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A flexible and participatory evaluation framework for historic villages in peri-urban areas in China: multi-dimensional value assessment for conservation and adaptive reuse
No full textHistoric villages in peri-urban areas hold significant value, including not only their conventional value as historic villages but also their unique value in urban-rural coordination, shaped by their transitional location. As key nodes where urban and rural influence converge, these villages are able to facilitate the exchange of urban-rural resources in terms of economy, ecology, culture, and infrastructure, driving urban-rural integration and mutual development. Conserving the natural and cultural environments of these villages can support urban-rural ecological sustainability and cultural diversity. Adaptive reuse of their physical fabric can also help incorporate them into urban-rural infrastructure and economic networks, therefore contributing to peri-urban governance while narrowing urban-rural gaps in living standards and fostering social stability.
Given the pressures of urbanisation in many areas of the world, it is becoming increasingly urgent to establish an evaluation framework that helps identify the multi-dimensional values of such villages in order to guide conservation and adaptive reuse strategies. Existing evaluation frameworks are often rigid and expert-driven, designed for historic villages in general rather than those in peri-urban areas. As a result, they cannot account for the unique value of urban-rural coordination. Moreover, historic villages vary significantly in their individual characteristics, and different stakeholders may perceive their values differently. This research therefore proposes a new flexible and participatory evaluation framework for historic villages in peri-urban areas to better accommodate contextual variations and diverse stakeholder perspectives.
The development process began with the creation of a preliminary evaluation framework, which incorporated multiple value dimensions and corresponding indicators. This framework was subsequently refined and validated using Structural Equation Modelling based on participant questionnaires obtained from China (n = 1013) and a case-study village in China (n = 319) to identify key multiple value dimensions and their corresponding indicators, assigning weightings accordingly. Then, two final frameworks were generated: one applicable at the national level in China and another tailored to a specific Chinese peri-urban case-study village.
The findings reveal that these villages embody a wide range of values, including historic, cultural, artistic, research, educational, ecological, residential, economic, and urban-rural coordination values and therefore both frameworks specify the indicators to measure these multiple values. A comparative analysis of the weightings between the two frameworks demonstrates significant differences, underscoring the need for flexibility in evaluation. And a comparative analysis of the weightings assigned by different stakeholders also reveals significant differences, emphasising the importance of a participatory approach. Additionally, in-depth interviews (n = 19) conducted in the case village further enriched the contextual understanding of stakeholder perspectives and provided detailed support for the weightings and application of the evaluation framework. Based on these stakeholder perspectives and taking into account the significant differences in weightings, conservation and adaptive reuse strategies for the case village were successfully formulated, while also offering a methodological approach applicable to historic villages in peri-urban areas globally. Establishing such an evaluation framework contributes to sustainable urban expansion and regeneration while fostering public participation in conservation and reuse
Development of an evidence-based measure of concentration for use in clinical trials of sound-based interventions for tinnitus in adults
Get PDFTheranostic apoferritin nanocages for brain tumours: dual delivery of temozolomide and lead sulfide quantum dots
Get PDFGlioblastoma (GBM) is the most common and aggressive (grade 4) primary brain tumour, arising from malignant transformation of glial cells, a consequence of genetic and epigenetic alterations. Its global incidence is 3-5 cases per 100, 000 person-years. GBM remains a clinical challenge, a consequence of treatment resistance, poor delivery because of restrictive barriers such as the blood brain barrier (BBB), ATP-binding cassette proteins, and tumour localisation. Median survival, with standard of care treatment which includes temozolomide (TMZ), is ~16 months. However, TMZ chemotherapy is limited by toxicity, drug resistance, chemical properties of TMZ, and poor drug accumulation at the tumour site. Resistance mechanisms include overexpression of O6-methylguanine-DNA methyltransferase (MGMT), drug efflux transporters (P-glycoprotein (P-gp)), base excision repair (BER), and mismatch repair (MMR) deficiency.
