Major depressive disorder (MDD) affects 300 million people worldwide and is a major contributor to the global burden of disease. The aetiology of depression, emerging through a gene x environment interaction, is still incompletely understood which prevents tailoring of treatment approaches. In addition to MDD core symptoms, such as anhedonia (a diminished anticipation or experience of pleasure), depressed patients suffer from a plethora of manifestations including cognitive impairments, which occur primarily in the domains of executive function, attention and memory. Patients remitted from affective symptoms of MDD often continue to display cognitive impairments. These cognitive deficits are the longest present residual symptom, predict treatment response and increase risk of relapse. Consequently, cognitive impairments need to be targeted more effectively by antidepressants for complete remission from MDD. Clinically relevant animal models are essential for developing, tailoring and testing such novel, pro-cognitive antidepressants. This PhD project aimed to establish a preclinical screening platform for the testing of pro-cognitive antidepressants, to improve understanding of MDD risk factors and consequent symptom development, and finally, to focus on clinical relevance of the applied techniques. The chronic mild stress (CMS) rodent model of depression was used, known for displaying the core symptom anhedonia, but also for a high construct, face and predictive validity. The environmental MDD risk factor 'stress' induces an anhedonic-like phenotype in a subgroup of exposed rats, whereas another subgroup of rats is resilient, as determined by the sucrose consumption test. The cognitive performance of different rat strains, including CMS anhedonic-like and resilient rats, was assessed employing the touchscreen operant platform, which was developed based on the Cambridge neuropsychological test automated battery (CANTAB) for assessing cognition in humans. Furthermore, a group of anhedonic-like rats was treated with the antidepressant vortioxetine, which acts as both a pro-cognitive and antidepressant treatment. Our results showed that stress exposure induced anhedonia in albino and pigmented rat strains, although stress did not affect cognitive performance of pigmented rats in a simple pairwise discrimination touchscreen task. Applying a more complex pairedassociates learning touchscreen task revealed impaired cognitive performance in the CMS anhedonic-like but not in the resilient phenotype. Furthermore, vortioxetine treatment reversed anhedonia in the CMS model and altered executive functions in treated rats. The expression of genes involved in the stress response, affective disorders and neuronal plasticity was altered in the prefrontal cortex and hippocampus owned to treatment and hedonic state. Thus, we have demonstrated that the CMS model exhibits both stress-induced cognitive alterations and depression-associated cognitive impairments in touchscreen tasks. Furthermore, touchscreen testing was sufficiently sensitive to detect alterations in cognitive performance due to pharmacological intervention. Overall, we established a potential platform for pro-cognitive antidepressant drug screening. Furthermore, brain derived neurotrophic factor (BDNF), involved in learning and memory, was examined in the context of depression. BDNF is reduced in MDD patients as well as in preclinical models in response to stress. Although this suggests that BDNF contributes to the aetiology of depression, studies including mice heterozygous for BDNF (BDNF+/-) have generated conflicting results. BDNF+/- rats may provide a more suitable model as (1) rats have a greater behavioural repertoire than mice, (2) classical behaviour tests are designed for rats, and (3) rats, like humans, produce peripheral BDNF. We found anhedonia and mild signs of anxiety in BDNF+/- rats, accompanied by prefrontal and hippocampal changes in expression of genes relevant in psychiatric disorders and underpinning learning. Thus, behavioural and molecular findings in BDNF+/- rats complement existing literature and suggest that rats are a more suitable model in BDNF research than mice. Overall, the project uncovered environmental and genetic manifestations of risk factors in translational models and established a novel tool for translational pro-cognitive antidepressant drug screening.

