This work explains the effect of failure on permeability anisotropy and dilation in sands. Shear failure is widely observed in field operations. There is incomplete understanding of the influence of shear failure in sand formations. Shear plane orientations are dependent on the stress anisotropy and that view is confirmed in this research. The effect of shear failure on the permeability is confirmed and calculated. Description of permeability anisotropy due to shear failure has also been discussed. In this work, three-dimensional discrete element modeling is used to model the behavior of uncemented and weakly cemented sand samples. Mechanical deformation data from experiments conducted on sand samples is used to calibrate the properties of the spherical particles in the simulations. Orientation of the failure planes (due to mechanical deformation) is analyzed both in an axi-symmetric stress regime (cylindrical specimen) and a non-axi-symmetric stress regime (right cuboidal specimen). Pore network fluid flow simulations are conducted before and after mechanical deformation to observe the effect of failure and stress anisotropy on the permeability and dilation of the granular specimen. A rolling resistance strategy is applied in the simulations, incorporating the stiffness of the specimens due to particle angularity, aiding in the calibration of the simulated samples against experimental data to derive optimum granular scale elastic and friction properties. A flexible membrane algorithm is applied on the lateral boundary of the simulation samples to implement the effect of a rubber/latex jacket. The effect of particle size distribution, stress anisotropy, and confining pressure on failure, permeability and dilation is studied. Using the calibrated micro-properties, simulations are extended to non-cylindrical specimen geometries to simulate field-like anisotropic stress regimes. The shear failure plane alignment is observed to be parallel to the maximum horizontal stress plane. Pore network fluid flow simulations confirm the increase in permeability due to shear failure and show a significantly greater permeability increase in the maximum horizontal stress direction. Using the flow simulations, anisotropy in the permeability field is observed by plotting the permeability ellipsoid. Samples with a small value of inter-granular cohesion depict greater shear failure, larger permeability increase and a greater permeability anisotropy than samples with a larger value of inter-granular cohesion. This is estimated by the number of micro-cracks observed. / text

Posttraumatic stress disorder (PTSD) is an anxiety disorder that may result from an exposure to a severely traumatic life-event. It is characterised by a delayed onset of psychological and physical symptoms including re-experiencing the event, avoidance of reminders associated with the trauma, increased autonomic arousal and distinct memory deficits. This disorder is also characterised by a maladaptive hypothalamic-pituitary-adrenal (HPA)-axis response and altered monoamine concentrations in the hippocampus and pre-frontal cortex. The Time Dependent Sensitization (TDS) model is a putative animal model of PTSD that is based on the concept of repeated trauma, using three acute stressors (TS) of intense severity followed by a mild situational reminder (RS) on day 7 subsequent to the acute stressors. The aims of this study were to determine if the Triple Stressor (TS) induces stress and if the situational reminder (RS) is necessary for the maintenance of the stress response over time and whether these two stress responses are qualitatively and quantitively different. This was done to further validate the TDS model and to characterize the development and progression of the stress-related pathology of PTSD. Methods used were High Performance Liquid Chromatography (HPLC) with electrochemical detection (biochemical correlates) for quantifying the monoamines dopamine (DA), noradrenaline (NA) and serotonin (5-HT) concentrations in the hippocampus and pre-frontal cortex (PFC); radio immuno assay (RIA) for the determination of plasma corticosterone concentrations (neuroendocrine parameter) and the use of the Elevated Plus Maze (EPM) to detect anxiety-like behaviour (behavioural analyses). The study was subdivided into an Acute and Re-Stress study (n = 10). In the Acute Study rats were exposed to TS as the only stressor. Group 1 was sacrificed immediately after TS, Group 2 was sacrificed 3 days post TS and Group 3 on day 7 post TS. In the Re-Stress Study both TS and RS were used as stressors. Group 4 was sacrificed immediately after the situational reminder, Group 5 was sacrificed 3 days post RS and Group 6 on day 7 post RS. A group of unstressed rats were used as Control. The results of this study found corticosterone concentrations elevated immediately after the TS (p<0.05). Exposure to the RS resulted in a profound hypocortisolism (p<0.05). These results indicate a possible disturbance in the regulation of the HPA-axis, which manifests as an enhanced negative feed-back upon re-introduction of the stressful situation. Changes in MA concentrations were evident. Although no definite fixed trend is apparent in this study, it is evident that the TDS model does induce monoamine dysregulation. Hippocampal NA. DA and 5-HT concentrations were noted to be elevated on day 7 post TS (p<0.05). On day 7 post RS only hippocampal 5HT was decreased significantly (p<0.05). Behavioural analyses indicate that stress related anxiety was not sustained after the TS but 7 days after the exposure to the RS rats were most anxious (p<0.05). The results confirm that the TDS model does induce PTSD-like symptoms in rats and that the situational reminder (RS) is necessary for the maintenance of the stress response. This model may be useful in the investigation of future experimental pharmacological interventions in the management of PTSD. / Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2005.