GBM imaging is essential for tumour characterisation, localisation, and surgery, particularly in addressing GBM-specific challenges such as anatomical barriers and deeply located tumours. Therefore, deep tissue imaging with near infrared region II (NIR-II, 1000-1700 nm) rather than near infrared region I (NIR-I, 650-900 nm) has gained attention. In this context, quantum dots (QDs), particularly lead sulfide quantum dots (PbS QDs), can be used in NIR-II/ short wave infrared (SWIR) probes for cancer imaging applications due to their advantageous properties, including stable optical emission when compared to traditional fluorescent agents. However, their potential toxicity is the major limitation for their use in cancer imaging.
This PhD project investigated a novel theranostic formulation for the treatment and monitoring of GBM, addressing the need for new targeted drug delivery systems (DDS) using nanoparticles (NPs) to overcome both diagnostic and therapeutic limitations. Therefore, the combination of diagnostic and therapeutic approach in one construct, called as theranostics, has gained attention. Among various DDS, apoferritin (AFt) is a promising candidate for improving delivery to the brain by exploiting overexpression of transferrin receptor 1 (TfR1) on GBM and BBB endothelial cells. Herein, we developed a dual function theranostic platform based on horse spleen AFt nanocages co-encapsulated with TMZ and PbS QDs, AFt-PbS-TMZ, for simultaneous TfR1 targeted delivery of therapeutic and imaging agents. AFt-PbS-TMZ (12.1 ± 0.6 nm in diameter from high resolution transmission microscopy) demonstrated high encapsulation efficiencies (74.4 ± 11.25% for TMZ, one QD for each cage) and pH-dependent TMZ release (70% at pH 5.5, 33% at pH 7.4; after 24 h at 37°C).
In two-dimensional (2D) in vitro cultures, PrestoBlue (PB) assay results with AFt-PbS-TMZ demonstrated enhanced inhibitory effects with lower IC50 values (3.5 ± 0.1 µM for U373M, 8.5 ± 0.7 µM for U373V, 10.9 ± 2.7 µM for U87MG) for GBM cells, whereas non-cancerous MRC-5 fibroblasts and human astrocytes exhibited IC50 > 30 µM (p < 0.001) post-treatment with 6 days, demonstrating GBM selectivity related to higher TfR1 expression in GBM cells, confirmed by western blot and flow cytometry methods. In addition, AFt delivery overcame TMZ resistance-mediated by MGMT; AFt-TMZ and AFt-PbS-TMZ overwhelmed the MGMT suicide repair protein, rapidly depleting its expression in MGMT-positive U373M cells.
To enable more predictive translation of 2D culture results into in vivo models, three-dimensional (3D) in vitro GBM models were utilised. In 3D spheroid cultures, AFt-PbS-TMZ leveraged AFt’s co-delivery advantages to achieve enhanced inhibition, IC50 was 5.0 ± 0.5 µM, and it significantly (p < 0.0001) reduced spheroid volume over 6 days. This was likely due to enhanced TfR1 expression in spheroid cultures compared to 2D monolayers. In addition, deep tissue photoluminescence (PL) studies confirmed that PbS QDs signalling in U87MG spheroid cultures post-treatment with AFt-PbS-TMZ for 6 days and can be imaged in vivo.
In conclusion, these findings highlight the potential of AFt-PbS-TMZ as an inherent TfR1 targeted theranostic agent, combining GBM therapy and imaging abilities in a single nano-sized (12 nm) platform. The pH-responsive TMZ release and NIR-II emission from PbS QDs have a potential to address both diagnostic and therapeutic needs of GBM
Evaluating the role of waxes on oil stability in frying applications.
No full textDeep-fat frying (DFF) is one of the most popular food processing methods. However, during this process, the oil is exposed to high temperatures, air, and water from the food, resulting in a degradation of the frying medium. Various strategies have been proposed to enhance oil stability during DFF, including blending different oils, genetic modification of the oil crops and antioxidant addition (Aladedunye et al., 2017; Erickson et al., 2023; Przybylski et al., 2013).
