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An actuatable cell encapsulation implant: Towards improving transplanted cell viability in Type 1 diabetes and beyond
No full textNon-communicable chronic diseases such as diabetes, neurodegenerative disease, cardiovascular disease, and cancer account for the highest disease burden worldwide and their prevalence continues to rise. A promising strategy for treating many of these conditions is the use of cell therapies which may serve as a more long-term, sustained therapeutic source to overcome shortcomings in drug release profiles, patient compliance, and treatment longevity. However, there still remains limited clinical translation and adoption despite accelerating rates of research and clinical trials in the field. One of the major reasons for this is the low engraftment and survival of injected cells, which has been shown to range as low as 1-32%. As a result, research has turned towards the development of cell encapsulation implants which would encase transplanted cells in semi-permeable membranes. This would protect them from the host immune system while also ensuring localized therapy delivery and the ability to easily monitor and remove the cells in case of adverse events, which is of substantial value for overcoming regulatory barriers.Irish Research Council Grant: GOIPG/2022/98
Investigation of behaviour, the endocannabinoid system, and phytocannabinoids in rat models of wound-related pain
No full textPain, anxiety, and depression are prevalent in individuals with chronic wounds and have a profound impact on their quality of life. Pain has been reported to be one of the most debilitating aspects of having a chronic wound. Despite their negative impact on individuals, there is a lack of management of pain and these comorbidities in current wound care strategies. Furthermore, there is a paucity of studies examining the molecular mechanisms underlying comorbid anxiety and depression associated with chronic wounds.
The endocannabinoid system is involved in many physiological processes, including mood, anxiety, and pain modulation, and has a role in skin homeostasis and wound healing. Therefore, the endocannabinoid system is a potential therapeutic target for the treatment of anxiety, depression, and pain associated with chronic wounds. Anxiety- and depression-related behaviour has not been extensively investigated in models of wound-related pain, and as far is known, has not been characterised in the dorsum incision or hind limb ischemia-reperfusion models of wound-related pain. There is evidence that phytocannabinoids may attenuate pain in several models of pain, but their effects on nociceptive behaviour following dorsum incision have not been examined previously. The work presented in this thesis tested the hypothesis that anxiety- and depression-related behaviour would be present in the dorsum incision and hind limb ischemia reperfusion models of wound-related pain and that the endocannabinoid system would be altered in brain regions associated with anxiety and depression. It was also hypothesised that the phytocannabinoids, cannabidiol and cannabigerol, would attenuate nociceptive behaviour in the dorsum incision model of wound-related pain. The overarching aims of the work presented herein were to 1) characterise anxiety- and depression-related behaviour and the endocannabinoid system in a rat incisional wound model and a rat model of ischemia-reperfusion injury, 2) investigate the effects of cannabidiol and cannabigerol on nociceptive behaviour following incision wound, and 3) investigate the effects of cannabidiol and cannabigerol on the endocannabinoid system.
There was no effect of dorsum incision or hind limb ischemia reperfusion injury on anxiety- or depression-related behaviour in male or female rats, but sex differences in locomotor activity and anxiety-related behaviour were present. Investigation into the endocannabinoid system following ischemia-reperfusion injury revealed that there were lower levels of 2-arachidonoyl glycerol in the contralateral amygdala of female HLIR rats compared to female shams 30 days post-injury. Investigation into the endocannabinoid system following dorsum incision revealed that male incision rats had lower levels of PEA and OEA in the contralateral hippocampus compared to male sham rats on post-incision day 35. Female incision rats had higher levels of mRNA encoding Faah in the contralateral amygdala compared to female shams on post-incision day 35.
Next, the effect of the phytocannabinoids, cannabidiol and cannabigerol, on nociceptive behaviour following dorsum incision was investigated. The impact of these phytocannabinoids on endocannabinoid and N-acylethanolamine levels, and the expression of their targets in brain regions involved in pain modulation were also assessed. Following dorsum incision, cannabidiol partially attenuated primary mechanical hypersensitivity in the dorsum, while cannabigerol attenuated primary and secondary hypersensitivity in the dorsum and hind paws. Cannabigerol increased circulating levels of PEA and OEA, and increased levels of PEA in the rostral ventromedial medulla. Cannabigerol also increased levels of mRNA encoding Pparg in the thoracic spinal cord and Faah in the periaqueductal grey, in a dose-specific manner.
