VictorJuiz/thesis huggingface dataset:
The Ambiguous Greek in Old French and Middle English Literature

This dissertation investigates how the Greeks of the Trojan War and Alexander the Great are presented in Old French and Middle English literature. These ancient Greeks are depicted ambiguously: they share some of the characteristics of Jews and Saracens as they are portrayed in medieval literature. The thesis begins with an overview of the frameworks used to define ancient Greek identity. These include the philosophical heritage Greece left to the medieval West; the framework of Jewish identity, encompassing “variable characterization” and the hermeneutics of supersession; and the historical template, seen through the Orosian paradigm of translatio imperii and the Trojan foundation myth. The first chapter examines the Roman de Troie of Benoît de Sainte-Maure. The Greeks of the Trojan War are noble and valorous, but through their gift of the Trojan horse and sack of Troy, they display the treachery associated with post-Incarnation Jews and the cruelty and violence associated with Saracens. Due to the myth that the Trojans founded the Roman people, through their siege of Troy, the Greeks seem like the movers of imperium, the authority to rule, from Troy to Rome, which will eventually become a Christian empire. In the second chapter, I turn to the depiction of Alexander in Thomas of Kent’s Roman de toute chevalerie and the Middle English Wars of Alexander. In the Roman de toute chevalerie, Alexander is ambiguous: he is chivalrous, learned, and even a proto-Christian, though he himself assumes some typical Saracen characteristics. Alexander participates in translatio imperii, holding the right to rule in its Orosian succession and providing a model of empire to Rome. The Wars of Alexander witnesses the changes wrought to Alexander’s depiction in the fourteenth century due to revised views of chivalry, eschatology and crusade. The third chapter investigates the depiction of the Greek Diomede in Chaucer’s Troilus and Criseyde, a depiction informed by classical ideas and Chaucer’s depictions of Jews and Saracens in his other works. Diomede is both treacherous and cruel, seen in his seduction of Criseyde, rather than in battle. The ending of the tale posits a proto-Christian identity for Troilus and the Trojans, and suggests that Diomede participates in the supersession of the Greeks by the Trojans. Greeks function as movers of imperium, and are necessary for the beginnings of Christian empire.

Keywords: medieval literature
Middle English
alterity
ancient Greeks
Saracens
Old French
Jews
Advisor: Akbari, Suzanne Conklin
A Passive Mid-infrared Sensor to Measure Real-time Particle Emissivity and Gas Temperature in Coal-fired Boilers and Steelmaking Furnaces

A novel technique for measuring gas temperature and spectral particle emissivity in high-temperature gas-particle streams is presented. The main application of this optical sensor is to improve the process control of batch unit operations, such as steelmaking furnaces. The spectral emission profile of CO and CO2 and the continuous particle emission in the 3.5 to 5 μm wavelength region was recorded and analyzed in real time with a low-resolution passive sensor. The sensor consisted of light collecting optics, a dispersion element (grating spectrometer) and a 64-pixel pyroelectric array. Wavelength and radiance calibrations were performed. The temperature of the gas-particle medium (Tg+p) followed from the least-squares minimization of the difference between the measured radiance in the 4.56-4.7 μm region –which saturates due to the large CO2 concentrations and path lengths in industrial furnaces– and the corresponding blackbody radiance. Particle emissivity (εp) was calculated at 3.95 μm from an asymptotic approximation of the Radiative Transfer Equation that yields the emerging radiance from a semi-infinite particle cloud. The major source of error in the magnitude of Tg+p and εp could come from particle scattering. Through the method of embedded invariance an expression was developed to estimate the lowering effect of particle size and volume fraction on the saturation of the 4.56-4.7 μm CO2 emission region. An iterative procedure for correcting the values of the gas-particle temperature and particle emissivity was applied to the datasets from the two industrial tests. Results from the measurement campaigns with the infrared sensor prototype at two full-scale furnaces are presented. A proof-of-concept test at a coal-fired boiler for electricity production was followed by more extensive measurements at a Basic Oxygen Furnace (BOF) for steelmaking. The second test provided temperature and particle emissivity profiles for eight heats, which highlighted the simplicity of the technique in obtaining in-situ measurements for modeling studies. Through the analysis of the particle emissivity profile in the BOF and the definition of a new variable –the minimum carbon time– a novel end-point strategy to stop the injection of high-purity oxygen during low-carbon heats in BOF converters was proposed.