In recent years, edible oleogels have gained widespread use in the food industry as alternatives to solid fats. Oleogelation structures liquid vegetable oils into solid-like gels using organogelators such as waxes and fatty acids. Initially used in products like spreads and dairy products, oleogels were first explored as a frying medium by Lim et al. (2017) who used soybean oil–carnauba wax oleogels for frying instant noodles. While the study focused on fried product quality, findings suggested improved oil stability and reduced oil uptake. Since 2021, research has expanded, though most studies still emphasise the effects on fried foods rather than the stability of the frying oil.
Therefore, the overall aim of this PhD research was to evaluate for the first time the effect of rice bran wax (RBW) on physiochemical behaviour and thermal stability of conventional sunflower (SFO) and high-oleic sunflower (HOSFO) during deep-fat frying. To achieve this goal, 0.06 and 0.15% (w/w) RBW-SFO and 0.06% (w/w) RBW-HOSFO dispersions were used as a frying medium. To evaluate the changes in the oil quality, this PhD research assessed the primary and secondary oxidation products measuring peroxide value, p-anisidine value, the thiobarbituric acid reactive substances (TBARS) value, conjugated diene and triene. The changes in fatty acid composition, viscosity, total polar materials formation and colour were monitored throughout the trying processes. High-performance thin-layer chromatography and the free fatty acid value were used to assess the extent of hydrolytic reactions. In addition, a two-part thermogravimetric study was used to determine fried oils' oxidative stability and thermal decomposition.
The experimental data suggest that adding RBW to conventional SFO enhanced oxidative stability during frying. Adding RBW to conventional SFO significantly reduced the formation of secondary oxidation products, the breakdown of triacylglycerols and the release of free fatty acids. Some enhancement in HOSFO stability was observed upon the incorporation of RBW. Adding RBW to both oils reduced the darkening of the oil.
The findings indicate that RBW contributes to protecting oil against thermal degradation. This effect is likely due to the presence of gamma-oryzanol in the wax, which plays a role in mitigating lipid oxidation and delaying oil deterioration. Analysis of the frying mediums suggests that incorporating RBW into SFO during prolonged frying enhances oil stability and extends its functional lifespan
Detecting microscale surface impurities in powder bed fusion through light scattering and machine learning
Get PDFLaser beam powder bed fusion (PBF-LB) is a leading metal additive manufacturing technique capable of producing complex components with high precision. However, the process is prone to forming microscale surface impurities such as balling, spatter, and surface pores, which can affect mechanical properties, surface finish, and overall part reliability. Detecting these impurities, particularly during fabrication, remains a significant challenge due to limitations in current inspection methods.
Although ex-situ techniques provide high-resolution analysis, they are often time-consuming, expensive, and/or unsuitable for real-time monitoring. In contrast, in-situ sensing approaches, while promising, frequently suffer from limited resolution, inconsistent accuracy across different machines, and a lack of reliability in detecting microscale impurities. Moreover, the real-time implementation of such methods is hindered by limitations in data acquisition, reconstruction, and analysis speed.
This thesis presents a novel method for detecting microscale surface impurities, which combines light scattering with machine learning (ML) to address these challenges. An optical setup was developed to capture light scattering patterns from PBF-LB surfaces. Experimental results demonstrated that surfaces with and without microscale impurities produce distinct scattering signatures. These signatures were subsequently used to classify the surfaces using ML algorithms.
To reduce the dependency on extensive experimental datasets, a simulation framework was established. Within this framework, light scattering patterns were generated using a model based on Beckmann-Kirchhoff (BK) theory. The surfaces input into this model were synthetically created using a generative adversarial network (GAN), enabling the generation of a large and diverse dataset. This approach considerably reduced the time and effort required to develop robust classification models.
The ML algorithms, once trained, achieved an accuracy of over 90% in detecting surface impurities. The system operates efficiently and possesses the potential for integration into a PBF-LB machine, enabling real-time, in-situ defect detection without interrupting the build process.
