Master of Science / Department of Mechanical and Nuclear Engineering / Melanie M. Derby / Oil-water separation is an important process in the petroleum industry. This research investigates the use of surface tension forces to improve current oil-water separation technologies. An understanding of oil-water flows in surface tension driven mini-channels is necessary. This work investigates the effects of mini-channel wall material and tube diameter, along with oil viscosity, on flow regimes and pressure drops in mini-channel oil-water flows. A horizontal closed-loop, adiabatic experimental apparatus was constructed and validated using single-phase water. 2.1-mm and 3.7-mm borosilicate glass, 3.7-mm stainless steel and 4.0-mm Inconel tubes, resulting in Eötvös numbers of 0.2, 0.6 and 0.7 were tested. The experimental data were analyzed and compared using two mineral oils (i.e., Parol 70 and 100) with densities of 840 kg/m³ for both and viscosities of 11.7 and 20.8 mPa-s, respectively. Experiments included a wide range of oil superficial velocities (e.g., 0.28-6.82 m/s for glass, 0.28-2.80 m/s for stainless steel and 0.21-2.89 for Inconel) and water superficial velocities (e.g., 0.07-6.77 for glass, 0.07-4.20 m/s for stainless steel and 0.06-3.86 m/s). Flow regimes were observed and classified as stratified, annular, intermittent, and dispersed flow regimes. Effects of tube diameter were observed. For example, the 2.1-mm glass tube had the smaller range of stratified flows and the larger range of annular and intermittent flows compared to the 3.7-mm glass tube. At the same oil and water superficial velocities and relatively the same flow regime, stainless steel and Inconel always displayed higher pressure drop than the glass tube. However, pressure drops were a strong function of flow regime; lowest pressure drops were found for annular flows and highest pressure drops for dispersed flows. Flow regime maps and pressure drop graphs were created. Overall effects of oil viscosity were modest; however, an increase in oil viscosity enhanced flow stability which affected flow regime transition points.

In recent years, space-time block coding (STBC) has emerged as an effective transmit-diversity technique to combat the detrimental effects of channel fading. In addition to STBC, high-order modulation schemes will be used in future wireless communication systems aiming to provide ubiquitous-broadband wireless access. Hence, advanced receiver schemes are necessary to achieve high performance. In this thesis, advanced and computationally-efficient receiver schemes are investigated and developed for single-carrier space-time (ST) block-coded transmissions over frequency-selective fading (FSF) channels. First, we develop an MMSE-based turbo equalization scheme for Alamouti ST block-coded systems. A semi-analytical method to estimate the bit error rate (BER) is devised. Our results show that the proposed turbo equalization scheme offers significant performance improvements over one-pass equalization. Second, we analyze the convergence behavior of the proposed turbo equalization scheme for Alamouti ST block-coded systems using the extrinsic information transfer (EXIT)-band chart technique. Third, burst-wise (BW)-STBC is applied for uplink transmission over FSF channels in block-spread-CDMA systems with multiuser interference-free reception. The performances of different decision feedback sequence estimation (DFSE) schemes are investigated. A new scheme combining frequency-domain (FD) linear equalization and modified unwhitened-DFSE is proposed. The proposed scheme is very promising as the error-floor behavior observed in the existing unwhitened DFSE schemes is eliminated. Fourth, we develop a FD-MMSE-based turbo equalization scheme for the downlink of ST block-coded CDMA systems. We adopt BW-STBC instead of Alamouti symbol-wise (SW)-STBC considered for WCDMA systems and demonstrate its superior performance in FSF channels. Block spreading is shown to be more desirable than conventional spreading to improve performance using turbo equalization. We also devise approximate implementations (AprxImpls) that offer better trade-offs between performance and complexity. Semi-analytical upper bounds on the BER are derived. Fifth, turbo multicode detection is investigated for ST block-coded downlink transmission in DS-CDMA systems. We propose symbol-by-symbol and chip-by-chip FD-MMSE-based multicode detectors. An iterative channel estimation scheme is also proposed. The proposed turbo multicode detection scheme offers significant performance improvements compared with non-iterative multicode detection. Finally, the impact of channel estimation errors on the performance of MMSE-based turbo equalization in ST block-coded CDMA systems is investigated. / Applied Science, Faculty of / Electrical and Computer Engineering, Department of / Graduate

