Yersinia pestis, l'agent de la peste, est une bactérie à Gram-négatif classée comme agent pathogène ré-émergent et potentielle arme de bioterrorisme. De plus, l'apparition d'une souche multi-résistance de cette bactérie souligne la nécessité de mieux comprendre comment cette bactérie hyper-virulente interagit avec son hôte. Afin d'identifier des facteurs génétiques de vulnérabilité à la peste, notre laboratoire travaille sur la réponse de souris résistantes versus sensibles à Y. pestis. Notre stratégie pour identifier les facteurs génétiques impliqués dans la résistance/sensibilité à la peste combine une approche de cartographie de QTL (Quantitative Trait Locus) et d'analyse d'expression génique. Nous avons précédemment décrit la lignée SEG/Pas, issue de Mus spretus, comme la première résistante à une souche virulente de Y. pestis, alors que la plupart des lignées murines de laboratoire, telle que la lignée C57BL/6J, sont extrêmement sensible à la bactérie. Des croisements entre SEG/Pas et C57BL/6J nous ont permis d'identifier trois QTL impliqués dans la résistance à Y. pestis, localisés sur les chromosomes 3, 4 et 6. Deux des QTL (situés sur les chromosomes 4 et 6) ont pu être confirmés par l'analyse de lignées congéniques. Plus de 40 % des femelles bi-congéniques hétérozygotes pour ces deux QTL ont survécu à l'infection, alors que tous les témoins C57BL/6J ont succombé. La dissection de ces deux QTL par l'analyse de lignées sous-congéniques, nous a permis d'affiner l'architecture génétique de la résistance à la peste chez SEG/Pas. Nous avons conclu qu'un minimum de quatre facteurs génétiques, au sein de ces deux QTL, sont nécessaires pour augmenter la résistance à Y. pestis chez la Souris. Cependant, la production de plusieurs lignées congéniques portant le QTL situé sur le chromosome 3, dont une lignée triple congénique, ne nous a pas permis de confirmer l'existence de ce QTL. En parallèle de l'analyse génétique, nous avons déterminé que les macrophages de SEG/Pas et de C57BL/6J présentaient des caractéristiques différentes après exposition à Y. pestis. Une analyse différentielle du profil transcriptionnel des macrophages de ces deux lignées a été réalisée à l'aide de puces à ADN. Nos résultats montrent une forte activation de la production cytokinique dans les macrophages de SEG/Pas en réponse à la bactérie, activation qui n'est pas observée dans la lignée C57BL/6J. Ces résultats suggèrent que les souris SEG/Pas sont capables de mettre en place une réponse immune innée plus forte ou peut-être plus précoce que C57BL/6J. Nous avons ensuite étudié par qRT-PCR l'expression en cinétique de 44 gènes dans des macrophages de SEG/Pas, C57BL/6J et des bi-congéniques portant les QTL sur les chromosomes 4 et 6. Cette étude nous a permis de confirmer que les souris SEG/Pas sont capables se mettre en place une forte réponse inflammatoire lors de l'infection. Cependant, aucune différence significative n'a été observée entre la lignée bicongénique et la lignée parentale C57BL/6J. D'autres expériences seront nécessaires afin de mieux comprendre les mécanismes biologiques impliqués dans la résistance intermédiaire de cette lignée. La dissection génétique associée à l'analyse de l'expression génique de ces lignées résistante et sensible permet d'augmenter notre compréhension de la réponse de l'hôte à Y. pestis. / Yersinia pestis, the agent of plague, is a deadly gram-negative bacterium classified as a re-emerging pathogen and class A biological weapon. The appearance of a multi-resistant strain highlights the need to better understand how this pathogen kills its host. To identify genetic factors of host susceptibility to plague, our laboratory is investigating the response of resistant versus susceptible mice to Y. pestis. Our strategy to decipher genetic determinants involved in resistance to plague combines Quantitative Trait Loci (QTL) mapping with gene expression analysis. We previously described the Mus spretus-derived SEG/Pas strain as the first to resist fully virulent Y. pestis, while most inbred strains, such as C57BL/6, are highly susceptible. Crosses between these two strains identified three QTLs (located on chromosome 3, 4 and 6) contributing to resistance. Two of the QTLs (on chromosome 4 and 6) were confirmed through creation of congenic mice. Up to 40% of the congenic mice heterozygous at these two QTLs, on a C57BL/6J background, survived