Although Rhodococcus equi (R. equi), previously known as Corynebacterium equi, was first isolated from pneumonic foals almost a century ago, it remains the most common cause of subacute or chronic granulomatous bronchopneumonia in foals. While the majority of foals exposed to R. equi develop a protective immune response (regressors), others exhibit a unique susceptibility to infection (progressors). The determinants for either outcome are not completely understood. Therefore, current diagnostic and preventive measures are suboptimal and require betterment. In light of this current need, we hypothesized that immunoglobulin G subisotype T [IgG(T)] against the virulence-associated protein A (VapA) of R. equi, and whole blood cytokine expression profile of foals predict the outcome of infection and can be used as diagnostic markers of clinical disease. Further, we hypothesized that the use of R. equi hyperimmune plasma (HIP) decreases severity of disease in naturally infected foals, playing an important role in disease prevention in the field. Lastly, we hypothesized that specific anti-Rhodococcus equi pili antibodies passively acquired by foals via colostrum after immunization of pregnant mares with a Rhodococcus equi pili-based candidate vaccine will confer protection against induced disease, and therefore have an immediate impact on R. equi pneumonia prophylaxis. The objectives of this study were: (1) to describe the humoral immune response of progressor and regressor foals to R. equi following experimental challenge and natural infection, (2) to compare the cytokine and cell-marker expression profile in whole blood of progressor and regressor foals after challenge, (3) to evaluate the Vap-A specific IgG profile of a commercially available HIP product and its value as a prophylactic tool on an endemic farm, and (4) to evaluate the efficacy of a vaccine based on the Rhodococcus equi pili (Rpl). Although the IgG(T) response of progressor foals after challenge or following natural infection tended to be more pronounced than that observed in regressor foals, its performance as a diagnostic test for predicting disease outcome was poor. Likewise, whole blood cell-marker and cytokine expression profiles of progressor and regressor foals were not significantly different, undermining its reliability as a diagnostic tool. Evaluation of the association of HIP VapA specific IgG profile and rhodococcal disease outcome in the field resulted in the conclusion that progressor foals received significantly less VapA specific IgG, suggesting that HIP may have provided some protection to regressor foals. Although HIP appeared to have provided some protection against clinical pneumonia, Rpl maternally-derived IgG failed to confer any advantage to foals born from vaccinated mares. The Rpl candidate vaccine failed to confer protection to foals after challenge, and did not decrease disease severity in comparison to a control group. In summary, the results of this study do not support the use of VapA specific IgG(T) or whole blood cytokine expression profile as predictors of disease outcome. Further, our results suggest a positive effect of HIP on disease outcome. Lastly, the presence of systemic and local Rpl antibodies was not protective in foals.

Mast cells are key players of the innate immune system due to their location at the interface of host and pathogen encounters, such as on mucosal surfaces or the skin. Secreting a variety of compounds, they communicate with other immune cells in a highly specific manner. Subsequently, reinforcements against foreign invaders are recruited while also defending the host, using bacteriolytic effector molecules. One type of pathogens which are competent challengers of the host’s immune system are Streptococci, causing a burden for humans and animals. Streptococcus equi subspecies equi is one example, a highly contagious horse pathogen with a silent carrier subset, causing “strangles”, a disease resulting in equine morbidity and mortality all over the world. The present study aimed to explore the virulence factors in S. equi responsible for immune system activation, represented by mast cells. Knockout mutants of the genes aroB, hasA, pyrC, recA, sagA and a combination of those, including a deletion strain of all superantigens (seeHILM), were co-cultivated with murine bone-marrow-derived mast cells (BMMCs). Mast cells alone and S. equi strain 4047 (wild-type) were used as controls. It was shown that 4 h after encounter of the bacteria, BMMCs responded with IL-6, TNF-α and MCP-1 secretion, indicating an inflammatory response to all strains except against the sagA mutant (ΔsagA) or the multi-deletion strain, the latter lacking several virulence factors including sagA. These results were confirmed at the mRNA-level where IL-6, TNF-α and Nr4a3 gene expression was significantly upregulated in BMMCs after 4 h incubation with wild-type S. equi. In contrast, when BMMCs were co-cultivated with sagA-deficient S. equi, no detectable upregulation was seen. These results were further confirmed in peritoneal-derived mast cells. After 24 h no secretion of cytokines was detected in response to ΔsagA mutants, in contrast to the strong cytokine output in response to wild-type S. equi. To elucidate the role of SagA, the precursor of streptolysin S (SLS), lysis was determined, and it was observed that ΔsagA does not lyse mast cells in contrast to wild-type with intact SLS. Transwell-based experiments indicated a partially contact-dependent response of mast cells to bacteria. Taken together, this study shows for the first time that SLS is the major mast cell activator produced by S. equi. I suggest the possible mechanism of cell death by lysis and reprogrammed signaling pathways of the host by sublytic concentrations of SLS, resulting in damage associated pattern-mediated signaling as well as auto- and paracrine amplification by inflammatory cytokines and other messenger molecules.

