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Emerging roles of protein O-GlcNAcylation in cardiovascular diseases: Insights and novel therapeutic targets
No full textYesCardiovascular diseases (CVDs) are the leading cause of death globally. While the major focus of pharmacological and non-pharmacological interventions has been on targeting disease pathophysiology and limiting predisposing factors, our understanding of the cellular and molecular mechanisms underlying the pathogenesis of CVDs remains incomplete. One mechanism that has recently emerged is protein O-GlcNAcylation. This is a dynamic, site-specific reversible post-translational modification of serine and threonine residues on target proteins and is controlled by two enzymes: O-linked β-N-acetylglucosamine transferase (OGT) and O-linked β-N-acetylglucosaminidase (OGA). Protein O-GlcNAcylation alters the cellular functions of these target proteins which play vital roles in pathways that modulate vascular homeostasis and cardiac function. Through this review, we aim to give insights on the role of protein O-GlcNAcylation in cardiovascular diseases and identify potential therapeutic targets in this pathway for development of more effective medicines to improve patient outcomes
Laser capture microdissection on surgical tissues to identify aberrant gene expression in impaired wound healing in type 2 diabetes
No full textNoThe global prevalence Type 2 diabetes mellitus (T2DM) is escalating at a rapid rate. Patients with T2DM suffer from a multitude of complications and one of these is impaired wound healing. This can lead to the development of non-healing sores or foot ulcers and ultimately to amputation. In healthy individuals, wound healing follows a controlled and overlapping sequence of events encompassing inflammation, proliferation, and remodelling. In T2DM, one or more of these steps becomes dysfunctional. Current models to study impaired wound healing in T2DM include in vitro scratch wound assays, skin equivalents, or animal models to examine molecular mechanisms underpinning wound healing and/or potential therapeutic options. However, these do not fully recapitulate the complex wound healing process in T2DM patients, and ex vivo human skin tests are problematic due to the ethics of taking punch biopsies from patients where it is known they will heal poorly. Here, a technique is described whereby expression profiles of the specific cells involved in the (dys)functional wound healing response in T2DM patients can be examined using surplus tissue discarded following amputation or elective cosmetic surgery. In this protocol samples of donated skin are collected, wounded, cultured ex vivo in the air liquid interface, fixed at different time points and sectioned. Specific cell types involved in wound healing (e.g., epidermal keratinocytes, dermal fibroblasts (papillary and reticular), the vasculature) are isolated using laser capture microdissection and differences in gene expression analyzed by sequencing or microarray, with genes of interest further validated by qPCR. This protocol can be used to identify inherent differences in gene expression between both poorly healing and intact skin, in patients with or without diabetes, using tissue ordinarily discarded following surgery. It will yield greater understanding of the molecular mechanisms contributing to T2DM chronic wounds and lower limb loss.European Commission 7th Framework Programme for Research and Technical Development - Marie Curie Innovative Training Networks (ITN), Grant agreement no 607886. Aveda, Hair Innovation & Technology, US
Two-Stage Stochastic Model to Invest in Distributed Generation Considering the Long-Term Uncertainties
No full textYesThis paper used different risk management indicators applied to the investment optimization performed by consumers in Distributed Generation (DG). The objective function is the total cost incurred by the consumer including the energy and capacity payments, the savings, and the revenues from the installation of DG, alongside the operation and maintenance (O&M) and investment costs. Probability density function (PDF) was used to model the price volatility in the long-term. The mathematical model uses a two-stage stochastic approach: investment and operational stages. The investment decisions are included in the first stage and which do not change with the scenarios of the uncertainty. The operation variables are in the second stage and, therefore, take different values with every realization. Three risk indicators were used to assess the uncertainty risk: Value-at-Risk (VaR), Conditional Value-at-Risk (CVaR), and Expected Value (EV). The results showed the importance of migration from deterministic models to stochastic ones and, most importantly, the understanding of the ramifications of every risk indicator
Use of gene-expression programming to estimate Manning's roughness coefficient for a low flow stream
No full textYesManning's roughness coefficient (n) has been widely used to estimate flood discharges and flow depths in natural channels. Therefore, although extensive guidelines are available, the selection of the appropriate n value is of great importance to hydraulic engineers and hydrologists. Generally, the largest source of error in post-flood estimates is caused by the estimation of n values, particularly when there has been minimal field verification of flow resistance. This emphasizes the need to improve methods for evaluating the roughness coefficients. Trinidad and Tobago currently does not have any set method or standardised procedure that they use to determine the n value. Therefore, the objective of this study was to develop a soft computing model in the calculation of the roughness coefficient values using low flow discharge measurements for a stream. This study presents Gene-Expression Programming (GEP), as an improved approach to compute Manning's Roughness Coefficient. The GEP model was found to be accurate, producing a coefficient of determination (R2) of 0.94 and Root Mean Square Error (RSME) of 0.0024
Scale model experiment on local scour around submarine pipelines under bidirectional tidal currents
