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Tech Competency and the Pink pc: Illuminating the iMac G3 and pc Builds
No full textWhere women were once historically at the forefront of computer programming, contemporary tech culture erases their participation. Today, however, tech-competency is showcased as feminine in online Pink pc build videos, which contest dominant narratives that place tech culture adjacent to geek masculinity. Before young people were building their own Pink pc’s, Apple’s G3 series represented an earlier articulation of feminine computer design. Apple’s rounded, colourful personal computer became an unconventional marker of femininity. Pink pc s challenge technology’s prevalent masculine-coding. Their hyperfeminine designs reflect possible agentic identity expression and resistance to hegemonic masculine taste values. Yet, the Pink pc also surfaces in corporate and post-feminist contexts and cultures, typically restricted by economic mobility. This article explores these contradictions through the Pink pc, from Apple’s G3 to Pink pc builds today, developing understandings towards feminist science and technology studies, invisible gaming cultures, and Critical Femininities.</p
The impact of LTOWB vs. standard component therapy on Transfusion-related complications in trauma resuscitation: a systematic review and meta-analysis
No full textBackground: Haemorrhage secondary to trauma is the leading cause of preventable fatalities. Low Titre O Whole Blood (LTOWB) has been reintroduced as a potential alternative to component therapy (CT) in trauma resuscitation due to its balanced composition. This systematic review and meta-analysis compares the incidence of transfusion related complications, including pulmonary embolism (PE), deep vein thrombosis (DVT), acute kidney injury (AKI), and acute respiratory distress syndrome (ARDS), in trauma patients receiving LTOWB versus CT.
Methods: A search of PubMed, Scopus, Embase and Web of Science databases was conducted to identify studies reporting adverse outcomes in adult civilian trauma patients receiving LTOWB or CT. Eligible studies were assessed for quality using the STROBE checklist. Meta-analyses were performed using RevMan software (Version 8.5.2, The Cochrane Collaboration, UK) to calculate pooled odds ratios (ORs) with 95% confidence intervals (CI) for PE, DVT, AKI, and ARDS.
Results: Ten studies met the inclusion criteria. No statistically significant differences were observed between LTOWB and CT groups for PE (OR 1.17, 95% CI 0.73-1.89, P = 0.51), DVT (OR 0.83, 95% CI 0.47-1.45, P = 0.51), AKI (OR 1.37, 95% CI 0.77-2.44, P = 0.28), or ARDS (OR 1.35, 95% CI 0.84-2.17, P = 0.21). Moderate heterogeneity was observed for some outcomes.
Conclusion: LTOWB offers a viable alternative to CT in trauma resuscitation without increasing the risk of transfusion related adverse outcomes. Further randomised controlled trials with standardised criteria are required to confirm LTOWB's safety and its role in reducing adverse outcomes.</p
Investigation of SARS-CoV-2 Proteins as Targets for Novel Therapies Against COVID-19
No full textThe coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presented an unprecedented global health challenge. Despite the rapid development of vaccines and antivirals, the ongoing emergence of new variants and associated side effects highlight the need for novel antiviral strategies. This thesis explores the usage of molecular dynamics (MD) simulations in advancing our understanding of SARS-CoV-2 protein dynamics and facilitating drug discovery efforts. By focusing on non-structural proteins (nsps) of SARS-CoV-2, this thesis aims to identify novel antivirals and characterize the dynamic interactions between these proteins and potential inhibitors.
A general introduction is given in Chapter 2 to provide a background on the COVID-19 pandemic and SARS-CoV-2 biology, outlining the proteome of the virus and discussing targets that have been used as antiviral therapies. The following chapters are self-contained studies exploring various nsps of SARS-CoV-2 as antiviral targets.
