Modulation of oxidative damage by selenium compounds

Myeloperoxidase (MPO) is the primary enzyme responsible for the production of strong oxidants by neutrophils in response to pathogens. One of the major oxidants produced is hypochlorous acid (HOCl), which can react with amine groups to form the secondary oxidants N-chloramines. These oxidants play a role in the destruction of pathogens, however they also have the potential to damage host cells, and have been implicated in numerous inflammatory diseases. This Thesis explores the potential for selenium containing compounds and enzymes to act as catalytic oxidant scavengers. Reaction rates between MPO-derived oxidants and selenium compounds were determined product characterization of products performed. The reduction of the oxidised products, selenoxides, was examined and the rate constant for the thiol reduction of selenoxides determined. It is demonstrated that selenium and sulfur containing enzymes are capable of scavenging these oxidants, as well as reversing the formation of selenoxides. The ability of selenium compounds to protect against damage induced by treatment of cells with HOCl and N-chloramines was also assessed. Overall, selenium containing compounds and enzymes show potential in scavenging these oxidants with endogenous thiols capable of reversing the oxidised selenium products, making them a potential therapeutic intervention in inflammatory conditions

Modulation of oxidative damage by selenium compounds

Myeloperoxidase (MPO) is the primary enzyme responsible for the production of strong oxidants by neutrophils in response to pathogens. One of the major oxidants produced is hypochlorous acid (HOCl), which can react with amine groups to form the secondary oxidants N-chloramines. These oxidants play a role in the destruction of pathogens, however they also have the potential to damage host cells, and have been implicated in numerous inflammatory diseases. This Thesis explores the potential for selenium containing compounds and enzymes to act as catalytic oxidant scavengers. Reaction rates between MPO-derived oxidants and selenium compounds were determined product characterization of products performed. The reduction of the oxidised products, selenoxides, was examined and the rate constant for the thiol reduction of selenoxides determined. It is demonstrated that selenium and sulfur containing enzymes are capable of scavenging these oxidants, as well as reversing the formation of selenoxides. The ability of selenium compounds to protect against damage induced by treatment of cells with HOCl and N-chloramines was also assessed. Overall, selenium containing compounds and enzymes show potential in scavenging these oxidants with endogenous thiols capable of reversing the oxidised selenium products, making them a potential therapeutic intervention in inflammatory conditions

Intonational variation in the North-West of England:The origins of a rising contour in Liverpool

This paper investigates intonation in the urban dialect of Liverpool, Scouse. Scouse is reported to be part of a group of dialects in the north of the UK where rising contours in declaratives are a traditional aspect of the dialect. This intonation is typologically unusual and has not been the subject of detailed previous research. Here, we present such an analysis in comparison to Manchester, a city less than 40 miles from Liverpool but with a noticeably different prosody. Our analysis confirms reports that rising contours are the most common realisation in Liverpool, specifically a low rise where final high pitch is not reached until the end of the phrase. Secondly, we consider the origin of declarative rises in Scouse with reference to the literature on new dialect formation. Our demographic analysis and review of previous work on relevant dialects suggests that declarative rises were not the majority variant when Scouse was formed but may have been adopted for facilitating communication in a diverse new community. We highlight this contribution of intonational data to research on phonological aspects of new dialect formation, which have largely considered segmental phonology or timing previously

Benchmarking Quantum Processor Performance at Scale

As quantum processors grow, new performance benchmarks are required to capture the full quality of the devices at scale. While quantum volume is an excellent benchmark, it focuses on the highest quality subset of the device and so is unable to indicate the average performance over a large number of connected qubits. Furthermore, it is a discrete pass/fail and so is not reflective of continuous improvements in hardware nor does it provide quantitative direction to large-scale algorithms. For example, there may be value in error mitigated Hamiltonian simulation at scale with devices unable to pass strict quantum volume tests. Here we discuss a scalable benchmark which measures the fidelity of a connecting set of two-qubit gates over $N$ qubits by measuring gate errors using simultaneous direct randomized benchmarking in disjoint layers. Our layer fidelity can be easily related to algorithmic run time, via $\gamma$ defined in Ref.\cite{berg2022probabilistic} that can be used to estimate the number of circuits required for error mitigation. The protocol is efficient and obtains all the pair rates in the layered structure. Compared to regular (isolated) RB this approach is sensitive to crosstalk. As an example we measure a $N=80~(100)$ qubit layer fidelity on a 127 qubit fixed-coupling "Eagle" processor (ibm\_sherbrooke) of 0.26(0.19) and on the 133 qubit tunable-coupling "Heron" processor (ibm\_montecarlo) of 0.61(0.26). This can easily be expressed as a layer size independent quantity, error per layered gate (EPLG), which is here $1.7\times10^{-2}(1.7\times10^{-2})$ for ibm\_sherbrooke and $6.2\times10^{-3}(1.2\times10^{-2})$ for ibm\_montecarlo.Comment: 15 pages, 8 figures (including appendices

How negative feedback and the ambient environment limit the influence of recombination in common envelope evolution

We perform 3D hydrodynamical simulations to study recombination and ionization during the common envelope (CE) phase of binary evolution, and develop techniques to track the ionic transitions in time and space. We simulate the interaction of a $2\,M_\odot$ red giant branch primary and a $1\,M_\odot$ companion modeled as a particle. We compare a run employing a tabulated equation of state (EOS) that accounts for ionization and recombination, with a run employing an ideal gas EOS. During the first half of the simulations, $\sim15$ per cent more mass is unbound in the tabulated EOS run due to the release of recombination energy, but by simulation end the difference has become negligible. We explain this as being a consequence of (i) the tabulated EOS run experiences a shallower inspiral and hence smaller orbital energy release at late times because recombination energy release expands the envelope and reduces drag, and (ii) collision and mixing between expanding envelope gas, ejecta and circumstellar ambient gas assists in unbinding the envelope, but does so less efficiently in the tabulated EOS run where some of the energy transferred to bound envelope gas is used for ionization. The rate of mass unbinding is approximately constant in the last half of the simulations and the orbital separation steadily decreases at late times. A simple linear extrapolation predicts a CE phase duration of $\sim2\,\mathrm{yr}$, after which the envelope would be unbound.Comment: Submitted to MNRA