the infection while all C57BL/6J mice died. Further dissection of these two QTLs, through the use of subcongenic strains, enabled us to refine the genetic architecture of resistance to plague in SEG/Pas mice. We concluded that a minimum of four genetic factors, within these two QTLs, are required to increased resistance to Y. pestis in mice. Despite production of numerous congenic strains, including triple congenic mice, we were not able to confirm the existence of the third QTL identified on chromosome 3. In parallel to genetic studies, we determined that SEG/Pas and C57BL/6J macrophages exhibit distinct characteristics upon in vitro exposure to Y. pestis. The underlying molecular differences were investigated by using microarrays. Our results show strong activation of cytokines in SEG/Pas macrophages in response to Y. pestis, which is not found in C57BL/6J macrophages. These results suggest that SEG/Pas mice are able to better activate innate immune response to Y. pestis than C57BL/6J mice.We further studied the expression of 44 genes in a kinetic study on macrophages in vitro of SEG/Pas, C57BL/6J and bicongenic mice (carrying QTLs on chromosome 4 and 6). This study confirmed that SEG/Pas mice are able to build a stronger inflammatory response at early time of infection. Nevertheless no significant differences were observed in the bicongenic strain compared to C57BL/6J. Further studies will be required to understand the mechanisms involved in the intermediate resistance of this strain. This combination of genetic dissection and gene expression analysis of resistant and susceptible mouse strains will enhance our ability to better understand the host response to plague.

This study revises a dominant narrative of the eighteenth-century, in which a secular modernity emerges in opposition to religious belief. It argues that a major challenge for writers such as Jonathan Swift and Daniel Defoe, and for English subjects generally, was to grasp the object world--including the modern technological object--in terms of its spiritual potential. I identify disputes around the liturgy and common prayer as a source of a folk psychology concerning mental habits conditioned by everyday interactions with devotional and cultural objects. Swift and Defoe therefore confront even paradigmatically modern forms (from trade items to scientific techniques) as a spiritual ecology, a network of new possibilities for practical piety and familiar forms of mental-spiritual illness. Texts like A Tale of a tub (1704) and Robinson Crusoe (1719) renew Reformation ideals for the laity by evaluating technologies for governing a nation of souls. Swift and Defoe's Protestantism thus appears as an active guide to understanding emotions and new experience rather than a static body of doctrine. Current historiography neglects the early modern sense that sectarian objects and rituals not only discipline religious subjects, but also provoke ambivalence and anxiety: Swift's Tale diagnoses Catholic knavery and Puritan hypocrisy as neurotic attempts to extract pleasure from immiserating styles of material praxis. Crusoe, addressed to more radical believers in spaces of trade, sees competent spiritual, scientific and commercial practice on the same plane, as techniques for overcoming fetishistic desires. Swift's orthodoxy of enforced moderation and Defoe's oddly worldly piety represent likeminded formulae for psychic reform, and not--as often alleged--conflicts between sincere belief and political or commercial interests. Gulliver's travels (1726) and A Journal of the plague year (1722) also link mind and governance through different visions of Protestant polity. Swift sees alienation from the national church--figured by a Crusoe or Gulliver--as refusal of common sense and problem solving. Defoe points to religious schism, exemplified by dissenters' exclusion from state church statistics, as a moral and medical failure: the city risks creating selfish citizens who also may overlook data needed to combat the plague. / text