To demonstrate the workflow of the investigation of compounds against viral targets, Chapter 3 presents a study targeting the exoribonuclease (ExoN) domain of nsp14. Using an in-house library of COVID-19 related compounds, molecular docking was performed. Trisjuglone, ararobinol, corilagin, and naphthofluorescein were identified as lead compounds. Protein-RNA docking was performed, showing that when ligands are bound to the ExoN site, the binding of RNA is disrupted. MD simulations were performed for the nsp10-nsp14 complex bound with lead compounds and protein dynamics was analysed. It was found that changes in protein structure were modest in response to ligand binding, with principal components analysis (PCA) showing that energetically favourable conformations were achieved. Ligand binding was stable and largely driven by hydrogen bond formation, with residues involved in RNA-binding frequently forming contacts. Encoded by nsp3, the SARS-CoV-2 papain-like protease (PLpro) was also studied in Chapter 3 using previously identified lead compounds: cyanidin-3-O-glucoside, hypericin, and rutin. As well as assessing stability within the naphthalene binding site, binding free energy calculations were performed using molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) methods.
Chapter 4 extends the investigation of SARS-CoV-2 PLpro using a combination of different in silico methods to characterise the lead compound, hypericin, followed by in vitro validation of inhibitory behaviour. MD simulations were performed on an extended timescale, showing that PLpro adopts two distinct conformations characterised by the expansion and contraction of the ubiquitin-like domain. Ligands were found to bind in a stable manner to the naphthalene-binding site of PLpro, driven by interactions with blocking loop 2. Using adaptive protein energy landscape exploration (PELE) Monte Carlo (MC) simulations, unbiased binding sites were identified to reinforce the preferential binding of ligands to canonical sites associated with inhibition of PLpro. Using enzymatic assays, hypericin demonstrated inhibition of protease and deubiquitinase activities within biologically relevant ranges.
The characterisation of novel inhibitors against SARS-CoV-2 Mpro, encoded by nsp5, is presented in Chapter 5 utilising a similar approach. Identified from previous docking studies, hypericin and cyanidin-3-O-glucoside were explored as inhibitors against Mpro. MD simulations revealed modest changes in overall protein structure in response to ligand binding, with hypericin showing stable binding to the catalytic site. Adaptive-PELE MC simulations showed that hypericin also demonstrated binding to potential allosteric sites located in domain III of the Mpro dimer. From in vitro fluorogenic Mpro assays, both compounds inhibited protease activities within biologically relevant concentrations.
The SARS-CoV-2 nsp10-nsp16 methyltransferase complex was studied in Chapter 6. Small molecules were docked to the S-adenosyl-L-methionine (SAM)-binding site of nsp16, and potential lead compounds were assessed with MD simulations. Among the six lead compounds identified through the initial screening process, only oleuropein demonstrated comparable activity to the control. Investigation of nsp10-nsp16 was extended in Chapter 7, with additional MD simulations performed for nine compounds. From this, a subset of compounds was further evaluated using a longer timescale for production runs: sinefungin, verbascoside, and ligstroside. These extended simulations showed more stable binding, with ligands forming contacts with key residues of the SAM-binding pocket.
Through the investigation of various SARS-CoV-2 proteins, a substantial collection of MD simulations was accumulated, culminating in the creation of a trajectory database presented in Chapter 7. The database is comprised of over 300 MD simulations, including simulations involving variant spike proteins, as well as the studies on nsp3, nsp5, nsp14, and nsp16 detailed in this thesis. The repository of COVID-19 related MD simulations has been made publicly accessible at https://epimedlab.org/trajectories/.
