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Autophagy is a highly conserved bulk degradation pathway, in which cells generate a unique double-membraned vesicle, called "autophagosome", to engulf cytoplasmic materials for lysosomal degradation. It targets long-lived proteins or damaged organelles under both basal or stressed conditions to maintain cellular homeostasis and cell survival. The core autophagy machinery has been well characterised and is regulated hierarchically by autophagy-related (ATG) proteins. ATG8 is a unique ubiquitin-like protein covalently conjugated on autophagosomes via lipidation reaction. The lipidated ATG8 is a key player along the whole autophagic process, from autophagosome biogenesis, membrane expansion, cargo recruitment, until autophagosome-lysosome fusion. To better understand how lipidated ATG8 mediates autophagosome membrane expansion and cargo recruitment, I employed various in vitro reconstitution approaches using artificial model membranes to investigate human lipidated ATG8 proteins (LC3s/GABARAPs). First, using a real-time lipidation assay, I found that the N-termini of LC3B/GABARAP are highly dynamic and associate with membrane after lipidation. The atomistic MD simulation and FRET assays indicate that N-termini of LC3B/GABARAP associate in cis with the membrane where ATG8 gets lipidated. This cis-membrane association is important to maintain membrane expansion and regulate autophagosome size in cells, consequently, resulting in an efficient degradation of cytosolic cargo p62. Afterwards, I investigated the function of lipidated ATG8 during cargo recruitment. The preliminary results show that p62 is prone to interact with membrane-bound ATG8. This suggests that the lipidated ATG8 may have a higher binding affinity to cytosolic substrates, for example p62, compared to cytosolic ATG8. More experiments are required to better understand the interaction between lipidated ATG8 and p62. Finally, I performed in vitro ATG8 lipidation reactions using the cell membranes derived from autophagic deficient cells, which could be the potential membrane models for the future studies. In this study, I proposed a model integrating the functions of ATG8 lipidation in membrane expansion.

Biological invasion of alien species usually has an adverse impact on ecology as alien species are often regarded as harmful species to the local ecosystems. A comprehensive understanding of spatial patterns of species spread during biological invasion is needed for efficient monitoring and control of harmful alien pests. Various growth-dispersal-type models of population dynamics predict that invasive species spread can follow two qualitatively different scenarios: propagation of a continuous population front and 'no-front' patchy invasion. Distinguishing between those two types of spatial pattern is important as patchy invasion may require a different approach to monitoring and control. However, a mathematical theory of patchy invasion is still missing and it remains unclear which parameter values in the underlying model result in the formation of patchy spatial patterns and how much this dynamical regime is different from the continuous front propagation. In this thesis we address the problem of spatial patterns recognition in biological invasion in terms of two biologically meaningful mathematical models. We employ several topological characteristics of spatial pattern to investigate various spatial density distributions. The topology of continuous front and patchy spatial structures will be carefully compared and conclusions about sensitivity and 'topological stability' of those spatial patterns will be derived.

The phenomena of Two-Phase Flow with large density ratio (about 1000:1) in porous media occurs in many environmental and industrial processes. This thesis aims to develop a numerical tool to simulate the Two-Phase Flow along curved solid boundaries with Lattice Boltzmann (LB) method. In addition, a modified Ghost Fluid Immersed Boundary (GFIB) model is proposed to capture the local interaction behaviour among fluids and curved boundaries. The code is first checked with the droplet test, capillary rise test, capillary bridge test and contact line dynamic test and all cases resulted in less than 5.0% error in comparison with the analytical solutions. Then it is further verified with capillary rise in porous media and the numerical pressure satisfies the theoretical one with 12.7% error. In addition, the parameter studies are conducted to gauge the influence of four main parameters in the model, including the interface thickness, the mobility, the domain size and the grid resolution with good results. As a result, the new code with the LB-GFIB model can provide an alternative way to study the complex process of Two-Phase Flow in the porous media.

