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Investigation of a Histidine-Based Probe for the Exploration of Proteomes
Get PDFLeishmaniasis is a neglected tropical disease which affects 0.7-1 million people per year. Current chemotherapies for leishmaniasis are toxic with long treatment times and reports of increasing resistance, which stresses the importance of this research area. Inositol phosphorylceramide synthase is a membrane bound enzyme that has no direct human homologue, which converts ceramide to inositol phosphorylceramide through the action of a highly conserved HHD catalytic triad. An ideal method to study this enzyme further would be through activity-based protein profiling, however, there are currently no activity-based probes reported that reacts with this type of active site. Therefore, an activity-based probe was designed based on the structure of diethyl pyrocarbonate, a compound known to bind covalently to active site histidine residues. The synthesised activity-based probe was shown to inhibit Leishmania major inositol phosphorylceramide synthase in a simple assay. In addition, the probe was shown to selectively bind to the active site histidine residue in two pure enzyme models; one of which has the same catalytic triad as inositol phosphorylceramide synthase, and the other was an acid base active site histidine residue. Further, this activity-based probe was able to isolate an overexpressed enzyme in the lysate of Escherichia coli as well as bind to intrinsic proteins. Following the function validation of the activity-based probe, preliminary work was started in Leishmania to isolate proteins identify expressed enzymes
Evaporation of Multicomponent Inkjet Printed Droplets
Get PDFInkjet printing allows for the controlled, contactless deposition of functional picolitre
droplets. Industrial applications of droplets are varied and use complex
formulations, the motivation of this thesis was to gain an understanding of how
different solutes change the evaporation behaviour of drying droplets. To that
end I studied solvent mixtures of ethanol, water and ethylene glycol (with and
without ethanol vapour) as well as solutions of sucrose, lactose, sodium chloride,
sodium nitrate and ammonium sulfate. Thus my experiments spanned volatile,
low volatility and involatile solutes with and without crystallisation. In each case
I measured the change in droplet profile over time and how that compared to a
volume-averaged model of droplet evaporation, the direction and speed of internal
(solutal Marangoni) flows by adding tracer particles, and the final deposits.
Using my model I found that all but ethanol-water mixtures developed large
concentration gradients, with involatile solutes accumulating at the liquid-vapour
interface and suppressing evaporation. Sugar droplets approached a high-viscosity
glassy state while salt droplets became supersaturated, leading to fast growing
crystalline structures nucleating. By using picolitre rather than microlitre sessile
drops I uncovered aerosol-like behaviour where salt droplets would stop nucleating
above a certain efflorescence relative humidity.
To directly measure concentration gradients we developed a novel reflectometry
experiment, printing droplets on a silica hemisphere and using the evolving
refractive index difference between droplet fluid and the substrate to determine
the composition. This allowed me to verify the presence of an ethanol residue persisting after the end of solutal Marangoni flows in ethanol-water droplets.
During the solutal Marangoni flows we observed particles migrating across flow streamlines to either the centre or liquid-vapour interface depending on the
system in question. From the reversal of migration direction in response to a flipped ethanol concentration gradient we suggest diffusiophoresis as the cause of
migration, as a number of other mechanisms were ruled out
A Culture of Inquiry: Scientific Thought and its Transmission in the Severn Valley, c. 1090–c. 1150
Get PDFThe twelfth century saw the first appearances of translations of Arabic documents into Latin on astronomy and mathematics in England. This thesis will investigate individuals in the twelfth century Severn Valley interested in the new scientific texts: who owned them, how they got them, and how they used them. Specifically, case studies in the reception of the new sciences will be developed for William of Malmesbury, Walcher of Great Malvern, and John of Worcester. These scholars were chosen because sufficient material survives to illustrate a before-and-after picture in their work, reflecting varying reactions to the new knowledge. A regional study of audience reception of the new sciences has not yet been undertaken. The underlying considerations of this thesis are the intellectual and institutional pre-conditions that may have supported these intellectual endeavours in the Severn Valley and also may have been a draw for scholars in the new sciences, such as Petrus Alfonsi and Adelard of Bath, who sought patronage and employment in the area
