O sistema complemento parece ter surgido com o aparecimento de C3 e fator B (FB), os únicos componentes encontrados nos organismos mais primitivos, o que sugere que a via alternativa seja a mais antiga. Fragmentos de cDNA codificantes para FB (Lox-FB) e C3 (Lox-C3) foram sintetizados a partir do RNA total isolado da glândula de veneno de Loxosceles laeta e amplificados por técnicas de RACE-PCR. Lox-FB apresenta uma organização de domínios clássica, composta por domínios CCP, vWFA e de serino protease. Os aminoácidos envolvidos na ligação ao C3b são conservados, no entanto, a tríade catalítica clássica não foi encontrada. Lox-C3 apresenta uma configuração de domínios similar a do C3 humano, contendo dois sítios putativos de processamento: um entre as cadeias α e γ, e outro entre as cadeias α e β, indicando que Lox-C3 seja composto por três cadeias. As análises filogenéticas indicaram que Lox-C3 e Lox-FB são mais próximos evolutivamente aos componentes equivalentes da aranha Hasarius adansoni, com valores de identidade de 53% e 43%, respectivamente. / The complement system seems to have arisen with the appearance of C3 and factor B (FB), the only components found in the most primitive organisms, suggesting that the alternative pathway is the oldest. cDNA fragments coding for the complement factor B (Lox-FB) and C3 (Lox-C3) were synthesized from total RNA Loxosceles laeta venom gland and amplified using RACE-PCR techniques. Lox-FB has a classical domain organization in mosaic, composed by CCPs, vWFA and serine protease domains. The amino acids involved in binding to C3b are conserved, however, the classical calatytic triad was not found. Lox-C3 presents a similar configuration of domains to C3 human and has two putative processing sites: the first one is located between α and γ chains and other between α and β chains, indicating that Lox-C3 is composed by three chains. The phylogenetic analyses indicated that Lox-C3 and Lox-FB are evolutionary closer to the equivalent components of Hasarius adansoni, with identity values of 53% and 43%, respectively.

Résumé confidentiel / Confidential abstract

Polylactide (PLA) is a biodegradable and biocompatible alternative to traditional petrochemicalbased polymers. Synthesised by the ring-opening polymerisation of lactide (LA), the dehydrated form of lactic acid, PLA sits within a renewable cycle, and can be used in many commodity and biomedical applications. The intrinsic stereochemistry of LA can lead to a variety of polymer microstructures, and current industrially used initiators allow no control over this. Within this thesis a series of investigations into the use of amine tris(phenolate) metal complexes as stereoselective initiators for the ROP of LA are discussed. Chapter 1 introduces the field of ring-opening polymerisation (ROP) via a coordination insertion mechanism, presents previously reported initiators, and examines the influence of stereocomplexation on the physical properties of PLA chains. This introductory chapter also includes an in-depth review of recent developments in poly(phenolate) complexes of Group 4 and rare earth metals. Chapter 2 describes the synthesis of a series of isopropoxide and zwitterionic Group 4 complexes featuring the amine tris(phenolate) ligand motif, with emphasis on the effect of ligand variation on complex structure. The potential of the resulting complexes as initiators for the ROP of LA is also investigated, with in depth kinetic studies allowing for a proposed diastereoselective mechanism of stereocontrol. Chapter 3 details the synthesis of a series of borohydride and amide Group 4 amine tris(phenolate) complexes, and investigates their potential as initiators for the ROP of rac-LA. Chain-end analysis and kinetic studies are included, providing the basis for mechanistic discussions. Chapter 4 focuses on the synthesis of stereoblock PLA materials in a stereospecific manner, and co-block PLA-PEG materials by the reinitiation of short-chain macroinitiators. The effect of stereocomplexation on the thermal properties of these materials is investigated. Chapter 5 concerns the synthesis of a series of isopropanol and zwitterionic rare earth complexes featuring the amine tris(phenolate) ligand motif. The potential of these complexes as initiators for the ROP of rac-LA is also investigated, but only slight stereocontrol was observed in selected cases. Chapter 6 provides details of procedures employed in the synthesis of ligands, complexes and polymers within this thesis, as well as details of the analytical techniques used in their characterisation.