En aéronautique, les contraintes sont telles que la masse des filtres peut représenterjusqu'à 50% de la masse totale du convertisseur. Ces dernières années, les convertisseursmulticellulaires parallèles entrelacés et magnétiquement couplés ont conduit à améliorer lesperformances des convertisseurs (densité de puissance, efficacité, dynamique,...). Denombreuses topologies de filtrages entrelacés existent, l'objectif principal de cette étude est detrouver parmi ces topologies celles qui sont les mieux adaptées à la réalisation d'un onduleurde tension 110Veff / 400Hz triphasé 25kVA. Il est démontré que le choix du type de matériaumagnétique a un impact déterminant sur le poids, le volume et les pertes du convertisseur. Quidit parallélisation, dit multiplication du nombre de semi-conducteurs. Ces nouvelles structuresdoivent garantir à la fois un rendement élevé, une masse faible et une continuté defonctionnement, même en cas de panne d'un semiconducteur de puissance ou de sacommande. Mais coupler les phases entre elles, impose un lien indissociable qui peut êtrenuisible au fonctionnement de la structure en cas de dysfonctionnement. Des solutionsexistent et sont abordées dans l'étude. Enfin, la réalisation pratique d'un prototype semiindustrielde convertisseur triphasé utilisant des transformateurs interphases est présentée. Ils'agit d'un onduleur réseau avionique triphasé avec reconstruction de neutre pour fonctionneren déséquilibré. Les résultats expérimentaux démontrent l'avantage d'un convertisseur

Posttraumatic stress disorder (PTSD) is an anxiety disorder that may result from an exposure to a severely traumatic life-event. It is characterised by a delayed onset of psychological and physical symptoms including re-experiencing the event, avoidance of reminders associated with the trauma, increased autonomic arousal and distinct memory deficits. This disorder is also characterised by a maladaptive hypothalamic-pituitary-adrenal (HPA)-axis response and altered monoamine concentrations in the hippocampus and pre-frontal cortex. The Time Dependent Sensitization (TDS) model is a putative animal model of PTSD that is based on the concept of repeated trauma, using three acute stressors (TS) of intense severity followed by a mild situational reminder (RS) on day 7 subsequent to the acute stressors. The aims of this study were to determine if the Triple Stressor (TS) induces stress and if the situational reminder (RS) is necessary for the maintenance of the stress response over time and whether these two stress responses are qualitatively and quantitively different. This was done to further validate the TDS model and to characterize the development and progression of the stress-related pathology of PTSD. Methods used were High Performance Liquid Chromatography (HPLC) with electrochemical detection (biochemical correlates) for quantifying the monoamines dopamine (DA), noradrenaline (NA) and serotonin (5-HT) concentrations in the hippocampus and pre-frontal cortex (PFC); radio immuno assay (RIA) for the determination of plasma corticosterone concentrations (neuroendocrine parameter) and the use of the Elevated Plus Maze (EPM) to detect anxiety-like behaviour (behavioural analyses). The study was subdivided into an Acute and Re-Stress study (n = 10). In the Acute Study rats were exposed to TS as the only stressor. Group 1 was sacrificed immediately after TS, Group 2 was sacrificed 3 days post TS and Group 3 on day 7 post TS. In the Re-Stress Study both TS and RS were used as stressors. Group 4 was sacrificed immediately after the situational reminder, Group 5 was sacrificed 3 days post RS and Group 6 on day 7 post RS. A group of unstressed rats were used as Control. The results of this study found corticosterone concentrations elevated immediately after the TS (p<0.05). Exposure to the RS resulted in a profound hypocortisolism (p<0.05). These results indicate a possible disturbance in the regulation of the HPA-axis, which manifests as an enhanced negative feed-back upon re-introduction of the stressful situation. Changes in MA concentrations were evident. Although no definite fixed trend is apparent in this study, it is evident that the TDS model does induce monoamine dysregulation. Hippocampal NA. DA and 5-HT concentrations were noted to be elevated on day 7 post TS (p<0.05). On day 7 post RS only hippocampal 5HT was decreased significantly (p<0.05). Behavioural analyses indicate that stress related anxiety was not sustained after the TS but 7 days after the exposure to the RS rats were most anxious (p<0.05). The results confirm that the TDS model does induce PTSD-like symptoms in rats and that the situational reminder (RS) is necessary for the maintenance of the stress response. This model may be useful in the investigation of future experimental pharmacological interventions in the management of PTSD. / Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2005.

