The ubiquity of pharmaceuticals and personal care products in water systems is well known. With the increasing implementation of water reuse schemes in the US, concern about potential health effects of these compounds in humans has risen. While potential synergistic effects of chronic low doses exposure to a cocktail of these compounds is still being studied, it is prudent to monitor and attenuate these trace organic compounds (TOrCs) from our water sources. This research initially focused on identifying suitable `indicator' TOrCs based on theoretical physico-chemical parameters and actual experimental data. It was concluded that an indicator list will be specific to the goal targeted with dependence on treatment process, occurrence and analytical ease. Quantification of these TOrCs are part per trillion levels in water requires accurate, precise and robust analytical techniques. The next part of this research was spent on developing three different analytical methods with LC-MS/MS for the sensitive detection of TOrCs in several different water matrices including raw sewage and final drinking water. The treatment efficacy of granular activated carbon for attenuation of TOrCs is studied in detail with emphasis on developing correlations between TOrC removal and bulk organic parameters of water like UV absorbance and fluorescence by using rapid small-scale column testing. The results indicate a correlation between removal of TOrCs and bulk organic parameters that is independent of water quality. The effectiveness of commercially available activated carbon based point-of-use (POU) devices for removal of a set of TOrCs from water was evaluated. The data indicated that POUs are a viable option for treatment of TOrCs but specific removal depends on type of device, water quality and amount of water treated. Finally, further research was targeted at identifying transformation products as a result of oxidation of polyfluorinated precursor materials in reclaimed waters. The results illustrated that toxic perfluorocarboxylic acids can be formed on oxidation of fluorotelomer unsaturated carboxylic acids that are known to be present in water.

As DNA sequence information becomes increasingly available, researchers are now tackling the great challenge of characterizing and identifying peptides and proteins from complex mixtures. Automatic database searching algorithms have been developed to meet this challenge. This dissertation is aimed at improving these algorithms to achieve more accurate and efficient peptide and protein identification with greater confidence by incorporating peak intensity information and peptide cleavage patterns obtained in gas-phase ion dissociation research. The underlying hypothesis is that these algorithms can benefit from knowledge about molecular level fragmentation behavior of particular amino acid residues or residue combinations.SeQuence IDentification (SQID), developed in this dissertation research, is a novel Bayesian learning-based method that attempts to incorporate intensity information from peptide cleavage patterns in a database searching algorithm. It directly makes use of the estimated peak intensity distributions for cleavage at amino acid pairs, derived from probability histograms generated from experimental MS/MS spectra. Rather than assuming amino acid cleavage patterns artificially or disregarding intensity information, SQID aims to take advantage of knowledge of observed fragmentation intensity behavior. In addition, SQID avoids the generation of a theoretical spectrum predication for each candidate sequence, needed by other sequencing methods including SEQUEST. As a result, computational efficiency is significantly improved.Extensive testing has been performed to evaluate SQID, by using datasets from the Pacific Northwest National Laboratory, University of Colorado, and the Institute for Systems Biology. The computational results show that by incorporating peak intensity distribution information, the program's ability to distinguish the correct peptides from incorrect matches is greatly enhanced. This observation is consistent with experiments involving various peptides and searches against larger databases with distraction proteins, which indirectly verifies that peptide dissociation behaviors determine the peptide sequencing and protein identification in MS/MS. Furthermore, testing SQID by using previously identified clusters of spectra associated with unique chemical structure motifs leads to the following conclusions: (1) the improvement in identification confidence is observed with a range of peptides displaying different fragmentation behaviors; (2) the magnitude of improvement is in agreement with the peptide cleavage selectivity, that is, more significant improvements are observed with more selective peptide cleavages.

