The removal of environmental noise in cellular communications by perceptual techniques

This thesis describes the application of a perceptually based spectral subtraction algorithm for the enhancement of non-stationary noise corrupted speech. Through examination of speech enhancement techniques, explanations are given for the choice of magnitude spectral subtraction and how the human auditory system can be modelled for frequency domain speech enhancement. It is discovered, that the cochlea provides the mechanical speech enhancement in the auditory system, through the use of masking. Frequency masking is used in spectral subtraction, to improve the algorithm execution time, and to shape the enhancement process making it sound natural to the ear. A new technique for estimation of background noise is presented, which operates during speech sections as well as pauses. This uses two microphones placed on opposite ends of the cellular handset. Using these, the algorithm determines whether the signal is speech, or noise, by examining the current and next frames presented to each microphone. This allows operation in non-stationary conditions, as the estimation is calculated for each frame, and a speech pause is not required for updating. A voting decision process decides the presence of speech or noise which determines which microphone the estimation is calculated from. The importance of an accurate noise estimate is highlighted with a new technique to reduce the effect of musical noise artifacts in the processed speech. This is a classic drawback of spectral subtraction techniques, and it is shown, that the trade off between noise reduction and speech distortion can be extended by this process. A new method for dealing with musical noise is described, which uses a combination of energy and variance examination of the spectrogram to segregate potential musical noise from desired speech sections. By examination of the spectrogram points surrounding musical noise sections, perceptually relevant values replace the corruption leading to cleaner enhanced speech. Any perceptual speech system requires accurate estimates of the clean speech masking thresholds, to prevent noisy sections being passed through the enhancement untouched. In this thesis, a method for the calculation of the estimated clean speech masking thresholds is derived. Classically, this requires an estimation of the clean speech before the thresholds can be derived, but this results in inaccuracy due to the presence of musical noise and spectral nulls. The new algorithm examines the thresholds produced by the corrupted speech, and the background noise, and from these determines the relationship between the two, to produce an estimate of the clean thresholds, with no operation performed on the actual speech signal. A discrepancy is found between the results for male and female speech, which, by examination of the perceptual process, is shown to be due to the different formant positions in male and female speech. Following the development of these parts, the entire enhancement algorithm is tested on a range of noise scenarios, using male and female speech. The results show, that the proposed algorithm is able to provide adequate performance in terms of noise reduction and speech quality

The figure: beach, verandah, backyard

This research undertakes to examine factors that contribute to make Australian national and cultural identity: shared history, narratives symbols, icons, places and memories that are united by a single political and geographical boundary. In particular, it considers the role of place on Australian national and cultural identity. This is a timely exercise since 'Australianess' is increasingly cited as a factor in federal government policy development. In order to address such a broad and complex area, the agenda has been limited to three specific locations: the beach, the verandah and the backyard. These sites have been selected first because of their prominent iconic status within the notion of 'Australianess' and, second, because of the underlying functional parallels that unite them. The present thesis contends that, unlike the function-specific sites where identity is neutralised by globalised standards of appearance, behaviour and harsh fluorescent light, the beach, the verandah and the backyard are ambiguous zones of in between that provide escape, shelter as well as spiritual sanctuary. The figures engage with the nominated locations in accordance with the significance, the meanings that they ascribe to that particular site. These meanings, however, vary greatly from person to person and from demographic to demographic, hence, the grasp of a universally binding sense of identity becomes a slippery proposition. National and cultural seity - the way we are and the way we perceive ourselves as a unified collective - is conditional to a number of factors, the most enduring and pervasive of these is the sense of place, the landscape, the way we affect it and, reciprocally, the way it affects us. National and cultural identity is never static, but remains in a state of perpetual evolution. It must be continually re-assessed in order to remain abreast of the cultural palimpsest as successive waves and generations of people from a variety of backgrounds, situations, ideas and forms of expression inscribe notions of self into their immediate environment