This thesis represents a comprehensive investigation of SARS-CoV-2 nsps, resulting in the identification of potential antivirals. The trajectory database established in this study serves as a valuable resource for the scientific community, facilitating future research and development of novel antiviral strategies. Beyond its immediate application to COVID-19, this work offers valuable insights into drug discovery workflows, enhancing our preparedness for potential future pandemics.</p
Small-Angle Neutron Scattering of P(NDI2OD-T2) Solutions: Importance of Network Structure for Data Interpretation and Film Morphology
No full textSmall-angle neutron scattering (SANS) is used to study the solution-phase behavior of the well-studied n-type semiconducting polymer P(NDI2OD-T2). To provide a global overview of polymer behavior, four different molecular weight samples are studied in three different solvents and at three different temperatures. The SANS data are interpreted in terms of a hierarchical model combining a cylinder model to explain scattering from individual rigid chains/aggregates at high scattering vector, q, and a Guinier-Porod model to explain the upturn in scattering at low q that appears in the SANS patterns of the higher molecular weight samples. In this way, the scattering patterns of P(NDI2OD-T2) solutions with different molecular weights, different solvents, and at different temperatures can all be adequately modeled and parametrized in terms of varying cylinder length, cylinder width, and mass fractal dimension. To connect the SANS results to thin film microstructure and charge transport, thin films are prepared and studied with atomic force microscopy and organic field effect transistor (OFET) measurements. Significantly, excess network formation in solution is associated with a decrease in the in-plane alignment of polymer chains and decrease in OFET mobility. Thus, while increased aggregation can enhance chain ordering and charge transport in thin films, excess aggregation in the form of a compact entangled network of these aggregates can be detrimental to the formation of ordered structures during solution deposition.</p
RMIT's Artificial Intelligence Assurance of Learning Typology Extended Guide
No full textRMIT's Artificial Intelligence Assurance of Learning Typology Extended Guide builds upon RMIT's Artificial Intelligence Assurance of Learning Typology. The extension resource provides educators with questions that act as important reflective considerations to aid educator decision-making when designing learning for generative artificial intelligence.The typology is a quick guide of the seven key themes required, including their associated factors and decisions, when designing curriculum and teaching activities. It is structured according to principles of constructive alignment as a logical sequence that enables decision-making as an educator to maintain academic quality.The typology considers artificial intelligence in a cooperative learning paradigm, where educators view artificial intelligence and students as collectively working together to achieve outcomes for appropriate use cases. Considering student collaboration with technology as similar to other collaborative work, such as group work, can be helpful. Group assessment work, which assesses both the process and the product, reflects collaborative work in relevant industries or professions.This is a public version of this resource with internal links removed. RMIT educators should access this resource with hyperlinks included, via the Educator Resource Hub SharePoint at https://rmiteduau.sharepoint.com/sites/EQ</p
A Heterogeneous Acid-Base Organocatalyst For Cascade Deacetalisation-Knoevenagel Condensations
No full textMultifunctional heterogeneous catalysts are an effective strategy to drive chemical cascades, with attendant time, resource and cost efficiencies by eliminating unit operations arising in normal multistep processes. Despite advances in the design of such catalysts, the fabrication of proximate, chemically antagonistic active sites remains a challenge for inorganic materials science. Hydrogen-bonded organocatalysts offer new opportunities for the molecular level design of multifunctional structures capable of stabilising antagonistic active sites. We report the catalytic application of a charge-assisted, hydrogen-bonded crystalline material, bis(melaminium)adipate (BMA), synthesised from melamine and adipic acid, which possesses proximate acid-base sites. BMA exhibits high activity for the cascade deacetalisation-Knoevenagel condensation of dimethyl acetals to form benzylidenemalononitriles under mild conditions in water; BMA is amenable to large-scale manufacture and recycling with minimal deactivation. Computational modelling of the melaminium cation in protonated BMA explains the observed catalytic reactivity, and identifies the first demethoxylation step as rate-limiting, which is in good agreement with time-dependent 1H NMR and kinetic experiments. A broad substrate scope for the cascade transformation of aromatic dimethyl acetals is demonstrated.</p
Multimethod Approach to Investigate the Factors Influencing High-Temperature Fuming of Bitumen
