NUI Maynooth Eprint Archive
Not a member yet
18159 research outputs found
Sort by
Critical Data Studies: An A to Z Guide to Concepts and Methods
No full textCritical Data Studies has come of age as a vibrant, interdisciplinary field of study. Taking data as its primary analytical focus, the field theorises the nature of data; examines how data are produced, managed, governed and shared; investigates how they are used to make sense of the world and to perform practical action; and explores whose agenda data-driven systems serve.
This book is the first comprehensive A-Z guide to the concepts and methods of Critical Data Studies, providing succinct definitions and descriptions of over 400 key terms, along with suggested further reading. The book enables readers to quickly navigate and improve their comprehension of the field, while also acting as a guide for discovering ideas and methods that will be of value in their own studies.
Critical Data Studies is essential reading for students and scholars from across the sciences, social sciences and humanities, as well as those who work with data professionally who want to extend and enrich their conceptual and practical understanding of data and their use
Supramolecular tools to combat antimicrobial resistance
No full textSince its advent in the 1960s, through the pioneering work of Lehn, Cram, and Pederson
– the field of supramolecular Chemistry has burgeoned and seen an array of applications
across the chemical and materials sciences. From Metal-organic frameworks which
exhibit notable chemical separation behaviours, to molecular receptors, and the
compounds which form Organic Light Emitting Diodes used by millions daily, there are
countless examples of the continuous advancements from the field. One such recent
interdisciplinary area gaining traction in recent years, is the application of supramolecular
chemistry concepts, and molecular design to the field of medicinal chemistry. For
example, there have been a plethora of reports of anion transporters, molecules which can
form association complexes with negatively charged ions and transport them across
membranes. These anion transporters have shown utility in the development of
therapeutics for Cystic Fibrosis, as anticancer therapeutics, and more recently as
antimicrobial agents.
Whilst the anticancer properties of anion transporters have been explored extensively,
and mechanistically characterised, there has been little effort made to further refine the
antimicrobial capacity of agents such as these. Furthermore, while several reports of
antimicrobial anionophores have been made – very little mechanistic underpinning has
been carried out. This Thesis, titled “Supramolecular tools to combat antimicrobial
resistance” aims to establish several classes of anionophores, and chemical tools to further
delve into the mechanistic subtleties of medicinally relevant supramolecular motifs.
Chapter 1 of this thesis provides a historical perspective on the supramolecular chemistry
of anion transport, paying particular attention to the medicinal relevance of anion
transporting motifs. In addition, there is a discussion of concepts employed by medicinal
chemists when designing antibiotics, aided through a discussion of historically relevant
examples, and the emergence of antimicrobial resistance. Following this, some of the
chemical biology techniques utilised throughout the course of this work are introduced
and discussed from a technical viewpoint.
Chapter 2 discusses the synthesis, supramolecular profiling, and mechanistic
underpinning of a series of four potent “squindole” antimicrobials. These compounds,
which can effectively bind, and transport Cl- across Large Unilamellar Vesicles (LUV’s),
exhibit potent antimicrobial activity, which was discerned to be as a result of a disruption
of chloride homeostasis.
Chapter 3 follows on from the previous chapter, where we aimed to synthesise
sophisticated bioconjugates of the most active lead compound, from chapter 2. Aided by
the use of “click” chemistry, we made significant progress towards the development of
natural product derived ion-pair receptors, for investigation as antimicrobials. Whilst we
could not arrive at a set of synthetic conditions which afforded target compounds, we
have made significant progress in this regard, and developed a series of biorthogonal
anion receptor motifs. In addition, through conjugation of lead compounds to
siderophores, we were able to expand the spectrum of activity to encompass Gramnegative
pathogens.
