Influence of constraining and confinement in the molecular mobility of low molecular weight materials

Dissertation presented to obtain a Ph.D. Degree in Chemical Physics

Eficiência energética em edifícios residenciais da cidade do Porto

O consumo de energia a nível mundial tem atingido valores históricos, devido ao crescimento da população mundial e ao aumento do consumo per capita. Nesta medida é extremamente importante existirem alternativas para que a redução do consumo de energia de todos os países seja uma realidade, evitando também as consequências ambientais, em particular as alterações climáticas, resultantes da utilização intensiva de combustíveis fósseis. Portugal, tal como outros países da União Europeia, tem que cumprir metas, pelo que é urgente encontrarem-se soluções de forma a diminuir o consumo de energia sem interferir com o nosso dia-a-dia. A cidade do Porto, tal como qualquer cidade, precisa de imensa energia desde os transportes até à indústria, passando pelos edifícios. Os edifícios, residenciais e de serviços, são responsáveis por mais de 50% de energia primária consumida no concelho do Porto, sendo que aos edifícios residenciais corresponde um consumo de 1.473 GWh/ano de energia primária, o que é um valor elevado. Numa primeira parte deste trabalho foi efetuado um levantamento de informação caracterizando a cidade do Porto relativamente ao seu edificado e consumos energéticos. Numa segunda parte propuseram-se medidas para reduzir o consumo para cada tipo de utilização de energia, nomeadamente preparação de refeições, AQS (água quente sanitária), aquecimento ambiente, frio (frigorífico, arcas, etc.), outros e iluminação. Para cada um destes tipos de utilização estudou-se, sempre que possível, a evolução do longo do tempo (2004 a 2012) e possíveis cenários de evolução para o futuro. Para além disso, também se estudou a evolução do mix de produção de energia elétrica de 2004 até 2012 e previsões da evolução do mix para o futuro. Nesta análise foi tido em conta o aspeto ambiental contabilizando-se, sempre que possível, as emissões de poluentes resultantes do consumo de energia. Por fim, efetuou-se uma avaliação técnica, ambiental e económica das medidas propostas. Pode dizer-se que a maioria das medidas propostas a serem implementadas conduziria a uma redução do consumo de energia e consequentemente a uma diminuição das emissões de poluentes, em particular dos gases com efeito de estufa (CO2). Em termos técnicos a maioria das medidas pode ser aplicada embora algumas delas envolvam custos de investimento significativos. Dada a conjuntura atual, seria importante obter o financiamento necessário para a implementação das medidas propostas e a divulgação de medidas já existentes, tais como os programas para AQS e janelas eficientes.

