N-linked glycosylation is the most common post-translational modification (PTM) of proteins that exist in nature. N-glycosylation and change in cells serve as a criterion to monitor the activity of developmental stages and diseases severity. Currently, there is an increasing application of mass spectrometry on glycoprotein for malicious, chronic or acute diseases, such as cancers, rheumatoid arthritis (RA) or influenza. In this dissertation, several mass spectrometric assays have been utilized to, quantitatively and qualitatively, characterize protein N-glycosylation at the glycan, glycopeptide and peptide levels. The goals are to identify serum-based RA biomarker (Chapter 2), or to determine possible glycan structures from monoclonal antibody (Chapter 3), or comprehensively to study one influenza glycoprotein, hemagglutinin (Chapter 4). In Chapter 2, LC-MS/MS with CID as MS 2 is the primary technique that is applied to collect raw data for RA biomarker screening; western blot is the verification method for newfound biomarkers. This mass spectrometry based comparative analysis of N-glycoprotein in RA and healthy patients’ sera reveal 41 potential biomarkers for RA that can be applied in clinical research. Chapter 3 describes another LC-MS/MS based method developed for the structural analysis of N-glycan released from the monoclonal antibody, immunoglobin G. Higher-energy collision dissociation (HCD) was the surprior technique utilized to identify glycopeptide fragments. The results show that 19 and 23 N-glycan structures were determined from standard and modified mAb samples respectively by using SimGlycan software, while 38 and 35 glycan structures were recognized by manually mapping respectively. 13 N-glycoforms, out of 26 overlapped glycan structures, were identified with significant alterations by comparing standard sample (sample A) and modified mAb (sample B) utilizing our method. In Chapter 4, we comprehensively studied hemagglutinin by using LC-MS/MS and MALDI from both proteomic perspective and glycomics prospective. After confirmed and verified protein sequence and glycosylation sites, galactose-specific quantitation was performed with exoglycosidase digestion combined HPLC with fluorescence detection. The MALDI-MS/MS based method was utilized to confirm glycan structures. The results in this dissertation provide insights into the significance of protein glycosylation alterations as RA biomarkers, and these quantitative methods can be reapplied to any other disease biomarkers screening for clinical researchers.

The study of prehistoric Maya settlements has been hampered by simplistic views of cultural ecology, over generalized ethnographic analogy, and a lack of attention to both natural and cultural site formation processes. As a result, Mayanists have tended to expect very little variety in archaeological features and have assumed cultural uniformity over wide ranges of time and space. Traditional research designs support these assumptions. Current knowledge of Maya social organization suggests that more structural variety may occur in Maya archaeological sites than is ordinarily discovered. Some of this variation is evidenced by features not currently visible on the ground-surface. The Nohmul Settlement pattern project employed a "purposive" sampling design to search for settlement variation over time and space. Several assumptions about surface-subsurface relationships were tested. Surface indications were not found to outline subsurface variety. Excavating at intervals from site center in both visible and "invisible" features, showed that the Nohmul community was affected by both centralizing and decentralizing influences and grouped into residential clusters resembling neighborhoods. The degree of centralization and the location of the clusters, as well as some of their characteristics, changed notably over Nohmul's 2500 year occupation.

The purpose of this study was to investigate the perceptions of principals who had served in their positions prior to and since the state-mandated implementation of site-based management. The study sought to determine if the state mandates impacted the principals' perceptions regarding the pre-existing site-based management in their district. The study also sought to determine relationships between support or lack of support and the principals' gender, age, ethnicity, years as principal, and educational level.

