Générer de la diversité cellulaire est essentiel en biologie du développement et pour préserver l'homéostasie des tissus chez l'adulte. Cela résulte du choix des cellules souches et progéniteurs à s'engager dans un destin particulier en réponse à des signaux extrinsèques et à des propriétés intrinsèques. L'objectif de ma thèse était d'élucider le rôle du cycle cellulaire dans le processus de neurogenèse (production de neurones) en utilisant comme paradigme le tube neural d'embryon de poulet. D'une part, j'ai développé une nouvelle stratégie d'imagerie permettant de mesurer la longueur des quatre phases du cycle cellulaire en temps réel dans les progéniteurs neuraux. D'autre part, j'ai réalisé des expériences de gain et perte de fonction d'un régulateur de l'entrée en mitose, la phosphatase CDC25B, dans les progéniteurs neuraux et montré que ce régulateur du cycle favorise les divisions neurogéniques au dépend des divisions prolifératives contrôlant ainsi la production neuronale. / Generating cell diversity is essential in developmental biology and to preserve tissue homeostasis in adulthood. This results from the choice of stem cells and progenitor cells to commit into a particular fate in response to extrinsic cues and to intrinsic properties. The aim of my PhD was to elucidate the role of the cell cycle in the neurogenesis process (i.e. in neuron generation) using the embryonic chick neural tube as a paradigm. On the one hand, I have developed a new real time imaging strategy to measure the length of the four cell cycle phases in neural progenitors. On the other hand, I performed gain and loss of function experiments of a regulator that control mitosis input, the CDC25B phosphatase, in neural progenitors and showed that this cell cycle regulator promotes neurogenic divisions at the expense of proliferative divisions, thus controlling neuronal production.

Most of the research on high strain rate effects on wood since the 1950s has been on impact loading. Very limited work has been conducted on full-scale wood specimens under blast loading. In North America, the prevalence of these structures makes them susceptible to unintended blast effects. The question on how to retrofit and protect these structures against blast loads has still not been addressed adequately, and design provisions for new wood structures against blast are not comprehensive. Far-field explosion effects were simulated using the University of Ottawa shock tube. Twenty-five light-frame wood stud walls were tested dynamically. The research program aimed to determine the response of light-frame wood stud walls to blast loads that correspond to the heavy to blow-out damage levels. The results showed that, under idealized simply supported end conditions, the stud walls failed in flexure. Under heavier loads, ripping of sheathing commonly used in light-frame wood structures was observed, which caused premature failure of the assembly because the load was not fully distributed to the studs. The use of stiffer sheathing or reinforcing the sheathing provided a better load path and the wall was capable of reaching its full capacity. The effect of using realistic boundary connection details was investigated, and the results showed that typical connection detailing performed poorly under blast loads. Designed steel brackets connecting the studs to the rim-joist allowed for the studs to reach their full capacity. An analytical single degree-of-freedom model was generated using material properties obtained from static testing. The model was validated using the experimental results from the shock tube testing. Also, a catcher system consisting of welded-wire-mesh was incorporated into the wall system in order to diminish debris throw.

Accounting for blast hazards has become one of the major concerns for civil engineers when analysing and designing structures. Recent terrorist attacks and accidental explosions have demonstrated the importance of mitigating blast effects on buildings to ensure safety, preserve life and ensure structural integrity. Innovative materials such as high-strength concrete, steel fibers, and high-strength steel offer a potential solution to increase resistance against extreme dynamic loading and improve the blast resilience of buildings. This thesis presents the results of an experimental and analytical study examining the effect of high-strength concrete, high-strength reinforcement and steel fibers on the blast behaviour of reinforced concrete columns. As part of the study, a total of seventeen reinforced concrete columns with different design combinations of concrete, steel fibers, and steel reinforcement were designed, constructed, and tested under gradually increasing blast loads using the University of Ottawa shock-tube facility. Criteria used to assess the blast performance of the columns and the effect of the test variables included overall blast capacity, mid-span displacements, cracking patterns, secondary fragmentation, and failure modes. The effect of concrete strength was found to only have a moderate effect on the blast performance of the columns. However, the results showed that benefits are associated with the combined use of high-strength concrete with steel fibers and high-strength reinforcement in columns tested under blast loads. In addition to the experimental program, a dynamic inelastic single-degree-of-freedom analysis was performed to predict the displacement response of the test columns. A sensitivity analysis was also conducted to examine the effect of various modelling parameters such as materials models, DIFs, and accumulated damage on the analytical predictions.

