10,792 research outputs found

    Variable optical elements for fast focus control

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    In this Review, we survey recent developments in the emerging field of high-speed variable-z-focus optical elements, which are driving important innovations in advanced imaging and materials processing applications. Three-dimensional biomedical imaging, high-throughput industrial inspection, advanced spectroscopies, and other optical characterization and materials modification methods have made great strides forward in recent years due to precise and rapid axial control of light. Three state-of-the-art key optical technologies that enable fast z-focus modulation are reviewed, along with a discussion of the implications of the new developments in variable optical elements and their impact on technologically relevant applications

    Visualisation of Fundamental Movement Skills (FMS): An Iterative Process Using an Overarm Throw

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    Fundamental Movement Skills (FMS) are precursor gross motor skills to more complex or specialised skills and are recognised as important indicators of physical competence, a key component of physical literacy. FMS are predominantly assessed using pre-defined manual methodologies, most commonly the various iterations of the Test of Gross Motor Development. However, such assessments are time-consuming and often require a minimum basic level of training to conduct. Therefore, the overall aim of this thesis was to utilise accelerometry to develop a visualisation concept as part of a feasibility study to support the learning and assessment of FMS, by reducing subjectivity and the overall time taken to conduct a gross motor skill assessment. The overarm throw, an important fundamental movement skill, was specifically selected for the visualisation development as it is an acyclic movement with a distinct initiation and conclusion. Thirteen children (14.8 ± 0.3 years; 9 boys) wore an ActiGraph GT9X Link Inertial Measurement Unit device on the dominant wrist whilst performing a series of overarm throws. This thesis illustrates how the visualisation concept was developed using raw accelerometer data, which was processed and manipulated using MATLAB 2019b software to obtain and depict key throw performance data, including the trajectory and velocity of the wrist during the throw. Overall, this thesis found that the developed visualisation concept can provide strong indicators of throw competency based on the shape of the throw trajectory. Future research should seek to utilise a larger, more diverse, population, and incorporate machine learning. Finally, further work is required to translate this concept to other gross motor skills

    TOWARDS AN UNDERSTANDING OF EFFORTFUL FUNDRAISING EXPERIENCES: USING INTERPRETATIVE PHENOMENOLOGICAL ANALYSIS IN FUNDRAISING RESEARCH

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    Physical-activity oriented community fundraising has experienced an exponential growth in popularity over the past 15 years. The aim of this study was to explore the value of effortful fundraising experiences, from the point of view of participants, and explore the impact that these experiences have on people’s lives. This study used an IPA approach to interview 23 individuals, recognising the role of participants as proxy (nonprofessional) fundraisers for charitable organisations, and the unique organisation donor dynamic that this creates. It also bought together relevant psychological theory related to physical activity fundraising experiences (through a narrative literature review) and used primary interview data to substantiate these. Effortful fundraising experiences are examined in detail to understand their significance to participants, and how such experiences influence their connection with a charity or cause. This was done with an idiographic focus at first, before examining convergences and divergences across the sample. This study found that effortful fundraising experiences can have a profound positive impact upon community fundraisers in both the short and the long term. Additionally, it found that these experiences can be opportunities for charitable organisations to create lasting meaningful relationships with participants, and foster mutually beneficial lifetime relationships with them. Further research is needed to test specific psychological theory in this context, including self-esteem theory, self determination theory, and the martyrdom effect (among others)

    Examining the Impact of Personal Social Media Use at Work on Workplace Outcomes

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    A noticable shift is underway in today’s multi-generational workforce. As younger employees propel digital workforce transformation and embrace technology adoption in the workplace, organisations need to show they are forward-thinking in their digital transformation strategies, and the emergent integration of social media in organisations is reshaping internal communication strategies, in a bid to improve corporate reputations and foster employee engagement. However, the impact of personal social media use on psychological and behavioural workplace outcomes is still debatebale with contrasting results in the literature identifying both positive and negative effects on workplace outcomes among organisational employees. This study seeks to examine this debate through the lens of social capital theory and study personal social media use at work using distinct variables of social use, cognitive use, and hedonic use. A quantitative analysis of data from 419 organisational employees in Jordan using SEM-PLS reveals that personal social media use at work is a double-edged sword as its impact differs by usage types. First, the social use of personal social media at work reduces job burnout, turnover intention, presenteeism, and absenteeism; it also increases job involvement and organisational citizen behaviour. Second, the cognitive use of personal social media at work increases job involvement, organisational citizen behaviour, employee adaptability, and decreases presenteeism and absenteeism; it also increases job burnout and turnover intention. Finally, the hedonic use of personal social media at work carries only negative effects by increasing job burnout and turnover intention. This study contributes to managerial understanding by showing the impact of different types of personal social media usage and recommends that organisations not limit employee access to personal social media within work time, but rather focus on raising awareness of the negative effects of excessive usage on employee well-being and encourage low to moderate use of personal social media at work and other personal and work-related online interaction associated with positive workplace outcomes. It also clarifies the need for further research in regions such as the Middle East with distinct cultural and socio-economic contexts

