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Developing a three dimensional (3D) in vitro model of adrenocortical carcinoma (ACC)
No full textAdrenocortical carcinoma (ACC) is a rare orphan disease and a rare cancer which carries a poor prognosis. The only licensed pharmacological treatment is mitotane, an insecticide. Typically, 2D cell culture models have been used to study ACC and represent the best available disease models for mechanistic insight of disease and therapeutics. However, these models have limited representation of disease in humans. Moreover, the rare nature of disease translates to a lack of human tissue specimens for research and culture, again limiting the investigation of disease mechanism in the context of ACC. As such all-cell lines and animal models are limited in their representation of human disease and hence multiple models are usually necessary to design investigative approaches to disease which help thoroughly understand and study the biology and propagation of this cancer. In the current thesis of work, we developed and characterize a spheroid model for primary tumour cell line, H295R and a metastatic cell line, MUC-1, showing a steroidogenic enzymatic cell profile. Additionally, we develop a collagen scaffold 3D model of H295R and MUC-1 that attempts to mimic the complexity of the extracellular matrix (ECM) supporting cell viability, metabolic activity, steroids production. Despite the lack of experimental replicates, altogether represents a preliminary data for a model to study ACC which retains its phenotype and steroidogenic properties
Global perspectives on operational excellence: unveiling critical failure factors and sustainable pathways
No full textPurpose The purpose of this global study is to investigate the critical failure factors (CFFs) in the deployment of operational excellence (OPEX) programs as well as the key performance indicators (KPIs) that can be used to measure OPEX failures. The study also empirically analyzes various OPEX methodologies adopted by various organizations at a global level. Design/methodology/approach This global study utilized an online survey to collect data. The questionnaire was sent to 800 senior managers, resulting in 249 useful responses. Findings The study results suggest that Six Sigma is the most widely utilized across the OPEX methodologies, followed by Lean Six Sigma and Lean. Agile manufacturing is the least utilized OPEX methodology. The top four CFFs were poor project selection and prioritization, poor leadership, a lack of proper communication and resistance to change issues. Research limitations/implications This study extends the current body of knowledge on OPEX by first delineating the CFFs for OPEX and identifying the differing effects of these CFFs across various organizational settings. Senior managers and OPEX professionals can use the findings to take remedial actions and improve the sustainability of OPEX initiatives in their respective organizations. Originality/value This study uniquely identifies critical factors leading to OPEX initiative failures, providing practical insights for industry professionals and academia and fostering a deeper understanding of potential pitfalls. The research highlights a distinctive focus on social and environmental performance metrics, urging a paradigm shift for sustained OPEX success and differentiating itself in addressing broader sustainability concerns. By recognizing the interconnectedness of 12 CFFs, the study offers a pioneering foundation for future research and the development of a comprehensive management theory on OPEX failures.peer-reviewe
Proactive esophageal cooling during laser cardiac ablation: A computer modeling study
No full textBackground and Objectives Laser ablation is increasingly used to treat atrial fibrillation (AF). However, atrioesophageal injury remains a potentially serious complication. While proactive esophageal cooling (PEC) reduces esophageal injury during radiofrequency ablation, the effects of PEC during laser ablation have not previously been determined. We aimed to evaluate the protective effects of PEC during laser ablation of AF by means of a theoretical study based on computer modeling. Methods Three-dimensional mathematical models were built for 20 different cases including a fragment of atrial wall (myocardium), epicardial fat (adipose tissue), connective tissue, and esophageal wall. The esophagus was considered with and without PEC. Laser-tissue interaction was modeled using Beer¿Lambert's law, Pennes' Bioheat equation was used to compute the resultant heating, and the Arrhenius equation was used to estimate the fraction of tissue damage (FOD), assuming a threshold of 63% to assess induced necrosis. We modeled laser irradiation power of 8.5¿W over 20¿s. Thermal simulations extended up to 250¿s to account for thermal latency. Results PEC significantly altered the temperature distribution around the cooling device, resulting in lower temperatures (around 22°C less in the esophagus and 9°C in the atrial wall) compared to the case without PEC. This thermal reduction translated into the absence of transmural lesions in the esophagus. The esophagus was thermally damaged only in the cases without PEC and with a distance equal to or shorter than 3.5¿mm between the esophagus and endocardium (inner boundary of the atrial wall). Furthermore, PEC demonstrated minimal impact on the lesion created across the atrial wall, either in terms of maximum temperature or FOD. Conclusions PEC reduces the potential for esophageal injury without degrading the intended cardiac lesions for a variety of different tissue thicknesses. Thermal latency may influence lesion formation during laser ablation and may play a part in any collateral damage.peer-reviewe