Chapter 4 takes a traditional “lead-refinement” approach to the development of
heterocyclic antimicrobial anionophores. Through scaffold hopping approaches, from
lead compounds of Chapter 2, we afforded three distinct heterocyclic subfamilies, each
of which exhibits antimicrobial effect against MRSA – to varying degrees. Using
conventional supramolecular approaches, in addition to cutting edge Chemical Biology
techniques, we studied, and verified an analogous mechanism of action to previous leads,
which is aided by the propensity for covalent modification of thiols in solution, which
may rationalise the observed antimicrobial effect.
Chapter 5 introduces a series of 13 structurally simplistic anion receptors, which show
varying anion binding propensities, but potent anion transport in-cellulo. This anion
transport behaviour manifests in potent antimicrobial activity against a range of
pathogens (both Gram-positive, and -negative), which we discerned to be linked to both
anion transport, and a disruption of membrane integrity. In addition, we successfully
synthesised a “caged anionophore” and carried out preliminary dissection of the spatiotemporal
control of anion transport in-cellulo.
Chapter 6 consists of a thesis summary which details the main findings for this project,
and potential future directions for each chapter. Chapter 7 includes the general
experimental procedures, synthetic methodology and compound characterisation, and
biological procedures for the work detailed in previous chapters. This is complimented
and followed by literature references and an appendix which is comprised of
spectroscopic and ancillary data which validates the work discussed in this thesis
Hybrid Optimal Control for an Active Mechanical Motion Rectifier for Wave Energy Converters via Separation Principle
No full textThe wave energy field is characterised by its continuous growth and development in research and technology. Over recent decades, different application issues have hindered the worldwide implementation of wave energy devices, and only a few have reached the commercialisation stage. Some of these inherent challenges have driven the creation of innovative wave energy system designs. In particular, active mechanical motion rectification (AMMR) is a novel proposal to rectify the energy flux in wave energy devices. The objective of active rectification is twofold. On the one hand, it increases the overall system efficiency by achieving a higher average output velocity in the generator. On the other hand, the AMMR introduces a new variable in the control design: A switching law to connect and disconnect the generator from the wave capture structure. Thus, the control design possesses two degrees of freedom, significantly increasing the complexity of the energy-maximising power take-off control problem. In this paper, the problem of designing an optimal control philosophy for an AMMR-based wave capture system is addressed. The problem is solved by proving that, a separation principle applies, and that the optimal control solution over a fixed interval, is independent of the optimal switching sequence selection. To illustrate the utility of the analytical results, a numerical example for a flap-type wave energy converter, utilising an AMMR-based power take-off, is presented
A qualitative study to explore post-primary principals’ view of the influence of staff conflict on school culture.
No full textThis thesis explores how post-primary principals construct, interpret, and make sense of the influence of staff conflict on school culture. The research objectives are threefold: to examine the experiences of post-primary principals in Munster of staff conflict on school culture; to explore the conflict resolution strategies employed by these principals; and to develop recommendations and approaches that will contribute to more effective ways of addressing staff conflicts which can influence school culture.
Utilising a qualitative methodology, the study involved semi-structured interviews with principals to gain in-depth insights into their perspectives and practices. The findings reveal the complex nature of staff conflicts, including their causes, manifestations, and impacts. Principals identified various factors contributing to conflicts, such as personality clashes, differing values, and power dynamics. The study highlights the dual nature of conflicts, with both constructive and destructive outcomes significantly influencing school culture.
The research highlights the importance of socio-emotional support systems for principals, including counselling services, peer support networks, mentorship programs, and professional development workshops focused on emotional intelligence and reflective practices. Additionally, it calls for comprehensive data collection on staff conflicts and regular updates to policies to provide clear guidelines for conflict resolution. By integrating relational leadership and sensemaking theories, the study provides a comprehensive framework for understanding the dynamic processes of leadership and conflict management. This integration emphasises the importance of building trust, fostering open communication, and adapting leadership strategies through reflective practice.
