VictorJuiz/thesis huggingface dataset:
Expanding the Capabilities of Constraint-based Metabolic Models for Biotechnology Purposes
Keywords: metabolism
modeling
optimization

Over the past decade, the constraint-based approach to metabolic modeling has become an important tool for understanding and controlling biology. Unfortunately, the application of this novel approach to systems biology in biotechnology has been limited by three significant technical issues: existing metabolic modeling methods cannot completely model the overflow metabolism, cannot model the metabolism of microbial communities, and cannot design strains optimized for productivity and titer. Three computational methods – the Flux Balance Analysis with Membrane Economics (FBAME) method, the Dynamic Multi-species Metabolic Modeling (DyMMM) framework, and the Dynamic Strain Scanning Optimization (DySScO) strategy – have been developed to resolve these issues respectively. First, the FBAME method, which adopts the membrane occupancy limitation hypothesis, was used to explain and predict the phenomenon of overflow metabolism, an important metabolic phenomenon in industrial fermentation, in Escherichia coli. Then, the DyMMM framework was used to investigate the community metabolism during uranium bioremediation, and demonstrated that the simultaneous addition of acetate and Fe(III) may be a theoretically viable uranium bioremediation strategy. Lastly, the DySScO strategy, which combines the DyMMM framework with existing strain design algorithms, was used to design commodity-chemical producing E. coli optimized for a balanced product yield, titer, and volumetric productivity. These novel computational methods allow for broader applications of constraint-based metabolic models in biotechnology settings.
The Evolution of the Hellenistic Polis: Case Studies in Politics and Political Culture
Keywords: History
Epigraphy
Hellenistic
City-State
Polis
Classics
Greek History
Ancient History
Sestos
Kos
Dyme
Priene

The following dissertation sets out to explore the evolution of a handful of civic institutions in the Hellenistic era. The first chapter focuses on the institution of the ephebeia and citizen-training. It centres on three documents: the gymnasiarchic law of Beroea (I. Beroeae 1 [ca. 167 BCE]), the oath of the agelaoi of Dreros (I. Cret. 1.9.1 [ca. 200 BCE]) and the honorary decree for Menas of Sestos. It argues first that citizen training programs of the Hellenistic period had higher rates of participation than the Athenian evidence seems to suggest, and second that three virtues of gymnastic training, euexia, eutaxia and philoponia, were also political and social virtues. The second chapter focuses on Zosimos of Priene (I. Priene 113 [ca. 100 BCE]) and the connection between his two most important reforms: instituting a system of duplicate record-keeping and funding rhetorical training for ephebes. It argues that the speeches of envoys and ambassadors (presbeutic rhetoric) constituted the dominant mode of Hellenistic rhetoric; within that genre, arguments based on history and on official records were considered the most effective. The third chapter focuses on Fabius' letter to Dyme (Syll.3 684 [144 BCE]). It argues that the destruction of Dyme's public archives was not part of a 'socialist' revolution, but rather was a means of rejecting changes to the citizen body forced on the city by Rome. The final chapter turns to the island of Kos. It explores Diokles' decree (IG XII.4.1 75 [ca. 200 BCE]) as an example of how the balance between self-interest and communal interests were negotiated.
Microfluidic Studies of Biological and Chemical Processes
Keywords: Microfluidic
Cell Encapsulation
Multi-modal Analysis
Microenvironments
Biopolymers
High-throughput

This thesis describes the development of microfluidic (MF) platforms for the study of biological and chemical processes. In particular the thesis is divided into two distinct parts: (i) development of a MF methodology to generate tunable cell-laden microenvironments for detailed studies of cell behavior, and (ii) the design and fabrication of MF reactors for studies of chemical reactions. First, this thesis presented the generation of biopolymer microenvironments for cell studies. In the first project we demonstrated a high-throughput MF system for generating cell-laden agarose microgels with a controllable ratio of two different types of cells. The MF co-encapsulation system was shown to be a robust method for identifying autocrine and/or paracrine dependence of specific cell subpopulations. In the second project we studied the effect of the mechanical properties on the behavior of acute myeloid leukemia (AML2) cancer cells. Cell-laden macroscopic agarose gels were prepared at varying agarose concentrations. A modest range of the elastic modulus of the agarose gels were achieved, ranging from 0.62 kPa to 20.21 kPa at room temperature. We observed a pronounced decrease in cell proliferation in stiffer gels when compared to the gels with lower elastic moduli. The second part of the thesis focuses on the development of MF platforms for studying chemical reactions. In the third project presented in this thesis, we exploited the temperature dependent solubility of CO2 in order to: (i) study the temperature mediated CO2 transfer between the gas and the various liquid phases on short time scales, and (ii) to generate bubbles with a dense layer of colloid particles (armoured bubbles). The fourth project involved the fabrication of a multi-modal MF device with integrated analytical probes. The MF device comprised a pH, temperature, and ATR-FTIR probes for in-situ analysis of chemical reactions in real-time. Furthermore, the MF reactor featured a temperature controlled feedback system capable of maintaining on-chip temperatures at flow rates up to 50 mL/hr.
Dynamic Structures of Protein Interaction Networks Predict Complex Phenotypes of Biological Systems
Keywords: network biology
cancer
systems biology