A metodologia BIM-FM aplicada a um caso prático

O crescente aumento da consciencialização da importância da fase de operação e manutenção, bem como a amplificação que a metodologia Building Information Modelling (BIM) tem obtido nos últimos anos, sugere uma necessidade de alterar a atual abordagem da gestão das instalações de forma a dotá-la das mais recentes inovações tecnológicas como seja a utilização do BIM. Os Building Information Models apresentam as características ideais para a integração da gestão das instalações, não só pela visualização do edifício, mas sobretudo pela potencialidade que a base de dados oferece, com informação referente a cada um dos componentes presentes e suas relações. O âmbito deste trabalho envolve assim a integração da gestão das instalações com o modelo BIM criado, representativo do edifício em estudo. Este trabalho começa com as definições do âmbito e dos objetivos que são propostos no Capítulo 1. No Capítulo 2, é elaborada uma pesquisa sobre o estado da arte atual de cada uma das metodologias BIM e FM, de forma a tomar conhecimento dos seus conceitos principais. Foi feito também um levantamento no campo do BIM-FM de forma a apurar as atuais soluções tecnológicas existentes, a forma como é feita a sua troca de informação e também alguns casos em que esta metodologia foi aplicada. Com base na informação recolhida sobre as metodologias e também nos casos práticos estudados, é realizado no Capítulo 3, capítulo central deste trabalho, a aplicação prática. A realização desta aplicação é dividida por 3 fases principais. Numa primeira fase é especificada e recolhida a informação necessária de ser obtida para a realização do modelo e a posterior aplicação do FM. A escolha da informação a recolher é feita ponderando todos os fatores existentes, mas de forma a cumprir os requisitos pedidos. Numa segunda fase, assente na compilação de informação recolhida anteriormente, realiza-se o modelo do edifício. A modelação, de forma a seguir o método de trabalho BIM é realizada por especialidades, sendo numa primeira fase realizada a especialidade de arquitetura e posteriormente, utilizando esse modelo como base, é feita a modelação das especialidades de águas, águas residuais, AVAC e eletricidade. Esta escolha foi também estimulada pela organização do software utilizado para a modelação, por módulos. Na última fase da aplicação do caso prático a informação inserida na fase de modelação do edifício é exportada para o software de FM, neste caso em específico, o IBM Maximo. Para a exportação destes dados foi utilizado o formato Construction Operations Building Information Exchange (COBie), de forma a garantir a integridade e conformidade da informação transferida. No Capítulo 4 deste trabalho são abordadas as especificidades relativas à informação existente, à modelação e à troca de dados entre o software de modelação e o software utilizado na gestão do edifício. São também sugeridos alguns temas para futuros desenvolvimentos com o intuito de ampliação dos campos de FM com o uso do modelo. O BIM-FM é um tema emergente na atualidade do BIM, sendo a sua utilização encarada como uma mais-valia ao processo BIM. A compilação da informação durante a fase de projeto e execução, aliada à existência do modelo torna a implementação do FM com o modelo BIM como uma sequência natural.

Inapparent lung involvement in patients with the subacute juvenile type of paracoccidioidomycosis

Three patients with the diagnosis of subacute juvenile paracoccidioidomycosis who, at the time of their first visit, had no signs or symptoms of lung involvement, were studied. Initially the diagnosis was confirmed by the observation of P. brasiliensis in biopsy material obtained from clinically involved lymphadenopathies. The lung X-rays done in all patients, did not reveal pathologic changes, although it was possible to observe and isolate the fungus from sputum samples obtained from the three patients. This fact reinforces the pulmonary genesis of the mycosis and proofs the existence of a pulmonary primary infection, even in patients with the juvenile manifestations, in whom the lung component is obscured by the predominant lymph node involvement.

Deciphering the role of Yap4 phosphorylation under stress conditions

The existence of molecular mechanisms of response, repair and adaptation, many of which are greatly conserved across nature, gives to the cell with the plasticity it requires to adjust to its ever-changing environment, a homeostatic event that is termed the stress response. In the budding yeast Saccharomyces cerevisiae there is a particular family of transcription factors, the Yap family, which has been shown to have a relevant role in yeast adaptation to several stress conditions. In particular, Yap1 is the major regulator of the transcriptional response to oxidative stress and Yap2 and Yap8 play important roles upon cadmium and arsenic exposure, respectively.(...)

Examination timetabling automation using hybrid meta-heuristics

Trabalho de projeto realizado para obtenção do grau de Mestre em Engenharia Informática e de Computadores

Relationship between the prevalence of antibodies to arbovirus and hepatitis B virus in the Vale do Ribeira region, Brazil

280 students, between 6 and 14 years old, residents in the Iguape county, southern coast of the State of São Paulo, were studied in order to identify the existence of a possible association between the prevalence of specific antibodies to the hepatitis B virus and the exposure to haematophagous mosquitoes, evaluated indirectly through the prevalence of antibodies to 17 arboviruses isolated in Brazil. The children were from 4 areas with different topographical characteristics: 89 of the children were from the urban zone of the town of Iguape, 89 were from the periurban zone, 30 were from the rural area with extensive banana plantations, and 72 were from the jungle zone. Previous studies had shown significantly higher prevalence of antibodies to different arboviruses in the cultivated zone and the jungle zone, when compared to the urban and periurban zones of Iguape. The detection of antibodies to the HBV surface antigen (HBs Ag) was done through the radioimmunoassay (Ausab, Abbott Laboratory). The cases considered positive were confirmed through the presence of anti-core HBV antibodies (anti-HBc-EIA Roche). A significantly higher prevalence of anti-HBV antibodies was observed in children from the jungle zone (26/72 = 36,1% ) when compared to those from the urban zone (5/89 = 5,6%), peri-urban (6/89 = 6,7%) or from the cultivated zone (0/30 = 0%). The result suggest the existence of a common factor in the dissemination of the arboviruses and the hepatitis B virus, supporting the hypothesis that mosquitoes may play an important role in the HBV transmission in tropical forested region.

