Global genomic diversity of a major wildlife pathogen: Ranavirus, past and present

Ranavirus is a genus of large double-stranded DNA viruses (family Iridoviridae) that parasitise three taxonomic classes of poikilothermic vertebrates. They are important wildlife pathogens of conservation and economic concern, posing significant threat to amphibian biodiversity and aquaculture commerce. Despite substantial advances since their discovery in the 1960s, the evolutionary history of ranaviruses remains poorly characterised. The aim of this thesis is to advance the characterisation of Ranavirus evolutionary dynamics to contemporary standards. A large whole-genome dataset was collated and scrutinised, combining all publicly available material with a novel collection of isolate genomes. Cutting-edge microbial genomics tools were applied to gain insight into ranavirus genetic diversity, phylogeography, and genome evolution. Delineation of the Ranavirus pan-genome served as a foundation to conduct phylogenetic and population genetic analyses. Where the limitations of alignment-based methodologies were met, alignment-free techniques were employed to make full use of all genomic information. Phylogenetic reconstructions uncovered unique genetic diversity incompatible with current taxonomic demarcations amongst several lineages of Ranavirus. Pervasive genetic recombination was detected across the genus, and certain lineages contained a high degree of ancestral polyphyly. Recurrent patterns linked to animal trade and aquaculture were detected. Extensively polyphyletic viruses were isolated from captive animals, and population genetic analysis revealed ancestry components shared by ranaviruses isolated from farmed animals on separate continents. Finally, phylodynamic analysis suggests human-mediated translocation of FV3-like ranaviruses began more than a century before present. The inadequacies of current Ranavirus taxonomy are highlighted by this work, and suggests a substantial diversity remains to be characterised. The processes by which ranaviral genetic diversity is generated appears particularly dynamic, with significant contributions made via recombination between distinct linages. Altogether, this thesis underscores the vital impact trade and captive rearing of fish and herpetofauna have had on the global spread of ranaviruses and their processes of genetic diversification. Finally, these results suggest that anthropogenic influences commenced decades earlier than previously thought, likely upon the acceleration of modern globalisation

Implementation of the frequency-modulated sideband search method for gravitational waves from low mass X-ray binaries

We describe the practical implementation of the sideband search, a search for periodic gravitational waves from neutron stars in binary systems. The orbital motion of the source in its binary system causes frequency-modulation in the combination of matched filters known as the $\mathcal{F}$-statistic. The sideband search is based on the incoherent summation of these frequency-modulated $\mathcal{F}$-statistic sidebands. It provides a new detection statistic for sources in binary systems, called the $\mathcal{C}$-statistic. The search is well suited to low-mass X-ray binaries, the brightest of which, called Sco X-1, is an ideal target candidate. For sources like Sco X-1, with well constrained orbital parameters, a slight variation on the search is possible. The extra orbital information can be used to approximately demodulate the data from the binary orbital motion in the coherent stage, before incoherently summing the now reduced number of sidebands. We investigate this approach and show that it improves the sensitivity of the standard Sco X-1 directed sideband search. Prior information on the neutron star inclination and gravitational wave polarization can also be used to improve upper limit sensitivity. We estimate the sensitivity of a Sco X-1 directed sideband search on 10 days of LIGO data and show that it can beat previous upper limits in current LIGO data, with a possibility of constraining theoretical upper limits using future advanced instruments.Comment: 20 pages, 5 figure

Radial evolution of sunward strahl electrons in the inner heliosphere

The heliospheric magnetic field (HMF) exhibits local inversions, in which the field apparently “bends back” upon itself. Candidate mechanisms to produce these inversions include various configurations of upstream interchange reconnection; either in the heliosphere, or in the corona where the solar wind is formed. Explaining the source of these inversions, and how they evolve in time and space, is thus an important step towards explaining the origins of the solar wind. Inverted heliospheric magnetic field lines can be identified by the anomalous sunward (i.e. inward) streaming of the typically anti-sunward propagating, field aligned (or anti-aligned), beam of electrons known as the “strahl”. We test if the pitch angle distribution (PAD) properties of sunward-propagating strahl are different from those of outward strahl.We perform a statistical study of strahl observed by the Helios spacecraft, over heliocentric distances spanning ≈ 0.3 – 1 AU. We find that sunward strahl PADs are broader and less intense than their outward directed counterparts; particularly at distances 0.3 – 0.75 AU. This is consistent with sunward strahl being subject to additional, path-length dependent, scattering in comparison to outward strahl.We conclude that the longer and more variable path from the Sun to the spacecraft, along inverted magnetic field, leads to this additional scattering. The results also suggest that the relative importance of scattering along this additional path length drops off with heliocentric distance. These results can be explained by a relatively simple, constant-rate, scattering process

Microgravimetric immunosensor for direct detection of aerosolized influenza A virus particles.