A new promising approach for wireless network optimization is from a cross-layer perspective. This thesis focuses on exploiting channel state information (CSI) from the physical layer for optimal transmission scheduling at the medium access control (MAC) layer. The first part of the thesis considers exploiting CSI via a distributed channel-aware MAC protocol. The MAC protocol is analysed using a centralized design approach and a non-cooperative game theoretic approach. Structural results are obtained and provably convergent stochastic approximation algorithms that can estimate the optimal transmission policies are proposed. Especially, in the game theoretic MAC formulation, it is proved that the best response transmission policies are threshold in the channel state and there exists a Nash equilibrium at which every user deploys a threshold transmission policy. This threshold result leads to a particularly efficient stochastic-approximation-based adaptive learning algorithm and a simple distributed implementation of the MAC protocol. Simulations show that the channel-aware MAC protocols result in system throughputs that increase with the number of users. The thesis also considers opportunistic transmission scheduling from the perspective of a single user using Markov Decision Process (MDP) approaches. Both channel state information and channel memory are exploited for opportunistic transmission. First, a finite horizon MDP transmission scheduling problem is considered. The finite horizon formulation is suitable for short-term delay constraints. It is proved for the finite horizon opportunistic transmission scheduling problem that the optimal transmission policy is threshold in the buffer occupancy state and the transmission time. This two-dimensional threshold structure substantially reduces the computational complexity required to compute and implement the optimal policy. Second, the opportunistic transmission scheduling problem is formulated as an infinite horizon average cost MDP with a constraint on the average waiting cost. An advantage of the infinite horizon formulation is that the optimal policy is stationary. Using the Lagrange dynamic programming theory and the supermodularity method, it is proved that the stationary optimal transmission scheduling policy is a randomized mixture of two policies that are threshold in the buffer occupancy state. A stochastic approximation algorithm and a Q-learning based algorithm that can adaptively estimate the optimal transmission scheduling policies are then proposed. / Applied Science, Faculty of / Electrical and Computer Engineering, Department of / Graduate

Synaptic transmission occurs as a result of either a spontaneous release of presynaptic vesicles or a batch release of presynaptic vesicles driven by action potentials. The physiological consequence of synaptic transmission driven by different patterns and frequencies of presynaptic stimulation has been extensively investigated. However, the physiological nature, mechanism as well as relevance of prolonged presynaptic stimulation have been poorly characterized. In this dissertation, I present three projects in which prolonged stimulation of synaptic transmission in different forms and different brain regions was studied for its effect on synaptic transmission, mechanisms and physiological relevance. In the first project, prolonged electrical stimulation (100 sec) at high frequency induced a deep synaptic depression in acute hippocampal slices, followed by a recovery of synaptic transmission after ~15 min. The deep synaptic depression was attributed to a complete depletion of presynaptic vesicle pools. In the second project, attempts were made to characterize the mechanism of nuclear activation of gene transcription induced by prolonged electrical stimulation (100 sec). Our results demonstrated that reduced inactivation of non-L-type calcium channels failed to provide calcium required for gene transcription, leaving the activation of gene transcription a selective function for L-type calcium channels. In the third project, we sought to study the physiological relevance of enhanced miniature events of inhibitory synapses induced by prolonged chemical stimulation. We showed that prolonged application (2 min) of nicotine to the striatal slice enhanced the frequency of miniature inhibitory currents that was accompanied with a reduction in the amplitude of evoked response. This reduction in the amplitude of evoked responses was ascribed to a compromised action potential invasion of presynaptic terminals possibly due to inactivation of sodium channels resulting from nicotine-induced depolarization. To summarize, prolonged stimulation of presynaptic vesicle release imposes significant influence upon neuron-to-neuron communication, with distinct mechanisms in different brain regions. / Medicine, Faculty of / Graduate

We investigate to which degree one could trace Bitcoin transactions and characterize purchasing behavior of online anonymous marketplaces by exploiting side channels. Using a list of addresses found by the FBI on Silk Road servers, and information on the marketplace's official guides, we infer the role played by each address in the list and classify them based on heuristics. We then attempt to trace Bitcoin transactions and show that the anonymity set size is greatly reduced using product review data and the address classification performed on the previous step. Finally, using clustering techniques based on transaction graph analysis, we assign addresses into user wallets, then group these wallets together based on spending patterns, to be able to characterize purchasing behavior.