Failure criteria play a vital role in the numerical analysis of reinforced concrete structures. The current failure criteria can be classified into two types, namely the empirical and theoretical failure criteria. Empirical failure criteria normally lack reasonable theoretical backgrounds, while theoretical ones either involve too many parameters or ignore the effects of intermediate principal stress on the concrete strength. Based on the octahedral shear stress model and the concrete tensile strength under the state of triaxial and uniaxial stress, a new failure criterion, that is, the simplified unified strength theory (UST), is developed by simplifiing the five-parameter UST for the analysis of reinforced concrete structures. According to the simplified UST failure criterion, the concrete strength is influenced by the maximum and intermediate principal shear stresses together with the corresponding normal stresses. Moreover, the effect of hydrostatic pressure on the concrete strength is also taken into account. The failure criterion involves three concrete strengths, namely the uniaxial tensile and compressive strengths and the equal biaxial compressive strength. In the numerical analysis, a degenerated shell element with the layered approach is adopted for the simulation of concrete structures. In the layered approach, concrete is divided into several layers over the thickness of the elements and reinforcing steel is smeared into the corresponding number of layers of equivalent thickness. In each concrete layer, three-dimensional stresses are calculated at the integration points. For the material modelling, concrete is treated as isotropic material until cracking occurs. Cracked concrete is treated as an orthotropic material incorporating tension stiffening and the reduction of cracked shear stiffness. Meanwhile, the smeared craclc model is employed. The bending reinforcements and the stirrups are simulated using a trilinear material model. To verify the correctness of the simplified UST failure criterion, comparisons are made with concrete triaxial empirical results as well as with the Kupfer and the Ottosen failure criteria. Finally, the proposed failure criterion is used for the flexural analysis of simply supported reinforced concrete beams. Also conducted are the punching shear analyses of single- and multi-column-slab connections and of half-scale flat plate models. In view of its accuracy and capabilities, the simplified UST failure criterion may be used to analyse beam- and slab-type reinforced concrete structures.

The surface integrity of a machined component that meets the demands of a specific application requirement is defined by several characteristics. The residual stress profile into the component is often considered as the critical characteristics as it carries a direct effect on the fatigue life of a machined component. A significant amount of effort has been dedicated by researchers to predict post process stress in a workpiece using analytical, experimental, and numerical modeling methods. Nonetheless, no methodology is available that can express the cutting process parameters and tool geometry parameters as functions of machined residual stress profile to allow process planning in achieving desired residual stress profile. This research seeks to fill that void by developing a novel approach to enable the extraction of cutting process and tool geometry parameters from a desired or required residual stress profile. More specifically, the model consists in determining the depth of cut, the tool edge radius and the cutting forces needed to obtain a prescribed residual stress profile for an orthogonal machining operation. The model is based on the inverse solution of a physics-based modeling approach of the orthogonal machining operation and the inverse solution of the residual stress prediction from Hertzian stresses. Experimental and modeling data are used to validate the developed model. The work constitutes a novel approach in engineering residual stress in a machined component.

The premise of the work presented here is to use a common analytical tool, Computational Fluid dynamics (CFD), along with a difference turbulence models. Eddy viscosity models as well as state-of-the-art Large Eddy Simulation (LES) were used to study the flow past bluff bodies. A suitable CFD code (CFX5.6b) was selected and implemented. Simulation of turbulent transport for the gas through the gaps of the randomly distributed spherical fuel elements (pebbles) was performed. Although there are a number of numerical studies () on flows around spherical bodies, none of them use the necessary turbulence models that are required to simulate flow where strong separation exists. With the development of high performance computers built for applications that require high CPU time and memory; numerical simulation becomes one of the more effective approaches for such investigations and LES type of turbulence models can be used more effectively. Since there are objects that are touching each other in the present study, a special approach was applied at the stage of building computational domain. This is supposed to be a considerable improvement for CFD applications. Zero thickness was achieved between the pebbles in which fission reaction takes place. Since there is a strong pressure gradient as a result of high Reynolds Number on the computational domain, which strongly affects the boundary layer behavior, heat transfer in both laminar and turbulent flows varies noticeably. Therefore, noncircular curved flows as in the pebble-bed situatio n, in detailed local sense, is interesting to be investigated. Since a compromise is needed between accuracy of results and time/cost of effort in acquiring the results numerically, selection of turbulence model should be done carefully. Resolving all the scales of a turbulent flow is too costly, while employing highly empirical turbulence models to complex problems could give inaccurate simulation results. The Large Eddy Simulation (LES) method would achieve the requirements to obtain a reasonable result. In LES, the large scales in the flow are solved and the small scales are modeled. Eddy viscosity and Reynolds stress models were also be used to investigate the applicability of these models for this kind of flow past bluff bodies at high Re numbers.