Author: Bc. Petra Žitná Title: Evaluation of the influence of regular slackline activity on the dynamic postural stability of the sport population aged 20-30 years Aim: The aim of this work is an attempt to objectively evaluate the influence of regular slackline sporting activity on dynamic postural stability in comparison with a standard named "Athles Norm 20-30" (further stated as "Norm AN") set for sporting population aged between 20 - 30 years. Methods: The measurements were carried out in the Laboratory of kinesiology at the Faculty of Physical Education and Sport, Charles University. There were tested 10 participants aged 20-30 years doing the slackline sport for long time. For testing the dynamic postural stability were used the Sensory Organization Test, Unilateral Stance and Head Shake - Sensory Organization Test. The measurements on the NeuroCom Smart Equi Test were preceded by carrying out the Stork Standing Balance Test both in standardized form and modification. After specifying the statistic difference between the measured values and Norm AN there was used the Welch Test with the significance level of α = 0.05. For evaluating the correlations there was used the Pearson Test. As a high degree of reliability there was accepted the value of r ≥ 0.70. Results: There were recorded...

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Cette thèse se décompose en deux parties. Dans un premier temps nous nous intéressons à la sélection bayésienne de variables dans un modèle probit mixte.L'objectif est de développer une méthode pour sélectionner quelques variables pertinentes parmi plusieurs dizaines de milliers tout en prenant en compte le design d'une étude, et en particulier le fait que plusieurs jeux de données soient fusionnés. Le modèle de régression probit mixte utilisé fait partie d'un modèle bayésien hiérarchique plus large et le jeu de données est considéré comme un effet aléatoire. Cette méthode est une extension de la méthode de Lee et al. (2003). La première étape consiste à spécifier le modèle ainsi que les distributions a priori, avec notamment l'utilisation de l'a priori conventionnel de Zellner (g-prior) pour le vecteur des coefficients associé aux effets fixes (Zellner, 1986). Dans une seconde étape, nous utilisons un algorithme Metropolis-within-Gibbs couplé à la grouping (ou blocking) technique de Liu (1994) afin de surmonter certaines difficultés d'échantillonnage. Ce choix a des avantages théoriques et computationnels. La méthode développée est appliquée à des jeux de données microarray sur le cancer du sein. Cependant elle a une limite : la matrice de covariance utilisée dans le g-prior doit nécessairement être inversible. Or il y a deux cas pour lesquels cette matrice est singulière : lorsque le nombre de variables sélectionnées dépasse le nombre d'observations, ou lorsque des variables sont combinaisons linéaires d'autres variables. Nous proposons donc une modification de l'a priori de Zellner en y introduisant un paramètre de type ridge, ainsi qu'une manière de choisir les hyper-paramètres associés. L'a priori obtenu est un compromis entre le g-prior classique et l'a priori supposant l'indépendance des coefficients de régression, et se rapproche d'un a priori précédemment proposé par Gupta et Ibrahim (2007).Dans une seconde partie nous développons deux nouvelles méthodes MCMC basées sur des populations de chaînes. Dans le cas de modèles complexes ayant de nombreux paramètres, mais où la vraisemblance des données peut se calculer, l'algorithme Equi-Energy Sampler (EES) introduit par Kou et al. (2006) est apparemment plus efficace que l'algorithme classique du Parallel Tempering (PT) introduit par Geyer (1991). Cependant, il est difficile d'utilisation