Conditional probability applied to the definition of limestone geochemical facies: A new Methodological Approach

A new method, based on linear correlation and phase diagrams was successfully developed for processes like the sedimentary process, where the deposition phase can have different time duration - represented by repeated values in a series - and where the erosion can play an important rule deleting values of a series. The sampling process itself can be the cause of repeated values - large strata twice sampled - or deleted values: tiny strata fitted between two consecutive samples. What we developed was a mathematical procedure which, based upon the depth chemical composition evolution, allows the establishment of frontiers as well as the periodicity of different sedimentary environments. The basic tool isn't more than a linear correlation analysis which allow us to detect the existence of eventual evolution rules, connected with cyclical phenomena within time series (considering the space assimilated to time), with the final objective of prevision. A very interesting discovery was the phenomenon of repeated sliding windows that represent quasi-cycles of a series of quasi-periods. An accurate forecast can be obtained if we are inside a quasi-cycle (it is possible to predict the other elements of the cycle with the probability related with the number of repeated and deleted points). We deal with an innovator methodology, reason why it's efficiency is being tested in some case studies, with remarkable results that shows it's efficacy. Keywords: sedimentary environments, sequence stratigraphy, data analysis, time-series, conditional probability.

Geography of the Information Society

All every day activities take place in space. And it is upon this that all information and knowledge revolve. The latter are the key elements in the organisation of territories. Their creation, use and distribution should therefore occur in a balanced way throughout the whole territory in order to allow all individuals to participate in an egalitarian society, in which the flow of knowledge can take precedence over the flow of interests. The information society depends, to a large extent, on the technological capacity to disseminate information and, consequently, the knowledge throughout territory, thereby creating conditions which allow a more balanced development, from the both the social and economic points of view thus avoiding the existence of info-exclusion territories. Internet should therefore be considered more than a mere technology, given that its importance goes well beyond the frontiers of culture and society. It is already a part of daily life and of the new forms of thinking and transmitting information, thus making it a basic necessity essential, for a full socio-economic development. Its role as a platform of creation and distribution of content is regarded as an indispensable element for education in today’s society, since it makes information a much more easily acquired benefit.”…in the same way that the new technologies of generation and distribution of energy allowed factories and large companies to establish themselves as the organisational bases of industrial society, so the internet today constitutes the technological base of the organisational form that characterises the Information Era: the network” (CASTELLS, 2004:15). The changes taking place today in regional and urban structures are increasingly more evident due to a combination of factors such as faster means of transport, more efficient telecommunications and other cheaper and more advanced technologies of information and knowledge. Although their impact on society is obvious, society itself also has a strong influence on the evolution of these technologies. And although physical distance has lost much of the responsibility it had towards explaining particular phenomena of the economy and of society, other aspects such as telecommunications, new forms of mobility, the networks of innovation, the internet, cyberspace, etc., have become more important, and are the subject of study and profound analysis. The science of geographical information, allows, in a much more rigorous way, the analysis of problems thus integrating in a much more balanced way, the concepts of place, of space and of time. Among the traditional disciplines that have already found their place in this process of research and analysis, we can give special attention to a geography of new spaces, which, while not being a geography of ‘innovation’, nor of the ‘Internet’, nor even ‘virtual’, which can be defined as one of the ‘Information Society’, encompassing not only the technological aspects but also including a socio-economic approach. According to the last European statistical data, Portugal shows a deficit in terms of information and knowledge dissemination among its European partners. Some of the causes are very well identified - low levels of scholarship, weak investments on innovation and R&D (both private and public sector) - but others seem to be hidden behind socio-economical and technological factors. So, the justification of Portugal as the case study appeared naturally, on a difficult quest to find the major causes to territorial asymmetries. The substantial amount of data needed for this work was very difficult to obtain and for the islands of Madeira and Azores was insufficient, so only Continental Portugal was considered for this study. In an effort to understand the various aspects of the Geography of the Information Society and bearing in mind the increasing generalised use of information technologies together with the range of technologies available for the dissemination of information, it is important to: (i) Reflect on the geography of the new socio-technological spaces. (ii) Evaluate the potential for the dissemination of information and knowledge through the selection of variables that allow us to determine the dynamic of a given territory or region; (iii) Define a Geography of the Information Society in Continental Portugal.