This work focuses on the use of network graph theory in biological networks. I explore how network graph theory informs our understanding of biological networks such as protein interaction networks. I show that the human protein interaction network forms dynamic, modular structures that organize cell signaling pathways into higher order units. The misregulation of the dynamic, modular structure of the protein interaction network in breast cancer tumours is associated with outcome of the disease, suggesting that the altered structure of the protein interaction network is directly related to the phenotype of the tumour. I also demonstrate that the human protein interaction network is fractal in nature and thus forms self-similar structures within the network. The fractal skeletons of the protein interaction network contain critical information and therefore can be used alone in determining the phenotype of breast cancer tumours by examing the disruption of dynamic network structures. The self-similar fractal backbones deconvolve the protein interaction network into layers of independent function, resulting in improved description of breast cancer outcome using the dynamic network modularity algorithm. Finally, I discuss how the discoveries and technologies described within can be improved and how these discoveries can lead to a network based modality of medicine.
Supply Chain Design - Competitive and Financial Perspectives
Keywords: Newsvendor
Game Theory
Location Problem
Risk Preference
Capital Structure
Executive Incentives

In this thesis we study problems in the context of inventory control and facility location. In chapter 2 we study the competition among risk averse newsvendors. We showed that the well-known result for the single-product monopoly firm, which states higher risk aversion causes the firm to reduce its order quantity, cease to hold under the competition. We concluded that the higher risk aversion does not necessarily cause both firms to reduce their order quantity. We showed that the impact of risk aversion on equilibrium quantities is a trade-off between two effects: (a) Own risk aversion increment which causes that the firm reduces its order quantity and (b) Effect of spillover demand from competitor which causes that the firm increases its order quantity. We also show which firm raises its order quantity as both firms become more risk averse depending on their attributes: profitability ratio (overstocking to understocking ratio), initial risk aversion level and demand characteristic (distribution and substitution). In Chapter 3, we study how the operational decisions of a firm's manager depend on her own incentives, the capital structure, and financial decisions in the context of the newsvendor framework. We showed that in contrast to common practices, tying the manager's compensation to stock price (equity value) may not be optimal for shareholders. We propose to tie the managers' compensation to the firm value or include a debt-like instrument in the compensation package to mitigate the risk taking behaviour of the managers. We also show how the board of directors can modify the compensation structure based on the state of the economy and publicly available information about company's demand. In Chapter 4, we study the effect of risk attitude of decision makers on well-known location problems with uncertain demand. In addition to providing mathematical formulations for those problems, we also discussed how we can solve these problems using linearization techniques. We also shed some light on the importance of considering the volatility and correlation structure. Furthermore, we apply a Bayesian updating method, a useful tool for updating the probability distribution to incorporate the consultants' view about uncertain factors in location problems.
Psalms Unbound: Ancient Concepts of Textual Tradition in 11QPsalms-a and Related Texts
Keywords: Dead Sea Scrolls
Psalms
Book History
Early Judaism

This dissertation investigates ways in which early Jewish communities conceptualized the production and collection of writing. Through a study of 11QPsalms-a, the Qumran Psalms Scroll, it shows how modern book culture (shaped by the canon, codex, print, authorial copyright, and scholarly editing) has distorted our understanding of ancient texts and fostered anachronistic questions about their creation and reception. Taking seriously what early Jewish texts have to say about their own writtenness and building upon earlier scholarship on scriptural multiformity, the dissertation also uses theoretical insights from the field of Book History to study the identity, assembly, and literary context of the Psalms Scroll as an example of the ancient textual imagination. Physical and discursive evidence suggest that no concept of a “Book of Psalms” existed as a coherent entity in the ancient Jewish imagination, but that psalms collections were conceptualized and created in looser, unbounded ways. New metaphors made possible by electronic text, which likewise cannot be constrained into the categories of print book culture, can encourage new ways of imagining ancient concepts of fluid textuality as well. After a study of the status and compilation of the Psalms Scroll (Ch. 1-2), the dissertation engages the question of Davidic authorship (Ch. 3). David was not imagined as the author of a particular psalms collection, but as the inaugurator of a variety of liturgical traditions. The identity between an individual figure and a specific text should be unbound in favour of a looser relationship, allowing for the continuing growth of traditions inspired by the figure. Chapters 4 and 5 present a reading of the Psalms Scroll and Davidic lore alongside two other traditions: Ben Sira and angelic ascent literature. Both possess literary links with the Psalms Scroll, but also shed light on the ways in which ancient communities imagined writing and understood their own relationship to their texts. Thus, reading across canonical and generic boundaries embeds psalms traditions in a richer context of reception and provides a fuller picture of the ancient textual imagination. The conclusion makes a comparative gesture toward the Nachleben of psalms collecting in Syriac Christianity.
Welfare Reforms in Post-Soviet States: A Comparison of Social Benefits Reform in Russia and Kazakhstan
Keywords: welfare reform
Russia
policy implementation
Kazakhstan

