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Electrolyte Solvation Structure Manipulation and Synthetic Optimization for Enhanced Potassium Storage of Tin Phosphide/Carbon Alloy-Based Electrode
No full textPhosphorus-based materials are considered to be reliable anode materials for potassium ion batteries (PIBs) due to their high theoretical capacity but suffer from inferior cycling stability and an unstable Solid Electrolyte Interface (SEI) layer. Herein, optimized ball-milled parameters and concentrated electrolytes are introduced to enhance the electrochemical performance of Sn4P3/C anodes. Consequently, the electrodes synthesized under optimized ball milling parameters could deliver a reversible capacity of 307.8 mA h g−1 in diluted Potassium hexafluorophosphate (KPF6) electrolyte. Moreover, compared with diluted bis(fluorosulfonyl)imide (KFSI) electrolyte, a robust inorganic KF-rich SEI layer can be formed on the electrode’s surface by employing concentrated KFSI electrolyte and provides more rapid K ion conduction rates. Meanwhile, a large proportion of the FSI− anions participated in the K+ solvation shell when the KFSI concentration increased. As a result, high specific capacities (225.1 mA h g−1 at 50 mA g−1 after 200 cycles) and excellent Coulombic efficiency (97.24% at 500 mA g−1 after 200 cycles) can be achieved. This work may deepen our understanding of synthetic optimization in electrode material design and the role of concentrated electrolyte in tunning the solvation structure, and also offer an insightful clue to the design of high-capacity phosphorus-based anodes.</p
For a rainbow to be seen, the sun must be behind an observer who is facing falling rain
No full textThis practice-led PhD project consisting of a manuscript of poetry and dissertation, explores poetry as a translation of, and emergence out of, a photography practice. Through this translation of one medium into another, I have devised the term ‘light-writing’, as both the form and method of my poetry. Drawing on queer theorists, affect theorists and poetics scholars, alongside a careful selection of critical writing made by practising poets and artists, I suggest that light-writing does critical aesthetic and theoretical work with the poetic image, and opens space for thinking and feeling with difference. This approach is demonstrated through a full-length manuscript of poetry, entitled In the Printed Version of Heaven, which layers the affective power of image to reach through varied forms of address, both observational and self-reflexive. Drawing on poetic techniques which generate juxtaposition, such as collage, ekphrasis, self-address, and negation, the lyric voice of these poems present simultaneously as: gentle-delusional-philosophical-threatening-gay.
The dissertation, For a Rainbow to be Seen, the Sun Must be Behind an Observer Who is Facing Falling Rain, as a critical form of light-writing, contextualises my poetry. It does this by framing each chapter around different concerns. These include the process of developing the manuscript, structuring devices used to organise the work, and questions of tone in relation to my lyric voice. Light-writing in this thesis is inscribed as both a form and method; for creating impossible images; navigating the crossing and collapse of boundaries; and for synthesising what I describe as a self-ridiculous lyric voice. In this diverse array of what light-writing signifies, including ascribing poetic images as slyly critical aesthetic surfaces, the project reveals itself as 'a special alignment of things'
Transforming Pakistan’s hospitals: are high-performance work systems and ethical leadership the answer?
No full textGlobally, public healthcare is under pressure to improve efficiency and effectiveness in providing high-quality healthcare within allocated budgets. The challenges facing healthcare in developing countries are exacerbated by high rates of poverty, rapid population growth and scarce resources. Based on the applications of social exchange and social learning theories, this thesis focused on the public healthcare sector in Pakistan and investigated the roles of contemporary human resource management (HRM) practices and ethical leadership (EL) in influencing employee attitudes and behaviours in two teaching tertiary care public hospitals in Lahore, Pakistan. In that respect, the thesis examined the extent to which high-performance work systems (HPWS) influenced employees’ affective commitment (AC) and organisational citizenship behaviour (OCB). Additionally, the thesis examined the mediation role of AC in the relationship between a) HPWS and OCB and b) EL and OCB. Finally, the thesis examined the moderating role of ethical leadership in several relationships between HPWS influenced AC and OCB.