Submitted by Leonardo Cavalcante (leo.ocavalcante@gmail.com) on 2018-04-27T15:32:09Z No. of bitstreams: 1 Arquivototal.pdf: 1846108 bytes, checksum: fb9211d08b5d703a2c5cc6f6f58d918c (MD5) / Made available in DSpace on 2018-04-27T15:32:09Z (GMT). No. of bitstreams: 1 Arquivototal.pdf: 1846108 bytes, checksum: fb9211d08b5d703a2c5cc6f6f58d918c (MD5) Previous issue date: 2017-02-20 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Plague is a zoonosis whose reservoir system is composed by communities of small mammals in foci that are independent in time and space. The small mammals’ assemblage of a focus is one of the factors that regulates the fluctuations on the transmission cycle through composition variance and population parameters of each species. The comprehension of the structure and dynamics of the reservoir system of a plague focus can be a predictive tool to foresee risk of epizootic events. The present dissertation analysed the Borborema Plateau Plague focus through a zoonosis and community ecology by studying the small mammals that compose the reservoir system. The first chapter demonstrates through theory that Plague is a complex ecological entity, with several models created to explain its dynamics, although the current knowledge has a bias caused by the epidemiological surveillance models. The second chapter performs an analysis of beta-diversity on the focus, with data from a field survey in Alagoa Grande and Areia, municipalities within the focus, with 3640 traps/night of sampling effort; recovery of data from vigilance campaigns from the Health District of Garanhuns in 1981, Museum registries and literature records; obtaining 30 localities with 29 species registered. The analysis indicated high compositional dissimilarity between localities (beta-diversity > 0.9), with dominance of turnover, but confirmed the unity of the small mammal metcommunity in the Borborema Plateau. The findings in this chapter recovered a partition in the small mammal community between the peridomestic and sylvatic habitats, with beta-diversity of 0.517. The analyses weren’t capable of delimitate the focus solely by its reservoir system. The chapter also introduces the concept of metafocus, areas with geographically restricted activity within the whole expansion of the focus, controlled by a series of variables, as a theoretical possibility to explain the focus’ activity pattern. The third chapter reports the epidemiological surveillance action performed in the two municipalities from within the focus, in the state of Paraíba, capturing 45 individuals, obtaining 27 samples for PCR and bacteriology, and 7 samples for serum analysis. With all test results being negative, the quiescence period in the focus is reaffirmed, but the vigilance measures must go on, as foci might reemerge after long innactive periods, and the current situation of epidemiologic transition. / Peste é uma zoonose cujo sistema reservatório é composto por comunidades de pequenos mamíferos em focos independentes no tempo e espaço. A comunidade de pequenos mamíferos tem papel importante na regulação e mediação das flutuações do ciclo de transmissão através de sua composição e parâmetros populacionais das espécies. A compreensão da estrutura e dinâmica da comunidade de pequenos mamíferos de um foco de peste é uma ferramenta preditora para o risco de eventos epizoóticos. A presente dissertação analisou o foco de Peste da Chapada da Borborema por uma perspectiva de ecologia de zoonoses e comunidades, através de seu sistema reservatório visando responder duas perguntas: há partição da comunidade de pequenos mamíferos entre peridomicílio e remanescentes nativos? E, qual é o perfil pestoso dos ambientes peridomiciliar e selvático. O primeiro capítulo demonstra que a Peste pode ser considerada uma entidade ecológica complexa, com diversos modelos para explicar sua dinâmica, embora ainda incompletos, dado o viés amostral causado pela rotina de vigilância. O segundo capítulo realiza uma análise de beta-diversidade no foco; através de coletas em campo em Alagoa Grande e Areia, municípios circunscritos ao foco, com esforço total de 3640 armadilhas/noite; resgate do registro histórico das coletas de pequenos mamíferos na região através de fichas de atividade de vigilância em zoonoses da Regional de Saúde de Garanhuns em 1981, Livros do Tombo de duas coleções e registros da literatura; obtendo 30 localidades com registro de 29 espécies. As coletas em campo e as coletas da Regional de Saúde foram suficientes em amostrar a fauna do local, tendo a riqueza registrada condizente com a projeção do estimador Chao 1. As análises indicaram alta dissimilaridade composicional entre as localidades (betadiversidade > 0.9), com dominância