OBJECTIFICATION AT WORK: A SYSTEMATIC REVIEW, EMPIRICAL TESTS, AND A RETHINK OF THE “HUMANS-AS-RESOURCES” FORMULA
Get PDFObjectification—treating human beings as instrumental tools that are deprived of agency and experience—is a common element in many management theories and practices. Objectification seems to cater to the needs of employers attempting to maximize profits by objectifying employees. However, objectification undermines target employees’ needs, interests, and well-being. This thesis seeks to address this dilemma by looking into relevant theories and empirical evidence with regard to workplace objectification. I first examine the prevailing logic of objectification in many of labor economics and management theories. Second, I report a systematic review of objectification research that summarizes and integrates what is known about the antecedents and consequences of objectification from three different perspectives: Objectifying others, self-objectification, and experiencing objectification. This review sheds light on the dilemma of objectification, by showing that people often objectify others in order to achieve their extrinsic goals, such as money and power, or to reduce subjectivity uncertainty, while thwarting the objectified targets’ fundamental control, belonging, and self-esteem needs. Third, I present an empirical paper. Despite the negative impacts of objectification on the victims, I argue that objectification may have positive ancillary implications for the perpetrators. Drawing from system justification theory, I posit that especially in an organization characterized by higher power distance, objectifying supervisors would be afforded more power by their subordinates because they would deem such behavior as more typical (i.e., descriptive justification) and more desirable (i.e., prescriptive justification). Two experiments and one field study with supervisor-subordinate dyads were conducted to test the hypotheses. The results showed that when power distance was higher, subordinates afforded more power to an objectifying supervisor through prescriptive (but not descriptive) justification. This thesis contributes to the objectification literature by offering a unifying framework of objectification and by demonstrating when and how supervisor objectification can be rationalized and perpetuated
Preaching and the Revelatory Plot: An Alternative to the Resolution Plot in Narrative Preaching
Get PDFAbstract
This thesis presents the case for the revelatory plot as a framework for narrative preaching. It offers an alternative to the resolution plot with its arc from conflict to climax and resolution and its emphasis on action and event. The revelatory plot is a more open form that prioritizes character and thought, with insights gained through earthed particulars. It is a minor plot form from literature and drama, but this thesis contends it is a significant form in some styles of art, from which preachers can learn. This synthesis of art, homiletics and the revelatory plot constitutes a new and deeply embodied approach.
A revelatory sermon form is developed that unfolds biblical narratives in order to expose emotional, physical, social-economic, political and spiritual realities that are frequently assumed but not stated in the text. This displays the faith of biblical characters practised in the complexities of life and creates a form of preaching where relevance is achieved through identification and recognition. The revelatory style uses language that carries a sense of the reality of God working in the everyday world and engages imagination in all its functions.
A cooperative hermeneutic — where author, text and reader create an arena to progress meaning — provides the hermeneutical underpinning. The epistemological foundation is a form of personal knowledge, and critical realism provides the philosophical standpoint. Theologically, this thesis draws on understandings of creation, the imago Dei and incarnation to affirm the material world and humanity as potential ways to learn about God. This is developed in a theology of revelation, with understandings of God coming through general revelation within an interpretive framework of special revelation. The central thesis is that sermons using a revelatory plot can deliver invitational, relevant and embodied preaching that affirms ordinary faith and embraces the complexity of Christian faith lived in the world
Is sexual dimorphism under present selection in humans?
