A Model of Lung Tumor Angiogenesis in a Biomimetic Poly(ethylene glycol)-based Hydrogel System

Tumor angiogenesis is critical to tumor growth and metastasis, yet much is unknown about the role vascular cells play in the tumor microenvironment. A major outstanding challenge associated with studying tumor angiogenesis is that existing preclinical models are limited in their recapitulation of in vivo cellular organization in 3D. This disparity highlights the need for better approaches to study the dynamic interplay of relevant cells and signaling molecules as they are organized in the tumor microenvironment. In this thesis, we combined 3D culture of lung adenocarcinoma cells with adjacent 3D microvascular cell culture in 2-layer cell-adhesive, proteolytically-degradable poly(ethylene glycol) (PEG)-based hydrogels to study tumor angiogenesis and the impacts of neovascularization on tumor cell behavior.

In initial studies, 344SQ cells, a highly metastatic, murine lung adenocarcinoma cell line, were characterized alone in 3D in PEG hydrogels. 344SQ cells formed spheroids in 3D culture and secreted proangiogenic growth factors into the conditioned media that significantly increased with exposure to transforming growth factor beta 1 (TGF-β1), a potent tumor progression-promoting factor. Vascular cells alone in hydrogels formed tubule networks with localized activated TGF-β1. To study cancer cell-vascular cell interactions, the engineered 2-layer tumor angiogenesis model with 344SQ and vascular cell layers was employed. Large, invasive 344SQ clusters developed at the interface between the layers, and were not evident further from the interface or in control hydrogels without vascular cells. A modified model with spatially restricted 344SQ and vascular cell layers confirmed that observed 344SQ cluster morphological changes required close proximity to vascular cells. Additionally, TGF-β1 inhibition blocked endothelial cell-driven 344SQ migration.

Two other lung adenocarcinoma cell lines were also explored in the tumor angiogenesis model: primary tumor-derived metastasis-incompetent, murine 393P cells and primary tumor-derived metastasis-capable human A549 cells. These lung cancer cells also formed spheroids in 3D culture and secreted proangiogenic growth factors into the conditioned media. Epithelial morphogenesis varied for the primary tumor-derived cell lines compared to 344SQ cells, with far less epithelial organization present in A549 spheroids. Additionally, 344SQ cells secreted the highest concentration of two of the three angiogenic growth factors assessed. This finding correlated to 344SQ exhibiting the most pronounced morphological response in the tumor angiogenesis model compared to the 393P and A549 cell lines.

Overall, this dissertation demonstrates the development of a novel 3D tumor angiogenesis model that was used to study vascular cell-cancer cell interactions in lung adenocarcinoma cell lines with varying metastatic capacities. Findings in this thesis have helped to elucidate the role of vascular cells in tumor progression and have identified differences in cancer cell behavior in vitro that correlate to metastatic capacity, thus highlighting the usefulness of this model platform for future discovery of novel tumor angiogenesis and tumor progression-promoting targets.

Dynamic classifiers for neonatal brain monitoring

Brain injury due to lack of oxygen or impaired blood flow around the time of birth, may cause long term neurological dysfunction or death in severe cases. The treatments need to be initiated as soon as possible and tailored according to the nature of the injury to achieve best outcomes. The Electroencephalogram (EEG) currently provides the best insight into neurological activities. However, its interpretation presents formidable challenge for the neurophsiologists. Moreover, such expertise is not widely available particularly around the clock in a typical busy Neonatal Intensive Care Unit (NICU). Therefore, an automated computerized system for detecting and grading the severity of brain injuries could be of great help for medical staff to diagnose and then initiate on-time treatments. In this study, automated systems for detection of neonatal seizures and grading the severity of Hypoxic-Ischemic Encephalopathy (HIE) using EEG and Heart Rate (HR) signals are presented. It is well known that there is a lot of contextual and temporal information present in the EEG and HR signals if examined at longer time scale. The systems developed in the past, exploited this information either at very early stage of the system without any intelligent block or at very later stage where presence of such information is much reduced. This work has particularly focused on the development of a system that can incorporate the contextual information at the middle (classifier) level. This is achieved by using dynamic classifiers that are able to process the sequences of feature vectors rather than only one feature vector at a time.

