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The protective mechanisms of protein disulphide isomerase in amyotrophic lateral sclerosis
No full textEmpirical thesis.Bibliography: pages 566-598.Chapter 1. General introductionn -- Chapter 2. Material and methods -- Chapter 3. PDI is protective against ALS-associated mutant cyclin F expressed in neuronal cells -- Chapter 4. Characterising the protective properties of PDI against misfolded proteins in ALS -- Chapter 5. The role of redox activity in the protective function of PDI -- Chapter 6. The role of PDI and its redox activity in FUS-linked ALS -- Chapter 7. Peptides based on PDI's active site are protective in neuronal cells expressing mutant SOD1 -- Chapter 8. General discussion -- References -- Appendices.Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disorder characterised by the degeneration of motor neurons. Numerous genes are linked to ALS both genetically and pathologically. Approximately 10% of ALS cases are familial, and of these cases, approximately 20% are due to mutations in the gene encoding superoxide dismutase 1 (SOD1), and approximately 10% are due to mutations in TAR DNA binding protein 43 (TDP-43) and fused in sarcoma (FUS). A major hallmark observed in ALS is the accumulation of misfolded proteins, containing either SOD1, TDP-43 and FUS, which form aggregates in the cytoplasm of degenerating motor neurons. However, the pathogenic mechanisms of disease in ALS remain poorly understood. Recent evidence suggests that dysfunction to the Endoplasmic Reticulum (ER), resulting in ER stress, is increasingly implicated in ALS pathogenesis. Protein Disulphide Isomerase (PDI) is an ER chaperone which functions as an oxidoreductase, utilising its disulphide interchange activity to oxidise, reduce and isomerase disulphide bonds. Our laboratory has previously demonstrated that PDI overexpression is protective against mutant SOD1, TDP-43 and FUS in neuronal cell cultures. Hence, here we examined that PDI overexpression is also protective against ALS mechanisms of pathogenesis triggered by mutant forms of novel ALS protein, Cyclin F. Previous studies have also identified that PDI's disulphide interchange activity is fundamental for its protective activity. Therefore, here we further investigated the properties of PDI which are important in mediating this activity. Results obtained suggest that PDI's a domain is essential for PDI's protective function, as well as its oxidase activity (capability to form disulphide bonds). These properties were verified in cell culture models expressing mutant FUS. Ultimately, there is a need for more effective therapeutics in ALS, thus, peptides mimicking PDI's a domain and oxidase activity were developed and analysed here for their protective effect in ALS cell models.Mode of access: World wide web1 online resource (xxii, 607 pages) colour illustration
Marine bioregions in Australia: numerical analysis of provinces on the east coast
No full textThesis by publication.Bibliography: pages 41-46.Introduction -- Methods -- Results -- Discussion -- Conclusions -- Appendices.Bioregions, distinct ecological assemblages of flora and fauna, have long been used to aid conservation decisions. Bioregions containing at-risk taxa have routinely been recommended for assignment as Marine Protected Areas (MPA). However, the number, location and extent of bioregions in Australia has been heavily debated over the previous few decades. The current consensus, based on coastal fishes, does not take into account the diverse benthic taxa present. A large dataset of Australian east coast molluscs, assembled from museum collection records of the last 100 years, was analysed to identify bioregions. Latitudinal bands were analysed with an array of methods previously utilised to identify bioregions elsewhere in the world. The number and size of provinces from each method were compared to form a consensus. Faunal turnover was high and consistent across the entire geographic extent, with no distinct separations into bioregions. There was strong support for a distinct Victoria/Tasmania province. Nitrate content, showed the strongest control over southern latitudes and it is likely this province is controlled by nutrient availability. These results suggest that Australian mollusc distributions are potentially controlled by oceanic currents and nutrient supply from southern waters, with the Bass Strait forming the only distinctive distribution control.1 online resource (59 pages : map
MdfA - a model multidrug efflux pump for single-molecule investigations of transport
