Linking innate and adaptive immunity to streptococcus pneumoniae

Streptococcus pneumoniae (the pneumococcus) most commonly colonizes the human nasopharyngeal mucosa without causing any symptoms. However, this organism has the potential to spread to normally sterile sites and cause pneumonia, meningitis or sepsis; diseases which are characterized by excessive inflammation. Despite the large burden of pneumococcal disease, relatively little is known about the mechanisms behind development of natural immunity to the pneumococcus. The purpose of this thesis was to study the role of human dendritic cells (DCs) in linking innate and adaptive immune responses to pneumococci. The immunological events in which DC-mediated T helper (Th) cell responses are generated were also investigated, as well as possible ways to modulate these responses. As a first part of this work, a novel role of the pneumococcal toxin pneumolysin in the evasion of DC-mediated immunosurveillance was described. Pneumolysin inhibited DC maturation, production of inflammatory cytokines and inflammasome activation, and induced caspase-dependent apoptosis of infected cells. Interestingly, murine DCs differed in their response to pneumolysin, emphasizing the need to study human responses to this human-specific pathogen In the second part of this work, we demonstrated that pneumococcus-infected monocytes and DCs efficiently promote the production of inflammatory Th1 and Th17 cytokines from autologous co-cultured memory cells. Live pneumococci and pneumococcal peptidoglycan triggered activation of DCs, which in turn induced the generation of Th cytokines via cell-to-cell contact and soluble components. Our work further revealed that the inflammatory response could be modulated with exogenous substances, such as recombinant cytokines, and cytokine- and receptor-blocking antibodies. Moreover, exposure of DCs to vitamin D skewed the response from an inflammatory Th1/Th17 phenotype towards a regulatory T cell phenotype. In the last part of this work, we focused on patients with primary immunodeficiencies (PIDs), suffering from frequent respiratory tract infections. The mechanisms behind the infectious susceptibility among these patients remain elusive and we hypothesized that it may be due to defects in the production of antimicrobial peptides (AMPs) in the nasal mucosa. We found that two patient groups, namely common variable immunodeficiency (CVID) and Hyper-IgE syndrome (HIES), had a dysregulated AMP response to bacteria in the upper respiratory tract. In addition, cells from these patients exhibited an impaired Th17 cytokine response. In order to improve management of patients with pneumococcal infections there is a need to elucidate the role of DC-mediated cytokine responses in the delicate balance between protective immunity and immunopathology. An increased understanding of these processes is also essential for the development of pneumococcal vaccines, designed to elicit cell-mediated immunity. The work presented in this thesis contributes to our understanding of the dynamic interplay between pneumococci and host cells, and provides the opportunity to explore the potential role of vitamin D in limiting the inflammatory response in pneumococcal disease

The permanency and effect of four organic sythetic insecticides on selected wool fabrics

Call number: LD2668 .T4 1948 O6Master of Scienc

Cloning of a putative human oncogenic virus, BK

Papova viruses are a group of non-enveloped icosahedral viruses which contain a double-stranded circular DNA genome in the supercoiled configuration. There are two subgroups, i.e., the papilloma and the polyoma viruses. The papilloma viruses are generally larger than the polyoma-viruses, having a genome of approximately 5 x 106 daltons compared with 3,3 x 106 daltons, and virions of approximately 55nm diameter as opposed to 41nm. The papilloma viruses generally produce benign epithelial proliferations in the host e.g., the human wart, and attempts to propagate these viruses in cells in culture have been unsuccessful. On the other hand, polyoma viruses can usually be propagated in tissue culture and do not appear to be associated with any widespread pathology in their natural hosts. Although there is no convincing evidence of polyoma viruses causing malignancies in their natural host, nonpermissive cells of other species may be transformed and these viruses therefore have oncogenic potential in particular laboratory animals. Polyoma . viruses infect eukaryotic cells, and investigation thereof should allow further elucidation of eukaryotic gene expression and regulation. Members of the polyoma group which have been extensively studied include polyoma virus itself, which infects mice, simian virus 40, (SV40),which infects rhesus monkey cells, and RKV which infects rabbits. Interest in this polyoma group of viruses has increased ever since 1965 when a new papovavirus strain, JC, was isolated from brain glial cells of a patient with progressive multifocal leukoencephalopathy (PML) and was thus the first polyomavirus infection of humans to be discovered. (ZuRhein and Chou, 1965). In 1971, an immunologically distinct polyomavirus, BK, was isolated from the urine of an immunocompromised recipient of a renal allograft (Gardner et al., 1971). Interest in these two viruses in particular has been compounded by their potential oncogenicity in humans, (see section 1.8)

