VictorJuiz/thesis huggingface dataset:
Effects of Phosphate-based Corrosion Inhibitors on Disinfectant Stability and HAA/NDMA Formation when in Contact with Copper, Iron, and Lead
Keywords: Distribution system
Secondary disinfectant
Haloacetic acid
N-nitrosodimethylamine
Corrosion inhibitor
Iron
Lead
Copper

This research examined the impacts of water quality, phosphate-based corrosion inhibitors and pipe wall exposure on free chlorine (HOCl)/chloramine (NH2Cl) degradation and haloacetic acid (HAA)/N-nitrosodimethylamine (NDMA) formation in simulated distribution system water mains and household plumbing at bench-scale and pilot scale. In bench-scale bottle tests, the reactivity of fresh/pre-corroded pipe materials with HOCl/NH2Cl in decreasing order was: ductile iron, copper, lead. The addition of phosphate-based corrosion inhibitors generally increased HOCl/NH2Cl degradation for fresh iron coupons, but decreased HOCl/NH2Cl decay only for fresh copper coupons. Generally, these corrosion inhibitors did not impact HAA formation. Copper corrosion products, including Cu(II), Cu2O, CuO and Cu2(OH)2CO3, catalyzed HAA and NDMA formation. For HAAs, copper catalysis increased with increasing pH from 6.6 to 8.6 and/or increasing concentrations of these copper corrosion products. Interactions of copper with natural organic matter (NOM), likely by complexation, and the subsequent increase in the reactivity of NOM were proposed to be the primary reason for the increased HAA formation.NDMA formation increased with increasing Cu(II) concentrations, DMA concentrations, alkalinity and hardness but was inhibited by the presence of NOM. The transformation of NH2Cl to dichloramine (NHCl2) and complexation of copper with DMA were proposed to be involved in elevating the formation of NDMA at pH 7.0. Finally, in pilot-scale modified pipe loop tests, copper catalysis of NDMA formation was confirmed, especially under laminar flow conditions, and iron was shown to possibly catalyze NDMA formation under turbulent conditions. Orthophosphate increased the catalytic effects of iron but decreased copper catalysis on NDMA formation by either modifying the properties of the iron-associated suspended particles or reducing the dissolved metal concentrations. Orthophosphate increased chloramine decay when in contact with iron, likely by promoting nitrite formation, but orthophosphate decreased chloramine decay for copper and lead by reducing the availability of metal corrosion products.
Tropical Severi Varieties and Applications
Keywords: Tropicalization
Severi Varieties
Subdivisions of Polygons

The main topic of this thesis is the tropicalizations of Severi varieties, which we call tropical Severi varieties. Severi varieties are classical objects in algebraic geometry. They are parameter spaces of plane nodal curves. On the other hand, tropicalization is an operation defined in tropical geometry, which turns subvarieties of an algebraic torus into certain polyhedral objects in real vector spaces. By studying the tropicalizations, it may be possible to transform algebro-geometric problems into purely combinatorial ones. Thus, it is a natural question, “what are tropical Severi varieties?” In this thesis, we give a partial answer to this question: we obtain a description of tropical Severi varieties in terms of regular subdivisions of polygons. Given a regular subdivision of a convex lattice polygon, we construct an explicit parameter space of plane curves. This parameter space is a much simpler object than the corresponding Severi variety and it is closely related to a flat degeneration of the Severi variety, which in turn describes the tropical Severi variety. We present two applications. First, we understand G.Mikhalkin’s correspondence theorem for the degrees of Severi varieties in terms of tropical intersection theory. In particular, this provides a proof of the independence of point-configurations in the enumeration of tropical nodal curves. The second application is about Secondary fans. Secondary fans are purely combinatorial objects which parameterize all the regular subdivisions of polygons. We provide a relation between tropical Severi varieties and Secondary fans.
Characterization of the Roles of TopoIIIα-RMI1 in Maintaining Genome Integrity
Keywords: BLM
topoisomerase IIIalpha
RMI1
genome integrity

