Staphylococcus aureus is an important opportunistic pathogen in humans and animals. In humans, there has been an increase in community-associated methicillin-resistant Staphylococcus aureus (MRSA) causing disease in healthy humans. The exact evolutionary origins and basis for its recent expansion are not yet clear. In livestock, S. aureus is an important cause of diseases of welfare and economic importance, including bovine mastitis. Molecular typing studies demonstrate that natural populations of S. aureus are highly clonal and largely adapted to a specific host, however there are some lineages that colonise multiple host species. In particular, clonal complex 97 (CC97) is a dominant bovine mastitis-associated lineage which has been isolated from other animal species, and more recently there are increasing reports of CC97 S. aureus from human infections worldwide. The basis for this wide host tropism is currently unknown. In order to investigate the evolutionary origins of S. aureus CC97, 43 strains were selected for whole genome sequencing, isolated from humans, cattle and pigs, from 18 different countries on 4 continents, ranging from 1956 to 2012. Phylogenetic analysis using high quality core genome single nucleotide polymorphisms (SNPs) resolved the single CC97 lineage into host-adapted sublineages, which were likely the result of 2 independent livestock-to-human host jumps estimated to have occurred at least 40 years ago. One of the human sublineages consisted of strains from 4 continents indicating global dissemination since the host jump occurred. In order to investigate the genetic basis for human host adaptation in S. aureus CC97, comparative genomic analysis of mobile genetic elements, nonsynonymous SNPs and small insertions and deletions was performed. Of note, independent acquisitions of genetic elements encoding antimicrobial resistance and specific mediators of human innate immune evasion were identified in the human-adapted S. aureus CC97 strains. These data are consistent with an important role for mobile genetic elements in the host adaptive evolution of S. aureus CC97. Also in the current study, a bovine-associated single locus variant of ST97 (ST71) was identified as a phylogenetic outgroup relative to all other S. aureus CC97 strains examined. Comparative genomic analysis of ST71 strains with representative bovine ST97 strains indicate that ST71 has a mosaic genome. A large region spanning the origin of replication demonstrated closest homology to non-CC97 ruminant-associated genotypes, with the remainder of the genome consistent with an ancestral ST97 genetic background. Recombination detection analysis predicts that one or more large-scale recombination events have occurred in the region that spans the origin of replication, resulting in variation in gene content between ST71 and ST97. The data highlight the potential role of homologous recombination in rapidly generating genomic diversity that might alter the phenotype of strains in the ecological niche of the bovine mammary gland. Overall, the study reveals the evolutionary history of a major pathogenic clone of S. aureus affecting multiple host species, and identifies the genetic events which have contributed to its success.

Abstract Lysyl hydroxylase (EC 1.14.11.4, procollagen-lysine 2-oxoglutarate 5-dioxygenase, PLOD) catalyses the formation of hydroxylysine in collagens and in the other collagen like proteins. Hydroxylysine participates in the formation of cross-links between collagen molecules and can bind to the carbohydrates, galactose and glucosylgalactose. Patients with the type VIA Ehlers-Danlos syndrome (EDS) have characteristically a deficiency in hydroxylysine of collagen in their skin that is caused by reduced activity of lysyl hydroxylase 1. In this work the mutations were studied in detail in four different Ehlers-Danlos VIA patients. The first patient characterized in this study had a duplication of seven exons in the lysyl hydroxylase gene 1. The mutation was caused by homologous recombination of two identical 44-nucleotide regions of Alu sequences in introns 9 and 16 in the gene. This study also suggests that uniparental isodisomy does not explain the homozygosity of the mutation. The second patient was found to have two mutations in the gene for lysyl hydroxylase 1 in a compound heterozygote state. The study resulted in the discovery of the first deletion mutation in the gene. The deletion was caused by an Alu-Alu recombination that removes about 3 kb from the gene including all the exon 17 sequences. The other mutation causes deletion of exon 16 from the mRNA. Deletion of the penultimate nucleotide of intron 15 destroys the consensus sequence of the intron/exon boundary and thus causes the deletion. The third patient was described to have a nonsense codon in exon 14 of one allele which causes a reduction in the amount of lysyl hydroxylase mRNA and leads to aberrant RNA splicing in the cell. The other allele was concluded to be operationally null. In the last work two novel null mutations were found in the gene for lysyl hydroxylase 1. The first was a one nucleotide deletion in the acceptor splice site of intron 4 and the other an insertion of a C nucleotide in exon 2. The abnormal alleles lead to markedly decreased lysyl hydroxylase mRNA levels. This work revealed many exon deleted splicing variants of lysyl hydroxylase mRNA which were first discovered in affected cells, but traces of similarly spliced mRNA species were also found in the cytoplasm of normal human skin fibroblasts. These data indicate that the splicing machinery of the cell is leaky. In this thesis, several types of stuctural mutations in the DNA were found to be responsible for lysyl hydroxylase deficiency in patients with type VIA variant of EDS. The different mechanisms causing these mutations were also studied in detail.