Assessment of EGM2008 over Britain using vertical deflections, and the problems with historical data

Vertical deflections synthesised from the Earth Gravitational Model 2008 (EGM2008) agree with astrogeodetic vertical deflections observed over mainland Britain to within ~1.2" RMS (north-south) and ~1.4" RMS (east-west), which is commensurate with values reported for North America, Australia and parts of continental Europe. For this assessment in Britain, there has been the additional need to transform the observed relative vertical deflections to absolute ones. Not applying horizontal datum transformations led to spurious results, so absolute vertical deflections must always be used to assess EGMs. Three datum transformations were trialled (three-parameter, seven-parameter and OSTN02), which show similar results when considering the estimated ~0.3" precision of these historical (1950 to 1976) astrogeodetic observations. Several other problems were encountered because of the historical nature of the data, comprising destruction of survey pillars, ambiguous station names, and a mixture of horizontal geodetic datums available in Britain

A Method to Validate Gravimetric Geoid Computation Software Based on Stokes's Integral Formula

A method is presented with which to verify that the computer software used to compute a gravimetric geoid is capable of producing the correct results, assuming accurate input data. The Stokes, gravimetric terrain correction and indirect effect formulae are integrated analytically after applying a transformation to surface spherical coordinates centred on each computation point. These analytical results can be compared with those from geoid computation software using constant gravity data in order to verify its integrity. Results of tests conducted with geoid computation software are presented which illustrate the need for integration weighting factors, especially for those compartments close to the computation point

AS VOZES DE DENTRO DA POESIA CABRALINA

 RESUMO: Neste artigo, tratamos da relação entre a performance vocal e a poesia de João Cabral de Melo Neto. A obra desse poeta é normalmente dividida em duas vertentes: uma de poesia reflexiva, destinada à leitura individual, e outra, de poesia comunicativa, afeita à leitura em voz alta. Reconsideramos essa separação com base na reflexão sobre as possibilidades de comunicação do texto poético por meio de sua execução vocal, ou vocalização. Para isso, discutimos, primeiramente, a configuração das vozes nas publicações que compõem a coletânea Morte e vida severina e outros poemas em voz alta. Depois, distinguindo o caráter exterior dessas vozes, buscamos identificar elementos para percepção e análise da voz que se manifesta na poesia cabralina como virtualidade, constituída pela materialidade sonora e pela subjetividade poética. Fazemos isso com poemas do livro Museu de tudo. Em conclusão, assinalamos que o caráter comunicativo do poema de João Cabral encontra campos de ação mais amplos quando é deslocado para o âmbito performativo da vocalização

Knowledge and information in global competition: a new framework for classifying and evaluating manipulative communication techniques

Mass media initiated exhibitions of information and knowledge streams account for a significant factor of opinion-forming in modern digitalized nations and thus influence their country's political development. Within the framework of a globalized environment, this information has the ability to shape worldwide opinion and international policy decisions across geographical boundaries. Similarly, however, information and knowledge that does not flow freely has an impact on the behind the scenes decisions of world affairs. Selective manipulation, consumed through hidden channels, is therefore a powerful tool for shaping both social and organizational environments. Currently no classification approaches exist in order to identify and evaluate this type of manipulation. Therefore, this article will discuss this type of manipulative communication and align each category into an assessment model. Forty-two varieties of manipulative arguments will be identified as well as classified along three-dimensions. A model has been developed which will serve as a tool to identify the degree and at which level manipulation was performed