Bloom syndrome is a rare autosomal recessive disorder that is caused by mutations in the BLM gene. BLM associates with TopoIIIα and RMI1 to form a complex that is essential to maintain genome integrity. This complex catalyzes a dissolution reaction that resolves recombination intermediates containing two Holliday junctions without crossing over of genetic material. Dissolution activity is remarkable because it accounts for the in vivo role of BLM-TopoIIIα-RMI1 in suppressing sister chromatid exchanges. To further understand the biochemical roles that each member of the BLM complex plays in dissolution, I generated single-stranded catenanes that resemble the proposed intermediates at the latest steps of dissolution. Using this substrate, I demonstrated that TopoIIIα is a single-stranded DNA decatenase that is specifically stimulated by BLM and RMI1. Interaction between TopoIIIα and RMI1 is essential for the optimal decatenase activity. Furthermore, binding of RPA to single-stranded DNA substrate inhibits TopoIIIα decatenase activity. However, complex formation between BLM, TopoIIIα and RMI enables TopoIIIα to displace RPA and catalyze decatenation. Since the decatenase activity is presumed to be involved in many aspects of DNA metabolism, I investigated the roles of RMI1 and TopoIIIα in DNA replication in vivo. Using the molecular combing technique, I showed that RMI1 functions downstream of BLM to promote normal replication fork progression. In addition, BLM, TopoIIIα and RMI1 colocalize with one another in response to replication stress. Finally, interaction between TopoIIIα and RMI1 is essential for nuclear localization of the complex and for the complex to promote recovery from replication stress. This work defines molecular functions for RMI1 and TopoIIIα in DNA replication and repair, providing insight into their roles as suppressors of genome instability.
A 1-1-1-1 MASH Delta-Sigma ADC using Dynamic Comparator-based OTAs
Keywords: DCBOTA
Delta-Sigma ADC

Low intrinsic transistor gain in nanometer CMOS technologies imposes implementation difficulties of switched-capacitor (SC) circuits based on a conventional OTA used in delta-sigma ADCs. Zero-crossing-based circuits (ZCBCs) have been proposed as replacements for conventional OTAs in SC circuits, but the efficiency of existing ZCBC-based delta-sigma ADCs trails that of state-of-art conventional delta-sigma ADCs. The dynamic comparator-based OTA (DCBOTA) is a novel circuit block that performs an equivalent operation of a conventional OTA in a SC circuit by repeatedly detecting the input (Vg) sign and applying output current pulses to move Vg toward zero. The current pulse amplitude, set to the maximum at the beginning of a charge transfer phase, is decremented each time Vg crosses zero. Once Vg crosses zero at the minimum current pulse amplitude, the operation above ceases. The discrete-time nature of Vg comparison and current pulse injection in the DCBOTA allows use of a dynamic regenerative comparator, which is fast and scaling friendly, instead of the slow scaling-unfriendly open-loop zero-crossing detector used in ZCBCs. A small final Vg step size is required for high settling accuracy, but it can result in a long settling time. Analysis reveals that the DCBOTA settling time is minimized with a current pulse scaling factor of 3.59 for any final Vg step size. The comparator and switch noise affects the settling DCBOTA settling accuracy. The relationship between the minimum Vg step size, comparator noise, and switch noise for a given input-referred noise is shown. The DCBOTA consists of a dynamic regenerative comparator, control logic, and current pulse driver. The comparator evaluates the Vg sign when enabled by the control logic. The control logic enables and resets the comparator, and controls the current pulse amplitude. The current pulse driver applies either a positive or negative output current pulse when triggered by the comparator output. A 1-1-1-1 MASH delta-sigma ADC using DCBOTAs fabricated in a 65-nm CMOS technology achieved 70.4 dB of peak SNDR over a 2.5-MHz bandwidth dissipating 3.89 mW of power from a 1.2-V supply. Measurements show linear ADC power scaling over sampling frequencies provided by the dynamic operation of the DCBOTAs.
Aspects of Composite Likelihood Estimation And Prediction
Keywords: Statistics
Composite likelihood