Perfluoroalkyl compounds (PFCs) are a group of chemical surfactants most notably used in non-stick and stain-resistance applications. Due to their wide-spread use and inherent resistance to degradation, several PFCs have become persistent environmental contaminants. Despite the high concentrations of PFCs reported in wild birds and their eggs, very little is known about the toxicological effects they have on avian species. This thesis investigates the developmental toxicity of PFCs in an avian model species: the domestic chicken (Gallus gallus domesticus). Egg injection experiments were performed to assess the in ovo toxicity of perfluorooctane sulfonate (technical grade, T-PFOS), perfluorooctanoic acid (PFOA), perfluorodecane sulfonate (PFDS) and perfluoroundecanoic acid (PFUdA). Real-time RT-PCR was then used to measure the transcription of candidate biomarker genes in the liver tissue of day 20 embryos. Candidate genes were selected based on their responsiveness to PFC exposure in previously conducted in vitro screening assays. In ovo exposure to PFOS resulted in a dose-dependent decrease in embryo pipping success (a measure of hatching success) with an LD50 of 93 μg/g (3.54 μg/g-672,910 μg/g, 95% confidence interval), however the expression of peroxisome proliferator-activated receptor alpha (PPARα)-regulated genes was not affected in liver tissue as hypothesized. PFOA, PFDS and PFUdA had no effect on the pipping success of chicken embryos. The expression of cytochrome P450 1A4 (CYP1A4) and liver fatty acid binding protein (L-FABP) mRNA increased in embryo liver tissue following in ovo exposure to PFUdA but was only statistically significant at 10 μg/g, which is several orders of magnitude higher than concentrations reported in wild bird eggs. The isomer-specific accumulation of PFOS in chicken embryo livers was also investigated using an in-port derivatization gas-chromatography/mass spectrometry (GC-MS) method. Prior to incubation, chicken eggs were injected with T-PFOS, composed of 63% linear isomer (L-PFOS) and 37.3% branched isomers. The isomer profiles in day-20 embryo liver tissue showed up to 20% enrichment in the proportion of L-PFOS, compared to T-PFOS, with a corresponding decrease in the proportion of branched isomers. This enrichment was inversely proportional to dose. Finally, the transcriptional profiles of cultured chicken embryonic hepatocytes (CEH) exposed to either T-PFOS or L-PFOS were compared using Agilent 4x44k Chicken (V2) Gene Expression microarrays. At equal concentrations (10 μM), T-PFOS altered the expression of significantly more genes (340 genes, >1.5 fold change, false discovery rate adjusted p<0.05) compared to L-PFOS (130 genes). Functional analysis showed that L-PFOS and T-PFOS affected genes involved in lipid metabolism, cellular growth and proliferation, and cell-cell signaling. Pathway and interactome analysis suggested that gene expression may be affected through RXR, oxidative stress response, TP53 signaling, MYC signaling, Wnt/β-catenin signaling and PPARγ and SREBP receptors. In all functional categories and pathways examined, T-PFOS had a more pronounced disruptive effect on transctional regulation than L-PFOS. In summary, egg injection experiments showed that T-PFOS (but not linear PFOA, PFDS or PFUdA) may affect the hatching success of the chicken at environmentally relevant concentrations. It was also demonstrated that the accumulation of PFOS in embryonic liver is isomer specific, and leads to an enrichment of L-PFOS. The increased transcriptional disruption caused by T-PFOS in cultured hepatocytes over L-PFOS suggests that the branched isomers may be largely responsible for the toxicological effects of PFOS. Combined, the results from this thesis demonstrate the importance of considering PFOS isomer burdens during risk assessment. In addition, gene expression analysis identified several candidate mechanisms for PFOS toxicity.

