Carbohydrates are abundant in nature and have functions ranging from energy storage to acting as structural components. Analysis of carbohydrate structures is important and can be used for, for instance, clinical diagnosis of diseases as well as in bacterial studies. The complexity of glycans makes it difficult to determine their structures. NMR spectroscopy is an advanced method that can be used to examine carbohydrates at the atomic level, but full assignments of the signals require much work. Reliable automation of this process would be of great help. Herein studies of Escherichia coli O-antigen polysaccharides are presented, both a structure determination by NMR and also research on glycosyltransferases which assemble the polysaccharides. The computer program CASPER has been improved to assist in carbohydrate studies and in the long run make it possible to automatically determine structures based only on NMR data. Detailed computer studies of glycans can shed light on their interactions with proteins and help find inhibitors to prevent unwanted binding. The WaaG glycosyltransferase is important for the formation of E. coli lipopolysaccharides. Molecular docking analyses of structures confirmed to bind this enzyme have provided information on how inhibitors could be composed. Noroviruses cause gastroenteritis, such as the winter vomiting disease, after binding human histo-blood group antigens. In one of the projects, fragment-based docking, followed by molecular dynamics simulations and binding free energy calculations, was used to find competitive binders to the P domain of the capsid of the norovirus VA387. These novel structures have high affinity and are a very good starting point for developing drugs against noroviruses. The protein targets in these two projects are carbohydrate binding, but the techniques are general and can be applied to other research projects. / At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 4: Submitted. Paper 5: Manuscript. Paper 6. Manuscript.

BACKGROUND: Abetalipoproteinemia (ABL) is a rare autosomal recessive disorder caused by mutations in the gene coding for microsomal triglyceride transfer protein (MTTP). AIM: To characterize the genetic basis of ABL in two unrelated patients. RESULTS: In the first patient, the substitution c.1911C>T in exon 12 of the MTTP gene, resulting in the protein substitution p.P552L, was discovered using mutation screening. The parents are heterozygous and the proband is a homozygous carrier of this substitution. Using restriction fragment length polymorphism (RFLP), 100 control subjects were analyzed and none carried the substitution indicating that it is a novel MTTP mutation. Sequencing of the other ABL patient showed that the proband carried a homozygous single base insertion, at position  c.2342IVS16+2-3insT, located at the donor splice-site of intron 16 resulting in skipping of exon 16 and truncation of the protein. The proband's mother is heterozygous for the insertion while the father does not carry the insertion. Multiplex ligation-dependent probe amplification (MLPA) did not identify any deletion encompassing exon 16 in the proband, father or mother. Nonpaternity was excluded using polymorphic markers from several chromosomes. Haplotype analysis using markers spanning chromosome 4 revealed  heterodisomy (two homologous chromosomes) of 4p and the distal part of 4q, and isodisomy (duplication of one chromosome) of 4q12-4q26. CONCLUSION: These data show that the cause of ABL in one of the patients is a missense mutation, p.P552L, while the cause of ABL in the other patient is due to uniparental disomy, probably resulting from non-disjunstion in meiosis I.

Massively parallel whole transcriptome sequencing and its ability to generate full transcriptome data at the single transcript level provides a powerful tool with multiple interrelated applications, including transcriptome reconstruction, gene/isoform expression estimation, also known as transcriptome quantification. As a result, whole transcriptome sequencing has become the technology of choice for performing transcriptome analysis, rapidly replacing array-based technologies. The most commonly used transcriptome sequencing protocol, referred to as RNA-Seq, generates short (single or paired) sequencing tags from the ends of randomly generated cDNA fragments. RNA-Seq protocol reduces the sequencing cost and significantly increases data throughput, but is computationally challenging to reconstruct full-length transcripts and accurately estimate their abundances across all cell types. We focus on two main problems in transcriptome data analysis, namely, transcriptome reconstruction and quantification. Transcriptome reconstruction, also referred to as novel isoform discovery, is the problem of reconstructing the transcript sequences from the sequencing data. Reconstruction can be done de novo or it can be assisted by existing genome and transcriptome annotations. Transcriptome quantification refers to the problem of estimating the expression level of each transcript. We present a genome-guided and annotation-guided transcriptome reconstruction methods as well as methods for transcript and gene expression level estimation. Empirical results on both synthetic and real RNA-seq datasets show that the proposed methods improve transcriptome quantification and reconstruction accuracy compared to previous methods.