This study presents the first application of simulated light scattering patterns derived from synthetically generated surfaces detecting microscale impurities on PBF-LB surfaces. It demonstrates a rapid, cost-effective, and highly accurate method for assessing surface quality. Although currently implemented ex situ, the system architecture is well-suited for future integration as a real-time, in-process monitoring solution, thereby supporting more reliable and intelligent additive manufacturing workflows
Female subjugation and liberation: an ecofeminist study of the selected novels of Shashi Deshpande and Bapsi Sidhwa
Get PDFUtilising the lenses of cultural ecofeminism and material ecofeminism, this study attempts to understand women's subjugation by patriarchy. Societal constructs are mostly built around dualism, women and their nature versus men and culture, wherein women and nature are regarded as inferior, and used for subjugation. This thesis also investigates how the institution of marriage, religion, and mythological beliefs are abused to dominate women in the societies of Pakistan and India as depicted by Bapsi Sidhwa in “The Bride” and Shashi Deshpande in “The Dark Holds No Terrors.” Women are forced to give up their identities and fundamental rights. Better health care, education, economic independence, and the right to make decisions for their lives are often denied in these societies. Women, nature, land, and animals are placed in parallel. They are exploited by men like non-living entities. For instance, women are often divorced by men if they cannot produce children. They are equated to barren land in these societies. They are killed for suspected infidelities and traded for settling blood feuds and financial debts. This research primarily focuses on female suppression and their independence. Material ecofeminism helps in understanding the ongoing exploitation of women, nature and other species for material gains, physical pleasure and satisfaction of men’s ego. To defy subordination, material ecofeminism encourages empowering women through better education and financial self-sustenance. Ecofeminism also engenders the idea of liberation of women for ecological protection. Owing to their intimate relationship, innate affection, and endowed spiritual linkage with nature, women can play a vital role in the protection of the environment, if given a chance. This research endeavours to establish that females are living beings. They have feelings. They are equally passionate beings with ambitions having their own material and physical needs. The study concludes that akin to other living beings, their potential is also defined by their determination and audaciousness. They have the ability to transcend all the impediments created by patriarchal subjugation
Recombinant expression of native Tritrypticin and optimisation of an In vivo biosynthesis platform for high-throughput peptide therapeutics discovery
No full textThe global increase in antibiotic-resistant bacteria poses a public health threat, heightened by overuse of antibiotics in livestock farming, the food industry, and healthcare. This demands for novel antimicrobial compounds to address the diminishing inefficacy of current antibiotics. Antimicrobial peptides (AMPs) ubiquitous in organisms' innate immune systems show potential with their broad-spectrum activity. This study investigates on Tritrypticin (TTC), a 13-residue bactericidal peptide rich in tryptophan. Derived from the C-terminal domain of the porcine bone marrow precursor molecule C12, that demonstrates antimicrobial properties against pathogens like Escherichia coli and Salmonella typhimurium. This study addresses the challenges in producing AMPs using recombinant expression in E. coli BL21 (DE3) and utilisation of the inducible, self-cleavable fusion protein, Synechocystis sp. (Ssp) DnaB intein, demonstrating potential for higher yields and scalable recombinant expression of AMP. The study identified the optimal recombinant protein expression conditions at low induction parameters (0.1 mM IPTG, 15°C, 200 rpm agitation, and 18 hours). Induction of the Ssp DnaB intein cleavage to release TTC was observed at pH 5, incubated at 25°C for 8 hours, and further enhanced with supplementation of non-ionic detergent and solvents such as Tween-20, Triton X-100, and dimethyl sulfoxide (DMSO). The extracellular secretion of the TTC peptides mediated by incorporating signal peptides (SPs), Outer Membrane Protein A (OmpA) and novel signal peptide 4 (NSP4), enabled the identification of antibacterial activity of TTC towards Bacillus subtilis ATCC 6633 through bacterial agar screening, demonstrating the excretion of TTC from E. coli BL21 (DE3) host. Utilising directed evolution techniques, error-prone PCR (epPCR) with imbalanced nucleotides and MnCl2 supplement, accelerated the generation of a diverse pool of mutant TTC producers, identification up to 66% of candidates and identified peptide mutations with arginine that enhanced antibacterial activity with larger inhibition zones against B. subtilis through the high-throughput bacterial screening method. Overall, the study investigates the potential of expressing AMPs in recombinant expression systems to allow more efficient peptide production and generate mutant peptides with potentially enhanced antimicrobial activity, rapidly identified by the high-throughput screening method. This research contributes to ongoing efforts to identify novel antibiotics to combat antibiotic-resistant pathogens and address the growing threat of antimicrobial resistance
Advances in Bismuth-Mediated Arylation and Phosphorus Redox Catalysis
No full textFollowing the recent growth of organopnictogen synthetic methods, there has been a renewed interest in organobismuth compounds as alternatives to transition metal catalysts for the electrophilic arylations of weak nucleophiles. At the same time, rationally designed phosphorus manifolds have emerged as powerful redox catalysts that have been implemented in numerous transformations.
