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eConveyancing and eSignatures in Ireland
No full textIn 2003, the Department of Justice, Equality and Law Reform and the Law Reform Commission established a joint project for the major reform and modernisation of land law and conveyancing law in Ireland. The ultimate goal of this project was to "modernise the substantive law which underpins the conveyancing system"1 and to introduce an eConveyancing system similar to those which had already been developed in other jurisdictions. A year later, the Law Reform Commission released a consultation paper which set out the proposals to implement the joint project and although the consultation paper did state that the process would involve three stages2 and would take "some years to develop",3 we are now nearly 20 years on and are no closer to the proposed eConveyancing system being introduced.peer-reviewe
NK cell line modified to express a potent, DR5 specific variant of TRAIL, show enhanced cytotoxicity in ovarian cancer models
No full textObjective
Ovarian cancer is a lethal gynaecological malignancy with unsatisfactory 5 year survival rates of 30–50 %. Cell immunotherapy is a promising new cancer treatment where immune cells, such as Natural Killer (NK) cells, are administered to enable the patient to fight cancer through direct cytotoxicity. NK cells orchestrate an adaptive immune response by enabling the release of tumour antigens. NK cell cytotoxicity and effector responses are largely driven by TRAIL engagement. In this study we investigated the cytotoxic potential of a human NK cell line that were modified to express a potent DR5 specific TRAIL variant. We hypothesised that this modification would enhance NK cell cytotoxicity against TRAIL sensitive and resistant ovarian cancer cell lines in vitro.
Methods
KHYG-1 human NK cells were modified with a TRAIL variant targeting DR5 (TRAILv-KHYG-1). Human ovarian cancer cell lines, OVCAR-3 and SKOV-3, were cultured with modified or non-modified NK cells at different effector:target (E:T) ratios for 4 or 16 h. Apoptosis was assessed by Annexin-APC and 7-AAD and measured using flow cytometry. Apoptotic cells were defined as annexin V 7-AAD double positive. Cytokine expression was measured by multiplex ELISA, and analysed by flow cytometry.
Results
Modified and non-modified NK cells significantly reduced OVCAR-3 cell viability as compared to OVCAR-3 cells that were cultured alone after 4 and 16 h treatment. OVCAR-3 cell viability was reduced after treatment with 1:1 E:T ratio with TRAILv-KHYG-1 cells after 16 h. On the contrary, neither NK cell line had any effect of SKOV-3 cell viability despite SKOV-3 cells having more DR5 surface expression compared to OVCAR-3 cells.
Conclusions
TRAILv-KHYG-1 cells significantly reduced OVCAR-3 cell viability as compared to non-modified NK cells. However, no significant reduction in viability was observed when SKOV-3 cell were cultured with either NK cells, despite having more DR5 surface expression compared to OVCAR-3 cells. These data indicate that mechanisms other than DR5 expression drive TRAIL resistance in ovarian cancer.E.B Dolan acknowledges funding from Science Foundation Ireland Technology Innovation and Development Award (18/TIDA/5950) and Irish Research Council Starting Laureate Award (IRCLA/2022/2766). E.B Dolan and A. Sheedy acknowledges funding from EPSRC and SFI for funding the lifETIME Centre for Doctoral Training (EP/S02347X/1). This publication has emanated from research supported in part by a grant from Science Foundation Ireland and the European Regional Development Fund (ERDF) under grant number 13/RC/2073_P2. M. Gurney was supported by Irish Clinical Academic Training (ICAT) Programme fellowship funding to MG. ICAT is supported by the Wellcome Trust and the Health Research Board (Grant Number 203930/B/16/Z), the Health Service Executive National Doctors Training and Planning and the Health and Social Care, Research and Development Division, Northern Ireland
“I couldn’t help but compare with other countries”: Migrant mothers’ lived experiences of Japan’s COVID-19 state of emergency
No full textThis article presents the lived experiences of English-speaking migrant mothers in Japan during the early COVID-19 pandemic when school and childcare facilities closed, there was a national State of Emergency (SoE) and foreign residents were banned from re-entering the country. I examine the influence of the intersecting identities and social locations of being a woman, a mother of a dependent child, and a migrant in Japan. For mothers in this research, the COVID-19 pandemic played out against a backdrop of global gender inequality, which intensifies when women become mothers and is notoriously extreme in Japan. Although non-Japanese people face institutional and social discrimination, these mothers occupy a relatively privileged position amongst migrants, in a country which values English language ability. Still, their daily lives were affected by social structures and inequalities, and by a government response that did not sufficiently mitigate the uneven impacts of the crisis. Mothers experienced stress from the surge in demand for unpaid care of family members in a context of ambiguity, exacerbated by an unmet need for information and, for many, a language barrier. Mothers turned to online communities to provide each other with social support and information; as well as accessing information in English from sources in other countries. Findings support the case for intersectionality-based policymaking and crisis response which utilise knowledge from lived experiences of people with intersecting characteristics, as these factors influence people’s experiences of and access to services, and the ways in which they are impacted by crises such as public health emergencies.peer-reviewe
LatentColorization: Latent diffusion-based speaker video colorization