Los compuestos organoborados son considerados de gran interés en síntesis orgánica debido a que el enlace C-B puede ser transformado en una amplia variedad de grupos funcionales. La adicción catalítica de H-B o B-B a enlaces C-C insaturados se considera uno de los procesos catalíticos con mayor control selectivo en la formación de dichos intermedios organoborados. En el capítulo primero de la presente tesis se muestra la evolución a través de la bibliografía de las tres principales reacciones de adición catalítica de boro a alquenos, como son hidroboración, diboración y -boración. El segundo capítulo describe por primera vez la hidroboración catalítica asimétrica tanto en version homogénea como heterogeneizada de sistemas alilícos heterofuncionalizados. También describe el primer ejemplo de diboración de fenil alil sulfonas con sistemas catalíticos de Pt modificados con ligandos N-heterocíclicos. El tercer capítulo muestra la diboración catalítica de alquenos con sistemas catalíticos formados por Cu, Pd e Ir modificados con ligandos NHC. La presencia de una base y la adicción de un exceso de diborano son esenciales para obtener un alto grado de actividad y selectividad. El cuarto capítulo muestra una efectiva síntesis de boro enolatos quirales usando metales de bajo coste como son Cu y Ni modificados con ligandos NHC quirales y ligandos difosfina quirales respectivamente. El quinto capítulo describe las reacciones tándem "in situ" tales como adición de boro-acoplamiento cruzado catalizadas por complejos de Pt modificado con ligandos carbenos y Pd modificados con ligandos difosfina. / Organoboron compounds are some of the most useful reagents in organic synthesis. The carbon-boron bond, once formed, can be cleaved in a variety of ways, with or without homologation, leading to a wide range of useful functional groups. The catalytic addition of H-B or B-B across to unsaturated C-C bond is one of the catalytic processes with higher selective control in the C-B bond formation. In the first Chapter of this thesis shows the evolution through the literature of the three main catalytic reactions of boron addition to alkenes, such as hydroboration, diboration and -boration.Chapter 2 describes the first attempt at the catalytic asymmetric hydroboration in both homogeneous and heterogenised version of functionalised allylic system. In addition, the first example of the diboration reaction of these mentioned substrates with complexes based on Pt modified with NHC ligands is described.Chapter 3 discusses catalytic diboration of alkenes based on Cu, Pd and Ir- catalytic system modified with NHC ligands. The presence of a base and the use of an excess of diboron reagent are essential to obtain high degree of activity and selectivity.Chapter 4 shows the successful synthesis of chiral boron enolates by using inexpensive metals such as copper and nickel modified with chiral NHC ligands and modulated chiral commercially available diphosphines respectively. In Chapter 5 describes complexes containing transition metals such as platinum and palladium modified with NHC ligands and P,P respectively capable to perform the in situ tandem catalytic boron-addition-Suzuki-Miyaura cross-coupling.

No description available.

<p>The objective of the study was to conduct an internal validation on miniSTR systems and apply it to cases received from the South African Missing Persons Task Team (SAMPTT). This was prompted by the fact that miniSTR systems have been shown to out perform some of the commercial kits available in the time of the study and provide an alternative to mtDNA when analysing degraded DNA from skeletal remains and that the DNA extracted from skeletal remains received from the SAMPTT would be degraded due to the remains generally being fragmented or charred and buried for many years. The miniSTR loci chosen for validation comprised the Combined DNA Index System (CODIS) thirteen core loci and were arranged into four triplexes and one uniplex.</p>

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal

Post-zygotic genetic variation has previously been shown in healthy individuals and linked to various disorders. The definition of post-zygotic or somatic variation is the existence of genetically distinct populations of cells in a subject derived from a single zygote. Structural changes in the human genome are a major type of inter-individual genetic variation and copy number variation (CNV), involving changes in the copy number of genes, are one of the best studied category of structural genetic changes. In paper I we reported a pair of healthy female monozygotic (MZ) twins discordant for aneuploidy of chromosomes X and Y, contributing to the delineation of the frequency of somatic variation in MZ twins. It also illustrates the plasticity of the genome for tolerating large aberrations in healthy subjects. In paper II we showed age-related accumulation of copy number variation in the nuclear genomes in vivo for both megabase- and kilobase-range variants. Using age-stratified MZ twins and single-born subjects, we detected megabase-range aberrations in 3.4% of people ≥60 years old but not in individuals younger than 55 years. Moreover, the longitudinal analysis of subjects with aberrations suggests that the aberrant cell clones are not immortalized and disappear from circulation. We also showed that sorted blood cells display different genomic profiles.  The detected recurrent rearrangements are candidates for common age-related defects in blood cells. This work might help to describe the cause of an age-related decline in the number of cell clones in the blood, which is one of the hallmarks of immunosenescence. In paper III we described a variable number tandem repeat (VNTR) ~4 kb upstream of the IFNAR1 gene, which was somatically variable.  We detected 14 alleles displaying inter- and intra-individual variation. Further analyses indicated strong clustering of transcription factor binding sites within this region, suggesting an enhancer. This putative VNTR-based enhancer might influence the transcriptional regulation of neighboring cytokine receptor genes and the pathways they are involved in. These three studies stress the importance of research on post-zygotic variation in genetics. Furthermore, they emphasize that biobanks should consider sampling of multiple tissues to better address this issue in the genetic studies.