The development and characterization of a quartz crystal microbalance (QCM) sensor for the direct detection of aerosolized influenza A virions is reported. Self-assembled monolayers (SAMs) of mercaptoundecanoic acid (MUA) are formed on QCM gold electrodes to provide a surface amenable for the immobilization of anti-influenza A antibodies using NHS/EDC coupling chemistry. The surface-bound antibody provides a selective and specific sensing interface for the capture of influenza virions. A nebulizer is used to create aerosolized samples and is directly connected to a chamber housing the antibody-modified crystal ("immunochip"). Upon exposure to the aerosolized virus, the interaction between the antibody and virus leads to a dampening of the oscillation frequency of the quartz crystal. The magnitude of frequency change is directly related to virus concentration. Control experiments using aerosols from chicken egg allantoic fluid and an anti-murine antibody based immunosensor confirm that the observed signal originates from specific viral binding on the chip surface. Step-by-step surface modification of MUA assembly, antibody attachment, and antibody-virus interaction are characterized by atomic force microscopy (AFM) imaging analysis. Using the S/N = 3 principle, the limit of detection is estimated to be 4 virus particles/mL. The high sensitivity and real-time sensing scheme presented here can play an important role in the public health arena by offering a new analytical tool for identifying bio-contaminated areas and assisting in timely patient diagnosis

Cardio classics revisited: focus on the role of amlodipine

Amlodipine is a long-acting, dihydropyridine calcium antagonist now widely used for lowering of elevated blood pressure. In recent years it has been shown to be effective in reducing both blood pressure and risk of cardiovascular (CV) events when used in combination with other antihypertensive agents of different classes. Strong evidence of cardiovascular benefit has been attained for combination of amlodipine with diuretics or angiotensin converting enzyme (ACE) inhibitors in a number of high-risk CV groups, including those with established coronary artery disease, diabetes, and at risk of renal disease. Combination therapies of amlodipine with other agents eliciting renin-angiotensin-aldosterone system blockade (angiotensin II receptor blockers or renin inhibitors) have been shown to be effective blood pressure-lowering strategies, but await the results of ongoing trials for direct evidence of benefit for renal disease progression and CV morbidity and mortality

Study of Determined Town and Village Green Applications: Final Report to Common Land Team, Defra

The purpose of the research, as set out in the Project Brief, was to ‘examine a sample of the sites which have been registered as town or village greens (TVGs) since January 2004 as well as a sample of those that have not been registered’. The common term for both successful and unsuccessful applications is that either outcome has been ‘determined’ by Commons Registration Authority (CRA), therefore the study was an investigation into determined town and village green (dTVG) applications. The project also set out to examine whether the sites were earmarked for development in local development plans or subject to planning applications. The full diversity of sites, both approved and rejected, was analysed

SUPPLY AND DEMAND RISKS IN LABORATORY FORWARD AND SPOT MARKETS: IMPLICATIONS FOR AGRICULTURE

Laboratory experimental methods are used to investigate the impacts of supply and/or demand risks on prices, quantities traded, and earnings within forward and spot market institutions. Random demand and/or supply shifts can be as much as 25 percent of the expected equilibrium outcome. Nevertheless, results suggest that the spot or forward trading institution itself has a greater influence on market outcomes than the presence of risk within the trading institutions. Sellers tend to have relatively higher earnings in a spot market than buyers, regardless of the risk. Total surplus, however, generally is greater in a forward market.laboratory markets, forward market, spot market, supply and/or demand risks, Demand and Price Analysis, Marketing,

SUPPLY AND DEMAND RISKS IN FORWARD AND SPOT MARKETS: IMPLICATIONS FOR AGRICULTURE

Laboratory methods are used to investigate the impacts of supply and/or demand risks on prices, quantities traded, and earnings within forward and spot market institutions. Results suggest that the spot or forward trading institution itself has a greater influence on market outcomes than supply/demand risks within the institution.Marketing,

Datasets related to in-land water for limnology and remote sensing applications: distance-to-land, distance-to-water, water-body identifier and lake-centre co-ordinates

Datasets containing information to locate and identify water bodies have been generated from data locating static-water-bodies with resolution of about 300 m (1/360 deg) recently released by the Land Cover Climate Change Initiative (LC CCI) of the European Space Agency. The LC CCI water-bodies dataset has been obtained from multi-temporal metrics based on time series of the backscattered intensity recorded by ASAR on Envisat between 2005 and 2010. The new derived datasets provide coherently: distance to land, distance to water, water-body identifiers and lake-centre locations. The water-body identifier dataset locates the water bodies assigning the identifiers of the Global Lakes and Wetlands Database (GLWD), and lake centres are defined for in-land waters for which GLWD IDs were determined. The new datasets therefore link recent lake/reservoir/wetlands extent to the GLWD, together with a set of coordinates which locates unambiguously the water bodies in the database. Information on distance-to-land for each water cell and the distance-to-water for each land cell has many potential applications in remote sensing, where the applicability of geophysical retrieval algorithms may be affected by the presence of water or land within a satellite field of view (image pixel). During the generation and validation of the datasets some limitations of the GLWD database and of the LC CCI water-bodies mask have been found. Some examples of the inaccuracies/limitations are presented and discussed. Temporal change in water-body extent is common. Future versions of the LC CCI dataset are planned to represent temporal variation, and this will permit these derived datasets to be updated

Adjusting for desert-dust-related biases in a climate data record of sea surface temperature

Atmospheric desert-dust aerosol, primarily from north Africa, causes negative biases in remotely sensed climate data records of sea surface temperature (SST). Here, large-scale bias adjustments are deduced and applied to the v2 climate data record of SST from the European Space Agency Climate Change Initiative (CCI). Unlike SST from infrared sensors, SST measured in situ is not prone to desert-dust bias. An in-situ-based SST analysis is combined with column dust mass from the Modern-Era Retrospective analysis for Research and Applications, Version 2 to deduce a monthly, large-scale adjustment to CCI analysis SSTs. Having reduced the dust-related biases, a further correction for some periods of anomalous satellite calibration is also derived. The corrections will increase the usability of the v2 CCI SST record for oceanographic and climate applications, such as understanding the role of Arabian Sea SSTs in the Indian monsoon. The corrections will also pave the way for a v3 climate data record with improved error characteristics with respect to atmospheric dust aerosol