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Charge-transfer luminophores: theranostic probes of the cellular environment
No full textLuminescent ruthenium(II) polypyridyl complexes and BODIPY-perylene charge-transfer compounds possess several remarkable properties that make them attractive for a range of applications including cellular imaging and phototherapy. These properties include large Stokes shifts, a crucial characteristic for enhancing the signal-to-noise ratio in fluorescence imaging. Moreover, their versatile synthetic chemistry allows for tailored designs for enhanced cellular imaging or for maximizing therapeutic efficacy. For example, the ability of these charge-transfer luminophores to generate cytotoxic reactive oxygen species upon photoexcitation makes them promising candidates for photodynamic therapy.
Presented in this thesis, are experimental findings on the Luminescent ruthenium(II) polypyridyl complexes and BODIPY-perylene charge-transfer compounds possess several remarkable properties that make them attractive for a range of applications including cellular imaging and phototherapy. These properties include large Stokes shifts, a crucial characteristic for enhancing the signal-to-noise ratio in fluorescence imaging. Moreover, their versatile synthetic chemistry allows for tailored designs for enhanced cellular imaging or for maximising therapeutic efficacy. For example, the ability of these charge-transfer luminophores to generate cytotoxic reactive oxygen species upon photoexcitation makes them promising candidates for photodynamic therapy.
Presented in this thesis, are experimental findings on the phototherapeutic potential of a Ru(II) parent complex Ru-bqp-ester and its peptide conjugates Ru-bqp-MPP and Ru-bqp-R8, which showed exceptional phototoxicity across a range of cancer and non-cancer cell lines. Conjugation to cell penetrating and signal peptides is a useful strategy for promoting cellular uptake and targeting specific organelles such as the mitochondria or the nucleus, however, guanine quadruplexes (G4s) are gaining increasing interest as therapeutic targets. Two G4 targeted Ru(II) complexes, Ru-TAP-PDC3 and Ru-RHAU, were investigated as probes for imaging and phototherapy. Ru-TAP-PDC3 is the first Ru(II) complex directed toward photodamage of G4s located in the mitochondrial genome and Ru-RHAU is the first reported dye capable of live cell imaging of stress granules (SGs), binding to G4s and inducing SGs in a time and concentration dependent manner. Additionally, a family of iodinated and non-iodinated BODIPY compounds were tested as Luminescent ruthenium(II) polypyridyl complexes and BODIPY-perylene charge-transfer compounds possess several remarkable properties that make them attractive for a range of applications including cellular imaging and phototherapy. These properties include large Stokes shifts, a crucial characteristic for enhancing the signal-to-noise ratio in fluorescence imaging. Moreover, their versatile synthetic chemistry allows for tailored designs for enhanced cellular imaging or for maximising therapeutic efficacy. For example, the ability of these charge-transfer luminophores to generate cytotoxic reactive oxygen species upon photoexcitation makes them promising candidates for photodynamic therapy.
Presented in this thesis, are experimental findings on the phototherapeutic potential of a Ru(II) parent complex Ru-bqp-ester and its peptide conjugates Ru-bqp-MPP and Ru-bqp-R8, which showed exceptional phototoxicity across a range of cancer and non-cancer cell lines. Conjugation to cell penetrating and signal peptides is a useful strategy for promoting cellular uptake and targeting specific organelles such as the mitochondria or the nucleus, however, guanine quadruplexes (G4s) are gaining increasing interest as therapeutic targets. Two G4 targeted Ru(II) complexes, Ru-TAP-PDC3 and Ru-RHAU, were investigated as probes for imaging and phototherapy. Ru-TAP-PDC3 is the first Ru(II) complex directed toward photodamage of G4s located in the mitochondrial genome and Ru-RHAU is the first reported dye capable of live cell imaging of stress granules (SGs), binding to G4s and inducing SGs in a time and concentration dependent manner. Additionally, a family of iodinated and non-iodinated BODIPY compounds were tested as potential photosensitisers, confirming a significant increase in phototoxicity upon iodination.
A key aim of this thesis was to investigate the phototherapeutic potential of novel Ru(II) or BODIPY-based photosensitisers in live cells and multicellular tumour spheroids, and extend the application of these compounds for cellular imaging and sensing using confocal microscopy. potential photosensitisers, confirming a significant increase in phototoxicity upon iodination.