Keywords: spectral particle emissivity
off-gas temperature
combustion diagnostics
mid-infrared emission spectroscopy
pyroelectric detector
optically thick assumption
gas-particle medium
coal-fired boiler
embedded invariance
particle scattering
Basic Oxygen Furnace (BOF)
oxygen lance end-point
steel composition and temperature
first turndown properties
remote sensing
asymptotic approximation of the Radiative Transfer Equation
Advisor: Thomson, Murray J.
Endothelial Injury In Cardiac Transplantation: The Role Of Endothelin Antagonism And Protein Kinases

BACKGROUND: Endothelial dysfunction is a principal player in the development of allograft vasculopathy and allograft failure. The hallmark of endothelial dysfunction is impaired nitric oxide bioavailability. Recent evidence implicates endothelin-1 as an integral component of endothelial dysfunction. Immunosuppressive drugs have also been associated with the development of graft vasculopathy. We speculated that endothelin-1 results in endothelial dysfunction by impairing nitric oxide homeostasis and is a player in hypoxia and reperfusion induced vasomotor injury. In addition, we hypothesized that endothelin-1 antagonism with bosentan will limit hypoxia and reperfusion injury and prevent immunosuppressive drug injury. METHODS: We utilized human saphenous vein endothelial cells to evaluate the effects of endothelin-1, hypoxia and reperfusion on endothelial function, protein kinase modulation and cell survival. We also employed a rodent model of chronic drug therapy to assess the effect of cyclosporine and rapamycin treatment on vasomotor function. We investigated the role of nitric oxide augmentation and bosentan in preventing hypoxia and reperfusion injury and in limiting immunosuppressive drug induced vasomotor dysfunction. RESULTS: Elevated endothelin-1 levels resulted in impaired nitric oxide release and endothelial function. The effects of endothelin-1 as well as hypoxia and reperfusion were mediated by altered protein kinase B and protein kinase C activity resulting in endothelial dysfunction. We revealed that endothelin-1 is a key player in hypoxia and reperfusion induced endothelial injury. The immunosuppressive drug cyclosporine induced vasomotor dysfunction while rapamycin preserved vessel homeostasis. Vasomotor dysfunction was characterized by impaired nitric oxide and endothelin-1 homeostasis. Bosentan limited the deleterious effects of endothelin-1, hypoxic injury, reperfusion injury and cyclosporine induced vasomotor impairment. CONCLUSIONS: Our study revealed that endothelin-1 exposure as well as hypoxia and reperfusion results in endothelial dysfunction by altering specific protein kinase C isoform activities and inhibiting protein kinase B. Cyclosporine induced vasomotor dysfunction was mediated by altered nitric oxide and endothelin-1 homeostasis while rapamycin was endothelial protective. Bosentan proved to be an effective therapy at preventing endothelin-1, hypoxia and reperfusion and cyclosporine induced endothelial dysfunction. Protein kinase C modulation as well as bosentan may prove to be NOVEL therapies to prevent endothelial injury during cardiac transplantation.

Keywords: Endothelin-1
Protein Kinase
Advisor: Rao, Vivek
Retrovirus-mediated Gene Therapy For Farber Disease