Hyperkalemic periodic paralysis, HyperKPP, is an inherited progressive disorder of the muscles caused by mutations in the voltage gated sodium channel (NaV1.4). The objectives of this thesis were to develop a technique for measurement symptoms in vivo using electromyography (EMG) and to determine the mechanism by which Ca2+ alleviates HyperKPP symptoms, since this is unknown. Increasing extracellular [Ca2+] ([Ca2+]e) from 1.3 to 4 mM did not result in any increases in45Ca2+ influx suggesting no increase in intracellular [Ca2+] ([Ca2+]i) acting on an intracellular signaling pathway or on an ion channel such as the Ca2+sensitive K+ channels. HyperKPP muscles have larger TTX-sensitive22Na+ influx than wild type muscles because of the defective NaV1.4 channels. When [Ca2+] was increased from 1.3 to 4 mM, the abnormal 22Na+ influx was completely abolished. Thus, one mechanism by which Ca2+alleviates HyperKPP symptoms is by reducing the abnormal Na+ influx caused by the mutation in the NaV1.4 channel.

The pentameric ligand gated ion channel super family plays a central role in fast synaptic communication between neurons and at the neuromuscular junction. Extensive studies on the prototypic pLGIC, the Torpedo nicotinic acetylcholine receptor (nAChR) have revealed an exquisite lipid sensitivity, with the nAChR adopting a novel uncoupled conformation in membranes lacking activating anionic and neutral lipids. The lipid-exposed transmembrane alpha-helix, M4, in each homologous subunit likely acts as a lipid sensor. One model proposes that activating lipids promote M4 “binding” to the adjacent alpha-helices, M1 and M3, to enhance interactions between the M4 C-terminus and the Cys-loop of the agonist-binding domain, with such interactions promoting coupling between the agonist site and channel gate. The first part of my thesis indirectly tests this hypothesis by exploring the effects of membrane hydrophobic thickness on nAChR function. Specifically, I tested the hypothesis that thicker membranes, which should promote alignment of M4 parallel to M1/M3 and thus helix-helix interactions, favor a coupled conformation. Although I found that the nAChR is uncoupled in all membranes tested, regardless of hydrophobic thickness, thicker membranes promote transitions from uncoupled to ultimately the desensitized state over the minutes to hours time frame. In contrast to anionic lipids, which influence function primarily via a conformational selection mechanism, membrane hydrophobic thickness influences function via a kinetic mechanism - thick membranes lower the activation energy between uncoupled and coupled conformations to promote conformational transitions. In the second part of my thesis, I used the two prokaryotic homologs, GLIC and ELIC, to explore how amino acid interactions at the interface between M4 and M1/M3 influence channel activity. Alanine scanning mutagenesis of this interface shows that disruption of almost any interaction in GLIC leads to a loss of folding and/or function, while analogous mutations in ELIC typically lead to no change or produce gains in function. Sequence comparisons with other members of the pLGIC superfamily suggest that the transmembrane domains of GLIC and ELIC represent two distinct archetypes. Each archetype may strike a different balance between the need for strong M4 binding to M1/M3 to promote folding and pentamer assembly, and the need for weaker interactions that allow for greater conformational flexibility during function.

This study investigates the relation between channel instability and sediment transport along an 80 km reach of lower Fraser River, British Columbia. The major processes governing instability, bank erosion and sedimentation were investigated by analyzing the patterns of morphologic change along the river over the last century. Morphologic changes were documented using historical maps and air photographs. The method of approach can be considered a "macroscopic" one since the investigation focused primarily on the gross patterns of change that occurred over periods of years to decades. It was found that this interval is the most appropriate time scale for investigating channel instability and sedimentation processes on a large stream such as the Fraser River. This is because the major features governing instability and sedimentation also develop over comparatively long time periods. Several examples are presented to illustrate how sequences of major channel instability have propagated along the river over periods of 10 to 30 years. These disturbances often initiated new patterns of sedimentation, local erosion and subsequent channel instability further downstream. The most common diagnostic feature associated with these travelling disturbances are relatively large, low amplitude, linguoidal-shaped "gravel sheets" that attach to more stable lateral bars and islands. These bars may cause strong flow impingement against previously stable banks and islands. As a result, rapid scour and erosion may be initiated even during periods of low discharge. Four different approaches were used to estimate the long term gravel transport rate along the river. These methods included direct measurements using trap samplers (carried out by Water Survey of Canada over a period of 12 years), a sediment budget calculation which related changes in transport through a reach to changes in the volume of sediment stored in the channel determined by surveys, a morphologic approach which used a simple model of sediment transfers through a reach, and finally theoretical bed load formulae. It was found that the sediment budget and the morphological model provided the most reliable and most generally applicable results. This was because the methods rely on observations of sediment movement over periods of years or decades. It was found that on Fraser River, the time scales of the major processes governing gravel bed load transport were also measured in years or decades. As a result, short term measurements such as from bed load trap samplers show only a poor correlation between transport rate and flow variables. Therefore, to estimate long term transport rates with these data, a very large number of observations is required to integrate the transport rates over time. / Arts, Faculty of / Geography, Department of / Graduate