Enabling dataspaces using foundation models: Technical, legal and ethical considerations and future trends
No full textFoundation Models are pivotal in advancing arti ficial intelligence, driving notable progress across diverse areas. When merged with dataspace, these models enhance our capabil ity to develop algorithms that are powerful, predictive, and honor data sovereignty and quality. This paper highlights the potential benefits of a comprehensive repository of Foundation Models, contextualized within dataspace. Such an archive can streamline research, development, and education by offering a comparative analysis of various models and their applications. While serving as a consistent reference point for model assessment and fostering collaborative learning, the repository does face challenges like un biased evaluations, data privacy, and comprehensive information delivery. The paper also notes the importance of the repository being globally applicable, ethically constructed, and user-friendly. We delve into the nuances of integrating Foundation Models within dataspace, balancing the repository’s strengths against its limitations.We would like to acknowledge Science Foundation Ireland (SFI/12/RC/2289 P2) for funding this research
The impact of climate change on the performance of residential buildings from an occupant-centric perspective – A systematic review
No full textEurope faces the challenge of providing affordable and high-quality housing for growing populations, while reducing its buildings’ energy consumption and phasing out fossil fuels. However, in the context of climate change, progressively warmer summers and increasingly frequent heatwave events not only intensify the risks of overheating, but they also impact building energy consumption and indoor environmental quality. To better understand these impacts, there is a need for the development of reliable methods to predict future weather scenarios and building performance that appropriately accounts for occupants. This systematic literature review aims to investigate methodologies and metrics for assessing performance of dwellings under future climate conditions, including health and wellbeing of building occupants. The PRISMA 2020 approach was applied to identify the current literature of case studies of dwellings’ performance under future weather scenarios. The Mendeley Reference Manager and the ASReview Lab were used to assist screening the papers, while the selected case studies were chosen based on relevance and quality criteria. The results of this review indicate that methods based on building simulation tools can be used to project building performance in response to Climate Change. While the current literature has been focusing on buildings’ thermal and energy performance, indoor air quality (IAQ) is still a topic not much explored. Additionally, despite the complexity and uncertainty on occupant’s behaviour, the application of uncertainty/sensitivity analysis associated with the use of computational tools can provide promising results for occupant-centric building performance in changing climate
Non–nucleophilic grignard synthesis of chiral bridged pyridine–oxazoline ligands for asymmetric catalysis
No full textThe enantioselective synthesis of chiral compounds, such as those required by the pharmaceutical industry, is an important tool in synthetic organic chemistry. Chiral catalysis is one tool used to achieve these syntheses and as such development of chiral enantiopure ligands is of upmost importance. Pyridine–oxazoline ligands have found widespread application in asymmetric catalysis. Surprisingly, however, research into PYOX ligands containing a carbon spacer between the pyridine and oxazoline rings has remained limited to just a few reports in the literature, and an extensive investigation into their synthesis and use as asymmetric catalysts has never been completed. Chapter 2 details the development of a synthetic route to novel bridged pyridine–oxazoline ligands. The ligands were prepared in two efficient steps (Scheme 1), initially preparing 2– pyridyl alkylnitriles, followed by their conversion into oxazolines ligands using chiral amino alcohols and zinc chloride. The 2–pyridyl nitriles were prepared via a novel SNAr alkylation reaction of 2–bromopyridine with alkyl nitriles using methylmagnesium chloride as a non– nucleophilic base in conjunction with an amine mediator. Metal complexes of these ligands were applied to several transition–metal catalysed test reactions including the allylic alkylation, Alder–Ene, Henry and the cyclopropanation reaction. The palladium complexes gave good conversions (up to 100%) and moderate enantioselectivities (up to 68%) in the asymmetric allylic alkylation reaction. This research has resulted in a recent publication in Synlett. The copper complexes of these ligands gave modest conversions (up to 73%) but low ee values (32%) in the asymmetric Alder–Ene. In the asymmetric Henry reaction, the copper complexes provided high conversions (up to 97%) and moderate ee values (up to 68%). The ligands were also screened in the asymmetric cyclopropanation reaction, where conversions of up to 84% were achieved, but low ee values (up to 30%). The work clearly established that functionalisation on the bridging carbon has a substantial impact on the resulting catalysts stereoselectivity. Scheme 1: Two–step synthetic route to chiral PYOX ligands Chapter 3 provides an in–depth exploration of the synthesis of phenyl–substituted bridged PYOX ligands. The synthesis of the nitriles again used a SNAr