During a period of unprecedented rapid urbanisation and social transformation in China, this thesis considers the children of internal rural migrants and their access to compulsory education in the regions where they settle. There are currently 38 million such children. Institutional and systemic challenges often bar them from receiving an education of adequate quality, equal to that of their peers. The thesis reviews the legal and regulatory framework covering childrens’ right to education at both international and national domestic levels. It then describes the actual experience of internal migrant children attempting to access schools, and analyses the main factors barring them from the education they are entitled to. These barriers are categorised in a ‘4-A’ conceptual framework – Availability, Accessibility, Acceptability, Adaptability. The research draws on a range of secondary data, supplemented by interviews conducted with personnel engaged in education in Beijing. The main findings are that, though the legal framework of rights is generally sufficient, inadequate institutional and normative arrangements and lack of government accountability (at all levels) work together to hinder proper implementation of relevant laws and regulations. The problem is exacerbated by the institutional barrier of hukou-based enrolment and registration, and deepened even further by the current cadre and local governance arrangements, with the information asymmetry they engender. The thesis concludes that, at central, provincial and municipal levels, adequate funding for the education of migrant children must be assured, especially in the dense receiving regions. A new enrolment system is required based on a child’s current place of residence. Finally, a reform of the current civil service and cadre management systems is needed, with a move away from current growth-oriented development strategies that impose policy burdens and subordinate the children’s good to the pursuit of economic targets.

Recognition and separation of sounds played by various instruments is very useful in labeling audio files with semantic information. This is a non-trivial task requiring sound analysis, but the results can aid automatic indexing and browsing music data when searching for melodies played by user specified instruments. Melody match based on pitch detection technology has drawn much attention and a lot of MIR systems have been developed to fulfill this task. However, musical instrument recognition remains an unsolved problem in the domain. Numerous approaches on acoustic feature extraction have already been proposed for timbre recognition. Unfortunately, none of those monophonic timbre estimation algorithms can be successfully applied to polyphonic sounds, which are the more usual cases in the real music world. This has stimulated the research on multi-labeled instrument classification and new features development for content-based automatic music information retrieval. The original audio signals are the large volume of unstructured sequential values, which are not suitable for traditional data mining algorithms; while the acoustical features are sometime not sufficient for instrument recognition in polyphonic sounds because they are higher-level representatives of raw signal lacking details of original information. In order to capture the patterns which evolve on the time scale, new temporal features are introduced to supply more temporal information for the timbre recognition. We will introduce the multi-labeled classification system to estimate multiple timbre information from the polyphonic sound by classification based on acoustic features and short-term power spectrum matching. In order to achieve higher estimation rate, we introduced the hierarchically structured cascade classification system under the inspiration of the human perceptual process. This cascade classification system makes a first estimate on the higher level decision attribute, which stands for the musical instrument family. Then, the further estimation is done within that specific family range. Experiments showed better performance of a hierarchical system than the traditional flat classification method which directly estimates the instrument without higher level of family information analysis. Traditional hierarchical structures were constructed in human semantics, which are meaningful from human perspective but not appropriate for the cascade system. We introduce the new hierarchical instrument schema according to the clustering results of the acoustic features. This new schema better describes the similarity among different instruments or among different playing techniques of the same instrument. The classification results show the higher accuracy of cascade system with the new schema compared to the traditional schemas. The query answering system is built based on the cascade classifier. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]

Various scholars have interpreted P.Mich.inv.1190, a papyrus manuscript that contains a Coptic ritual formulary, as a healing or protective formulary dealing with childbirth, possibly working alongside a surgical process of caesarean section, as a ritual aid in abortion, a curse to cause bleeding, or as consisting of two distinct formularies where the first is a curse for bleeding and the latter is an erotic spell. In response to these diverse interpretations, I argue that single-sheet Coptic ritual formularies would have been used multiple times and for multiple purposes over the course of their composition, compilation, or transmission. Therefore, each different interpretation of P.Mich.inv.1190 can potentially be valid, and would all be grouped under a broad purpose of ritual bodily manipulation. This report takes up the case study of P.Mich.inv.1190’s use for healing to develop a theoretical framework of affective labor that addresses the ways in which ritual bodily manipulation would be experienced as efficacious. The formulary distributes affective labor among those involved in a ritual according to the existing social relationships between them, thereby also reinforcing the intersecting power dynamics at play. In developing this framework, I then turn back to the multiple other uses of the formulary to establish that the distribution of affective labor undergirds the efficacy of the ritual for any of its possible purposes.