Host-Associated Differentiation (HAD) is the formation of genetically divergent hostassociated lineages maintained by ecological isolation. HAD is potentially an important route to ecological speciation in parasites including many insects. While HAD case studies are accumulating, there is a dearth of negative results in the literature making it difficult to know how common the phenomenon really is or whether there are specific traits of parasites which promote HAD. To address these two problems, studies are needed which both publish negative results (i.e., parasites not showing HAD) and test for HAD in multiple parasite species on the same pair of host species (i.e., control for host plant effects). In this study, HAD was tested in three species of herbivorous insects and one parasitoid species on the same two host tree species: pecan and water hickory. The insects were selected based on the presence or absence of two traits, parthenogenesis and endophagy. A test for HAD was considered “positive” when population substructure was explained by host-association. To test for the presence of HAD, insects were sampled sympatrically to eliminate geographical isolation as a confounding factor, sampling was replicated spatially to assure that HAD persisted, and multiple loci were sampled from each individual. Genetic data was analyzed using cluster analyses. HAD was found in both pecan leaf phylloxera and yellow pecan aphid but not in pecan bud moth or in the parasitoid of the yellow pecan aphid, Aphelinus perpallidus. Interestingly, both taxa showing HAD are parthenogenetic and both taxa not showing HAD reproduce sexually. Species showing HAD were tested for the presence of a pre-mating reproductive isolating mechanism (RIM) which could be maintaining HAD despite the potential for gene flow. Selection against migrants to the alternative host was tested in yellow pecan aphid using a no-choice fitness experiment. The overall contribution of this RIM to total isolation was positive and ranged from 0.614 to 0.850. The RIM of “habitat preference” was tested in pecan leaf phylloxera using a dual-choice preference experiment. In this species, preference was only detected for phylloxera originating from water hickory suggesting that host discrimination ability may be a less important factor promoting differentiation in phylloxera.

Blumeria graiminis f. sp. hordei (powdery mildew) is an obligate biotroph infecting hordeum vulgare (barley). It is one of the most devastating pathogens of barley, decreasing barley yield in great extent. In order to decrease barley loss, numerous studies are being conducted for overcoming the disease from the sides of both pathogen and host. However the pathogen is evolving very rapidly preventing the effective use of pesticides such as fungisides or development of resistant barley varieties by crossing race-specific resistance varieties, varieties having R genes, with susceptible but high yield producing varieties. In order to understand the mechanism of pathogen-host interactions, and producing enduring solutions for the problem of yield loss in barley molecular tools need to be used. In this thesis study, Amplified Fragment Length Polymorphism (AFLP) molecular marker method is used in order to reveal the molecular characterization of Turkish Blumeria graminis f. sp. hordei varieties collected from &Ccedil / ukurova region in Turkey. Thirty-nine samples were analyzed with eigth universal races, of which virulence genes are studied. AFLP studies were conducted on LI-COR 4300 DNA Analyzer system. Bioinformatics analysis was performed with NTSYS program. By the help of this Numerical Taxonomic System, similarity, dissimilarity, clustering, dendograms, two-dimensional scatter plots, and three-dimensional perspective plots were obtained. By the light of these analyses Turkish Blumeria graminis f. sp. hordei varieties together with universal races are grouped into three clusteres. In conclusion, studying Turkish Blumeria graminis f. sp. hordei isolates and comparing them with universal races is a unique study in terms of characterizing the Turkish Bgh isolates for the first time, and can be used as a frontier study for studying Resistance genes, by reverse genetic tools.