In conclusion, these findings provide evidence of sex differences in anxiety-related behaviour and alterations in the endocannabinoid system in two models of wound-related pain. The data presented in this thesis also provides preclinical evidence to support the contention that cannabidiol and cannabigerol may have therapeutic potential for the alleviation of incisional wound-related pain.Taighde Éireann -Research Ireland Government of Ireland Postgraduate Scholarship Programme (GOIPG/2023/2741)
Taighde Éireann—Research Ireland, and is co-funded under the European Regional Development Fund (13/RC/2073-P2)
β-Arrestin1 act as a rheostat for ERα and TP53 signalling in ER-positive breast cancer and modulate response to therapy
No full textBreast cancer is the most common cancer in women worldwide, with 2.3 million new cases in 2022. Globally, it was estimated that more than 666,000 women died from breast cancer in 2022. Approximately 70% of breast cancer cases are hormonal positive cancer characterized by expression of the oestrogen receptor α (ERα). Endocrine therapy (ET) targeting the ERα is the main treatment for patients with hormone receptor-positive breast cancer. Resistance to ET is a major problem in ER positive breast cancer, with recurrence and metastasis occurring in up to 40% of patients. Drugs that can reverse endocrine resistance when used in combination with endocrine therapy are urgently needed, and targeting gene synthetic lethality provide a new approach to it.
β-Arrestin1 (ARRB1) is a member of the arrestins protein family and acts as a scaffold for regulating proteins through G protein-coupled receptor signalling. Recent studies have shown that it plays an important role in different cancers and is a key regulator of cancer development and progression. Cytoplasmic ARRB1 promotes liver and colorectal cancer by activating AKT signalling pathway. Nuclear ARRB1 enhances the progression of breast and prostate cancer via regulation of the HIF1A activity; promotes lung cancer by increasing E2F1 activity. Nuclear ARRB1 also associated with androgen receptor and augments its activity in prostate cancer. However, the tumour-suppressor role of ARRB1 has also been observed. Overexpression of ARRB1 inhibited the growth of human neuroblastoma cells through regulating p27 transcription in the nucleus and inhibited the progression of T-cell acute lymphoblastic leukaemia cells and triple-negative breast cancer (TNBC) cells via ARRB1 binding partners in the cytoplasm. These reports suggest that ARRB1 plays a diverse, context-dependent role in cancer. Surprisingly, not much is known about the role of ARRB1 in ER-positive breast cancer.
Earlier work in our group has shown significant downregulation of ARRB1 mRNA and protein during conditions of EnR stress in multiple ER-positive breast cancer cell lines. PERK signalling was required for the downregulation of ARRB1. Further, we showed ARRB1 expression was upregulated by TP53.
Here we have studied the crosstalk of ARRB1 with ER signalling, UPR pathway and TP53, the main aims of the study are to:
1) Evaluate the functional interactions between ARRB1 and ER in breast cancer.
2) Investigate the role of ARRB1 in regulating the response to endocrine therapy and cell fate during EnR stress.
3) Determine the role of ARRB1 in regulating expression and function of TP53 in ER-positive breast cancer.
Result 1: Functional interactions between ARRB1 and ER in breast cancer. We found that ARRB1 enhances transactivation activity of ERα through physical interaction with ERα. In addition, ARRB1 enhances the transactivation activity of ER WT and point mutants (ER Y537S and ER D538G) but has no effect on the activity of fusion mutants ESR1 DAB2 and ESR1 YAP1) of ERα, it suggests that the binding site is in the ligand-binding domain of ERα. We demonstrated that ARRB1 positively regulates the growth and proliferation of ER-positive breast cancer, promotes E2-dependent growth. We further reveal that ARRB1 increases the expression of ER target genes like PGR, GREB1 and EGR, but has no effect on ERα protein expression.
Results 2: Role of ARRB1 in regulating the response to endocrine therapy and cell fate during EnR stress. ARRB1 overexpression provided resistance against tamoxifen and fulvestrant while knock-down of ARRB1 had opposite effect. We found that ARRB1 inhibits the activation of the PERK pathway during conditions of UPR but has no effect on IRE1-XBP1 or ATF6 pathway. ARRB1 expression protected cells from UPR-induced cell death. From a list of clinically approved drugs with relatively higher bioavailability we found that Spiperone treatment remarkably reduced ARRB1 expression. Spiperone-mediated reduction of ARRB1 expression is linked to the ability of Spiperone to activate UPR. Further, we demonstrated that targeted downregulation of ARRB1 with Spiperone, could enhance the sensitivity towards tamoxifen.
Results 3: Role of ARRB1 in regulating expression and function of TP53 in ER-positive breast cancer. Next, we evaluated the role of ARRB1 on TP53 response pathway. We observed increased expression and function of TP53 after treatment with DNA damage reagents (5FU, cisplatin & Doxorubicin) in ARRB1 overexpressing cells. Moreover, ARRB1 knockdown cells showed decreased expression and function of TP53 after treatment with DNA damage reagents (5FU, cisplatin & Doxorubicin). Further ARRB1 co-expression enhances the transactivation of TP53 in reporter assays. Furthermore, ARRB1 enhanced 5FU-induced cell death and compromised the recovery and growth of cells after a short-term exposure to 5FU.