This study enhances our understanding of mitochondrial transcription factor A (TFAM) and its pivotal roles in maintaining mitochondrial DNA (mtDNA) integrity through a series of investigations. First, we focused on Glutamic acid 187 (E187) in the β-elimination reaction, which is an essential step in mtDNA repair. Using kinetic analyses and comprehensive computer simulations, we demonstrated how E187 accelerates the reaction rates quantitatively, providing critical insights into the molecular mechanisms that facilitate DNA repair within mitochondria.Next, our study has demonstrated the intrinsic 5’dRp lyase activity of TFAM, observed through in vitro experiments. The activity rate is comparable with that of polymerase β, implying TFAM's vital role in the mitochondrial Base Excision Repair (BER) pathway. Such functionality is particularly significant since it indicates TFAM can reduce the accumulation of toxic DNA repair intermediates. These intermediates if unrepaired, could lead to mitochondrial dysfunction, thus highlighting the broader implications of TFAM in maintaining cellular health and preventing disease progression. Finally, we are working on developing an innovative mass spectrometry method to detect TFAM-DNA-protein complexes (DPCs) in cells. This novel method aims to provide structural insights into the ways TFAM interacts with damaged mtDNA and allow us to detect other protein candidates that are binding with AP-mtDNA under physiological condition. The development of this technique is an important step towards understanding the complex dynamics of mtDNA-protein interactions within mitochondria. Taken together, the above projects help with our understanding of TFAM's molecular interactions and regulatory roles and broaden our knowledge of mtDNA stability. By elucidating the mechanisms that protect mtDNA integrity, our research contributes to the broader scientific understanding of mitochondrial function and its impact on cellular health.

Projects account for 20%–40% of all economic activity (Schoper et al., 2018). They are the main vehicle for achieving organizational strategies (Kwak & Anbari, 2009). Despite this, the rates of project success remain low. Many researchers point to project governance as a key factor in improving project success (Crawford et al., 2008). In that light, a key focus in this thesis is the role of project sponsors in project governance, particularly their relationships with project managers and project teams by way of formal and informal governance mechanisms. However, little is understood about the interplay between two major types of governance mechanisms, formal and informal, regarded as either substitutes or complements. This lack of understanding can be attributed to two factors: (1) a lack of a holistic and dynamic perspective in developing project governance mechanisms and (2) little consideration of project sponsors’ cognitive barriers in implementing the governance mechanisms. This thesis draws on Yin-Yang and mindfulness theories to explore whether and how an appropriate balance can be established between complementary yet conflicting project governance mechanisms, with a view to project performance. Three Chinese case studies were conducted to verify the usefulness of Yin-Yang principles in guiding the interplay of formal and informal governance mechanisms and the importance of the project sponsor’s mindfulness in balancing the governance mechanisms. The case studies suggest this approach may enhance the project’s performance.

This dissertation consists of three essays in international finance. The first two essays study emerging market sovereign risk with a focus on local currency denominated sovereign bonds. The third essay examines econometric tools for robust inference in the presence of missing observations, an issue frequently encountered by researchers in international finance., Economics

Objective: I sought to determine the systolic intensification threshold, time-to-intensification and time-to-follow-up associated with the lowest risk of cardiovascular events or death in primary care patients with hypertension. Methods: A retrospective cohort study of 88,756 patients was performed. Systolic intensification threshold, time-to-intensification and time-to-follow-up were analyzed with respect to risk of acute cardiovascular event or death. The Cox model was adjusted for age, sex, smoking status, socioeconomic deprivation, history of diabetes, cardiovascular disease or CKD, Charlson Comorbidity Index, BMI, medication possession ratio, and baseline blood pressure. Results: During median follow-up of 37.4 months, 9,985 participants experienced acute cardiovascular event or death (11.3%). Systolic intensification thresholds of 130-150 mmHg were associated with no difference in risk, while higher thresholds were associated with progressively greater risk. Risk increased progressively from the lowest (0-1.4 months) to the highest quintile of time to medication intensification. The highest quintile of time to-follow-up (>2.7 months) was also associated with increased risk. Conclusions: Systolic intensification threshold higher than 150 mmHg, delays of greater than 1.4 months before medication intensification following systolic blood pressure elevation, and delays of greater than 2.7 months before blood pressure follow-up following medication intensification were associated with increased risk for acute cardiovascular events or death.