No full textTheoretical thesis.Bibliography: pages i-vii.Chapter 1. Introduction -- Chapter 2. Materials and methods -- Chapter 3. Characterisation of MdfA mediated efflux of R6G -- Chapter 4. Single - cell imaging of direct R6G efflux by MdfA_CL_V44C/V307C in E. coli -- Chapter 5. Conclusions and future directions.MdfA is an Escherichia coli multidrug efflux pump that has a broad - substrate profile that encompasses cationic, neutral and zwitterionic antimicrobials. MdfA is proposed to operate by an alternating access mechanism, a major substrate translocation mechanism thought to occur throughout a diverse range of transport proteins. However, direct visual evidence for this transport mechanism has not been obtained for any protein. The aim of this research is to explore MdfA as a model for conducting single - molecule Förster resonance energy transfer (sm - FRET) experiments to allow for direct visualisation of the alternating access mechanism, by direct observation of fluorescent substrate transport in parallel with protein domain movement. A prerequisite for this work is to identify a highly fluorescent substrate. This thesis aimed to determine whether MdfA and a Cys - variant of MdfA designed for FRET studies can recognise and transport the highly fluorescent monovalent cation rhodamine 6G (R6G) using fluorescence binding and transport assays. The results demonstrate that R6G is a substrate of MdfA, and that the Cys - variant of MdfA retains sufficient activity as a model for future sm - FRET studies. Moreover, this thesis reports on the first direct visualisation of fluorescence transport mediated by a multidrug efflu x pump at the single - cell level in real - time.1 online resource (VI, 50, vii pages
Environmental protection and community rights: the constitution, mining and the enforcement of community rights for people in rural Thailand
No full textTheoretical thesis.Bibliography: pages 78-891. Introduction -- 2. The Problem -- 3. Methods -- 4. Community rights and sustainable development in mining -- 5. Community rights and mining in Thailand -- 6. Community rights and mining in Australia -- 7. Analysis -- 8. ConclusionSince 1945 human rights have been included in state obligations and duties in the Charter of United Nations and other legal agreements. These instruments describe the need to respect, protect, and fulfill the rights of people of every nationality, place of residence, gender,ethnicity, colour, religion, language, or other status. Human rights have been further elaborated in the context of community or group rights as third generation rights. They are sometimes referred to as "solidarity rights" and mentioned in many international contexts such as in the Universal Declaration of Human Rights, the Rio Declaration, the Convention on Biological Diversity and its Nagoya Protocol. This third generation of human rights includes rights to goods, such as development, peace, a healthy environment, communication,humanitarian assistance, and a share in the common heritage of mankind.Community rights, pertaining to environmental protection have been included in the Constitution of the Kingdom of Thailand since 1997. However, cases have been reported of violations of the written law and the enforcement of community rights. These cases provide the evidence of a gap between the law and its enforcement. This study investigates this gap,particularly in relation to community rights and the mining of natural resources in rural localities in Thailand. Australian laws and practices provide the comparative context for this investigation, including some case studies. This study proposes ways of closing the gap between the Constitution and its enforcement that will aide Thailand's future strengthening of community rights and environmental protection for rural people. These proposals include: a Community Rights Act, policies and additional inclusions in the current legislation.1 online resource (94 pages
Expertise in visual search of medical and non-medical images
No full textTheoretical thesis.Bibliography: pages 202-206Chapter 1: General introduction -- Chapter 2: The time course of rapid target detection and localisation -- Chapter 3: Finding cancer in mammograms: if you know it's there, do you know where? -- Chapter 4: The influence of prior expectation and expertise on attentional cueing in medical images -- Chapter 5: General discussion.This thesis aims to understand the crucial cognitive mechanisms that underpin visual search in medical images and the influence of expertise. Research suggests that experienced radiologists use information from an initial glance at an image to set the basis of their diagnosis. This research explores the information that can be extracted from images regarding the presence and location of a target. I use two stimulus types: real medical images on which I test both novices and expert radiologists, and natural scenes as a model for radiologist search. In Chapter 1, I present an overview of the literature relevant to these aims. Chapter 2 presents two experiments where I showed that a target could be both detected and located in a natural scene after a brief presentation (33 ms), but that visual clutter interferes with performance in a predictable way. In Chapter 3, I showed radiologists were able to detect and localise an abnormality in a mammogram presented for 250 ms at levels better than guessing.Crucially I demonstrated that a normal patient variant, high