We show that ARRB1 is at interface of ER signalling, UPR pathway and TP53 pathway in breast cancer. The results revealed the complex role of ARRB1 in ER-positive breast cancer cells. On the one hand, it contributes to endocrine resistance in ER positive breast cancer cells, and on the other hand, it increases the sensitivity towards DNA-damage inducing agents (5FU). The results presented in thesis suggest that reduction of ARRB1 can sensitize the cells to endocrine therapy. The patients with increased ARRB1 and wild type TP53 will respond better to 5FU treatment
Towards a unified framework of intercultural communication competence: A multidisciplinary approach
No full textThis thesis examines the relationship between intercultural communication competence (ICC) and team effectiveness in multicultural teams. Effective ICC is critical for multicultural teams to achieve high levels of efficiency and effectiveness in a hyper-competitive, complex, and dynamic environment. In recent years, scholarly interest in ICC has grown exponentially. However, studies on ICC across disciplines are severely fragmented; specifically, there is a dearth of studies in the area of multicultural project teams. The field of ICC struggles with inconsistencies and challenges. There is a lack of clarity in the definition of ICC across disciplines, and many existing ICC models are overly abstract, theoretical, and lack empirical validation. Furthermore, robust scales and tools to measure ICC accurately are in short supply.
This study advances a holistic understanding of ICC by theoretically proposing and empirically validating a unified model for ICC in multicultural teams. A systems perspective is employed to transcend disciplinary silos and ensure a more holistic and unified approach. To do this, a systematic review of 85 peer-reviewed articles published between 1976 and 2021 was conducted. This analysis presents an understanding of prior work focusing on the evolution of the concept and the emerging trends, a synthesis of the definitions, models and frameworks, and an analysis of the characteristics and components of ICC. Findings from this analysis informed the development of a model for ICC. This model integrates antecedents, consequences and mediating mechanisms for empirical investigation and validation in the context of multicultural project teams. It was validated by employing partial least squared structured equation model analysis (PLS-SEM) using data from 323 experienced industry professionals.
The key findings of this study indicate significant relationships between factors such as Active Listening, Acknowledge, Recommend, and Negotiate, and ICC. These factors influence ICC in various ways, with some effects being mediated by Empathy or Attitude Towards Other Cultures (ATOC). Crucially, the study demonstrates that ICC has a direct positive impact on Team Effectiveness. It thereby underscores the importance of fostering positive attitudes towards other cultures, empathy, active listening, and effective negotiation strategies to enhance intercultural communication competence and team performance. The unified model and the new scale developed to measure ICC and team effectiveness represent significant contributions, offering validated and reliable tools for future research and practical application
Development of cobalt-based catalysts for water electrolysis
No full textThe present thesis investigates the synthesis, structural modification, and electrochemical characterisation of cobalt based catalysts for alkaline and acidic water splitting. The focus is on the impact of iron (Fe) and manganese (Mn) doping on cobalt phosphate and cobalt oxide electrocatalysts, particularly their influence on structure and morphological changes and knock-out effects on the catalytic performance. The thesis is divided into eight chapters, beginning with an introduction to the research context, followed by research objectives and methodology, the main results contained in four chapters covering material synthesis, characterization and electrochemical testing, and finishing with the main conclusions of this work.
Chapter 1
This chapter establishes the motivation behind the study by discussing the global need for sustainable hydrogen production. It introduces electrochemical water splitting, emphasizing the role of oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) catalysts. The fundamental principles of electrocatalysis in alkaline and acidic environments are reviewed, followed by a discussion on the limitations of conventional electrocatalysts. The chapter concludes with an overview of cobalt-based materials, highlighting their tunability via doping and structural modifications.
Chapter 4
This chapter explores the impact of morphology and Mn doping on the OER activity of cobalt oxide (Co3O4) in acidic conditions. Co3O4 catalysts with different morphologies, including sheets, flowers, and cubes, were synthesized and evaluated for their OER performance. Sheets morphology shows superior catalytic performance due to a greater number of exposed active sites and improved charge transfer kinetics. Mn-doped Co3O4 sheets were then prepared to investigate the role of Mn in enhancing catalytic activity. It was reported in literature that Mn doping was found to enhance stability by strengthening the Mn-O bond, reducing cobalt dissolution, and potentially activating self-healing mechanisms. The work in this chapter highlights the potential of Mn as a strategic dopant for improving the durability and efficiency of platinum group metal free (PGM-free) OER catalysts in acidic environments.
Chapter 5
This chapter focuses on the synthesis and electrochemical evaluation of ammonium cobalt phosphate (NCP) catalysts for OER and HER in alkaline conditions. Cobalt phosphate is identified as a promising electrocatalyst due to its structural stability, high electronegativity of phosphate ions, and variable cobalt oxidation states that facilitate electron transfer. The study explores the role of morphology, composition, and doping strategies in optimizing catalytic performance. NCP nanosheets were synthesized via a surfactant-free co-precipitation method, with controlled size and thickness achieved by varying solvent viscosity. The impact of Fe and Mn doping on catalytic activity was investigated, leveraging their ability to introduce structural defects, alter electronic properties, and enhance charge transfer. Fe doping was found to lower the overpotential for OER, while Mn doping stabilized reaction intermediates, improving HER performance.