do turnover, mas confirmaram a unidade da metacomunidade do Planalto da Borborema. Os achados do capítulo resgataram uma partição da comunidade de pequenos mamíferos entre o ambiente peridomiciliar e os remanescentes de vegetação nativa, com uma beta-diversidade de 0.517. O foco não é delimitável à partir apenas do sistema reservatório. Apresenta-se também a noção do metafoco, locais de atividade pontual e difusa dentro do território total do foco, com regime controlado por uma combinação de fatores ambientais ótimos, como uma possibilidade teórica para explicar a atividade do foco. O terceiro capítulo faz um inquérito epidemiológico nos dois municípios circunscritos ao foco no estado da Paraíba amostrados no capítulo anterior, capturando 45 indivíduos em campo, dos quais se obteve amostras para análises bacteriológicas e moleculares (27) e sorologia (7). Com todos os resultados negativos, temos a reafirmação do período quiescente do ciclo de transmissão, mas alertando que a quiescência não descarta as medidas de vigilância, dado que os focos podem reemergir, e o panorama epidemiológico mundial alerta para um período de transição zoonótica.

Yersinia pestis, agent causal de la peste, persiste dans la nature maintenu par un cycle enzootique dans des foyers conduisant à la réémergence de la maladie. En Afrique du Nord, où une réémergence a eu lieu après des années de ‘silence’, nous avons répertorié les différents épisodes ainsi que le nombre de cas en sur six pays à compter de 1940 en mettant en évidence l’importation de la maladie et un mode de contamination négligé, la transmission par voie orale. Une étude en Algérie sur 237 micromammifères confirme deux foyers et en revèle trois nouveaux porteurs d’un nouveau génotype (MST) de biotype Orientalis. Apodemus sylvaticus est par la même ajouté à la liste des rongeurs pestiférés. La projection des foyers de peste ainsi actualisés sur une carte géographique et écologique met en évidence la proximité des foyers de peste aux points d’eau saumâtre. Une étude statistique a confirmé une corrélation significative entre foyer de peste/eau salée à une proximité minimale <3 km en comparaison à des zones d’eau douce. Des échantillons environnementaux salés ont permis l’isolement d’une souche Y. pestis Algeria 3. Cette découverte confortée par l’observation expérimentale de la résistance de Y. pestis à un milieu hyper salé à 150g/L NaCl se traduisant par un protéome spécifique en réponse à ce stress avec une forme d’adaptation de type forme L de la bactérie dans ce type d’environnement. Notre travail éclaire de façon originale un facteur méconnu de persistance tellurique de Y. pestis, conditionnant la réémergence de la peste dans des foyers séculaires au Maghreb contrairement aux rivages Nord de la Méditerranée où la peste autochtone a disparu depuis un siècle. / Yersinia pestis, the causal agent of plague, persists in nature maintained by an enzootic cycle in foci leading to the re-emergence of the disease. In North Africa, where re-emergence took place after years of 'silence', we have listed the various episodes and the number of cases in six countries from 1940 onwards, highlighting the importation of the disease and A method of neglected contamination, oral transmission. A study in Algeria on 237 micromammals confirms two foci and reveals three new carriers of a new genotype (MST) of orientalis biotype. Apodemus sylvaticus is by the same added to the list of plague rodents. The projection of the plague foci thus updated on a geographical and ecological map highlights the proximity of plague foci to brackish water points. A statistical study confirmed a significant correlation between plague / salt water at a minimal proximity <3 km compared to freshwater areas. Saline environmental samples allowed the isolation of a Y. pestis Algeria 3 strain. This discovery was confirmed by the experimental observation of the resistance of Y. pestis to a hyper-saline medium at 150 g / L NaCl resulting in a specific proteome In response to this stress with an adaptation form of form L of the bacterium in this type of environment. Our work illuminates in an original way an unknown factor of telluric persistence of Y. pestis, conditioning the re-emergence of the plague in secular centers in the Maghreb unlike the northern shores of the Mediterranean where the indigenous plague has disappeared for a century.