Farber disease is a rare lysosomal storage disease (LSD) caused by a deficiency of acid ceramidase (AC). Patients show a classic triad of symptoms including subcutaneous granulomas, laryngeal involvement and painful swollen joints. The most common and severe form has neurological manifestations and patients typically die by the age of two. Current treatment consists of symptomatic supportive care and allogeneic bone marrow transplantation (BMT). However, BMT has shown limited success. Gene therapy has previously been shown to be a promising treatment strategy for monogenetic diseases and has the potential to treat the underlying cause of the disease. Presented here is the first report of in vivo testing of retrovirus-mediated gene therapy strategies for the treatment of Farber disease. Retroviral vectors were engineered to overexpress AC and a cell surface marker, human CD25. Transduction with these viral vectors corrected the enzymatic defect in Farber patient cells and in vivo administration of the lentiviral vector led to long-term expression of the marking transgene as well as increased AC expression in the liver. To determine the effect of over-expression of AC, human CD34+ cells were transduced and transplanted into NOD/SCID animals. It was found that transgene-expressing cells could reconstitute the host. To address the neurological manifestations of Farber disease, vascular endothelial growth factor (VEGF) was investigated as an agent to transiently open the blood brain barrier for entry of lentivirus. It was found that in addition to increasing the amount of therapeutic virus in the brain, VEGF treatment also increased transduction in other organs. Further, to address the concerns of insertional mutagenesis associated with using integrating vectors, an immunotoxin-based strategy was developed as a safety system to clear transduced cells. It was found that a CD25-targeted immunotoxin could eliminate both transduced hematopoietic cells as well as tumor cells over-expressing CD25. This strategy can be employed following gene therapy should an unwanted proliferative event occur. Together, these studies represent considerable advances towards the development of a cure for Farber disease, demonstrating both therapeutic potential and also containing a built-in safety system.

Keywords: Gene Therapy
Lysosomal Storage Disease
Farber Disease
Retrovirus
Advisor: Medin, Jeffrey A.
Asymptotic Optimization of Risk Measures

Value-at-Risk (VaR ) is an industrial standard for monitoring market risk in an investment portfolio. It measures potential osses within a given confidence level. VaR was first used by major financial institutions in the early 1990’s, and widely developed after the release of J.P. Morgan’s Riskmetrics Technical Document in 1996. The efficient calculation, implementation, interpretation and optimization of VaR are a challenge in the practice of risk management when the number of market factors in the portfolio is high. In this thesis, we are concerned with the quadratic analytical estimation of VaR and we present a methodology for an approximation to VaR that is based on the principal components of a sensitivity-adjusted covariance matrix. The result is an explicit expression in terms of portfolio deltas, gammas, and the mean and covariance matrix. It can be viewed as a non-linear extension of the linear model given by the delta-normal-VaR of RiskMetrics, a standard calculation for the risk in the financial sector. We obtain an asymptotic expansion for VaR in the limit when the confidence level approaches 1 and precise estimates of the reminder. We then optimize the approximated VaR with respect to the gradient or delta of the portfolio, a quantity which can be changed by trading the underlying assets (stocks), without entering into any derivative transactions. This analysis provides an optimal trading strategy of the portfolio that minimizes the risk.

Keywords: optimization
Value-at-Risk
Advisor: Sulem, Catherine
Cellular Mechanisms of the Systemic Inflammatory Response Following Resuscitated Hemorrhagic Shock: The Role of Reactive Oxygen Species and Toll-like Receptor 4

Acute Respiratory Distress Syndrome (ARDS) following hemorrhagic shock/resuscitation (S/R) is an important contributor to late morbidity and mortality in trauma patients. S/R promotes ARDS by inducing oxidative stress that primes cells of the innate immune system for excessive responsiveness to small inflammatory stimuli, termed the “twohit” hypothesis. Activated alveolar macrophages (AM) play a central role and when recovered from S/R animals exhibit an exaggerated responsiveness to lipopolysaccharide (LPS) with increased activation of the proinflammatory transcription factor NF-κB, and augmented expression of cytokines. LPS triggers AM signalling through Toll like receptor 4 (TLR4), which resides in plasma membrane lipid rafts. The objective of this work is to define cellular mechanisms of macrophage priming by oxidative stress following shock resuscitation. The main hypothesis investigated is that altered cellular distribution of TLR4 can lead to macrophage priming and antioxidant resuscitation strategies can diminish these effects. AM of rodents, exposed in vivo to oxidant stress following S/R, increase their surface levels of TLR4, which in turn results in augmented NF-κB translocation in response to small doses of LPS. Furthermore, in vitro H2O2 treatment of RAW 264.7 macrophages results in similar TLR4 surface translocation. Depletion of intracellular calcium, disruption of the cytoskeleton or inhibition of the Src kinases prevents the H2O2-induced TLR4 translocation, suggesting the involvement of receptor exocytosis. Further, fluorescent resonance energy iii transfer between TLR4 and lipid rafts as well as biochemical raft analysis demonstrated that oxidative stress redistributes TLR4 to surface lipid rafts. Preventing the oxidant-induced movement of TLR4 to lipid rafts using methyl-ß-cyclodextrin precluded the increased responsiveness of cells to LPS after H2O2 treatment. Further, AM priming by oxidative stress can be diminished by early exposure to resuscitation regimens with direct or indirect systemic antioxidant effects, such as 25% albumin, N-acetylcysteine and hypertonic saline. Hyperosmolarity was found to modulate AM TLR4 gene and protein expression. Collectively, these studies suggest a novel mechanism whereby oxidative stress might prime the responsiveness of cells of the innate immune system. Targeting the TLR4 signalling pathway early during shock resuscitation may represent an anti-inflammatory strategy able to ameliorate late morbidity and mortality following S/R.

