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Development of novel ciliopathy specific promoter sequences for optimal gene therapy transgene expression in syndromic inherited retinal diseases
No full textThis thesis was submitted for the award of Master of Philosophy and was awarded by Brunel University LondonBardet-Biedl syndrome (BBS) is a syndromic ciliopathy characterised by progressive
retinal degeneration, obesity, polydactyly, renal dysfunction, and cognitive impairment.
More than 26 genes have been implicated in the BBS disease pathogenesis, many of
which encode components of the BBSome, or associated chaperonin complexes
required for ciliary trafficking in photoreceptors. The genetic heterogeneity, large
coding sequences, and systemic manifestations of BBS are the main significant
challenges for developing retinal gene therapeutics. In addition to the limited
packaging capacity of the adeno-associated virus (AAV) vectors and the need for
photoreceptor-specific transgene expression. Synthetic promoters are increasingly
recognised as critical tools to optimize transgene delivery for BBS gene therapy.
Native endogenous promoters have several fundamental limitations in terms of their
size, cis-elements distribution and mode of induction, these factors reflected
insufficient transcriptional activity. Synthetic promoters, by contrast, can be engineered
to achieve spaciotemporal transgene expression levels. These synthetic promoters
are capable for driving the transgene’s expression specifically in the target cells with
the required levels. Although there are different approaches have been tested to
develop human-based synthetic promoters, in this study we utilized a new approach,
by conjugating transcription factors binding sites (TFBS) which can enhance the
expression of BBS cDNAs expressed from recombinant AAV vectors. Based on the
simple-enrichment analysis results, the promoters of BBS genes sequences were
significantly enriched with a group of transcription factor response elements (TFREs)
such as RFX, SP transcription factors. We designed the sequences of the resulted
TFREs into heterotypic clusters to create BBS gene specific synthetic promoters’
library. This library is composed of six different candidate promoter constructs (CPCs)
cloned upstream minimal promoters YBTATA and minP. All CPCs activities were tested
in HEK293Ts and ARPE-19 cells. The transcriptional activity of the CPCs was
compared in ARPE-19 cells during ciliogenesis when BBS genes are active, 24-hr
serum-starvation, and in serum-containing condition. During ciliogenesis, some CPCs
containing proximal and distal regulatory binding sites showed increased transcriptional activity by driving the green fluorescent protein expression (GFP) in
comparison to same CPCs activity in serum-containing media.
Our synthetic promoters offer a versatile and powerful means of achieving optimal
transgene expression for BBS gene therapy. By combining compact size, cell -type
specificity, and potential inducibility, our synthetic promoters addressed critical barriers
shown by natural promoters.The University of Jordan, that supported my research through scholarships, grants, and travel funds
Characterising phase transition and thermal behaviour of phase change material with nanobubbles: A comparative molecular dynamics study
No full textData availability:
Data will be made available on request.Global warming and the rising demand for sustainable energy have intensified interest in efficient thermal energy storage. Phase change materials (PCMs) offer high latent heat storage capacity but have poor thermal performance. By incorporating nanoscale additives, nano-enhanced PCMs can improve overall efficiency in renewable energy applications. Nanobubbles (NBs), gaseous cavities under 1 μm, have unique properties that make them promising candidates for various industrial applications, including in the energy and power sectors. Molecular-level approaches can provide valuable insights into the thermal effects of NBs. In this study, molecular dynamics simulations were employed to simulate the phase transition behaviour and thermal properties of NB enhanced dodecane. This study explored different NBs of hydrogen, nitrogen, and oxygen and compared with the pure dodecane in comparative analysis. The findings demonstrate that the incorporation of NBs, particularly hydrogen NB, depresses the liquid-to-solid transition temperature of dodecane. Additionally, the presence of NBs enhances both thermal conductivity and specific heat capacity, with nitrogen NBs yielding the highest increase in thermal conductivity by approximately 14 %. Furthermore, nitrogen and hydrogen NBs were identified as promising candidates for high-temperature applications due to their stability over a wide temperature range; however, their presence also results in an increase in viscosity