Chapter 6
Inspired by Chapter 4, this study investigates Fe-doped Co3O4 sheets for alkaline OER, using a systematic low Fe doping approach to optimize performance. Catalysts were tested in a three-electrode system, including temperature dependence studies and 100 h stability test. It was reported in literature that Fe3+ doping modifies the Co-O bond structure, enhancing electrical conductivity and optimizing O* and OOH* adsorption energies, reducing overpotentials. However, excessive Fe leads to FeOOH formation, negatively impacting conductivity. In this study, we aimed to improve the catalytic behaviour of previously synthesised Co3O4 catalysts by introducing a dopant element to modify their crystal structure and chemical composition slightly. To address the intrinsic slow reaction kinetics at the anode, we have developed Fe doped cobalt oxide electrocatalyst to facilitate the OER process. The incorporation of iron atoms modifies the electronic framework of pristine cobalt oxide, thereby catalyzing an enhancement in OER performance. Iron doped cobalt oxide catalysts were synthesized using varying Fe ratios via the hydrothermal approach and subsequently calcined at 450°C. The results demonstrate that even small concentrations of Fe significantly impact the catalytic performance for the OER. Moreover, while higher Fe concentrations enhance performance, there is a saturation point beyond which further doping leads to the formation of cobalt ferrite (CoFe2O4) instead of maintaining the Fe-doped Co3O4 structure.
Chapter 7
As an extension of Chapter 6, this chapter evaluates Fe-doped Co3O4 sheets. The catalysts were integrated into an anion exchange membrane water electrolysis (AEMWE) cell to assess their performance under practical operating conditions. The PGM-free AEMWE cell demonstrated excellent performance, reaching 1000 mA·cm-2 at 1.92 V, approaching industrial-scale operation requirements. The PGM-free electrolyser exhibited promising performance at current densities up to 2000 mA·cm-2, maintaining low cell voltages and exceptional durability. Over 100 hours of operation at 1000 mA·cm-2, the average degradation rate was 1.3 mV·h-1, which later decreased to 0.4 mV·h-1 as the initial membrane-related degradation stabilized. Additionally, X-ray photoelectron spectroscopy (XPS) and post-mortem analysis were conducted to investigate changes in the electronic structure and surface composition after electrochemical testing. These analyses provided deeper insights into catalyst stability and the role of systematic low-level Fe doping in maintaining long-term OER activity.
Chapter 8
This chapter summarises the main outcomes of the work carried out in this thesis, highlighting the influence of morphology and elemental doping on the performance of cobalt-based catalysts across different water-splitting environments. It also discusses the broader significance of these findings, assesses the practical applicability of the developed materials, and presents perspectives for future research
Microbial ecology and the role of conductive materials in sulfate-rich anaerobic digestion systems using different reactor configurations
No full textAnaerobic digestion (AD) is widely applied as an efficient technology for the treatment of sulfate-rich wastewater, enabling simultaneous organic removal and energy recovery. However, the existence of sulfate fundamentally alters microbial community structure and metabolic networks, intensifying competition and cooperation among key functional groups, especially between various types of sulfate-reducing bacteria (SRB) and methanogens. In addition, hydrogen sulfide (H₂S), as the terminal product of sulfate reduction, exerts severe toxicity on methanogens and other key functional microorganisms, threatening methane production and process stability. Although much attention has been given to SRB and H₂S inhibition, the ecological differentiation and metabolic roles of incomplete oxidizing SRB (IO-SRB) and complete oxidizing SRB (CO-SRB) with methanogens, as well as their adaptive responses to H₂S stress, remain poorly understood. Moreover, conductive materials (CMs) have shown great potential in enhancing anaerobic digestion of sulfate-rich wastewater by improving electron transfer. However, how the effectiveness of CMs varies under different reactor operational modes that shape microbial communities and system performance are still unclear. To comprehensively address these knowledge gaps, this study systematically investigates the distinct ecological roles, interspecies interactions, and stress adaptation mechanisms of key functional microorganisms under different reactor configurations and with the addition of CMs
Four ethanol-fed bioreactors were operated under two operational modes (sequencing batch reactor, SBR; and continuous flow-reactor, CFR) and two chemical oxygen demand to sulfate (COD/sulfate) ratios (1 and 2) to systematically explore strategies for enriching IO-SRB and/or CO-SRB and their microbial interactions with other microorganisms. Compared to SBRs, CFRs could enhance sulfate removal and demonstrated higher microbial activities in sulfate and ethanol degradation. IO-SRB competed with ethanol-oxidizing bacteria (EOB) in all reactors, and IO-SRB's contribution to ethanol degradation increased from 62.9%-67.1% to 69.0%-82.1% as the COD/sulfate ratio decreased from 2 to 1. Moreover, CO-SRB competed acetoclastic methanogens (AM) exclusively in CFRs, as CO-SRB could not be efficiently enriched in SBRs. Low COD/sulfate ratios facilitated the enrichment of Desulfococcus (CO-SRB), and the CFR operational mode further strengthened its enrichment. Additionally, hydrogenotrophic SRB outperformed hydrogenotrophic methanogens in all four reactors. In general, IO-SRB and CO-SRB possessed distinct microbial interactions with methanogens, with potential syntrophic relationships between IO-SRB and AM while competitive relationships between CO-SRB and AM.
