Due to tuberculosis (TB) being one of the top ten diseases in Africa with the highest mortality rate, a crucial objective is to find the appropriate medication to cure patients and prevent people from contracting the disease. Since this statistic is not improving sufficiently, it is evident that there is a need for new anti-TB drugs. One of the main challenges in developing new and effective drugs for the treatment of TB is to identify the combinations of effective drugs when subsequent testing of patients in pivotal clinical trials are performed. During the early weeks of the treatment of TB, trials of the early bactericidal activity assess the decline in colony-forming unit (CFU) count of Mycobacterium TB in the sputum of patients containing smear-microscopy-positive pulmonary TB. A previously published dataset containing CFU counts of treated patients over 56 days is used to perform joint modeling of the nonlinear data over time and the patients’ sputum culture conversion (i.e., the time-to-event outcome). It is clear from the results obtained that there is an association between the longitudinal and time-to-event outcomes. / Mini Dissertation ( MSc (Advanced Data Analytics))--University of Pretoria, 2021. / South African Medical Research Council (SAMRC) / Statistics / MSc (Advanced Data Analytics) / Restricted

This thesis presents research focused on developing statistical methods with emphasis on techniques that can be used for the analysis of data in imaging studies and sparse estimations for applications in high-dimensional data. The first contribution addresses the pixel/voxel-labeling problem for spatial hidden Markov models in image analysis. We formulate a Gaussian spatial mixture model with Potts model used as a prior for mixture allocations for the latent states in the model. Jointly estimating the model parameters, the discrete state variables and the number of states (number of mixture components) is recognized as a difficult combinatorial optimization. To overcome drawbacks associated with local algorithms, we implement and make comparisons between iterated conditional modes (ICM), simulated annealing (SA) and hybrid ICM with ant colony system (ACS-ICM) optimization for pixel labelling, parameter estimation and mixture component estimation. In the second contribution, we develop ACS-ICM algorithm for spatiotemporal modeling of combined MEG/EEG data for computing estimates of the neural source activity. We consider a Bayesian finite spatial mixture model with a Potts model as a spatial prior and implement the ACS-ICM for simultaneous point estimation and model selection for the number of mixture components. Our approach is evaluated using simulation studies and an application examining the visual response to scrambled faces. In addition, we develop a nonparametric bootstrap for interval estimation to account for uncertainty in the point estimates. In the third contribution, we present sparse estimation strategies in linear mixed model (LMM) for longitudinal data. We address the problem of estimating the fixed effects parameters of the LMM when the model is sparse and predictors are correlated. We propose and derive the asymptotic properties of the pretest and shrinkage estimation strategies. Simulation studies is performed to compare the numerical performance of the Lasso and adaptive Lasso estimators with the pretest and shrinkage ridge estimators. The methodology is evaluated through an application of a high-dimensional data examining effective brain connectivity and genetics. In the fourth and final contribution, we conduct an imaging genetics study to explore how effective brain connectivity in the default mode network (DMN) may be related to genetics within the context of Alzheimer’s disease. We develop an analysis of longitudinal resting-state functional magnetic resonance imaging (rs-fMRI) and genetic data obtained from a sample of 111 subjects with a total of 319 rs-fMRI scans from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. A Dynamic Causal Model (DCM) is fit to the rs-fMRI scans to estimate effective brain connectivity within the DMN and related to a set of single nucleotide polymorphisms (SNPs) contained in an empirical disease-constrained set. We relate longitudinal effective brain connectivity estimated using spectral DCM to SNPs using both linear mixed effect (LME) models as well as function-on-scalar regression (FSR). / Graduate

Master's thesis deals with the Red Hill, a place situated inside the urban area of Brno, close to the historic center, close to the newly established and still growing campus of Masaryk University. Red hill with its gardening colony remains blank space on the map of Brno, the goal here was to create a functional urban structure that would place the space in the city map. Not to make an urban mash on the peripherals, but build a real city organism into the hearth of the city Brno.

This thesis deals with robot path planning by means of ant colony optimization algorithms. The theoretical part of this thesis introduces basics of path planning problematics. The theoretical part either deals with ant algorithms as optimization and path planning tools. The practical part deals with design and implementation of path planning by means of ant algorithms in Java language.

This thesis deals with the implementation of the metaheuristic algorithms into the Drools Planner. The Drools Planner is an open source tool for solving optimization problems. This work describes design and implementation of Ant colony optimization metaheuristics in the Drools Planner. Evaluation of the algorithm results is done by Drools Planner benchmark with different kinds of optimization problems.