In this thesis, we first prove that under mild stochastic assumptions, work-conserving disciplines are asymptotically optimal for minimizing total completion time. As a byproduct of our analysis, we obtain a tight upper bound on the competitive ratios of work-conserving disciplines on minimizing the metric of flow time.We next study the multiple-processor multitask scheduling problem in both deterministic and stochastic models. We consider and analyze Modified Shortest Remaining Processing Time (M-SRPT) scheduling algorithm, a simple modification of SRPT, which always schedules jobs according to SRPT whenever possible, while processes tasks in an arbitrary order. The M-SRPT algorithm is proved to achieve a competitive ratio of $\Theta(\log \alpha +\beta)$ for minimizing response time, where $\alpha$ denotes the ratio between maximum job workload and minimum job workload, $\beta$ represents the ratio between maximum non-preemptive task workload and minimum job workload. In addition, the competitive ratio achieved is shown to be optimal (up to a constant factor), when there are constant number of machines. We further consider the problem under Poisson arrival and general workload distribution (i.e, M/GI/$N$ system), and show that M-SRPT achieves asymptotically optimal mean response time when the traffic intensity $\rho$ approaches $1$, if job size distribution has finite support. Beyond finite job workload, the asymptotic optimality of M-SRPT also holds for infinite job size distributions with certain probabilistic assumptions, for example, M/M/$N$ system with finite task workload.

The vigorous development of human civilization has significantly increased the energy consumption in recent years. There is a great need to use renewable energy sources to substitute the depleting traditional fossil fuels, such as crude oil, natural gas and coal. The development of low-cost and high-performance energy storage devices (ESDs) and systems have drawn great attention due to their feasibility as backup power supply and their applications in portable electronics and electric vehicles. Supercapacitors are among the most important ESDs because of their long charging-discharging cycle life, high power capability and a large operating temperature range. In this thesis, high-performance activated carbons (ACs)-based SCs have been synthesized from two biomass materials in both “bottom-up” and “top-down” patterns, including high fructose corn syrup and soybean residues, which are economic and environmental friendly. Firstly, a hydrothermal carbonization (HTC) - physical activation method is presented to synthesize activated carbons from high fructose corn syrup (HFCS). The effect of the activation time on the geometrical and porous characteristics of the ACs is investigated. The electrochemical performance of the supercapacitor cells made from AC treated at 850ºC for 4 hours are found as the best with a specific capacitance of 168 F/g at 0.2 A/g in 6 M KOH aqueous system. Secondly, a two-step HTC process followed by a physical activation to prepare activated carbons from soybean residue is presented. The effect of activation temperature on geometrical and porous characteristics of the ACs is studied. The ACs activated at 850ºC are found partly crystallized and exhibit a specific capacitance of 227 F/g at 2 mV/s. To understand the effect of mechanical deformation of the electrode materials on the electrochemical performance of electrical double-layer supercapacitors, a series of compression tests of HFCS-based ACs are further conducted in both dry and wet conditions. The nominal stiffness of the compressed ACs is calculated from the unloading curves. For both dry and wet disks the stiffness get increased with increased compression load, where the wet ones get higher stiffness than that of the dry ones. A simple model of porous materials is used to explain the increase in the stiffness of a compressed disk with the increase of pressure. Lastly, the effect of mechanical deformation on the electrochemical impedance of HFCS-based ACs is studied. When increasing the mechanical pressure from 4 to 81.5 KPa, the system resistance shows a relatively stable trend around 1 ohm, while the charge transfer resistance shows a dramatic dependence on mechanical pressure decreasing from 420 ohms to 1.5 ohms.