Uppsatsen syftar till att analysera hur försvarsmakten omhändertar krigsvetenskapens variabler för ledning –teknik, människa och metod– i dess tre nivåer; den militärstrategiska, den operativa samt den taktiska.Metoden som används utgörs av en kvalitativ metod som analyserar försvarsmaktens inriktande och styrande dokumentation.Resultatet visar att försvarsmakten till stor del omhändertar krigsvetenskapens teorier om ledningssystem.Det finns idag en otydlighet hur begreppet ledning omhändertas av försvarsmakten. Från att historiskt varit en egenskap hos en befälhavare har ledning i nutid utvecklats till något som har karaktäriserats till att utgöra ett system där människor möter metoder och teknik med syfte att skapa en planerad samordning av en given verksamhet med givna komponenter i en mer eller mindre känd kontext. Ledning inom försvarsmakten definieras olika beroende på vilket reglemente, doktrin eller anvisning som behandlar området.Forskningsmässigt är ämnesområdet är relativt nytt, även om företeelsen ledning troligvis har funnits så länge som människan har ägnat sig åt strid och krigskonst. Genom systematisering, vetenskapligt intresse och inte minst en teknisk utveckling, har behovet av att studera krigets ledning ökat för att kunna behålla och utveckla krigföringsförmåga.

Thesis (Ph. D.)--University of Alabama at Birmingham, 2007. / Title from first page of PDF file (viewed Feb. 7, 2008). Includes bibliographical references.

Masters in Public Administration - MPA / In recent years the concept of public participation has been embraced by governments around the world to promote citizen involvement in decision making processes both to deepen local democracy and to ensure greater effectiveness in the delivery of public services. Implementing effective participatory systems, however, has proven to be especially challenging in highly diverse societies. Despite the best intentions of policy makers, the issue of exclusion, in particular, remains problematic as participatory systems frequently fail to address the concerns of poor communities who may not even be aware of their existence. Taking as a case study the C3 notification system introduced by the City of Cape Town to facilitate citizen reporting on faulty public services, this study examined the extent to which the design and implementation of a participatory model is of benefit to poor communities in the township of Langa. Based on a qualitative methodology, which included a series of interviews with municipal officials and office bearers as well as residents of Langa, the research examined the extent to which the notification system is used by local communities and to what effect. Viewed through the lens of social exclusion theory, the findings point to the fact that the C3 system was not only based on a best-practice model imported from an advanced Western nation, but it was oriented to the needs of more affluent citizens and, as such, it failed to take into account the specific needs of poor households who frequently lack even basic services and hence have nothing to report on. As a consequence, what was intended as a mechanism for promoting greater citizen participation in service delivery processes has effectively excluded a significant proportion of the most poor and vulnerable.