The city of Philippi was founded as a Roman military colony in 42 BC, directly following one of the largest battles of antiquity, the civil war battle of Philippi. This study shows that one hundred years later, at the time of writing of Paul’s letter to the Philippians, the identity of the city was still deeply connected to its military history. The apostle Paul found in the historical and sociological ties of the Philippians with the military reasons for drafting his letter in a rhetorical arrangement similar to the historical reports of commander’s speeches to his assembled troops before battle. Not only does the vocabulary of Paul’s ethical commands parallel the general’s harangues, as has been previously pointed out by Biblical scholarship, but in Paul’s letter one also finds correspondences to the three largest motifs of the general’s speeches: the objective of the war, the confidence for victory and the rewards for courage and obedience. The major unified theme of Philippians is the mutual military-partnership for the advance of the gospel in a hostile context (Phil. 1:7-12; 1:20; 2:19-24; 2:25-30; 3:12-15; 4:3; 4:10-19). Paul in his letter to the Philippians uses consistently military imagery – and not once athletic imagery, as typically assumed by exegetical scholars – to demonstrate that the courageous sharing of the faith will always result in victory for the one who proclaims Christ. This victory is guaranteed through the unsurpassable abilities of the supreme general, Jesus Christ, whose death on the cross and whose resurrection is portrayed as a military victory and whose exaltation by God the Father acknowledges Christ as the victorious general in an universal extent (Phil. 2:8-11). The victory of the gospel campaign is further guaranteed by the LORD’s initiation of the war for the spread of the faith and by His presence with those who fight in His behalf for the spread of the good news (Phil. 1:5-7; 2:12-13; 2:14-15; 3:1; 4:4). Victory in the Philippian context means either the reception of the gospel by unbelievers or the death of the messenger on account of rejection of and opposition to the gospel; the suffering of the emissary of the gospel serves to glorify Christ and it is compensated by the superior enjoyment of Christ at the resurrection (Phil. 1:19-25). The reward, which God promises to the messenger of the gospel is several times stated in Philippians to be the exalted experience of fellowship with Christ at the resurrection (Phil. 1:21; 3:8-11; 3:20-21; 4:3). The reading of Philippians in light of the appropriation of military terminology confirms that Paul’s main purpose in writing Philippians is to encourage his partners to continue to take risks, to be unafraid of suffering and to make sacrifices in order to boldly testify about Christ and to continue to financially contribute to the mission of spreading the faith. The book of Philippians challenges the contemporary self-centred prosperity culture of the church to take risks and make sacrifices for the proclamation of Christ to unbelievers, sacrifices, which are supremely compensated by a life for the glory of Christ and the surpassing promise of the enjoyment of the glory of God in His Son Christ Jesus. / Thesis (PhD)--University of Pretoria, 2013. / gm2014 / New Testament Studies / unrestricted

<p>Evidence from experimental models of epilepsy support that prolonged seizures (status epilepticus, SE) promote pathological hippocampal synaptodendritic remodeling which contributes to the development of seizures and cognitive decline. One potential mechanism underlying the SE-induced sequelae is microgliosis. </p> <p>Evidence from models of experimental epilepsy supports a significant spatiotemporal correlation between SE-induced decreases in the microtubule associated protein 2 (Map2) loss and microgliosis in the hippocampus. In addition, pharmacological suppression of microgliosis after SE with the drug rapamycin attenuated the losses of Map2 and the dendritic ion channels Kv.4.2 and HCN1 in the hippocampus. This microglia suppression paralleled a recovery of the SE-induced recognition and spatial memory deficits. Based on these studies, we hypothesized that the inhibition of microgliosis during epileptogenesis will attenuate the SE-induced hippocampal dendritic and cognitive pathology. To further investigate the role of microgliosis in the SE-induced dendritic pathology, we tested the efficacy of a more selective inhibitor <a>of the survival and proliferation of </a>microglia, PLX3397, using the pilocarpine model of SE and acquired epilepsy. PLX3397 binds to colony stimulating factor 1 receptor (CSF1R) on microglia and inhibits the downstream signaling responsible for survival and proliferation of these cells. </p> <p>To test this hypothesis, we induced SE in male rats with pilocarpine (280-300mg/kg) <a>while and controls (Ctrl) received saline. </a>Rats were randomly assigned to a diet of either chow alone (vehicle; Veh) or chow with PLX3397 (50mg/kg) for 20 days post-SE. At two weeks post-SE, rats were subjected to novel object recognition (NOR) and Barnes maze (BM) to evaluate hippocampal-dependent recognition memory, and spatial learning and memory, respectively. Following the behavioral assessments, rats were sacrificed for brain analysis at 20 days post-SE. We used histological analysis to determine the amount of microgliosis with IBA1 and dendritic stability with Map2. We used western blotting to measure the protein levels of molecules involved in the crosstalk between microglia and astrocytes: GFAP, IL-6, C3, and iC3b. We also measured the protein levels of the dendritic ion channels Kv4.2 and HCN1, and the synaptic marker PSD95.</p> <p>NOR showed that the Ctrl+Veh and Ctrl+PLX3397 groups spent significantly more time exploring the novel object (<i>p</i> < .05), while the SE+Veh and SE+PLX3397 did not. Similar results were observed in the BM test, Ctrl+Veh and Ctrl+PLX3397 groups had a faster latency to find the target compared to the SE+Veh and SE+PLX3397 groups (<i>p</i> < .05). These data suggest that recognition and spatial memory deficits induced by SE were not attenuated by treatment with PLX3397. We found that the PLX3397 treatment significantly decreased microgliosis in Ctrl+PLX3397 rats compared to Ctrl+Veh rats (<i>p</i> < .05). As expected, we found a significant increase in the number of microglial cells in hippocampi of SE+Veh rats compared to Ctrl+Veh rats (<i>p</i> < .05). Interestingly, in the PLX3397-treated SE group, we observed two distinctive groups which we categorized as responders and non-responders when compared to the SE+Veh group. The SE+PLX responders had significantly decreased microgliosis compared to the SE+Veh group (<i>p</i> < .05). The SE+PLX non-responders had higher levels of microgliosis compared to the SE+Veh group (<i>p</i> < .05). We found levels of GFAP were increased in the SE+Veh group compared to the Ctrl+Veh group (<i>p</i> < .05). Treatment with PLX3397 in the SE group reduced these levels compared to the vehicle treated SE group (<i>p</i> < .05). We also found increases in C3 and iC3b following the induction of SE compared to Ctrl+Veh group (<i>p</i> < .05), and these levels remained similar in the SE+PLX3397 group compare to the SE+Veh group (<i>p</i> > .05). There was a reduction in Map2 immunoreactivity as well as the protein levels of Kv4.2 and PSD95 in the SE+Veh group compared to the Ctrl+Veh group (<i>p</i> < .05). We found that treatment with PLX3397 recovered the SE-induced loss of Map2 labeled dendrites compared to SE+Veh group (<i>p</i> < .05). However, treatment with PLX3397 did not recover the SE-induced reduction Kv4.2 and PSD95 (<i>p</i> > .05). <a>In parallel, we found that a group of SE+PLX3397 animals did not have reduced microgliosis compared to the SE+Veh group (<i>p </i>< .05), and therefore was categorized as a non-responder group. </a></p> Our findings are the first to show that blocking CSF1R signaling with PLX3397 suppressed microgliosis in the hippocampus, partially recovered the SE-induced decline of Map2 immunoreactivity in the hippocampal CA1 region but had no effect in the recognition or spatial memory deficits. These data suggest that while hippocampal microgliosis may play a role in the disruption of dendritic structural stability in the hippocampus it does not seem to critically contribute to the memory decline that occurs during epileptogenesis.