    Optimizing transcriptomics to study the evolutionary effect of FOXP2

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    The field of genomics was established with the sequencing of the human genome, a pivotal achievement that has allowed us to address various questions in biology from a unique perspective. One question in particular, that of the evolution of human speech, has gripped philosophers, evolutionary biologists, and now genomicists. However, little is known of the genetic basis that allowed humans to evolve the ability to speak. Of the few genes implicated in human speech, one of the most studied is FOXP2, which encodes for the transcription factor Forkhead box protein P2 (FOXP2). FOXP2 is essential for proper speech development and two mutations in the human lineage are believed to have contributed to the evolution of human speech. To address the effect of FOXP2 and investigate its evolutionary contribution to human speech, one can utilize the power of genomics, more specifically gene expression analysis via ribonucleic acid sequencing (RNA-seq). To this end, I first contributed in developing mcSCRB-seq, a highly sensitive, powerful, and efficient single cell RNA-seq (scRNA-seq) protocol. Previously having emerged as a central method for studying cellular heterogeneity and identifying cellular processes, scRNA-seq was a powerful genomic tool but lacked the sensitivity and cost-efficiency of more established protocols. By systematically evaluating each step of the process, I helped find that the addition of polyethylene glycol increased sensitivity by enhancing the cDNA synthesis reaction. This, along with other optimizations resulted in developing a sensitive and flexible protocol that is cost-efficient and ideal in many research settings. A primary motivation driving the extensive optimizations surrounding single cell transcriptomics has been the generation of cellular atlases, which aim to identify and characterize all of the cells in an organism. As such efforts are carried out in a variety of research groups using a number of different RNA-seq protocols, I contributed in an effort to benchmark and standardize scRNA-seq methods. This not only identified methods which may be ideal for the purpose of cell atlas creation, but also highlighted optimizations that could be integrated into existing protocols. Using mcSCRB-seq as a foundation as well as the findings from the scRNA-seq benchmarking, I helped develop prime-seq, a sensitive, robust, and most importantly, affordable bulk RNA-seq protocol. Bulk RNA-seq was frequently overlooked during the efforts to optimize and establish single-cell techniques, even though the method is still extensively used in analyzing gene expression. Introducing early barcoding and reducing library generation costs kept prime-seq cost-efficient, but basing it off of single-cell methods ensured that it would be a sensitive and powerful technique. I helped verify this by benchmarking it against TruSeq generated data and then helped test the robustness by generating prime-seq libraries from over seventeen species. These optimizations resulted in a final protocol that is well suited for investigating gene expression in comprehensive and high-throughput studies. Finally, I utilized prime-seq in order to develop a comprehensive gene expression atlas to study the function of FOXP2 and its role in speech evolution. I used previously generated mouse models: a knockout model containing one non-functional Foxp2 allele and a humanized model, which has a variant Foxp2 allele with two human-specific mutations. To study the effect globally across the mouse, I helped harvest eighteen tissues which were previously identified to express FOXP2. By then comparing the mouse models to wild-type mice, I helped highlight the importance of FOXP2 within lung development and the importance of the human variant allele in the brain. Both mcSCRB-seq and prime-seq have already been used and published in numerous studies to address a variety of biological and biomedical questions. Additionally, my work on FOXP2 not only provides a thorough expression atlas, but also provides a detailed and cost-efficient plan for undertaking a similar study on other genes of interest. Lastly, the studies on FOXP2 done within this work, lay the foundation for future studies investigating the role of FOXP2 in modulating learning behavior, and thereby affecting human speech