Possible oral transmission of acute Chagas' disease in Brazil

In October, 1986, 7 to 22 days after a meeting at a farm in Paraíba state, 26 individuals presented with a febrile illness associated with bilateral eyelid and lower limb edema, mild hepatosplenomegaly, lymphadenopathy and, occasionally a skin rash. A 11-year-old boy exhibited atrial premature complexes and a 74-year-old patient developed acute heart failure. In two patients hospitalized in São Paulo city, acute Chagas' disease was diagnosed by the demonstration of circulating Trypanosoma cruzi. At autopsy in a fatal case, acute Chagas' cardiomyopathy was demonstrated. Xenodiagnosis were positive in 9 out of 14 tested patients. A specific IgG immune response was found in all patients and specific IgM antibodies were identified in 20 out of 22 tested patients. A epidemiological survey showed the existence of Triatoma brasiliensis in the outbuildings of this farm, but none in the house where most of the guests stayed. A high rate of infection with Trypanosoma cruzi was found in opossums. These observations together with those related to the food consumed by the patients, lead the authors to suggest that the human infections resulted from oral contamination probably originating from naturally infected marsupials in the area or crushed infected bugs.

Upper Paleocene-Early Eocene mollusks of Silveirinha (Figueira da Foz, West Central Portugal)

A collection of fossil gastropods and bivalves assembled at the Thanetian/Ypresian vertebrate site of Silveirinha (Figueira da Foz, West Central Portugal) is analysed from the point of view of systematics and palaeoecology. The diversity is scarce but the age and exceptional characteristics of the site are factors that substantiate a detailed study. The taxa identified are: Bithynia soaresi sp. nov., Gyraulus antunesi sp. nov., Chlamys sp. and Cardiiacea gen. sp. indet. The prevailing of freshwater gastropods and the occurrence of 2 fragments of marine bivalves suggest a palaeoenvironmental setting that is in conformity with interpretations already established, which are based both in sedimentologic and vertebrate data. These interpretations point out the existence of a freshwater environment opened from time to time to marine influences, resulting from a palaeoatlantic coast placed some kilometres westwards.

Epidemiology of Schistosoma mansoni infection in a low-endemic area in Brazil: clinical and nutritional characteristics

A cross-sectional case-control study designed to evaluate the role of malnutrition in the association between the intensity of Schistosoma mansoni infection and clinical schistosomiasis, was conducted in an area with both low frequency of infection and low morbidity of schistosomiasis in Brazil. Cases (256) were patients with a positive stool examination for S. mansoni; their geometrical mean number of eggs/gram of feces was 90. Controls (256) were a random sample of the negative participants paired to the cases by age, sex and length of residence in the area. The clinical signs and symptoms found to be associated with S. mansoni infection, comparing cases and controls, were blood in stools and presence of a palpable liver. A linear trend in the relative odds of these signs and symptoms with increasing levels of infection was detected. Adjusting by the level of egg excretion, the existence of an interaction between palpable liver and ethnic group (white) was suggested. No differences in the nutritional status of infected and non-infected participants were found.