In addition, this study investigated the tolerance and adaptive mechanisms of functional microorganisms to H2S. Long-term experiments demonstrated that CFRs combined with a COD/sulfate ratio of 1 achieved superior sulfate reduction and ethanol degradation rates under H2S stress, while SBRs with a COD/sulfate ratio of 2 facilitated methanogenic activity. Batch inhibition experiments revealed that EOB and IO-SRB exhibited greater H2S tolerance in CFRs, with EOB (IC50 = 51.2-185.1 mg/L) generally outperforming IO-SRB (IC50 = 47.4-97.7 mg/L). While AM and CO-SRB showed enhanced H2S tolerance in SBRs compared to CFRs, particularly AM in SBR with the COD/sulfate ratio of 2 (IC50 = 113.2 mg/L). Microbial adaptation analysis demonstrated that SBRs promoted Methanothrix enrichment, enhancing detoxification capacity by specifically increasing the relative abundance of genes encoding thiosulfate sulfurtransferase to mitigate H₂S toxicity. Desulfomicrobium and Geobacter were significantly enriched in CFRs, and they mitigated H2S inhibition through increased cytochrome bd oxidase and cysteine synthase genes, respectively. Furthermore, thioredoxin and cysteine desulfurase protein repair genes sustained microbial metabolism under H₂S stress.
This study further compared SBRs and CFRs amended with magnetite (Fe₃O₄) or powdered activated carbon (PAC) for treating sulfate-rich wastewater. CM amendments significantly accelerated sulfate reduction, volatile fatty acids degradation, and methane production, especially with the addition of Fe₃O₄. Maximum methanogenesis rates in CFRs increased from 31.2 to 51.0 and 39.7 mg COD/(g VSS·h) with the addition of Fe₃O₄ and PAC, respectively. Methanogenesis in SBRs was severely inhibited by elevated H2S concentrations, and supplementation with 1 g/L CMs failed to alleviate this inhibition. However, CFRs favored direct ethanol-to-acetate conversion, whereas SBRs activated ethanol-to-propionate metabolic pathway mediated by Desulfobulbus. CM additions led to increased sludge conductivity and electron transport activity. Specifically, PAC strongly enhanced electron transfer in CFRs by promoting e-pili and cytochrome gene abundances, whereas Fe₃O₄ in SBRs predominantly acted as an external conductive conduit, partially substituting intrinsic microbial conductive structures. Key SRB, including Unclassified_f_Desulfovibrionaceae, Desulfomicrobium, Desulfolutivibrio, and Desulfovibrio, dominated the expression of e-pili and cytochrome genes associated with the direct interspecies electron transfer, which was promoted by CFR operation through the enrichment of SRB. Microbial co-occurrence network analysis further highlighted Desulfovibrio, Methanothrix, and Geobacter as central keystone species mediating robust syntrophic electron transfer networks. These findings provide critical insights for optimizing sulfate-rich wastewater treatment through strategic selection of reactor modes and CMs.
Overall, this study provides a comprehensive understanding of how reactor configurations, COD/SO₄²⁻ ratio, and CM amendments modulate the enrichment, interaction, and resilience of key functional microorganisms in sulfate-rich anaerobic systems. By distinguishing the ecological roles of IO-SRB and CO-SRB and elucidating their interactions with methanogens under varying COD/SO₄²⁻ ratios and operational modes, this work reveals fundamental microbial mechanisms governing electron competition and H₂S stress response. The findings underscore the critical importance of tailoring reactor strategies and material interventions to drive electron flow, enhance syntrophic cooperation, and stabilize process performance. These insights contribute valuable guidance for the rational design and optimization of anaerobic treatment processes treating sulfate-rich wastewaters, advancing both theoretical microbial ecology and practical engineering applications
Technology-based instructional media to enhance Indonesian high school students’ English speaking self-efficacy
No full textTechnology is everywhere, shaping how we learn, communicate and engage with the world. Despite widespread adoption of technology in language education, two key challenges remain underexplored in English as a Foreign Language (EFL) contexts like Indonesia: the persistent issue of low self-efficacy in English speaking, and the lack of accessible, contextually appropriate instructional resources tailored to students’ needs. While numerous studies have explored speaking instruction through communicative and multimedia-based approaches, few have directly addressed how to design interventions that foster students’ belief in their ability to speak English. At the same time, collaborative learning, an approach rooted in communicative pedagogy, has shown promise in creating supportive, student-centred environments where learners can practise speaking, receive peer feedback, and gradually build confidence. However, there are no reported technology-based resources that are purposefully designed to support English speaking self-efficacy through collaborative learning.