Leveraging Data Science to Investigate Intelligence Failures
No full textThis article challenges the conventional assumption underpinning the ‘First Law of Intelligence Failure’ – that warning signs are always available, but ignored, prior to intelligence breakdowns. Employing advanced natural language processing and machine learning techniques, the authors analyse declassified US State Department cables from the 1970s, focusing on two case studies often deemed intelligence failures: the Soviet invasion of Afghanistan and the Iranian Revolution. Using semantic outlier and change-point detection algorithms, they test whether meaningful signals (‘signal in the noise’) or emergent patterns (‘connecting the dots’) were more prevalent prior to failure than in earlier, ‘successful’ periods. The study finds this is not consistently the case, suggesting that indicators are not uniformly available or discernible before failures occur. By demonstrating the limitations of this study, the article concludes that the binary framing of intelligence as either success or failure is analytically flawed and potentially misleading. It offers a proof-of-concept for applying data science to intelligence analysis and advocates for a more nuanced understanding based on baselines and deviations, rather than retrospective judgements shaped by hindsight.The author(s) reported there is no funding associated with the work featured in this article
Women scholars' coping narratives in generating research impact cases in the UK: insights from Sisyphus, Hestia and Tyche
No full textPurpose:
We explore how women management scholars navigate “doing” research impact. Drawing on the voices of women leaders of research impact cases in UK business schools, we identify and theorise three distinct autobiographical narratives of coping. To inform systemic changes for more equitable national research policy implementation, we highlight barriers that deter individuals from becoming impactful scholars.
Design/methodology/approach:
This qualitative study comprises semi-structured interviews with 15 mid/late career women research impact case study leaders who were purposively selected to reflect on their lived experiences of impact case study generation.
Findings:
A thematic analysis revealed three mythological archetypes: Sisyphus (a figure in Greek mythology whose eternal repetitive and futile punishment was to roll a boulder uphill, only for it to roll back down), Hestia (the Greek Goddess of the hearth) and Tyche (the Greek Goddess of luck and change). Our empirical study contributes to understanding how individual women management scholars experience and cope with the UK’s research impact policy agenda in the neoliberal university.
Research limitations/implications:
The interviewees’ accounts of coping with REF (Research Excellence Framework) impact case studies are subjective and have influenced the research process and findings. The study has important practical and policy implications.
Practical implications:
The study has important practical and policy implications.
Originality/value:
We call for more inclusive systemic opportunities in business schools in terms of who “does impact” and how they are supported in coping with the demands of research impact work. We advocate rethinking traditional heroic paradigms of academic labour (Harley, 2019), to enable women impact case writers to shift from Sisyphean struggles to greater recognition, inclusion and support for their contributions.No funding was received for this research
Design and Analysis of a Photonic Crystal Fiber Sensor for Identifying the Terahertz Fingerprints of Water Pollutants
Get PDFData Availability Statement:
No data was used in this research.Ensuring the purity of water sources is a paramount global challenge, necessitating the development of highly sensitive and rapid detection technologies. In this work, a novel Zeonex-based photonic crystal fiber (PCF) sensor is designed and numerically analyzed for the effective differentiation of pure and polluted water by identifying their unique fingerprints in the terahertz (THz) spectrum. The proposed structure features a rectangular core for analyte infiltration, surrounded by a unique hybrid cladding, meticulously engineered with four inner “mode-shaping” rectangular air holes and an outer “confinement” ring of elliptical air holes. This complex topology is strategically designed to maximize the core-power fraction while ensuring robust mode confinement, enabling the exceptional performance metrics observed. The guiding properties and sensing performance of the sensor are rigorously scrutinized using the Finite Element Method (FEM) over a broad frequency range of 0.5 to 3 THz, accommodating analytes with refractive indices from 1.33 to 1.46. This range is specifically chosen to cover the refractive index of pure water (≈1.33) and a broad spectrum