Normalt sett skyddar komplementsystemet kroppen mot infektioner och patogener. Vid vissa typer av njursjukdomar, framför allt vid C3-glomerulopati, förekommer autoantikroppar som kallas ”nephritic factors” (NeF). Sådana antikroppar stabiliserar enzymkomplex (konvertas) i komplementsystemet, vilket leder till destruktiv komplementaktivering via den alternativa vägen. Syftet med studien var att utveckla minst en metod för att analysera C5NeF på kliniska prover.  C5NeF In-House ELISA analyserade bindning av C5NeF till C5-konvertas. Analys av C5-klyvning i löslig fas kvantifierade mängden C5a som bildats vid stabilisering av C5-konvertas. Cut-off för analyserna bestämdes genom analys av prover från 20 friska blodgivare. Tolv patientprover med möjlig förekomst av C5NeF analyserades. För att utesluta falskt positiv reaktion i C5NeF in-house ELISA analyserades även förekomst av antikroppar mot specifika enskilda komplementproteiner. Åtta patientprover var positiva i C5NeF In-House ELISA, fem patientprover uppvisade positivt resultat för C3NeF, vilket inte var oväntat utifrån tidigare publikationer som visat att det är vanligt att patienter med C5NeF också ofta är positiva för C3NeF. Tre patientprover erhöll positivt resultat i endast C5NeF In-House ELISA och två av dessa var positiva i analys av C5-klyvning i löslig fas. Studien resulterade i etablering av en metod för analys av C5NeF. / Normally the complement system protects the body from infections and pathogens. In certain types of kidney diseases, mainly C3-glomerulopathy, autoantibodies called ”Nephritic Factors” (NeF) are found. NeFs stabilize enzyme complexes (convertases) in the complement system, an event which leads to destructive complement activation via the alternative pathway. The purpose of this study was to develop at least one method to analyse C5NeF on clinical samples.  C5NeF In-House ELISA analysed binding of C5NeF to C5 convertases. Analysis of C5-cleavage in the soluble phase measured the amount of C5a formed when C5-convertase was stabilized. Cut-off for the analyses was determined through analysis of 20 blood donor samples from healthy individuals. Twelve patient samples with possible C5NeF were analysed. To exclude false positive results in C5NeF In-House ELISA analysis of antibodies against specific single complement factors was performed.  Eight patient samples were positive in C5NeF In-House ELISA, five patient samples showed positive result for C3NeF, a finding which was not unexpected as previous publications have shown that concomitant presence of C3NeF and C5NeF is common in C3-glomerulopathy. Where most patients are positive for both C3NeF and C5NeF. Three patient samples received positive result in only C5NeF In-House ELISA and two of these samples were positive in the analysis of C5-cleavage in soluble phase. In conclusion, in this study a method to examine C5NeF was developed.

No description available.

INTRODUÇÃO: Indivíduos com SZ (esquizofrenia) fumam até três vezes mais que a taxa da população em geral. Constatou-se que fumantes com esquizofrenia fumam mais intensamente do que comparados com fumantes não esquizofrênicos. Adicionalmente, existem relatos não sistemáticos de que apesar de alta taxa de tabagismo, os esquizofrênicos apresentam proporcionalmente pouca lesão pulmonar comparado com tabagistas de igual consumo sem esquizofrenia. Esta diferença, se confirmada, poderia sugerir mecanismos diferentes de reação a agentes exógenos nos sistema respiratório, e entre estes mecanismos diferentes poderia estar o sistema de complemento, já evidenciado em estudos do grupo de pesquisa, porém sem controle para tabagismo. Este estudo investigou se a capacidade de difusão pulmonar em SZ é maior que em NSZ, e se o sistema complemento C3 e C4 é diferente entre SZ e NSZ e ao mesmo tempo está associado a difusão pulmonar de forma diferente em SZ e NSZ. OBJETIVOS: comparar a capacidade de difusão pulmonar e complemento C3 e C4 em pacientes fumantes com e sem esquizofrenia e analisar se existe evidência de mecanismos diferentes mediando prejuízo na capacidade de difusão em tabagistas com e sem SZ. MÉTODOS: esse é um estudo caso controle pareado, desenhado para ser multicêntrico, no momento descrevendo resultados de um centro. Recrutados 30 tabagistas sendo 15 SZ e 15 NSZ pareados por sexo, idade e tempo de tabagismo. Foram medidos complemento C3 e C4, espirometria e difusão pulmonar, dependência de nicotina pelo Teste de Fargerstrom e psicopatologia psiquiátrica nos portadores de esquizofrenia pelo Escala Breve de Avaliação Psiquiátrica (BPRS). Os pacientes foram oriundos do centro colaborador do estudo no HCPA. RESULTADOS: C3 foi significantemente maior em SZ quando comparado com controles (p=0,041), e C4 não mostrou diferença. Houve associação negativa entre o C4 e a capacidade de difusão somente no grupo controle (r=-0,692; p=0,009), sem diferença significativa no grupo de esquizofrênicos (r=0,451; p=0,141). Os grupos foram equivalentes em idade, grau de dependência de nicotina, porém foram diferentes em relação a ocupação (p=0,001). O grupo