Quadrupole ion trap(QIT) mass spectrometry has become one of the most widelyused tools in the analysis of the structure of small molecules. The motion of the ionsstored in the quadrupole ion trap is extremely important. This ion motion within thequadrupole ion trap is controlled by several factors including the m/z ratio and thecollisional cross section of the ion. Investigation of ion motion within the QIT has thepotential to elucidate a new way to separate ions based on these factors. DC tomographyexperiments allow for the trajectory of the ion motion to be measured withoutmodifications to the ion trap. The ability to use DC tomography for separation ofisomeric ions on a commercial GC/MS system was investigated.Investigation of the mass range within the ion trap is necessary for the analysis ofa wide range of molecules. The ability of the quadrupole ion trap to perform MS/MSanalyses can provide insight into the structural information of many compounds.However, there exists a low mass cut-off (LMC) within the quadrupole ion trap and thusinformation about the low m/z fragments from a parent ion is lost. Schwartz and coworkerspresented a new technique labeled pulsed q dissociation (PQD) at the 53rdAnnual ASMS Conference in San Antonio TX in 2005. PQD eliminates the LMC byperforming CID at a qz of 0.4 but, then immediately lowering the q level before the massscan in a linear ion trap. By operating the quadrupole ion trap in this same manner, lowm/z product ions can be detected. This technique and elucidation of the energetic processcontained within PQD were explored further using a modified commercial quadrupoleion trap and the results discussed in this work.

Les séquences répétées en tandem sont constituées de motifs adjacents. Elles constituent une classe de séquences génétiques dont font partie microsatellites et minisatellites. Dans cette thèse, nous traitons le problème de la comparaison de séquences répétées en tandem sous un modèle évolutif particulier. Plus précisément, nous nous intéressons au problème de leur alignement dans lequel, en plus des trois opérations classiques, mutation, insertion et délétion, nous considérons l'amplification en tandem et la contraction en tandem. L'amplification copie un facteur de la séquence, c'est-à-dire un ou plusieurs caractère(s), et met le ou les exemplaire(s) du facteur copié à côté du facteur original, la contraction est l'événement inverse. L'amplification (resp. la contraction) est dite « n-aire d'ordre m », si elle copie (resp. retire) m motif(s) n fois. Nous proposons une méthode donnant un score d'alignement, qui est une métrique, entre deux séquences répétées en tandem, sous un modèle comprenant les cinq opérations précédemment citées où l'amplification et la contraction sont unaires d'ordre 1. Le problème est difficile car les opérations ne sont pas commutatives. Notre solution fait appel à de l'algorithmique de graphe. Nous avons réalisé un programme nommé MS_Align qui implémente cette méthode. Il s'agit du premier programme capable d'aligner des cartes de minisatellites. À l'aide de ce programme, nous avons étudié des données biologiques provenant du minisatellite humain MSY1. Comme nous le montrons, notre modèle évolutif s'applique bien à ce type de séquences d'ADN. Nous avons construit à partir de nos résultats des arbres phylogénétiques semblables à ceux obtenus grâce à d'autres marqueurs du chromosome Y indépendants de MSY1, nos arbres offrent une meilleure résolution. Une partie de cette thèse est consacrée au problème général où nous relaxons les contraintes sur les amplifications et contractions.

A hole-collecting interlayer layer for organic solar cells, NiO, processed by atomic layer deposition (ALD) was studied. ALD-NiO film offered a novel alternative to efficient hole-collecting interlayers in conventional single-junction organic solar cells. Next, surface modifications with aliphatic amine group containing polymers for use as electron-collecting interlayers were studied. Physisorption of the polymers was found to lead to large reduction of the work function of conducting materials. This approach provides an efficient way to provide air-stable low-work function electrodes for organic solar cells. Highly efficient inverted organic solar cells were demonstrated by using the polymer surface modified electrodes. Lastly, charge recombination layers of the inverted tandem organic solar cells were studied. Efficient charge recombination layers were realized by using the ALD and the polymer surface modification. The charge recombination layer processed by ALD provided enhanced electrical and barrier properties. Furthermore, the polymer surface modification on the charge recombination layers showed large work function contrast, leading to improved inverted tandem organic solar cells. The inverted tandem organic solar cells with the new charge recombination layer showed fill factor over 70% and power conversion efficiency over 8%.