The study employed a case study research approach in which mixed methods were utilised to obtain the perspectives of both leaders and employees through qualitative and quantitative methods. The leadership perspective was based on semi-structured interviews and hospital documentation. Data included ten key informants from Peace Hospital (Case 1) and 12 key informants from Hope Hospital (Case 2) to develop an in-depth understanding of their leadership roles and the HRM practices in their hospitals. The data were analysed through thematic analysis. The themes were identified through the questions in the interview schedule and the literature review. Later, the employees’ perspectives were obtained through a large-scale survey of 266 front-line doctors and nurses from Peace Hospital and 548 front-line doctors and nurses from Hope Hospital. The survey obtained information on employees’ workplace experiences and perceptions related to HPWS, ethical leadership, AC, and OCB. The data were analysed using SPSS for descriptive and inferential analysis and AMOS for hypothesis testing while applying a structural equation modelling approach.
Four main themes emerged from the qualitative data analysis. The first theme highlighted the structure and practice of HRM in both hospitals. This theme had three sub-themes: recruitment and selection, training and development, performance appraisal and career development. The second theme was leadership and managerial challenges, using the lens of contemporary HRM practices (i.e., HPWS). This theme was also divided into three sub-themes: status differentials, information sharing and teamwork. The third theme was related to employee outcomes – attitudes and behaviour focusing on employees’ commitment and behaviours. The fourth theme was related to the leadership and managerial qualities of successful leaders.
From the quantitative data analyses, several major substantive findings emerged. First, for Peace Hospital, an increase in employee perception of HPWS had a significant but negative impact on OCB. However, for Hope Hospital, an increase in employee perception of HPWS led to a positive and significant effect on OCB. Second, for both hospitals, affective commitment played a mediating role in improving the effect of HPWS on OCB. However, for Peace Hospital, the mediating effect of affective commitment on OCB transformed the negative effect of HPWS on OCB into a positive effect. Third, for Peace hospital, employee perception of ethical leadership moderated the mediating effect of affective commitment on the relationship between HPWS and OCB. On the contrary, for Hope hospital, employee perception of ethical leadership did not moderate the mediating effect of affective commitment on the relationship between HPWS and OCB. Fourth, for both hospitals, all four direct relationships between HPWS and affective commitment, ethical leadership and affective commitment, ethical leadership and OCB, and affective commitment and OCB showed a positive and significant effect. Finally, for both hospitals, affective commitment mediated the relationship between ethical leadership and OCB.
Theoretically, this study offered new insights into the mechanisms through which HPWS and EL impact employees’ attitudes and behaviour within a public healthcare setting. Specifically, the study argues for the role of ethical leadership at the supervisory level for the effective implementation of HPWS. The study further explains how the interaction between high-performance work systems and ethical leadership influence employees’ attitudes and behaviour. To the best of the author’s knowledge, this study is one of the first to examine the moderated mediating effects of HPWS and ethical leadership on the relationship between affective commitment and OCB in a public healthcare sector of a developing country. Thus, it extends and contributes to the literature on HPWS and ethical leadership theory and consequently lays the ground for future research to explore these constructs in other developing countries.
In practical terms, this thesis offered several practical applications of the findings to the public health sector, particularly in the Punjab province. First, during the time of transition to improve public health outcomes, the Pakistani government could prioritise the development of HRM at all levels of the public health sector. Findings from this thesis suggested that contemporary HRM practices, such as HPWS, had the potential to improve the performance of employees and public hospitals in the country by influencing employees’ attitudes and behaviours. Moreover, supervisors with ethical leadership could be encouraged and promoted to leadership roles so that ethical behaviour could be instilled in front-line employees. These findings could also be useful when designing appropriate ethical leadership training programmes for public healthcare sector leaders. Through the understanding of how ethical leaders motivated their followers, managers would be able to enhance those attributes associated with leadership effectiveness and thus increase performance outcomes among public healthcare sector employees.
