Numerical investigation of deformation and failure mechanisms of osteopontin-hydroxyapatite interfaces and mineralized collagen fibril arrays

This thesis is a comprehensive study of deformation and failure mechanisms in bone at nano- and micro-scale levels. It explores the mechanical behaviour of osteopontin-hydroxyapatite interfaces and mineralized collagen fibril arrays, through atomistic molecular dynamics and finite element simulations. This thesis shows some main factors contributing to the excellent material properties of bone and provides some guidelines for development of new artificial biological materials and medical implants.

Nonprofit Service Delivery for Government : Accountability Relationships and Mechanisms

When government purchases social services under contract from a nonprofit organisation, a clear accountability relationship is created. The NPO must give an account for the use of the funds and achievement of outcomes to the funder. This paper explores how accountability is enacted in two different types of funding relationships in Queensland. Support is found for the argument that different relationships have different approaches to accountability.

Stress at the synapse : signal transduction mechanisms of adrenal steroids at neuronal membranes

As the key neuron-to-neuron interface, the synapse is involved in learning and memory, including traumatic memories during times of stress. However, the signal transduction mechanisms by which stress mediates its lasting effects on synapse transmission and on memory are not fully understood. A key component of the stress response is the increased secretion of adrenal steroids. Adrenal steroids (e.g., cortisol) bind to genomic mineralocorticoid and glucocorticoid receptors (gMRs and gGRs) in the cytosol. In addition, they may act through membrane receptors (mMRs and mGRs), and signal transduction through these receptors may allow for rapid modulation of synaptic transmission as well as modulation of membrane ion currents. mMRs increase synaptic and neuronal excitability; mechanisms include the facilitation of glutamate release through extracellular signal-regulated kinase signal transduction. In contrast, mGRs decrease synaptic and neuronal excitability by reducing calcium currents through N-methyl-D-aspartate receptors and voltage-gated calcium channels by way of protein kinase A- and G protein-dependent mechanisms. This body of functional data complements anatomical evidence localizing GRs to the postsynaptic membrane. Finally, accumulating data also suggest the possibility that mMRs and mGRs may show an inverted U-shaped dose response, whereby glutamatergic synaptic transmission is increased by low doses of corticosterone acting at mMRs and decreased by higher doses acting at mGRs. Thus, synaptic transmission is regulated by mMRs and mGRs, and part of the stress signaling response is a direct and bidirectional modulation of the synapse itself by adrenal steroids.

Perturbed Lignification Impacts Tree Growth in Hybrid Poplar-A Function of Sink Strength, Vascular Integrity, and Photosynthetic Assimilation

The effects of reductions in cell wall lignin content, manifested by RNA interference suppression of coumaroyl 3'-hydroxylase, on plant growth, water transport, gas exchange, and photosynthesis were evaluated in hybrid poplar trees (Populus alba 3 grandidentata). The growth characteristics of the reduced lignin trees were significantly impaired, resulting in smaller stems and reduced root biomass when compared to wild-type trees, as well as altered leaf morphology and architecture. The severe inhibition of cell wall lignification produced trees with a collapsed xylem phenotype, resulting in compromised vascular integrity, and displayed reduced hydraulic conductivity and a greater susceptibility to wall failure and cavitation. In the reduced lignin trees, photosynthetic carbon assimilation and stomatal conductance were also greatly reduced, however, shoot xylem pressure potential and carbon isotope discrimination were higher and water-use efficiency was lower, inconsistent with water stress. Reductions in assimilation rate could not be ascribed to increased stomatal limitation. Starch and soluble sugars analysis of leaves revealed that photosynthate was accumulating to high levels, suggesting that the trees with substantially reduced cell wall lignin were not carbon limited and that reductions in sink strength were, instead, limiting photosynthesis.

Cytokine expression and secretion by skeletal muscle cells : regulatory mechanisms and exercise effects

Cytokines are important mediators of various aspects of health and disease, including appetite, glucose and lipid metabolism, insulin sensitivity, skeletal muscle hypertrophy and atrophy. Over the past decade or so, considerable attention has focused on the potential for regular exercise to counteract a range of disease states by modulating cytokine production. Exercise stimulates moderate to large increases in the circulating concentrations of interleukin (IL)-6, IL-8, IL-10, IL-1 receptor antagonist, granulocyte-colony stimulating factor, and smaller increases in tumor necrosis factor-α, monocyte chemotactic protein-1, IL-1β, brain-derived neurotrophic factor, IL-12p35/p40 and IL-15. Although many of these cytokines are also expressed in skeletal muscle, not all are released from skeletal muscle into the circulation during exercise. Conversely, some cytokines that are present in the circulation are not expressed in skeletal muscle after exercise. The reasons for these discrepant cytokine responses to exercise are unclear. In this review, we address these uncertainties by summarizing the capacity of skeletal muscle cells to produce cytokines, analyzing other potential cellular sources of circulating cytokines during exercise, and discussing the soluble factors and intracellular signaling pathways that regulate cytokine synthesis (e.g., RNA-binding proteins, microRNAs, suppressor of cytokine signaling proteins, soluble receptors).

Is climate change litigation an effective strategy for promoting greater action to address climate change? What other legal mechanisms might be appropriate?

