NUI Maynooth Eprint Archive
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A Bayesian deep-learning framework for assessing the energy flexibility of residential buildings with multicomponent energy systems
No full textThis paper addresses the challenge of assessing uncertainty in energy flexibility predictions, which is a significant open question in the energy flexibility assessment field. To address this challenge, a methodology that quantifies the flexibility of multiple thermal and electrical systems is developed using appropriate indicators and considers the different types of uncertainty associated with building energy use. A Bayesian convolutional neural network is developed to capture aleatoric and epistemic uncertainty related to energy conversion device operation and temperature deviations resulting from exploiting building flexibility. The developed prediction models utilise residential occupancy patterns and a sliding window technique and are periodically updated. The energy systems evaluated include a heat pump, a photovoltaic system, and a stationary battery, and use synthetic datasets obtained from a calibrated physics-based model of an all-electric residential building for two occupancy profiles. Simulation results indicate that building flexibility potential predictability is influenced by weather conditions and/or occupant behaviour. Furthermore, the day-ahead and hour-ahead prediction models show excellent performance for both occupancy profiles, achieving coefficients of determination between 0.93 and 0.99. This methodology can enable electricity aggregators to evaluate building portfolios, considering uncertainty and multi-step predictions, to shift electricity demand to off-peak periods or periods of excess onsite renewable electricity generation in an end-user-customised manner
On the behaviour of a combined wind-wave energy conversion platform under energy-maximising control conditions
No full textClimate changes are increasingly impacting human welfare and, together with population growth, are rising the energy demand. To mitigate their negative effects, the need to harvest energy from renewable sources, while reducing the dependency on fossil fuels, has become pressing. This has led to the pursuit of new concepts that can exploit natural resources efficiently. In this scenario, offshore wind-wave hybrid platforms have been recently promoted: sharing facilities, infrastructure, and grid connections, gives these systems the potential to increase energy production at a lower cost. However, an efficient realisation of these two combined technologies requires two potentially conflicting control objectives: On the one hand, for the wind turbine, a reduced motion of the platform is required, which essentially translates to enhanced stability of the structure, so that its behaviour resembles standard onshore wind technologies. On the other hand, to maximise the energy produced, wave energy converters (WECs) require optimal control technology which often leads to large amplitude motion, potentially conflicting with the stability required for the wind turbine. The aim of this study is to provide a better understanding of how the energy-maximising control problem for WEC systems interacts with both conversion systems, and to elucidate their corresponding synergies. A semi-submersible platform with an incorporated flap-type WEC is analysed from a closed-loop perspective, with the control system designed to maximise the energy produced by the WEC
Novel design of dual-action Pt(iv) anticancer pro-drugs based on cisplatin and derivatives of the tyrosine kinase inhibitors imatinib and nilotinib
No full textTyrosine kinases (TKs) are emerging as important targets in cancer therapy and some of their inhibitors, TKIs (e.g. imatinib and nilotinib), are FDA-approved drugs that are used as selective anti-cancer therapeutics against cell lines that overexpress TKs. Many examples of metal-based complexes functionalised with TKIs are reported in the literature but very few have been functionalised with platinum. Here we report the design, a detailed computational analysis/simulation, the complete chemical characterisation and the preliminary biological evaluation of two novel Pt(IV) anticancer pro-drugs based on cisplatin tethered with a derivative of either imatinib or nilotinib in the axial position. Pt(IV) complexes are a strategic scaffold in combination therapy due to their axial ligands that can be functionalised to form dual action drugs. The activation by reduction releases the Pt(II) core and the axial ligands upon cellular internalisation. The antiproliferative activity and the TK inhibition properties of the novel adducts are analysed with a theoretical approach and confirmed in vitro with preliminary biological assays
Gliotoxin-mediated bacterial growth inhibition is caused by specific metal ion depletion
No full textOvercoming antimicrobial resistance represents a formidable challenge and investigating bacterial
growth inhibition by fungal metabolites may yield new strategies. Although the fungal non-ribosomal
peptide gliotoxin (GT) is known to exhibit antibacterial activity, the mechanism(s) of action are
unknown, although reduced gliotoxin (dithiol gliotoxin; DTG) is a zinc chelator. Furthermore, it