lorsqu'il est couplé avec un échantillonneur de Gibbs, et nécessite un stockage important de valeurs. Nous proposons un algorithme combinant le PT avec le principe d'échanges entre chaînes ayant des niveaux d'énergie similaires dans le même esprit que l'EES. Cette adaptation appelée Parallel Tempering with Equi-Energy Moves (PTEEM) conserve l'idée originale qui fait la force de l'algorithme EES tout en assurant de bonnes propriétés théoriques et une utilisation facile avec un échantillonneur de Gibbs.Enfin, dans certains cas complexes l'inférence peut être difficile car le calcul de la vraisemblance des données s'avère trop coûteux, voire impossible. De nombreuses méthodes sans vraisemblance ont été développées. Par analogie avec le Parallel Tempering, nous proposons une méthode appelée ABC-Parallel Tempering, basée sur la théorie des MCMC, utilisant une population de chaînes et permettant des échanges entre elles. / This thesis is divided into two main parts. In the first part, we propose a Bayesian variable selection method for probit mixed models. The objective is to select few relevant variables among tens of thousands while taking into account the design of a study, and in particular the fact that several datasets are merged together. The probit mixed model used is considered as part of a larger hierarchical Bayesian model, and the dataset is introduced as a random effect. The proposed method extends a work of Lee et al. (2003). The first step is to specify the model and prior distributions. In particular, we use the g-prior of Zellner (1986) for the fixed regression coefficients. In a second step, we use a Metropolis-within-Gibbs algorithm combined with the grouping (or blocking) technique of Liu (1994). This choice has both theoritical and practical advantages. The method developed is applied to merged microarray datasets of patients with breast cancer. However, this method has a limit: the covariance matrix involved in the g-prior should not be singular. But there are two standard cases in which it is singular: if the number of observations is lower than the number of variables, or if some variables are linear combinations of others. In such situations we propose to modify the g-prior by introducing a ridge parameter, and a simple way to choose the associated hyper-parameters. The prior obtained is a compromise between the conditional independent case of the coefficient regressors and the automatic scaling advantage offered by the g-prior, and can be linked to the work of Gupta and Ibrahim (2007).In the second part, we develop two new population-based MCMC methods. In cases of complex models with several parameters, but whose likelihood can be computed, the Equi-Energy Sampler (EES) of Kou et al. (2006) seems to be more efficient than the Parallel Tempering (PT) algorithm introduced by Geyer (1991). However it is difficult to use in combination with a Gibbs sampler, and it necessitates increased storage. We propose an algorithm combining the PT with the principle of exchange moves between chains with same levels of energy, in the spirit of the EES. This adaptation which we are calling Parallel Tempering with Equi-Energy Move (PTEEM) keeps the original idea of the EES method while ensuring good theoretical properties and a practical use in combination with a Gibbs sampler.Then, in some complex models whose likelihood is analytically or computationally intractable, the inference can be difficult. Several likelihood-free methods (or Approximate Bayesian Computational Methods) have been developed. We propose a new algorithm, the Likelihood Free-Parallel Tempering, based on the MCMC theory and on a population of chains, by using an analogy with the Parallel Tempering algorithm.

