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Unlocking glioblastoma: breakthroughs in molecular mechanisms and next-generation therapies
No full textGlioblastoma (GB) remains the most aggressive primary brain tumor in adults, characterized by rapid progression, recurrence, and resistance to conventional therapies. Despite advancements in surgical resection, radiation, and chemotherapy, long-term survival rates remain low. This review comprehensively explores GB’s molecular classification, pathological mechanisms, epidemiology, and emerging therapeutic strategies. Key genetic mutations in TP53, MAPK/ERK, PI3K/AKT/mTOR, and many more signaling pathways, such as Notch, Wnt, Hedgehog, TGF-β, and NF-κB drive tumor progression, therapy resistance, and immune evasion. Diagnostic advances, including multi-modal imaging and molecular profiling, have improved early detection and precision therapy selection. Conventional treatments such as temozolomide and radiation therapy provide modest benefits, but novel approaches offer promising alternatives. Immunotherapy, targeting checkpoint inhibitors and tumor vaccines, has emerged as a potential avenue for enhancing tumor control. Nanotechnology-based drug delivery, particularly liposomal formulations and CRISPR-Cas9 gene editing improves blood–brain barrier penetration and reduces systemic toxicity. Targeted inhibitor-based therapies, including angiogenesis inhibitors, help limit tumor vascularization. Furthermore, a systematic review of 16 clinical trials highlights the emerging trends in combinatorial strategies, their adverse events, and outcomes, which remain pivotal for optimizing GB management. This review synthesizes current research while emphasizing future directions that could revolutionize GB therapeutic approaches and improve patient survival.peer-reviewe
Open-source Raman spectra of chemical compounds for active pharmaceutical ingredient development
No full textRaman spectroscopy is utilised extensively in pharmaceutical analysis for tasks such as drug discovery, quality control and active pharmaceutical ingredient (API) development. Despite this, access to open-source Raman spectral datasets for modelling and analysis is often a challenge. In laboratory settings, small spectral libraries are typically compiled for one-shot identification of intermediates or unknown chemicals, which restricts availability to comprehensive and high-quality reference data. In this work, we introduce a new open-source Raman dataset consisting of pure chemical compounds commonly employed in the development of APIs. By curating and publishing this dataset, we aim to provide the scientific community with access to high-quality, reusable data. Containing 3,510 samples spanning 32 compounds, this data can be utilised for referencing and can potentially facilitate in the development of more accurate and generalisable calibration models when access to reference data is limited.This publication has emanated from research conducted with the financial support of Taighde Éireann - Research Ireland Centre’s for Research Training in Artificial Intelligence under grant number 18/CRT/6223 and the University of Galway. For the purpose of Open Access, the author has applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission. The authors would like to express their sincere gratitude to Matthew Webberley and SK Pharmteco for providing the necessary facilities and supporting the data acquisition.peer-reviewe
Disrupting membranes, controlling cell fate: the role of pore-forming proteins in cell death and therapy
No full textPore-forming proteins (PFPs), characterized by their ability to form pores or disrupt membranes are now recognized as key executioners of cell death, either as effectors of the immune system (non-cell-autonomous function), or of regulated cell death programs (cell autonomous function). To perforate membranes, most PFPs transition from water-soluble monomers or oligomers into multimeric and often supramolecular complexes, a process achieved via substantial structural transition of the PFP. Although they share the general ability to perforate cellular or intracellular membranes, PFPs differ in their membrane-binding preferences, the structural and functional characteristics of the pores they form (such as pore size, pore structure and ability to trigger membrane rupture) and the cell death mechanism they induce or execute. Herein, we review the specific traits of all key human PFPs, including their membrane specificity, regulation of their activity and the structure of the membrane pores they form, followed by insights into the therapeutic potential of PFPs and harnessing their abilities for cancer therapy.Open Access funding provided by the IReL Consortiumpeer-reviewe
The complexity of procedural fidelity in precision teaching: A qualitative analysis