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / Quando um conversor opera com uma larga diferenÃa entre os nÃveis de tensÃo de entrada e de saÃda, normalmente à possÃvel identificar uma reduÃÃo significante no seu desempenho. A razÃo disto à o aumento da quantidade de energia processada, que primeiramente precisa ser armazenada em um elemento passivo (indutor), antes de ser entregue à carga. à possÃvel dizer que quÃo maior for a quantidade dessa energia âindiretaâ, menor serà a eficiÃncia do sistema. Tal situaÃÃo à especialmente crÃtica para inversores e retificadores com correÃÃo de fator de potÃncia (PFC), visto que a razÃo cÃclica dos interruptores abrange praticamente todos os possÃveis valores. Em casos em que a diferenÃa entre o valor de pico da tensÃo CA e o valor mÃdio da tensÃo CC à grande, o Ãndice de modulaÃÃo à desviado consideravelmente de 1 e, consequentemente, maiores perdas sÃo esperadas. Para lidar com tal situaÃÃo, à proposto um retificador com caracterÃstica abaixadora e elevadora utilizando uma funÃÃo chamada de bypass. Esta funÃÃo permite que o retificador escolha entre os dois barramentos o que melhor se adapta ao nÃvel de saÃda desejado em funÃÃo do ponto de operaÃÃo da tensÃo senoidal de entrada, maximizando a eficiÃncia. Algumas das vantagens esperadas com a utilizaÃÃo da funÃÃo bypass sÃo: reduÃÃo das perdas totais por meio da operaÃÃo parcial com estÃgio Ãnico; maior nÃmero de nÃveis de tensÃo, reduzindo a corrente de modo comum e o volume do filtro de entrada, alÃm de resultar em menores esforÃos de tensÃo sobre os semicondutores; e, finalmente, reduÃÃo de perdas adicionais e no tamanho do sistema, visto que o conversor Buck de saÃda à projetado para apenas uma fraÃÃo da potÃncia total. Em adiÃÃo, sÃo apresentadas possÃveis configuraÃÃes de conversores de potÃncia para o carregamento de baterias de veÃculos elÃtricos. Topologias de retificadores trifÃsicos com PFC com corrente de entrada senoidal e tensÃo de saÃda controlada sÃo analisadas e propostas, e suas funcionalidades e caracterÃsticas bÃsicas descritas brevemente. FÃrmulas analÃticas para o cÃlculo dos esforÃos de tensÃo e corrente sobre os semicondutores de potÃncia sÃo fornecidas. A fim de avaliar comparativamente o desempenho das topologias selecionadas, fatores adimensionais de referÃncia sÃo definidos com base nos esforÃos elÃtricos sobre os semicondutores e no volume dos indutores. As caracterÃsticas do sistema proposto, incluindo princÃpio de operaÃÃo, estratÃgia de modulaÃÃo, equaÃÃes de dimensionamento e cÃlculos de perdas e eficiÃncia, sÃo descritas em detalhes. Finalmente, a viabilidade do conceito de bypass à demonstrada por meio de resultados experimentais obtidos a partir de um protÃtipo de 22 kW. / When operating with large differences between input and output voltage levels, it is normally possible to identify a significant reduction on the performance of practically all topologies in regard of conversion efficiency. Reason for this is the increasing amount of processed energy that needs to be firstly stored in a passive element (inductor) before reaching the load. It is therefore possible to say that the higher the amount of such âindirectâ energy is; the lower will be the converter efficiency. Such situation is especially critical when considering the operation of inverters or controlled rectifiers with power factor correction (PFC) because the converter sweeps practically all the possible values of duty cycle. In the case the difference between peak AC value and DC value is large; the modulation index will strongly deviate from 1. Consequently, even higher amount of losses are expected. In order to deal with the above referred drawbacks, it is proposed a 5-level three-phase PFC rectifier with an innovative approach, named bypass concept. This function allows the converter to switch between one of the available DC-links that best matches the required output levels depending on the operating point of the sinus wave, thus maximizing the efficiency. Furthermore, the referred bypass function enables direct access to the required lower voltage level by the load, reducing significantly the amount of losses. The 5-level operation allows the voltage steps to be lower than those found in three and two-level topologies, from where lower harmonic contents, reduction of common mode current and EMI