The present knowledge of angular distributions of neutron-induced fission is limited to a maximal energy of 15 MeV, with large discrepancies around 14 MeV. Only 238U and 232Th have been investigated up to 100 MeV in a single experiment. The n_TOF Collaboration performed the fission cross section measurement of several actinides (232Th, 235U, 238U, 234U, 237Np) at the n_TOF facility using an experimental set-up made of Parallel Plate Avalanche Counters (PPAC), extending the energy domain of the incident neutron above hundreds of MeV. The method based on the detection of the 2 fragments in coincidence allowed to clearly disentangle the fission reactions among other types of reactions occurring in the spallation domain. I will show the methods we used to reconstruct the full angular resolution by the tracking of fission fragments. Below 10 MeV our results are consistent with existing data. For example in the case of 232Th, below 10 MeV the results show clearly the variation occurring at the first (1 MeV) and second (7 MeV) chance fission, corresponding to transition states of given J and K (total spin and its projection on the fission axis), and a much more accurate energy dependence at the 3rd chance threshold (14 MeV) has been obtained. In the spallation domain, above 30 MeV we confirm the high anisotropy revealed in 232Th by the single existing data set. I'll discuss the implications of this finding, related to the low anisotropy exhibited in proton-induced fission. I also explore the critical experiments which is valuable checks of nuclear data. The 237Np neutron-induced fission cross section has recently been measured in a large energy range (from eV to GeV) at the n TOF facility at CERN. When compared to previous measurements, the n TOF fission cross section appears to be higher by 5-7 % beyond the fission threshold. To check the relevance of n TOF data, we simulate a criticality experiment performed at Los Alamos with a 6 kg sphere of 237Np. This sphere was surrounded by enriched uranium 235U so as to approach criticality with fast neutrons. The simulation predicts a multiplication factor keff in better agreement with the experiment (the deviation of 750 pcm is reduced to 250 pcm) when we replace the ENDF/B- VII.0 evaluation of the 237Np fission cross section by the n TOF data. We also explore the hypothesis of deficiencies of the inelastic cross section in 235U which has been invoked by some authors to explain the deviation of 750 pcm. The large distortion that should be applied to the inelastic cross sections in order to reconcile the critical experiment with its simulation is incompatible with existing measurements. Also we show that the nubar of 237Np can hardly be incriminated because of the high accuracy of the existing data. Fission rate ratios or averaged fission cross sections measured in several fast neutron fields seem to give contradictory results on the validation of the 237Np cross section but at least one of the benchmark experiments, where the active deposits have been well calibrated for the number of atoms, favors the n TOF data set. These outcomes support the hypothesis of a higher fission cross section of 237Np.