A composite likelihood is usually constructed by multiplying a collection of lower dimensional marginal or conditional densities. In recent years, composite likelihood methods have received increasing interest for modeling complex data arising from various application areas, where the full likelihood function is analytically unknown or computationally prohibitive due to the structure of dependence, the dimension of data or the presence of nuisance parameters. In this thesis we investigate some theoretical properties of the maximum composite likelihood estimator (MCLE). In particular, we obtain the limit of the MCLE in a general setting, and set out a framework for understanding the notion of robustness in the context of composite likelihood inference. We also study the improvement of the efficiency of a composite likelihood by incorporating additional component likelihoods, or by using component likelihoods with higher dimension. We show through some illustrative examples that such strategies do not always work and may impair the efficiency. We also show that the MCLE of the parameter of interest can be less efficient when the nuisance parameters are known than when they are unknown. In addition to the theoretical study on composite likelihood estimation, we also explore the possibility of using composite likelihood to make predictive inference in computer experiments. The Gaussian process model is widely used to build statistical emulators for computer experiments. However, when the number of trials is large, both estimation and prediction based on a Gaussian process can be computationally intractable due to the dimension of the covariance matrix. To address this problem, we propose prediction methods based on different composite likelihood functions, which do not require the evaluation of the large covariance matrix and hence alleviate the computational burden. Simulation studies show that the blockwise composite likelihood-based predictors perform well and are competitive with the optimal predictor based on the full likelihood.
Bayesian Methods for Genetic Association Studies
Keywords: winner's curse
spike and slab prior
Hierarchical Bayes Model
Bayesian Model Averaging
Latent variable model
pleiotropy
genetic association studies
Markov chain Monte Carlo
path sampling
Bayesian inference

We develop statistical methods for tackling two important problems in genetic association studies. First, we propose a Bayesian approach to overcome the winner's curse in genetic studies. Second, we consider a Bayesian latent variable model for analyzing longitudinal family data with pleiotropic phenotypes. Winner's curse in genetic association studies refers to the estimation bias of the reported odds ratios (OR) for an associated genetic variant from the initial discovery samples. It is a consequence of the sequential procedure in which the estimated effect of an associated genetic marker must first pass a stringent significance threshold. We propose a hierarchical Bayes method in which a spike-and-slab prior is used to account for the possibility that the significant test result may be due to chance. We examine the robustness of the method using different priors corresponding to different degrees of confidence in the testing results and propose a Bayesian model averaging procedure to combine estimates produced by different models. The Bayesian estimators yield smaller variance compared to the conditional likelihood estimator and outperform the latter in the low power studies. We investigate the performance of the method with simulations and applications to four real data examples. Pleiotropy occurs when a single genetic factor influences multiple quantitative or qualitative phenotypes, and it is present in many genetic studies of complex human traits. The longitudinal family studies combine the features of longitudinal studies in individuals and cross-sectional studies in families. Therefore, they provide more information about the genetic and environmental factors associated with the trait of interest. We propose a Bayesian latent variable modeling approach to model multiple phenotypes simultaneously in order to detect the pleiotropic effect and allow for longitudinal and/or family data. An efficient MCMC algorithm is developed to obtain the posterior samples by using hierarchical centering and parameter expansion techniques. We apply spike and slab prior methods to test whether the phenotypes are significantly associated with the latent disease status. We compute Bayes factors using path sampling and discuss their application in testing the significance of factor loadings and the indirect fixed effects. We examine the performance of our methods via extensive simulations and apply them to the blood pressure data from a genetic study of type 1 diabetes (T1D) complications.
Genetic Considerations in the Evolution of Sexual Dimorphism
Keywords: sexual dimorphism
sexual conflict
sexual selection
intersexual genetic correlation

