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Synthesis and Chemistry of Novel Aryl Sulfonamides and Initial Studies of Their Biological Activity
No full textThe full text will be available at the end of the embargo: 21st Jan 202
Design, Synthesis and Biological Evaluation of Inhibitors of Polysialyltransferases PST and STX. Design, synthesis and biological evaluation of a range of N-modified mannosamines, sialic acids and analogues from in silico screening as inhibitors of PolySia-NCAM biosynthesis with anti-migration activity.
No full textPolysialylated NCAM (polySia-NCAM) is re-expressed in a number of tumours, including small cell lung carcinoma and neuroblastoma and is strongly associated with aggressive, invasive and metastatic tumours in the clinic. SiRNA knockdown of the polysialyltransferases (polySTs), the enzymes responsible for polysialylation of neural cell adhesion molecule (NCAM), has been shown to abolish cell migration. PolySia-NCAM is thus a highly attractive novel therapeutic target. A library of potential polyST inhibitors has been synthesised, using substrate-based design and computational chemistry. Compounds synthesised include N-acylmannosamine analogues, thio-linked CMP-sialic acid analogues, N-acyl modified sialic acids and compounds incorporating elements of both approaches. Novel methodology development in the synthesis of many of the compounds is described, notably a novel route to N-acyl sialosides. In addition, compounds identified from in silico screening were considered. Routes to synthesis and isolation of analogues of biologically active compounds are described. Using an enzyme assay, compounds were evaluated for their ability to reduce polySia synthesis through polyST inhibition. Effects of agents on polySia expression in cells, and the ability of compounds to reduce cell migration in vitro was studied using a wound healing ‘scratch assay’.
The data from these experiments revealed a number of potent modulators of polySia assembly and their efficacy in reducing cell migration, as well as the limits of the biosynthetic pathway to accept unnatural sialic acid precursors. This is the first example of polyST inhibition modulating tumour cell migration, and points to the potential of the polysialyltransferases as a therapeutic target in metastatic tumours.EPSRC and BACRThe full text will be available at the end of the extended embargo: 5th March 202
Pharmacological investigations into matrix metalloproteinase-activated anti-tumour prodrugs. In vitro metabolic and pharmacological investigations into a series of colchicine-based peptide prodrugs activated by tumour-expressed matrix metalloproteinases
No full textMatrix metalloproteinases (MMPs) play a significant role in degrading the extra- cellular matrix in cancer development and metastasis. Overexpression of matrix metalloproteinases in tumour tissues relative to normal tissues has been exploited as a target for peptide-based therapeutics, to improve therapeutic index of currently used agents. The stability of MMP-activated prodrugs in normal tissue or organs is a significant challenge for their success in the clinic. In an in vitro study, the stability of twenty six prodrugs was studied in mouse liver, kidney, lung and tumour homogenates using HPLC and LC/MS. Selected agents were studied in vivo. Each prodrug has a characteristic amino acid sequence with dominant FITC N-terminal end cap. All prodrugs were conjugated to a colchicine derivative (ICT 2552) which is a vascular disrupting agent causing tumour vasculature shutdown and consequently, tumour necrosis. ICT 3146, ICT 3019, ICT 3120 and ICT 3115 prodrugs showed significant stability in normal tissues and considerable activation in certain tumour tissues compared to the lead compound ICT 2588. Also, the selectivity of promising prodrugs to the MMP family was confirmed by using leupeptin (serine, cysteine and threonine protease inhibitor), pepstatin A (aspartate protease inhibitor), phosphoramidon (nepralysin inhibitor), ilomastat (metalloproteinase inhibitor) and BML-P115 (matrix metalloproteinase inhibitor). Moreover, members of the MMP family responsible for cleaving the selected prodrugs were identified using recombinant MMP enzymes. Furthermore, a LC/MS-MS method was developed to specifically detect and quantify MMP-16 protein expression in H460 tumour. MMP- 16 was responsible for the cleavage of ICT 3146 and ICT 3115. Therefore, MMP-activated prodrugs could be a useful therapeutic approach to avoid off-site toxicities of currently used anti-tumour agents.The full text will be available at the end of the extended embargo: 5th March 202