has been demonstrated that GT synergises with vancomycin to inhibit growth of Staphylococcus
aureus. Here we demonstrate, without precedent, that GT-mediated growth inhibition of both
Gram positive and negative bacterial species is reversed by Zn2+ or Cu2+ addition. Both GT, and the
known zinc chelator TPEN, mediate growth inhibition of Enterococcus faecalis which is reversed by
zinc addition. Moreover, zinc also reverses the synergistic growth inhibition of E. faecalis observed
in the presence of both GT and vancomycin (4 µg/ml). As well as zinc chelation, DTG also appears
to chelate Cu2+, but not Mn2+ using a 4-(2-pyridylazo)resorcinol assay system and Zn2+ as a positive
control. DTG also specifically reacts in Fe3+-containing Siderotec™ assays, most likely by Fe3+ chelation
from test reagents. GSH or DTT show no activity in these assays. Confirmatory high resolution mass
spectrometry, in negative ion mode, confirmed, for the first time, the presence of both Cu[DTG] and
Fe[DTG]2 chelates. Label free quantitative proteomic analysis further revealed major intracellular
proteomic remodelling within E. faecalis in response to GT exposure for 30–180 min. Globally,
4.2–7.2% of detectable proteins exhibited evidence of either unique presence/increased abundance
or unique absence/decreased abundance (n= 994–1160 total proteins detected), which is the first
demonstration that GT affects the bacterial proteome in general, and E. faecalis, specifically. Unique
detection of components of the AdcABC and AdcA-II zinc uptake systems was observed, along with
apparent ribosomal reprofiling to zinc-free paralogs in the presence of GT. Overall, we hypothesis
that GT-mediated bacterial growth inhibition appears to involve intracellular zinc depletion or reduced
bioavailability, and based on in vitro chelate formation, may also involve dysregulation of Cu2+
homeostasis
On the complementarity of wave, tidal, wind and solar resources in Ireland
No full textThis paper presents a complementarity assessment of the four renewable resources, i.e. wave, tidal, wind
and solar, around the Island of Ireland (including Northern
Ireland). A particular focus is given to the potential benefits
of combining relatively unexploited but significant marine
renewable energy resources (wave and tidal) in Ireland,
with more established renewable technologies, such as
wind and solar. New complementarity metrics, based on
the mathematical principle of total variations, variance and
standard deviation, are utilised here, since they can be used
to assess the complementarity of more than two resources.
The results show clear benefits of diversifying the resource
mix with the highest complementarity achieved for combining all four resources
Characterisation of structure-to-function relationships in free and protein-linked glycans by computer simulation techniques.
No full textComplex carbohydrates (glycans) are the most abundant biopolymers in Nature.
They functionalize proteins and lipids and form a thick coating on the surface of
cells, which facilitates the cell’s movement and its interaction with toxins, viruses,
and other cells. This is usually accomplished through a ”handshake” recognition
between proteins and glycans. Many proteins have their surfaces decorated with
glycans (or glycosylated). It is known that the type of glycans present can
influence the protein’s function and stability. In my extensive research, I employed
thorough molecular dynamics (MD) simulations to delve into the subtle yet crucial
modifications affecting the N-glycan architecture in various biological contexts.
I investigated modifications involving core α(1-3)-Fuc and β(1-2)-Xyl in standard
N-glycoforms found in plants and invertebrates, known to be immunogenic in
humans. MD simulations disclosed notable changes in the 3D structure and
dynamics of N-glycans, underscoring their pivotal role in selective recognition by
lectin receptors and antibodies. The detailed, atomistic-level analysis emphasised
that these functionalizations predominantly impact the local spatial vicinity of
the modified monosaccharide. Consequently, a novel approach was proposed that
employs structural 3D units or glycoblocks to predict the architecture of N-glycans.
My focus shifted to characterising human oligomannose N-glycans free and
glycosylated on the CD16a Fc γ Receptor(FcγRIIIa). Through conventional MD
simulations, I unraveled a complex architecture shaped by a network of transient
hydrogen-bonding interactions. Specific glycoforms exhibited distinct sets of
constraints, determining the accessibility for further functionalisation and shedding
light on glycoform-specific interactions in modulating antibody-dependent cellular
cytotoxicity (ADCC).
Then I investigated the impact of SARS-CoV-2 S N-glycosylation variations on
protein function. MD simulations revealed that altering the size of N-glycans at
specific sites influenced the stability of receptor binding domain (RBD) conformations,
providing insights into the structural dynamics of the virus and potential
implications for viral infectivity. Comparative analysis of ancestral sequences
suggested the contribution of changes in the topology of the glycan shield to the
increased activity of SARS-CoV-2 relative to closely related coronaviruses.