of common chemical and biological pollutants. The simulation results demonstrate the exceptional performance of the sensor. For polluted water, the sensor achieves an ultra-high relative sensitivity of 99.6% with a negligible confinement loss of 1.4 × 10⁻¹¹ dB/m at an operating frequency of 3 THz. In contrast, pure water exhibits a high sensitivity of 96% and a confinement loss 9.4 × 10⁻⁶ of dB/m at the same frequency, showcasing a remarkable capability to distinguish between different water qualities. The superior sensitivity, extremely low loss, and structurally feasible design make the proposed PCF sensor an up-and-coming candidate for real-time water quality monitoring within the THz domain.This research received no external funding
Digital Competencies for a FinTech-Driven Accounting Profession: A Systematic Literature Review
Get PDFData Availability Statement:
The data for this study were retrieved from publicly available academic databases, namely [Scopus, Web of Science, EBSCO]. The search strings and selection criteria are described in the methodology section, and the final list of articles included in the synthesis is provided within the manuscript.Financial Technology (FinTech) is fundamentally reshaping the accounting profession, accelerating the shift from routine transactional activities to more strategic, data-driven functions. This transformation demands advanced digital competencies, yet the scholarly understanding of these skills remains fragmented. To provide conceptual and analytical clarity, this study defines FinTech as an ecosystem of enabling technologies, including artificial intelligence, data analytics, and blockchain, that collectively drive this professional transition. Addressing the lack of systematic synthesis, the study employs a systematic literature review (SLR) guided by the PRISMA 2020 framework, complemented by bibliometric analysis, to map the intellectual landscape. The review focuses on peer-reviewed journal articles published between January 2020 and June 2025, thereby capturing the accelerated digital transformation of the post-pandemic era. The analysis identifies four dominant thematic clusters: (1) the professional context and digital transformation; (2) the educational response and curriculum development; (3) core competencies and their technological drivers; and (4) ethical judgement and professional responsibilities. Synthesising these themes reveals critical research gaps in faculty readiness, curriculum integration, ethical governance, and the empirical validation of institutional strategies. By offering a structured map of the field, this review contributes actionable insights for educators, professional bodies, and firms, and advances a forward-looking research agenda to align professional readiness with the realities of the FinTech era.This research received no external funding
Ubiquitous synchronised semi-immersive cycle training: A technical architecture development and user pilot study
No full textData Availability:
Parts of the data, beyond what is in the paper, is confidential. Anonymised, non-confidential data can be made available upon reasonable request.The application of virtual reality (VR) technology for immersive training shows promise in a variety of tasks, including cycling. However, methods that use head mounted displays (HMDs) are bulky, expensive and difficult to work with for larger groups of students. In this paper, we explore the utility of common and ubiquitous mobile devices in semi-immersive cycle training. We present the development of a technical architecture for synchronised semi-immersive training, featuring centralised 360°
video playback controls for instructors. We conducted interviews with four groups of students aged 9-11 and three instructors. Furthermore, we collected survey data from 67 students across three different groups. We report that students and instructors alike, find this approach to be effective, immersive and highly accessible.Funding for development of the apps was provided by the Bikeability Trust, for which we are deeply grateful
Epigenomic subtyping of late‐onset Alzheimer's disease reveals distinct microglial signatures and molecular inflammatory phenotypes
Get PDFBasic Science and Pathogenesis poster presentation at The Alzheimer’s Association International Conference (AAIC25), Toronto, Canada, 27-31 July 2025.Background:
Growing evidence suggests that the heterogeneity of late-onset Alzheimer's disease (LOAD) plays a significant role in treatment failure. In recent years, molecular subtyping of AD has increasingly leveraged omics data to uncover distinct molecular profiles that may underlie the observed heterogeneity in disease manifestation and mechanisms. This has been particularly transformative as traditional classification methods based on clinical or pathological features alone have proven insufficient.
