This study is concerned with the compositional analysis of Roman and early post-Roman glass from both domestic assemblages and the remains derived from glass working and producing sites in Britain, using Inductively Coupled Plasma Spectrometry (ICPS). Samples analysed were from glassworking waste from Mancetter (midsecond century), Leicester (third century) and Worcester (first to third centuries), glass production debris, probably manufactured from the raw materials, in conjuncton with a domestic assemblage, from Coppergate (first to fourth centuries, or possibly later), and a domestic assemblage from Fishergate (spanning both the Roman and immediate post- Roman periods). All the glass analysed was shown to be of a typical and uniform soda-limesilica composition, except for a small number of vessel fragments from York which were higher in calcium. Any compositional differences between blue-green glasses typologically dated either to the Roman or Saxon periods, were found not to be consistent. Analysis of the colourless glass showed that the majority appeared to be actively decolorized using antimony, in conjunction with apparent differences In the compositions of the raw materials, when compared to glass of the same date in other 0 colours. Compositional differences between melted waste from Mancetter, Leicester and Worcester, were apparent, but not to an extent which allowed characterization to be successful. Analysis of glassmelting pots from Coppergate showed some high temperature glassworking (and possibly glassmaking) could have occurred. Other debris, thought to be indicative of glassmaking was also analysed and compared to the composition of the Roman domestic assemblage.

Carbon nanotube templated microfabrication (CNT-M) is a term describing a grouping of processes where carbon nanotubes (CNTs) serve a structural role in the fabrication of a material or device. In its basic form, CNT-M is comprised of two steps: produce a template made from carbon nanotubes and infiltrate the porous template with an additional material. Vertically aligned carbon nanotube (VACNT) templates can be grown to heights ranging from microns to millimeters and lithographically patterned to a desired form. Deposition of an existing thin film material onto a CNT template will coat all template surfaces and can produce a near solid material with dimensions on the millimeter scale with resulting material properties coming primarily from the thin film. Progress within CNT-M falls broadly within one of two categories: control of the CNT template's properties and form, or control of infiltration and new materials.Three-dimensional CNT templates were developed to allow patterned multilayer VACNT structures. In one embodiment, VACNTs were grown below an existing, patterned and capillary-formed VACNT structure by reusing the original catalyst in combination with newly deposited catalyst to create a CNT-based microneedle array on a VACNT support. In another embodiment, VACNTs were mechanically coupled from the initial stages of growth to create a smooth, low porosity surface on which a secondary, patterned CNT forest was grown using standard film deposition and lithographic techniques.A microfabrication compatible thermal barrier was produced using CNTs as a sacrificial template for silicon oxide. The resulting thermal barrier exhibited a thermal conductivity that could be tuned across 2 orders of magnitude based on the degree to which the sacrificial template was removed. Carbon infiltrated carbon nanotubes (CI-CNTs) were produced that exhibited a Young's modulus ranging from 5GPa to 26GPa based on controlled process parameters. Porosity, centroid position, and the second moment of area was calculated from SEM images of CI-CNT structures using an automatic pore identification technique. The porosity results suprisingly show little to no porosity gradient across the width of the structure and a nearly linear increase in porosity from the top to bottom. This work advances the understanding of existing CNT-M processes and demonstrates novel techniques for producing future CNT templates.