This research elaborates the concept of Resource Recombination in firms from a Dynamic Capability perspective. With the investigation of the role of Dynamic Capabilities in the process of Resource Recombination, this research addresses some existing shortcomings in the Dynamic Capability literature, where there is a crucial need to better understand the interrelationship between Dynamic Capabilities, the firm`s resource base, and innovation in form of Resource Recombinations. Examining the effect of a specific set of Dynamic Capabilities - namely the firm`s Sensing Capacity, Learning Capacity, Integrating Capacity and Coordinating Capacity - on Resource Recombination in firms, this research sheds light on what it is that explains the competitive heterogeneity and variance in resource value creation across firms. Addressing this issue, this research contributes to the resource and competence based research by presenting and empirically testing a conceptual model of factors influencing Resource Recombination in firms. The conceptual model is developed based on a thorough literature review, before being further tested, refined and validated using a mixed method research approach, entailing both qualitative and quantitative research steps. Hereto, empirical data from 208 target respondents is analysed applying structural equation modelling (SEM) principles, including structural path analysis and hypothesis testing, model re-specification, as well as mediation and moderation analyses. In line with the resource based view (RBV), empirical findings confirm that the firm`s resource endowments explain - in part - value creation in firms. But moreover this study found that the effectiveness of those resource endowments to provide productive performance outcomes depends on the extent to which firms possess specific Dynamic Capabilities: Sensing and Learning capacities are important for building the potential value of resources for Resource Recombination, while Integrating and Coordinating capacities are necessary for realising the value creation potential of those resources by developing new Resource Recombinations. Accordingly, regarding their role and effects towards Resource Recombination, two different types of Dynamic Capabilities can be distinguished: Potential Building Dynamic Capabilities and Value Realizing Dynamic Capabilities, whereby both capacity modes have complementary roles and are critical to the achievement of superior performance. Moreover, empirical evidence is given that the firm`s Entrepreneurial Orientation and Networking Orientation are important antecedents for the development of Dynamic Capabilities, and consequently Resource Recombinations. The principal aim of this research was to bring clarity to the notion of Dynamic Capabilities, their role and effects towards building Resource Recombinations in firms. With the Dynamic Capability framework and conceptual model presented, this research offers a more precise definition of the firm`s Dynamic Capabilities, shedding light on their role and effects towards developing new Resource Recombinations and separating them from their antecedents and consequences. Therewith, this research not only contributes towards opening up the black box of Resource Recombination in firms, but moreover helps to establish Dynamic Capabilities as a theoretically, well-founded and useful construct for strategic management. By explicitly embedding the Dynamic Capability perspective in resource based explanations for value creation, this research extends the traditional focus of the RBV, working towards a more dynamic interpretation of the RBV. It thereby tries to overcome the identified limitations of past research in this field.