Future research directions could consider whether, in addition to the role of ethical leadership established in this study, other leadership styles (such as authentic leadership, servant leadership, and transformational leadership) play a role in the attainment of the individual, team, and organisational outcomes within the public healthcare sector. For example, new case studies focusing on employees from different provinces with extended stakeholders, such as leaders from the Health Ministry and patients, could be considered. Further, future studies could use non-self-report measures and collect data from multiple sources such as supervisors and co-workers. Additionally, future research could focus on longitudinal and experimental designs to improve the credibility of the causality of these relationships. Lastly, the role of culture and contextual factors warrants further investigation in the field of HRM in developing countries
Measuring and predicting the impact of private protected areas
No full textBiodiversity is in decline globally, and protected areas (PAs) are a cornerstone of the policy response for reducing this decline, with calls to protect 30% of the world’s ecosystems by 2030. While most PAs are public, such as national parks, private protected areas (PPAs) are an important contributor to biodiversity conservation, as many threatened species and habitats exist on privately owned land. The number and size of PPAs have been increasing globally and they will likely play a significant role in meeting the 2030 targets. However, the efficacy of PPAs in reducing biodiversity loss is not well understood. This can be measured by estimating the 'impact' of a PPA: the observed outcome under protection relative to the counterfactual without the protection. Strategically locating PPAs in areas where they will have a greater impact will result in greater reductions in biodiversity loss — however, it is first necessary to robustly estimate the impacts of existing PPAs.
This thesis aims to advance understanding of PPA impacts in reducing biodiversity loss, drawing on a diverse range of literature ranging from conservation science through to machine learning, statistics, and impact evaluation. Specifically, I develop a novel framework that incorporates individual and program-level PPA impacts, as well as estimating both past and future impacts. I analyse the extent to which biases in the locations of PPAs, relative to threatening processes, differ from PAs, and demonstrate an approach for integrating impact into conservation planning. All research was conducted in Australia, which is an ideal testbed for studying PPAs, since PPAs are scattered throughout the territory, and it is home to some of the oldest PPAs in the world. In addition, Australia has high-quality spatial data available to support the research objectives of this thesis.
First, I analyse how the location of PPAs nationally are associated with covariates that represent biodiversity and the likelihood of areas being cleared for agriculture and urban development, and examine how that compares to public PAs. Previous work has shown that public PAs tend to occur in biassed locations (e.g., low land capability and remote areas). It is not clear the extent to which PPAs are similarly biassed, and I examine this question at the level of the Australian continent. I find that the PPAs tend to target areas of high threatened species richness; however, they are, on average, placed in areas that have lower risk of being cleared compared to if they were placed randomly on private land. I find that this bias towards unproductive land is greater in PPAs compared to public PAs.
Next, I demonstrate a transparent and robust workflow using synthetic control design, statistical matching, and time-series data of woody vegetation cover to estimate impact for individual PPAs in the state of Victoria, Australia. Typically, conservation programs are assessed by estimating average impact, but this masks variations among individual PPAs. By combining individual impacts, I also estimate the program-level impact using a meta-analytic approach. Using this framework, I demonstrate that, while the covenants in the Goldfields region of Victoria have, on average, led to improved woody vegetation cover (0.3-0.8% per year), there is significant variation among the individual covenants (-4 to +7% change per year). This variation could be explained by ecological factors, and differing management requirements and landholder behaviours.
Understanding both the past and likely future impacts is crucial for a comprehensive assessment of the conservation value provided by PPAs. While estimating past impact helps us to estimate the efficacy of existing programs, future impact enables us to anticipate the potential future benefits; combining the two provides a longer baseline over which to measure impact. However, there is limited research that looks at past and future impact in an integrated framework. I develop a method combining predictive modelling, scenario analysis, and statistical matching to assess past and future impacts of PPAs in the North Coast Bioregion of New South Wales (NSW), Australia. I evaluate the past (2010-2020) and future (2020-2030) impacts of 119 PPAs in preventing woody vegetation loss. I find a positive but marginal effect of PPAs in avoiding past and future woody vegetation loss, with an average annual avoidance rate of 0.10% in the past and 0.12% in the future.
Systematic conservation planning is a method for spatially locating PAs to identify cost-effective areas to protect biodiversity. Here, I compare four strategies for prioritising PPAs and evaluate their performance based on return on investment (ROI) of prioritised areas, calculated as the ratio of impact and cost. Using data on habitat suitability of 306 threatened species, a spatial layer of predicted risk of woody vegetation loss, and land acquisition costs in the North Coast Bioregion of NSW, Australia, I undertake prioritisations based on: (i) representation of threatened species; (ii) representation and cost; (iii) impact of avoiding habitat loss; and (iv) impact and cost. I calculate the landscape-level ROI and find, as expected, the strategy combining impact and cost outperforms other strategies — but, surprisingly, only by a factor of 1.3 compared to representation with cost. Impact and cost improves on impact only by a factor of 3.6 and representation only by a factor of five. Examining species-level ROI shows that using impact and cost also provides greater conservation benefits for rare species compared to other strategies. This case study shows how incorporating impact and cost may have significant benefits to prioritisations, but shows that adding cost alone has a relatively greater benefit than moving to impact alone.