A key aim of this thesis was to investigate the phototherapeutic potentialof novel Ru(II) or BODIPY-based photosensitisers in live cells and multicellular tumour spheroids, and extend the application of these compounds for cellular imaging and sensing using confocal microscopy.phototherapeutic potential of a Ru(II) parent complex Ru-bqp-ester and its peptide conjugates Ru-bqp-MPP and Ru-bqp-R8, which showed exceptional phototoxicity across a range of cancer and non-cancer cell lines. Conjugation to cell penetrating and signal peptides is a useful strategy for promoting cellular uptake and targeting specific organelles such as the mitochondria or the nucleus, however, guanine quadruplexes (G4s) are gaining increasing interest as therapeutic targets.
Two G4 targeted Ru(II) complexes, Ru-TAP-PDC3 and Ru-RHAU, were investigated as probes for imaging and phototherapy. Ru-TAP-PDC3 is the first Ru(II) complex directed toward photodamage of G4s located in the mitochondrial genome and Ru-RHAU is the first reported dye capable of live cell imaging of stress granules (SGs), binding to G4s and inducing SGs in a time and concentration dependent manner. Additionally, a family of iodinated and non-iodinated BODIPY compounds were tested as potential photosensitisers, confirming a significant increase in phototoxicity upon iodination.
A key aim of this thesis was to investigate the phototherapeutic potential of novel Ru(II) or BODIPY-based photosensitisers in live cells and multicellular tumour spheroids, and extend the application of these compounds for cellular imaging and sensing using confocal microscopy
Gyrofluid simulations of filaments in tokamak edge plasmas
Full text linkCross field transport in the edge of magnetically confined plasmas is known to be turbulent in nature, specifically the transport is composed largely of plasma filaments. Understanding and quantifying this transport is of key importance when considering particle and heat loads for future devices.
Filament velocity scaling laws, derived using linearised drift-fluid models, and reproduced through fluid simulations are of key importance when considering filament propagation. They are also used in statistical models of the edge that relate filamentary fluctuations to mean scrape-off-layer (SOL) profiles. These same velocity scaling laws are reproduced herein both computationally and theoretically with a deviation identified and explained in the limit of small filament widths. Filament simulations have been carried out using a gyrofluid model known as GEM (electromagnetic gyrofluid model), implemented in the BOUT++ (BOUndary Turbulence in C++) framework, both with the inclusion of finite Larmor radius (FLR) effects and also with the gyroaverage operators taken in the limit of small Larmor radius to resemble drift-fluid models. Simulations were carried out over a range of filament sizes and a simplified slab geometry was employed with parameters chosen to represent typical conditions in the edge of the Mega Ampere Spherical
Tokamak (MAST). Good agreement with the sheath-limited velocity scaling relation is found in both the drift-fluid limit and when FLR effects are included. Agreement is also found with the inertial limit when simulations with GEM are carried out in the drift-fluid limit. However, a deviation from the inertial velocity scaling relation is observed when
FLR effects are included. This deviation is explained through linearisation of the underlying equations. Finally, edge profiles and radial heat flux decay length are interpreted through radially averaged profiles of self-consistent turbulent simulations that include both the core and the SOL
Health literacy interventions and health literacy-related outcomes for older adults: a systematic review
Full text linkBackground Older adults, identified as 65 years and over, a population for which low health literacy is prevalent, represented most people attending primary health care services provided by the Health Service Executive (HSE) in Ireland in 2019. Any limitation in a person’s health literacy, specifically their ability to access, understand and use health information, can affect their ability to make healthcare related decisions. Information on the evidence for health literacy interventions is also required by healthcare providers and policy makers to inform decision-making
and service development to improve outcomes for older people. This review aimed to synthesise the evidence on health literacy interventions and health literacy-related outcomes for older adults. The specific objectives were to (1) identify what health literacy interventions exist in relation to older adults’ ability to access, understand, and use health
information, (2) determine the health literacy-related outcomes of these interventions, and (3) identify any trends or patterns which may exist between intervention type and outcome. Methods: This review was conducted by following PRISMA guidelines. The electronic databases PubMed, Embase and Scopus were searched for relevant studies concerning health literacy interventions for older persons. Study
data were subsequently analysed using a narrative thematic approach in the context of the three key health literacy characteristics; the ability to access, understand and use health information.
Results: Thirty-four studies were identified that met the inclusion criteria. The findings show a potential link between individual-focused health literacy interventions and positive health literacy-related outcomes in relation to older persons’ ability to understand and use health information. The review also found that use of health literacy level assessment tools varied with studies either using different tools for the same older adult cohort, or failing to assess pre-intervention health literacy levels altogether.