The first two chapters of this dissertation seek to understand how climate change affects labor market outcomes and manufacturing firms in developing country contexts. Chapter One provides worker-level evidence in Brazil on different labor market adjustment margins with respect to extreme heat shocks and the underlying transmission mechanism. Exploiting rich employer-employee matched data, I find that quarterly heat shocks lead to significant increases in the propensity of manufacturing-worker layoff through the direct labor productivity channel. A significant proportion of manufacturing workers who experienced heat-related layoffs fail to find any formal employment within 36 months. These results show that heat shocks lead to persistent negative employment effect in the formal manufacturing labor market due to failure in job transitions over the medium run. In Chapter Two, I turn the focus to manufacturing firms in Indonesia. In a heterogeneous firm model with capital-biased productivity, I incorporate temperature shocks through the direct labor productivity channel and illustrate howless productive firms decide on production and re-optimize factor intensity as temperature increases. Empirically, I match gridded daily weather data with the Indonesian firm-level industrial surveys. I find that under heat shocks, the initially less productive firms are more likely to exit, highlighting the presence of survival bias intrinsic to firm-level intensive margin analysis. Second, on the aggregate, resources reallocate from less to more productive firms within industries. Among surviving firms, we observe factor substitution from unskilled to skilled workers, and firms switching from using domestic to foreign intermediate inputs. Chapter Three investigates how global commodity price booms affect land use and forest management, and the factors that influence sustainable environmental practices of mining firms. We employ a spatial and temporal lens, by collecting proprietary data on more than 30,000 mines located around the world and matching the location of these mines to high-resolution satellite imagery. This allows a granular study of the relationship between commodity prices and loss of forest cover worldwide, as well as the spatial distribution of global mines in relation to changes in land-use patterns and local economic activities as measured by nighttime luminosity. We find a positive elasticity of forest cover loss. Mine owners from rich countries display larger disparity in the elasticity of forest cover loss when operating in low versus high income countries. Our estimates suggest that the early 2000s "commodity super-cycle" contributes to roughly 8%-20% of the observed total deforestation around mining sites and that mining-induced deforestation is not limited to the immediate surroundings of mining pits.

The ground motion parameters such as amplitude, frequency content and the duration can be affected by the local site condition and may result in amplification or de-amplification to the original bedrock motion. Shear wave velocity is an important site parameter to describe the site condition and is widely used in estimating site response, classifying sites in recent building codes and loss estimation. This dissertation is aimed at: modeling the spatial variation of shear wave velocity using geostatistical tools; improve the random field framework for estimating soil properties to account for multiple sources of data; develop finite element model to qualify the uncertainty propagation in dynamic site response; introduce the response surface concept into seismic hazard analysis and quantifying the uncertainty propagation in dynamic site response caused by the variation of shear wave velocity and design parameters. To model the spatial variation of shear wave velocity, a multiscale random field-based framework is presented and applied to map Vs30 - the time-averaged shear wave velocity in the top 30 meters of subsurface material - over extended areas. In this framework, the random field concept is employed to model the horizontal variation of shear wave velocity. Suzhou Site is selected as the research area and its measured shear wave velocity data is combined with the U.S. Geological Survey (USGS) slope-based Vs30 map for mapping the Vs30 around whole research area. Moreover, a different method of integrating multiple sources of data is used and tested based on a synthetic digital field. To quantify the uncertainty propagation in dynamic site response caused by the variation of shear wave velocity, the finite element method (FEM) is developed and combined with random field realizations of shear wave velocity profiles. A viscoelastic constitutive model is implemented in the FEM model to account for the non-linear hysteresis response of subsurface materials under cyclic loadings. The analyzed site responses, as well as the input parameters generated with Monte Carlo simulations (MCS), are then used to study the peak acceleration at site surface subjected to a given input seismic wave. Finally, the response surface method and the first order second-moment method (FOSM) are integrated into dynamic site response analysis to characterize the variation of site performance caused by spatial variation of shear wave velocity. Through illustrative examples, the effectiveness, advantage, practicability, and significance of improved random field framework and developed uncertainty propagation evaluation methodology are demonstrated.