Generalized synchronization in a system of several non-autonomous oscillators coupled by a medium

An abstract theory on general synchronization of a system of several oscillators coupled by a medium is given. By generalized synchronization we mean the existence of an invariant manifold that allows a reduction in dimension. The case of a concrete system modeling the dynamics of a chemical solution on two containers connected to a third container is studied from the basics to arbitrary perturbations. Conditions under which synchronization occurs are given. Our theoretical results are complemented with a numerical study.

Analysis of the Respiratory Dynamics During Normal Breathing by Means of Pseudophase Plots and Pressure–Volume Loops

This paper reports on the analysis of tidal breathing patterns measured during noninvasive forced oscillation lung function tests in six individual groups. The three adult groups were healthy, with prediagnosed chronic obstructive pulmonary disease, and with prediagnosed kyphoscoliosis, respectively. The three children groups were healthy, with prediagnosed asthma, and with prediagnosed cystic fibrosis, respectively. The analysis is applied to the pressure-volume curves and the pseudophase-plane loop by means of the box-counting method, which gives a measure of the area within each loop. The objective was to verify if there exists a link between the area of the loops, power-law patterns, and alterations in the respiratory structure with disease. We obtained statistically significant variations between the data sets corresponding to the six groups of patients, showing also the existence of power-law patterns. Our findings support the idea that the respiratory system changes with disease in terms of airway geometry and tissue parameters, leading, in turn, to variations in the fractal dimension of the respiratory tree and its dynamics.

Mediterranean spotted fever and identification of new agents of rickettsioses in Portugal : epidemiological determinants, host and microbial features in portuguese patients