Method:
We applied data-driven clustering to genome-wide DNA methylation (DNAm) data from three independent post-mortem AD brain cohorts (n = 831). To determine the brain cell-type specificity of the findings identified using bulk DNAm profiles, we isolated four nuclei populations from PFC tissue of 20 donors with low neuropathology from the Brains for Dementia Research (BDR) cohort.
Result:
This study identified two distinct epigenetic subtypes of LOAD using genome-wide DNAm. Data-driven clustering revealed reproducible LOAD subtypes characterized by cell-type-specific DNAm profiles. Bulk transcriptomic analyses further emphasize divergent biological mechanisms driving these subtypes, with subtype 1 (LOAD-S1) enriched in immune-related processes and subtype 2 (LOAD-S2) in neuronal and synaptic functions. Subtype-specific microglial single-cell transcriptional signatures revealed that LOAD-S1 represents a state of chronic innate immune hyperactivation and impaired resolution, while LOAD-S2 displays a dynamic inflammatory profile, balancing pro-inflammatory signals with reparative and regulatory mechanisms (see Figure).
Conclusion:
These subtype-specific immune signatures provide critical insights into the molecular heterogeneity of LOAD and highlight potential therapeutic targets tailored to the immune dysregulation observed in each subtype
Estimating the environmental impact of diets based on individual-level dietary intake data: infographics on the FAO/WHO GIFT platform
Get PDFData availability statement:
The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found at https://www.fao.org/gift-individual-food-consumption/en/.Generative AI statement:
The authors declare that no Gen AI was used in the creation of this manuscript.
Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible.Integrating environmental impacts into dietary assessment is crucial to promote healthy diets from sustainable food systems. Nonetheless, the environmental impacts of individual dietary intake are rarely reported. This paper describes how environmental impacts are integrated into dietary data through the FAO/WHO Global Individual Food Consumption Data Tool (FAO/WHO GIFT). The environmental infographics available on FAO/WHO GIFT offer a user-friendly interface to understand the average footprint of diets, identifying contributing food groups, and exploring variations in environmental impacts. The infographics present estimates for three environmental indicators - greenhouse gas emissions, water use, and land use of dietary intake, allowing users to assess the environmental implications of different diets. Tools to monitor and assess dietary environmental impact, such as those offered by FAO/WHO GIFT, are essential for informing transformation towards healthy diets from sustainable food systems.This research was funded by the Gates Foundation, grant numbers INV-010508 and INV-053345, and the Food and Agriculture Organization of the United Nations
Modelling of Aerostatic Bearings with Micro-Hole Restriction
Get PDFData Availability Statement:
The original contributions presented in this study are included in the article. Further inquiries can be directed to the corresponding author.Aerostatic bearings incorporating micro-hole restrictors with diameters on the order of tens of microns demonstrate superior static and dynamic stiffness characteristics, while significantly reducing air consumption, and are increasingly adopted in precision engineering applications. This paper investigates the modelling of aerostatic bearings with micro-hole restrictors. First, a refined discharge coefficient formula is developed, incorporating the orifice length-to-diameter ratio effect using the computational fluid dynamics (CFD) simulation results on a centrally fed circular aerostatic bearing. A numerical solution scheme is proposed using the developed discharge coefficients to enable more accurate and efficient prediction of the bearing performance and flow characteristics. Finally, the proposed numerical approach is implemented using the finite difference method (FDM) and demonstrated through a circular thrust air bearing case study. The results are validated against both CFD simulations and experimental measurements, showing excellent agreement and confirming the reliability of the FDM-based numerical model. Numerical and experimental investigations consistently demonstrate that micro-hole-restricted air bearings can achieve both high load capacity and high stiffness, having the potential for application in more complex air bearing designs and systems.This research received no external funding
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