Dans Mortuaires, une pièce de théâtre en fragments, deux soeurs se rencontrent dans une chambre d'hôtel; Jiji, la plus vieille, vient de retrouver les cendres de leur mère, morte dix ans auparavant; elle voudrait enterrer l'urne définitivement, alors que la plus jeune, Ge, tient à la garder près d'elle. Ce sera l'occasion pour les soeurs de faire valoir leur propre désir et de célébrer la morte, de reprendre contact avec ce qui reste d'elle dans leur mémoire. Le texte se présente sous forme de mini-scènes sans continuité, bien qu’étant toutes reliées, comme un dialogue interrompu, une cérémonie rejouant la mise en pièces du corps. La fragmentation de la mémoire constitue le projet esthétique de la pièce, dont le ressort dramatique tourne autour du souvenir endeuillé et du corps mort. La mort-vivance comme motif d'écriture dans « Aurélia » de Gérard de Nerval est un essai portant sur le rapport qu'entretient Nerval avec les morts dans le récit, ceux-ci constituant son moteur d'écriture. Au moyen de théories telles que la psychanalyse (Freud, Jackson), la sociologie (Muray) et la théorie de la lecture (Picard), il sera démontré que Nerval, dans Aurélia, se fait spirite en faisant revenir les morts au moyen du rêve. L'écriture se pose comme un lieu de rencontre entre les vivants et les morts, un espace dans lequel chacun doit se faire mort-vivant pour aller retrouver l'autre. Les frontières se brouillent et il devient difficile pour Nerval, ainsi que pour le lecteur, de distinguer le rêve de la réalité. / In Mortuaires, a drama in fragments, two sisters meet in a hotel room; Jiji, the oldest, has just found their mother's ashes, dead 10 years ago; she would like to bury the urn, but the youngest, Ge, intends to keep it. It will be the occasion for them to emphasize on their own desire and, much more, to celebrate the dead mother, to reconnect with what remains of her in their memory. The text presents small scenes without continuity, although linked, like an interrupted dialogue, a ceremony replaying the body's breaking into pieces. The memory's fragmentation is the esthetic project of the drama, whose basic dramatic's spring turns around remembering, mourning, and the place of the dead body. La mort-vivance comme motif d'écriture dans « Aurélia » de Gérard de Nerval is an essay studying the connexion between Nerval and the dead ones. In the story, these ones are very important in the process of writing. Using theories such as psychoanalysis (Freud, Jackson), sociology (Muray) and reading theory (Picard), it will be shown that Nerval, in Aurélia, is a medium and tries to take the dead ones back through dream. The writing of his dreams creates for Nerval a place where the living and the dead ones can meet, a place where everyone has to become a living dead to be in contact with others. In that way, boundaries are blurring and it becomes increasingly hard for Nerval, as for the reader, to distinguish dream from reality.

La matière-source du Cycle des astres est une écriture du présent consignée à la volée, des instantanés du quotidien qui laisse trace dans une écriture-temps aux formes hétéroclites. À la fois inscription du présent et trace du passé, la double temporalité des textes participe à la construction narrative d’une œuvre de création où coexistent premiers jets, poésie et autographie, et à l’articulation d’un projet d’écriture où se déploie la construction du Sens. Je me suis intéressée au recyclage des archives, aux jeux de temporalités, mais principalement à la construction narrative du récit et à son effet sur la subjectivité à l’œuvre dans le texte. À partir d’une lecture critique de L’Événement d’Annie Ernaux, je propose dans Le surgissement à l’œuvre une analyse de l’écriture fragmentaire et hétérogène comme moyen pour saisir la réalité à travers l’expérience d’une conscience subjective incarnée dans un texte qui rétablit la cohérence à l’œuvre. / The source/matter for Le Cycle des astres stems from a stenography of the present, snapshots of daily-life that leave trace through diversified forms of writing that I called écriture-temps. The inscription of the present becoming signs from the past represent the double temporality of the texts used as material used in my creative work where drafts, poetry and autography co-occur, and leave trace of a writing project in which the construction of Meaning unfolds through the process. I studied the recycling of archives and the interplay of temporalities, but mostly the construction of the narrative put forward by the text, and its effect on subjectivity. Du surgissement à l’oeuvre furthers this exploration of fragmentary and heteregeneous writing through a critical reading of Annie Ernaux's L’Événement. Writing is shown here as a means by which the essence of a subjective experience is embodied in a text that reestablishes its coherence.