de esquizofrênicos apresenta maior proporção de desempregados e em benefício do que os controles. Desta forma, apesar de C3 mais aumentado em esquizofrênicos, este sistema aparentemente não media perda de difusão pulmonar, enquanto que aparentemente C4 mostra diferença quanto a prejuízo de difusão em esquizofrênicos tabagistas (maior C4 associado a menor capacidade de difusão somente nos tabagistas sem esquizofrenia). CONCLUSÃO: Quanto ao sistema complemento, houve maior ativação do C3 em tabagistas portadores de esquizofrenia comparados com tabagistas sem esquizofrenia, o que corrobora pesquisas anteriores que descrevem ativação do sistema complemento na SZ indicado pelo aumento dos níveis de C3. Curiosamente, somente nos controles tabagistas foi identificada associação entre aumento de C4 e redução da capacidade de difusão pulmonar. Nos pacientes com esquizofrenia não houve relação entre ativação de C4 e prejuÍzo de difusão pulmonar, o que sugere um padrão de ativação do sistema de complemento diferente dos sujeitos normais, preferencialmente pela via C3 e não pela via C4. Este fator não parece estar afetado pela diferença em escolaridade e trabalho, visto que era esperado que o aumento fosse maior nos esquizofrênicos devido a maior gravidade representada por menor índice de trabalho e menor escolaridade. Este estudo, se confirmado em amostras maiores envolvendo os outros centros colaboradores, pode confirmar existência de mecanismos diferentes de reação inflamatória em esquizofrenia. / Background: Subjects with SZ (schizophrenia) smoke up to three times the rate of the general population. It was found that smokers with schizophrenia smoke more intensely than smokers compared with non-psychiatric. Additionally, there are no systematic reports that despite high rates of smoking, people with schizophrenia have proportionately less lung injury compared with smokers without schizophrenia equal consumption. This difference, if confirmed, would suggest different mechanisms of response to exogenous agents in the respiratory system, and between these different mechanisms could be the complement system, as evidenced in studies of the research group, but not control for smoking. This study investigated whether the pulmonary diffusion capacity in SZ is higher than in non-SZ, and the complement C3 and C4 is different between SZ and NSZ and if at the same time is associated with pulmonary diffusion differently in SZ and NSZ. OBJECTIVES: To compare the pulmonary diffusion capacity and complement C3 and C4 in smokers with and without schizophrenia and examine whether there is evidence of different mechanisms mediating impaired diffusion capacity in smokers with and without SZ. METHODS: This is a matched case-control study, designed as a multicenter, when describing the results of a center. Recruited 30 smokers and 15 non-schizophrenics and 15 schizophrenics matched for sex, age and duration of smoking. We measured C3 and C4 complement, spirometry and DLCO, nicotine dependence and the test Fargerstrom psychiatric psychopathology in patients with schizophrenia by Brief Psychiatric Rating Scale (BPRS). The patients came from the study's collaborating center at HCPA. RESULTS: C3 was significantly higher in SZ compared to controls (p = 0.041), and C4 showed no difference. There was a negative association between C4 and the ability to broadcast only in the control group (r =- 0.692, p = 0.009), no significant difference in the schizophrenic group (r = 0.451, p = 0.141). The groups were equivalent in age, degree of nicotine dependence, but were different in relation to occupation (p = 0.001). The schizophrenic group has a higher proportion of unemployed and for the benefit of the controls. Thus, although most of C3 increased in schizophrenics, this system apparently did not measure loss of pulmonary diffusion, while C4 shows apparent difference in the loss of diffusion in schizophrenic smokers (greater C4 associated with a lower diffusion capacity in smokers without schizophrenia only) . CONCLUSION: As the complement system, activation of C3 was higher in smokers with schizophrenia compared with smokers without schizophrenia, which corroborates previous studies that describe activation of the complement system in SZ indicated by increased levels of C3. Interestingly, only smokers in controls been identified association between increased C4 and reduction of pulmonary diffusion capacity. In patients with schizophrenia there was no relationship between activation of C4 and prejuízo pulmonary diffusion, which suggests a pattern of activation of the complement system different from normal subjects, preferably through C3 and not via C4. This factor does not seem to be affected by the difference in schooling and work, as it was expected that the increase was greater in schizophrenics because of greater severity represented by lower rates of work and less schooling. This study, if confirmed in larger samples involving other collaborating centers, can confirm the existence of different mechanisms of inflammatory response in schizophrenia.