No full textWhile current research predominantly focuses on image-based colorization, the domain of video-based colorization remains relatively unexplored. Many existing video colorization techniques operate frame-by-frame, often overlooking the critical aspect of temporal coherence between successive frames. This approach can result in inconsistencies across frames, leading to undesirable effects like flickering or abrupt color transitions between frames. To address these challenges, we combine the generative capabilities of a fine-tuned latent diffusion model with an autoregressive conditioning mechanism to ensure temporal consistency in automatic speaker video colorization. We demonstrate strong improvements on established quality metrics compared to existing methods, namely, PSNR, SSIM, FID, FVD, NIQE and BRISQUE. Specifically, we achieve an 18% improvement in performance when FVD is employed as the evaluation metric. Furthermore, we performed a subjective study, where users preferred LatentColorization to the existing state-of-the-art DeOldify 80% of the time. Our dataset combines conventional datasets and videos from television/movies. A short demonstration of our results can be seen in some example videos available at https://youtu.be/vDbzsZdFuxM.10.13039/501100001602-Science Foundation Ireland through the SFI Centre for Research Training in Artificial Intelligence (Grant Number: 18/CRT/6223)
10.13039/501100021525-Insight SFI Research Centre for Data Analytics (Grant Number: 12/RC/2289_P2)
SFI Centre for Research Training in Digitally-Enhanced Reality (d-real) (Grant Number: 18/CRT/6224
Sovereignty and the persistence of the aesthetic
No full textBritish constitutional thought tends to understand sovereignty in legalistic terms, with the concept often equated with the doctrine of parliamentary sovereignty. As Loughlin and Tierney have recently argued, this approach obscures the political considerations which undergird the legal precept. In this article we argue that this approach misses a third, and essentially important, dimension to sovereignty. Law, politics and aesthetics all play equally important parts in constituting the essential structure of the concept. We elaborate this claim through a reading of some prominent accounts of sovereignty within the history of political modernity. At bottom, aesthetics is concerned with the ways in which the body's senses are stimulated and ordered; it therefore includes pictorial representation, ideation and imagination, as well as affect, instinct and habituated feeling. We argue that these different elements are usefully understood as all pertaining to a distinctive, and persistent, aesthetic dimension which is essential to the sovereignty concept.peer-reviewe
Prevention of pressure ulcers from the perspective of frailty, pre-frailty, and health and social inequalities: An opinion paper
No full textPressure ulcers affect many people in acute care and community settings. People with pressure ulcers may have delayed ulcer healing due to various factors, such as malnutrition and frailty. Prevention of pressure ulcers by addressing individual risk factors is essential, as it can help maintain skin integrity and functional ability, prevent or delay frailty, reduce care-associated costs, and improve quality of life [1]. There are key factors leading to both frailty and pressure ulcers but the psychosocial aspects of these factors are often overlooked. In the current literature and clinical practice, the key concepts related to the bio-psychosocial aspects of frailty and pressure ulcer prevention are under-explored and not fully considered as part of routine care services. To address this gap in research and practice, a group of experts were invited to an online panel discussion. The expert panel included academics, researchers, and specialist clinical professionals in key leadership roles such as consultant geriatricians, advanced nurse practitioners and tissue viability nurse specialists, the national lead for older person services in Ireland, and the lead person for the National Wound Care Strategy in England (further details of all panel members are available in Table 1).This work was supported by the European Pressure Ulcer Advisory Panel Seed Funding.peer-reviewe
Every speech and language therapist can be an ethical leader: Demonstrating ethical leadership in childhood disability services (Part 2/2)
No full textThe aim of the paper is to facilitate speech and language therapists to reclaim agency and demonstrate ethical leadership as they advocate for their clients, services and profession. Building on the language of ethics introduced in the first of these two linked papers (anonymized for peer review with (McAllister et al., 2024)), we apply the language of ethics to two hypothetical scenarios situated in childhood disability services in Ireland; we discuss three levels of ethical leadership: ethical leadership in, ethical leadership of and ethical leadership for. We argue that the use of an ethical approach may be valuable for the speech and language therapist, especially in a context of resource limitations. We hope that use of ethical approaches will facilitate speech and language therapists to embed ethical leadership in everyday practice and that the speech and language therapy community and service providers consider ethics more explicitly in service planning and delivery.peer-reviewe
The potential of neurotrophin-loaded biomaterials to enhance stem cell-derived brain repair for Parkinson's disease
No full textExtensive preclinical and clinical research have demonstrated the potential of cell-derived brain repair for Parkinson’s disease showing that cells can survive, integrate and reinnervate the Parkinsonian brain ultimately providing functional recovery to patients. Although the historical source of dopaminergic neurons for cell replacement therapies had been foetal-derived cells, the ethical concerns related to their supply and various logistical issues have encouraged the field of brain repair to switch towards the transplantation of stem cell-derived dopaminergic progenitors.