are observed. Finally, the output DC-DC converters are designed for only a fraction of the nominal power, having a rather reduced impact on additional losses and also on the converter size. In addition, possible power electronics configurations for charging of EVs are presented. Suitable three-phase PFC rectifier topologies with sinusoidal input currents and controlled output voltage are analyzed and proposed, and their functionality and basic characteristics briefly described. Analytical formulas for calculating the current stresses on the power semiconductors are provided, and in order to evaluate comparatively the performance of selected topologies, dimensionless benchmark factors are derived concerning the semiconductor stresses and the volume of the main inductive components. The characteristics of the proposed system, including the principle of operation, modulation strategy, dimensioning equations and calculated losses and efficiency, are described in detail. Finally, the feasibility of the bypass concept is demonstrated by means of experimental results obtained from a 22 kW hardware prototype.

Two new three-dimensional rock mass strength criteria are developed in this dissertation by extending an existing rock mass strength criterion. These criteria incorporate the effects of the intermediate principal stress, minimum principal stress and the anisotropy resulting from these stresses acting on the fracture system. In addition, these criteria have the capability of capturing the anisotropic and scale dependent behavior of the jointed rock mass strength by incorporating the effect of fracture geometry through the fracture tensor components. Another significant feature of the new rock mass strength criterion which has the exponential functions (equation 6.7) is having only four empirical coefficients compared to the existing strength criterion which has five empirical coefficients; if the joint sets have the same isotropic mechanical behavior, the number of the empirical coefficients reduces to two in this new strength criterion (equation 6.10). The new criteria were proposed after analyzing 452 numerical modeling results of the triaxial, polyaxial and biaxial compression tests conducted on the jointed rock blocks having one or two joint sets by the PFC3D software version 5. In this research to have several samples with the same properties a synthetic rock material that is made out of a mixture of gypsum, sand and water was used. In total, 20 joint systems were chosen and joint sets have different dip angles varying from 15 to 60 at an interval of 15 with dip directions of 30 and 75 for the two joint sets. Each joint set also has 3 persistent joints with the joint spacing of 42 mm in a cubic sample of size 160 mm and the joints have the same isotropic mechanical behavior. The confining stress combination values were chosen based on the uniaxial compressive strength (UCS) value of the modeled intact synthetic rock. The minimum principal stress values were chosen as 0, 20, 40 and 60 percent of the UCS. For each minimum principal stress value, the intermediate principal stress value varies starting at the minimum principal stress value and increasing at an interval of 20 percent of the UCS until it is lower than the strength of the sample under the biaxial loading condition with the same minimum principal stress value. The new rock mass failure criteria were developed from the PFC3D modeling data. However, since the joint sets having the dip angle of 60 intersect the top and bottom boundaries of the sample simultaneously, the joint systems with at least one of the joint sets having the dip angle of 60 were removed from the database. Thus, 284 data points from 12 joint systems were used to find the best values of the empirical coefficients for the new rock mass strength criteria. λ, p and q were found to be 0.675, 3.16 and 0.6, respectively, through a conducted grid analysis with a high R2 (coefficient of determination) value of 0.94 for the new criterion given by equation 6.9 and a and b were found to be 0.404 and 0.972, respectively, through a conducted grid analysis with a high R2 value of 0.92 for the new criterion given by equation 6.10. The research results clearly illustrate how increase of the minimum and intermediate principal stresses and decrease of the joint dip angle, increase the