Conclusions: The potential trend found between individual-focused interventions and positive health literacy
outcomes suggests that implementing health literacy-related interventions directly to the individual is key. Furthermore, our study found an inconsistency amongst the included studies in relation to the implementation of health literacy assessment tools, with different tools used across most studies, and some studies choosing not to
utilise any assessment tool
Sacrificial Love (Of Cyborgs, Saviors, and Driller, a Real Robot Killer) in the Comics Descender and Ascender
Full text linkSeeking to examine cases of sacrificial love for another that is empathetic, unconditional, and morally redemptive, I focus on writer Jeff Lemire’s and artist Dustin Nguyen’s heralded comic series, Descender and Ascender (published by Image Comics starting in 2015 and 2018, respectively). In the first main subsection, I argue how illustrative fictional cases (some involving robots) can mirror inter-human ethical struggles in our own world and examine what I call the “The R2-D2 and Wall-E Syndrome”. Next, I look at some representative theoretical, literary, and biblical examples of sacrifice, especially regarding morally problematic theories about Jesus’ death on the cross, a classic Western example of sacrificial love. I then provide a brief context for why I chose Descender and Ascender and highlight some of the main themes and characters in the comics. In doing so, I draw from three main examples: the cyborg and mother Effie (Queen Between), the companion robot TIM-21, and the robot Driller (“a real killer”), where I gleam key traits of sacrificial love as empathetic, unconditional, and morally redemptive. I close with how to distinguish unholy and holy forms of sacrificial love and reflect on how the examples of sacrificial love in the comics ultimately complement my reading of Jesus’ sacrificial death on the cross while adding some stipulations to his oft-quoted saying: “No one has greater love than this, to lay down one’s life for one’s friends” (John 15:13)
Academic freedom in Irish higher education
Full text linkAcademic freedom has been the subject of considerable debate, in terms of the academic practices of academics and students, and the role of democratic principles in higher education. It has been argued that academic freedom is being threatened in several European countries, including those within the EU. To explore how academic freedom is experienced by academics and postgraduate students in one European country, Ireland, that has witnessed significant changes in higher education, we interviewed 15 academics and 10 postgraduate students. Results indicate general satisfaction with the level of academic freedom in Ireland. However, participants also expressed concerns relating to university autonomy, which can also affect academic freedom. The findings also indicate that the transformation of universities into institutions operating under the control of external entities and structures can be problematic. As such, we argue that the use of these institutions as tools for market driven policies poses the risk of limiting academic freedom for both academics and students
Diplomatic Training and Spaces of Anticolonial Worldmaking
Full text linkFocusing on training for African diplomats from newly independent countries in Cameroon, Kenya, and Zimbabwe, this paper makes the case for spaces of diplomatic training as sites for anticolonial “worldmaking” (Getachew 2019; Worldmaking After Empire: The Rise and Fall of Self-Determination). Recent scholarship has highlighted the value of African leaders’ visions but largely overlooked the actors, spaces, and practices through which these visions were to be enacted. Drawing on archival evidence from Africa, Europe, and North America, and oral history interviews, we argue that worldmaking projects were grounded, learnt, and transformed in places such as the classrooms and study tours we explore. Whilst many accounts of anticolonial and subaltern geopolitical projects focus on grassroots activism beyond and against the state, we argue we also need to attend to the contributions of those—like African diplomats in training—who critiqued Eurocentric and colonial international relations from subaltern positions whilst remaining privileged within the context of the postcolonial state
Exploring how the tradition of well-being in Catholic Thought impacts well-being approaches in Catholic Schools.
Full text linkWell-being is a multidimensional concept that is growing in interest and relevance globally. It is of increasing relevance in education, with schools needing to balance the academic success of students with maintaining and nurturing their levels of well-being. In the Catholic tradition, well-being is not a commonly used term. Instead, the language of human
flourishing is used to express a multidimensional understanding of well-being that refers to humans achieving their full potential in all dimensions: physical, mental, emotional, spiritual and relational. Research into the discourse between student well-being provision in schools and a Catholic tradition of human flourishing is limited. This project addresses the research gap relating to how Catholic schools draw on human flourishing from a Catholic perspective to inform provision for student well-being. It is a cross-national study and the participating schools are situated in the Archdioceses of Dublin and Birmingham. This study adopts a qualitative,
case-study methodology and semi-structured interviews are used as the method of data collection. The findings demonstrate that some Catholic schools do draw upon teachings and tradition within the Catholic Church to inform their approach to student well-being provision. Catholic
schools in Birmingham demonstrated confidence in the Catholic tradition and its ability to positively impact upon the well-being of students. This confidence was not shared in the Dublin schools, where students were more vocal about their negative perception of the Catholic Church. This has resulted in the Catholic tradition being left to flounder in Dublin
Catholic schools. The implications of this are discussed in detail and recommendations for further research are proffered
Targeted Therapeutic Strategies in Pancreatic and Gastroesophageal Cancers: Precision Medicine Approaches to Overcoming Drug Resistance and Advancing Organoid Development
No full textPancreatic ductal adenocarcinoma (PDAC) and gastroesophageal cancer (GEC) are among the most lethal malignancies. The absence of early symptoms means that most patients are diagnosed at late stages with advanced disease. Despite progress in treatment, the overall prognosis remains poor mainly due to their inherent and/or acquired resistance to
conventional therapies. The efficacy of new treatment strategies has been hampered by the lack of efficient preclinical models recapitulating the heterogeneity and complexity of these cancers resulting in the ineffective clinical translation of novel targeted therapeutic options.