Resumo: a febre botonosa, também conhecida por febre escaro-nodular (FEN) é uma doença endémica nos Países da bacia do Mediterrâneo, África, Médio Oriente, Índia e Paquistão. O agente etiológico responsável por esta patologia é a bactéria Rickettsia conorii. Contudo, em alguns países, como Portugal e Itália, esta patologia é causada por duas estirpes diferentes: R conorii Malish e R conorii Israeli spotted fever strain. O principal vector e reservatório é o ixodídeo Rhipicephalus sanguineus. Mesmo com uma elevada taxa de subnotificação detectada no nosso País, a taxa incidência da FEN é de 8.4/105 habitantes (1989-2005), uma das mais altas quando comparada coom a de outros países da bacia do Mediterrâneo. De todos os distritos portugueses, Bragança e Beja são aqueles que apresentam as taxas de incidência mais elevadas, 56,8/105 habitantes e 47,4 / 105 habitantes respectivamente. Em Portugal, as alterações climáticas verificadas na última década, nomeadamente a subida das temperaturas médias anuais, parecem ter influenciado o ciclo de vida do vector e a sua dinâmica sazonal, permitindo ao R. sanguineus completar mais de um ciclo de vida por ano. Este facto, e a possibilidade deste vector se manter activo noutros meses do ano, nomeadamente nos meses de inverno, tem influenciado consequentemente o padrão de distribuição anual dos casos de FEN. A febre escaro-nodular caracteriza-se clinicamente como uma doença exantemática, com um processo de vasculite generalizado. Apesar de na generalidade ser considerada uma doença benigna (quando tratada atempadamente e com terapêutica adequada e específica)e de estarem descritos casos graves em cerca de 5-6% dos doentes, em Portugal essa percentagem aumentou e consequentemente levou a um aumento de casos fatais. Este facto tornou-se mais evidente em 1997, no Hospital Distrital de Beja e no Hospital Garcia de Orta, onde a taxa de letalidade atingiu os 32% e 18% respectivamente.Para além dos factores de co-morbilidade encontrados nos doentes mais graves, como diabetes mellitus, ou o atraso na instituição da terapêutica específica, foi colocada de que a estirpe R. conorii Israel spotted fever strain pudesse ser mais virulenta ou então estivesse associada a diferentes manifestações clínicas que dificultassem o diagnóstico clínico e a instituição atempada da terapêutica. Houve ainda a necessidade de avaliar alguns parâmetros imunológicos dos doentes e tentar identificar que factores, nomeadamente que citoquinas, poderiam estar envolvidos na resposta a uma infecção por R.conorii.Face a estas questões foi avaliada e comparada a epidemiologia, manifestações clínicas e laboratoriais de 140 doentes (71 infectados com R. conorii Malish e 69 infectados com R. conorii Israel spotted fever strain). Concluiu-se que existe uma sobreposição de manifestações clinicas entre os dois grupos de doentes, mas que a percentagem da escara de inoculação é significativamente inferior em doentes infectados com R. conorii Israel spotted fever strain. Dos resultados mais importantes encontrados neste estudo concluiu-se que a estirpe R. conorii Malish e é demonstrado, pela primeira vez, estatisticamente que o alcoolismo é um factor de risco para a morte de doentes com FEN. Associadas a factores de um mau prognósitco da doença, estão as manifestações gastrointestinais, que poderão ser ou não reflexo de alterações do sistema nervoso central, e ainda a alteração de parâmetros laboratoriais como a presença de hiperbilirubinemia e aumento dos valores da ureia.A maior parte dos estudos realizados sobre os mecanismos da resposta imunitária à infecção por R. conorii e as interacções hospedeiro - agente etiológico têm sido elucidados com base em modelos animais. Poucos estudos têm sido efectuados em doentes e nenhum estudo prévio tinha sido realizado no sentido de avaliar localmente (escara/pele) quais os mediadores ou outras moléculas envolvidas na resposta imunitária às rickettsioses. Foi avaliado o nível de expressão génica de RNA mensageiro (RNAm)de diferentes citoquinas em amostras de pele de doentes com FEN pela técnica de PCR em tempo real.Os resultados deste estudo mostraram que, quando comparado com o grupo controlo, os 23 doentes analisados apresentavam níveis estatisticamente significativos, mais elevados de expressão génica de interferão (IFN-γ, Tumor necrosis factor (TFN-α, interleucina 10 (IL-10, RANTES (regulated by activation, normal T-cell-expressed and secreted chemokine)e indolamina 2-3 desoxigenase (IDO),uma enzima envolvida no controlo e limitação do crescimento intracelular das rickettsias, através da degradação do triptofano. Seis dos 23 doentes apresentaram ainda niveis de expressão elevados de óxido nítrico indutível (iNOS)que actua como microbicida. Encontrou-se uma correlação positiva entre a expressão de RNAm de TNF-α, γ, iNOS e IDO e os casos menos graves de FEN sugerindo um tipo de resposta imunitária tipo Th1, i.e. com papel protector na resposta à infecção.Verificou-se também que os valores de expressão genética do RNAm de IL-10, estavam inversamente correlacionados com a expressão do RNAm de TNF-α e IFN-γ. Os casos menos graves de FEN parecem assim envolver um balanço entre a resposta pró-inflamatória e anti-inflamatória. Já os níveis de expressão génica do RNAm de IL-10 estavam inversamente correlacionados com a expressão RNAm de TNF-α e IFN-γ. Os casos menos graves de FEN parecem assim envolver um balanço entre uma resposta pró-inflamatória e anti-inflamatória. Já os níveis de expressão RNAm da quimoquina RANTES foram estatisticamente mais elevados em doentes graves.Nesta dissertação é ainda