CEMP) star (3%) while 20% of halo stars with [Fe/H]< 2.0 are CEMP stars. In order to verify the predicted old ages of our stars, we also investigated their kinematics. We found that half the stars examined have tightly bound orbits; remaining within the inner Galaxy rather than being merely halo stars passing through the bulge region. This is crucial, as the oldest stars are predicted to have the lowest binding energies. The two most metal-poor stars in our sample have binding energies low enough that there is a 50% chance they formed at redshifts of z > 12, which would make them the oldest known objects in the Universe

    Estimating stellar ages and metallicities from parallaxes and broadband photometry - successes and shortcomings

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    A deep understanding of the Milky Way galaxy, its formation and evolution requires observations of huge numbers of stars. Stellar photometry, therefore, provides an economical method to obtain intrinsic stellar parameters. With the addition of distance information - deriving reliable ages from photometry is a possibility. We have developed a Bayesian method that generates 2D probability maps of a star's age and metallicity from photometry and parallax using isochrones. Our synthetic tests show that including a near-UV passband enables us to break the degeneracy between a star's age and metallicity for certain evolutionary stages. It is possible to find well-constrained ages and metallicities for turn-off and sub-giant stars with colours including a U band and a parallax with uncertainty less than ~20%. Metallicities alone are possible for the main sequence and giant branch. We find good agreement with the literature when we apply our method to the Gaia benchmark stars, particularly for turn-off and young stars. Further tests on the old open cluster NGC 188, however, reveal significant limitations in the stellar isochrones. The ages derived for the cluster stars vary with evolutionary stage, such that turn-off ages disagree with those on the sub-giant branch, and metallicities vary significantly throughout. Furthermore, the parameters vary appreciably depending on which colour combinations are used in the derivation. We identify the causes of these mismatches and show that improvements are needed in the modelling of giant branch stars and in the creation and calibration of synthetic near-UV photometry. Our results warn against applying isochrone fitting indiscriminately. In particular, the uncertainty on the stellar models should be quantitatively taken into account. Further efforts to improve the models will result in significant advancements in our ability to study the Galaxy.Comment: Accepted for publication in A&A. 22 pages, 19 figures (+ 6 pages of appendix). Abstract abridged for the arXi

    Dive tourism in Luganville, Vanuatu: shocks, stressors and vulnerability to climate change

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    Luganville is a developing dive tourism destination region (DTDR) in Vanuatu, which relies on tourism. This article reports on the shocks and stressors faced by Luganville’s dive tourism sector and climate change’s exacerbation of these. The study’s methodology was based on rapid rural appraisal and case study principles, involving methods of semistructured interviews, group discussions, and personal observations. Data were analyzed using a thematic analysis approach. Key shocks identified include cyclones, earthquakes, effect on demand due to media footage, and changes to international flights. Main stressors were starfish outbreaks and environmental degradation. Unlike the indigenous communities, expatriates show little concern for the potential impact of climate change, presenting response challenges that must incorporate different perspectives to develop effective adaptation options. Special Issue : scuba diving touris

    The detailed chemical composition of the terrestrial planet host Kepler-10

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    Chemical abundance studies of the Sun and solar twins have demonstrated that the solar composition of refractory elements is depleted when compared to volatile elements, which could be due to the formation of terrestrial planets. In order to further examine this scenario, we conducted a line-by-line differential chemical abundance analysis of the terrestrial planet host Kepler-10 and 14 of its stellar twins. Stellar parameters and elemental abundances of Kepler-10 and its stellar twins were obtained with very high precision using a strictly differential analysis of high quality Canada–France–Hawaii Telescope, Hobby–Eberly Telescope and Magellan spectra. When compared to the majority of thick disc twins, Kepler-10 shows a depletion in the refractory elements relative to the volatile elements, which could be due to the formation of terrestrial planets in the Kepler-10 system. The average abundance pattern corresponds to ∼13 Earth masses, while the two known planets in Kepler-10 system have a combined ∼20 Earth masses. For two of the eight thick disc twins, however, no depletion patterns are found. Although our results demonstrate that several factors [e.g. planet signature, stellar age, stellar birth location and Galactic chemical evolution (GCE)] could lead to or affect abundance trends with condensation temperature, we find that the trends give further support for the planetary signature hypothesis

    HIP 10725: The first solar twin/analogue field blue straggler

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    Context. Blue stragglers are easy to identify in globular clusters, but are much harder to identify in the field. Here we present the serendipitous discovery of one field blue straggler, HIP 10725, that closely matches the Sun in mass and age, but with a metallicity slightly lower than solar. Aims. We characterise the solar twin/analogue HIP 10725 to assess whether this star is a blue straggler. Methods. We employed spectra with high resolution (R ~ 105) and high signal-to-noise ratio (330) obtained with UVES at the VLT to perform a differential abundance analysis of the solar analogue HIP 10725. Radial velocities obtained by other instruments were also used to check for binarity. We also studied its chromospheric activity, age, and rotational velocity. Results. HIP 10725 is severely depleted in beryllium ([ Be/H ] ≤ −1.2 dex) for its stellar parameters and age. The abundances relative to solar of the elements with Z ≤ 30 show a correlation with condensation temperature, and the neutron capture elements produced by the s-process are greatly enhanced, while the r-process elements seem normal. We found its projected rotational velocity (vsini = 3.3 ± 0.1 km s-1) to be significantly higher than solar and incompatible with its isochrone-derived age. Radial velocity monitoring shows that the star has a binary companion. Conclusions. Based on the high s-process element enhancements and low beryllium abundance, we suggest that HIP 10725 has been polluted by mass transfer from an AGB star that probably had an initial mass of about 2 M⊙. The radial velocity variations suggest the presence of an unseen binary companion, probably the remnant of a former AGB star. Isochrones predict a solar-age star, but this disagrees with the high projected rotational velocity and high chromospheric activity. We conclude that HIP 10725 is a field blue straggler, rejuvenated by the mass-transfer process of its former AGB companion

    Abnormal P300 in people with high risk of developing psychosis

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    Background Individuals with an “at-risk mental state” (or “prodromal” symptoms) have a 20–40% chance of developing psychosis; however it is difficult to predict which of them will become ill on the basis of their clinical symptoms alone. We examined whether neurophysiological markers could help to identify those who are particularly vulnerable. Method 35 cases meeting PACE criteria for the at-risk mental state (ARMS) and 57 controls performed an auditory oddball task whilst their electroencephalogram was recorded. The latency and amplitude of the P300 and N100 waves were compared between groups using linear regression. Results The P300 amplitude was significantly reduced in the ARMS group [8.6 ± 6.4 microvolt] compared to controls [12.7 ± 5.8 microvolt] (p < 0.01). There were no group differences in P300 latency or in the amplitude and latency of the N100. Of the at-risk subjects that were followed up, seven (21%) developed psychosis. Conclusion Reduction in the amplitude of the P300 is associated with an increased vulnerability to psychosis. Neurophysiological and other biological markers may be of use to predict clinical outcomes in populations at high risk

    The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

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    Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients
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