No full textPrecision Teaching (PT) is a system that involves precisely defining and measuring the frequency of behavior to facilitate timely and effective data-based decisions to accelerate behavioral repertoires (Evans et al., Behavior Analysis in Practice, 14(3), 559–576 2021). When combined with instruction and practice approaches, PT has demonstrated efficacy in accelerating learning in academic skills. However, its use in public schools is minimal. One reason for this may be the limited amount of research exploring teacher-implemented PT and how PT fits within the context of busy classrooms. Procedural fidelity is an important concept to consider when procedures are implemented in complex and uncontrolled environments. The present study employed qualitative methods to explore expert practitioners’ and researchers’ perspectives on procedural fidelity, fidelity errors, and their perceived impact when implementing PT. The data were thematically analyzed and are discussed with regard to three overarching themes and their subthemes: (a) The Complexity of Procedural Fidelity in PT, (b) Maintaining Fidelity without Losing Flexibility, and (c) It’s a System. This study is an initial exploration of expert perspectives on procedural fidelity in PT, which can help inform future quantitative evaluations of the impact of fidelity errors on participant outcomes. Findings suggest that participants believed PT is a flexible system tolerant of some fidelity errors but that no component of the system should be omitted completely. Implications of these findings for research and practice are discussed alongside the strengths and limitations of this study.Open Access funding provided by the IReL Consortium. This research was funded by the Irish Research Council under the Government of Ireland Postgraduate Research Scholarship.peer-reviewe
Carbon nanotubes–Elium nanocomposite sensor for structural health monitoring of unidirectional glass fibre reinforced epoxy composite
No full textThe emergence of new technologies in composite manufacturing and inspection has contributed to significant advancements in the wind energy industry. Unidirectional (UD) glass fibre reinforced epoxy composites are widely used in the manufacturing of wind turbine blades due to their good fatigue resistance. One of the important subjects in wind turbine blades is periodic repair and maintenance. Delamination and crack propagation are common structural issues that make regular inspection necessary in the composites. This study presents a structural health monitoring approach using a novel thermoplastic sensor for damage assessment in UD glass fibre epoxy composite. The thermoplastic sensor, composed of thermoplastic Elium and carbon nanotube materials, was prepared using the material extrusion filament technique. The electrical resistance of the filament was assessed under cyclic loading. The prepared material in the filament shape was embedded in the intermediate layer of UD glass fibre-epoxy composite. To evaluate damage propagation, flexural and electrical tests were carried out on the prepared smart composite laminate simultaneously. Three point flexural bending test was conducted for mechanical test and relative resistance change was recorded using a Wheatstone bridge circuit. Sharpe increase in the electrical output indicated that the smart composite is sensitive to damage extension under flexural load. This electro-mechanical evaluation on the composite laminate highlights the potential of the proposed technology for health monitoring of large composite structures, such as wind turbine blades.This project is funded by Taighde Éireann – Research Ireland, formerly Science Foundation Ireland under Grant number 22/IRDIFB/10946. This project is being supported with financial contribution from the Sustainable Energy Authority of Ireland and the Marine Institute under the SEAI National Energy Research, Development & Demonstration Funding Programme 2024, Grant number 24/RDD/01098, Funding Programme 2023, Grant number 23/RDD/1019, and Funding Programme 2022, Grant number 22/RDD/876.peer-reviewe
Decomposition of Jacobians and Shimura subvarieties of Ag
No full textUsing the decomposition of Jacobians with group action, we prove the non-existence of some Shimura subvarieties in the moduli space of ppav
Ag arising from families of dihedral and quaternionic covers of the complex projective line P1peer-reviewe
Social capital in large-scale agile software product management: A multi-case study
No full textContext
Large fintech organizations are increasingly adopting agile methodologies to enhance product development capabilities. However, implementing agile at scale presents unique challenges, particularly related to collaboration essential for successful software product management (SPM). Social capital, comprising structural, cognitive, and relational dimensions, may play a crucial role in facilitating the collaboration needed to overcome these challenges.
Objectives
We examine the role of social capital in large-scale agile SPM, focusing on how it facilitates coordination, collaboration, and, ultimately, success, in complex, product-focused environments.
Methods
We employ a multi-case study approach, comprising 33 interviews, observations, and document analysis, analyzing two Scandinavian fintech companies that have adopted large-scale agile practices organized around product areas.
Results
Our findings, viewed through the lens of social capital theory, show that its three dimensions help explain how large-scale organizations adopting SPM manage dependencies and enable product-focused coordination. Specifically, the structural dimension helps illuminate how networks are formed; the cognitive dimension clarifies how shared understanding of product visions and development practices emerges; and the relational dimension highlights how trust is cultivated among product development actors across multiple operational levels (i.e., product team, product area, organizational, and external levels). Together, these dimensions offer insight into how agile practices are effectively implemented at scale.
