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A hantavirose (infecção por Hantavírus) é uma das zoonoses que vem preocupando as autoridades sanitárias de todo o mundo. Sua ocorrência se deve principalmente os distúrbios ecológicos é transmitida ao homem através de inalação de partículas virais contida na excreta de roedores. São conhecidas duas doenças humanas distintas causadas pelo Hantavírus: a Febre Hemorrágica com Síndrome Renal (FHSR) e a Síndrome Pulmonar e Cardiovascular (SPCVH). O objetivo deste estudo foi verificar a ocorrência de anticorpos IgG anti-hantavírus, através do ELISA, em populações da Amazônia e Sudeste brasileiro, que vivem em contato com os roedores silvestres, utilizando a proteína recombinante do vírus Araraquara expressa em Escherichia coli. Do total de estudados 1308 soros humanos estudados, na Amazônia (1078) encontramos 59 soros positivos (5%). Na cidade Machadinho do OesteRO os soros coletados durante o ano 2003, foram analisados 638, onde foram encontrados 20 soros positivos (4,5%); e no Rio Machado RO. foram analisados 435 soros da população ribeirinha onde foram encontrados 39 (5%) soros positivos, respectivamente. Após análise realizada em 151 soros humanos provenientes do Vale do Ribeira, em 2007; e 84 no Pontal do Paranapanema, em 2008, foram observados 14 positivos (9%) e 6 (7%) das amostras, respectivamente. / The genus Hantavirus of the family Bunyaviridae includes a large number of rodent-borne viruses that are distributed worldwide. The occurrence is due mainly to ecological disturbances and it is transmitted to the humans through inhalation of virus particles contained in the excreta of wild rodents. Two different human diseases known to be caused by Hantavirus: are Hemorrhagic Fever with Renal Syndrome (HFRS) and Hantavirus Cardiopulmonary Syndrome (HPS). The main objective of this study was detected antibody against hanatavirus (IgG) by ELISA, in Amazon region and Brazilian Southwest populations who live in contact with the wild rodents, using recombinant protein (antigen) of the Araraquara virus expressed in Escherichia coli. We study 1308 human sera (1078 from Amazon region) and there were found 59 (5%) positive sera. From the city of Machadinho do Oeste RO (2003 year), 633 sera were analysed, where there were found to be 20 positive (4.5%) serums. In Machado river RO (2005 year), 435 sera of the river-dwelling population were analysed where there were found 39 (5%) positive sera, respectively. After analysis was accomplished for 151 human sera coming from the Vale do Ribeira - SP, in 2007, and 84 from the Pontal do Paranapanema - SP, in 2008, 14 (9%) and 6 (7%) of the samples were observed to be positive, respectively.

A hantavirose (infecção por Hantavírus) é uma das zoonoses que vem preocupando as autoridades sanitárias de todo o mundo. Sua ocorrência se deve principalmente os distúrbios ecológicos é transmitida ao homem através de inalação de partículas virais contida na excreta de roedores. São conhecidas duas doenças humanas distintas causadas pelo Hantavírus: a Febre Hemorrágica com Síndrome Renal (FHSR) e a Síndrome Pulmonar e Cardiovascular (SPCVH). O objetivo deste estudo foi verificar a ocorrência de anticorpos IgG anti-hantavírus, através do ELISA, em populações da Amazônia e Sudeste brasileiro, que vivem em contato com os roedores silvestres, utilizando a proteína recombinante do vírus Araraquara expressa em Escherichia coli. Do total de estudados 1308 soros humanos estudados, na Amazônia (1078) encontramos 59 soros positivos (5%). Na cidade Machadinho do OesteRO os soros coletados durante o ano 2003, foram analisados 638, onde foram encontrados 20 soros positivos (4,5%); e no Rio Machado RO. foram analisados 435 soros da população ribeirinha onde foram encontrados 39 (5%) soros positivos, respectivamente. Após análise realizada em 151 soros humanos provenientes do Vale do Ribeira, em 2007; e 84 no Pontal do Paranapanema, em 2008, foram observados 14 positivos (9%) e 6 (7%) das amostras, respectivamente. / The genus Hantavirus of the family Bunyaviridae includes a large number of rodent-borne viruses that are distributed worldwide. The occurrence is due mainly to ecological disturbances and it is transmitted to the humans through inhalation of virus particles contained in the excreta of wild rodents. Two different human diseases known to be caused by Hantavirus: are Hemorrhagic Fever with Renal Syndrome (HFRS) and Hantavirus Cardiopulmonary Syndrome (HPS). The main objective of this study was detected antibody against hanatavirus (IgG) by ELISA, in Amazon region and Brazilian Southwest populations who live in contact with the wild rodents, using recombinant protein (antigen) of the Araraquara virus expressed in Escherichia coli. We study 1308 human sera (1078 from Amazon region) and there were found 59 (5%) positive sera. From the city of Machadinho do Oeste RO (2003 year), 633 sera were analysed, where there were found to be 20 positive (4.5%) serums. In Machado river RO (2005 year), 435 sera of the river-dwelling population were analysed where there were found 39 (5%) positive sera, respectively. After analysis was accomplished for 151 human sera coming from the Vale do Ribeira - SP, in 2007, and 84 from the Pontal do Paranapanema - SP, in 2008, 14 (9%) and 6 (7%) of the samples were observed to be positive, respectively.