The thesis concludes with practical recommendations for educational policy, including the development of clear conflict resolution policies, mandatory training for principals and staff, and the allocation of resources for support services. The findings highlight the critical role of principals in shaping a positive and inclusive school culture through conflict management. This research contributes valuable knowledge to the field of educational leadership, offering strategies to support principals and enhance the overall school environment, ultimately benefiting both staff and students
“I never thought about how much of a juggle it would be”: motherhood and work in contemporary Lithuanian and Irish creative industries
No full textThis article explores the experiences of Irish and Lithuanian mothers in creative work who detail challenges they face and the various strategies they develop to sustain creative work and care for their children. The study draws from 24 interviews which were carried out with mothers in both countries at various stages in their careers. Our study stresses the importance of national context in research on European creative workers, since national and localised differences feature little in creative industries literature. By assessing mothers in their national contexts, we argue that mothers may share overall experiences of juggling work and family life, of the requirement to solve childcare issues and of challenges they face while working in creative industries. However, crucially, key differences emerge in how Lithuanian and Irish mothers position their professional and maternal identities. Differences arise in the solutions that Lithuanian and Irish mothers use and in the extent to which challenges may be negated, particularly across generations. We relate each of these differences to the localised contexts in which the creative workers mother
Combination chemotherapy: a modern approach to target cancer with dual-action Tyrosine Kinase inhibitor-Platinum based drugs.
No full textPlatinum complexes as anticancer drugs (i.e. cisplatin, carboplatin, oxalilplatin) were
discovered decades ago and have been approved and are worldwide used to treat a
variety of tumours. Their activity is limited by dose-dependent side effects (nephro-,
neuro- and ototoxicity) and the lack of selectivity toward cancer tissue with respect to
healthy cells remains one of the major drawbacks. Combination chemotherapy is a
burgeoning strategy that consists of combining in the same molecule two different drugs
with two different mechanisms of action that can operate simultaneously, targeting
different features on the cancer cell. Tyrosine kinases (TK) are promising targets in
oncology and play a major role in cell regulation pathways (e.g. metabolism,
transcription, cell division and programmed cell death) and TK deregulation is often
related to cancer onset. Currently, the activity of platinum-based drugs against certain
tumours, is limited because resistance is often acquired after few chemotherapeutic
cycles. The aim of this project is to exploit the combination chemotherapy strategy to
develop new drugs that will target cancer, combining in one unique molecule, the DNA
damaging activity of platinum with TK inhibitors. Imatinib, Nilotinib and Sunitinib are
known TKs inhibitors that are FDA approved to treat solid tumors, such as
gastrointestinal stromal cancer and renal cell carcinoma. The two active components
(platinum(II) and TK inhibitor) are released simultaneously upon intracellular reduction
or hydrolysis, and work in cooperation to increase the overall anticancer efficacy
Heterogeneous effects of blood pressure screening
No full textThis is the first study that investigates the heterogeneous effects of blood pressure (BP) screening on subsequent
changes in BP in a high-income country. We use data from clinical health assessments carried out in 2010
(baseline) and 2014 (follow-up) as part of a nationally-representative longitudinal study on ageing in Ireland.
We focus on individuals who at baseline do not report a previous hypertension diagnosis and employ a
Regression Discontinuity Design by comparing outcomes at follow-up on either side of the BP cutoff that
separates normal to abnormal BP at baseline. We find that the BP screening reduces BP at follow-up, with
larger and more precisely estimated effects for males, middle-age individuals (as opposed to older individuals),
and individuals without public health insurance coverage
New Cisalpine Celtic inscriptions from canton Ticino (CH)
No full textA presentation of two hitherto unpublished Cisalpine Celtic graffiti from Ticino, Switzerland
(LexLep TI·55 and TI·56).
During an autopsy trip to Ticino, Switzerland, for the research project Celtic Language and
Identity in Northern Italy and the Alpine Region in October 2023,1
I was shown two unpublished graffiti, written in the Lepontic alphabet, from find places in the canton – one in storage at
the Ufficio cantonale dei beni culturali in Bellinzona, one on exhibition in the Museo Castello
di Montebello.2 The present short paper presents the inscriptions, which have also been included
in the digital edition Lexicon Leponticum (LexLep) with the sigla TI·55 and TI·56
Investigations into Esophageal Epithelial Basal Cell Differentiation: Fluorescent Reporters and Mechanosensing
No full textThe esophageal disease, Eosinophilic Esophagitis (EoE) is a chronic and allergic disease.
