Interaction of tumor necrosis factor-alpha and the renin angiotensin system in the pathogenesis of hypertension

Hypertension is a major predisposing factor for the development of cardiovascular and renal diseases. The renin-angiotensin system (RAS) plays a pivotal role in the pathogenesis of cardiovascular diseases such as hypertension, myocardial infarction, heart failure, and stroke. Angiotensin II (Ang II), the effector peptide of the RAS, activates a wide spectrum of signaling responses via the Ang II type-I receptor that mediate its physiological control of blood pressure, thirst and sodium balance. For the past two decades, increasing evidence has demonstrated that the circulatory RAS and local/tissue RAS components (heart and brain) may contribute to the development of hypertensive response. Currently, hypertension is considered a low-grade inflammatory condition induced by interaction of the RAS with various pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α). Several in vitro and in vivo studies suggest the existence of a cross-talk between Ang II and TNF-α, implying an important role for TNF-α in blood pressure regulation. However, the functional importance of TNF-α in Ang II-induced response is unclear. In this dissertation, we examined the hypothesis that TNF-α is involved in the Ang II-induced hypertensive response and explored the interaction of Ang II and TNF-α in the heart and brain in the pathogenesis of hypertension. To examine this interaction, the effects of chronic administration of Ang II was evaluated in TNF-α knockout mice to dissect out the role played by TNF-α in the Ang II-induced effects. Additionally, the role of reactive oxygen species and the transcription factor nuclear factor-kappaB (NF-κB), were examined in this interaction between Ang II and TNF-α. Furthermore, to understand the role of central control of blood pressure via the hypothalamic paraventricular nucleus, an important cardiovascular regulatory center in the brain, we studied the effect of TNF-α blockade and Angiotensin Converting Enzyme 2 overexpression within the brain on blood pressure control. Overall, these studies demonstrate a functional interaction between the RAS and TNF-α in hypertension and the possible roles of oxidative stress and NF-κB in mediating the Ang II-induced hypertensive response. These findings provide an important clue in our quest for understanding the pathophysiology of hypertension and other cardiovascular diseases

Estimation of burst pressure of pipelines with interacting corrosion clusters based on machine learning models

Acknowledgments The first author would like to thank the Ghana National Petroleum Corporation (GNPC) Foundation for funding the PhD studies at the University of Aberdeen. The first author also acknowledges the research support from Net Zero Technology Centre and University of Aberdeen through their partnership in the UK National Decommissioning Centre.Peer reviewedPublisher PD

Probabilistic finite element-based reliability of corroded pipelines with interacting corrosion cluster defects

Open Access via the Elsevier agreement The first author would like to thank the Ghana National Petroleum Corporation (GNPC) Foundation for funding the PhD studies at the University of Aberdeen, United Kingdom. The first author also acknowledges the research support from Net Zero Technology Centre and University of Aberdeen through their partnership in the UK National Decommissioning CentrePeer reviewedPublisher PD

Unavailability assessment of redundant safety instrumented systems subject to process demand

Sriramula’s work within the Lloyd’s Register Foundation Centre for Safety and Reliability Engineering at the University of Aberdeen is supported by Lloyd’s Register Foundation. The Foundation helps to protect life and property by supporting engineering-related education, public engagement and the application of re-search.Peer reviewedPostprin

Impact of common cause failure on reliability performance of redundant safety related systems subject to process demand

Acknowledgments The authors would like to thank the anonymous reviewers for their constructive comments and feedback.Peer reviewedPostprin

Efficient response modelling for performance characterisation and risk assessment of ship-iceberg collisions

The authors are grateful for the support provided through the Lloyd’s Register Foundation Centre. The Foundation helps to protect life and property by supporting engineering-related education, public engagement and the application of research.Peer reviewedPostprin

Uncertainty modeling in reliability analysis of floating wind turbine support structures

Acknowledgments: The first author would like to thank the Petroleum Technology Development Fund (PTDF), Nigeria for the funding of this PhD research.Peer reviewedPostprin

Stochastic load effect characterization of floating wind turbine support structures

The first author would like to thank the Petroleum Technology Development Fund (PTDF), Nigeria for their sponsorship.Peer reviewedPublisher PD

Reliability modelling of redundant safety systems without automatic diagnostics incorporating common cause failures and process demand

Sriramula’s work within the Lloyd’s Register Foundation Centre for Safety and Reliability Engineering at the University of Aberdeen is supported by Lloyd’s Register Foundation. The Foundation helps to protect life and property by supporting engineering-related education, public engagement and the application of re-search.Peer reviewedPostprin

Calibration of safety factors for offshore wind turbine support structures using fully coupled simulations

Peer reviewedPostprin