Macrophage-derived foam cells play a predominant role in the deposition of arterial plaques during the early stages of atherosclerosis. The deposition of arterial plaques is known to be effected by several factors, including a person’s dietary habits. The consumption of a high-fat (>60% of calories from fat) meal is known to elevate serum LDL and triglycerides, which have been previously implicated in the formation pf foam cells. One limitation of current research models is that it is not possible to directly measure foam cells in vivo. Thus, the purpose of the present study was to validate the use of blood derived monocytes as a proxy measure of foam cells. In order to complete this objective, we evaluated monocyte oxLDL phagocytosis capacity following consumption of a high-fat meal. Eight men and women participated in the present study and venous blood samples were collected prior to the meal, 1-h, 3-h, and 5-h post-meal. Monocytes (CD14+/16- and CD14+/16+) were evaluated for adhesion molecule expression (CD11a, CD11b, and CD18), scavenger R (CD36) expression, and oxLDL phagocytosis using an image-based flow cytometry method developed in our laboratory for this purpose. Data was statistically analyzed for significance using a single-factor ANOVA with repeated measures and a p < 0.05. Consumption of a high-fat meal caused an increase significant increase in the proportion of pro-inflammatory monocytes (CD14+/16+) and a decrease in classic monocytes (CD14+/16-), with the greatest difference occurring at 5 h post prandial (p = 0.038). We also found that pro-inflammatory monocyte expression of adhesion molecules and CD36 increased in a manner that would promote in vivo movement of monocytes into the subendothelial space. Finally, over the course of the 5 h postprandial period, the majority of oxLDL uptake occurred in pro-inflammatory compared to classic monocytes. These results suggest that consuming a high-fat meal increases the potential of monocytes to become foam cells for at least 5 h postprandial.

Le bacille de la peste, Yersinia pestis, a une vie parasitaire au cours de laquelle il oscille le plus souvent d’un hôte mammifère à l’autre par l’intermédiaire des puces, et plus rarement par voie aéroportée. Comme tel, Yersinia pestis doit rapidement ressentir et répondre aux variations brutales de son environnement afin se maintenir dans la nature. C’est pourquoi, nous avons étudié le rôle des systèmes de régulation à deux composants dans la peste compte tenu que ces systèmes sont connus pour avoir un rôle clef dans l’adaptation des bactéries aux changements environnementaux. En plus du système PhoP-PhoQ dont l’importance chez le mammifère et la puce a été précédemment révélée, nous avons découvert que quatre systèmes sont requis pour le cycle de la peste. Plus particulièrement, l'un d'entre eux permet une colonisation optimale du tube digestif de la puce alors que les 3 autres systèmes sont impliqués dans la production de biofilm, un processus indispensable à une transmission optimale du bacille par les puces. Nous avons aussi découvert que le système OmpR-EnvZ est l’unique système, en plus du système PhoP-PhoQ, requis pour la production de la peste bubonique, septicémique et pulmonaire. Nos travaux, menés in vitro, ex-vivo et in vivo suggèrent que le rôle du système OmpR-EnvZ serait de protéger la bactérie contre les effecteurs toxiques sécrétés par les polynucléaires neutrophiles dans les tissus et, ceci tout au long du processus infectieux. / Plague bacillus, Yersinia pestis has a parasitic lifestyle in which it is mainly transmitted between mammilian hosts through the bite of infected fleas, and in rare cases through infected droplets. Thus, Yersinia pestis must rapidly sense and respond to wide and brutal changes of its environment in order to survive. We aimed at decipher the role of two component regulatory systems in plague, as they are known to be key players in bacterial adaptation to the environment. In addition to the already described PhoP-PhoQ system, we found out that four systems are required for plague cycle. We showed that one of these systems is important for an optimal colonization of the flea's digestive tract, while the three others are required for biofilm production, an essential step in the bacillus transmission by the fleas. We also found out that OmpR-EnvZ, in addition to PhoP-PhoQ, is the only one to be important to produce bubonic, septicemic and pulmonary plague. Our in vitro, ex-vivo and in vivo works suggest that the OmpR-EnvZ system would be to protect bacterial against toxic effectors that are produced by polymorphonuclear leukocytes all along the infectious process.