Surface wind stress modeled for the Panama Seaway with the Community Climate System Model 3

The early Pliocene warm phase was characterized by high sea surface temperatures and a deep thermocline in the eastern equatorial Pacific. A new hypothesis suggests that the progressive closure of the Panamanian seaway contributed substantially to the termination of this zonally symmetric state in the equatorial Pacific. According to this hypothesis, intensification of the Atlantic meridional overturning circulation (AMOC) - induced by the closure of the gateway - was the principal cause of equatorial Pacific thermocline shoaling during the Pliocene. In this study, twelve Panama seaway sensitivity experiments from eight ocean/climate models of different complexity are analyzed to examine the effect of an open gateway on AMOC strength and thermocline depth. All models show an eastward Panamanian net throughflow, leading to a reduction in AMOC strength compared to the corresponding closed-Panama case. In those models that do not include a dynamic atmosphere, deepening of the equatorial Pacific thermocline appears to scale almost linearly with the throughflow-induced reduction in AMOC strength. Models with dynamic atmosphere do not follow this simple relation. There are indications that in four out of five models equatorial wind-stress anomalies amplify the tropical Pacific thermocline deepening. In summary, the models provide strong support for the hypothesized relationship between Panama closure and equatorial Pacific thermocline shoaling.

Wind Shear, Gust, and Yaw-Induced Dynamic Stall on Wind-Turbine Blades

This study examined the effect of a spanwise angle of attack gradient on the growth and stability of a dynamic stall vortex in a rotating system. It was found that a spanwise angle of attack gradient induces a corresponding spanwise vorticity gradient, which, in combination with spanwise flow, results in a redistribution of circulation along the blade. Specifically, when modelling the angle of attack gradient experienced by a wind turbine at the 30% span position during a gust event, the spanwise vorticity gradient was aligned such that circulation was transported from areas of high circulation to areas of low circulation, increasing the local dynamic stall vortex growth rate, which corresponds to an increase in the lift coefficient, and a decrease in the local vortex stability at this point. Reversing the relative alignment of the spanwise vorticity gradient and spanwise flow results in circulation transport from areas of low circulation generation to areas of high circulation generation, acting to reduce local circulation and stabilise the vortex. This circulation redistribution behaviour describes a mechanism by which the fluctuating loads on a wind turbine are magnified, which is detrimental to turbine lifetime and performance. Therefore, an understanding of this phenomenon has the potential to facilitate optimised wind turbine design.

Essays in dynamic optimal taxation: working experience, unemployment scarring and poverty

This thesis investigates the design of optimal tax systems in dynamic environments. The first essay characterizes the optimal tax system where wages depend on stochastic shocks and work experience. In addition to redistributive and efficiency motives, the taxation of inexperienced workers depends on a second-best requirement that encourages work experience, a social insurance motive and incentive effects. Calibrations using U.S. data yield higher expected optimal marginal income tax rates for experienced workers for most of the inexperienced workers. They confirm that the average marginal income tax rate increases (decreases) with age when shocks and work experience are substitutes (complements). Finally, more variability in experienced workers' earnings prospects leads to increasing tax rates since income taxation acts as a social insurance mechanism. In the second essay, the properties of an optimal tax system are investigated in a dynamic private information economy where labor market frictions create unemployment that destroys workers' human capital. A two-skill type model is considered where wages and employment are endogenous. I find that the optimal tax system distorts the first-period wages of all workers below their efficient levels which leads to more employment. The standard no-distortion-at-the-top result no longer holds due to the combination of private information and the destruction of human capital. I show this result analytically under the Maximin social welfare function and confirm it numerically for a general social welfare function. I also investigate the use of a training program and job creation subsidies. The final essay analyzes the optimal linear tax system when there is a population of individuals whose perceptions of savings are linked to their disposable income and their family background through family cultural transmission. Aside from the standard equity/efficiency trade-off, taxes account for the endogeneity of perceptions through two channels. First, taxing labor decreases income, which decreases the perception of savings through time. Second, taxation on savings corrects for the misperceptions of workers and thus savings and labor decisions. Numerical simulations confirm that behavioral issues push labor income taxes upward to finance saving subsidies. Government transfers to individuals are also decreased to finance those same subsidies.