Il est reconnu que les résultats électoraux au Canada varient grandement selon la région. Afin de trouver des explications à ce phénomène, il convient d’étudier comment les grandes régions du Canada se distinguent les unes des autres sur le plan politique. La présente recherche amorce cette étude sous l’angle de l’idéologie. Elle tente de déterminer en quoi l’idéologie politique diffère d’une région à l’autre du pays. Elle s’appuie sur les données des études électorales canadiennes de 2008. On a recours à des questions évaluant les préférences des répondants par rapport à plusieurs enjeux politiques pour répondre à la question de recherche. On conduit en premier lieu une analyse factorielle, qui identifie six facteurs qui ont structuré l’opinion publique lors de l’élection de 2008. Ensuite, des tests T sont conduits pour vérifier si les moyennes de ces facteurs idéologiques sont statistiquement différentes d’une région à l’autre. Les résultats montrent que les différences régionales sont souvent significatives et suivent les hypothèses. Toutefois, les résultats touchant à la privatisation de la santé ainsi qu’au Manitoba et à la Saskatchewan vont à l’encontre des attentes. / It is widely known that electoral results in Canada vary greatly from one region to the next. To explain this phenomenon, it is only appropriate to study how Canadian regions differ from each other politically. The current research is especially interested in regional variations in political ideology. The research relies on data from the 2008 Canadian Electoral Studies. It uses opinion statements to assess respondents’ political preferences to answer the research question. A factor analysis is conducted from these variables to highlight six ideological dimensions. Furthermore, t-tests are used to verify if regional differences on these ideological dimensions are statistically significant. Results show that differences across regions are very often significant and follow hypotheses. However, results regarding the privatization of healthcare and the Midwest run counter to expectations.

The conversion of native forest to agricultural land has been an on-going issue threatening the health of New Zealand’s freshwater systems. However, despite the fact that this has been occurring since early European settlement, our understanding of the mechanistic relationships between riparian vegetation and stream condition are poorly developed. This research investigated: (i) how forests affect downstream benthic macroinvertebrate communities in pasture and the environmental factors driving community change; (ii) how upstream forest size impacted the rate of change in downstream environmental drivers and associated macroinvertebrate community structure; and (iii) whether the addition of coarse particulate organic matter (a single potential driver of forest community structure) can reset community structure to that of a forested state. Physico-chemical conditions, basal energy resources, and macroinvertebrates were surveyed in several New Zealand headwater streams. At Mount Egmont National Park, 10-12 sites were surveyed across a longitudinal forest-pasture gradient in each of five streams flowing from continuous forest to dairy farmland. My results showed that forests can have marked effects downstream. From the forest edge, water temperatures increased consistently, with a rise of approximately 0.2ºC per 100 m of downstream distance. By contrast, coarse particulate organic matter (CPOM) decreased rapidly downstream of the forest, however, low levels of “forest-derived” CPOM were still present 300m downstream from the forest edge. These environmental changes drove significant shifts in macroinvertebrate community structure. Moreover, pasture communities were markedly different from those in forest, despite being only 100 m from the forest edge. In particular, total macroinvertebrate and EPT richness and densities decreased, and communities shifted from evenly distributed allochthonous-based communities to autochthonous-based communities, highly dominated by molluscs (e.g., Potamopyrgus spp.) Subsequent surveys of 6-8 sites across a longitudinal forest-pasture gradient in each of eleven streams flowing from forest fragments of different sizes into grazed pastures throughout the Canterbury region, indicated that stream temperature increased more rapidly downstream of small- and medium-sized fragments, than larger fragments. A Berger-Parker dominance index also indicated that macroinvertebrates responded principally to water temperature, with communities being more highly dominated by temperature-tolerant molluscs in streams flowing from small-sized forest fragments. Several headwater streams in Canterbury were also highly retentive, with marked CPOM rarely exported beyond 50 m downstream of the forest. Experimental additions of leaf litter to the pasture reaches of the same streams dramatically increased amounts of stored benthic CPOM. Although non-significant, trends indicated that EPT and shredder densities increased at litter addition sites, providing promise that CPOM can function as a mechanism directly enhancing healthy stream communities. My findings support the contention that when the replanting of entire stream reaches is infeasible, the use of riparian management strategies which focus on the planting of intermittent patches along stream banks can potentially improve stream habitat and community health downstream.