No full textYesIn nearshore regions, bidirectional tidal flow is the main hydrodynamic factor, which induces local scour around submarine pipelines. So far, most studies on scour around submarine pipelines only consider the action of unidirectional, steady currents and little attention has been paid to the situation of bidirectional tidal currents. To deeply understand scour characteristics and produce a more accurate prediction method in bidirectional tidal currents for engineering application, a series of laboratory scale experiments were conducted in a bidirectional current flume. The experiments were carried out at a length scale of 1:20 and the tidal currents were scaled with field measurements from Cezhen pipeline in Hangzhou Bay, China. The experimental results showed that under bidirectional tidal currents, the scour depth increased significantly during the first half of the tidal cycle and it only increased slightly when the flow of the tidal velocity was near maximum flood or ebb in the following tidal cycle. Compared with scour under a unidirectional steady current, the scour profile under a bidirectional tidal current was more symmetrical, and the scour depth in a bidirectional tidal current was on average 80% of that under a unidirectional, steady current based on maximum peak velocity. Based on previous research and the present experimental data, a more accurate fitted equation to predict the tidally induced live-bed scour depth around submarine pipelines was proposed and has been verified using field data from the Cezhen pipeline
Experimental investigations on the structural behaviour of reinforced geopolymer beams produced from recycled construction materials
Get PDFYesConcrete requires a vast amount of aggregate and cement production. Although there are some efforts in the literature to reduce the amount of Portland cement in the concrete mixture to lessen the greenhouse gas release, a limited number of studies were conducted to investigate the possibility of using this geopolymer mixtures to serve as a structural component. Therefore, this study firstly aimed to produce geopolymer concrete from construction and demolition waste-based precursors, including masonry units (red clay brick, roof tile, hollow brick, etc.) and glass. In addition, recycled aggregates produced from the concrete waste portion of the CDW were used to obtain 100% recycled construction material on the scale of the binder and aggregate phase. Then, this study investigated the possible use of this proposed geopolymer concrete to produce structural components that perform similar to conventional concrete. Therefore, the structural properties of reinforced geopolymer concrete beams produced from the recycled construction demolition wastes were evaluated in this study by conducting laboratory experiments. To this end, bending tests were performed on reinforced conventional concrete beam specimens and reinforced geopolymer concrete beam specimens. The test observations clearly showed that construction demolition waste could be recycled to produce new constructional components, considering its advantage of promoted sustainability.The authors gratefully acknowledge the European Union's Horizon 2020 Research and Innovation Programme's financial assistance under Grant Agreement No: 869336 and Acronym: ICEBERG and the financial assistance of the Scientific and Technical Research Council (TUBITAK) of Turkey and the British Council under Grant no:218M102. This work was also supported by Newton Prize 2020
Three Essays on the Role of Corporate Governance in Firms' Spending on R&D and Controlling Earnings-Management Practices: The Role of Independent Directors’ Tenure and Network in Controlling Earnings-Management Practices; The Impact of Board Diversity on the Corporate Propensity to R&D Spending; The Association between Directors’ Multiple-Board Sittings, Tenure, Financial Expertise, and R&D Spending
Get PDFThis thesis comprises three research essays. The study documents empirical
evidence around the research themes by analysing a sample of the UK’s listed non-financial firms from 2005 to 2018. It applied panel data analysis (fixed or random effects) techniques and the potential endogeneity issue is controlled by using the two-step system, GMM. Earnings-management research holds that manipulating a firm's real activities is more damaging to its long-term growth and value than accruals manipulation. Therefore, by building on agency theory and emphasising board
monitoring, first essay investigates the role of independent directors’ tenure and
connection to several boards in controlling real earnings management (REM). This study finds that independent directors elected to board before appointment of current
CEO are negatively associated with the level of REM. Furthermore, this research
provides evidence that REM is higher in those firms whose INDs are connected to
several boards at a time. Though economically insignificant in most of the models,
this research also shows that the association between INDs’ tenure and REM varies
with the phases of their tenure. Directors in the early stage of their tenure are
observed as being less effective in controlling REM. However, as INDs’ tenure
grows, they employ better oversight over management's conduct, thereby reducing
REM. Contrary to this, the extended tenure of INDs is associated with higher REM.
These results collectively suggest that the board monitoring role protects the stakes
of shareholders/stakeholders by constraining REM; when INDs are free from the
influence of CEO, they are not over-committed due to their presence on several
boards, and they have moderate board tenure which is neither too short nor too long.
Furthermore, drawing on collective contributions and group performance
perspectives, second essay explores the role of board diversity in the firm’s R&D
investment decisions. Additionally, building on a fault-line argument about a team's
demographic attributes, the current research decomposes the impact of
demographic and cognitive diversity on R&D spending. The research observes a
positive relationship between board diversity and the level of R&D spending.
Moreover, this research documents that cognitive diversity is positively associated
with R&D investment. However, demographic diversity has an insignificant
relationship with firms’ spending on R&D projects. Further, this study confirms that
demographic diversity negatively moderates the relationship between cognitive
diversity and R&D investment. These results suggest that the board's attributes as
a group carry the significance to influence the decisions having strategic importance.
The findings on the sub-dimensions of board diversity imply that board
functional/cognitive diversity is more relevant to corporate decisions and outcomes
than is demographic diversity.