Acceleration and visualization of Dynamic Network Optimization

With the emerging prevalence of smart phones and 4G LTE networks, the demand for faster-better-cheaper mobile services anytime and anywhere is ever growing. The Dynamic Network Optimization (DNO) concept emerged as a solution that optimally and continuously tunes the network settings, in response to varying network conditions and subscriber needs. Yet, the DNO realization is still at infancy, largely hindered by the bottleneck of the lengthy optimization runtime. This paper presents the design and prototype of a novel cloud based parallel solution that further enhances the scalability of our prior work on various parallel solutions that accelerate network optimization algorithms. The solution aims to satisfy the high performance required by DNO, preliminarily on a sub-hourly basis. The paper subsequently visualizes a design and a full cycle of a DNO system. A set of potential solutions to large network and real-time DNO are also proposed. Overall, this work creates a breakthrough towards the realization of DNO.

Achievable rates and outage probability of cognitive radio with dynamic frequency hopping under imperfect spectrum sensing

In this study, the authors propose simple methods to evaluate the achievable rates and outage probability of a cognitive radio (CR) link that takes into account the imperfectness of spectrum sensing. In the considered system, the CR transmitter and receiver correlatively sense and dynamically exploit the spectrum pool via dynamic frequency hopping. Under imperfect spectrum sensing, false-alarm and miss-detection occur which cause impulsive interference emerged from collisions due to the simultaneous spectrum access of primary and cognitive users. That makes it very challenging to evaluate the achievable rates. By first examining the static link where the channel is assumed to be constant over time, they show that the achievable rate using a Gaussian input can be calculated accurately through a simple series representation. In the second part of this study, they extend the calculation of the achievable rate to wireless fading environments. To take into account the effect of fading, they introduce a piece-wise linear curve fitting-based method to approximate the instantaneous achievable rate curve as a combination of linear segments. It is then demonstrated that the ergodic achievable rate in fast fading and the outage probability in slow fading can be calculated to achieve any given accuracy level.

Local Storage Meets Local Demand: A Technical Solution to Future Power Distribution System

Future power systems are expected to integrate large-scale stochastic and intermittent generation and load due to reduced use of fossil fuel resources, including renewable energy sources (RES) and electric vehicles (EV). Inclusion of such resources poses challenges for the dynamic stability of synchronous transmission and distribution networks, not least in terms of generation where system inertia may not be wholly governed by large-scale generation but displaced by small-scale and localised generation. Energy storage systems (ESS) can limit the impact of dispersed and distributed generation by offering supporting reserve while accommodating large-scale EV connection; the latter (load) also participating in storage provision. In this paper, a local energy storage system (LESS) is proposed. The structure, requirement and optimal sizing of the LESS are discussed. Three operating modes are detailed, including: 1) storage pack management; 2) normal operation; and 3) contingency operation. The proposed LESS scheme is evaluated using simulation studies based on data obtained from the Northern Ireland regional and residential network.

Footbridge system identification using wireless inertial measurement units for force and response measurements

With the main focus on safety, design of structures for vibration serviceability is often overlooked or mismanaged, resulting in some high profile structures failing publicly to perform adequately under human dynamic loading due to walking, running or jumping. A standard tool to inform better design, prove fitness for purpose before entering service and design retrofits is modal testing, a procedure that typically involves acceleration measurements using an array of wired sensors and force generation using a mechanical shaker. A critical but often overlooked aspect is using input (force) to output (response) relationships to enable estimation of modal mass, which is a key parameter directly controlling vibration levels in service.