Bacteria of the genus Streptococcus are common asymptomatic colonisers of humans and animals. As opportunistic pathogens they can however, depending on their host’s immune status and other circumstances, cause mild to very severe infections. Streptococci are highly intertwined with specific host species, but can also cause zoonosis or anthroponosis in more uncommon hosts. Prolonged and reoccurring infections require immune evasion strategies to circumvent detection and eradication by the host’s immune defence. A substantial part of the immune defence against bacterial pathogens is mediated by immunoglobulins. This thesis is based on work to identify and characterise immunoglobulin degrading enzymes secreted by different Streptococcus species as a means to sabotage and evade antibody-mediated immune responses. Stoichiometric and kinetic analysis of the IgG degrading enzyme IdeS from the important human pathogen S. pyogenes revealed that IdeS cleaves IgG, opposed to previous publications, as a monomer following classical Michaelis-Menten kinetics. The IdeS homologue of S. suis, IdeSsuis, did however not cleave IgG, but was highly specific fo rporcine IgM. S. suis was found to possess yet another protease, IgdE, capable of cleaving porcine IgG. Both of these proteases were shown to promote increased bacterial survival in porcine blood during certain conditions. IgdE is the founding member of a novel cysteine protease family (C113). Novel streptococcal members of this protease family were shown to specifically degrade certain IgG subtypes of the respective Streptococcus species’ main host. The observed substrate specificity of IgdE family proteases reflects the host tropism of these Streptococcus species, thereby giving insights into host-pathogen co-evolution. The abundance of immunoglobulin degrading enzymes among Streptococcus species indicates the importance of evasion from the antibody mediated immune responses for streptococci. These novel identified immunoglobulin degrading enzymes of the IdeS and IgdE protease families are potential valid vaccine targets and could also be of biotechnological use.

Author: Anna Šalbabová Title: Influence of acrobatic sports on dynamic postrual stability Objectives: The aim of this study is to evaluate an influence of acrobatic sports on dynamic postural stability with greater focus on vestibular system and reaction time of the subjects and to compare those qualities with non-acrobatic subjects who have no history of acrobatic training. Methods: Assessments were performed on NeuroCom Smart Equi Test device, which is located in laboratory of kinesiology at the UK FTVS. There were 20 subjects divided into 2 groups 10 subject each. One group made of 10 acrobatic athletes, the second group of 10 non- acrobatic subjects with no history of acrobatic training. The age of all subjects ranges from 20 to 34 years. For the testing of dynamic postural stability were used Sensory Organization Test (SOT), Motor Control Test (MCT), Head Shake - Sensory Organization Test (HS-SOT). For assessment of vestibulo-ocular reflex was used Dynamic Visual Acuity Test (DVAT), which cannot be performed without Perception Time Test (PPT). Results: The results have shown significantly better reaction times of acrobatic group in MCT and better results of acrobatic group in Head Shake - SOT in half of the performed tests. SOT and DVAT have shown no significant data. Conclusion: This study...

In this study, the spin-splitting energy of the lowest conduction bands in bulk zincblende and wurtzite structures of III-V semiconductors had been investigated by the linear combination of atomic orbital (LCAO) method, the atomic bond-orbital model (ABOM), and the two-band k¡Dp (2KP) model. Spin-splitting calculation for zincblende structures: We develop a 16-band atomic bond-orbital model (ABOM) to compute the spin splitting induced by bulk inversion asymmetry in zincblende materials. This model is derived from the linear combination of atomic orbital (LCAO) scheme such that the characteristics of the real atomic orbitals can be preserved to calculate the spin splitting. The Hamiltonian of 16-band center-zone ABOM (CZABOM) is based on a similarity transformation performed on the nearest-neighbor LCAO Hamiltonian with a second-order Taylor expansion over k at the £F point. The spin-splitting energies in bulk zincblende semiconductors, GaAs and InSb, are calculated, and the results agree with the LCAO and first-principles calculations. However, we find that the spin-orbit coupling between bonding and antibonding p-like states, evaluated by the 16CZABOM, dominates the spin splitting of the lowest conduction bands in the zincblende materials. Spin-splitting calculation for wurtzite structures: The spin-splitting energies in biaxially strained bulk wurtzite material AlN are calculated using the linear combination of atomic orbital (LCAO) method, and the equi-spin-splitting distributions in k-space near the minimum-spin-splitting (MSS) surfaces are illustrated. These data are compared with those derived analytically by two-band k¡Dp (2KP) model. It is found that the results from these two methods are in good agreement for small k. However, the ellipsoidal MSS surface under biaxial compressive strain does not exist in the 2KP model, because the data points are far from the £F point. Instead, three basic shapes of the MSS surface occur in the wurtzite Brillouin zone: a hyperboloid of two sheets, a hexagonal cone, and a hyperboloid of one sheet, evaluated from the LCAO method across the range of biaxial strains from compressive to tensile. The shapes of the equi-spin-splitting (ESS) surfaces near these MSS surfaces have also three types: a hyperboloid of one sheet, an approximate, asymmetric hyperboloid surface, and an opposing hyperboloid of one sheet.

