NUI Maynooth Eprint Archive
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Nonparametric multivariate survival analysis of activated lymphocyte cell fates.
No full textUpon challenge, lymphocytes multiply and diversify to combat the infection,
however, the mechanisms that drive this process are not well understood. A
theoretical model has been proposed to explain how a diverse selection of
cell fates is achieved, the Cyton model [Hawkins et al, 2007, PNAS]. In that
model the censorship caused by competing drives for lymphocytes to undergo
certain fates results in complex correlations and impacts the observed
distribution of times to cellular events. In [Duffy et al, 2012, Science] the
competition hypothesis is tested for consistency with data collected using
a novel experimental procedure. Through the implementation and development
of a collection of multivariate nonparametric statistical techniques, we
create a set of tools that can aid the study of competition hypotheses in
biological systems. As a worked example these tools are used to study data
collected for the experiments in [Duffy et al, 2012, Science] to challenge some
of the underlying assumptions of their parametric analysis. As an additional
illustration further unpublished data collected during the experiments is used
to study the time at which B cells divide, die and differentiate when they
have already undergone class switching, allowing us to address the question
of a cell type dependent change
IPCC, 2023: Climate Change 2023: Synthesis Report, Summary for Policymakers. Contribution of Working Groups I, II and III to the Sixth Assessment Report of the Intergovernmental Panel on Climate Change [Core Writing Team, H. Lee and J. Romero (eds.)]. IPCC, Geneva, Switzerland.
No full textThis Synthesis Report (SYR) of the IPCC Sixth Assessment Report (AR6) summarises the state of knowledge of climate change,
its widespread impacts and risks, and climate change mitigation and adaptation. It integrates the main findings of the Sixth
Assessment Report (AR6) based on contributions from the three Working Groups1
, and the three Special Reports. The summary for Policymakers (SPM) is structured in three parts: SPM.A Current Status and Trends, SPM.B Future Climate Change, Risks, and
Long-Term Responses, and SPM.C Responses in the Near Term.This report recognizes the interdependence of climate, ecosystems and biodiversity, and human societies; the value of diverse forms of knowledge; and the close linkages between climate change adaptation, mitigation, ecosystem health, human well-being
and sustainable development, and reflects the increasing diversity of actors involved in climate action.
Based on scientific understanding, key findings can be formulated as statements of fact or associated with an assessed level of
confidence using the IPCC calibrated language
Optimising industry learners’ online experiences – lessons for a post-pandemic world
No full textThis study examines the experiences and impact COVID-19 has had on industry online learners. Exploring initially the term ‘industry learner' and explaining the background to the design of the online modules the learners participated on. The design and delivery of this programme resulted in minimal impacts from the COVID-19 pandemic. The study explores qualitative reports of industry learners’ experiences, and these are analysed using thematic analysis. The findings suggest that the design principle of maximising social interaction, at peer to peer and peer to educator levels, resulted in an enhanced student experience. Group based interactions were recognised by learners as both an occasional source of friction, but also as a valuable proxy for industry leadership roles and workplace group dynamics. This highlights the complex enhancing and inhibiting nature of group-based learning. Implications for further optimisation of online and blended learning environments are explored and associated future research priorities are identified
MIF Licensing Enhances Mesenchymal Stromal Cell Efficacy in Allergic Asthma
No full textHuman mesenchymal stromal cells (MSCs) rely on specific inflammatory disease
microenvironments in order to carry out their anti-inflammatory actions in vivo. One
of the barriers to the success of MSC therapy is the inability to identify potential
responders. Macrophage migration inhibitory factor (MIF) has been identified to play
a pivotal role in the pathogenesis of several inflammatory disorders including asthma.
The aim of this thesis was to develop an understanding into the interaction between
MIF and MSCs in a house dust mite (HDM) model of allergic asthma. Using
humanised mice with either high- or low-expressing MIF promoter polymorphisms,
we identified a dominant role of MIF allelic variants with the high expressing CATT7
mice exhibiting a more severe asthma phenotype. The CATT7 mice experienced
significantly higher levels of eosinophilia, airway remodelling, and airway
hyperresponsiveness. In vitro studies revealed the ability of high levels of hMIF to
improve MSC migration, expansion and immunomodulation, thus, identifying MIF as
a potential agent to enhance MSC therapeutic efficacy. High hMIF environments in
vivo potentiated MSCs therapeutic effects with MSCs able to significantly attenuate
airway inflammation and ameliorate airway remodelling in CATT7 mice compared to
CATT5 or wildtype. Furthermore, we demonstrated that licensing MSCs with high
levels of hMIF prior to administration can further enhance therapeutic efficacy
through the upregulation of COX-2 expression. The data presented herein contributes
to a broader understanding on how disease microenvironments can affect MSC
therapeutic efficacy and identifies MIF as a potential biomarker for MSC success
Towards data-driven and data-based control of wave energy systems: Classification, overview, and critical assessment
No full textCurrently, a significant effort in the world research panorama is focused on finding efficient solutions to a
carbon-free energy supply, wave energy being one of the most promising sources of untapped renewable
energy. However, wave energy is not currently economic, though control technology has been shown
to significantly increase the energy capture capabilities. Usually, the synthesis of a wave energy control
strategy requires the adoption of control-oriented models, which are prone to error, particularly arising from
unmodelled hydrodynamics, given the complexity of the hydrodynamic interactions between the device and
the ocean. In this context, data-driven and data-based control strategies provide a potential solution to some
of these issues, using real-time data to gather information about the system dynamics and performance. Thus
motivated, this study provides a detailed analysis of different approaches to the exploitation of data in the
design of control philosophies for wave energy systems, establishing clear definitions of data-driven and databased control in this field, together with a classification highlighting the various roles of data in the control
synthesis process. In particular, we investigate intrinsic opportunities and limitations behind the use of data in