Get PDFLike most mammalian species, humans show sexual dimorphism: the two sexes exhibit sextypical morphological traits. Humans show dimorphism in the facial structure, body size/shape, physical strength, the amount of and distribution of muscle and fat mass, voice pitch, finger ratios, and the growth of facial and body hair. Such dimorphisms are argued to be sexually selected. This thesis focussed on testing biological fitness benefits as a function of exaggerated sexual dimorphism (masculinity in men; femininity in women) in humans. In Chapter 2, a comprehensive meta-analysis showed that men’s body masculinity (increased strength/muscularity) significantly predicted greater mating/reproductive success. A more masculine voice pitch, increased height, and higher testosterone levels positively predicted mating, but not reproduction. Facial masculinity and finger ratios did not significantly predict either. Chapter 3 focussed on women’s traits. Novel analyses of two archival datasets indicated that women with more appealing faces reported fewer births, but greater offspring survival. Furthermore, a systematic literature review showed no consistent associations between women’s traits and reproductive outcomes, and meta-analyses of men’s and women’s fitness as a function of facial attractiveness showed no relationships. In Chapter 4, we tested whether more dimorphic parents had offspring who showed better health and/or earlier sexual onset in two samples. We detected very few significant associations, whereby fathers with greater facial dominance, strength, and height had offspring in better health, and more facially attractive and healthy-looking fathers had offspring who showed earlier sexual onset. Meta-analysing the relationships between parental facial traits and offspring health across the two samples revealed effects close to zero. Lastly, in Chapter 5 we tested whether more masculine men had partners who were more feminine/attractive, healthier, and/or had higher mate value in two U.K. samples. Men with more masculine bodies had more facially appealing partners, and more facially appealing men had higher partner-rated mate value but self-reported somewhat worse health. Except for the meta-analytic effects in Chapter 2, none of the significant effects here remained after correcting for multiple comparisons. The only robust associations we detected were thus with respect to masculinity in men’s bodies increasing fitness outcomes. Overall, the results from this thesis give very limited support to the notion that other dimorphic traits confer men and women fitness benefits. The implications for human sexual selection models are discussed
Examining the Potential for Isotope Analyses of Carbon, Nitrogen, and Sulphur in Burned Bone from Experimental and Archaeological Contexts.
Get PDFThe aim of this project was to determine whether isotope analyses of carbon, nitrogen and sulphur can be conducted on collagen extracted from burned bone. This project was conducted in two phases: a controlled heating experiment and an archaeological application. The controlled heating experiment used cow (Bos taurus) bone to test the temperature thresholds for the conservation of δ13C, δ15N, and δ34S values. These samples were also used to test the efficacy of Fourier Transform Infrared spectroscopy (FTIR) and colour analysis, for determining the burning intensities experienced by bone burned in unknown conditions.
The experiment showed that δ13C values were relatively unchanged up to 400°C (<2‰ variation), while δ15N values were relatively stable up to 200°C (0.5‰ variation). Values of δ34S were also relatively stable up to 200°C (1.4‰ variation). Colour change and FTIR data were well correlated with the change in isotope ratios. Models estimating burning intensities were created from the FTIR data.
For the archaeological application, samples were selected from two early Anglo-Saxon cemetery sites: Elsham and Cleatham. Samples were selected from both inhumed and cremated individuals. Among the inhumed individuals δ13C values suggested a C3 terrestrial diet and δ15N values suggested protein derived largely from terrestrial herbivores, as expected for the early Anglo-Saxon period. However, δ34S values suggested the consumption of freshwater resources and that this consumption was related to both the age and sex of the individual.
The experimental data shows that there is potential for isotope analyses of cremated remains, as during the cremation process heat exposures are not uniform across the body. The samples selected for the archaeological application, however, were not successful. Bone samples heated in controlled conditions produced viable collagen for isotope analysis; however, there are several differences between experiments conducted in a muffle furnace and open-air pyre cremation that need to be investigated further. Additionally, the influence of taphonomy on collagen survival in burned bone needs to be quantified. Finally, methods of sample selection need to be improved to find bone samples from archaeologically cremated remains that are most likely to retain viable collagen. While there is significant research that must be conducted before this research can be widely applied there are a multitude of cultures that practised cremation throughout history and around the world that could be investigated through the analyses proposed in this project
Locating Truth in the Search for Certainty: A Comparison of Foundationalism in Irenaeus’ Second-Century Writings and in Twenty-First-Century Evangelicalism
Get PDFWith a vast library of literature written on Irenaeus of Lyons, this thesis seeks to offer particular insights regarding prominent secondary literature on the bishop and his legacy in modern evangelicalism. This essay finds that key literature positioned as introductions to Irenaeus do not integrate key sources which are necessary to establish the second-century context of his writings. Instead they rely on Irenaeus’ own account of his context, and a skewed, fourth-century, Eusebian generalisation of earliest Christianity. The mistake of deliberating ideas without analysis of those being targeted is echoed in evangelicalism and, in particular, evangelical appropriations of Irenaeus’ material. This essay also finds that language of the ‘obviousness’ of one’s ideology and claims to ‘common sense’ reduces non-Irenaean and non-evangelical ideologies from the level of ideas to the level of moral integrity. If this reduction is rushed, authors place their literature less in a genre of academic investigation on the level of ideas and closer to a rhetorical exhortation which aims to elevate certainty in the current self.
