Browsing by Author "Miller, Eric"

Now showing 1 - 6 of 6
  • Thumbnail Image
    Item
    AMPA Glutamate Receptor Trafficking in Models of Disease
    (2013-08) Miller, Eric
    The signaling between neurons in the brain underlies many crucial processes - from the beating of the heart to remembering that you have a meeting at noon. Indeed, it is proposed that changes in the way neurons communicate with each other form the basis of learning and memory. In this dissertation I will explore the ways in which neurological diseases can affect these integral neuronal functions and explain the changes on a cellular and molecular level. Deficits in AMPAR signaling are found in numerous diseases. I will explore the mechanisms of these deficits using in vitro models of three diseases: opioid-related cognitive deficits and addiction, Alzheimer's disease, and Parkinson's disease-related dementia. Background information is presented in the first chapter. In the second chapter the signaling pathways underlying morphine-induced synaptic deficits are delineated. I found that calcineurin is necessary for both functional and structural deficits in AMPAR signaling, while CaMKII is necessary for only the structural deficits. The role of tau in synaptic deficits cause by soluble Abeta; oligomers, which are found at elevated levels in Alzheimer's disease patients, are probed in the third chapter. I found that treatment with soluble Abeta; oligomers leads to phosphorylation- dependent mislocalization of tau to dendritic spines. Furthermore, treatment with soluble Abeta; oligomers leads to decreases in AMPAR signaling that require calcineurin activity and GluR1 residue S845, much like the mechanisms of AMPAR internalization in neurons treated with morphine. The fourth chapter unveils a novel role of tau and GSK3 in synaptic deficits found in neurons expressing A53T alpha-synuclein. In fact, I discovered that tau is involved in AMPAR signaling deficits found in neurons expressing A53T alpha- synuclein. Furthermore, both mislocalization of tau and synaptic deficits require phosphorylation of tau by GSK3. This dissertation shows that divergent pathways mediate structural and functional plasticity found in neurons exposed to morphine. Also, I show that deficits in AMPAR signaling in both Alzheimer's disease and Parkinson's disease involve tau mislocalization. These findings shed new light on the signaling pathways involved in AMPAR signaling deficits found in neurological diseases and provide new therapeutic targets for pharmacological interventions.
  • Thumbnail Image
    Item
    The case for microsimulation frameworks for integrated urban models
    (Journal of Transport and Land Use, 2018) Miller, Eric
    The primary objective of this paper is to "make the case" for adoption of microsimulation frameworks for development of integrated urban models. Similar to the case of activity-based travel models, microsimulation in integrated urban models enables such models to deal better with: heterogeneity and non-linearity in behavior; identification of the detailed spatial and socioeconomic distribution of impacts, benefits and costs; tracing complex interactions across agents and over time; providing support for modelling memory, learning and adaptation among agents; computational efficiency; and emergent behavior. The paper discusses strengths, weaknesses and challenges in microsimulating urban regions, including the extent to which microsimulation models are still subject to Lee’s famous "seven sins of large-scale modelling," as well as the extent to which they may help alleviate or reduce these sins in operational models. The paper concludes with a very brief discussion of future prospects for such models.
  • Thumbnail Image
    Item
    Microsimulation framework for urban price-taker markets
    (Journal of Transport and Land Use, 2013) Farooq, Bilal; Miller, Eric; Chingcuanco, Franco; Giroux-Cook, Martin
    In the context of integrated transportation and other urban engineering infrastructure systems, there are many examples of markets, where consumers exhibit price-taking behavior. While this behavior is ubiquitous, the underlying mechanism can be captured in a single framework. Here, we present a microsimulation framework of a price-taker market that recognizes this generality and develop efficient algorithms for the associated market-clearing problem. By abstracting the problem as a specific graph theoretic problem (i.e., maximum weighted bipartite graph), we are first able to exploit algorithms that are developed in graph theory. We then explore their appropriateness in terms of large-scale integrated urban microsimulations. Based on this, we further develop a generic and efficient clearing algorithm that takes advantage of the features specific to urban price-taker markets. This clearing solution is then used to operationalize two price-taker markets, from two different contexts, within a microsimulation of urban systems. The initial validation of results against the observed data generally shows a close match.
  • Thumbnail Image
    Item
    A multidimensional decisions modeling framework for built space supply
    (Journal of Transport and Land Use, 2013) Farooq, Bilal; Miller, Eric; Haider, Murtaza
    The spatial and temporal distribution of built space supply plays an important role in shaping urban form and thus the general travel pattern in an urban area. Within an integrated framework, we are interested in modeling the decisions of a builder in terms of when, where, what type, and how much built space to build. We present a multidimensional discrete-continuous model formulation for the built space supply decisions that are based on expected profit maximization. The framework is applied to estimate a model for supply of new office space in the greater Toronto area (GTA) for the 1986 to 2006 period. To our knowledge, this work is the first that models the where, when, how much, and what type of office space to build in a single econometric framework at a fairly disaggregate spatial zoning system. The results indicate risk taker behavior on the builders’ part, while market conditions and supply of resources (labor, construction cost, etc.) are also found to be important factors in decision making.
  • Thumbnail Image
    Item
    Special section: Innovations in location choice modeling underlying activity-travel behavior
    (Journal of Transport and Land Use, 2014) Scott, Darren M.; Ho-Yin Lee, Brian; Miller, Eric
    This special section of the Journal of Transport and Land Use focuses on location choice modeling underlying activity-travel behavior and includes five manuscripts that were originally presented in Toronto, Canada at the Thirteenth International Conference on Travel Behaviour Research, organized by the International Association for Travel Behaviour Research (IATBR).
  • Thumbnail Image
    Item
    Temporal transferability of models of mode-destination choice for the Greater Toronto and Hamilton Area
    (Journal of Transport and Land Use, 2014) Fox, James; Daly, Andrew; Hess, Stephane; Miller, Eric
    Transport planning relies extensively on forecasts of traveler behavior over horizons of 20 years and more. Implicit in such forecasts is the assumption that travelers’ tastes, as represented by the behavioral model parameters, are constant over time. In technical terms, this assumption is referred to as the "temporal transferability" of the models. This paper summarizes the findings from a literature review that demonstrates there is little evidence about the transferability of mode-destination models over typical forecasting horizons. The literature review shows a relative lack of empirical studies given the importance of the issue. To provide further insights and evidence, models of commuter mode-destination choice been developed from household interview data collected across the Greater Toronto and Hamilton Area in 1986, 1996, 2001, and 2006. The analysis demonstrates that improving model specification improves the transferability of the models, and in general the transferability declines as the transfer period increases. The transferability of the level-of-service parameters is higher than transferability of the cost parameters, which has important implications when considering the accuracy of forecasts for different types of policy. The transferred models over-predict the key change in mode share over the transfer period—specifically, the shift from local transit to auto driver between 1986 and 1996—but under-predict the growth in commuting tour lengths over the same period.