EoE is driven by food allergens which trigger Type 2 inflammation in the esophagus and causes
symptoms such as vomiting, stomach pain, and difficulty swallowing. Increasing in prevalence,
EoE poses a significant quality of life burden to patients. Left untreated, either due to diagnostic
delay or ineffective treatments, EoE patients can develop fibrosis of the esophagus (FS-EoE)
with worsening symptoms including food impaction and esophageal stricture. Histopathologic
manifestations of the disease include basal zone hyperplasia, which worsens the barrier function
of the epithelium. To date, there is no published research mechanistically linking fibrotic tissue
stiffening to hyperproliferation in EoE. We sought to explore the molecular mechanisms of this
hyperproliferation and fibrosis.
In order to map hyperproliferation, we sought to use KRT14 as a marker of
proliferative basal cells. To map epithelial cell differentiation, we sought to use KRT13 and
KRT4 as markers of differentiated suprabasal cells. Esophageal biopsy from control and EoE
patients were stained for basal and suprabasal cell markers, KRT14 and KRT13/KRT4,
respectively. Here we have confirmed that KRT14 and KRT4 can be used to map the basal
and suprabasal layers, respectively, in esophageal epithelium. In EoE epithelium, there is an
expansion of the basal (KRT14+) and early suprabasal (KRT14-
KRT13+KRT4-
) cell layers.
While KRT14 has been assessed in EoE tissue, here, we quantified KRT14+ basal expansion
on a protein level. Likewise, while sequencing has revealed increases in suprabasal cell markers,
here, we have quantified KRT13 and KRT4 on a protein level.
To understand epithelial cell differentiation in vitro, we confirmed that this stratification
pattern was recapitulated in submerged and 3D ALI model systems, with KRT14 expressed in
proliferative basal cells, and KRT4 expressed in differentiated, barrier-forming suprabasal cells.
The promoters for KRT14 and KRT4 were therefore used to successfully drive expression of
fluorescent proteins, DsRed and eGFP, respectively.
In order to understand the relationship between fibrosis and hyperproliferation in FS-EoE, the proliferation-associated and mechano-sensing transcriptional co-factor, Yes-associated protein (YAP) was assessed for its role in esophageal epithelial cells and EoE. While
YAP has been studied in muscle in EoE, here, for the first time, we investigate the role of YAP
in non-FS- and FS-EoE tissue and in esophageal epithelial cells. We have found that YAP-mediated transcription is increased in EoE and further increased in FS-EoE tissue. We have found that YAP protein not excluded from nuclear localization in EoE tissue. YAP is not
sequestered at cell-cell junctions, mirroring EoE-related barrier deficits. We found that in vitro,
YAP cellular location is responsive to cell density and ECM stiffness in esophageal epithelial
cells. Pharmacologic-induced nuclear YAP translocation, via XMU-MP-1 was seen to increase
migration of EPC2-hTERT cells, in an EMT-like manner in submerged cultures. In air-liquid
interface (ALI) cultures, pharmacologic upregulation of nuclear YAP is shown to decrease
barrier function in an EMT-like manner and enriched the suprabasal cell population.
Therefore, in EoE and FS-EoE, YAP signaling likely contributes to decreased barrier and
fibrosis through EMT and to basal zone hyperplasia through maintenance of the KRT13+ cell
population
Not a set of norms or a set of practices
No full textIn this paper, we consider the 'eliminativist' character of Hershovitz's non-positivist theory. Focusing on chapter 5 of Law Is A Moral Practice, we ask whether Hershovitz's theory takes full advantage of the explanatory advantages of viewing non-positivism in explicitly eliminativist terms