descrita uma nova rickettsiose presente em Portugal, causada pela bactéria R. sibirica mongolitimonae, que foi identificada laboratorialmente por isolamento do agente, e por detecção do DNA em biopsia de pele. A presença deste agente foi ainda corroborada pela detecção em paralelo do mesmo agente no ixodídeos como R. africae like e em pulgas como R. felis e R.typhi alertam para a possibilidade de existência de outras rickettsioses que possam estar diagnosticadas em Portugal. Abstract: Mediterranean spotted fever (MSF), a tick-borne disease caused by Rickettsia conorii, is widley distributed in the Old World, being endemic in the southern Europe, Africa, Middle East, India and Pakistan. In Portugal two strains cause disease: R.conorii Malish and R.conorii Israeli spotted fever.Rhipicephalus sanguineus, the brown dog tick, is considered the main vector and reservoir. MSF is characterized by seasonality, and most of cases are encountered in late spring and summer, peaking in July and August. However, CEVDI/INSA laboratory has observed that the incidence of MSF cases has changed during winter season.The increasing annual averages of air temperatures and warmer and drier winters might have influenced the dynamics of the life cycle and activity of R. sanguineus, and indirectley the number MSF cases during the so called MSF off-season.In the period of 1989-2005, the incidence rate of MSF was 8.4/105 inhabitants, one of the highest rates compared with other endemic countries. In the Portugal during the same period, the highest incidence rates were reported in the districts of Bragança, with 56.8/105 inhabitants, and Beja, with 47.4/105 inhabitants. Severe cases of MSF are reported in 6% of the patients, but it seems that this pattern of disease in Portugal has been changing.This factor became more evident in 1997, with a reported case fatality rate of 32% and 18% in patients with MSF admited at Beja and Garcia Orta Hospitals, respectively. Although it was found that diabetes mellitus and delay in therapy have been implicated as a risk factor for death, the hypothesis was considered, that the new ISF strain isolated from Portugueses patients in the same year (1997)causes different or atypical clinical conorii Malish strain. The local (skin biopsies) immune response to R. conorii infection was also evaluated.A prospective study was performed to characterized epidemiological, clinical, laboratory features and determined risk factors for a fatal outcome. One hundred forty patients (51% patients were infected with Rickettsia conorii Malish stain and 49% with Israeli spotted fever strain)with diagnosis documented with identification of the causative rickettsial strain were admitted to 13 Portugueses Hospitals during 1994-2006.Comparison of the clinical manifestations of MSF caused by Malish and ISF strains revealed tremendous overlap that would not permit clinical recognition of the strain envolved, but an eschar was observed in a significantly higher percentage of patients with Malish than ISF strain.A fatal outcome was significantly more likely for patients with ISF strain infection meaning that ISF strain was more virulent than Malish strain, and also alcoholism was a host risk factor for a fatal outcome.The pathophysiology of a fatal outcome involved significantly greater incidence of petechial rash, gastrointestinal symptoms, confusion/obtundation, dehydration, tachypnea, hepatomegaly, leukocytosis, coagulopathy, azotemia, hyperbilirubinemia, and elevated hepatic enzymes and creatine kinase. Multivariate analysis revealed that acute renal failure and hyperbilirubinemia were most strong associated with a fatal oucome of infections with both strains.The immune response to R. conorii infection determined with both strains. The immune response to R. conorii infection determined by the expression levels of inflammatory and immune mediators in skin biopsies collected from untreated patients with Mediterranean spotted fever reveal that intralesional expression of mRNA of TNF-α, IFN-γ, IL-10, RANTES, and indoleamine-2, 3-dioxygenase (IDO)an enzyme involved in limiting rickettsial growth by tryptophan degradation, were elevated in skin of MSF patients compared to controls. Six patients had elevated levels of inducible nitric oxide synthase (NOS2, a source microbicidal nitric oxide.Positive correlations among TNF-α, IFN-γ, NOS2,IDO and mild-to-moderate disease suggested that type 1 polarization plays a protective role. Significantly high levels of intralesional IL-10 were inversely correlated with IFN-γ and TNF-α. The chemokine RANTES was significantly higher in patients with several MSF. It seems that MSF patients with mild-to-moderate disease have a strong and balanced intralesional pro-inflammatory and anti-inflammatory response, while severe disease is associated with higher chemokine expression.Whether these findings are simply a correlate of mild and severe disease or contribute to anti-rickettsial immunity and pathogenesis remains to be determined.In this dissertation is also described a new rickettsiois present in Portugal caused by R.sibirica mongolitimonae strain, identified based on agent isolation and DNA detection by PCR technique in a skin biopsy.The presence of this agent corroborated by its detection also in Rhipicephalus pusillus tick. Also, pathogenic tick and flea-borne rickettsial agents such as R. africae strain detected in Rhipicephalus bursa tick, and R.felis and R.typhi detected in different fleas species raise the alert for the possible existence of other rickettsioses in Portugal that might be underdiagnosed.