Statement of problem: We have shown that the C677T 5,10 methylenetetrahydrofolate reductase (MTHFR) variant is associated with elevated maternal serum α-fetoprotein (MSAFP), the most common screening test for neural tube defects (NTD). Therefore, past contradictory studies of NTDs and C677T MTHFR may have been biased because of changes in case populations after prenatal diagnosis and termination of pregnancy. Further, an unexplained elevation of MSAFP is known to increase the risk for later pregnancy complications. Is the C677T MTHFR variant a predisposing genetic variant for both NTDs and later complications of pregnancy? Methods: A retrospective study of women with pregnancies resulting in NTD outcome and women with unexplained elevations of MSAFP was undertaken. Women and their partners were genotyped for the C677T MTHFR allele. Couples with a pregnancy resulting in a NTD outcome were compared to couples whose pregnancy outcome did not involve. Couples with unexplained elevations of MSAFP who did and did not have later complications of pregnancy were also compared. Allele frequencies for all groups were then compared against the previously established Manitoba population allele frequency (based on 977 consecutive newborn metabolic screening bloodspots). A review of all studies of NTDs and association with the C677T MTHFR variant was undertaken to determine if the association between the variant and MSAFP is a source of bias. NTD incidence was examined before and after folic acid food fortification introduced in Canada in 1999. Results: There is an increase in the allele frequency of the C677T MTHFR variant in parents with an unexplained elevated MSAFP followed by later complications of pregnancy. The C677T MTHFR variant is also a contributing genetic factor to NTDs worldwide. The incidence of NTDs in Manitoba has decreased by 37% since food fortification with folic acid was introduced. Conclusions: The C677T MTHFR variant is a contributing genetic factor to both later complications of pregnancy after an unexplained elevation of MSAFP and to NTDs. This variant is folate sensitive and folic acid fortification has reduced the incidence of NTDs.

Chez les vertébrés, la neurulation représente les premiers stades de développement du système nerveux durant l'embryogenèse. Elle consiste en la formation, à partir du neuroectoderme, des premières ébauches du système nerveux. Ce processus est finement régulé par un réseau complexe de gènes et le dérèglement de l'un d'entre eux peut entraîner le développement d'une maladie congénitale. Le traitement et la prévention de ces maladies passent par le savoir et la compréhension des différents processus impliqués dans le développement du système nerveux. La souris est un bon modèle d'étude in vivo de la neurogenèse et la technologie Cre-LoxP permet de contrôler l'activation spatiotemporelle d'un transgène. Cependant, aucun modèle de souris ne cible spécifiquement la plaque postérieure durant la neurulation de l'embryon. L'enhancer intronique Cdx2NSE a été caractérisé comme capable de récapituler l'expression du gène Cdx2 dans la plaque neurale postérieure. Notre nouvelle lignée de souris transgénique Cdx2NSE-Cre est capable d'exprimer la recombinase Cre dès le jour embryonnaire 7.5 (E.7.5) dans la plaque neurale postérieure. Elle permet ainsi de cibler le tube neural avec comme limite antérieure la partie caudale du rhomboncéphale. Dans ces mêmes limites, toutes les structures dérivées des cellules de la crête neurale vont également être ciblées par notre nouveau modèle murin, ce qui en fait un très bon outil pour l'étude de la neurogenèse. Le mécanisme de régulation des protéines Cdx spécifiquement dans le neuroectoderme est à ce jour toujours méconnu. L'étude in vitro de ce même enhancer Cdx2NSE nous a permis de montrer que les trois principales voies de signalisation impliquées dans le développement neural et dans l'induction des cellules de la crête neurale, à savoir les voies FGF, BMP et Wnt canonique, sont capables d'en réguler son expression sous le contrôle du gène rapporteur de la luciférase. Enfin, différentes études suggèrent une implication des protéines Cdx dans l'induction des cellules de la crête neurale et dans la fermeture du tube neural, notamment par la régulation de Pax3. Les enhancers de la crête neurale de Pax3 NCE1 et NCE2 sont effectivement régulés par la voie Wnt-Cdx (Sanchez-Ferras et al., 2012) mais un troisième enhancer de la crête neurale (NCE3) a été également caractérisé (Dagenhardt et al., 2010). Nos résultats préliminaires en essai luciférase nous suggèrent une régulation positive de cet enhancer NCE3 par les protéines Cdx1 et Cdx2. ______________________________________________________________________________ MOTS-CLÉS DE L’AUTEUR : neurogenèse, Cdx2NSE, souris, voies de signalisation, Cdx, Pax3, NCE3

The physical properties within the two-dimensional flow produced by the reflection of a plane shock of intermediate strength at a wedge, have been determined by analysis of the particle trajectories. The particle trajectories were obtained by high speed photography of smoke tracers within the flow. Trajectories were determined for different initial positions of the tracers relative to the wedge. The conservation of mass equation was used to determine the density at points within the flow. A knowledge of the shock configurations within the flow, together with the Rankins-Hugoniot equation, was used to determine the pressure immediately behind the incident and reflected shocks. The isentropic equation of state was used to determine the pressure after the passage of the reflected shock. The pressure determined in this manner agreed, within the limits of experimental error, with that obtained using a piezo-electric transducer. The temperature, velocity of sound, and particle velocity at points within the flow were also determined. / Graduate / 0605