Therefore, we explored the impact of traditional two-dimensional (2D) and threedimensional (3D) culture conditions on cancer stem cell (CSC) markers, epithelialmesenchymal transition, hypoxia profiles, and treatment responses in PDAC systems. We found that 3D cultures more closely mimic the tumour microenvironment and exhibit distinct cellular behaviours, suggesting that 3D organoids provide a more accurate model for studying treatment responses and therapeutic resistance.
Acquired drug resistance to 5-FU (the backbone chemotherapeutic of treatment regimens for PDAC and GEC) in two patient-derived organoids (PDOs) were developed to investigate the mechanisms of chemotherapeutic resistance and identify novel targeted therapeutic
strategies. Transcriptomic and proteomic analyses identified key dysregulated therapeutic vulnerabilities. Phototoxic peptide conjugates targeting the modulators of drug resistance, and pharmacological inhibitors circumvented the development of resistance. Finally, we
established and characterised PDOs from treatment-naïve GEC patients and demonstrated the feasibility of using PDOs to evaluate sensitivity to chemotherapy. Here we identified actionable targets from the genomic and transcriptomic landscape of the organoids matched to their original tumour to highlight the translatability of precision medicine. Our research
demonstrated that advanced 3D organoid systems represent valuable tools for modelling drug resistance and offer opportunities to discover novel therapeutic approaches to prevent the emergence of drug resistance, to improve patient outcomes through more effective and
personalised treatments
Laser modification for the increased lifetime of a commercial Stainless-Steel Alloys
Full text linkThis research explores laser-induced surface processing to modify surface properties, enhancing the durability and performance of Pulsed Electric Field (PEF) systems. PEF systems use electromagnetic pulses to lyse bacterial cell walls for food pasteurization. However, electrode corrosion and biofouling pose challenges. This study investigates laser-induced oxidation to mitigate metal ion release during PEF operations.
The research focuses on three core areas: (1) expanding a thermokinetic model to predict oxide layer composition and color, (2) optimizing laser oxidation to improve corrosion resistance, and (3) integrating the modified surface into a PEF system.
A model for Nd:YAG laser oxidation of 316L stainless steel was developed using a factorial Design of Experiments (DoE). X-ray photoelectron spectroscopy (XPS) and optical reflectance spectroscopy determined elemental composition and color variations. Oxide layers exhibited a Cr/Fe ratio from 0.13 to 4.5, with controlled color changes via single-pass laser processing.
Further, corrosion resistance was analyzed through laser processing, examining surface chemistry, morphology, and electrochemical properties. Factorial DoE analysis showed lower areal energy samples had superior corrosion resistance and minimal defects, confirmed by cyclic polarization and electrochemical impedance spectroscopy (EIS).
Finally, PEF trials integrated DoE, morphological analysis, metal ion release (via ICP-QMS), waveform capture (DAQ system), and impedance spectroscopy. Pulse waveform variations demonstrated a three-fold reduction in metal ion release in laser-treated samples.
This study offers key insights into optimizing laser parameters to enhance corrosion resistance and surface chemistry, improving metal performance in PEF systems. These advancements contribute to sustainable food processing by extending PEF system lifespan while maintaining efficiency and product quality
Knowledge production and learning in housing struggles
Full text linkThis article examines the impact of advocacy for non-housing issues and its spillover onto housing movements. Adopting the viewpoint that activism is a social practice that generates knowledge, this study analyses how activists in social movements produce, share, and disseminate knowledge through fieldwork research conducted in Dublin, Ireland. The findings reveal that knowledge transmission, critical
thinking, and innovation are crucial for fostering productive dialogue among groups engaged in strategic housing action. Moreover, the research demonstrates that housing movements contribute to the development of novel cognitive and epistemic solutions through their practical and discursive interactions with other non-housing
social movements. These results make a meaningful contribution to housing studies and social movement studies by shedding light on the political and social dynamics that give rise to new knowledge and innovative housing practices