levels of breast density,affects performance. I conducted an in-depth analysis which emphasises the importance of considering factors such as stimulus variability, response imprecision, and participant guessing. In Chapter 4, I investigated the extent to which expertise guides attention based on prior experience with the prevalence of cancer, using a novel cueing paradigm where a chest radiograph (with or without a suspicious nodule) formed a prime. For naïve observers, an artificially boosted nodule in the prime radiograph guided attention, validating the task. Radiologists viewing true, more subtle nodules did not show the same effect, nor did they show any attentional guidance from cancer prevalence. However, more experienced radiologists seemed to be more sensitive to the subtle nodules than less experienced radiologists, suggesting that viexpertise might boost nodule salience. Finally, in Chapter 5, the implications of these findings are discussed in a broader context along with suggestions for areas of future research. Overall, my research shows that there is a large amount of information available after observers first look at a scene or medical image; more than previously thought. Further, the visual complexity of the display affects performance. Together, the experiments presented in this thesis advance the scientific understanding of the type of information available in the first glance and has clear implications for radiologist teaching and clinical benefits.1 online resource (255 pages
Auditory and visual ERP correlates of gender agreement processing in Dutch and Italian
No full textTheoretical thesis.Bibliography: pages 154-159.Chapter 1: General introduction -- Chapter 2: Syntactic and semantic gender processing in reading: an ERP study on Italian -- Chapter 3: Syntactic and semantic gender processing in listening: an ERP study on Italian -- Chapter 4: Gender and number agreement processing in reading: an ERP study on Dutch -- Chapter 5: Gender and number agreement processing in listening: an ERP study on Dutch -- Chapter 6: General discussion and conclusion.The present thesis revolves around the processing of (linguistic) gender and gender agreement in reading/listening. It focuses on real-time processing which is why event-related potentials (ERPs) were chosen as the preferred experimental method. The studies presented here address questions that pertain to psycholinguistic issues related to gender agreement processing, as well as methodological aspects related to the use of ERPs in agreement studies. The majority of agreement studies apply the so-called 'violation paradigm' (e.g., Osterhout, McLaughlin, Kim, Greenwald, & Inoue, 2004), which means presenting participants with sentences containing agreement errors (agreement mismatch). Since each experiment in this thesis contained a violation paradigm, it is more appropriate to talk about gender disagreement rather than gender agreement processing. Two central issues act as the backbone of this work. Firstly, we study the relationship between gender disagreement and the repair and reanalysis processes as reflected by the late syntactic component (P600; Friederici, 2002; Kaan & Swaab, 2003). In the first two experiments (Chapters 2 and 3), this is achieved by comparing syntactic and semantic gender in Italian. This study is intertwined with the issue of whether semantics can influence syntactic processing and how this is reflected in the P600 component. The last two experiments (Chapters 4 and 5) also investigate the repair mechanism, but by comparing gender and number disagreement in Dutch. The second issue investigated in the current thesis is methodological. It relates to the role of input modality (visual or auditory) and real-time processing with ERPs. Each experiment in this thesis was conducted as a reading study first (Chapters 2 and 4) and then as a listening study (Chapters 3 and 5), thus allowing us to manipulate stimulus duration, as well as the violation recognition point while using identical stimuli. By so doing, we were able to compare reading and listening in terms of the presence/absence of language-related ERP components, as well as their temporal and topographic characteristics. By combining the two research goals, we obtained a more detailed picture of the processes underlying gender agreement and their relationship to language-related ERP components. This introduction provides a general framework for the 4 ensuing experimental chapters. It firstly introduces the technique (ERPs) and its application in the sentence processing field. Afterwards, the theoretical framework for four studies is provided. The introduction ends with the predictions stemming from such framework and with a presentation of the structure of the thesis.Mode of access: World wide web1 online resource (ix, 181 pages) illustration
Deterritorializing gender in Sydney's breakdancing scene: a B-girl's experience of B-boying