Concerned with the question of why governments display varying degrees of success in implementing social reforms, (judged by their ability to arrive at coherent policy outcomes), my dissertation aims to identify the most important factors responsible for the stagnation of social benefits reform in Russia, as opposed to its successful implementation in Kazakhstan. Given their comparable Soviet political and economic characteristics in the immediate aftermath of Communism’s disintegration, why did the implementation of social benefits reform succeed in Kazakhstan, but largely fail in Russia? I argue that although several political and institutional factors did, to a certain degree, influence the course of social benefits reform in these two countries, their success or failure was ultimately determined by the capacity of key state actors to frame the problem and form an effective policy coalition that could further the reform agenda despite various political and institutional obstacles and socioeconomic challenges. In the case of Kazakhstan, the successful implementation of the social benefits reform was a result of a bold and skilful endeavour by Kazakhstani authorities, who used the existing conditions to justify the reform initiative and achieve the reform’s original objectives. By contrast, in Russia, the failure to effectively restructure the old Soviet social benefits system was rooted largely in the political instability of the Yeltsin era, and a lack of commitment to the reforms on the part of key political actors. And when the reform was finally launched, its ill-considered policies and the government’s failure to form the broad coalition and effectively frame the problem led to public protests and subsequent reform stagnation. Based on in-depth fieldwork conducted in Russia and Kazakhstan in 2006 and 2008, my study enriches the literature on the transformation of post-communist welfare regimes, and contributes important insights to the central question in the literature on public policy, that is, when, why and how policies change. It also enhances our understanding of political and public policy processes in transitional and competitive authoritarian contexts.
Type III Secreted Effectors as Molecular Probes of Eukaryotic Systems
Keywords: host-pathogen interaction
type III effectors

Successful bacterial pathogens manipulate crucial intracellular host processes as a virulence strategy. One particular potent mechanism utilized by bacterial phytopathogens is to inject virulence factors (effectors) directly into the host cell. While many effectors have been identified and shown to suppress plant immune responses, very few have well-characterized enzymatic activities or host targets. To overcome the challenges of functional analysis of effectors, I designed two heterologous screens to characterize effector proteins of the bacterial phytopathogen Pseudomonas syringae. Specifically, my objective was to identify those P. syringae effectors that target evolutionarily conserved host proteins or processes and to subsequently elucidate the molecular mechanisms of these effectors. The first heterologous screen that I performed was to utilize tandem-affinity-purification (TAP)-tagged effectors in human cells to identify potential interacting host proteins. The second heterologous screen iii utilized a high-throughput genomics approach in yeast, known as the pathogenic genetic array (PGA), to characterize P. syringae effectors. Using the first heterologous approach, I have identified HopZ1a as the first bacterial phytopathogen effector that binds tubulin. I have shown that HopZ1a is an acetyltransferase activated by the eukaryotic co-factor, phytic acid. In vitro, activated HopZ1a acetylates itself and tubulin. In Arabidopsis thaliana, activated HopZ1a causes microtubule destruction, disrupts the secretory pathway and suppresses cell wall-mediated defense. The acetyltransferase activity of HopZ1a is dependent on the conserved catalytic cysteine residue (C216) and a conserved lysine residue (K289). Using the second heterologous screen in yeast, I have shown that HopZ1a may target the mitogen-activated protein kinase (MAPK) signaling cascades. Together, my work has identified novel eukaryotic targets and elucidated the virulence functions of HopZ1a.
Plato on Pleasure, Intelligence and the Human Good: An Interpretation of the Philebus
Keywords: Plato
Philebus
Timaeus
pleasure
intelligence
knowledge
the human good
the good life
moral psychology
cognition
perception
sensation
intentionality
consciousness
aisthēsis
phronēsis
nous
hēdonē
health
disease
animals
gods
soul
body
desire
expectation
memory
recollection
false pleasure
pain