This study responds to these gaps following this overarching research question: How can technology-based instructional media be designed and implemented in the Indonesian context to enhance senior high school students’ self-efficacy in speaking English through the integration of technology, collaborative learning strategies and pedagogical approaches aligned with related sources of self-efficacy. The research employs a design-based research (DBR) methodology grounded in Bandura’s (1986) Socio-Cognitive Theory and Vygotsky’s (1978) Constructivist Learning Theory. The integration of Socio Cognitive Theory of Bandura about self-efficacy and Vygotsky’s Constructivist Theory, which emphasises collaborative learning and technology-mediated interaction, seeks to bridge the gap between theoretical insights and practical applications in language education.
Four Phases of DBR as outlined by Reeves (2006) were followed: problem analysis, solution development, iterative cycles of testing and refinement, and reflection. The problem analysis phase began with a reflective examination of the researcher’s personal experiences as both an English language learner and an English language educator, followed by an extensive literature review on English language teaching in foreign language contexts. During the solution development phase, referred to as design cycle one, six technology-based instructional media were collaboratively designed by pre-service English teachers. These initial designs underwent comprehensive review and modification based on participant feedback. The iterative testing, refinement, and reflection phases, referred to as design cycle two and design cycle three involved the classroom implementation of this technology-based instructional intervention. In design cycle two, the researcher served as the instructor, facilitating the implementation process. Subsequently, in design cycle three, nine Indonesian teachers delivered the lessons after completing a theory-pedagogy workshop designed to equip them with the necessary knowledge and skills to integrate the instructional media into their teaching.
The findings revealed that the designs of the technology-based instructional media effectively enhance students’ English speaking self-efficacy. This research brings contribution in two areas: pedagogical contributions (the development of innovative teaching practices and the design principles that inform English teachers and instructional media developers on how to create their own instructional materials to enhance students’ self-efficacy), and theoretical contributions (advancing theories in technology-based instructional design, specifically to enhance students’ self-efficacy in speaking English). While the study highlights the influence of technology-based instructional media integrated with collaborative learning strategies and pedagogical approaches aligned with related sources of self-efficacy in improving students’ speaking self-efficacy, further research is needed to explore their impact on students’ actual speaking proficiency. Additionally, the instructional media content may require adjustment or modification for applicability in different educational contexts.
Keywords: Technology, Instructional Media, English Speaking, Self-Efficacy, EFL Teaching in IndonesiaThis work is funded by the Indonesia Endowment Funds for Education, Ministry of Finance and the Center of Higher Education Funding, Ministry of Education, Culture, Research, and Technology of Republic of Indonesia.This work is funded by the Indonesia Endowment Funds for Education, Ministry of Finance and the Center of Higher Education Funding, Ministry of Education, Culture, Research, and Technology of Republic of Indonesia
Peptide and protein modification for biological and therapeutic applications
No full textFor the first two years of my Ph.D. programme, I conducted research under the supervision of Dr. Kurt Hoogewijs. This research is outlined in Chapter 1. Following Dr. Kurt Hoogewijs departure from the university, I remained at the University of Galway, where I joined the research group of Dr. Eddie Myers. This research is outlined in Chapter 2.
Chapter 1
Mitochondria are known as the powerhouse of the cell as they produce 90% of the energy the body needs to sustain life and support organ function. Mitochondrial diseases are a group of disorders caused by mutations in the nuclear or mitochondrial genes, affecting ~ 1 in 4,000 people. At present, there is no effective treatment for these progressive and life-threatening diseases. One of the most common mitochondrial diseases is MELAS (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes), which is caused by a point mutation in the gene encoding mitochondrial tRNALeu(UUR)3. Previous studies have shown that the 16-mer LARS2β32_33 peptide derived from mitochondrial leucyl-tRNA synthetase exerts rescuing activity on the mutated mt-tRNA-Leu. In this study, we investigate the structure-affinity relationship of these peptides and identify the truncated form of the LARS2β32_33 peptide that binds to tRNALeu(UUR) by using microscale thermophoresis. Truncation of several N-terminal amino acid residues of LARS2β32_33 provides peptides with retained binding affinity to the tRNA. Alanine scans have highlighted the particular importance of hydrophobic residuesfor binding affinity to the tRNALeu(UUR) . Interestingly, the LARS2 β32_33 peptide also has binding affinity for non-cognate mt-tRNA Lys, Val, Ala and Ala(mouse). This data provides critical insight for the development of peptidomimetic therapeutics based on LARS2β32_33 peptides as potential widespread therapeutics for mitochondrial diseases.