The ability to learn and change future behaviour based on past experiences is crucial for the life and survival of animals. For various behaviours exhibited by animals it is clear that in a seemingly homogeneous population not all individuals behave the same way, even in invertebrates. In crickets (Gryllus bimaculatus), a model system for the mechanisms of intra-specific aggression, agonistic experiences with the underlying impact of neuromodulators have been identified as a cause of inter-individual differences. For mammals and humans, the experience of adversity and stress can have detrimental effects on cognitive abilities and chronic defeat stress is used as a model for depression. In crickets the equivalent, the chronic social defeat stress paradigm, has been established. This thesis first sets out to construct a new model for measuring a conditioned response from multiple behavioural aspects and quantify learning in individual crickets. Video tracking of responses revealed behavioural variables that were included in a binary logistic regression analysis, whereas the resulting multi-variable model proves to be superior to other models constructed and can give the probability of an individual exhibiting a conditioned response. With this, learning indices can be calculated for each individual trained in a differential appetitive olfactory paradigm. With the method at hand, this thesis reveals that the experience of chronic social stress impairs learning in crickets, susceptible and resilient to defeat stress alike. The experience of multiple wins, however, does neither improve nor decrease learning abilities, but a long-term winner effect on aggression could be shown. Although inter-individual differences in learning are present, the aggressive state of crickets is not correlated to the learning indices. The application of serotonergic drugs that block receptors or act as re-uptake inhibitors reveal the influence of serotonin on learning within this paradigm. In addition to maintaining reduced aggressiveness, serotonin promotes the impairment of learning after the experience of chronic social defeat stress.:1 INTRODUCTION.....................................................................................................1 2 MATERIALS AND METHODS............................................................................... 8 2.1 Experimental animals...................................................................................... 8 2.2 Appetitive olfactory conditioning..................................................................... 8 2.2.1 Odour application and rewarding....................................................... 8 2.2.2 Absolute conditioning paradigm........................................................ 10 2.2.3 Differential conditioning paradigm.................................................... 11 2.3 Experimental setup for video-tracking.............................................................. 12 2.4 Binary logistic regression model....................................................................... 13 2.4.1 Binary groups for model building...................................................... 13 2.4.2 Variables of a behavioural response................................................... 14 2.4.3 Calculating a conditioned odour response probability (Presp) ............ 15 2.5 Evaluation of learning with the binary logistic model...................................... 17 2.6 Evaluation of aggression with a standardised fight.......................................... 18 2.7 Multiple agonistic experiences......................................................................... 19 2.7.1 Chronic social defeat stress................................................................ 19 2.7.2 Multiple wins..................................................................................... 20 2.8 Serotonin......................................................................................................... 20 2.8.1 Pharmacological treatments............................................................... 20 2.8.2 Methiothepin and ketanserin.............................................................. 21 2.8.3 Fluoxetine with non-chronic defeat................................................... 21 2.9 Additional data analysis and statistic................................................................ 22 3 RESULTS............................................................................................................ 23 3.1 Binary logistic regression model for quantifying learning............................... 23 3.1.1 Behavioural variables of a conditioned odour response.................... 23 3.1.2 Model building and selection............................................................. 29 3.1.3 Odour response probabilities (Presp)................................................... 31 3.1.4 Application of the regression model to assess the quantification of learning.................................................................................................... 34 3.2 The influence of agonistic experiences on aggression and learning................. 39 3.2.1 Chronic social defeat stress................................................................ 39 3.2.2 Multiple experiences of winning........................................................ 46 3.2.3 Correlation of aggression and learning............................................... 48 3.2.4 Summary of learning capacities – multiple experiences.................... 50 3.3 The influence of serotonergic drugs on learning after chronic defeat.............. 51 3.3.1 Methiothepin and ketanserin.............................................................. 51 3.3.2 Fluoxetine........................................................................................... 57 3.3.3 Summary of learning capacities – chronic defeat and serotonin........ 60 4 DISCUSSION....................................................................................................... 63 4.1 The semi-automated measurement of olfactory learning in individually assayed crickets................................................................................................................... 64 4.2 The influence of multiple agonistic experiences on learning........................... 71 4.3 The role of serotonin in chronic social defeat influenced learning................... 77 4.4 Overall conclusion and outlook........................................................................ 80 5 SUMMARY........................................................................................................... 82 6 ZUSAMMENFASSUNG........................................................................................ 87 7 REFERENCES.................................................................................................... 93 8 APPENDIX................................................................................................... 106 8.1 Figures and tables................................................................................... 106 8.2 Publications and published abstracts....................................................... 108 8.3 Curriculum vitae....................................................................................... 109 8.4 Acknowledgements.................................................................................. 111