Millions of individuals affected by disorders or injuries that cause severe motor impairments have difficulty performing compound manipulations using traditional input devices. This thesis first explores how effective various assistive technologies are for people with motor impairments. The following questions are studied: (1) What activities are performed? (2) What tools are used to support these activities? (3) What are the advantages and limitations of these tools? (4) How do users learn about and choose assistive technologies? (5) Why do users adopt or abandon certain tools? A qualitative study of fifteen people with motor impairments indicates that users have strong needs for efficient text entry and communication tools that are not met by existing technologies. To address these needs, this thesis proposes three dwell-free input methods, designed to improve the efficacy of target selection and text entry based on eye-tracking and head-tracking systems. They yield: (1) the Target Reverse Crossing selection mechanism, (2) the EyeSwipe eye-typing interface, and (3) the HGaze Typing interface. With Target Reverse Crossing, a user moves the cursor into a target and reverses over a goal to select it. This mechanism is significantly more efficient than dwell-time selection. Target Reverse Crossing is then adapted in EyeSwipe to delineate the start and end of a word that is eye-typed with a gaze path connecting the intermediate characters (as with traditional gesture typing). When compared with a dwell-based virtual keyboard, EyeSwipe affords higher text entry rates and a more comfortable interaction. Finally, HGaze Typing adds head gestures to gaze-path-based text entry to enable simple and explicit command activations. Results from a user study demonstrate that HGaze Typing has better performance and user satisfaction than a dwell-time method.

Rhodococcus rhodochrous DAP 96253, a well-known industrial bacterium, had various 1-hexene monooxygenase (1-HMO) activities when grown on YEMEA plates supplemented with eight different carbohydrates. Besides, 1-HMO exhibited different storage temperature preferences. Lactose could induce the highest 1-HMO activity in R. rhodochrous DAP 96253 while the cells showed the lowest 1-HMO activity when trehalose was the supplement. The 1-HMO activity of R. rhodochrous DAP 96253 was not maintained when stored at 37°C as well as at 4°C and 25°C. Trehalose-induced 1-HMO activity of R. rhodochrous DAP 96253 was more stable from Day 0 to Day 21 at all these three temperatures, compared with the other seven carbohydrates. Immobilization of enzymes can maintain enzyme activity longer, offer easier enzyme storage conditions and make some enzymes reusable, much research has been done in this area. In this study, R. rhodochrous DAP 96253, grown on YEMEA plates supplemented by glucose and urea, was investigated using whole bananas as the inducer of 1-HMO activity and different immobilization methods to maintain this enzyme activity. It was shown that calcium-alginate polyvinyl alcohol (PVA) beads could maintain 1-HMO activity of R. rhodochrous DAP 96253 more stable than calcium-alginate beads. Whole bananas exhibited very obvious effects of inducing 1-HMO activity of R. rhodochrous DAP 96253. A number of recent studies have clearly demonstrated that induced cells of R. rhodochrous DAP 96253 can prolong the shelf-life of post-harvested fruits. With USDA estimates of 40% of all harvested produce in the US not being consumed because of loss of quality, the ability to extend the period of ripeness of produce has great potential to improve the quality of nutrition. Modification or degradation of those signals (primary and secondary) associated with ripening in fruit or the perception of those signals represents a potential mode of action for delayed ripening by induced cells of R. rhodochrous DAP 96253. Ethylene and cyanide are the two primary signals in ripening. In this study, the role of 1-HMO from induced cells was investigated by time-course experiments focusing on 1-HMO activity and stability. In addition, fruit volatile organic compounds (VOCs) were detected and compared by GC-FID and GC/MS over the course of fruit ripening. The results show a correlation between 1-HMO activity and stability in delayed fruit ripening. It was further demonstrated that the presence of secondary signal fruit VOCs enhanced 1-HMO activity. Aromatic profiles of treated fruits, by GC-FID and GC/MS, show a consistent picture of VOCs associated with earlier fruit ripening stages.