Lastly, I explore the role of C-mannosylation in Thrombospondin Type 1 Repeats
(TSR) in proteins, focussing on TSR 1 in BAI1. MD simulations highlighted
position-specific effects and the profound influence of the glycan type on stability.
The transition between glycan types, including α-mannose, α-rhamnose,
α-quinovose, and β-mannose, unveiled nuanced impacts on folding energy and
structural dynamics, offering valuable insights for therapeutic protein engineering
and drug development.
These findings enhance our understanding of the intricate relationships between
glycan dynamics and protein function, paving the way for novel approaches in glycoscience
research and therapeutic interventions
PCP Pincer Complexes of Titanium in the +3 and +4 Oxidation States
No full textTi(IV) and Ti(III) complexes using the tBuPCP ligand
have been synthesized (tBuPCP = C6H3-2,6-(CH2Pt
Bu2)2). The
[
tBuPCP]Li synthon can be reacted with TiCl4(THF)2 to form
(tBuPCP)TiCl3 (1) in limited yields due to significant reduction of
the titanium synthon. The Ti(III) complex (tBuPCP)TiCl2 (2) has been
further characterized. This can have half an equivalent of halide
abstracted to form [{(tBuPCP)TiCl}2{μ-Cl}][B(C6F5)4] (3) and can
also be methylated, forming (tBuPCP)TiMe2 (4). All the Ti(III)
complexes have been characterized using EPR and X-ray crystallography, giving insight into their electronic structures, which are further
supported by DFT calculations
Prevalence of perceived discrimination and associations with mental health inequalities in the UK during 2019–2020: A cross-sectional study
No full textExperiencing discrimination is associated with poorer mental health and the demographic patterning of discrimination may explain social inequalities in mental health. The present research examined prevalence of perceived discrimination in the UK and associations with social inequalities in mental health. Data were taken from the UK Household Longitudinal Study (n = 32,003). Population subgroups (sex, age, ethnicity, health, religiousness, income, education, and occupation), perceived personal discrimination (personal experience) and perceived belonging to a discriminated group (identified as belonging to a group discriminated against in this country), and probable mental health problems (GHQ-12 assessed, cut off 4+) were reported on in 2019/2020. Nineteen percent of participants perceived personal discrimination in the last year, 9% perceived belonging to a discriminated group, and 22% had probable mental health problems. There were significant inequalities in both perceived discrimination and mental health. Being a younger adult, of mixed ethnicity, having health problems, having a university degree, and being unemployed increased risk of mental health problems and these associations were partially explained by perceived discrimination being more common among these groups. Perceived discrimination is common among UK adults, but prevalence differs by population subgroup. Perceived discrimination may contribute to social inequalities in mental health
Staidr: Bridging Online, Offline, and Hybrid Learning Through Collaborative Methodologies.
No full textStaidr was developed as a tool to enable students to collaborate effectively
in online, offline and hybrid environments. The project has been developed
over the last two years, and this thesis details the journey from initial research
through the development of the platform, the resulting validation of this platform
and the underlying methodology.
Three studies were conducted throughout this project: a pilot study to fully
understand the effectiveness of the pedagogical methodology, followed by a
more accelerated study to introduce the online platform. We encapsulated our
evaluation by performing a final year-long study examining the effects of our
application on a university class throughout two semesters.
Overall, both the methodology and platform have been well received by
educators and students alike. Our feedback indicated a clear use case for such
a platform, and further developments will only improve its significance
The Role Of Disability Studies in the Advancement of EU Law Scholarship
No full textOver the past thirty years, disability has become a discrete strand of European Union (EU) law. The most significant legal developments have occurred in the past ten years, being propelled by the EU accession to the UN Convention on the Rights of Persons with Disabilities (CRPD), and enhanced by a line of case law of the Court of Justice (CJEU). In line with the advancement of an overall EU disability policy framework, the protection of the rights of persons with disabilities has been recently boosted by the enactment of new legislation, such as the Web Accessibility Directive and the European Accessibility Act. Against this background, the chapter discusses the extent to which academic contributions on EU disability law, while revolving around these key legal developments and case law, have built upon a copious and multifaceted disability studies scholarship. It argues that the rejection of the medical model of disability, the embracement of social model, and the current human rights approach to disability have supported critical appraisals of CJEU decisions and discursive reviews of the EU policy agenda. The chapter contends that disability studies have informed the whole academic debate on the concept of disability, and the discussion on the principles of equality and accessibility. Finally, the chapter posits that disability studies will enhance the transformative role played by the CRPD in the EU legal framework