Host survival during plague, caused by the Gram-negative bacterium Yersinia pestis, is favored by a robust early innate immune response initiated by IL-1β and IL-18. Precursors of these cytokines are expressed downstream of TLR signaling and are then enzymatically processed into mature bioactive forms, typically by caspase-1 which is activated through a process dependent on multi-molecular structures called inflammasomes. Y. pestis evades immune detection in part by using a Type three secretion system (T3SS) to inject effector proteins (Yops) into host cells and suppress IL-1β and IL-18 production. We investigated the cooperation between two effectors, YopM and YopJ, in regulating inflammasome activation, and found that Y. pestis lacking both YopM and YopJ triggers robust caspase-1 activation and IL-1Β/IL-18 production in vitro. Furthermore, this strain is attenuated in a manner dependent upon caspase-1, IL-1β and IL-18 in vivo, yet neither effector appears essential for full virulence. We then demonstrate that YopM fails to inhibit NLRP3/NLRC4 mediated caspase-1 activation and is not a general caspase-1 inhibitor. Instead, YopM specifically prevents the activation of a Pyrin-dependent inflammasome by the Rho-GTPase inhibiting effector YopE. Mutations rendering Pyrin hyperactive are implicated in the autoinflammatory disease Familial Mediterranean Fever (FMF) in humans, and we discuss the potential significance of this disease in relation to plague. Altogether, the Y. pestis T3SS activates and inhibits several inflammasome pathways, and the fact that so many T3SS components are involved in manipulating IL-1β/IL-18 underscores the importance of these mechanisms in plague.

The spread of infectious agents has been observed as long as their hosts have existed. The spread of infectious diseases in human populations, however, is more than an academic concern, causing millions of deaths every year, and prompting collective surveillance and intervention efforts worldwide. These surveillance data, used in conjunction with statistical methods and mathematical models, present both challenges and opportunities for advancements in scientific understanding and public health. Early mathematical modeling of infectious diseases in humans began by assuming homogeneous contact among individuals, but has since been extended to account for many sources of non-homogeneity in human contact. Detecting the degree of epidemic mixing between geographically separated populations, in particular, remains a difficult problem. The difficulty occurs because although disease case reports have been collected by many governments for decades, case reporting is imperfect, and transmission events themselves are nearly impossible to observe. The degree to which epidemic coupling can be detected from case reports is the central theme of this thesis. We present a careful, biologically motivated and consistent derivation of the transmission coupling (fully derived in Chapter 4). In Chapter 2 we consider the simple scenario of an epidemic spreading from one population to another, and present both numerical and analytic methodology for estimating epidemic coupling. Chapter 3 considers the problem of estimating epidemic coupling among populations undergoing recurrent epidemics, such as those of childhood diseases which have been widely observed. In Chapter 4 we present a method for estimating coupling among an arbitrary number of populations undergoing an epidemic, and apply it to estimate coupling among the parishes of London, England, during the Great Plague of 1665. / Thesis / Doctor of Philosophy (PhD)

Made available in DSpace on 2016-04-27T19:31:47Z (GMT). No. of bitstreams: 1 Ana Margarida Furtado Arruda Rosemberg.pdf: 11239263 bytes, checksum: 73ecd6b65fbfc478387d16b082e62ea6 (MD5) Previous issue date: 2008-05-05 / The objective of this research is to show the war against Tuberculosis in São Paulo city from 1899 to 1947; the life and work of Clemente Ferreira, pioneer in the fight against Tuberculosis in Brazil, and, also the importance of this disease in popular language and in the minds of those working in this field at this time. Its describes the setting up and work of the Liga Paulista against Tuberculosis, a charitable organization founded in 1899 by Clemente Ferreira and collaborators, pointing out its main weapons: dispensary, prevention