PPAs contribute significantly to the global conservation effort, but there is limited information on the extent to which PPAs have achieved conservation impact. The research in this thesis has contributed to the advancement of PPA impact evaluation. However, the approaches developed for measuring impact are also applicable to public PAs and other effective area-based conservation measures. This thesis helps us to understand the impact that PPAs have achieved to date, and supports the planning and implementation of more impactful PPAs, thus supporting the 2030 framework for expanding the global PA network
Exploratory analysis of the use of real-time 4D reconstruction during cold spray additive manufacturing
No full textIn-process spatio-temporal three-dimensional reconstruction, also known as 4D reconstruction, allows for early detection of deviations from the design in robotic additive manufacturing, thus providing the opportunity to rectify in an early stage to save both time and money. However, experiments have shown that in-process model reconstruction is made more difficult by the dynamic nature of the scene due to sensor and object movements, the three-dimensional growth of the build object, the textureless RGB quality of typical build surfaces, and computational complexity.
This thesis proposes a framework to perform real-time, in-process 4D reconstruction for freeform additive manufacturing processes such as cold spray that deal with a real-time dynamic and evolving scene that includes object change. Temporal point clouds from three cameras in eye-in-hand configurations are acquired and segmented to extract the region of interest (build object). Then the multiview, multi-camera registration of segmented 3D points is addressed in real-time via combining geometrically constrained Fiducial marker tracking and plane-based registration without drift accumulation. Finally, the registered point clouds are fused via voxel fusion of growing parts to reconstruct the 3D model of the object with smoothened surfaces.
The solution is deployed and verified in a robotic cold spray cell with different test scenarios and shape complexities. The results have shown a 3D registration accuracy of up to RMSE 0.923mm translation and 0.801◦ angular in real-time performance with a 60fps frame rate. Furthermore, the capability to reconstruct a high-quality model been demonstrated by using the low-cost sensor. In addition, the reconstructed 4D model has been used to analyse the deformation error of the cold spray deposited object
Novel lattice structures based on triply periodic minimal surfaces
No full textLattice structures present exciting properties, such as high stiffness-to-weight ratio, strength-to-weight ratio, and energy absorption, which are potential candidates for various engineering applications. The mechanical properties of these materials are mainly determined by the architecture and relative density (RD) of the structure and the property of the base material. At the early research stage on lattice structures, foams were extensively investigated for their mechanical performance and utilised for various engineering applications. However, their stochastic topology led to challenges in controlling and optimising the mechanical responses of foams. With the advances in manufacturing techniques, it is now feasible to fabricate complicated geometries with excellent accuracy at different length scales. More attention has been drawn to designing appropriate topologies for lattice structures to enhance mechanical properties and multifunctionality and improve manufacturability. Recently, a novel family of bio-inspired lattice structures, namely triply periodic minimal surfaces (TPMS), has attracted attention from the research community since they exhibited superior mechanical and promising multifunctional properties.
This work aims to study the mechanical properties and energy absorption of TPMS-based lattice structures under various loading conditions. Meanwhile, the strategies for improving the mechanical properties and energy absorption of TPMS-based lattices are also explored. Firstly, the flexural properties and energy absorption of TPMS lattices are evaluated in Chapter 2. A numerical model and analytical formulation were developed and validated by experimental data to predict the mechanical responses of sandwich beams with TPMS lattice cores under 3-point bending. A comprehensive parametric study was conducted to evaluate the effect of TPMS type, lattice core density and face-panel thickness on the flexural properties of sandwich structures with TPMS lattice cores. The results showed that the geometrical parameters and the relative density of the TPMS lattices had a considerable influence on their flexural properties and energy absorption. Among the TPMS lattices investigated, TPMS IWP lattices presented the highest flexural stiffness and strength.