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The present study considers the numerical simulation of the different flow characteristics involved in the conjugate heat transfer analysis of an internally cooled gas turbine blade. Conjugate simulations require full coupling of convective heat transfer in fluid regions to the heat diffusion in solid regions. Therefore, accurate prediction of heat transfer quantities on both external and internal surfaces has the uppermost importance and highly connected with the performance of the employed turbulence models. The complex flow on both surfaces of the internally cooled turbine blades is caused from the boundary layer laminar-to-turbulence transition, shock wave interaction with boundary layer, high streamline curvature and sequential flow separation. In order to discover the performances of different turbulence models on these flow types, analyses have been conducted on five different experimental studies each concerned with different flow and heat transfer characteristics. Each experimental study has been examined with four different turbulence models available in the commercial software (ANSYS FLUENT13.0) to decide most suitable RANS-based turbulence model. The Realizable k-&epsilon / model, Shear Stress Transport k-&omega / model, Reynolds Stress Model and V2-f model, which became increasingly popular during the last few years, have been used at the numerical simulations. According to conducted analyses, despite a few unreasonable predictions, in the majority of the numerical simulations, V2-f model outperforms other first-order turbulence models (Realizable k-&epsilon / and Shear Stress Transport k-&omega / ) in terms of accuracy and Reynolds Stress Model in terms of convergence.

<div>Adversity stemming from socioeconomic risks poses a considerable threat to the wellbeing of parents and youth. Research has shown that children’s exposure to cumulative(consisting of multiple co-occurring risks), chronic(experienced across more than one timepoint), and early(experienced during the birth-to-three-year period) socioeconomic adversity is particularly detrimental to their development. The first aim of this dissertation was therefore to create a measure of socioeconomic adversity that incorporates multiple risk indicators, and that could be used to tap into both the chronicity and timing of exposure. Using this measure, the problem that this dissertation aimed to address is the conflicting evidence that effective parenting is crucial in facilitating positive outcomes in at-risk youth, but that parenting itself is severely compromised in families experiencing socioeconomic adversity. Therefore, the overarching goal of this dissertation was to identify protective factors that can be leveraged to promote positive cascades for parents and youth in the context of socioeconomic adversity. Paper 1 analyzed whether social capital facilitates parental resilience, or the capacity of parents to deliver competent and high-quality parenting to children despite the presence of socioeconomic risks. Paper 2 assessed whether positive parenting in turn facilitates adolescent resilience and well being, or the reduction of maladaptive outcomes and presence of flourishing outcomes despite their exposure to this adversity. Given differences in the experiences of socioeconomic adversity as well as its effects on parents and youth across race-ethnicities, a major goal of this work was to test dissertation aims separately within Black, Hispanic, and White families. Overall, Paper 1 findings suggest that social participation and perceived neighborhood control may attenuate the effects of socioeconomic adversity on positive parenting for Black and White mothers respectively. For Hispanic mothers, social cohesion was found to be a promotive factor for positive parenting in the context of socioeconomic adversity. Paper 2 results indicate that socioeconomic adversity is indirectly associated with higher levels of adolescent substance use in Black youth, and lower levels of adolescent wellbeing in White youth, through lowered self-regulation in middle childhood. However, higher levels of positive parenting in early and middle childhood seemed to weaken these negative effects within non-Hispanic families. These results reinforce the need to enhance social and neighborhood capital for parents facing socioeconomic adversity, in order to facilitate positive parenting behaviors that may in turn protect youth from its negative effects.<br></div>

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Magister Psychologiae - MPsych / The outcome of child abuse, i.e. physical, emotional and/or sexual, and child neglect is multifactorial. The severity, duration and nature of abuse and the child’s vulnerabilities are all contributory factors with regards the outcome of abuse. Children who are traumatized are likely to be profoundly affected. Studies have shown and nearly every researcher agrees that early childhood traumas lie at the root of many emotional and psychological illnesses. It has been noted that drug abuse is a major problem in the Western Cape. This thesis explored the relationship between subjectively perceived childhood trauma and drug dependence in an in-patient treatment-seeking sample of adults in the Cape Town Metropolitan Area in the Western Cape. This thesis presents the results of a measure of childhood trauma, namely the Childhood Trauma Questionnaire [CTQ] and a measure of drug dependence, the Drug Use Disorder Identification Test [DUDIT]. The sample consisted of 52 participants and included both males and females. Only participants who were identified as drug dependent were included in the study. Patients who were actively psychotic and/or alcohol dependent were not included in the study. Ethical clearance was obtained from the University of the Western Cape’s higher degree ethical committee. The anonymity of the participants, the importance of responding openly and honestly and the sensitive nature of the questions were highlighted during the test administration. Questionnaires were administered in accordance with the guidelines stipulated in the respective manuals. The data was analysed through correlation. The study found a positive correlation between childhood emotional abuse and drug dependence, and childhood physical abuse and drug dependence.