No full textTheoretical thesis.Bibliography: pages 285-336Abstract -- Candidate declaration -- Acknowledgements -- Introduction. Where it all began -- Chapter 1. Analysing the breaking 'body' in Sydney -- Chapter 2. Mapping the Hip-Hop assemblage -- Chapter 3. The politics of dancing bodies -- Chapter 4. Just a (B-) girl ' : policing gendered transgressions -- Chapter 5. (De) locating (De)territorializations in the breaking assemblage -- Chapter 6. Potentiality of breaking: people to come -- Conclusion looking to the future -- References - Discography -- Videography -- AppendicesThis thesis critically interrogates how masculinist practices of breakdancing offers a site for the transgression of gendered norms. Drawing on my own experiences as a female within the male-dominated breakdancing scene in Sydney, first as a spectator, then as an active crew member, this thesis questions why so few female participants engage in this creative space, and how breakdancing might be the space to displace and deterritorialise gender. I use analytic autoetthnography and interviews with scene members in collaboration with theoretical frameworks offered by Deleuze and Guttari, Butler, Bourdieu and other feminist and post-structuralist philosophers, to critically examine how the capacities of bodies are constituted and shaped in Sydney's breakdancing scene, and to also locate the potentiality for moments of transgression. In other words, I conceptualize the breaking body as not a 'body' constituted through regulations and assumptions, but as an assemblage open to new rhizomatic connections. Breaking is a space that embraces difference, whereby the rituals of the dance not only augment its capacity to deterritorialize the body, but also facilitate new possibilities for performativities beyond the confines of dominant modes of thought and normative gender construction. Consequently, this thesis attempts to contribute to what I perceive as a significant gap in scholarship on hip-hop, breakdancing, and autoethnographic explorations of Deleuze-Guattarian theory.Mode of access: World wide web1 online resource (345 pages) illustrations, photo
Exploring melismatic singing and the effects of emotional expression in contemporary music
No full textTheoretical thesis.Bibliography: pages 81-96.Chapter one -- Chapter two -- Chapter three -- Chapter four -- Chapter five -- Chapter six.The technique and use of melisma is an under researched area in contemporary vocal studies. Melisma refers to the singing of several notes on one syllable and is a popular vocal technique or device used in a variety of genres. This thesis explores the way melisma may be communicated in Contemporary Popular Music (CPM). This includes the types and contexts of melisma. The thesis is divided into two stages of data collection and analysis. The first stage analyses stylistically different songs from two popular artists, Jessica Mauboy and Justin Timberlake. The purpose of this analysis was to explore the way melisma may be used by CPM artists and to determine whether the use of melisma is influenced by stylistic changes, vocal ability and/or song context. The analyses included a comparison of studio recordings and live recordings from various media platforms. The second stage comprised of semi - structured interviews that were conducted in order to identify the attitudes, views, and understandings of professional singers who engage with melisma in their performance practice. The thesis concludes with a discussion of emergent themes derived from the findings.1 online resource (111 pages
Recreating the images of Chan Master Huineng: a systemic-functional approach to translations of the Platform sutra
No full textTheoretical thesis.Includes bibliographical references.1. Introduction -- 2. Translation of Chinese Buddhist texts, Huineng, and the Platform sutra -- 3. Same Chan master, different images : the story of Huineng and its translations -- 4. Verbs of saying and images of Huineng -- 5. Personal pronouns and images of Huineng -- 6. MOOD & MODALITY and images of Huineng -- 7. Images of Huineng on book covers and in verbal texts -- 8. Paratextual attitude and the image of Huineng -- 9. Text complexity and images of Huineng -- 10. Conclusion.This research applies systemic functional linguistics (SFL) to the comparison of four English translations of the Platform Sutra (Wong 1930; Heng 1977; Cleary 1998 and Cheng 2011), in the field of descriptive translation studies. The Platform Sutra is an ancient Chan Buddhist text that records the public sermons and personal conversations of the Chan master Huineng (638-713).The focus of the research is on the image of Huineng recreated in each translation, with the concept of 'image' defined as the semantic consequence of patterned lexicogrammatical choices in translating the Platform Sutra. The study specifically answers the following two research questions: 1. To what extent is the image of Huineng represented differently in the translations of the Platform Sutra? What particular image is recreated in each translation and how did the translator achieve this? and, 2. Why