No full textBitumen is heated at high temperatures during asphalt paving applications. In these circumstances, there is the possibility for fuming. These fumes can vary in intensity and, if significant, may attract complaints. The bitumen’s chemical composition depends on the crude oil from which it originates. A tool to screen bitumen and evaluate its potential to release fumes would be highly beneficial. In this study, three methods have been employed to investigate a series of bitumen samples that were known to produce complaints by (a) quantifying benzene, toluene, ethylbenzene, and m, o, p-xylene (BTEX), (b) measuring the partition coefficients of these analytes, and (c) measuring the volatile mass of bitumen exposed to isothermal heating. It was found that the concentration of BTEX varied significantly between bitumen samples. The partition coefficients of these analytes are substantially the same between samples. Finally, the volatile mass of each sample varies significantly between samples, independent of bitumen grade or country of origin. These volatile masses correlate strongly with fuming complaints from bitumen and can be used as predictors of bitumen fuming risk.</p
Structural Evolution of Liquid Metals and Alloys
No full textLow-melting liquid metals are emerging as a new group of highly functional solvents due to their capability to dissolve and alloy various metals in their elemental state to form solutions as well as colloidal systems. Furthermore, these liquid metals can facilitate and catalyze multiple unique chemical reactions. Despite the intriguing science behind liquid metals and alloys, very little is known about their fundamental structures in the nanometric regime. To bridge this gap, this work employs small angle neutron scattering and molecular dynamics simulations, revealing that the most commonly used liquid metal solvents, EGaIn and Galinstan, are surprisingly structured with the formation of clusters ranging from 157 to 15.7 Å. Conversely, noneutectic liquid metal alloys of GaSn or GaIn at low solute concentrations of 1, 2, and 5 wt%, as well as pure Ga, do not exhibit these structures. Importantly, the eutectic alloys retain their structure even at elevated temperatures of 60 and 90 °C, highlighting that they are not just simple homogeneous fluids consisting of individual atoms. Understanding the complex soft structure of liquid alloys will assist in comprehending complex phenomena occurring within these fluids and contribute to deriving reaction mechanisms in the realm of synthesis and liquid metal-based catalysis.</p
Cost factors affecting the utilisation of secondary materials in the construction sector: A systematic literature review
No full textThe building and construction sector accounts for a substantial portion of the consumption of natural resources and the generation of waste. The use of secondary materials in this sector offers a promising avenue to reduce reliance on primary materials and curb waste generation. However, the utilisation of these materials is heavily influenced by cost considerations and a comprehensive understanding of the associated costs is lacking. Therefore, this study systematically reviewed key literature to identify cost categories and factors that influence the cost of utilising secondary materials in construction projects. The PRISMA method was employed for asystematic review of the literature from 2013 to 2023. Furthermore, the study explored strategies for enhancing cost performance. The results delineated 13 distinct cost categories within five phases of materials' extended service life (i.e. end-of-life, secondary production, design and planning, installation in existing/new site and operation) and 53 factors influencing the cost performance of secondary materials. Additionally, 22 diverse strategies were identified to enhance this performance. The paper recommends two approaches to implement these strategies: establishing government-led platforms to promote these strategies and enhancing waste education. The findings hold significance for practitioners and policymakers aiming to enhance resource efficiency in construction projects towards a Circular Economy (CE).</p
Application of the DEMATEL approach to analyse the root causes of building defects
No full textBuilding defects are a common phenomenon in the construction industry. The negative consequences of building defects are not limited to waste generation or low resource efficiency. This challenge can have several direct and indirect implications such as cost overruns, unforeseen delays in project completion time, building occupants’ dissatisfaction and health and safety risks. Despite the increase in the number of studies investigating building defects in recent years, little is known about the prioritisation of their causes by considering the interaction among the causes of defects. Therefore, this study employed the decision-making trial and evaluation laboratory (DEMATEL) method to bridge this gap. Experts' opinion was sought using a questionnaire developed in the form of a matrix and semi-structured interview questions. Thereafter, the interactions among the causes of building defects were analysed and the most prominent causes are identified. The study showed that materials, workmanship and design are the major causes of building defects. Despite being specific context, the findings can be the basis for further research in this area with a focus on a range of different building typologies. Furthermore, the recommendations provided will act as a facilitator to minimise the occurrence of building defects. Lastly, the research findings can be considered in the planning stage of any construction project, to ensure the construction quality, reduce potential waste and enhance the circular economy and resource efficiency in the built environment sector.</p