Planar cell polarity (PCP) refers to the coordinated orientation, movement, or structure of cells within the plane of a tissue. Zebrafish PCP mutants such as the vangl2 mutant exhibit defects in convergent extension, neural tube morphogenesis, and ciliary positioning. Tmem14a is a putative tetraspanin protein that was identified as an potential interactor of Vangl2 in a membrane yeast-two hybrid screen. GFP-tagged versions of Tmem14a are localized to the trans-Golgi network in zebrafish neuroepithelial cells. Knockdown of Tmem14a activity results in convergent extension defects, an ectopic accumulation of cells in the neural tube, and disorganized cilia. The localization of GFP-tagged Tmem14a to the trans-Golgi network suggested that Tmem14a plays a role in the trafficking of core PCP components to the cell membrane. Indeed, the membrane localization of GFP-Vangl2 was disrupted in Tmem14a morphants. Thus, Tmem14a is an interactor of Vangl2 and a novel regulator of vertebrate planar cell polarity signaling.

Planar cell polarity (PCP) refers to the coordinated orientation, movement, or structure of cells within the plane of a tissue. Zebrafish PCP mutants such as the vangl2 mutant exhibit defects in convergent extension, neural tube morphogenesis, and ciliary positioning. Tmem14a is a putative tetraspanin protein that was identified as an potential interactor of Vangl2 in a membrane yeast-two hybrid screen. GFP-tagged versions of Tmem14a are localized to the trans-Golgi network in zebrafish neuroepithelial cells. Knockdown of Tmem14a activity results in convergent extension defects, an ectopic accumulation of cells in the neural tube, and disorganized cilia. The localization of GFP-tagged Tmem14a to the trans-Golgi network suggested that Tmem14a plays a role in the trafficking of core PCP components to the cell membrane. Indeed, the membrane localization of GFP-Vangl2 was disrupted in Tmem14a morphants. Thus, Tmem14a is an interactor of Vangl2 and a novel regulator of vertebrate planar cell polarity signaling.

Lighter structural and energy absorbing materials are essential to increase fuel efficiency in transportation systems and have provided a motivation to investigate the use of new joining techniques based on the use of high strength and high tenacity adhesives. Current joining techniques, such as spot-welding, limit the possible weight reduction that can be achieved if lighter sections, dissimilar materials and/or novel geometries were to be used. Adhesive materials can address many limitations of current joining techniques. To take advantage of the available numerical codes for the simulation of bonded structures during dynamic crash events, a constitutive model for structural adhesive material using cohesive elements was assembled from the measured properties of two structural adhesives; DP-460NS and EC-2214 (3M, Canada). To verify that the proposed cohesive model accurately describes the behavior of the materials a two stage approach was used. First, a cohesive element formulation of the adhesive material was implemented to investigate a Double Cantilever Beam (DCB) (ASTM test D3433-99). The results of the simulation were compared against available experimental data. Second, using sub-size crush tube structures assembled from steel sections that were adhesively bonded, quasi-static and impact events were performed. The results from the experiment were compared against the numerical simulation of the same structure using cohesive elements to describe the adhesive joint. Later, Tie-Breaks were implemented to reduce computational times. Both types of elements successfully represented the adhesive joint and the numerical model of the crush tube was in good agreement with the overall load-displacement behavior of the experimental crush tubes. The use and testing of sub-size structures not only permitted the validation of the numerical models; it also investigated the feasibility of adhesive-only joints in automotive structures that may be exposed to crash scenarios. Sub-sized tubes were used due to equipment capacity limits, but an analysis was undertaken to demonstrate appropriate structural scaling. Even though the results between the experiments and the simulations were in very good agreement, it is clear that current cohesive material models and Tie-Breaks cannot incorporate strain rate effects, which may be important under dynamic impact conditions. Although testing in the literature has reported that the mechanical properties of the bond are affected by the properties of the joined materials as well as the geometry of the joint, these effects in the case of crush tube structures seem perhaps negligible in view of the simulation results.

The design and construction of a state-of-the-art ultra-high vacuum spectrometer for the performance of angle-resolved inverse photoemission spectroscopy is presented. Detailed descriptions of its most important components are included, especially the Geiger-Muller ultraviolet photodetectors. By building on recent developments in the literature, we expect our spectrometer to achieve resolution comparable or superior to that of other prominent groups, and in general be one of the foremost apparatus for studying the momentum dependence of the unoccupied states in strongly correlated materials. Summaries of the theory of angle-resolved inverse photoemission spectroscopy and the basics of ultra-high vacuum science are also included.

The problem of condensation of steam on a vertical tier of horizontal tubes is investigated by both analytical and experimental methods in this study. A computer program is written to perform the analysis of laminar film condensation on the horizontal tubes. The program is capable to calculate condensate film thickness and velocity distribution, as well as the heat transfer coefficient within the condensate. An experimental setup was also manufactured to observe the condensation phenomenon. Effects of tube diameter and temperature difference between steam and the tube wall on condensation heat transfer have been analytically investigated with the computer program. Experiments were carried out at different inclinations of the tier of horizontal tubes. Effects of the steam velocity and the distance between the horizontal tubes are also experimentally investigated. Results of the experiments are compared to those of the studies of Abdullah et al., Kumar et al. and Nusselt as well as to the analytical results of the present study.

No description available.

No description available.