As the most current research mainly focused on the mechanical responses of TPMS lattices fabricated by a single material, the idea of improving the compressive properties of TPMS lattices by fibre-reinforced polymer (FRP) composites is evaluated in Chapter 3. A comprehensive analysis of the number of unit cells, print direction and relative density effects on the mechanical properties of 3D printed composite TPMS gyroid lattices was conducted experimentally and numerically. The impact of the slenderness ratio on the compression buckling properties of FRP TPMS gyroid lattices was also studied. The results showed that FRP TPMS gyroid lattices presented higher elastic modulus when loaded along the printing direction. FRP composite TPMS gyroid lattices showed a bending and stretching mixed deformation mode under compression. The critical buckling load was more sensitive to the changes in slenderness ratio at higher relative density. A transition from plastic yielding to elastic buckling occurred with an increase in the slenderness ratio.
Apart from incorporating FRP composite as base material to improve the mechanical properties and energy absorption of TPMS lattices, a novel strategy to design honeycomb-like lattices with exceptional and tuneable mechanical properties and energy absorption based on the topology of TPMS is introduced in Chapter 4. Firstly, the method to create honeycomb-like structures based on the topology of TPMS was presented. Then, a numerical model was developed and validated by experimental results to evaluate the mechanical properties of G-Honeycomb and P-Honeycomb lattices. The mechanical performances of P-Honeycomb and G-Honeycomb were analysed at various relative densities and compared with conventional square honeycombs. G-Honeycomb and P-Honeycomb presented higher elastic modulus and plateau stress than conventional square honeycombs at the same relative density. The idea of designing TPMS lattices with tuneable mechanical responses was demonstrated by introducing a density gradient and creating a G-P hybrid structure with the topology of G-Honeycomb and P-Honeycomb in different regions. The linear elastic, plateau, and densification three stages behaviour under compressive loadings of G-Honeycomb and P-Honeycomb can be turned into a gradual stiffening response, presenting tailorable and progressive failure modes. The G-P hybrid structure can also present distinct properties at different compressive strains, which can be controlled by the level-set approximation equation.
Moreover, the mechanical properties and energy absorption of TPMS lattice under high strain rate compression and close-in blast are investigated in Chapter 5. The mechanical responses of TPMS lattice under high strain rate compression were evaluated based on numerical simulations and validated by analytical analysis. The results showed that TPMS gyroid lattices presented higher dynamic compression strength than conventional honeycomb structures. A comprehensive parametric study on the effects of core thickness, the number of layers and TPMS topology on the blast resistance of TPMS lattices were conducted. It is found that the initial peak of reaction force transmitted through the TPMS lattices increased with an increase in the thickness while the specific energy absorption reduced. By comparison, the number of layers in the TPMS lattices posed a negligible effect on the maximum reaction and energy absorption. Among the TPMS types investigated, TPMS primitive exhibited the best performance under blast loading compared to other TPMS lattices in terms of energy absorption. Additionally, uneven energy absorption across layers and stress concentration on top layers were found when TPMS lattices were subjected to impulsive loadings.
The idea of designing functionally graded (FG) TPMS lattices to improve their mechanical properties and energy absorption when subjected to dynamic compression and blast loading is discussed in Chapter 6. A finite element model was developed and validated by experimental results. The performances of the composite sandwich panel made of functionally graded TPMS gyroid lattice core and steel facets under blast were evaluated. The results showed that for the uniform TPMS gyroid lattices, most impulsive energy was absorbed by only part of the core, while there was insignificant plastic deformation found at the bottom layers. Clear material densification was observed near the blast centre's core section. The introduction of the functionally graded TPMS gyroid lattice core noticeably improved the performance of the sandwich panel when subjected to shock impact. All the structures with FG gyroid cores can effectively reduce the stress transmitted to the concrete base compared to the baseline design. Furthermore, uniform distribution of the stress field was observed within the FG TPMS lattice.