Doctor of Philosophy / Department of Computing and Information Sciences / Doina Caragea / The large volume of data generated in the recent years has created opportunities for discoveries in various fields. In biology, next generation sequencing technologies determine faster and cheaper the exact order of nucleotides present within a DNA or RNA fragment. This large volume of data requires the use of automated tools to extract information and generate knowledge. Machine learning classification algorithms provide an automated means to annotate data but require some of these data to be manually labeled by human experts, a process that is costly and time consuming. An alternative to labeling data is to use existing labeled data from a related domain, the source domain, if any such data is available, to train a classifier for the domain of interest, the target domain. However, the classification accuracy usually decreases for the domain of interest as the distance between the source and target domains increases. Another alternative is to label some data and complement it with abundant unlabeled data from the same domain, and train a semi-supervised classifier, although the unlabeled data can mislead such classifier. In this work another alternative is considered, domain adaptation, in which the goal is to train an accurate classifier for a domain with limited labeled data and abundant unlabeled data, the target domain, by leveraging labeled data from a related domain, the source domain. Several domain adaptation classifiers are proposed, derived from a supervised discriminative classifier (logistic regression) or a supervised generative classifier (naïve Bayes), and some of the factors that influence their accuracy are studied: features, data used from the source domain, how to incorporate the unlabeled data, and how to combine all available data. The proposed approaches were evaluated on two biological problems -- protein localization and ab initio splice site prediction. The former is motivated by the fact that predicting where a protein is localized provides an indication for its function, whereas the latter is an essential step in gene prediction.

Dendroclimatologists often approach field work with the intent of reconstructing a particular climate variable (e.g. temperature, streamflow, precipitation). Although guidelines exist for species and site selection, isolating the signal of interest is difficult in areas with complex terrain or a lack of ideal sites. In this case study, I suggest climatological techniques for a more efficient sampling scheme and apply these techniques to identify criteria for selecting sites sensitive to winter precipitation in the north-central Rocky Mountains. These techniques include examining factors influencing the regional response of tree growth to climate by utilizing the International Tree-Ring Databank (ITRDB), using eigenvector analyses to identify modes of variability between sites, and delineating climate regions based on the variable of interest through climate regionalization. Results suggest that low- or mid-elevation Pseudotsuga menziesii sites should be targeted for maximizing the winter precipitation signal in the case study area. The season of precipitation impacting growth was found to be a major component of the overall variability between sites.

Size selective reactivity has been observed in pure aluminum cluster anions as a result of Lewis acid and base pairs. Using this a starting point, the goal of this study has been to explore how reactivity is affected with the addition of one or more ligand, which may induce active sites on the surface of the metal clusters. To study this, a theoretical investigation was undertaken on Al13Ix- and Al14Iy- (x=0-2, y=2-4) and their reactivity with methanol. The hypothesis was that iodine can induce a Lewis base site on the opposite side of the cluster, which may enhance reactivity. In results that are consistent with preliminary experimental data, it was found that the Al13Ix- series has a large energy barrier with respect to the cleavage of the O-H bond of methanol. The clusters of the series act as an extremely poor Lewis acids, and as a result, these clusters are relatively inert to methanol etching. On the other hand, the Al14Iy- series has a low barrier and is expected to react rapidly with methanol. The series is found to be most reactive at an aluminum adatom that is bound to an iodine due to the iodine extracting charge from the aluminum cluster creating a strong Lewis acid site.

This thesis uses the techniques of atomic force microscopy (AFM) and conductiveAFM (CAFM) to study defect sites on GaN films. In particular, these defect sites demonstrate current leakage under reverse-bias conditions that are detrimental to device fabrication. Two growth techniques that were used to improve this leakage behavior for samples in this study included: epitaxial lateral overgrowth (ELO) and nano-ELO using a Si3N4 film. Both techniques decrease defects such as threading dislocations by controlling the nucleation and growth behavior of the GaN films. The EL0 technique uses a patterned dielectric film to laterally grow micron-wide regions (referred to as 'wings') that minimize dislocation defects. Our CAFM studies indicate that ELO films have no detectable leakage sites in these wing regions; however, between these regions the films have typical leakage site densities seen for standard films on the order of 107cm-3. The nano-ELO technique utilizes a porous Si3N4 film to reduce defects over the entire film, and CAFM data indicate nearly a factor of ten reduction in leakage site densities. The nano-ELO technique is therefore optimal for an overall improvement in film quality, whereas the ELO technique is suitable for device fabrication in patterned regions with optimized film quality.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.