The CSA S850 Blast standard provides guidelines that can be used to enhance the blast performance of reinforced concrete structures. In the case of beams, the standard requires the use of top continuity (compression) bars and well-detailed transverse steel to ensure strength and ductility under blast loads. However, the requirements in the CSA S850 standard are intended for normal-strength concrete structures. Given the increased use of high-strength concrete (HSC) in practice, there is a need to explore the effects of modern blast designs on the behavior of HSC structures subjected to blast loads. Accordingly, this project examines the effect of modern reinforcement detailing on the static, dynamic and post-blast performance of high-strength concrete beams. The study further examines the ability to use fibers to relax such detailing and simplify construction. A total of seventeen beams are tested. Static testing is conducted under four-point bending, with blast testing conducted using the University of Ottawa shock-tube. The post-blast behavior of the beams is assessed by conducting residual static tests on the blast-damaged specimens. The parameters investigated include the effects of: blast detailing vs. nominal detailing, steel fibers, the effect of longitudinal steel ratio (in compression and tension) and tie spacing. The results show that under static loads, the use of blast detailing significantly improves the flexural behavior of the beams in terms of ductility. Likewise, the provision of continuity (compression) bars and closely spaced ties is found to improve blast performance by better controlling displacements, increasing blast resistance, limiting damages and allowing for important post-blast residual capacity. The use of steel fibers and relaxed detailing (increased tie spacing) is found to increase resistance and improve cracking behavior under static loads, with an ability to match the blast performance of more heavily-detailed HSC specimens. The use of fibers also allowed for substantial post-blast capacity. Finally, the steel ratio (in tension, in compression and in the transverse direction) was found to affect the blast behavior of the HSC beams. In addition to the experiments, the analytical study predicts the static and blast response of the tested beams using sectional analysis and non-linear SDOF modeling. Results show that the analysis methodology was able to predict the static and blast responses of the blast-detailed and fiber-reinforced HSC beams with reasonable accuracy.

High-performance liquid chromatography (HPLC) is the most widely used analysis technique. However, its sensitivity is limited. Sample preconcentration methods, such as fiber-based solid-phase microextraction (SPME) and in-tube SPME (capillary microextraction) offer improved detection limits. It is, however, difficult to couple fiber SPME on-line with HPLC due to the need for complicated desorption devices. Such coupling is further complicated due to the limited solvent stability of the extracting phase both in the fiber and in-tube formats of SPME. In this research, surface-bonded sol-gel sorbents were developed to provide the solvent stability required for effective on-line hyphenation of capillary microextraction (CME) with HPLC. These sol-gel sorbents were prepared using (1) silica-based, (2) titania-based, and (3) germania-based sol-gel precursors. Sol-gel reactions were performed within fused silica capillaries to create a number of organic-inorganic hybrid sorbents in the form of surface-bonded coatings: (1) alkyl (methyl, octyl, octadecyl), (2) polydimethyldiphenylsiloxane, (3) titania poly(tetrahydrofuran), and (4) germania tri-block polymer. The sol-gel coated microextraction capillaries were capable of efficiently extracting a wide variety of analytes, including polycyclic aromatic hydrocarbons, ketones, aldehydes, aromatic compounds, amines, alcohols, and phenols with ng/L to pg/L detection limits. The sol-gel methyl coating demonstrated a counterintuitive ability to extract polar analytes. Sol-gel polydimethyldiphenylsiloxane coatings were found to be resistant to high temperature solvent exposure (150°C and 200°C), making them suitable for use in high-temperature liquid phase separations. To better understand how extraction takes place, effects of alkyl chain length and sol-gel precursor concentration were evaluated in the study on sol-gel alkyl coatings. The sol-gel titania poly(tetrahydrofuran) coating was also capable of extracting underivatized aromatic acids and polypeptides at pHs near their respective isolectric points. The sol-gel titania poly(tetrahydrofuran) coatings and the sol-gel germania tri-block polymer coatings demonstrated impressive resistance to extreme pH conditions, surviving prolonged exposure to 1.0 M HCl (pH approx. 0.0) and 1.0 M NaOH (pH approx. 14.0) with virtually no change in extraction behavior. Sol-gel germania tri-block polymer coatings were also stable under high temperature solvent conditions (200°C). In addition, for the first time, the analyte distribution constants between a sol-gel germania coating and the aqueous samples (Kcs) were determined.