jointed rock block strength. This dissertation also illustrates how different confining stress combinations and joint set dip angles result in different jointed rock mass failure modes such as sliding on the joints, failure through the intact rock and a combination of the intact rock and joint failures. To express the new rock mass strength failure criteria, it was necessary to determine the intact rock strengths under the same confining stress combinations mentioned earlier. Therefore, the intact rock was also modeled for all three compression tests and the intact rock strengths were found for 33 different confining stress combinations. Suitability of six major intact rock failure criteria: Mohr-Coulomb, Hoek-Brown, Modified Lade, Modified Wiebols and Cook, Mogi and Drucker-Prager in representing the intact rock strength was examined through fitting them using the aforementioned 33 PFC3D data points. Among these criteria, Modified Lade, Modified Mogi with power function and Modified Wiebols and Cook were found to be the best failure criteria producing lower Root Mean Square Error (RMSE) values of 0.272, 0.301 and 0.307, respectively. Thus, these three failure criteria are recommended for the prediction of the intact rock strength under the polyaxial stress condition. In PFC unlike the other methods, macro mechanical parameters are not directly used in the model and micro mechanical parameter values applicable between the particles should be calibrated using the macro mechanical properties. Accurate calibration is a difficult or challenging task. This dissertation emphasized the importance of studying the effects of all micro parameter values on the macro mechanical properties before one goes through calibration of the micro parameters in PFC modeling. Important effects of two micro parameters, which have received very little attention, the particle size distribution and the cov of the normal and shear strengths, on the macro properties are clearly illustrated before conducting the said calibration. The intact rock macro mechanical parameter values for the Young’s modulus, uniaxial compression strength (UCS), internal friction angle, cohesion and Poisson's ratio were found by performing 3 uniaxial tests, 3 triaxial tests and 5 Brazilian tests on a synthetic material made out of a mixture of gypsum, sand and water and the joint macro mechanical parameter values were found by conducting 4 uniaxial compression tests and 4 direct shear tests on jointed synthetic rocks with a horizontal joint. Then the micro mechanical properties of the Linear Parallel Bond Model (LPMB) and Modified Smooth Joint Contact Model (MSJCM) were calibrated to represent the intact rock and joints respectively, through the specific procedures explained in this research. The similar results obtained between the 2 polyaxial experiments tests of the intact rock and 11 polyaxial experimental tests of the jointed rock blocks having one joint set and the numerical modeling verified the calibrated micro mechanical properties and further modification of these properties was not necessary. This dissertation also proposes a modification to the Smooth Joint Contact Model (SJCM) to overcome the shortcoming of the SJCM to capture the non-linear behavior of the joint closure varying with the joint normal stress. Modified Smooth Joint Contact Model (MSJCM) uses a linear relation between the joint normal stiffness and the normal contact stress to model the non-linear relation between the joint normal deformation and the joint normal stress observed in the compression joint normal stiffness test. A good agreement obtained between the results from the experimental tests and the numerical modeling of the compression joint normal test shows the accuracy of this new model. Moreover, another shortcoming associated with the SJCM application known as the interlocking problem was solved through this research by proposing a new joint contact implementation algorithm called joint sides checking (JSC) approach. The interlocking problem occurs due to a shortcoming of the updating procedure in the PFC software related to the contact conditions of the particles that lie around the intended joint plane during high shear displacements. This problem increases the joint strength and dilation angle and creates unwanted fractures around the intended joint plane.