The work detailed in this thesis aims to contribute to the advances of Group 15 chemistry by focusing on two areas: the development of bismuth-mediated arylation reactions for the synthesis of valuable quaternary amino acids (Chapters 2 and 3) and the mechanistic investigation and synthetic application of a novel phosphorus-catalysed Staudinger reaction (Chapter 4).
Chapter 1 offers a theoretical background on the reactivity of phosphorus and bismuth, with a focus on the ligand coupling reaction, the key elementary step in all the projects of this thesis.
Chapter 2 describes the development of an electrophilic bismuth-arylation of a phosphonium enolates (Kukhtin Ramirez intermediate). The reaction offers a modular access to α,α-diaryl amino esters from readily available α-keto esters. However, despite the broad scope, the reaction lacks stereocontrol over the newly formed quaternary centre.
Chapter 3 focuses on expanding the scope of the previously discussed methodology while introducing diastereocontrol in the Bi-mediated arylation. To achieve this, the arylation of αnitro compounds in combination with L-proline tert-butyl ester as auxiliary was explored. Subsequent reduction of the nitro group would lead to the formation of an arylated quaternary amino acid. Preliminary investigation on the diastereoselective arylation of amino acid imines will also be presented.
Ultimately, Chapter 4 outlines the studies on a P(III)/P(V) catalytic Staudinger reaction. By leveraging the reactivity of a bifunctional phosphine, a tandem catalytic reduction-amidation sequence was developed. Moreover, kinetic studies provided insights into critical aspects of the catalytic cycle, such as the impact of catalyst poisoning as phosphine oxide and the key role of Brønsted bases in accelerating the reaction rate
Business proposal: Codedsphere solutions development platform
No full textThis dissertation presents the business plan for Codedsphere, a Malaysia based custom software development company founded in 2024. Codedsphere aims to revolutionize the software development industry by creating a global platform that fosters a community of skilled developers who are treated as partners rather than employees. The company’s innovative model emphasizes transparency, fairness, and collaboration, positioning it to capitalize on the rapidly growing demand for customized software solutions.
The plan outlines Codedsphere's vision to become the world’s premier platform for innovation, transforming ideas into powerful solutions across industries. The company’s mission is to revolutionize the delivery of technology innovation by fostering a global community of developers and clients, collaboratively transforming ideas into groundbreaking solutions. Codedsphere’s business strategy focuses on building a robust developer community, sourcing clients through quality networking, and ensuring fair and transparent operations.
The market analysis indicates significant opportunities within the global IT outsourcing industry, which is projected to grow from 777.80 billion by 2028. Codedsphere plans to leverage this growth by strategically positioning itself with its proprietary software development platform and a global network of developers. The financial analysis shows a positive Net Present Value (NPV) of $2,566,090 and an Internal Rate of Return (IRR) of 36.95%, emphasize the profitability and sustainability of the business.
Key risks identified include market competition, underperforming partners, and clients unwilling to pay for services rendered. To mitigate these risks, Codedsphere will implement a comprehensive evaluation and support system, ensuring high-quality service delivery and client satisfaction. The plan also details Codedsphere's organizational structure, emphasizing a flat and scalable model that supports both full-time employees and partners.
Finally, the financial forecast aligns with Codedsphere's phased business strategy, projecting substantial revenue growth over five years. The company’s equity distribution plan ensures that founders, early team members, and investors are incentivized for long-term growth, with additional equity reserved for future employees and strategic partners.
This business plan illustrates how Codedsphere is poised to become a leader in the custom software development industry, offering a unique value proposition that aligns with market demands and technological advancements
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