In Turkey, the majority of the historic city centres have been continuously occupied since early ages onwards and where still occupation exists. The multi-layered structure of historic centres both can indicate the historical continuity of cities and enhance urban consciousness, if urban archaeological resources are handled effectively into planning process. However, the recent policies and strategies don&amp / #8217 / t allow the handling of urban archaeological resources, especially invisible sub-soil resources, into planning and decision-making process. In this thesis, it is aimed to formulate a basic methodological framework for the handling of urban archaeological resources into planning process of historic city centres in Turkey. Therefore, the study is handled in two parts / a conceptual methodological framework part and an exploratory case study.In the conceptual part, a basic equation is studied to research the factors on the conservation and evaluation of real urban archaeological potential. Then, the methodological framework is examined in detail in izmir Historic City Centre that has been inhabited since 324 B.C. Consequently, the terms of equi-property areas, which are used to define ideal potential of archaeological resources, and urban archaeological character zones, which are described as the basic units of planning and conservation policies, are developed to determine exact management strategies for urban archaeological resources.

The present thesis gives a summary of results obtained through theoretical and experimental studies of systems with relevance to copper smelting and converting. Many chemical elements are involved in the copper production pro­cesses and a detailed experimental study would be very time- consuming and expensive. A complicating fact is also the corrosivity of the liquid phases towards container material. A powerful alternative is equilibrium calculations, in which models for the liquid phases as well as reliable basic thermodynamic data are needed. In the present thesis, a generalized structure based model for liquid silicates was developed and used in assessments of the sys­tems PbO-SiO2, Fe-O-SiO2, CuO0.5-SÌO2 and Cu-Fe-O-SiO2. In the model, the non-ideal silicate melt is treated as an ideal solu­tion but containing a few complexes. The PbO-Si02 melt could be described by introducing the complexes Pb3Si207, Pb4Si4010 and Pb13Si12O37 in addition to the components PbO and Pb2Si04. The species considered in the Fe-O-SiO2 melt were FeO, FeO1.5, Fe2Si04, Fe3Si207, Fe3Si6O15 and in the CUO0.5-SiO2 melt CuO0.5 ana CU4SiO4. Trie calculated phase diagrams, the activities of me­tal oxides and the oxygen partial pressures were all in good agreement with the published data. Two of the papers in this thesis concern the determination of Gibbs free energies for Cu2S(s,l) and Ca2Fe2O5(s) through emf measurements utilizing a solid electrolyte. Activities and termi­nal solubilities in the solid solution [Fet,Ca]0 were also deter­mined. The results obtained from the quantitative equilibrium calcula­tions for conventional copper smelting and converting were used to outline the overall reactions taking place and the outcome of changes in process parameters. Comparison with observed values, however, showed that the copper and magnetite contents in slag were calculated too low. These discrepancies could be completely explained by using a non-equilibrium approach in which the con­verter was assumed to consist of several segments with concentra­tion gradients between the segments. / digitalisering@umu.se