<p> This study focuses on developing a new online recursive numerical algorithm for a coupled nonlinear inverse heat conduction-microstructure problem. This algorithm is essential in identifying, designing and controlling many industrial applications such as the quenching process for heat treating of materials, chemical vapor deposition and industrial baking. In order to develop the above algorithm, a systematic four stage research plan has been conducted. </P> <p> The first and second stages were devoted to thoroughly reviewing the existing inverse heat conduction techniques. Unlike most inverse heat conduction solution methods that are batch form techniques, the online input estimation algorithm can be used for controlling the process in real time. Therefore, in the first stage, the effect of different parameters of the online input estimation algorithm on the estimate bias has been investigated. These parameters are the stabilizing parameter, the measurement errors standard deviation, the temporal step size, the spatial step size, the location of the thermocouple as well as the initial assumption of the state error covariance and error covariance of the input estimate. Furthermore, three different discretization schemes; namely: explicit, implicit and Crank-Nicholson have been employed in the input estimation algorithm to evaluate their effect on the algorithm performance. </p> <p> The effect of changing the stabilizing parameter has been investigated using three different forms of boundary conditions covering most practical boundary heat flux conditions. These cases are: square, triangular and mixed function heat fluxes. The most important finding of this investigation is that a robust range of the stabilizing parameter has been found which achieves the desired trade-off between the filter tracking ability and its sensitivity to measurement errors. For the three considered cases, it has been found that there is a common optimal value of the stabilizing parameter at which the estimate bias is minimal. This finding is important for practical applications since this parameter is usually unknown. Therefore, this study provides a needed guidance for assuming this parameter. </p> <p> In stage three of this study, a new, more efficient direct numerical algorithm has been developed to predict the thermal and microstructure fields during quenching of steel rods. The present algorithm solves the full nonlinear heat conduction equation using a central finite-difference scheme coupled with a fourth-order Runge-Kutta nonlinear solver. Numerical results obtained using the present algorithm have been validated using experimental data and numerical results available in the literature. In addition to its accurate predictions, the present algorithm does not require iterations; hence, it is computationally more efficient than previous numerical algorithms. </p> <p> The work performed in stage four of this research focused on developing and applying an inverse algorithm to estimate the surface temperatures and surface heat flux of a steel cylinder during the quenching process. The conventional online input estimation algorithm has been modified and used for the first time to handle this coupled nonlinear problem. The nonlinearity of the problem has been treated explicitly which resulted in a non-iterative algorithm suitable for real-time control of the quenching process. The obtained results have been validated using experimental data and numerical results obtained by solving the direct problem using the direct solver developed in stage three of this work. These results showed that the algorithm is efficiently reconstructing the shape of the convective surface heat flux. </p> / Thesis / Doctor of Philosophy (PhD)

The nucleotide excision repair (NER) pathway is essential for repair of UV-induced bulky DNA lesions. NER is divided into two subpathways: global genome repair (GGR) and transcription-coupled repair (TCR). UVC radiation has been shown to result in the formation of bulky DNA lesions, which are removed by NER. Previous published reports have shown a role for the p53 tumour suppressor protein in GGR and TCR, but the involvement of p53 in TCR has been controversial. In addition, it has also been suggested that hypoxia affects NER and expression of p53. In the present work, the role of p53, hypoxia and HIF-lα in NER was investigated. It was determined that p53 overexpression in primary human fibroblasts resulted in up-regulation of both the GGR and TCR subpathways of a UV -damaged reporter gene. Pre-treatment of cells with low UVC-fluence and p53 overexpression also induced an upregulation of GGR and TCR. These results are consistent with a p53-dependent upregulation of TCR and GGR of the UVC-damaged reporter gene, as well with a UV-inducible TCR and GGR that is dependent on p53 expression prior to UV treatment. Hypoxia coupled to low pH induced a transient up-regulation of p53 expression and NER in human primary normal fibroblasts and a concomitant decrease in UVC sensitivity. In contrast, in tumour cells hypoxia coupled to low pH resulted in a delayed, but not absent up-regulation of NER, which was p53-independent and did not result in a decrease in UVC sensitivity. We report here that it is the early transient p53-dependent up-regulation induced by hypoxia coupled to acidosis in human primary normal fibroblasts that may play a significant role in cellular UVC sensitivity. These data suggest a different cellular NER response to hypoxia compared to hypoxia coupled to low pH. The NER response to hypoxia and hypoxia coupled with acidosis was also different in primary cells when compared to tumour-derived cells. It was demonstrated that expression of dominant-negative HIF-lα in rat prostate tumour cells results in a reduction in host cell reactivation (HCR) of a UV-damaged reporter gene when compared to that in wild-type HIF-lα cells under normoxic conditions suggesting that basal HIF-lα expression may play an important role in NER. In addition we showed that hypoxia induced an up-regulation of NER in human primary normal fibroblasts that was delayed, but not absent in TCR-deficient CSB cells, suggesting a role for hypoxia in up-regulation of the GGR pathway of NER of a UVdamaged reporter gene. In contrast, HIF-lα-overexpression under conditions of hypoxia resulted in a down-regulation of NER in normal fibroblasts, which was delayed, but not absent in CSB fibroblasts. These results suggest that HIF-1α and CSB are involved in a hypoxia-induced NER response. This work provides further evidence that both GGR and TCR are p53-dependent. In addition, this study provides evidence that hypoxia and hypoxia coupled to acidosis can up-regulate NER in both primary and tumour cells, and that HIF-lα and the CSB protein play an important role in a hypoxia-induced NER response. / Thesis / Doctor of Philosophy (PhD)