Overhead Speaker System

There is provided a sound system comprising: a first reflector arranged overhead and to reflect sound into a listening environment, a sound emitting device comprising a sound source and a second reflector, the sound source being configured to direct a sound beam with a first beam angle into the second reflector, the sound emmiting device being any of a horn or parabolic loudspeaker. The second reflector is shaped to reflect the sound beam with a second beam angle towards the first reflector, and the first reflector is shaped such as it reflects the sound beam back to the listening environment with a third beam angle. The second beam angle is less than the first beam angle, and the third beam angle is greater than the second beam angle. There is further provided a sound system wherein three of more reflectors are used to reflect sound back down to the listening environment. Additionally, at least one sound absorbing device of a three dimensional shape is positioned in between the overhead reflectors

Serum AZD7442 (tixagevimab–cilgavimab) concentrations and in vitro IC50 values predict SARS‐CoV‐2 neutralising antibody titres

Abstract Objectives The evolution of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) necessitates rapid methods for assessing monoclonal antibody (mAb) potency against emerging variants. Authentic virus neutralisation assays are considered the gold standard for measuring virus‐neutralising antibody (nAb) titres in serum. However, authentic virus‐based assays pose inherent practical challenges for measuring nAb titres against emerging SARS‐CoV‐2 variants (e.g. storing infectious viruses and testing at biosafety level‐3 facilities). Here, we demonstrate the utility of pseudovirus neutralisation assay data in conjunction with serum mAb concentrations to robustly predict nAb titres in serum. Methods SARS‐CoV‐2 nAb titres were determined via authentic‐ and lentiviral pseudovirus‐based neutralisation assays using serological data from three AZD7442 (tixagevimab–cilgavimab) studies: PROVENT (NCT04625725), TACKLE (NCT04723394) and a phase 1 dose‐ranging study (NCT04507256). AZD7442 serum concentrations were assessed using immunocapture. Serum‐based half‐maximal inhibitory concentration (IC50) values were derived from pseudovirus nAb titres and serum mAb concentrations, and compared with in vitro IC50 measurements. Results nAb titres measured via authentic‐ and lentiviral pseudovirus‐based neutralisation assays were strongly correlated for the ancestral SARS‐CoV‐2 virus and SARS‐CoV‐2 Alpha. Serum AZD7442 concentrations and pseudovirus nAb titres were strongly correlated for multiple SARS‐CoV‐2 variants with all Spearman correlation coefficients ≥ 0.78. Serum‐based IC50 values were similar to in vitro IC50 values for AZD7442, for ancestral SARS‐CoV‐2 and Alpha, Delta, Omicron BA.2 and Omicron BA.4/5 variants. Conclusions These data highlight that serum mAb concentrations and pseudovirus in vitro IC50 values can be used to rapidly predict nAb titres in serum for emerging and historical SARS‐CoV‐2 variants

Nirsevimab binding-site conservation in respiratory syncytial virus fusion glycoprotein worldwide between 1956 and 2021: an analysis of observational study sequencing data

