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. / February 2005

No description available.

La formation du tube neural et l'induction de la crête neurale sont des processus importants qui se passent au cours de la neurulation. Le système nerveux central se forme à partir du tube neural, alors que le système nerveux périphérique, le squelette cranio-facial et les mélanocytes se forment à partir de la crête neurale. Cependant, plusieurs maladies génétiques liées au développement anormal du tube neural et de la crête neurale existent chez l'homme. Donc, notre équipe s'est intéressée à faire une recherche au niveau moléculaire dans ce domaine. Le développement du tube neural et des cellules de la crête neurale est influencé par la présence de plusieurs voies de signalisation y compris la voie Wnt. Nous avons focalisé notre étude sur la transcription du gène Pax3 qui code pour un facteur de transcription qui s'exprime dans le tube neural et les cellules pré-migratoires de la crête neurale. L'induction de Pax3, des cellules de la crête neurale ainsi que l'expression des gènes Cdx (Cdx1, Cdx2 et Cdx4) se font par la voie de signalisation Wnt. Le chevauchement de l'expression des gènes Pax3 et Cdx se passe lors de l'induction de la crête neurale à la plaque neurale postérieure aussi bien que pendant la formation du tube neural et des cellules de la crête neurale. Les résultats préliminaires par ChIP ont montré la présence physique de Flag-Cdx1 et Flag-EnRCdx1 sur le promoteur proximal de Pax3. Notre étude par RT-PCR sur la régulation de l'expression de Pax3 par les facteurs de transcription Cdx a démontré la régulation endogène de Pax3 par ces protéines dans les cellules Neuro2a. L'essai Luciférase montre l'induction de l'expression de Pax3 par la surexpression des protéines Cdx et la diminution de son expression par la surexpression du dominant négatif EnRCdx1 dans les cellules Neuro2a. Après avoir identifié les sites potentiels de liaison pour les protéines Cdx sur le promoteur proximal de Pax3, nous avons procédé à une délétion des différentes régions de ce promoteur. On a remarqué la forte induction du promoteur au niveau de NCE (Neural Crest Enhancer). Pourtant, la mutation en combinaison de ces sites n'a pas montré la diminution de l'activité de ce promoteur. Étant donné la présence d'un site potentiel de liaison pour Brn1 sur le promoteur proximal de Pax3, notre étude par l'essai Luciférase a mis en évidence une synergie entre les co-facteurs Cdx2 et Brn1 dans les cellules Neuro2a. Le même phénomène a été observé dans les cellules P19. Pourtant, la mutation du site de Brn1 n'a pas diminué l'activité du promoteur proximal de Pax3. En conclusion, nos résultats mettent en évidence la non fonctionnalité des sites de liaison pour les facteurs de transcription Cdx sur le promoteur proximal de Pax3 ainsi que la synergie entre la protéine Cdx2 et son co-facteur Brn1 dans les cellules Neuro2a ce qui suggère que la régulation directe de Pax3 par les protéines Cdx n'implique pas de liaison des Cdx à l'ADN. ______________________________________________________________________________ MOTS-CLÉS DE L’AUTEUR : Neurulation, tube neural, crête neurale, neuroectoderme, système nerveux, voie de signalisation Wnt, transcription, facteur de transcription

Plastic  deformation of tubes can be achieved in numerous ways. One of the most useful type is CNC tube bending machines which is used in many industries such as aerospace, automotive, HVAC systems and so on. It is important that all components of system should mate properly after producing and because of this bend shaping requires sensitive operation on each components to ensure regularity of production processes with high quality end-product. Thus, the CNC tube bending industry to become widespread. However it brings some troubleshooting like wrinkling, springback, breakage and ovalisation. This failures depends on geometry of the material such as bending radius, tube thickness and also friction factor between dies and the tube. Effects of all parameters should be examined before generating the theory for a best solution. Therefore, prediction of the required moment for the proper bending process with low cost and shortened production time is needed. All of these requirements can be achieved through a C++ form application program.

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.

A study of two-phase flow in annular channels with annular gaps of less than 1 mm is useful for the design and safety analysis of high power density systems such as accelerator targets and nuclear reactor cores. Though much work has been done on pressure drop in two-phase flow, designers rely mostly on empirical models and correlations; hence, it is valuable to study their applicability for different channel sizes, geometries, and gas qualities. The pressure drop along a concentric annular test section was measured for cases of either constant quality or variable quality along its length (such as in sub-cooled and flow boiling). A porous tube was used to inject gas along the inner surface of the annular channel, thereby simulating the case of flow boiling along the inner surface. The data were compared to predictions of various models and correlations. Additionally, the effect of wall vibrations on the pressure drop was examined. Experiments were conducted by imposing vibrations of known amplitudes and frequencies on the outer tube of the annulus. Wall vibrations were thought to be important for flow in microchannels where the vibration amplitudes may be significant compared to the channel hydraulic diameter. The results obtained in this investigation indicate that the pressure drop correlation given by Beattie and Whalley provides the best agreement with the data for both porous tube gas injection (i.e. variable quality) and constant quality two-phase flow within the narrow annulus. Furthermore, the results show that there is a minimal effect of vibrations on two-phase pressure drop over the range of frequencies and amplitudes studied.