Function of the adult nervous system relies on the appropriate establishment of neural circuits during embryogenesis. In vertebrates, the neurons that make up motor circuits form in distinct domains along the dorsoventral (DV) axis of the neural tube. Each domain is characterized by a unique combination of transcription factors (TFs) that promote a specific fate, while repressing the fates of adjacent domains. The prdm12 TF is required for the expression of eng1b and the generation of V1 interneurons in the p1 domain, but the details of its function remain unclear. We used CRISPR/Cas9 genome editing technology to generate the first germline mutants for the prdm12 gene and used this resource, together with classical luciferase reporter assays and co-immunoprecipitation experiments, to study prdm12b function in zebrafish. We also generated germline mutants for bhlhe22 and nkx6.1 to examine how these TFs act with prdm12b to control p1 formation. We find that prdm12b mutants lack eng1b expression in the p1 domain and also possess an abnormal Mauthner cell-dependent escape response. Using cell culture-based luciferase reporter assays, we demonstrate that Prdm12b acts as transcriptional repressor, most likely by recruiting EHMT2/G9a. We also show that the Bhlhe22 TF binds to the Prdm12b zinc finger domain to form a Bhlhe22:Prdm12b complex. However, bhlhe22 mutants display normal eng1b expression in the p1 domain. While prdm12 has been proposed to promote p1 fates by repressing expression of the nkx6.1 TF, we do not observe an expansion of the nkx6.1 domain upon loss of prdm12b function, nor is eng1b expression restored upon simultaneous loss of prdm12b and nkx6.1. We conclude that prdm12b germline mutations produce a phenotype that is indistinguishable from that of morpholino-mediated loss of prdm12 function. In terms of prdm12b function, our results indicate that Prdm12b acts as transcriptional repressor and interacts with both EHMT2/G9a and Bhlhe22. However, bhlhe22 function is not required for eng1b expression in vivo, perhaps indicating that other bhlh genes can compensate for its loss during embryogenesis. Lastly, we do not find evidence for nkx6.1 and prdm12b acting as a repressive pair in the formation of the p1 domain – suggesting that prdm12b is not solely required to repress non-p1 fates, but is also needed to promote p1 fates.

One of the first embryonic structures generated during early human development is the neural tube. The embryonic process of neurulation, including neural tube closure, is necessary for proper brain and spinal cord development, whereas improper closure leads to neural tube defects including anencephaly, spina bifida, and craniorachischisis. The mechanism by which these defects occur is unknown, but some evidence suggest that redox disruption may play a role. Cellular redox state is important in regulating key processes during neural tube closure, including differentiation, proliferation, gene expression, and apoptosis. This study aims to determine whether redox potential shifts and these key processes are affected similarly or differentially after treatment with three neural tube defect-inducing developmental toxicants: ceramide (C2), valproic acid (VPA), and fumonisin (FB1). Using the P19 cell model of neurogenesis, in both undifferentiated and terminally differentiated cells, we analyzed glutathione (GSH) redox (Eh) potential to evaluate the effect of each toxicant over time. We show that in C2 and VPA treated cultures an oxidizing shift occurs, but interestingly, FB1 treatment results in a reducing shift in embryonic GSH Eh as compared to untreated cultures. Using the chick embryo model, comparable redox shifts were observed as were seen in P19 cells, supporting similarity between the models. To better understand how differential shifts in the redox state can result in similar defects, we then examined potential variances in neuronal differentiation and cellular proliferation, survival, metabolism, adhesion, and gene expression under each treatment. We report changes to cellular and embryonic endpoints that support dysmorphogenesis, likely the result of oxidizing or reducing stress that altered redox state. These results support the need for broad comparative analyses such as this to determine whether toxicants that cause the same types of defects, whether NTDs or others, act through similar or different mechanisms. This can better inform preventative measures used to reduce the risk and occurrence of birth defects.