reaction. The corresponding phenyl–substituted bridged PYOX ligands were successfully synthesized. These ligands were very liable with easy reaction at the acidic bridgehead C–H. This led to difficulty in isolating single stereoisomers of the ligands. The discovery of zinc complexes of the ligands opened up an alternative approach for isolation of zinc complexes of single stereoisomers of these ligands (Scheme 2). This newfound method facilitates the isolation process but also allows their application as catalytic precursors in asymmetric catalytic reactions. Scheme 2: Synthesis of a phenyl–substituted PYOX–ZnCl2 ligand. In Chapter 4, a novel three–step synthetic pathway for the production of alkyl phenyl– substituted bridged PYOX ligands is outlined (Scheme 3). The ligand synthesis allowed for two stereochemistries at the bridgehead with a single chiral configuration at the oxazoline. The resulting diastereomers could in most cases be separated allowing access to single enantiomers of diastereomers for testing. The stereochemistry of the stereocentre at the bridging carbon of a novel PYOX ligand was determined by X–ray crystallography of a PYOX–CuCl2 complex. The ligands were applied to three asymmetric reactions and the catalytic results are reported.2026-06-2
Universality of the angled shear wave identity in soft viscous solids
No full textMechanical stress within biological tissue can indicate an anomaly, or can be vital of its function, such as stresses in arteries. Measuring these stresses in tissue is challenging due to the complex, and often unknown, nature of the material properties. Recently, a method called the angled shear wave identity was proposed to predict the stress by measuring the speed of two small amplitude shear waves. The method does not require prior knowledge of the material’s constitutive law, making it ideal for complex biological tissues. We extend this method, and the underlying identity, to include viscous dissipation, which can be significant for biological tissues. To generalise the identity, we consider soft viscoelastic solids described by a generalised Newtonian viscous stress, and account for transverse isotropy, a feature that is common in muscle tissue, for instance. We then derive the dispersion relationship for small-amplitude shear waves superimposed on a large static deformation. Similarly to the elastic case, the identity is recovered when the stress in the material is coaxial with the transverse anisotropy. A key result in this paper is that to predict the stress in a viscous material one would need to measure the wave attenuation as well as the wave speed. The case of viscoelastic materials with memory is also discussed.HB has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement TBI-WAVES – H2020-MSCA-IF-2020 project No 101023950. ALG is grateful for the support from the European Commission Horizon 2020/H2020 - Shift2Rail
Multiple reference and nanosensitive optical coherence tomography
No full textThe commercial availability of miniaturized optics and the need for flexibility in many clinical applications have driven a desire for the reduction in OCT system form factor and cost while maintaining fit for purpose imaging performance. Multiple Reference Optical Coherence Tomography (MR-OCT) is a modified Time-Domain OCT with a partial mirror before the scanning reference mirror. MR-OCT unlocks opportunities to realize low-cost and miniature OCT for specific applications using off-the-shelf components and conventional production methods. In this thesis, our emphasis is on optimizing the imaging performance of MR-OCT and enhancing its capabilities by integrating a nanosensitive OCT algorithm designed to detect structural changes at the nanoscale level. First, to improve MR-OCT sensitivity, we implemented a digitally balanced detection scheme with a polarization-based optical configuration. Balancing the signals in the digital domain increased the efficiency of common-mode rejection and presented an average sensitivity improvement of 5 ± 0.5 dB over its analogue balanced detection counterpart. The superior sensitivity of digitally balanced detection helped to increase the image contrast in Scotch tapes and mouse eyes. Additionally, in the context of the polarization-based optical configuration, we modelled the properties of the MR-OCT signal for a birefringent sample. We show that the quarter-wave plate in the sample arm of the Michelson interferometer can be adjusted to optimize the signal returning from a birefringent sample, thereby improving the visibility of structures of interest. The theory and techniques discussed in this study will be helpful for a wider OCT community to understand and minimize signal degradation due to birefringence in Time-Domain and Fourier-Domain OCT systems. Next, we implemented nanosensitive optical coherence tomography (nsOCT) in the MROCT system. Nanosensitive OCT (nsOCT) is a technique that enables OCT systems to detect nanoscale structural alterations. Incorporation of nsOCT advances the potential of MR-OCT without adding extra cost or form factor. Nanosensitive OCT uses the spectral encoding of the spatial frequency approach to extract high spatial frequency information in the signal originating from periodic structures. A theoretical basis for nsOCT is presented. We demonstrate that the integration of nsOCT with either Spectral Domain or MR-OCT enables the differentiation between two Bragg’s gratings with axial structures separated by approximately 10 nm. We also show the capability of nanosensitive MR-OCT to identify sub-micron structural changes resulting from an induced superficial alkali burn on an excised rabbit cornea.