Overall, this work evaluates the mechanical properties and energy absorption of TPMS lattices under various loading conditions and proposes design strategies to improve the mechanical performance of TPMS lattices. TPMS lattices demonstrated promising flexural properties and resistance against dynamic loading. Meanwhile, fabricating TPMS lattices with fibre-reinforced material and designing honeycomb-like structures based on TPMS topology could improve their compressive properties and energy absorption. The results of this study could provide insights into future research on designing lightweight and functional lattice materials for various engineering applications
A model of the factors influencing consumer usage of B2C/C2C e-marketplaces
No full textThis research aimed to determine the key factors affecting the adoption and usage of B2C and C2C e-marketplace in Saudi Arabia; drawing upon the theories of Hofstede’s cultural dimensions for individuals and the UTAUT2 model. Also, the factors namely Brand Awareness, Security, Word of Mouth, and Value-added services have been included in this study. These factors focus on the depth of e-marketplace and how they interact to influence e-marketplace adoption as well as its usage. This study used a quantitative research approach. A survey was used to collect data from active Internet e-marketplace users. The analysis was carried out using Structural Equation Modelling (SEM). This research adds to the e-marketplace body of knowledge through a theoretical framework which will also show adoption and usage behaviour of consumers in Saudi Arabia. As few studies have investigated this topic, the current study provides a valuable contribution in the field. The findings of this study differs from previous research. Surprisingly, the results show no significant relationship exists between security, word of mouth, value-added services, effort expectancy, facilitating conditions, hedonic motivation, power distance, individualism versus collectivism and e-marketplace use in Saudi Arabia. On the other hand, brand awareness, habit, Masculinity versus femininity, price value, social influence and performance expectancy influences e-marketplace usage. The findings of this study lead to guidelines that will facilitate government as well as business organisations to understand how they can promote and enhance the level of e-marketplace adoption and its usage among potential consumers particularly in developing countries such as KSA. Moreover, it assists in clearing the way for companies to develop their online presence and satisfy their customers’ demand and also, assist the government in developing the e-marketplace sector
Participation as inhabitation: designer-citizens negotiating postdisaster housing reconstruction
No full textThe urgency, complexity, and uncertainty that distinguish postdisaster housing reconstruction produce a debate concerning the effectiveness of command-and-control methods versus participatory approaches. Participatory planning models of disaster recovery construct humans as sociopolitical subjects who possess local knowledge needed by built environment practitioners to effectively design and restore settlements. However, these models tend to overlook the role of non-human agents (e.g., materials and everyday household items) in how reconstruction site inhabitants improvise upon their dwelling, in order to negotiate the regimes of citizenship that ground experiences of disaster. Consequently, this ethnographic study of and with a small island fisherfolk community aims to develop an ecological view of citizen participation that emphasises the 'livingness' of architecture for postdisaster housing reconstruction Specifically, this research views participation as a mode of inhabitation in which designer-citizens merge with social, political, material, and environmental forces to continue living through catastrophe. The broader aim is to illuminate the relationality of postdisaster housing reconstruction through contribution to theory at the junctures of anthropology, citizenship, and design, and by extension, to understand how the “policy-practice defect” in disaster management can be better addressed by built environment practitioners
Investigation the roles of AZR1 and CDR1 genes of candida glabrata in antifungal drug resistance
No full textFungal infections are on the rise around the world every day. There are approximately 300 fungi known to be pathogenic to humans. One of the most prevalent fungal diseases is candidiasis, caused by infection with Candida species. In the last several decades Candida glabrata, which is phylogenetically more closely related to the non-pathogenic yeast Saccharomyces cerevisiae than to any other pathogenic Candida species, and it has become the second cause of candidiasis globally. Candida glabrata causes systemic infections that are high in mortality, and are difficult to treat due to reduced antifungal susceptibility. Due to the extensive use of antifungal drugs, multidrug resistance has been clearly documented in many pathogenic fungi. This poses a severe challenge to treatment (Control, and Prevention, 2019, Marquez, and Quave, 2020, Lamoth et al., 2018, Gow et al., 2022). Moreover, the phenomenon of multiple drug resistance is characterized by the simultaneous acquisition of resistance to a large variety of structurally, and functionally non-related cytotoxic chemicals. The effectiveness of treatment is reduced due to the action of transmembrane protein pumps which efflux the drug out of the fungal cell. It is crucial to gain extensive knowledge of the mechanisms underlying the perseverance of antimicrobial resistance to reduce the number of pathogenic agents resistant to multiple drugs. In addition, several mechanisms have been documented in human fungal pathogens, including C. glabrata, that contribute to multidrug resistance (MDR) development. That is including overexpression of or mutations in the gene encoding the target enzyme of an antifungal, lanosterol 14α demethylase, and transcriptional activation of genes encoding drug efflux pump proteins within the ATP-binding cassette (ABC family), as well as within the Major Facilitator Superfamily (MFS family).