Conclusion
Our study finds that social capital is a critical enabler of effective SPM in large-scale agile contexts. Its three dimensions support the collaboration and relational networks necessary for agility at scale. These insights suggest that fostering social capital should be prioritized in agile transformations to address the sociotechnical complexities inherent in large-scale SPM.The Research Council of Norway supported the work through the projects 10xTeams (grant 309344) and Transformit (grant 321477). The contribution by Astri Barbala was supported, in part, by Taighde Éireann – Research Ireland under Grant number 13/RC/2094_2. Co-funded by the European Union under the Systems, Methods and Context (SyMeCo) programme grant agreement number 101081459.peer-reviewe
Regulation of propionate degradation in anaerobic reactors: Roles of sludge retention time and organic carbon composition across different operational configurations
No full textPropionate accumulation is a challenge in anaerobic digestion due to the syntrophic lifestyle, slow growth rate, and environmental sensitivity of syntrophic propionate-oxidizing bacteria. The effects of sludge retention times (SRTs; i.e., 10 and 25 days, and without desludge) and carbon source compositions (a mixture of ethanol/acetate/propionate or sole propionate) on propionate degradation and microbial community structure were examined in sequencing batch reactors (SBRs) and continuous flow reactors (CFRs). SBRs outperformed CFRs in methanogenic propionate degradation, with nearly complete chemical oxygen demand (COD) removal achieved by day 13 (SBR with a mixture of ethanol/acetate/propionate) and day 41 (SBR with sole propionate), compared to day 54 in the CFR with sole propionate. The COD removal efficiency in the CFR with a mixture of ethanol/acetate/propionate stabilized at approximately 70 %. Reactors with a 10-day SRT were unable to efficiently remove propionate across different operational modes and carbon sources. Batch experiments showed that reactors utilizing mixed carbon sources exhibited shorter lag phases, increased acetate degradation activities, and higher maximum methane production rates compared to those using the sole propionate. SBRs enriched Syntrophobacter (16.0 %–22.8 %) and Desulfobulbus (4.1 %–5.0 %), whose relative abundances in CFRs were only 4.1 %–13.5 % and 1.0 %–1.2 %, respectively. Additionally, the relative abundance of genes involved in propionate oxidation increased by 9.7 %–47.0 % in SBRs compared to CFRs. A strategy involving the utilization of long SRTs, SBR operation mode, and mixed carbon sources was proposed to improve system startup and propionate removal in anaerobic reactors.This research was supported by the Sustainable Energy Authority of Ireland (SEAI; 21/RDD/600). Tingxia Liu thanks the scholarship from China Scholarship Council (No: 202206690019). Guangxue Wu thanks the support from Galway University Foundation.peer-reviewe
In their Own (W)right Lady Augusta Gregory and Frances Brown: A series of multimodal feminist theatre practices for the recovery and re-presentation of Irish women writers
No full textAuthor also known as playwright Shirley-Anne Bonner
Contains original play scripts for reference only. Please contact author for performance rights: [email protected]
The Legends of Ulster- adaptation of Frances Brown's ghostly and humorous Donegal tales for the stage.
In My Mind's Eye -a biographical play about Frances Brown 3F 1MThis thesis compares the legacies of writers Lady Augusta Gregory (1852-1932), and Frances Brown (“The blind poetess of Ulster” 1816-1879). The intersection of their professional experiences, reception, and representation, resistant strategies, and subsequent marginalisation, substantiates the case for multi-modal practice as research based interventions. In order to rehabilitate and reactivate their literary and theatrical legacies in both scholarly and public domains, I trial feminist drama and theatre methodologies to rehabilitate the artistic legacies of marginalised women writers and (re)introduce them to the cultural memory and to new publics.
This thesis contends that intentionally feminist theatre practices offer unique and powerful methodologies which can mitigate against the marginalising factors of the canon, institutionalised sexism, gender -biased scholarship and discriminatory theatre programming. My chief methodology is practice as research (PaR), involving playwriting as research, performance, adaptation and Drama in Education, which challenge received narratives of Gregory and Brown’s achievements. In Chapters One and Two I introduce both writers, my research question and frameworks, as well as the Frances Browne Literary Festival as a site for feminist intervention.
In Chapter Three, through my dramatisation of Brown’s The Legends of Ulster, I interrogate the use of dialect, as historical and contemporary subversive feminist and counter-canonical tools. In Chapter Four my play In My Mind’s Eye demonstrates how biographical playwriting can combine naturalism and non-naturalism effectively as a feminist tool, and problematise ableist approaches in drama. Chapter Five establishes the potential of both intertextuality and narratology in playwriting in the recovery and re-presentation of women writers and their work. My elaboration of Drama in Education techniques with primary school children on Lady Gregory’s The Golden Apple emerge in Chapter Six as a feminist research methodology, reconnecting children with their theatrical heritage, and conscientising them to gender imbalance in the theatre.
By creating affective responses in audiences, stimulating debate, creating awareness and ultimately effecting some degree of conscientisation; social, political and cultural change become possible. Future recommendations include the application of these feminist techniques to other marginalised writers and their non-canonical works, ground-up activism e.g. the literary festival as a site of feminist intervention, and the implementation of Drama in Education strategies at second and third level.Irish Research Council Government of Ireland Postgraduate Scholarshi
Do images really do the talking? Analyzing the significance of images in tamil troll meme classification
No full textA meme is a part of media created to share an opinion or emotion across the internet. Due to their popularity, memes have become the new form of communication on social media. However, they are used in harmful ways such as trolling and cyberbullying progressively due to their nature. Various data modelling methods create different possibilities in feature extraction and turn them into beneficial information. The variety of modalities included in data plays a significant part in predicting the results. We try to explore the significance of visual features of images in classifying memes. Memes are a blend of both image and text, where the text is embedded into the picture. We consider a meme to be trolling if the meme in any way tries to troll a particular individual, group, or organisation. We try to incorporate the memes as a troll and non-trolling memes based on their images and text. We evaluate if there is any major significance of the visual features for identifying whether a meme is trolling or not. Our work illustrates different textual analysis methods and contrasting multimodal approaches ranging from simple merging to cross attention to utilising both worlds’—visual and textual features. The fine-tuned cross-lingual language model, XLM, performed the best in textual analysis, and the multimodal transformer performs the best in multimodal analysis.peer-reviewe