INTRODUÇÃO: Indivíduos com SZ (esquizofrenia) fumam até três vezes mais que a taxa da população em geral. Constatou-se que fumantes com esquizofrenia fumam mais intensamente do que comparados com fumantes não esquizofrênicos. Adicionalmente, existem relatos não sistemáticos de que apesar de alta taxa de tabagismo, os esquizofrênicos apresentam proporcionalmente pouca lesão pulmonar comparado com tabagistas de igual consumo sem esquizofrenia. Esta diferença, se confirmada, poderia sugerir mecanismos diferentes de reação a agentes exógenos nos sistema respiratório, e entre estes mecanismos diferentes poderia estar o sistema de complemento, já evidenciado em estudos do grupo de pesquisa, porém sem controle para tabagismo. Este estudo investigou se a capacidade de difusão pulmonar em SZ é maior que em NSZ, e se o sistema complemento C3 e C4 é diferente entre SZ e NSZ e ao mesmo tempo está associado a difusão pulmonar de forma diferente em SZ e NSZ. OBJETIVOS: comparar a capacidade de difusão pulmonar e complemento C3 e C4 em pacientes fumantes com e sem esquizofrenia e analisar se existe evidência de mecanismos diferentes mediando prejuízo na capacidade de difusão em tabagistas com e sem SZ. MÉTODOS: esse é um estudo caso controle pareado, desenhado para ser multicêntrico, no momento descrevendo resultados de um centro. Recrutados 30 tabagistas sendo 15 SZ e 15 NSZ pareados por sexo, idade e tempo de tabagismo. Foram medidos complemento C3 e C4, espirometria e difusão pulmonar, dependência de nicotina pelo Teste de Fargerstrom e psicopatologia psiquiátrica nos portadores de esquizofrenia pelo Escala Breve de Avaliação Psiquiátrica (BPRS). Os pacientes foram oriundos do centro colaborador do estudo no HCPA. RESULTADOS: C3 foi significantemente maior em SZ quando comparado com controles (p=0,041), e C4 não mostrou diferença. Houve associação negativa entre o C4 e a capacidade de difusão somente no grupo controle (r=-0,692; p=0,009), sem diferença significativa no grupo de esquizofrênicos (r=0,451; p=0,141). Os grupos foram equivalentes em idade, grau de dependência de nicotina, porém foram diferentes em relação a ocupação (p=0,001). O grupo de esquizofrênicos apresenta maior proporção de desempregados e em benefício do que os controles. Desta forma, apesar de C3 mais aumentado em esquizofrênicos, este sistema aparentemente não media perda de difusão pulmonar, enquanto que aparentemente C4 mostra diferença quanto a prejuízo de difusão em esquizofrênicos tabagistas (maior C4 associado a menor capacidade de difusão somente nos tabagistas sem esquizofrenia). CONCLUSÃO: Quanto ao sistema complemento, houve maior ativação do C3 em tabagistas portadores de esquizofrenia comparados com tabagistas sem esquizofrenia, o que corrobora pesquisas anteriores que descrevem ativação do sistema complemento na SZ indicado pelo aumento dos níveis de C3. Curiosamente, somente nos controles tabagistas foi identificada associação entre aumento de C4 e redução da capacidade de difusão pulmonar. Nos pacientes com esquizofrenia não houve relação entre ativação de C4 e prejuÍzo de difusão pulmonar, o que sugere um padrão de ativação do sistema de complemento diferente dos sujeitos normais, preferencialmente pela via C3 e não pela via C4. Este fator não parece estar afetado pela diferença em escolaridade e trabalho, visto que era esperado que o aumento fosse maior nos esquizofrênicos devido a maior gravidade representada por menor índice de trabalho e menor escolaridade. Este estudo, se confirmado em amostras maiores envolvendo os outros centros colaboradores, pode confirmar existência de mecanismos