On solid surfaces, laboratory strain Saccharomyces cerevisiae BY4742 forms horizontally and vertically stratified colonies. Central part of the colony differentiates into U and L cells occupying upper and lower colony regions, respectively. There are many morphological and physiological differences between these two cell types. However, molecular mechanisms of the vertical stratification are still largely unknown. In this study, I analyzed effects of the deletion and overexpression of Sch9p a Rim15p kinases with crucial role in nutrient sensing pathways, of transcription activators Msn2p and Msn4p involved i stress response and of post-diauxic shift transcription factor Gis1p in yeast colony differentiation and U and L cell survival. Microscopic analyses showed changes in morphology of cells in colonies of these strains and decreased ability of vertical stratification in colonies of the strain rim15Δ and partially in colonies of the strain PTEF-SCH9. Moreover, changed level of these proteins significantly affected long-term survival of U and L cells. Obtained data suggest an involvement of nutrient sensing pathways in colony formation and development.

This thesis deals with the development of mining and mining colonies in the Ostrava region and also deals with the interpretation of interviews with miners performing their profession in the Ostrava-Karviná mining district between years 1950 and 1994. It focuses not only on the development of the environment and mining conditions in the Ostrava region, but also reasons and motivations for choosing a demanding and often life-threatening profession, as mining is. The thesis is produced using inductive method, where the processes at the individual level apply to wider groups. Such processing allows me to process interviews with witnesses alongside traditional written sources. The finding of the thesis is the fact that there are three main motives for the choosing of mining profession, which are family tradition, the possibility of not participating in two-year compulsory military training and last but not least, the above-standard wage. The thesis offers another view on how workers in socialist Czechoslovakia lived.

This thesis follows previous works of our group (Rieger T. et al., 2008; Cepl J. et al., 2010 and Patkova I. et al., 2012), where we focused on the morphology of the bacterial colonies Serratia marcescens and its variety caused by changing of the inoculation conditions on nutrient agar. When bacterial colonies S. marcescens are grown on nutrient agar enriched with glucose isolated enough from other colonies in its living space, it can form coloured structured colonies, which we named morphotype "fountain" (F). This morpotype becomes ideal for following studies of mutual influencing of the bacterial colonies, because of its ability of pigmentation change or structure loss caused by altering surrounding inoculation conditions. We noticed in normal sowed agar plates, that bacterial colonies, which grows in the close distance with other colonies develop their pigmentation sooner, than colonies, that grows more isolated. We studied how is this influencing happening and what are the necessary conditions for it. We proved, that different species of bacterial macrocolonies (S. marcescens - morphotype (M), S. rubidea and E. coli) emits into the nutrient agar informative signal, which makes the recipient colonies S. marcescens reacts on this signal with the same manner (X structure). It looks, that this is...