This paper concludes that to engage in a discussion on the merit of ideas, in both Irenaeus studies and in evangelical appropriations of Irenaeus, critical empathy with non-Irenaean material or non-evangelical material must be demonstrated, respectively.
Among secondary contributions, this paper seeks to incorporate a heightened esteem for Irenaeus’ other extant piece, Demonstration; includes a diagram and associated analysis of the bishop’s truth verification network not before illustrated; and includes the beginnings of a critique of the viewpoints that (a) fundamentalistic evangelicalism and its key tenets (like biblical inerrantism) existed from earliest Christianity, but also (b) that fundamentalistic evangelicalism began with Enlightenment thinking. Instead, this essay attempts to show that the foundationalism which is key to fundamentalistic evangelicalism existed in similar but not identical forms to those in the second century
Between Formenlehre and Cognition: A Puzzle-Based Investigation into the Perceptibility of Classical Syntax
Get PDFA hybrid of theory-based analysis and empirical enquiry, this dissertation seeks to investigate the perceptibility of Classical syntax, ultimately striving to bridge the knowledge gaps that have long existed between the fields of analysis and cognitive science. In particular, the study looks to address the following unknowns: 1) recognition of initial tonic; 2) recognition of tight-knit and loose thematic constructions; and 3) understanding of the contextual nature of cadence. The study centres on the reconstruction of Classical piano sonatas that have been segmented into puzzle pieces using form-functional and sonata theories, an approach that enables the application of syntactical and formal perspectives in an empirical setting, thus giving this study its novelty. The following were hypothesised: 1) sequential accuracy, the ability to process Classical syntax and level of formal training are linearly related; 2) functional recognition, however, is found in any individual familiar with Western musical style regardless of educational background; 3) understanding of Classical syntax is largely Mozartean.
The experiments were carried out virtually and were targeted at subjects that were representative of the spectrum of theoretical expertise. Results collected confirm the ability of subjects to organise formal functions, discern initial tonic given a random mix of harmonic shades, recognise the difference between tight-knit and loose themes and their significance, as well as the prevalence of Mozartean idiom in the cognitive faculty and the linear relationship between expertise and accuracy. Inasmuch as these findings strongly suggest that form-functional relationships are audible, the dissertation argues for the incorporation of both analysis and empirical science in music education, a combination that results in a richer understanding and deeper appreciation of musical processes
Visual Methods of Monitoring the Effect of Wettability on Fines Migration in Sandstones
Get PDFGlobal energy demands are changing, with focus on replacement of hydrocarbons with renewables. However, the reliance on hydrocarbons cannot be removed in the short term, so any methods to improve the efficiency and environmental profile of hydrocarbon extraction are needed. Hydrocarbon extraction rate may be reduced if the formation becomes damaged during the extraction process. This damage may be particularly problematic during low salinity enhanced oil recovery (EOR) and although there are many mechanisms by which this may happen, the mechanism which is of particular interest in this work is that of fines migration, especially in combination with variation of wettability.
This work considers a variety of different methods to investigate the ways in which fine mineral particles move when encountering surfaces with variable wettability, and new test methods to rapidly assess the fines migration potential of a sandstone. Throughout this work, 3D printing is used to assist in these investigations, and hence firstly a comprehensive study of the wettability of commonly used 3D printing materials was undertaken which showed good agreement with the literature. Contributions to the wettability of aspects of the printing process resulting in variation of roughness was also evaluated but did not correlate at the length scales studied. Secondly, a study of the likelihood of removal of fines from sandstones by ultrasonic treatment in various salinity brines was performed, finding increased removal in low salinity brines and giving general agreement to those previously reported in the literature. Finally, several conceptual experiments looking at methods to monitor the movement of fine particles over surfaces of variable wettability, including drop spread and flow through 3D printed flow cells with individual particle tracking, were carried out. The results were compared to flow simulations and showed good agreement between particle tracking and simulated flow
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