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal. / Des creux d’interférence sont fréquemment observés dans les spectres d’absorption de complexes d’éléments de transition. Ces creux résultent de l’interaction entre des états électroniques excités de multiplicité de spin différente. Un modèle de puits de potentiel couplés pour les états électroniques est nécessaire pour l’analyse des spectres d’absorption. Une équation analytique, dérivée de ce modèle, permet de calculer les spectres d’absorption non-résolus. L’impact d’une variation de chaque paramètre sur l’allure des spectres calculés est présenté. Le calcul avec l’équation analytique de spectres d’absorption peu résolus de complexes du nickel(II) de coordination octaédrique reproduit bien la région du maximum de la bande et du creux. Les paramètres obtenus sont quantitatifs et ont une signification physique. Le modèle est aussi employé pour l’analyse des spectres avec des progressions vibroniques résolues, mais dont les différences entre progressions sont non-constantes. Les calculs numériques exacts reproduisent bien les écarts entre les maxima des progressions et leur intensité. / Interference dips are often observed in absorption spectra of transition metal complexes. These dips resuit from the interaction between excited states with different spin multiplicities. A mode! of coupled potential wells for the electronic states is required to analyse the absorption spectra. The pararneters of an analytical equation derived from this modet are varied individually. The analytical equation is used to calculate the unresolved absorption spectra of octahedral nickel(II) complexes. The calculated spectra reproduce well the experimental ones, especially in the regions of the dip and of the maximum of the band. The values for the parameters ohtained from the equation are physically relevant, quantitative and give precise information on excited-state properties for the complexes studied. Numerical calculations of absorption spectra showing resolved progressions with nonconstant energy intervals are done with the model and reproduce well the intervals between the maxima of the progression and their intensities.

This study assessed the effect of cow milk (CM) and sheep milk (SM) consumption on the micro-structure, mechanical function, and mineral composition of rat femora in a male weanling rat model. Male weanling rats were fed a basal diet with a 50% reduction in calcium and phosphorus content (low Ca/P-diet) supplemented with either SM or CM. Rats were fed for 28 days, after which the femora were harvested and stored. The femora were analyzed by μ-CT, three-point bending, and inductively coupled plasma–mass spectrometry (ICP-MS). The addition of either milk to the low Ca/P-diet significantly increased (p < 0.05) trabecular bone volume, trabecular bone surface density, trabecular number, cortical bone volume, and maximum force, when compared to rats that consumed only the low Ca/P-diet. The consumption of either milk resulted in a significant decrease (p < 0.05) in trabecular pattern factor, and cortical bone surface to volume ratio when compared to rats that consumed only the low Ca/P-diet. The results were achieved with a lower consumption of SM compared to that of CM (p < 0.05). This work indicates that SM and CM can help overcome the effects on bone of a restriction in calcium and phosphorus intake.

The angiotensin II (Ang II) type 1 receptor (AT1R) is involved in the regulation of blood pressure (through vasoconstriction) and water and ion homeostasis (mediated by interaction with the endogenous agonist). AT1R can also be activated by auto-antibodies (AT1R-Abs), which are associated with manifold diseases, such as obliterative vasculopathy, preeclampsia and systemic sclerosis. Knowledge of the molecular mechanisms related to AT1R-Abs binding and associated signaling cascade (dys-)regulation remains fragmentary. The goal of this study was, therefore, to investigate details of the effects of AT1R-Abs on G-protein signaling and subsequent cell proliferation, as well as the putative contribution of the three extracellular receptor loops (ELs) to Abs-AT1R signaling. AT1R-Abs induced nuclear factor of activated T-cells (NFAT) signaling, which reflects Gq/11 and Gi activation. The impact on cell proliferation was tested in different cell systems, as well as activation-triggered receptor internalization. Blockwise alanine substitutions were designed to potentially investigate the role of ELs in AT1R-Abs-mediated effects. First, we demonstrate that Ang II-mediated internalization of AT1R is impeded by binding of AT1R-Abs. Secondly, exclusive AT1RAbs- induced Gq/11 activation is most significant for NFAT stimulation and mediates cell proliferation. Interestingly, our studies also reveal that ligand-independent, baseline AT1R activation of Gi signaling has, in turn, a negative effect on cell proliferation. Indeed, inhibition of Gi basal activity potentiates proliferation triggered by AT1R-Abs. Finally, although AT1R containing EL1 and EL3 blockwise alanine mutations were not expressed on the human embryonic kidney293T (HEK293T) cell surface, we at least confirmed that parts of EL2 are involved in interactions between AT1R and Abs. This current study thus provides extended insights into the molecular action of AT1R-Abs and associated mechanisms of interrelated pathogenesis.