    Masculinities, vulnerability and negotiated identity: Understanding the reporting behaviours of men who experience violence or otherwise harmful behaviour, within a sex work context

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    Context The focus of sex work related discussions most commonly falls on female providers of sexual services, and male purchasers. As a result, the often victim-oriented policy response in England and Wales falls short of truly addressing the needs of men who are involved in the sale of sex, with there being limited support available for them and a systemic approach which does not fully recognise the potential for men to face harm within this context. Methods The aim of this study is to explore experiences of and reactions to violence, and otherwise harmful behaviours, faced by men in the context of their sex working, by understanding the lived realities of a sample of men who engage in this type of work. The study takes a phased approach which combines an initial informative quantitative survey, with three subsequent phases of semi-structured interviews with male sex workers, sex work-focused practitioners and police officers. The method is guided by feminist research principles which suggest that reality is situated within those with lived experience, and also by an element of co-creation which has grounded this study within the perspectives of male sex workers from its conception. Findings The findings of this research suggest that all of the men involved in the study had faced at least one of the violent or otherwise harmful behaviours outlined, though reporting of these behaviours was not at all common. Discussions with the male sex working participants, practitioners and the police highlighted the issues related to the structural influences of authority, such as the police, and the social environment, and the internalisation of these wider factors, which create barriers to reporting for groups such as male sex workers and others who face similar social marginalisation. Conclusions This study challenges existing gendered understandings of violence and otherwise harmful behaviour within a sex work context, by highlighting the harmful experiences of men. By exploring these experiences and the reporting behaviours of those involved, the study also proposes a new framework for understanding barriers to reporting, which suggests that these are formed through the influences of formal and informal measures of social control, and the internalisation of these outside influences by the individual. By better understanding the experiences of men, and the barriers to their reporting, this study attempts to nuance a gendered discussion. Within, I propose that in order to better support male sex workers, responses must begin by appreciating the heterogeneity of those involved in sex work and the influence of their individual circumstances and the social environment on their willingness to seek support

    Investigations on influenza A virus morphology

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    Clinical isolates of influenza A virus (IAV) typically form a pleomorphic population of virions that present as a continuum of morphologies broadly classified as filaments, bacilli, and spheres. Laboratory strains of IAV, however present mainly as spherical and bacilliform particles, suggesting a role for filaments in vivo. How these filaments form is not fully understood, but it has previously been shown that mutations in the viral matrix protein (M1) can be determinants of filament formation. In this work we show that filament formation also depends on multiple other genetic factors. To this end, we compared two IAV strains A/equine/Ohio/03 (O/2003) and A/equine/South Africa/4/03 (SA/2003) and found that SA/2003 could form filaments while O/2003 could not, despite no differences in their M1 sequences. To map the genetic basis of this difference, we generated reassortant viruses between O/2003 and SA/2003 and identified segments 1 (encoding polymerase basic protein 2, PB2), 4 (haemagglutinin, HA) and 6 (neuraminidase, NA) as determinants of morphology. We established that single mutations in segments 4 and 6, which alter the HA and NA proteins, alter virion morphology. To our surprise, we also identified three synonymous mutations in segment 1 of the virus that were determinants of filament formation despite not altering any known protein. We then extended this work to unravel the associated mechanisms of this change and found despite some differences in the activity of NA, contribution of HA to filament production, and differences in segment 1 RNA structure, there was no clear underlying mechanism. Given, that we were unable to identify the mechanisms associated with the change in morphology, we further extended this work to identify the factors involved in morphogenesis. To characterize IAV filament morphogenesis we employed cryogenic electron tomography (Cryo-ET) of vitrified equine fibroblasts (E. Derm). Although we were unable to identify any additional factors associated with IAV budding, we were able to generate a robust pipeline for studying filament formation. These results show that M1 is not the only determinant of IAV morphology, and that the ability to form filaments, a poorly studied but natural characteristic of IAV infection, is in fact modulated by multiple proteins and RNA determinants

    Principles of Massively Parallel Sequencing for Engineering and Characterizing Gene Delivery