<div>Due to reduced pain, shortened hospital stay and recovery, minimally invasive surgery (MIS) is becoming more and more popular in healthcare systems. MIS requires some devices for the motion and force transformation from outside to the inside of the body of a patient, and the strangled cables play a significant role in developing the instrumentations to serve for such purposes. However, current design and selection of a strangled cable is mostly intuitive that depend greatly on designers’ experiences and availability of experimental data, which leads to non-optimized designs and longer design cycles. In this thesis, both of analytical modelling and numerical simulation are proposed to build the relation of applied torque and deflection of part, so that a strangled cable with a given configuration can be characterized in term of its load-deflection relation. The defined relation has its great significance and application potential in the design optimization and precise controls of medical devices for MISs.Besides the various patterns of strangled cables, a Helical hollow strand (HHS®) tube is a special type of strangled cables with single- or multiple- layer configurations., In each layer, each of the helical wires touches its two neighboring helical wires, and it has a coreless hollow at the center. Its primary application is to carry a torsional load in a twisting mode. As an extreme, there is a possibility that all helical wires touch each other, and this forms a statically indeterminate contact obstacle in design analysis. Numerical simulation would predict that contacts occur simultaneously at all possible contacting points under the circumference that the strand is fixed at one end against rotation. In addition, the friction at contacts will affect the torsional deformation; therefore, these contacts must be taken into consideration in the development of analytical and numerical simulation models.This thesis reports the results of the investigation on the characteristics of Helical hollow strand tube (HHS®), more specifically, the relation of torsional deflection and the applied torque over a tube in the clockwise (CW) direction. The numerical simulation approach to predict the torsional deflection of HHS with various design parameters and configurations is emphasized. </div><div><br></div>

Hydraulic energy is one of the most important sources in the world for electricity production. Nowadays the trend is to limit the production of the electricity from fossil fuels and to protect the environment. The main idea is to use more renewable energy sources such as wind and solar energy. Unfortunately, these alternative sources are strongly dependent on current weather conditions, which causes the instability of the electrical grid. Luckily pumped storage and hydraulic power plants provide the solution. However, it requires an extension of the operating range of the hydraulic machines. For that reason, the water turbines now operate over and extended range of regimes, that can be quite far from the best efficiency point. Hence two types of unstable two-phase flows in the Francis turbine draft tube occur: part load overload. This diploma’s thesis is focused on the Francis turbine operating at the part load. During part load conditions the helical vortex rope is being developed in the draft tube, it causes pressure pulsation and it can lead to the hydro-acoustic resonance, which damages the elements of the power plant. The aim is to eliminate the pulsation by jet control of the swirling flow in the draft tube. In the diploma’s thesis, various approaches to jet control of the flow in conical diffuser are tested using the computational fluid dynamics.

The thesis builds on the project FSI-S-14-2394, in which the biaxial state of tension of longitudinally welded tubes made from material 17 240 was investigated. The experiment was carried out under dynamic conditions on an impact tester, which was designed with structural simplicity and ease of observation of the experiment in mind. Deformation was recorded by high-speed cameras and a dynamometer. Results of the experiment were processed by measuring devices and subsequently used in a simulation created using a software utilizing the finite element method. Simulations were created for samples DA8 and DB9. These samples were selected because they did not crack and were fully stamped. Results of the simulation correspond to the values measured by high-speed cameras and a dynamometer with a small variance. Based on comparison of the results, it can be states that the simulation is technically acceptable.