institution, sanatorium and hospital. Also included is the functioning of the model Clemente Ferreira Dispensary, the first of its kind in the struggle against Tuberculosis in São Paulo city in the first 30 years of the 20th century. Furthermore the role of the journal Defesa contra a Tísica the official organ of Liga Paulista in making the population and law makers aware of the importance of relating the seriousness of Tuberculosis and the necessity of the government to take responsibility and support the fight. This work also analyzes those involved in this area in popular language and in what they thought. It shows the importance of charitable associations at the beginning of the 20th century to make the control of Tuberculosis in Brazil and, specifically, in São Paulo city, a matter of interest and responsibility of the state / Esta pesquisa se propõe a mostrar a guerra travada contra a tísica, na capital paulista, de 1899 a 1947; a vida e a obra de Clemente Ferreira, pioneiro da luta contra a tuberculose no Brasil e as representações da tuberculose nas linguagens sociais e no imaginário dos tisiólogos, no mesmo período. Descreve a criação e a atuação da Liga Paulista contra a Tuberculose, uma sociedade beneficente fundada, em 1899, por Clemente Ferreira e colaboradores, destacando os seus armamentos: dispensário, preventório, sanatório e hospital. Evidencia a ação do Dispensário-Modêlo Clemente Ferreira , baluarte da luta contra a tuberculose na capital de São Paulo, nos primeiros 30 anos do século XX. Mostra, ainda, a importância da revista Defesa Contra a Tísica , órgão oficial da Liga Paulista, na conscientização da população e dos governantes em relação à gravidade da tuberculose e a necessidade do governo assumir e apoiar a luta. Este trabalho, também, analisa as representações da tuberculose nas linguagens sociais e no imaginário dos tisiólogos. Evidencia, enfim, a importância das associações filantrópicas no começo do século XX, para tornar o controle da tuberculose, no Brasil e, em particular, em São Paulo, uma questão de interesse e responsabilidade do Estado

This thesis describes the construction of a mobile Insect Monitoring Radars (IMR) and investigations of: the reliability of IMRs for observing insect migration in inland Australia; possible biases in IMR migration estimates; the relation between an insect???s size and its radar properties; radar discrimination between insect species; the effect of weather on the migrations of Australian plague locusts and of moths; the scale of these migrations; and here IMRs are best located. The principles of entomological radar design, and the main features of insect migration in inland Australia, are reviewed. The main procedures used in the study are: calculation of radar performance and of insect radar cross sections (RCSs); reanalysis of a laboratory RCS dataset; statistical analysis of a fouryear dataset of IMR and weather observations; and a field campaign using both two existing fixed IMRs and the new mobile unit. Statistical techniques used include correlation, multiple regression, discriminant analysis, and principal components analysis. The original results of this work include design details of the mobile IMR, extension of radar performance calculations to IMRs and evaluation of flight speed biases, a holistic approach to IMR design, the relation of insect RCS magnitudes and polarization patterns to morphological variables, an estimate of the accuracy of the retrieved parameters, evaluations of three approaches (oneparameter, theory-based, and a novel two-stage method) to target identification, and verification of inferred target identities using results from nearby light traps. Possible sites for future IMRs are identified. The major conclusions are that: a mobile IMR can be built with a performance equal to that of a fixed IMR but at half the cost; significant biases in the signal processing results arise from insect speed; locusts and moths can be distinguished if all RCS parameters are used; IMRs can be designed to match particular requirements; weather has a significant effect on insect migration, the best single predictor of insect numbers being temperature; moonlight has no effect; the spatial correlation of migration properties falls to 50% at a separation of 300 km; and migrating insects can be carried by the wind for 500 km in a single night