This research investigated the effect of exposure of C. glabrata cells to the antifungals fluconazole, acetic acid, and simvastatin, with disruption of the genes encoding an ABC transporter (CDR1), and MFS transporter (AZR1). These genes were chosen because they are predicted to have roles in antifungal resistance due to their overexpression in azole-resistant clinical isolates (CDR1), the role of the homolog in S. cerevisiae (AZR1), and as AZR1 has not been deleted previously in C. glabrata. By analysing the deletion mutants of these genes, the relative contribution of each gene to drug resistance can be determined. Bioinformatic analysis was performed to identify all members of the ABC, and MDR gene families in S. cerevisiae, C. glabrata, and C. albicans homologs. This analysis identified the homologs of the CDR1, and AZR1 genes in these species, and showed that C. glabrata Cdr1p was more closely related to S cerevisiae Pdr5p, then with C. albicans Cdr1p. For more, it was found that C. glabrata Cdr1p is very similar to C. glabrata Cdr2/Pdh1p when compared with other genes in C. glabrata. Likewise, C. glabrata Azr1p was most similar to S. cerevisiae Azr1p, whereas C. albicans Seg11p was the least similar. To research gene function, the PRODIGE method was used to successfully generate a CDR1 deletion mutant by homologous integration of the knockout construct. Some adjustment of the method, including redesigning the primers to have higher G+C content in the homology region, was necessary to obtain a deletion mutant of the AZR1 gene. Compared with wildtype, the CDR1 mutant, and AZR1 mutant showed increased susceptibility to antifungals suggesting these genes play a significant role in azole particularly fluconazole, and acetic acid resistance. Based on the results of this study, AZR1 is vital in protecting the plasma membrane against acetic acid, hence the name. It is noteworthy that, statins were initially used to control cholesterol levels in humans, but studies have demonstrated that they possess antifungal activity in vitro. In this project, simvastatin was used as
chemicals with antifungal activity. Neither the CDR1 nor AZR1 knockout mutant showed significantly different growth in the presence of simvastatin compared to wildtype C. glabrata. Therefore, the cholesterol lowering drug simvastatin has also been demonstrated to be effective as an antifungal agent and inhibits the growth of C. glabrata, as well as other pathogenic yeasts. Overall, this research shows that C. glabrata is a promising model for studying the genetics of resistance to multiple antifungals. This project has characterized the role of a previously uncharacterized gene, AZR1 in C. glabrata, in resistance to antifungals. Furthermore, this study has uncovered the potential for the repurposing of drugs from the statins such as simvastatin as potential antifungals for the treatment of candidiasis
Fabrication of ferroelectric tunnel junctions for the implementation of artificial synapses
No full textFerroelectric materials are ideal candidates for the realisation of memristors, thanks to the non-volatile resistance states and fast resistance switching. Ferroelectric memristors are studied as memory units for the fabrication of dense memory arrays to implement hardware neuromorphic networks. This architecture would satisfy the requests of high process speed of large amount of data and low power consumption. The latter are the limits of the modern Von- Neumann architecture, which is experiencing the so-called memory bottleneck. Among ferroelectric materials, hafnium zirconium oxide (HZO) is characterised by robust ferroelectricity at a nanometric thickness and is compatible with the complementary-metal-oxide-semiconductor (CMOS) technology, thus industrially transferable. The objectives of this work are the realisation and optimisation of HZO-based ferroelectric tunnel junction (FTJ) memristors for the implementation of memory arrays, using the crossbar integration method. One of the major challenges associated to the use of HZO is the degradation of the ferroelectric properties when its thickness is reduced to very few nanometers. Throughout the thesis, different approaches to increase the scalability of HZO without compromising its ferroelectricity are explored. Structural, physical, and chemical properties of HZObased heterostructures are investigated by means of spectroscopic techniques and electrical characterisations are performed to evaluate their ferroelectric behaviour. The correlation between the structural properties of HZO and of electrode/oxide interfaces, and the ferroelectric performances is highlighted and used for the optimisation of ultra-thin HZO-based devices for neuromorphic applications