A multitude of preclinical trials have shown that these cells can survive, differentiate in situ and provide amelioration of motor deficits in animal models leading to the initiation of four clinical trials with the aim to test safety, tolerability and efficacy of both embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC)-derived grafts for patients. However, the preclinical literature suggests poor in vivo survival and maturation of these progenitors undermining the realisation of the full potential of stem cell replacement therapies.
In this context, injectable biomaterials have the potential to address these challenges. Specifically, neurotrophin (NTF)-loaded biomaterials could provide the transplanted cells with long-term NTF delivery overcoming the issue of trophic withdrawal post-grafting. Moreover, injectable in situ gelling collagen hydrogels could provide supportive benefits by acting as a matrix for cell adherence, by creating a physical barrier against the host’s neuroimmune cells and by providing the transplanted cells with a NTF-rich microenvironment to aid their survival after transplantation and consequent in situ dopaminergic differentiation.
Thus, the overall aim of this project was to assess the potential of NTF-enriched biomaterials for enhancing in situ survival and maturation of human iPSC-derived dopaminergic progenitors in Parkinsonian rats, particularly in immunosuppressed (rather than immunodeficient) rats. Specifically, we firstly conducted a systematic review of the preclinical literature to assess the extent of survival and dopaminergic differentiation of human ESC and iPSC-derived dopaminergic progenitors (DAPs) in the brain of Parkinsonian models. We found that cell survival was very variable (between 0% and 500%) but relatively high, with a median of 51%. However, although also very variable (between 0% and 46%), dopaminergic maturation was poor with a median of 3% of the transplanted cells.
Therefore, in an effort to improve survival and differentiation outcomes of cells in preclinical models, we firstly tested two systems - biomaterial microcarriers and engineered mesenchymal stem cells - for the delivery of glial cell line-derived neurotrophic factor (GDNF) in a sustained manner. However, these showed either to not being biocompatible or to not be suitable for co-transplantation with iPSC-DAPs.
In parallel, a recently conducted study in our group showed the ability of a GDNF and brain-derived neurotrophic factor (BDNF) functionalised collagen hydrogel to dramatically enhance survival and differentiation of iPSC-DAPs in the brains of athymic nude rats (T-cell deficient) but not in the brains of cyclosporine suppressed rats (T-cell suppressed). Therefore, the focus of this research switched to the hydrogel. Particularly, we firstly studied the immunological profiles of athymic nude rats and cyclosporine suppressed rats after transplantation of iPSC-DAPs either alone, with NTFs, in a hydrogel or in a NTF-enriched hydrogel. We found that cyclosporine suppressed rats were not fully immunosuppressed at the time of transplantation as residual T-cell populations were found infiltrating the brains in the peri-transplant area and circulating in the bloodstream.
Next, we used an alternative immunosuppression regime to assess the potential of a NTF-enriched collagen hydrogel for enhancing in situ survival and maturation of iPSC-derived dopaminergic progenitors in immunosuppressed Parkinsonian rats. Although the beneficial effect of this hydrogel was not as pronounced as seen in immunodeficient rats, in immunosuppressed hosts it still showed a beneficial effect on the corridor test performance, and in terms of consistency of survival and differentiation of the cells which generated significantly denser grafts compared to when transplanted alone.