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    The advent of massively parallel sequencing and synthesis technologies have ushered in a new paradigm of biology, where high throughput screening of billions of nucleid acid molecules and production of libraries of millions of genetic mutants are now routine in labs and clinics. During my Ph.D., I worked to develop data analysis and experimental methods that take advantage of the scale of this data, while making the minimal assumptions necessary for deriving value from their application. My Ph.D. work began with the development of software and principles for analyzing deep mutational scanning data of libraries of engineered AAV capsids. By looking at not only the top variant in a round of directed evolution, but instead a broad distribution of the variants and their phenotypes, we were able to identify AAV variants with enhanced ability to transduce specific cells in the brain after intravenous injection. I then shifted to better understand the phenotypic profile of these engineered variants. To that end, I turned to single-cell RNA sequencing to seek to identify, with high resolution, the delivery profile of these variants in all cell types present in the cortex of a mouse brain. I began by developing infrastructure and tools for dealing with the data analysis demands of these experiments. Then, by delivering an engineered variant to the animal, I was able to use the single-cell RNA sequencing profile, coupled with a sequencing readout of the delivered genetic cargo present in each cell type, to define the variant’s tropism across the full spectrum of cell types in a single step. To increase the throughput of this experimental paradigm, I then worked to develop a multiplexing strategy for delivering up to 7 engineered variants in a single animal, and obtain the same high resolution readout for each variant in a single experiment. Finally, to take a step towards translation to human diagnostics, I leveraged the tools I built for scaling single-cell RNA sequencing studies and worked to develop a protocol for obtaining single-cell immune profiles of low volumes of self-collected blood. This study enabled repeat sampling in a short period of time, and revealed an incredible richness in individual variability and time-of-day dependence of human immune gene expression. Together, my Ph.D. work provides strategies for employing massively parallel sequencing and synthesis for new biological applications, and builds towards a future paradigm where personalized, high-resolution sequencing might be coupled with modular, customized gene therapy delivery.</p

    'Inventions and adventures': the work of the Stevenson engineering firm in Scotland, c. 1830 - c. 1890

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    This thesis examines the work of the nineteenth-century Stevenson civil engineering firm to argue that civil engineering should be approached geographically both because it takes place in and is shaped by particular spaces, but also because the result of such work reshapes space and the relationship between places. Geographers have extensively analysed the ways in which humans have worked to alter environments, but relatively little attention has been paid to engineering as a socially and geographically transformative process, to the technical questions and to the engineering professionals whose work brought about such change. This thesis analyses engineers as social and technical agents of environmental change, rather than viewing their role as the simple implementation of directives developed elsewhere and by others. It combines insights from the history and historical geography of science, environmental history and the history of technology to make a case for the relevance of an historical geography of engineering. The thesis explores these issues through the work of the Stevenson family. The Stevensons were an Edinburgh-based and internationally-renowned firm of engineers who specialised in the construction of coastal infrastructure. The start and end dates of the thesis indicate, broadly, the careers of David and Thomas Stevenson, who jointly managed the family firm under the name D. & T. Stevenson between 1850 and 1886. The empirical basis for this thesis draws upon the detailed analysis of the firm’s archival records: technical publications, project reports, diaries, correspondence, maps, plans and diagrams. The work of the Stevensons—their engineering epistemologies, practices, and professional identities— are examined through four diverse projects undertaken by the firm in the nineteenth century. These projects are: the training of new engineers; surveying and designing improvement works for the rivers Tay and Clyde; the implementation of a coastal sound-based fog signal network; and the failed attempt to expand Wick harbour through the construction of a breakwater. These projects highlight the range of activities undertaken by nineteenth-century engineers and illustrate the ‘making’ of engineers and the work they did by highlighting training and learning, surveying, maintenance, testing, evaluation, repair and the explanation of failure. With reference to these projects and by drawing upon relevant contextual material, the thesis examines the conceptualisation of geographical space and natural forces in engineering, the relationship between science and engineering, the nature of expertise and notions of engineering judgement, and the role of family, legacy and reputation in securing professional credibility and status. This approach challenges older historiographical traditions which portrayed engineers as individual geniuses. The thesis instead understands engineering to be a combination of specialist knowledge and tacit skill and situates engineers within their social and institutional networks of power and authority. In pointing out that some engineering works failed, the thesis challenges the tendency in histories of engineering works to focus on success. It makes the case for an historical geography of engineering as a way of understanding engineering as an activity, a status and as processes which changed human-environment relations
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