This paper describes the use of wireless inertial measurement units (IMUs), designed for biomechanics motion capture applications, for the modal testing of a 109 m footbridge. IMUs were first used for an output-only vibration survey to identify mode frequencies, shapes and damping ratios, then for simultaneous measurement of body accelerations of a human subject jumping to excite specific vibrations modes and build up bridge deck accelerations at the jumping location. Using the mode shapes and the vertical acceleration data from a suitable body landmark scaled by body mass, thus providing jumping force data, it was possible to create frequency response functions and estimate modal masses.

The modal mass estimates for this bridge were checked against estimates obtained using an instrumented hammer and known mass distributions, showing consistency among the experimental estimates. Finally, the method was used in an applied research application on a short span footbridge where the benefits of logistical and operational simplicity afforded by the highly portable and easy to use IMUs proved extremely useful for an efficient evaluation of vibration serviceability, including estimation of modal masses.

Data-Driven Dynamic Modeling of Coupled Thermal and Electric Outputs of Microturbines

Microturbines are among the most successfully commercialized distributed energy resources, especially when they are used for combined heat and power generation. However, the interrelated thermal and electrical system dynamic behaviors have not been fully investigated. This is technically challenging due to the complex thermo-fluid-mechanical energy conversion processes which introduce multiple time-scale dynamics and strong nonlinearity into the analysis. To tackle this problem, this paper proposes a simplified model which can predict the coupled thermal and electric output dynamics of microturbines. Considering the time-scale difference of various dynamic processes occuring within microturbines, the electromechanical subsystem is treated as a fast quasi-linear process while the thermo-mechanical subsystem is treated as a slow process with high nonlinearity. A three-stage subspace identification method is utilized to capture the dominant dynamics and predict the electric power output. For the thermo-mechanical process, a radial basis function model trained by the particle swarm optimization method is employed to handle the strong nonlinear characteristics. Experimental tests on a Capstone C30 microturbine show that the proposed modeling method can well capture the system dynamics and produce a good prediction of the coupled thermal and electric outputs in various operating modes.

Identification of Microturbine Model for Long-term Dynamic Analysis of Distribution Networks

As one of the most successfully commercialized distributed energy resources, the long-term effects of microturbines (MTs) on the distribution network has not been fully investigated due to the complex thermo-fluid-mechanical energy conversion processes. This is further complicated by the fact that the parameter and internal data of MTs are not always available to the electric utility, due to different ownerships and confidentiality concerns. To address this issue, a general modeling approach for MTs is proposed in this paper, which allows for the long-term simulation of the distribution network with multiple MTs. First, the feasibility of deriving a simplified MT model for long-term dynamic analysis of the distribution network is discussed, based on the physical understanding of dynamic processes that occurred within MTs. Then a three-stage identification method is developed in order to obtain a piecewise MT model and predict electro-mechanical system behaviors with saturation. Next, assisted with the electric power flow calculation tool, a fast simulation methodology is proposed to evaluate the long-term impact of multiple MTs on the distribution network. Finally, the model is verified by using Capstone C30 microturbine experiments, and further applied to the dynamic simulation of a modified IEEE 37-node test feeder with promising results.