is a certain image of Huineng recreated in one translation but not the others?The first question is to be answered by conducting a bottom-up analysis from the level of lexicogrammar to that of semantics; and the second question can only be satisfactorily answered by taking the context into consideration.The methodology of the study integrates quantitative and qualitative analyses, with the analytical tools adopted being SysFan (Wu 2000), SysConc (Wu 2003) and Wmatrix (Rayson 2003).The analyses of the four translations are conducted in the form of journal articles from the perspectives of verbs of saying, personal pronouns, MOOD and MODALITY, multimodality and evaluation, and textual complexity, which are within the ideational, interpersonal and textual metafunctions respectively. Results show that different images of the same Chan master Huineng have been recreated in each translation, which are reflected through the recurrent lexicogrammatical choices in the ideational, interpersonal and textual systems, though the influence of each system varies. Both the recreating of images and the lexicogrammatical choices can be further interpreted by taking the context of translation (Field, Tenor, Mode) into consideration.The significance of the present study lies in both its comprehensive analysis of different translations of the same source text from a systemic functional perspective, and its emphasis on religious texts as an invaluable resource for both SFL and translation studies.Mode of access: World wide web1 online resource (xvi, 242 pages diagrams, graphs, table
Bacterial biofilms in healthcare: transmission and control
No full textThesis by publication.Bibliography: pages 252-308.Introduction. So here the tale begins! -- Chapter 1. Literature review -- Chapter 2. Materials and methods -- Chapter 3. Transmission of bacteria from biofilms on dry surfaces -- Chapter 4. Is combination therapying the way forward to biofilm eradication? -- Chapter 6. Impact of positive pressure use combined with disinfectants on eradicating bacterial biofilms in healthcare settings -- Chapter 7. Use of hospital grade chlorine to eradicate bacterial biofilms from healthcare settings -- Chapter 8. General discussion and conclusion -- References -- Appendix.It is estimated that more than 99% of bacteria form biofilm where they survive safely in the slime taking refuge from antimicrobials, host immune responses and environmental stress conditions.Scientific literature demonstrates that more than 85% of chronic infections are currently attributed to biofilm development in human tissues (chronic otitis media, non-healing skin ulcers, persistent perionditis, chronic osteoarthritis) on prosthetic medical devices (contact lenses, implants etc.) and on medical equipment (endoscopes, urinary catheters etc.)Transmission and control of bacterial biofilm to reduce these infections has been quite a challenge for clinicians and scientists worldwide, especially owing to the tough resistive life style of bacteria inside biofilms. This study investigated if bacteria residing in environmental biofilms are a potential source for healthcare associated infections by determining:1) The transferral rate of bacteria from dry-surface biofilms via gloved and un-glovedhands ; 2) Determining the killing efficacy of commonly used disinfectants and sterilisation protocols against dry-surface and traditional hydrated biofilms ; 3) Investigating the killing efficacy of combining a physical stress (topical negative pressure and positive pressure ≤10 atmospheres) with a chemical stress (disinfectants/antiseptics) on dry and hydrated biofilms.To study, in-vitro bacterial biofilm was cultured in PC2 laboratory on coupons using Communicable Disease Control and Prevention biofilm reactor and then tested for transmission and various treatments.We found that dry-surface biofilm bacteria are highly transmissible. Although gloved hands transferred up to six folds fewer bacteria than bare hands, total bacterial numbers transferred was more than the dose required to cause infection.Heat treatment as per the prevailing infection control guidelines, successfully eradicated bacteria in hydrated biofilm, but failed to eradicate dry-surface biofilm when autoclaved at 121°C for up to 30 minutes. Similarly, commonly used disinfectants failed to kill dry surfacebiofilm. However, enhanced killing of biofilm bacteria was achieved when compression pressure treatment was combined with biocides.The current thesis establishes high transmissibility of bacteria from dry surface biofilm affirming it to be a potential source of hospital acquired infections whilst demonstrating that current practised methods of decontamination/sterilization are insufficient to eradicate biofilms forming on dry surfaces. However, promising results were achieved after biofilm treatment with combined pressure and biocides therapy encouraging further evaluation of combination disinfection.Mode of access: World wide web1 online resource (xx, 310 pages) colour illustration