In conclusion, a NTF-enriched collagen hydrogel has the potential to improve the efficacy of stem cell replacement therapies in Parkinson’s disease by providing dopaminergic progenitors with a supportive microenvironment throughout delivery and during the first week post-transplantation. However, further studies are required to allow the NTF-enriched collagen hydrogel to realise its full potential in immunosuppressed hosts, rather than immunodeficient, and further functionalisation is required in order to achieve sustained neurotrophic factors delivery in the brain
Permanent neutrality in international law
No full textPermanent neutrality is a legal status whereby individual states are bound to remain neutral and adhere to the law of neutrality in all circumstances wherein that body of law is applicable. Permanently neutral states must also comply with certain peacetime duties in order to ensure that their neutrality during future conflicts remains possible. From the recognition of the permanent neutrality of Switzerland by the Congress of Vienna in 1815 to the modern day, permanent neutrality has been a constant feature of the international stage. It is thus curious that the issue has remained largely underexplored in mainstream contemporary international law scholarship. Even while the law of neutrality has seen renewed attention in recent years,1 permanent neutrality has been overlooked. For example, permanent neutrality has been largely absent from the recent resurgence in scholarly attention and debates on the law of neutrality during the Russian invasion of Ukraine.2 The concept has thus, at least in the English-speaking world, been largely relegated to the musty pages of 19th and 20th century scholarship. Alternatively, permanent neutrality receives, at best, a brief mention in larger studies on neutrality, war, and international law.3 This thesis endeavours to reintroduce permanent neutrality into the contemporary world of international legal scholarship, and to situate it back alongside the law of neutrality as a topic deserving of academic study. This thesis is therefore orientated around the following research questions: (i) (ii) (iii) how is the permanent neutrality of states established, and how does it come to an end; what is the effect of permanently neutral status on states other than the permanently neutral state; and what are the rights and duties of permanently neutral states during both wartime and peacetime?Irish Research Council & NUI EJ Phelan Fellowship in International Law2026-08-2
Exploration of inflammatory modulators nitric oxide and HERV-K in prostate cancer progression and diagnosis reveals a role for nitric oxide regulation of STAT3
No full textProstate cancer (PCa) remains a highly prevalent cancer worldwide, with approximately 500 yearly deaths attributed to it in Ireland. Inflammation bears responsibility for the emergence of several prostatic conditions, including PCa. NOS2 is a powerful and prolonged producer of nitric oxide (NO), which can be activated by inflammation, and has been implicated in prostate carcinogenesis and lethality. Chronic NO exposure has been shown to induce malignant transformation in normal prostate cells. This study aimed to explore whether long-term, chronic NO exposure would similarly confer PCa cell lines with increased aggressiveness. Results showed that chronic NO exposure conferred PCa cell lines with increased rates of proliferation, migration, and invasion. These chronically exposed cells also displayed increased chemoresistance, upregulated transcription of various pro-tumorigenic genes, and increased total STAT3 protein. STAT3, a master transcription factor, mediates several processes of cancer and has been associated with PCa. The relationship between STAT3 and NO is unclear, and this study further aimed to explore any relationship NO and its chronic exposure may have on STAT3 activity in PCa. Results indicated that NO can indeed phosphorylate STAT3 in PCa cells. Further, it was found that STAT3 inhibitors Niclosamide and STATTIC impede several Epithelial-to-Mesenchymal Transition (EMT) behaviours in PCa cells. Following chronic NO exposure, PCa cells were more sensitive to Niclosamide. The combination of DETA/NO and STAT3 inhibitors yielded a powerful additive cytotoxic effect. Inflammation and PCa have also been linked to Human Endogenous Retrovirus-K (HERV-K), an ancient viral integration to the genome which is largely silenced in somatic tissue. Elevated HERV-K(HML2) gag mRNA expression in PBMCs has previously been associated with PCa diagnosis. This study aimed to corroborate those findings and expand whether HERV-K(HML2) mRNA may contribute to improved PSA accuracy in diagnosing PCa and discern between Benign Prostatic Hyperplasia (BPH) and PCa. In the patient cohort, HERV-K gag and env2 mRNA was significantly elevated in PCa patients compared to BPH. In summary, this study has shown that chronic NO exposure induces increased aggressive behaviour in PCa cells, while also exposing a potential therapeutic opportunity via STAT3 inhibition, and thereby connecting NO and STAT3 in PCa. We also further argued the potential of HERV-K(HML2) as a potential biomarker for PCa diagnosis.2026-07-1