Keywords: TLR4 Macrophage Trauma Shock Resuscitation Lipopolysaccharide ARDS MODS SIRS
Advisor: Rotstein, Ori D.
The Development of an Adaptable Surface Modification Architecture for Microfluidic Applications

A framework to compartmentalize microfluidic surfaces was developed. Substrates are separated from surface modifying agents with an intermediate binding layer (IBL). The IBL is comprised of two compounds which bind together using a non-covalent interaction; a host compound is immobilized on the substrate, and a guest compound is conjugated to the surface modifying agent. The primary benefit of the IBL architecture is adaptability: substrates and surface compounds become modular components with standard connectors. Beta-Cyclodextrin (BCD) and adamantane (AD) were selected as the model immobilized host and conjugated guest, respectively. A quartz crystal microbalance (QCM) was assembled and developed to study the BCD/AD complexation interaction. Kinetic, thermodynamic, and Langmuir isotherm data were reported for AD-derivatives binding with immobilized BCD. QCM was also used to investigate neutravidin (NA) binding onto AD-PEG and AD-PEG-biotin coatings immobilized to t-BCD surfaces. QCM was an effective platform to validate the use of BCD/AD as the IBL interaction prior to microfluidic implementation. The BCD/AD IBL was successfully demonstrated in a microfluidic environment. Microfluidic devices were fabricated using the soft-lithographic technique. Adapted surface modifications were visualized using fluorescein isothiocyanate (FITC) probes within the microfluidic device and detected using confocal laser scanning microscopy (CLSM). Surface modifications were applied to demonstrate the fundamental functions of surface passivation, specific binding, and visualization using the IBL architecture. Consistent with QCM data, AD-PEG passivated the surface and AD-PEG-biotin specifically bound NA to the BCD surface. Thus, an adaptable surface modification architecture for microfluidic applications was developed and demonstrated.

Keywords: surface modification
microfluidic
adaptable architecture
quartz crystal microbalance
Advisor: Cheng, Yu-Ling
Design and Analysis of Sequential Clinical Trials using a Markov Chain Transition Rate Model with Conditional Power

Background: There are a plethora of potential statistical designs which can be used to evaluate efficacy of a novel cancer treatment in the phase II clinical trial setting. Unfortunately, there is no consensus as to which design one should prefer, nor even which definition of efficacy should be used and the primary endpoint conclusion can vary depending on which design is chosen. It would be useful if an all-encompassing methodology was possible which could evaluate all the different designs simultaneously and allow investigators an understanding of the trial results under the varying scenarios. Methods: Finite Markov chain imbedding is a method which can be used in the setting of phase II oncology clinical trials but never previously evaluated in this scenario. Simple variations to the transition matrix or end-state probability definitions can be performed which allow for evaluation of multiple designs and endpoints for a single trial. A computer program is written in R which allows for computation of p-values and conditional power, two common statistical measures used for evaluation of trial results. A simulation study is performed on data arising from an actual phase II clinical trial performed recently in which the study conclusion regarding the efficacy of the potential treatment was debatable. Results: Finite Markov chain imbedding is shown to be useful for evaluating phase II oncology clinical trial results. The R code written for evaluating the simulation study is demonstrated to be fast and useful for investigating different trial designs. Further detail regarding the clinical trial results are presented, including the potential prolongation of stable disease of the treatment, which is a potentially useful marker of efficacy for this cytostatic agent. Conclusions: This novel methodology may prove to be an useful investigative technique for the evaluation of phase II oncology clinical trial data. Future studies which have disputable conclusions might become less controversial with the aid of finite Markov chain imbedding and the possible multiple evaluations which is now viable. Better understanding of activity for a given treatment might expedite the drug development process or help distinguish active from inactive treatments