Sexual differences are dramatic and widespread across taxa. However, a common genome between males and females should hinder phenotypic divergence. In this thesis I have used experimental, genomic, and theoretical approaches to study processes that can facilitate and maintain differences between males and females. I studied two mechanisms for the evolution of sexual dimorphism - condition-dependence and gene duplication. If sex-specific traits are costly, then individuals should only express such traits when they possess enough resources to do so. I experimentally manipulated adult condition and found that the sex-biased gene expression depends on condition. Second, duplication events can permit different gene copies to adopt sex-specific expression. I showed that half of all duplicate families have paralogs with different sex-biased expression patterns between members. I investigated how current sexual dimorphism may support novel dimorphism. With regards gene duplication, I found that related duplicates did not always have different expression patterns. However, duplicating a pre-existing sex-biased gene effectively increases organismal sexual dimorphism overall. From a theoretical perspective, I investigated how sexually dimorphic recombination rates allow novel sexually antagonistic variation to invade. Male and female recombination rates separately affect invasion probabilities of new alleles. Finally, I examined the assumption that a common genetic architecture impedes the evolution of sexual dimorphism. First, I conducted a literature review to test whether additive genetic variances in shared traits were different between the sexes. There were few significant statistical differences. However, extreme male-biased variances were more common than extreme female-biased variances. Sexual dimorphism is expected to evolve easily in such traits. Second, I compared these results to findings from the multivariate literature. In contrast to single trait studies, almost all multivariate studies of sexual dimorphism have found variance differences, both in magnitude and orientation, between males and females. Overall, this thesis concludes that sexual dimorphism can evolve by processes that generate novel sexual dimorphism or that take advantage of pre-existing dimorphism. Furthermore, a common genome is not necessarily a strong barrier if genetic variances differ between the sexes. It will be an exciting challenge to understand how mutation and selection work together to allow organisms differ in their ability evolve sexual dimorphism.
The Jeweled Fish Hook: Monastic Exemplarity in the Shalu Abbatial History
Keywords: Buddhism
Tibet
Biography
History

This dissertation is an in-depth study of the nineteenth-century Shalu Abbatial History, a collection of biographies of abbots and other important religious masters, or lamas, from the Tibetan monastery of Shalu, located in the Tibetan region of Tsang. Examining the History in conjunction with the autobiography of its author, Losel Tengyong (b. 1804), and vis-à-vis other texts from Shalu, reveals, I argue, that the Shalu Abbatial History is a guidebook of conduct that prescribes to the Shalu monk, its intended reader, a discrete pattern of exemplarity that constitutes the author's own particular vision of what a noble lama should be within the Shalu tradition. The constitution of this pattern of exemplarity is examined within four themes of virtuous conduct: the dedication to resolving congregational conflicts, the literalist observance of the Buddhist disciplinary code contained within the Vinaya, the devotion to the preservation of books, and the power to successfully exploit violent rituals to protect the monastic tradition. The prescriptive vision, moreover, constituted by these four virtuous themes, lies not only within the History itself, but also more broadly in the intertextual connections that clarify this prescription and infuse it with meaning from the Shalu tradition—the world that has generated, and is reflected within, the text.
CD200: A Novel Therapeutic Target for Chronic Lymphocytic Leukemia
Keywords: CD200
CLL
immunotherapy