The work reported in this thesis presents a general overview of the dynamic response of short-span railway bridges considering soil-structure interaction. The study aims to identify the effect of the surrounding and underlying soil on the global stiffness and damping of the structural system. This may lead to better assumptions and more efficient numerical models for design.A simple discrete model for calculating the dynamic characteristics of the fundamental bending mode of single span beam bridges on viscoelastic supports was proposed. This model was used to study the effect of the dynamic stiffness of the foundation on the modal parameters (e.g. natural frequency and damping ratio) of railway beam bridges. It was shown that the variation in the underlying soil profiles leads to a different dynamic response of the system. This effect depends on the ratio between the flexural stiffness of the bridge and the dynamic stiffness of the foundation-soil system but also on the ratio between the resonant frequency of the soil layer and the fundamental frequency of the bridge. The effect of the surrounding soil conditions on the vertical dynamic response of portal frame bridges was also investigated both numerically and experimentally. To this end, different numerical models (i.e. full FE models and coupled FE-BE models) have been developed. Controlled vibration tests have been performed on two full-scale portal frame bridges to determine the modal properties of the bridge-soil system and calibrate the numerical models. Both experimental and numerical results identified the substantial contribution of the surrounding soil on the global damping of short-span portal frame bridges. A simplified model for the surrounding soil was also proposed in order to define a less complicated model appropriate for practical design purposes. / <p>QC 20180315</p>

The naturally occurring dipeptide carnosine (-alanyl-L-histidine) specifically attenuates tumor growth. Here, we ask whether other small imidazole-containing compounds also affect the viability of tumor cells without affecting non-malignant cells and whether the formation of histamine is involved. Patient-derived fibroblasts and glioblastoma cells were treated with carnosine, L-alanyl-L-histidine (LA-LH), -alanyl-L-alanine, L-histidine, histamine, imidazole, -alanine, and L-alanine. Cell viability was assessed by cell-based assays and microscopy. The intracellular release of L-histidine and formation of histamine was investigated by high-performance liquid chromatography coupled to mass spectrometry. Carnosine and LA-LH inhibited tumor cell growth with minor effects on fibroblasts, and L-histidine, histamine, and imidazole affected viability in both cell types. Compounds without the imidazole moiety did not diminish viability. In the presence of LA-LH but not in the presence of carnosine, a significant rise in intracellular amounts of histidine was detected in all cells. The formation of histamine was not detectable in the presence of carnosine, LA-LH, or histidine. In conclusion, the imidazole moiety of carnosine contributes to its anti-neoplastic effect, which is also seen in the presence of histidine and LA-LH. Despite the fact that histamine has a strong effect on cell viability, the formation of histamine is not responsible for the effects on the cell viability of carnosine, LA-LH, and histidine.

Characterization of new pharmacological targets is a promising approach in research of neurorepair mechanisms. The G protein-coupled receptor 17 (GPR17) has recently been proposed as an interesting pharmacological target, e.g., in neuroregenerative processes. Using the well-established ex vivo model of organotypic slice co-cultures of the mesocortical dopaminergic system (prefrontal cortex (PFC) and substantia nigra/ventral tegmental area (SN/VTA) complex), the influence of GPR17 ligands on neurite outgrowth from SN/VTA to the PFC was investigated. The growthpromoting effects of Montelukast (MTK; GPR17- and cysteinyl-leukotriene receptor antagonist), the glial cell line-derived neurotrophic factor (GDNF) and of two potent, selective GPR17 agonists (PSB-16484 and PSB-16282) were characterized. Treatment with MTK resulted in a significant increase in mean neurite density, comparable with the effects of GDNF. The combination of MTK and GPR17 agonist PSB-16484 significantly inhibited neuronal growth. qPCR studies revealed an MTK-induced elevated mRNA-expression of genes relevant for neuronal growth. Immunofluorescence labelling showed a marked expression of GPR17 on NG2-positive glia. Western blot and RT-qPCR analysis of untreated cultures suggest a time-dependent, injury-induced stimulation of GPR17. In conclusion, MTK was identified as a stimulator of neurite fibre outgrowth, mediating its effects through GPR17, highlighting GPR17 as an interesting therapeutic target in neuronal regeneration.