In recent times a widespread consensus on the reality and gravity of anthropogenic climate change has emerged. Perceived inadequacies in the Australian government’s legal and policy responses to climate change issues have resulted in environmental activists increasingly turning to the courts as a strategy to promote greater action to address adverse climate impacts. The efficacy of this strategy for achieving climate goals is limited by the time and expense of litigating, the restrictions inherent in environmental law administrative challenges, and the possibility that judicial decisions may be overruled by the legislature. To date, climate change litigation in Australia has met with varied success, yet its significance extends beyond the court room as an important mechanism for raising public, political and commercial awareness about climate change issues. Ultimately, however, the types of far-reaching changes needed to mitigate and manage adverse climate impacts require strong regulatory backing. The most effective approach to addressing the complex challenges posed by climate change is a coordinated suite of regulatory measures spearheaded by the Federal Government.

Computational micromodel for epigenetic mechanisms

Characterization of the epigenetic profile of humans since the initial breakthrough on the human genome project has strongly established the key role of histone modifications and DNA methylation. These dynamic elements interact to determine the normal level of expression or methylation status of the constituent genes in the genome. Recently, considerable evidence has been put forward to demonstrate that environmental stress implicitly alters epigenetic patterns causing imbalance that can lead to cancer initiation. This chain of consequences has motivated attempts to computationally model the influence of histone modification and DNA methylation in gene expression and investigate their intrinsic interdependency. In this paper, we explore the relation between DNA methylation and transcription and characterize in detail the histone modifications for specific DNA methylation levels using a stochastic approach.

Multi-layered model of individual HIV infection progression and mechanisms of phenotypical expression

Cite as: Perrin, Dimitri (2008) Multi-layered model of individual HIV infection progression and mechanisms of phenotypical expression. PhD thesis, Dublin City University.

Impact of mobility constraints on epidemic broadcast mechanisms in delay-tolerant networks

In this paper, we investigate the effect of mobility constraints on epidemic broadcast mechanisms in DTNs (Delay-Tolerant Networks). Major factors affecting epidemic broadcast performances are its forwarding algorithm and node mobility. The impact of forwarding algorithm and node mobility on epidemic broadcast mechanisms has been actively studied in the literature, but those studies generally use unconstrained mobility models. The objective of this paper is therefore to quantitatively investigate the effect of mobility constraints on epidemic broadcast mechanisms. We evaluate the performances of three classes of epidemic broadcast mechanisms - P-BCAST (PUSH-based BroadCast), SA-BCAST (Self-Adaptive BroadCast), and HP-BCAST (History-based P-BCAST) - with a random waypoint mobility model with mobility constraints. Our finding includes that the existence of mobility constraints significantly improves the reach ability and dissemination speed of epidemic broadcast mechanisms while degrading their efficiency.

Building cross-scale models of epigenetic mechanisms

Epigenetic changes correspond to heritable modifications of the chromosome structure, which do not involve alteration of the DNA sequence but do affect gene expression. These mechanisms play an important role in normal cell differentiation, but aberration is associated also with several diseases, including cancer and neural disorders. In consequence, despite intensive studies in recent years, the contribution of modifications remains largely unquantified due to overall system complexity and insufficient data. Computational models can provide powerful auxiliary tools to experimentation, not least as scales from the sub-cellular through cell populations (or to networks of genes) can be spanned. In this paper, the challenges to development, of realistic cross-scale models, are discussed and illustrated with respect to current work.

The protective mechanisms of first aid training within a school-based program for early adolescents

This thesis was concerned with the protective mechanisms of first aid training in the context of peer support. Using a randomised control trial design the current program of research explores first aid training in the school setting and identifies the key components of effective school-based first aid training programs. In particular, examining whether first aid training and associated knowledge could be protective for early adolescents. This broader framing considered whether first aid impacted on increasing behaviour and attitudes towards helping an injured friend, and reducing personal risk taking and related injury.

Legal mechanisms for maximising community engagement with formal evacuation messaging: How well are these understood?

Study/Objective This program of research examines the effectiveness of legal mechanisms as motivators to maximise engagement and compliance with evacuation messages. This study is based on the understanding that the presence of legislative requirements, as well as sanctions and incentives encapsulated in law, can have a positive impact in achieving compliance. Our objective is to examine whether the current Australian legal frameworks, which incorporate evacuation during disasters, are an effective structure that is properly understood by those who enforce and those who are required to comply. Background In Australia, most jurisdictions have enacted legislation that encapsulates the power to evacuate and the ability to enforce compliance, either by the use of force or imposition of penalty. However, citizens still choose to not evacuate. Methods This program of research incorporates theoretical and doctrinal methodologies for reviewing literature and legislation in the Australia context. The aim of the research is to determine whether further clarity is required to create an understanding of the powers to evacuate, as well as greater public awareness of these powers. Results & Conclusion Legislators suggest that powers of evacuation can be ineffective if they are impractical to enforce. In Australia, there may also be confusion about from which legislative instrument the power to evacuate derives, and therefore whether there is a corresponding ability to enforce compliance through the use of force or imposition of a penalty. Equally, communities may lack awareness and understanding of the powers of agencies to enforce compliance. We seek to investigate whether this is the case, and whether even if greater awareness existed, it would act as an incentive to comply.