The Philebus is devoted to the question what constitutes the good for a human being. Although Socrates initially favors a life of pure intelligence against the hedonist’s life of pure pleasure, he quickly concedes that some pleasures actually enhance the life of intelligence. In order to determine which pleasures deserve a place in the best life, Socrates undertakes a lengthy investigation into the nature of pleasure. Commentators have long been frustrated in their attempt to uncover a single, unified account that explains in a plausible way the extraordinary variety of pleasures analyzed in the dialogue. I argue that this search for a generic account of pleasure is misguided, because one of the main purposes of Socrates’ division of pleasure is to expose its essentially heterogeneous nature. Pleasures can be bodily or psychic, pure or mixed with pain, truth apt or not, healthy or diseased, and inherently measured or unmeasured, and there are no essential properties which all of these diverse phenomena share. The inclusion of some pleasures in the final ranking of the goods at the end of the Philebus represents a dramatic shift in Plato’s attitude towards certain pleasures, and so it is not surprising that many scholars misinterpret the force of this conclusion. Even in the Republic where the pleasures of reason are favorably compared to the pleasures of spirit and appetite, intellectual pleasures are judged to be more pleasant and real than other pleasures, but they are nowhere judged to be better or praised as genuine goods. In the Philebus, not only are some pleasures unambiguously ranked among the highest goods, but Socrates gives no indication that these pleasures are good only in some qualified or extrinsic way. Instead, certain pleasures make their own positive contribution to the goodness of the best human life, making the mixed life more valuable and choiceworthy than the unmixed life of intelligence.
An Integrated Two-stage Innovation Planning Model with Market Segmented Learning and Network Dynamics
Keywords: Product Planning
Diffusion
Discrete Choice
Bayesian Learning

Innovation diffusion models have been studied extensively to forecast and explain the adoption process for new products or services. These models are often formulated using one of two approaches: The first, and most common is a macro-level approach that aggregates much of the market behaviour. An advantage of this method is that forecasts and other analyses may be performed with the necessity of estimating few parameters. The second is a micro-level approach that aims to utilize microeconomic information pertaining to the potential market and the innovation. The advantage of this methodology is that analyses allow for a direct understanding of how potential customers view the innovation. Nevertheless, when individuals are making adoption decisions, the reality of the situation is that the process consists of at least two stages: First, a potential adopter must become aware of the innovation; and second the aware individual must decide to adopt. Researchers, have studied multi-stage diffusion processes in the past, however a majority of these works employ a macro-level approach to model market flows. As a result, a direct understanding of how individuals value the innovation is lacking, making it impossible to utilize this information to model realistic word-of-mouth behaviour and other network dynamics. Thus, we propose a two-stage integrated model that utilizes the benefits of both the macro- and micro-level approaches. In the first stage, potential customers become aware of the innovation, which requires no decision making by the individual. As a result, we employ a macro-level diffusion process to describe the first stage. However, in the second stage potential customers decide whether to adopt the innovation or not, and we utilize a micro-level methodology to model this. We further extend the application to include forward looking behaviour, heterogeneous adopters and segmented Bayesian learning, and utilize the adopter's satisfaction levels to describe biasing and word-of-mouth behaviour. We apply the proposed model to Canadian colour-TV data, and cross-validation results suggest that the new model has excellent predictive capabilities. We also apply the two-stage model to early U.S. hybrid-electric vehicle data and results provide insightful managerial observations.
The Influence of Synthesis Temperature on the Crystallographic and Luminescent Properties of NaYF4-based Upconverters and their Application to Amorphous Silicon Photovoltaics
Keywords: Upconversion
Photovoltaics
Solar
Rare Earth

There are several factors which conspire to limit the efficiency of solar cells. One of these is the fact that a solar cell is unable to absorb photons of energy less than the band gap of the semiconductor from which it is made; in the case of some high-band gap materials such as amorphous silicon – the model system used in this study – this can mean that as much as 50% of the solar spectrum is unusable. Upconversion phosphors – materials which can, by way of two or more successive photon absorptions, convert low energy (typically near infrared) light into high energy (typically visible) light – offer a potential solution to this problem as they can be used to convert light, which would otherwise be useless to the cell, into light which can be used for power generation. In this thesis we work towards the application of NaYF4-based upconverters to enhanced efficiency amorphous silicon (a-Si) photovoltaic power generation. We begin by synthesizing these upconverters at a range of temperatures and studying the crystallographic and spectroscopic properties of the resulting materials, elucidating heretofore undocumented trends in their luminescence and crystallography, including the effect of synthesis temperature on upconversion intensity, crystallite size, and lattice parameter. We also investigate the emission quantum yield of these materials, beginning with an in depth discussion and investigation of two methods for recording absolute quantum yields. We demonstrate that the quantum yields of the materials may vary by a factor of over 100, depending on the synthesis conditions. After we have fully characterized these properties we turn our attention to the application of these materials to amorphous silicon solar cells, for which we provide a proof of concept by demonstrating the effect of upconversion luminescence on the photoconductance of an a-Si film. We conclude by developing a roadmap for future improvements in the field.