Finally, we used the nsOCT technique for detecting structural changes in stem cells. On imaging pellets of mesenchymal stromal cells following labelling with different concentrations of plasmonic gold nanostars, the nsOCT detected that the mean spatial period of MSC pellets increases after labelling with increasing concentrations of nanostars. In the study of the MSC pellets chondrogenesis differentiation model, the nsOCT results indicated that the spatial period increased during the progression in the formation of the precartilage condensation matrix and decreased during its transformation into an aggrecanrich cartilage matrix. We validated the spatial period changes identified by nsOCT by conducting a Fourier analysis on TEM and histology images obtained from corresponding samples.2025-02-2
The developmental potential of stem cells in Hydractinia symbiolongicarpus
No full textHydractinia is a sessile, colonial invertebrate and a member of the phylum Cnidaria. They possess a remarkable population of adult stem cells known as i-cells which are the source of Hydractinias impressive regenerative ability. Previous work had identified the presence of i-cells during embryogenesis and metamorphosis. I was able to show the first appearance of putative i-cell progenitors in early embryogenesis in Hydractinia. i-cell progenitors first appeared at the 32/64-cell stage, often with many individual cells at once expressing Piwi1 (which is an i-cell marker). The true developmental potential of these putative i-cell progenitors remains to be studied. Past studies have shown that a population of i-cells can give rise to all somatic cell lineages as well as germ cells in Hydractinia. However, whether this population consisted of distinct, lineage-committed i-cells or pluripotent cells has not yet been confirmed. This work determines the developmental potential of a single i-cell in Hydractinia. Making use of Hydractinia’s remarkable growth, plasticity, I established a method for transferring a single i-cell from a double transgenic Piwi1::GFP Beta-Tubulin::mScarlet reporter colony into a wild type animal via stolonal contact. This method allowed tracing all progeny of a single grafted icell in the host tissue in vivo. I observed that wild type Hydractinia tissue possessing an initial single transgenic donor i-cell developed into a chimeric animal with a mixture of cells derived from the transgenic donor and the wild type recipient. Donor-derived cells, representing all major somatic lineages and germ cells were scattered in the recipient’s tissues in both feeding and sexual polyps, and in the stolonal compartment. This study shows that Hydractinia possesses pluripotent i-cells. Additionally, somatic cell types in Hydractinia did not exhibit any stem cell like qualities such as continuous proliferation and passive displacement
Structural performance testing of a composite demonstrator made with recyclable composite materials
No full textCurrently, wind energy is the largest contributor to Ireland's renewable electricity supply. In Ireland, there were approximately 275 MW of new wind farms connected in 2023. The typical design life span of a wind turbine is 25 years. Most parts of a wind turbine can be reused or recycled, such as steel towers, copper cables, and electrical equipment. However, the blades currently can't be easily recycled, which can cause a high volume of composite waste. By 2030, composite waste from the wind industry is expected to exceed 130,000 tonnes/year. Therefore, it is vital to develop novel wind turbine blades that contribute to the material circularity. In this research, the structural performance of a composite demonstrator, which represents the main structure of a wind turbine blade, is studied. This 5-m long demonstrator was manufactured using glass fibre and Elium® resin, a recyclable material. To ensure the manufactured demonstrator can withstand the design forces, it underwent a series of static loadings, which are introduced by a hydraulic actuator, in the large structures laboratory at the University of Galway. The T-boltconnectors of the demonstrator failed under a load of 36.1 kN. Based on the observations and strain gauge recordings, there is no damage occurred in the thermoplastic composite components. These preliminary test results show that it is positive to use thermoplastic materials in wind turbine blade manufacturing.The authors would like to acknowledge the support from Sustainable Energy Authority of Ireland (SEAI) Research Development, and Demonstration Funding Programme 2021 through grant numbers 21/RDD/601, 21/RDD/630 and 21/RDD/655. The research was also supported by Science Foundation Ireland (SFI) through the MaREI Research Centre for Energy, Climate, and Marine (grant no 12/RC/2302_2). The authors would also like to acknowledge the support of Marine Institute, funded under the Marine Research Programme by the Government of Ireland (PDOC/21/03/01)