>Magister Scientiae - MSc / This is a pilot study to investigate the relationship between disease gene status and the structure of the human genome with specific reference to regions of recombination. It compares certain characteristics of a control set of genes, with no reported association or function in any known disease, with a second set of well-curated genes with a known association to a disease. One of the benefits of recombination is the introduction of new combinations of genetic variation in the genome. Recombination hotspots are regions on the chromosome where higher than normal frequencies of breaking and rejoining between homologous chromosomes occur during meiosis. The hotspot regions exhibit both a non-random distribution across the human genome and varying frequencies of breaking and rejoining. The study analyzed a set of features that represent general properties of human genes; namely base composition (percentage GC content), genetic variation (single nucleotide polymorphisms - SNPs), gene length, and positional effect (distance from chromosome end), in both the disease-associated gene set and the control set. These features were linked to recombination hotspots in the human genome and the frequency of recombination at these hotspots. Descriptive statistics was used to determine differences between the occurrences of these features in disease-associated genes compared to the control set, as well as differences in the occurrence of these same features in subset of genes containing an internal recombination hotspot compared to the genes with no internal recombination hotspot. The study found that disease-associated genes are generally longer than those in the control set, which is consistent with previous studies. It also found that disease-associated genes are much more likely to contain a recombination hotspot than those genes with no disease association. The study did not, however, find any association between disease gene status and the other set of features; namely GC content, SNP numbers or the position of a gene on the chromosome. Further analysis of the data suggested that the increased probability of disease-associated genes containing a recombination hotspot is most likely an effect of longer gene length and that the presence of a recombination hotspot is not sufficient in its own right to cause disease gene status.

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The recombination reaction Na + S02 + Ar was investigated at 787 16 K and at pressures from 1.7 to 80 kPa. NaI vapor was photolyzed by an excimer laser at 308 nm to create Na atoms, whose concentration was monitored by time-resolved resonance absorption at 589 nm. The rate constant at the low pressure limit is ko = (2.7 0.2) x 10-21 cm6 molecule-2 s~1. The Na-SO 2 dissociation energy E0 = 170 35 kJ mol1 was calculated with RRKM theory. The equilibrium constant gave a lower limit E0 > 172 kJ mol~ 1. By combination of these two results, E0 = 190 15 kJ mol~ 1 is obtained. The high pressure limit is k, = (1 - 3) x 10-10 cm3 molecule 1 s~1, depending on the extrapolation method used. Two versions of collision theory were employed to estimate k,.. The 'harpoon' model shows the best agreement with experiment.

This work deals with properties and physical phenomena occurring in semiconductor materials. In details are described generation - recombination processes in a state of thermodynamic disequilibrium. The output of work is a software application simulating waveforms of energy levels in the band's own models and impurity semiconductors, depending on the type of semiconductor, impurities concentration and temperature. Finally, the processed virtual lab experiment deliverable in the educational process.

Title: Recombination centers in semiinsulating CdTe Author: Jakub Zázvorka Department / Institute: Institute of Physics of Charles University Supervisor of the master thesis: prof. Ing. Jan Franc, DrSc., Institute of Physics of Charles University Abstract: The properties of CdTe for application as a radiation detector are influenced through the presence of deep levels in the bang gap. These energy levels complicate the charge collection and the detector efficiency. Contactless resistivity mapping (COREMA) represents a good option for material characterization without the necessity of metal contacts application. The time-dependent charge measurement was investigated on an adjusted apparatus in FMF Freiburg. Theoretical model of charge transport based on band bending on the sample surface was proposed and a non-exponential behavior was calculated. Using this, the resulted parameter tendencies and their connection with deep level trap or recombination center were explained. A correlation was observed between resistivity, photoconductivity and a near midgap level photoluminescence. Parameter profiles were explained using the theory of Fermi level shift relative to the near midgap level. Three deep levels were observed on samples grown at the Charles University in Prague. Their photoluminescence supports the...

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