Based on the monitoring perspective (agency theory) and resource provision view
(resource dependency theory), third essay investigates the role of independent directors’ specific attributes in the corporate propensity to R&D investment. The
study documents a positive association between INDs’ moderate (median) tenure
and the firm’s spending on R&D projects, but early and extended tenure is observed
as being insignificant. INDs with a presence on three or fewer boards are observed
to promote R&D investment. However, INDs sitting on more than three boards
negatively affect the firm’s propensity to invest in R&D initiatives. Financially expert
INDs are negatively associated with corporate R&D investments, suggesting that
such directors may resist funding these projects beyond optimal risk level because
of their expertise. These results suggest that INDs’ monitoring and advising
competence improves as they spend time on the firm’s board, but that extended
tenure is counterproductive as it impairs INDs’ impartiality. Furthermore, INDs’
capital (resources) accruing from connection to multiple boards is only beneficial for
the firm’s strategic decisions if their monitoring role is not compromised because of
their over-commitment (busyness).Mirpur University of Science and Technology (MUST
Teacher Perceptions of Fundamental Movement Skills and their Assessment in Primary Schools
Get PDFYesEvidence suggests that children struggle to acquire age-appropriate fundamental movement skills (FMS), despite their importance for facilitating physical activity. This has led to calls for routine school-based screening of children’s FMS. However, there is limited research exploring schools’ capacity to conduct such assessments. This study investigated what factors might affect the adoption and implementation of FMS assessments in primary schools. School staff (n=853) completed an online questionnaire developed using the Capability, Opportunity, Motivation and Behaviour (COM-B) model. A majority reported that knowledge of pupils’ FMS ability would be beneficial (65.3%), and 71.8% would assess FMS if support was provided. Barriers included: Capability – few possessed knowledge of FMS (15%); Opportunity – teachers reported 30-60 minutes as acceptable for assessing a class, a substantially shorter period than current assessments require; Motivation – 57.2% stated FMS assessments would increase workload stress. Solutions to these issues are discussed using the COM-B theoretical framework
Analysis of Challenges for Blockchain Adoption within the Indian Public Sector: An Interpretive Structural Modelling Approach
Get PDFYesPurpose – Blockchain is one of the most significant emerging technologies that is set to
transform many aspects of industry and society. However, it has several major technical, social,
legal, environmental and ethical complexities that offer significant challenges for mainstream
use within the public sector. The Covid-19 pandemic has compelled many public sector
employees to work remotely, highlighting a number of challenges to blockchain adoption
within the Indian context signifying the pertinence of this research topic in the post-pandemic
era. This study offers insight to researchers and policymakers alike on how such challenges are
interdependent within this important subject.
Design/methodology/approach – We explored 16 unique sets of challenges selected from the
literature and gathered data from nine experts from government settings, healthcare and
education sectors and academia who have significant knowledge and experience of blockchain
implementation and use in their respective organisations. The implementation of Interpretive
Structural Modelling (ISM) and MICMAC provided a precise set of driving, linkage and
dependent challenges that were used to formulate the framework.
Findings – The developed ISM framework is split into six different levels. The results suggest
that the bottom level consists of challenges such as ‘Lack of standards (C9)’ and ‘Lack of
validation (C10)’ form the foundation of the hierarchical structure of blockchain adoption.
However, the topmost level consists of a highly dependent challenge termed ‘adoption of
blockchain in the public sector (C16)’. The research filters the selected set of five challenges
to develop a parsimonious model and formulated six propositions to examine the impact of
‘lack of standard (C9)’, ‘lack of validation (C10)’ on ‘security issues (C3)’ and ‘privacy
concerns (C2)’, which eventually determine individuals’ ‘reluctance to use blockchain
technology (C12)’.
Originality/Value – This research fills a key gap in exiting research by exploring the key
challenges in blockchain adoption within the public sector by developing a valuable framework
to model this important topic. To the best of our knowledge, this is the first paper to address
these challenges and develop a parsimonious model for challenges of blockchain adoption in
the public sector settings
The role of subjective social status in living well for carers of people with dementia: findings from the Improving the experience of Dementia and Enhancing Active Life (IDEAL) programme
Get PDFYesWe investigated how carers of people with dementia evaluate their standing in their community and wider society, and if this is related to ‘living well’. We used baseline data from the Improving the experience of Dementia and Enhancing Active Life programme and found that carers rated their standing in society higher than in their local community. Higher evaluations of both were associated with enhanced life satisfaction, well-being and quality of life. Initiatives that increase support or engagement in the community or wider society may help to increase carers’ perceptions of their social status, enhancing their ability to ‘live well’.The IDEAL study was funded jointly by the Economic and Social Research Council (ESRC) and the National Institute for Health Research (NIHR) through grant ES/L001853/2. The ESRC is part of UK Research and Innovation (UKRI). ‘Improving the experience of Dementia and Enhancing Active Life: a longitudinal perspective on living well with dementia. The IDEAL-2 study’ was funded by the Alzheimer’s Society, grant number 348, AS-PR2-16-001