Background: Nirsevimab is an extended half-life monoclonal antibody to the respiratory syncytial virus (RSV) fusion protein that has been developed to protect infants for an entire RSV season. Previous studies have shown that the nirsevimab binding site is highly conserved. However, investigations of the geotemporal evolution of potential escape variants in recent (ie, 2015-2021) RSV seasons have been minimal. Here, we examine prospective RSV surveillance data to assess the geotemporal prevalence of RSV A and B, and functionally characterise the effect of the nirsevimab binding-site substitutions identified between 2015 and 2021. Methods: We assessed the geotemporal prevalence of RSV A and B and nirsevimab binding-site conservation between 2015 and 2021 from three prospective RSV molecular surveillance studies (the US-based OUTSMART-RSV, the global INFORM-RSV, and a pilot study in South Africa). Nirsevimab binding-site substitutions were assessed in an RSV microneutralisation susceptibility assay. We contextualised our findings by assessing fusion-protein sequence diversity from 1956 to 2021 relative to other respiratory-virus envelope glycoproteins using RSV fusion protein sequences published in NCBI GenBank. Findings: We identified 5675 RSV A and RSV B fusion protein sequences (2875 RSV A and 2800 RSV B) from the three surveillance studies (2015-2021). Nearly all (25 [100%] of 25 positions of RSV A fusion proteins and 22 [88%] of 25 positions of RSV B fusion proteins) amino acids within the nirsevimab binding site remained highly conserved between 2015 and 2021. A highly prevalent (ie, >40·0% of all sequences) nirsevimab binding-site Ile206Met:Gln209Arg RSV B polymorphism arose between 2016 and 2021. Nirsevimab neutralised a diverse set of recombinant RSV viruses, including new variants containing binding-site substitutions. RSV B variants with reduced susceptibility to nirsevimab neutralisation were detected at low frequencies (ie, prevalence <1·0%) between 2015 and 2021. We used 3626 RSV fusion-protein sequences published in NCBI GenBank between 1956 and 2021 (2024 RSV and 1602 RSV B) to show that the RSV fusion protein had lower genetic diversity than influenza haemagglutinin and SARS-CoV-2 spike proteins. Interpretation: The nirsevimab binding site was highly conserved between 1956 and 2021. Nirsevimab escape variants were rare and have not increased over time. Funding: AstraZeneca and Sanofi

Nirsevimab binding-site conservation in respiratory syncytial virus fusion glycoprotein worldwide between 1956 and 2021: an analysis of observational study sequencing data

BACKGROUND: Nirsevimab is an extended half-life monoclonal antibody to the respiratory syncytial virus (RSV) fusion protein that has been developed to protect infants for an entire RSV season. Previous studies have shown that the nirsevimab binding site is highly conserved. However, investigations of the geotemporal evolution of potential escape variants in recent (ie, 2015-2021) RSV seasons have been minimal. Here, we examine prospective RSV surveillance data to assess the geotemporal prevalence of RSV A and B, and functionally characterise the effect of the nirsevimab binding-site substitutions identified between 2015 and 2021. METHODS: We assessed the geotemporal prevalence of RSV A and B and nirsevimab binding-site conservation between 2015 and 2021 from three prospective RSV molecular surveillance studies (the US-based OUTSMART-RSV, the global INFORM-RSV, and a pilot study in South Africa). Nirsevimab binding-site substitutions were assessed in an RSV microneutralisation susceptibility assay. We contextualised our findings by assessing fusion-protein sequence diversity from 1956 to 2021 relative to other respiratory-virus envelope glycoproteins using RSV fusion protein sequences published in NCBI GenBank. FINDINGS: We identified 5675 RSV A and RSV B fusion protein sequences (2875 RSV A and 2800 RSV B) from the three surveillance studies (2015-2021). Nearly all (25 [100%] of 25 positions of RSV A fusion proteins and 22 [88%] of 25 positions of RSV B fusion proteins) amino acids within the nirsevimab binding site remained highly conserved between 2015 and 2021. A highly prevalent (ie, >40·0% of all sequences) nirsevimab binding-site Ile206Met:Gln209Arg RSV B polymorphism arose between 2016 and 2021. Nirsevimab neutralised a diverse set of recombinant RSV viruses, including new variants containing binding-site substitutions. RSV B variants with reduced susceptibility to nirsevimab neutralisation were detected at low frequencies (ie, prevalence <1·0%) between 2015 and 2021. We used 3626 RSV fusion-protein sequences published in NCBI GenBank between 1956 and 2021 (2024 RSV and 1602 RSV B) to show that the RSV fusion protein had lower genetic diversity than influenza haemagglutinin and SARS-CoV-2 spike proteins. INTERPRETATION: The nirsevimab binding site was highly conserved between 1956 and 2021. Nirsevimab escape variants were rare and have not increased over time. FUNDING: AstraZeneca and Sanofi