Keywords: Markov chain
clinical trial
conditional power
phase II
Advisor: Lou, W. Y. Wendy
Cell Targeted Ribosome Inactivating Proteins Derived from Protein Combinatorial Libraries

Combinatorial protein libraries based on a protein template offer a vast potential for deriving protein variants harboring new receptor specificity while retaining other tem-plate functions to serve as library search-engines, cell-routing sequences and therapeutic domains. This concept was tested with the design and synthesis of protein libraries where short random peptide motifs were embedded directly within the catalytic A subunit of the bacterial ribosome-inactivating protein (RIP) known as Shiga-like toxin 1 (SLT-1). More precisely, a seven amino acid peptide epitope (PDTRPAP) was inserted between residues 245-246 of its A subunit (SLT-1APDTRPAP) and shown to preserve catalytic function while exposing the epitope. SLT-1 A chain libraries harboring tripep-tide and heptapeptide random elements were subsequently constructed, screened and shown to express more than 90% of expected cytotoxic A chain variants. Finally, more than 9,000 purified SLT-1 A chain variants were screened using their ribosome-inactivating function in a cell-based assay to identify mutants that are able to kill human melanoma 518-A2 cells. This search led to the striking discovery of a single chain RIP that displays selectivity for a panel of human melanoma cell lines as well as minimal immunogenicity when injected repeatedly into mice. This directed evolution of a RIP template provides a broad platform for identifying cell type specific cytotoxic agents.

Keywords: Protein libraries
cytotoxicity
anti-cancer agents
shiga like toxin 1
ribosome inactivating protein
Advisor: Gariepy, Jean
Sparse Canonical Correlation Analysis

Large scale genomic studies of the association of gene expression with multiple phenotypic or genotypic measures may require the identification of complex multivariate relationships. In multivariate analysis a common way to inspect the relationship between two sets of variables based on their correlation is Canonical Correlation Analysis, which determines linear combinations of all variables of each type with maximal correlation between the two linear combinations. However, in high dimensional data analysis, when the number of variables under consideration exceeds tens of thousands, linear combinations of the entire sets of features may lack biological plausibility and interpretability. In addition, insufficient sample size may lead to computational problems, inaccurate estimates of parameters and non-generalizable results. These problems may be solved by selecting sparse subsets of variables, i.e. obtaining sparse loadings in the linear combinations of variables of each type. However, available methods providing sparse solutions, such as Sparse Principal Component Analysis, consider each type of variables separately and focus on the correlation within each set of measurements rather than between sets. We introduce new methodology - Sparse Canonical Correlation Analysis (SCCA), which examines the relationships of many variables of different types simultaneously. It solves the problem of biological interpretability by providing sparse linear combinations that include only a small subset of variables. SCCA maximizes the correlation between the subsets of variables of different types while performing variable selection. In large scale genomic studies sparse solutions also comply with the belief that only a small proportion of genes are expressed under a certain set of conditions. In this thesis I present methodology for SCCA and evaluate its properties using simulated data. I illustrate practical use of SCCA by applying it to the study of natural variation in human gene expression for which the data have been provided as problem 1 for the fifteenth Genetic Analysis Workshop (GAW15). I also present two extensions of SCCA - adaptive SCCA and modified adaptive SCCA. Their performance is evaluated and compared using simulated data and adaptive SCCA is applied to the GAW15 data.

Keywords: Public Health Sciences
Biostatistics
Statistics
Advisor: Tritchler, David
Beyene, Joseph