Perfluoroalkyl compounds (PFCs) are a group of chemical surfactants most notably used in non-stick and stain-resistance applications. Due to their wide-spread use and inherent resistance to degradation, several PFCs have become persistent environmental contaminants. Despite the high concentrations of PFCs reported in wild birds and their eggs, very little is known about the toxicological effects they have on avian species. This thesis investigates the developmental toxicity of PFCs in an avian model species: the domestic chicken (Gallus gallus domesticus). Egg injection experiments were performed to assess the in ovo toxicity of perfluorooctane sulfonate (technical grade, T-PFOS), perfluorooctanoic acid (PFOA), perfluorodecane sulfonate (PFDS) and perfluoroundecanoic acid (PFUdA). Real-time RT-PCR was then used to measure the transcription of candidate biomarker genes in the liver tissue of day 20 embryos. Candidate genes were selected based on their responsiveness to PFC exposure in previously conducted in vitro screening assays. In ovo exposure to PFOS resulted in a dose-dependent decrease in embryo pipping success (a measure of hatching success) with an LD50 of 93 μg/g (3.54 μg/g-672,910 μg/g, 95% confidence interval), however the expression of peroxisome proliferator-activated receptor alpha (PPARα)-regulated genes was not affected in liver tissue as hypothesized. PFOA, PFDS and PFUdA had no effect on the pipping success of chicken embryos. The expression of cytochrome P450 1A4 (CYP1A4) and liver fatty acid binding protein (L-FABP) mRNA increased in embryo liver tissue following in ovo exposure to PFUdA but was only statistically significant at 10 μg/g, which is several orders of magnitude higher than concentrations reported in wild bird eggs. The isomer-specific accumulation of PFOS in chicken embryo livers was also investigated using an in-port derivatization gas-chromatography/mass spectrometry (GC-MS) method. Prior to incubation, chicken eggs were injected with T-PFOS, composed of 63% linear isomer (L-PFOS) and 37.3% branched isomers. The isomer profiles in day-20 embryo liver tissue showed up to 20% enrichment in the proportion of L-PFOS, compared to T-PFOS, with a corresponding decrease in the proportion of branched isomers. This enrichment was inversely proportional to dose. Finally, the transcriptional profiles of cultured chicken embryonic hepatocytes (CEH) exposed to either T-PFOS or L-PFOS were compared using Agilent 4x44k Chicken (V2) Gene Expression microarrays. At equal concentrations (10 μM), T-PFOS altered the expression of significantly more genes (340 genes, >1.5 fold change, false discovery rate adjusted p<0.05) compared to L-PFOS (130 genes). Functional analysis showed that L-PFOS and T-PFOS affected genes involved in lipid metabolism, cellular growth and proliferation, and cell-cell signaling. Pathway and interactome analysis suggested that gene expression may be affected through RXR, oxidative stress response, TP53 signaling, MYC signaling, Wnt/β-catenin signaling and PPARγ and SREBP receptors. In all functional categories and pathways examined, T-PFOS had a more pronounced disruptive effect on transctional regulation than L-PFOS. In summary, egg injection experiments showed that T-PFOS (but not linear PFOA, PFDS or PFUdA) may affect the hatching success of the chicken at environmentally relevant concentrations. It was also demonstrated that the accumulation of PFOS in embryonic liver is isomer specific, and leads to an enrichment of L-PFOS. The increased transcriptional disruption caused by T-PFOS in cultured hepatocytes over L-PFOS suggests that the branched isomers may be largely responsible for the toxicological effects of PFOS. Combined, the results from this thesis demonstrate the importance of considering PFOS isomer burdens during risk assessment. In addition, gene expression analysis identified several candidate mechanisms for PFOS toxicity.

Hlavním cílem této práce je studium aktuálního problému adheze mezi kompozitními materiály, a určení vlivu složení mezivrstvy v pevnosti adhezivního spoje mezi vláknové (FRC) a částicové (PFC) kompozity, používané ve stomatologii. FRC tyčinky byly vytvořené na bázi komerční dimetakrylatové pryskyřice a skleněných S vláken. PFC byl vytvořen ze směsi pryskyřic (bis-GMA a PEGDMA), plněných drceným barnatým sklem. Celkově bylo připraveno a vyzkoušeno 84 vzorků. Vzorky byly rozdělené do pěti hlavních skupin. První skupina byla vytvořena ze série vzorků bez mezivrstvy. Zbylé čtyři skupiny byly rozděleny dle složení mezivrstvy (tloušťky a druhu pryskyřic). Částicové kompozity vzorků se lišily obsahem plniva (0, 10, 40 hm %). FRC tyčinky byly stejné pro všechny vzorky. Univerzální testovací přístroj ZWICK Z010 byl použit k zjištění smykové pevnosti adhezivního spoje všech vzorků. Rastrovací elektronový mikroskop byl použít k pozorování místa porušení. Ze získaných výsledků vyplívá, že s přidáváním mezivrstvy mezi vláknovým a částicovým narůstá smyková pevnost spoje. Důležitost těchto výsledků je způsobená tím, že v posledních letech použití těchto materiálů ve stomatologii narůstá a adheze zůstává jeden z hlavních problémů při klinické praxi.

The thesis is focused on design the switching power supply according to Push-pull topology rules. The work describes basic theoretic principles of Push-pull topology with design of circuit and circuit elements.