Chapter 2
Post-translational modifications (PTMs) have a profound effect on protein structure and function, influencing many cellular processes and disease progression. Lysine residues are known to undergo a particularly diverse range of PTMs, but the function of some of these modifications remains unclear. Accessing pure, well-defined, site-specifically modified proteins is vital for understanding the mechanisms in which they are involved. Owing to the superior nucleophilicity of the cysteine thiolate and the rarity of cysteine in the human proteome (ca. 2%), thisresidue is often exploited forsite-specific installation of PTM mimics2 . γ-Thialysine, the simplest cysteine-derived lysine analogue, exhibits comparable structural and chemical properties, justifying its use as a representative lysine mimic. Herein, we have developed a fast and easily accessible method that enables the transformation of cysteine residues into γ-thialysine derivatives by using cyclic sulfamidates. These reagents demonstrate excellent selectivity and high conversion rates and can be employed under mild reaction conditions. The transformation involves ring-opening of the cyclic sulfamidate to form intermediate sulfamic acid derivatives, which, depending on the nature of the substituent on the nitrogen atom, undergo buffermediated desulfonation to the desired γ-thialysine analogues. We demonstrate the installation of various γ-thialysine PTMs into small molecule, peptide and protein model systems. This work highlights cyclic sulfamidates as privileged reagentsforselective alkylation of cysteine residues and shows promise for subsequent applications in therapeutic or biological research
Enabling innovation: Analysing the role of design thinking as a dynamic capability in enhancing team creativity and project performance
No full textDesign Thinking (DT), as an approach to fostering innovation, has garnered significant attention in both professional practice and academic research across various disciplines. In today’s rapidly evolving landscape, driving innovation requires renewed approaches that prioritise agility, adaptability, and other organisational capabilities to effectively navigate uncertainty and complexity. Consequently, this study examines DT as a dynamic capability (DC), emphasising its role in enabling organisations to sense opportunities, seize them effectively, and reconfigure resources to enhance innovation. By fostering creative problem-solving, DT not only strengthens the ability to innovate but also contributes to team creativity and project performance. Viewing DT through this lens is particularly important, as it provides a structured yet flexible framework that fosters innovation while ensuring organisations remain competitive in dynamic and uncertain markets. However, despite its potential, it is an emerging area, and the domain lacks coherence and clarity, particularly in understanding the dynamic nature of DT and its role as a DC. To address this, the present exploratory study aims to contribute to the growing body of research on DT by (1) synthesising and critically reviewing DT literature through bibliometric and thematic analyses, examining DT's definitions, measurement approaches, benefits, and developing a comprehensive nomological network that categorises its antecedents, moderators, mediators, and outcomes across individual, team, and organisational levels, (2) developing a theoretical framework derived from the nomological network, and identifying the key constructs that underpin the model, (3) examining the relationship between DT and team creativity and project performance, as well as antecedents to DT practices and the mediators and moderators that influence the interplay between DT practices and outcomes (4) empirically validating the model using advanced statistical analysis.
To do this, a systematic literature review (SLR) comprising 93 journal papers published between 2010 and 2024 was conducted to help understand the domain and inform the development of a nomological network. This provides a typology for discussing the growing state of the art in the area of DT and innovation. Following this analysis, a theoretical model was developed, and hypotheses were generated. To test these hypotheses, a quantitative research approach was employed, involving the collection of empirical data from 363 experienced individuals engaged in innovation projects. The collected data was then analysed using Smart PLS, a Partial Least Squares Structural Equation Modelling (PLS-SEM) technique, to evaluate the proposed relationships and validate the hypotheses.
The key findings of this study reveal several significant relationships among the examined factors. Collaboration was identified as an important antecedent of DT. The analysis uncovered a direct significant relationship between DT and team creativity and project performance, and this relationship is mediated by entrepreneurial orientation (EO). Additionally, trust was identified as a key moderator of the relationship between collaboration and DT, playing a particularly salient role in strengthening this association. Furthermore, the findings indicate that team diversity moderates the relationship between DT and both team creativity and project performance, underscoring its critical influence on these innovation outcomes.