Previous in vitro studies have demonstrated that AQP1, traditionally viewed as a water channel, also facilitates the passage of CO2 and ammonia across cell membranes. This thesis summarizes the first in vivo studies confirming a physiologically-relevant role for AQP1 in acid-base balance and nitrogenous waste excretion. Zebrafish embryos were microinjected with a translation-blocking morpholino oligonucleotide targeted to the zebrafish AQP1 paralog, AQP1a. Closed-system respirometry, total CO2 analysis, tritiated water fluxes and measurement of ammonia excretion were performed on larvae at 4 days post-fertilization (dpf). Knockdown of AQP1a significantly reduced rates of water, CO2 and ammonia excretion. Use of phenylhydrazine, a haemolytic agent, provided evidence that the yolk sac epithelium AQP1a (and not erythrocyte AQP1a) is the major site of CO2 and ammonia movements. Further, the hypothesis that AQP1a and the Rh glycoprotein Rhcg1, another multi-functional gas channel, act in concert to regulate CO2 and ammonia excretion was explored. Exposure to conditions impairing ammonia excretion (such as high external ammonia (HEA) or alkaline water) modulated AQP1a protein expression in 4 dpf zebrafish larvae experiencing knockdown of Rhcg1. Chronic HEA exposure triggered a significant compensatory increase in AQP1a protein abundance in Rhcg1 morphants. Exposure of Rhcg1 morphants to pH 10 water, however, caused a significant decrease in AQP1a protein expression. Interestingly, when AQP1a mRNA and protein levels were examined in Rhcg1 morphants and vice versa, no changes were observed. Overall, zebrafish AQP1a was found to be a multi-functional transporter of water, CO2 and ammonia, though the exact relationship it holds with other such gas channels bears further exploration.

Calcium-activated chloride channels (CaCCs) are ubiquitously expressed in a plethora of cell types and, consequently, are involved in numerous cellular processes as diverse as epithelial secretion, regulation of cardiac excitability and smooth muscle contraction. Current pharmacology of CaCCs is limited to compounds with low potency and poor selectivity. The lack of knowledge surrounding the molecular identity of the CaCC has greatly hindered the development of more specific drugs and has impaired our understanding of the channel physiology and biophysics. The recent discovery that the TMEM16A gene codes for CaCCs has offered hope for new developments in these areas. CaCCs have been suggested as possible targets to treat a variety of conditions including asthma as well as pulmonary and systemic hypertension. Due to the ubiquitous expression of CaCCs and the ability of the channel to interact with a number of pharmacological compounds with diverse chemical structures however, it was hypothesised that TMEM16A could be a possible source for off-target drug effects and may represent a concern for safety pharmacology. The principal aim of this thesis was to assess the functional significance of TMEM16A in the cardiovascular system, as this is one of the major systems of concern for safety pharmacology and accounts for the largest number of post-market drug withdrawals. The main findings of this study can be summarised as follows: 1) RT-PCR analysis revealed a ubiquitous expression of TMEM16A in tissues of the rat and human cardiovascular systems, including systemic and pulmonary arteries as well as cardiac tissue. Analysis also revealed the presence of multiple TMEM16A splice variants in all rat tissues examined, in addition to a number of other TMEM16x family members. 2) Myography experiments using the “classical” CaCC blocker niflumic acid and newly identified TMEM16A blockers confirmed a functional role for TMEM16A in phenylephrine-induced vascular smooth muscle contraction. 3) The suitability of currently available Cl- channel blockers for use as pharmacological tools for TMEM16A research was assessed using conventional whole-cell patch clamp and high-throughput electrophysiology techniques to respectively compare their potencies and selectivity over other cardiovascular ion channels. Of the compounds tested, DIDS and T16Ainh-A01 appeared the most suitable blockers; however all compounds had a degree of non-selectivity, raising concerns for their use in functional studies. In conclusion, these findings provide evidence for the ubiquitous expression and functional significance of TMEM16A within the cardiovascular system and support the hypothesis that TMEM16A is a concern for safety pharmacology and should be included into future pre-clinical safety assays. The inadequacy of current inhibitors however highlights the urgency for the development of novel potent and selective channel modulators for future TMEM16A research.