diferentes de reação inflamatória em esquizofrenia. / Background: Subjects with SZ (schizophrenia) smoke up to three times the rate of the general population. It was found that smokers with schizophrenia smoke more intensely than smokers compared with non-psychiatric. Additionally, there are no systematic reports that despite high rates of smoking, people with schizophrenia have proportionately less lung injury compared with smokers without schizophrenia equal consumption. This difference, if confirmed, would suggest different mechanisms of response to exogenous agents in the respiratory system, and between these different mechanisms could be the complement system, as evidenced in studies of the research group, but not control for smoking. This study investigated whether the pulmonary diffusion capacity in SZ is higher than in non-SZ, and the complement C3 and C4 is different between SZ and NSZ and if at the same time is associated with pulmonary diffusion differently in SZ and NSZ. OBJECTIVES: To compare the pulmonary diffusion capacity and complement C3 and C4 in smokers with and without schizophrenia and examine whether there is evidence of different mechanisms mediating impaired diffusion capacity in smokers with and without SZ. METHODS: This is a matched case-control study, designed as a multicenter, when describing the results of a center. Recruited 30 smokers and 15 non-schizophrenics and 15 schizophrenics matched for sex, age and duration of smoking. We measured C3 and C4 complement, spirometry and DLCO, nicotine dependence and the test Fargerstrom psychiatric psychopathology in patients with schizophrenia by Brief Psychiatric Rating Scale (BPRS). The patients came from the study's collaborating center at HCPA. RESULTS: C3 was significantly higher in SZ compared to controls (p = 0.041), and C4 showed no difference. There was a negative association between C4 and the ability to broadcast only in the control group (r =- 0.692, p = 0.009), no significant difference in the schizophrenic group (r = 0.451, p = 0.141). The groups were equivalent in age, degree of nicotine dependence, but were different in relation to occupation (p = 0.001). The schizophrenic group has a higher proportion of unemployed and for the benefit of the controls. Thus, although most of C3 increased in schizophrenics, this system apparently did not measure loss of pulmonary diffusion, while C4 shows apparent difference in the loss of diffusion in schizophrenic smokers (greater C4 associated with a lower diffusion capacity in smokers without schizophrenia only) . CONCLUSION: As the complement system, activation of C3 was higher in smokers with schizophrenia compared with smokers without schizophrenia, which corroborates previous studies that describe activation of the complement system in SZ indicated by increased levels of C3. Interestingly, only smokers in controls been identified association between increased C4 and reduction of pulmonary diffusion capacity. In patients with schizophrenia there was no relationship between activation of C4 and prejuízo pulmonary diffusion, which suggests a pattern of activation of the complement system different from normal subjects, preferably through C3 and not via C4. This factor does not seem to be affected by the difference in schooling and work, as it was expected that the increase was greater in schizophrenics because of greater severity represented by lower rates of work and less schooling. This study, if confirmed in larger samples involving other collaborating centers, can confirm the existence of different mechanisms of inflammatory response in schizophrenia.