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On short timescales, the brain represents, transmits, and processes information through the electrical activity of its neurons. On long timescales, the brain stores information in the strength of the synaptic connections between its neurons. This thesis examines the surprising implications of two separate, well documented microscopic processes — the stochastic gating of ion channels and the plasticity of dendritic spines — for neural information processing and storage. Electrical activity in neurons is mediated by many small membrane proteins called ion channels. Although single ion channels are known to open and close stochastically, the macroscopic behaviour of populations of ion channels are often approximated as deterministic. This is based on the assumption that the intrinsic noise introduced by stochastic ion channel gating is so weak as to be negligible. In this study we take advantage of newly developed efficient computer simulation methods to examine cases where this assumption breaks down. We find that ion channel noise can mediate spontaneous action potential firing in small nerve fibres, and explore its possible implications for neuropathic pain disorders of peripheral nerves. We then characterise the magnitude of ion channel noise for single neurons in the central nervous system, and demonstrate through simulation that channel noise is sufficient to corrupt synaptic integration, spike timing and spike reliability in dendritic neurons. The second topic concerns neural information storage. Learning and memory in the brain has long been believed to be mediated by changes in the strengths of synaptic connections between neurons — a phenomenon termed synaptic plasticity. Most excitatory synapses in the brain are hosted on small membrane structures called dendritic spines, and plasticity of these synapses is dependent on calcium concentration changes within the dendritic spine. In the last decade, it has become clear that spines are highly dynamic structures that appear and disappear, and can shrink and enlarge on rapid timescales. It is also clear that this spine structural plasticity is intimately linked to synaptic plasticity. Small spines host weak synapses, and large spines host strong synapses. Because spine size is one factor which determines synaptic calcium concentration, it is likely that spine structural plasticity influences the rules of synaptic plasticity. We theoretically study the consequences of this observation, and find that different spine-size to synaptic-strength relationships can lead to qualitative differences in long-term synaptic strength dynamics and information storage. This novel theory unifies much existing disparate data, including the unimodal distribution of synaptic strength, the saturation of synaptic plasticity, and the stability of strong synapses.

Student Number : 0413336G - MSc(Eng)dissertation - School of Chemical and Metallurgical Engineering - Faculty of Engineering and the Built Environment / This dissertation reports systematic work aimed at determining the plastic deformation mechanisms that led to strains at fracture as high as 4.7% in WC-Co alloys at 1000°C when subjected to 3-point bending tests. The three grades investigated have a Co content of 15wt% and WC grain sizes of 1.3, 0.35 and 0.3 μ m respectively and were received after they were tested in bending. Fractography, macrostructural and microstructural investigations were carried out in attempts to identify the mechanisms leading to the large strains. Techniques used included light microscopy, scanning electron microscopy (SEM), field emission scanning electron microscopy (FESEM), energy dispersive spectroscopy (EDS) and quantitative image analysis. Through comparisons of the results from the three grades at various temperatures, it was possible to establish that the large strain at 1000°C are mainly due to cracking and cobalt drift. During the fractographic investigations it was found that the grades which contained VC as a grain refiner exhibited steps on the WC grains and that fracture propagated preferentially along the stepped WC grain boundaries.

Learning and memory storage is believed to occur at the synaptic connections between neurons. During the last decades it has become clear that synapses are plastic at short and long time scales. Furthermore, experiments have shown that short and long-term synaptic plasticity interact. It remains unclear, however, how is this interaction implemented and how does it impact information processing and learning in cortical networks. In this thesis I present results on the mechanisms and function of this interaction. On the mechanistic level this form of plasticity is known to rely on a presynaptic coincidence mechanism, which requires the activation of presynaptic NMDA receptors (preNMDARs). In a collaborative effort I used mathematical modeling combined with experiments to show that preNMDARs reroute information flow in local circuits during high-frequency firing, by specifically impacting frequency-dependent disynaptic inhibition mediated by Martinotti cells. In order to accurately characterize how do preNMDARs regulate the release machinery, I developed a probabilistic inference framework that provides a distribution over the relevant parameter space, rather than simple point estimates. This approach allowed me to propose better experimental protocols for short-term plasticity inference and to reveal connection-specific synaptic dynamics in the layer-5 canonical microcircuit. This framework was then extended to infer short-term plasticity from preNMDAR pharmacological blockade data. The results show that preNMDARs up-regulate the baseline release probability and the depression time-constant, which is consistent with experimental analysis and that their impact appears to be connection-specific. I also show that a preNMDAR phenomenological model captures the frequency-dependence activation of preNMDARs. Furthermore, preNMDARs increase the signal-to-noise ratio of synaptic responses. These results show that preNMDARs specifically up-regulate high frequency synaptic information transmission. Finally, I introduce a pre- and postsynaptic unified mathematical model of spike-timing- dependent synaptic plasticity. I show that this unified model captures a wide range of short-term and long-term synaptic plasticity data. Functionally, I demonstrate that this segregation into pre- and postsynaptic factors explains some observations on receptive field development and enable rapid relearning of previously stored information, in keeping with Ebbinghaus’s memory savings theory.