Data-Driven Dynamic Prediction of Interrelated Heat and Electric Outputs of Microturbines

Microturbines are among the most successfully commercialized distributed energy resources, especially when they are used for combined heat and power generation. However, the interrelated thermal and electrical system dynamic behaviors have not been fully investigated. This is technically challenging due to the complex thermo-fluid-mechanical energy conversion processes which introduce multiple time-scale dynamics and strong nonlinearity into the analysis. To tackle this problem, this paper proposes a simplified model which can predict the coupled thermal and electric output dynamics of microturbines. Considering the time-scale difference of various dynamic processes occuring within microturbines, the electromechanical subsystem is treated as a fast quasi-linear process while the thermo-mechanical subsystem is treated as a slow process with high nonlinearity. A three-stage subspace identification method is utilized to capture the dominant dynamics and predict the electric power output. For the thermo-mechanical process, a radial basis function model trained by the particle swarm optimization method is employed to handle the strong nonlinear characteristics. Experimental tests on a Capstone C30 microturbine show that the proposed modeling method can well capture the system dynamics and produce a good prediction of the coupled thermal and electric outputs in various operating modes.

Extracting bridge frequencies from dynamic responses of two passing vehicles

A conventional way to identify bridge frequencies is utilizing vibration data measured directly from the bridge. A drawback with this approach is that the deployment and maintenance of the vibration sensors are generally costly and time-consuming. One of the solutions is in a drive-by approach utilizing vehicle vibrations while the vehicle passes over the bridge. In this approach, however, the vehicle vibration includes the effect of road surface roughness, which makes it difficult to extract the bridge modal properties. This study aims to examine subtracting signals of two trailers towed by a vehicle to reduce the effect of road surface roughness. A simplified vehicle-bridge interaction model is used in the numerical simulation; the vehicle - trailer and bridge system are modeled as a coupled model. In addition, a laboratory experiment is carried out to verify results of the simulation and examine feasibility of the damage detection by the drive-by method.

Implementation of a drive-by monitoring system for transport infrastructure utilising GNSS

Ageing and deterioration of infrastructure is a challenge facing transport authorities. In particular, there is a need for increased bridge monitoring in order to provide adequate maintenance, prioritise allocation of funds and guarantee acceptable levels of transport safety. Existing bridge structural health monitoring (SHM) techniques typically involve direct instrumentation of the bridge with sensors and equipment for the measurement of properties such as frequencies of vibration. These techniques are important as they can indicate the deterioration of the bridge condition. However, they can be labour intensive and expensive due to the requirement for on-site installations. In recent years, alternative low-cost indirect vibrationbased SHM approaches have been proposed which utilise the dynamic response of a vehicle to carry out “drive-by” pavement and/or bridge monitoring. The vehicle is fitted with sensors on its axles thus reducing the need for on-site installations. This paper investigates the use of low-cost sensors incorporating global navigation satellite systems (GNSS) for implementation of the drive-by system in practice, via field trials with an instrumented vehicle. The potential of smartphone technology to be harnessed for drive by monitoring is established, while smartphone GNSS tracking applications are found to compare favourably in terms of accuracy, cost and ease of use to professional GNSS devices.

A generic strategy for dynamic load balancing of distributed memory parallel computational mechanics using unstructured meshes

A large class of computational problems are characterised by frequent synchronisation, and computational requirements which change as a function of time. When such a problem is solved on a message passing multiprocessor machine [5], the combination of these characteristics leads to system performance which deteriorate in time. As the communication performance of parallel hardware steadily improves so load balance becomes a dominant factor in obtaining high parallel efficiency. Performance can be improved with periodic redistribution of computational load; however, redistribution can sometimes be very costly. We study the issue of deciding when to invoke a global load re-balancing mechanism. Such a decision policy must actively weigh the costs of remapping against the performance benefits, and should be general enough to apply automatically to a wide range of computations. This paper discusses a generic strategy for Dynamic Load Balancing (DLB) in unstructured mesh computational mechanics applications. The strategy is intended to handle varying levels of load changes throughout the run. The major issues involved in a generic dynamic load balancing scheme will be investigated together with techniques to automate the implementation of a dynamic load balancing mechanism within the Computer Aided Parallelisation Tools (CAPTools) environment, which is a semi-automatic tool for parallelisation of mesh based FORTRAN codes.