Investigation of cytochrome p450 isoforms 1A1, 1B1 and 2W1 as targets for therapeutic intervention in head and neck cancer. Probing CYP1A1, 1B1 and 2W1 activity with duocarmycin bioprecursors
No full textThe full text will be available at the end of the embargo: 30th July 202
Modulation of BMP and TGFβ signalling pathways in pulmonary arterial hypertension (PAH)
No full textThe full text will be available at the end of the embargo: 30th July 202
Drivers and economic consequences of quality of disclosure of non-GAAP measures
No full textThe full text will be available at the end of the embargo period: 31st December 2026
Development of novel tumour-activated peptide prodrugs of ATR/ATM inhibitor, AZD6738
No full textThe full text will be available at the end of the embargo period: 3rd April 2026The author's name as given on this thesis is Francis MPRAH BARNIEH. His publications use the name format Francis M. Barnieh
A Study On Employee’s Intention To Adopt Green Practices At The Workplace In The Context Of The Hotel Industry
Get PDFThis study aims to examine the effect of organisational commitment and
employee’s pro-environmental behaviour at home on their intention to adopt
green practices at the workplace in the context of hotel industry, by taking the
theory of planned behaviour as a conceptual framework. Hotel employees play
a critical role that affects customers' experiences, which then affects the overall
hotel performance. However, the mechanism that affects their behavioural
intention has yet to be investigated properly. Thus, a survey was conducted to
collect the data from employees working in green and non-green hotels in
Malaysia. Overall, there were 407 responses received, which represented a
response rate of 55.75 percent. Then, a set of hypotheses was tested using
the structural equation modelling. The empirical results indicate that
organisational commitments have a positive effect on the attitude for engaging
in a green behaviour and subjective norm, which in turn influenced employees’
intention to adopt green practices at work. Meanwhile, employees’ pro environmental behaviour at home has an indirect impact on employee’s
intention to adopt green practices in the workplace through their attitude for
engaging in a green behaviour, subjective norms, and perceived behavioural
control. The findings lead to a theoretical contribution by incorporating another
theory into the theory of planned behaviour, which is the social bond theory through organisational commitment and spill-over effect through pro environmental behaviour at home. Subsequently, a practical recommendation
from this research is attainable to policy makers and hotel providers in order
for them to understand and increase employees’ willingness to adopt green
practices at the workplace.The full text will be available at the end of the embargo: 15th Dec 202
A Novel Approach to Enhancing Security and Performance in Mobile Cloud Computing Using SDN, NFV, and CASB
No full textYesThe expansion of mobile cloud computing (MCC) has led to a rapid evolution in how data and services are delivered across geographically dispersed infrastructures. While MCC enables flexibility, scalability, and ubiquitous access, it presents critical security and performance challenges. This paper proposes a comprehensive architecture that leverages Software-Defined Networking (SDN), Network Function Virtualization (NFV), and Cloud Access Security Broker (CASB) to enhance the resilience, scalability, and manageability of MCC systems. We introduce a layered architecture where SDN controls the network plane, NFV deploys dynamic security functions, and CASB enforces data governance in cloud services. Through extensive experimentation using Mininet and traffic simulation tools, we evaluate the system’s latency, throughput, scalability, and security performance under various traffic conditions. Results demonstrate that the proposed solution achieves latency overhead under 5ms, successfully mitigates more than 90% of DDoS attacks, and scales efficiently to handle up to 10,000 firewall rules with less than 10% performance degradation. This integrated solution promises to strengthen MCC deployments, particularly in critical sectors like finance, healthcare, and smart cities.The full text will be available at the end of the publisher's embargo: 11th Aug 2026
Impact of Robot Companions on Customer Experience and Restaurant Service Outcomes in Dining Contexts
No full textYesThe advent of social robot introduces a new variable into this dynamic, expanding robots’ roles from task-oriented to companion roles in human interactions across various settings. This study explores the impact of robotic companions on dining experiences, focusing on consumer satisfaction, wellbeing, and business outcomes like amount of spending and of tip