Overall, the findings of this research make significant contributions to the field of DT. Firstly, the study synthesises a growing area of research and provides a comprehensive overview of DT studies. Secondly, it brings valuable insights and empirical evidence to show how DT can be understood as a DC to enable organisations to sense opportunities, seize them, and transform their resources to enhance creativity and project performance. Thirdly, it offers insightful thoughts into the antecedents, consequences, mediators and moderators of DT enabling its theoretical and empirical advancement. Finally, it pinpoints future research directions to scholars and brings practical suggestions for practitioners who seek to implement best practices in organisations toward enhancing team creativity and achieving high project performance
Tetracycline in anaerobic digestion: Inhibitory effects and strategies for enhanced removal
No full textTetracycline is a widely used antibiotic that is frequently detected in various environmental matrices, due to its incomplete metabolism in humans and animals. The presence of tetracycline poses potential environmental risks. In anaerobic digestion systems, tetracycline can lead to the accumulation of volatile fatty acids, suppression of methane production, and inhibition of functional microorganisms. As a recalcitrant contaminant, tetracycline can be removed from anaerobic digestion systems through adsorption and biodegradation, with removal efficiency influenced by operational parameters and the presence of co-metabolizable substrates. In recent years, the addition of conductive materials, such as powdered activated carbon (PAC), has been reported as a promising strategy to enhance system performance. These materials promote electron transfer, regulate redox conditions, and facilitate the microbial activity. Therefore, a comprehensive understanding of the system-level and microbial-level responses of anaerobic digestion systems to environmental disturbances, such as tetracycline, is essential for optimizing the treatment of antibiotic-contaminated wastewater or waste.
This study aims to: (i) elucidate the response of the anaerobic digestion system to tetracycline stress at both the system performance and functional gene levels; (ii) regulate the metabolism of complex carbon sources and enhance tetracycline removal by enriching microorganisms with distinct characteristics through operational parameter adjustment; and (iii) explore the application of conductive materials (PAC) for alleviating tetracycline inhibition and enhancing its removal via synergistic adsorption and biodegradation.
Two operational modes, continuous-flow reactors (CFRs) and sequencing batch reactors (SBRs), were employed in this study under conditions with or without tetracycline addition, to assess the systems capacity for pollutant removal, microbial activity, and community dynamics. The results showed that tetracycline inhibited the maximum methane production rate by 24.5% in CFRs and 48.8% in SBRs. In addition, propionate accumulation was observed in tetracycline-added systems. Under steady-state conditions, over 80% of tetracycline removal was attributed to biodegradation. At the microbial level, long-term tetracycline exposure reduced the abundance of methanogens and propionate-oxidizing bacteria. Compared to SBRs, CFRs exhibited better recovery ability under shock loading, and showed advantages in propionate degradation and methane production. CFRs also facilitated the maintenance of key functional microbes. Subsequently, PAC addition further improved both system performance and tetracycline removal. PAC increased the maximum methane production rate by 15.6% in CFRs and 13.8% in SBRs, and enhanced tetracycline biodegradation by 24.4% and 19.2%, respectively. The genes encoding carbon dioxide reduction in Methanothrix and the presence of Geobacter suggested the possible involvement of direct interspecies electron transfer in methane production, particularly in PAC-added CFRs.
In addition, this study further explored the system-level and gene-level responses of anaerobic digestion to tetracycline stress. At the reactor level, the effects of tetracycline dosage and sludge origin were investigated. In systems with laboratory seed sludge, increasing tetracycline concentrations (0 - 5 mg/L) inhibited ethanol production and potentially suppressed subsequent acetogenesis. When the concentration exceeded 5 mg/L, butyrate accumulated and its degradation was inhibited. Methane production was clearly impaired even with 2.5 mg/L tetracycline. In contrast, systems with farm sludge maintained stable chemical oxygen demand removal but exhibited no methane production capability. Both types of sludge exhibited tetracycline biodegradation capacity, and the biodegradation efficiency was not concentration-dependent.
Metagenomic analysis further revealed mode-dependent microbial adaptation strategies. In CFRs, the microbial community was dominated by taxa resistant to tetracycline toxicity, exhibiting cohesive microbial interactions and strong functional redundancy. Meanwhile, SBRs relied on resilient microbial communities to adapt to fluctuating conditions. As for tetracycline resistance genes, ribosomal protection proteins were primarily enriched in CFRs, whereas SBRs accumulated high energy-dependent efflux pump genes. For example, the relative abundance of tetZ was actively reduced under resource-limited conditions in SBRs. With regard to energy metabolism, tetracycline stress stimulated an increase in ATPase gene abundance. While F-type ATPase genes predominated in SBRs, methanogens in CFRs played a major role in maintaining energy metabolism under antibiotic pressure. Further analysis indicated a strong coordination between genes involved in ATPase synthesis and extracellular electron transfer.
This study reveals the destabilization mechanisms and adaptive pathways of anaerobic digestion systems under tetracycline stress from the perspectives of system performance, microbial community dynamics, and functional genes. A regulatory framework combining operational mode and SRT adjustment with PAC enhancement is investigated. The findings demonstrate the important role of operational parameters in stabilizing system performance and shaping functional microbes, while highlighting the synergistic effects of PAC in alleviating antibiotic inhibition and enhancing reactor performance. Gene-level analysis uncovers a dynamic trade-off between resistance burden and energy metabolism, highlighting microbial strategies for ecological adaptation under antibiotic pressure. This study establishes both theoretical and engineering foundations for enhancing the anaerobic digestion of antibiotic-contaminated wastewater and waste, and provides a conceptual framework for future investigations into microbial metabolism-energy-resistance regulation mechanisms