Thermocompression bonding of gold is a promising technique for achieving low temperature, wafer-level bonding without the application of an electric field or complicated pre-bond cleaning procedure. The presence of a ductile layer influences the fracture behavior of the bonds. The fabrication process was described. In addition, the effect of plasticity was explored by varying the gold bonding thickness between 0.23 to 1.4 µm. Wafers were bonded at 300°C and two different pressures: 1.25 and 7 MPa. The bond toughness of the specimens were characterized using a four-point bend delamination technique. Cohesive failure was found to be the dominant fracture mode in the thicker films. Bonds made with thin gold films failed adhesively and at lower strain energy release rates. / Singapore-MIT Alliance (SMA)

Petroleum exploration and production in recent years have moved into increasingly deeper water off the continental shelf. Some of these facilities are anchored in water depths in excess of 1000 meters. Exploration and production in deep water present new technological challenges where traditional fixed platforms have given way to floating structures. Today suction caissons are the most commonly used anchorage system for permanent offshore oil production facility. The objective of this study is to numerically predict the ultimate capacity of suction caissons in normally consolidated and lightly overconsolidated clays. Representative soil profile from the Gulf of Mexico and the North Sea are taken and analyzed for suction caissons with length over diameter ratios of 2, 4, 6 & 8. Normalized failure load interaction diagrams are generated for each of the cases. The location of optimum attachment point is also reported for each of the cases. General purpose finite element computer program ABAQUS is used for the numerical prediction. The finite element study is carried out with three-dimensional models using hybrid elements. A simplified elastic perfectly plastic model with von-Mises yield criterion is used for the study. The saturated clay is treated as an incompressible material. Results of the study compares well with existing simplified method for estimating load capacity of suction caisson anchors.

Competition plays a fundamental role in structuring ecological communities, and is a particularly important interaction for sessile organisms such as plants (Goldberg & Fleetwood 1987; Tilman 1994). To mitigate the negative effects of competition on fitness, plants can alter their phenotypes and reproductive traits through plastic responses. For example, decreases in the red to far-red ratio of light signal the presence of competitors, inducing a suite of responses known as shade avoidance syndrome (Franklin 2008). My thesis examines the impact of the competitive environment on reproductive output, the phenotypes Impatiens capensis produce and natural selection acting on shade avoidance responses. I found that heterospecific competitors affect both the phenotypes of I. capensis, and selection on shade avoidance traits. I also found evidence of population differentiation in hypocotyl lengths and flowering time. My thesis elucidates the influence of competition on the evolution of phenotypic plasticity in Impatiens capensis.

Competition plays a fundamental role in structuring ecological communities, and is a particularly important interaction for sessile organisms such as plants (Goldberg & Fleetwood 1987; Tilman 1994). To mitigate the negative effects of competition on fitness, plants can alter their phenotypes and reproductive traits through plastic responses. For example, decreases in the red to far-red ratio of light signal the presence of competitors, inducing a suite of responses known as shade avoidance syndrome (Franklin 2008). My thesis examines the impact of the competitive environment on reproductive output, the phenotypes Impatiens capensis produce and natural selection acting on shade avoidance responses. I found that heterospecific competitors affect both the phenotypes of I. capensis, and selection on shade avoidance traits. I also found evidence of population differentiation in hypocotyl lengths and flowering time. My thesis elucidates the influence of competition on the evolution of phenotypic plasticity in Impatiens capensis.

Petroleum exploration and production in recent years have moved into increasingly deeper water off the continental shelf. Some of these facilities are anchored in water depths in excess of 1000 meters. Exploration and production in deep water present new technological challenges where traditional fixed platforms have given way to floating structures. Today suction caissons are the most commonly used anchorage system for permanent offshore oil production facility. The objective of this study is to numerically predict the ultimate capacity of suction caissons in normally consolidated and lightly overconsolidated clays. Representative soil profile from the Gulf of Mexico and the North Sea are taken and analyzed for suction caissons with length over diameter ratios of 2, 4, 6 & 8. Normalized failure load interaction diagrams are generated for each of the cases. The location of optimum attachment point is also reported for each of the cases. General purpose finite element computer program ABAQUS is used for the numerical prediction. The finite element study is carried out with three-dimensional models using hybrid elements. A simplified elastic perfectly plastic model with von-Mises yield criterion is used for the study. The saturated clay is treated as an incompressible material. Results of the study compares well with existing simplified method for estimating load capacity of suction caisson anchors.