the process of control synthesis, providing a comprehensive review together with critical considerations aimed
at directly contributing towards the development of efficient data-driven and data-based control systems for
wave energy devices
Design considerations for a hybrid wind-wave platform under energy-maximising control
No full textThe environmental impact of emissions of fossil fuels and their rising prices, together with countries' commitment to mitigate the effect of the alarming and rapid climate changes, have been a crucial thrust to investigate new solutions to have an energy supply depending on renewable energies. In this scenario, offshore wind-wave hybrid platforms have been recently promoted: sharing facilities, infrastructure, and grid connections, give 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 movement 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 requirement for the wind turbine. The aim of this study is to investigate the effects of design changes on the dynamics of the hybrid wind-wave platform under energy-maximising control, which can be analysed in terms of the principle of impedance-matching. A semi-submersible platform with an incorporated flap-type WEC will be analysed both from a closed-loop and open-loop perspective, and the control system will be designed to maximise the energy produced by the WEC. Design changes on the wind-wave conversion platform will be in terms of flap dimensions, starting from a nominal geometry based on the so-called Oyster system. Analyses will be conducted by both increasing and decreasing the flap depth from the nominal case, to investigate the effect of the different geometries on the interactions between the WEC and the platform. A frequency-domain analysis of the overall input/output (velocity) system will be presented, highlighting the situations that can enhance the potential of both devices and exploit their synergies
The aggregate gains of eliminating gender and ethnic gaps in the Malaysian labor market
No full textWe use microdata to calculate the gains of eliminating gender and ethnic labor market gaps in Malaysia for the period 2010–2017. We document significant gaps in terms of participation in the labor market and entrepreneurship, distinguishing between employers and self-employed. Female-male ratios are 64% for labor market participation, 82% for self-employment, and 32% for being employers. Across different age and ethnic groups, gender gaps in labor force participation are particularly pronounced for older workers and in entrepreneurship for Chinese workers. Our results indicate substantial income gains if gender and ethnic gaps were eliminated. Eliminating the entrepreneurship gender gaps increases income per capita by 6.54% in the long run. When we also include the employment gender gap, the long-run gains are 26.18%. The elimination of ethnic gaps could in the long run result in a smaller but still sizeable increase in income per capita of 11.5%
Preservation of long-term memory in older adults using a spaced learning paradigm
No full textHow much information we retain depends on type/schedule of training. It has been widely acknowledged that spaced learning is advantageous compared to massed learning for cognitively healthy young adults and should be considered an educational standard. Literature would suggest that the spacing effect is preserved with age, though it is unclear whether this effect translates to more ecologically valid concepts such as face-name associations, which are particularly susceptible to deterioration with age. Two experiments were conducted to investigate the effects of spacing across recent/remote retention intervals, and the effect of age on spacing in cognitively healthy older adults using the Face-Name Pairs task. Experiment 1 results suggest that the beneficial memory effects of spacing are particularly observed with long-term memory. Experiment 2 results suggest that older adults are impaired at learning compared to younger adults, that the spacing effect influences both older and younger adults at longer intervals, and that spaced-trained participants display similar forgetting patterns at longer intervals, irrespective of age. These results may have some implications regarding improving the conditions under which optimum retention occurs (namely, whether spacing is beneficial when learning ecologically valid concepts at longer intervals outside of laboratory settings), and may provide insight into the effect of age on our ability to learn and remember face-name associations
Health misinformation and freedom of expression: considerations for policymakers
No full textHealth misinformation, most visibly following the COVID-19 infodemic, is an urgent threat that hinders the success of public health policies. It likely contributed, and will continue to contribute, to avoidable deaths. Policymakers around the world are being pushed to tackle this problem. Legislative acts have been rolled out or announced in many countries and at the European Union level. The goal of this paper is not to review particular legislative initiatives, or to assess the impact and efficacy of measures implemented by digital intermediaries, but to reflect on the high constitutional and ethical stakes involved in tackling health misinformation through speech regulation. Our findings suggest that solutions focused on regulating speech are likely to encounter significant constraints, as policymakers grasp with the limitations imposed by freedom of expression and ethical considerations. Solutions focused on empowering individuals – such as media literacy initiatives, fact-checking or credibility labels – are one way to avoid such hurdles
Glucagon‐like peptide‐1 therapy in people with obesity restores natural killer cell metabolism and effector function
No full textPeople with obesity (PWO) have functionally defective natural killer (NK) cells, with a decreased capacity to produce cytokines and kill target cells, underpinned by defective cellular metabolism. It is plausible that the changes in peripheral NK cell activity are contributing to the multimorbidity in PWO, which includes an increased risk of cancer. This study investigated whether therapy with long‐acting glucagon‐like peptide‐1 (GLP‐1) analogues, which are an effective treatment for obesity, could restore NK cell functionality in PWO.
Methods
In a cohort of 20 PWO, this study investigated whether 6 months of once weekly GLP‐1 therapy (semaglutide) could restore human NK cell function and metabolism using multicolor flow cytometry, enzyme‐linked immunosorbent assays, and cytotoxicity assays.
Results
These data demonstrate that PWO who received GLP‐1 therapy have improved NK cell function, as measured by cytotoxicity and interferon‐γ/granzyme B production. In addition, the study demonstrates increases in a CD98‐mTOR‐glycolysis metabolic axis, which is critical for NK cell cytokine production. Finally, it shows that the reported improvements in NK cell function appear to be independent of weight loss.
Conclusions
The restoration, by GLP‐1 therapy, of NK cell functionality in PWO may be contributing to the overall benefits being seen with this class of medication