Pulse Tube Cryocoolers (PTC) is widely used in aerospace and missile guiding systems where extreme reliability and ruggedness are crucial. PTCs, in particular, are a class of rugged refrigeration systems that are capable of maintaining temperatures as low as 4 K, without a moving part in their cold end. The operation of PTCs is based on complicated and poorly-understood solid-fluid interactions involving periodic flows of a cryogenic fluid in micro porous structures. Currently, PTCs is often modeled as one-dimensional flow fields using methods whose relevance to cryocoolers is at best questionable. Furthermore, recent CFD-based investigations have underscored the need for adequate closure relations representing periodic flows in anisotropic micro porous media, and have shown that multi-dimensional effects can be significant in PTCs. The objectives of this investigation were to experimentally measure and correlate the anisotropic hydrodynamic parameters for typical micro porous structures that are used in the regenerators of PTCs fillers; perform modeling and CFD-based simulations to elucidate the component and system-level thermo-fluidic processes in modern pulse tube cryocooler designs; and perform a preliminary CFD-based assessment of the effect of miniaturization on the thermal performance of a current PTC design. In the experiments, the measurement and correlation of the directional (axial and radial) permeabilities and Forchheimer s inertial coefficients of meshed screen, sintered mesh, foam metal, and stacked micro-machined plate regenerator fillers were of interest. Hydrodynamic parameters under steady-state conditions were addressed first. Pressure drops were measured for purely axial flow in cylindrical test sections and predominantly radial flows in annular test sections that contained regenerator fillers of interest, under steady-state conditions. The permeabilities and Forchheimer s inertial coefficients were then obtained in an iterative process where agreement between the data and the predictions of detailed CFD simulations addressing the entire test sections and their surroundings were sought. Periodic flows were then addressed. Using high frequency pressure transducers and hot wire anemometry, instantaneous pressures and mass fluxes are measured under periodic purely axial flow conditions. CFD simulations of the experiments were then performed, whereby permeabilities and Forchheimer coefficients that bring about agreement between data and simulation results were calculated.

An experimental investigation of heat and mass transfer in a horizontal tube falling-film ammonia-water absorber was conducted. A tube bank consisting of four columns of six 9.5 mm (3/8 ) nominal OD, 0.292 m (11.5 ) long tubes was installed in an absorber shell that allowed heat and mass transfer measurements and optical access. A test facility consisting of all the components of a functional absorption chiller was fabricated specifically for this investigation. Several variations of the basic system set up were fabricated to enable testing over the wide range of conditions (nominally, desorber solution outlet concentrations of 5 - 40% for three nominal absorber pressures of 150, 345 and 500 kPa, over solution flow rates of 0.019 0.034 kg/s.) Measurements at the absorber were used to determine heat transfer rates, overall thermal conductances, solution-side heat and vapor-side mass transfer coefficients for each test condition. For the range of experiments conducted, the solution heat transfer coefficient varied from 923 to 2857 W/m2-K while the vapor mass transfer coefficient varied from 0.0026 to 0.25 m/s and the liquid mass transfer coefficient varied from 5.51×10-6 to 3.31×10-5 m/s depending on the test condition. The solution heat transfer coefficient increased with increasing solution flow rate; however, the vapor and liquid mass transfer coefficients seem to remain unaffected with the variations in solution flow rate and were found to be primarily determined by the vapor and solution properties. The experimental heat and mass transfer coefficients were compared with the relevant studies from the literature. Based on the observed trends, heat transfer correlations and mass transfer correlations in the vapor and liquid phases were developed to predict heat and mass transfer coefficients for the range of experimental conditions tested. These correlations can be used to design horizontal tube falling-film absorbers for ammonia-water absorption systems.

The bottleneck of forming small radius tube is that traditional processing methods can¡¦t effectively produce smaller bend radius tube in domestic industry now. First, this study will propose methods without mandrel, based on traditional bending way of rotary draw bending to form small bending radius tubes. This paper investigate results of traditional bending mode without mandrel in second part. By using finite element analysis, find the effects on wall-thinning, wall-thickening and ovility with different processing parameters. Also using the research results to obtain forming ranges. Through heating tubes we explore the possibility of hot forming of parameters and to find the impacts on bending tubes which heating under different parameters. We use the results above to find out the hot forming ranges. In heating and quenching of rotary draw bending experiments, we found that heating tubes under the same processing parameter can effectively enhance the formability and successfully derive better products of small radius bending tubes, to accomplish non-mandrel rotary bending process of small bending radius.

In recent years, with advances in medical treatment, the demand of medical beauty market has increased year by year. With the continuous innovation of nanotechnology, medical technology with nanometer level is becoming the one of the most important issue of the development of medical biotechnology in recent years. In order to make the products effective, the products have to be transported into the human skin. In traditional medical treatments, the devices of contacting type or invading type were adopted, and might cause some infected problems. To avoid these situations, some medical companies have developing the non-contact type device¡Ð gene gun. This device use nitrogen as motive force to atomize the thin film of the injection products, then delivering these products to derma. This research utilizes computational fluid dynamics software to build the FEM simulation model of Venturi tube inside of a gene gun. Then, analyzing the speed and atomization of fluid which inside or outside of Venturi tube. A FEM simulated mechanism for the atomization of multiphase flow was constructed in this research successfully. The effects of variations of some geometric parameters of Venturi tube on the atomization of thin film were studied also. The obtained results can shorten cost and time in relevant development.