The ability of cancer cells to escape anti-tumor immune responses is acknowledged as one of the hallmarks of cancer. Overexpression of immunoregulatory molecules is one mechanism responsible for the immunsuppressive network that is characteristic of the tumor microenvironment. In this thesis, we investigated the role of CD200, a potent immunoregulatory molecule, in Chronic Lymphocytic Leukemia. We showed that functional blockade of CD200 on lymphoma cells or primary CLL cells, both of which express CD200 at high levels, augmented cytotoxic killing of these cells by effector CD8+ T cells in vitro. We also identified and characterized a previously unrecognized soluble form of CD200, sCD200, present in elevated levels in CLL plasma when compared to plasma from controls. The data reported show that patients with high sCD200 levels have more aggressive disease, inferring that sCD200 may be a novel prognostic marker for CLL. The in vivo function of sCD200 was investigated for its ability to support engraftment of CLL splenocytes in NOD.SCID mice. Infusion of sCD200hi CLL plasma, but not sCD200lo normal plasma, enhanced engraftment of CLL-splenocytes in vivo, an effect which was abrogated by depletion of sCD200 from CLL plasma. The prolonged engraftment of CLL cells seen in this model (>6 months) suggests these mice represent a useful pre-clinical model for drug screening. The effect of CD200 blockade was tested in this model, and was found to be as effective in eliminating engrafted CLL cells as rituximab. Investigation of the mechanisms leading to the release of sCD200 from CLL cells showed that sCD200 was produced following ectodomain shedding by ADAM proteases and MMPs. Results from studies reported in this thesis support the hypothesis that CD200 plays a major role in CLL biology, and suggests it may represent a novel therapeutic target for CLL.
Effects of Unilateral and Bilateral Cochlear Implantation on Cortical Activity Measured by an EEG Neuroimaging Method in Children
Keywords: Cochlear Implant
Auditory Pathway
Neuroplasticity
Beamformer
Source Localization
Electroencephalography

Bilateral implantation of a cochlear implant (CI) after a >2 year period of unilateral hearing with a second implant has been shown to result in altered latencies in brainstem responses in children with congenital deafness. In this thesis, a neural source localization method was developed to investigate the effects of unilateral CI use on cortical development after the implantation of a 2nd CI. The electroencephalography (EEG) source localization method is based on the linearly constrained minimum variance (LCMV) vector beamformer and utilizes null constraints to minimize the electrical artifact produced by the CI. The accuracy of the method was assessed and optimized through simulations and comparisons to beamforming with magnetoencephalography (MEG) data. After using cluster analyses to ensure that sources compared across subjects originate from the same neural generators, a study was done to examine the effects of unilateral CI hearing on hemispheric lateralization to monaural responses. It was found that a >2 year period of unilateral hearing results in expanded projections from the 1st implanted ear to the contralateral auditory area that is not reversed by implantation of a 2nd CI. A subsequent study was performed to examine the effects of unilateral CI hearing on the contributions of the 1st and 2nd implanted ears to the binaural response. It was found that in children with > 2 years of unilateral hearing, the binaural response is dominated by the 1st implanted ear. Together, these results suggest that the delay between the 1st and 2nd CI should be minimized in bilateral implantation to avoid dominance of auditory pathways from the 1st implanted ear. This dominance limits developmental competition from the 2nd CI and potentially contributes to poorer performance in speech detection in noise tasks.
Neural Changes Associated with Treatment Outcome in Children with Externalizing Problems
Keywords: EEG
children
treatment
antisocial

The current thesis directly investigated whether changes in the neural correlates of self-regulation (SR) are associated with the effectiveness of treatment for children’s externalizing problems. In order to test this, seventy-one children 8–12 years of age with clinical levels of externalizing behaviour and their parents completed a 12-week cognitive behavioural therapy program (12 sessions) with a parent management training component that was aimed at improving SR. Electroencephalogram (EEG) correlates of SR were evaluated before and after treatment with a go/no-go task requiring inhibitory control on the children. Results showed that event-related potential (ERP) correlates of SR, such as the frontal N2 and frontal P3 event-related potential magnitudes, differed between the clinical sample and a matched comparison group before treatment: the clinical sample had larger N2 magnitudes and smaller frontal P3 magnitudes. Children who showed improvement (45%) with treatment demonstrated a decrease in the magnitude of the N2 in comparison with children who did not improve. For improvers only, source analysis during the time period of the N2 modeled activation decreases in dorsomedial and ventromedial prefrontal cortex as well as the anterior medial temporal lobe. A decrease in N2 magnitudes and corresponding reductions in source activation, in children who improved with treatment, might reflect improved efficiency in the neural mechanisms of SR. These findings may be important steps toward a better identification of neural markers of SR and a better understanding of the mechanisms of treatment efficacy.