Evolutionary novelty, the origin of new characters such as the turtle shell or the flower, is a fundamental problem for an evolutionary view of life. Accordingly, it is a central research topic in contemporary biology involving input from several biological disciplines and explanations at several levels of organization. As such it raises questions relative to scientific collaboration and multi-level explanations. Novelty is also involved in theoretical debates in evolutionary biology. It has been appropriated by evo-devo, a scientific synthesis linking research on evolution and development. Thanks to its focus on development, evo-devo claims to explain the mechanistic origin of novelties as new forms, while the Modern Synthesis can only provide statistical explanation of evolutionary change. The origin of an evolutionary novelty is a historical emergence of a new character involving form and function. I focus on three neglected dimensions of the problem of novelty, the functional-historical approach to the problem, research on novelty in the Modern Synthesis era and novelty in plants. I compare the evo-devo approach to novelty to a functional-historical approach of novelty. I focus on its origin in Darwin and its presence in the Modern Synthesis. The comparison of the two approaches reveals distance between conceptual frameworks and proximity in explanatory practices. This is partly related to unwarranted conceptual opposition. In particular, I list several ways of distinguishing novelty and adaptation, some of which are not conceptually sound. I then focus on the relation between novelty and adaptation in the Modern Synthesis era, and on the relation of novelty to other fundamental biological problems (speciation, origin of higher taxa, complexity). Pushing this approach further, I challenge the view that the Modern Synthesis excluded development and reached a hardened consensus. Finally, I analyse how Günter Wagner's developmental theory of novelty applies to novelties in plant.

Thesis (PhD) -- Macquarie University, Division of Society, Culture, Media and Philosophy, Dept. of Sociology, 2008. / Bibliography: p. 233-248. / Academic vessels: STS and HPS -- SSK : scientism as empirical relativism -- Latour and actor-network-theory -- Tensions and dilemmas in science studies -- Kuhn - paradigm of an uncritical turn -- Critical theory of technology: Andrew Feenberg -- Critical theory and science studies: Jürgen Habermas -- Concluding remarks: normativity and synthesis. / Science Studies is an interdisciplinary area of scholarship comprising two different traditions, the philosophical History and Philosophy of Science (HPS) and the sociological Science and Technology Studies (STS). The elementary tension between the two is based on their differing scholarly values, one based on philosophy, the other on sociology. This tension has been both animating the field of Science Studies and complicating its internal self-understanding. --This thesis sets out to reconstruct the main episodes in the history of Science Studies that have come to formulate competing constructions of the cultural value and meaning of science and technology. It tells a story of various failed efforts to resolve existing antimonies and suggests that the best way to grapple with the complexity of the issues at stake is to work towards establishing a common ground and dialogue between the rival disciplinary formations: HPS and STS. --First I examine two recent theories in Science Studies, Sociology of Scientific Knowledge (SSK) and Actor-Network Theory (ANT). Both of them are found to be inadequate as they share a distorted view of the HPS-STS divide and both try to colonise the sociology of science with the tools of HPS. The genesis of this colonizing impulse is then traced back to the Science Wars which again is underpinned by a lack of clarity about the HPS-STS relationship. This finding further highlights the responsibility of currently fashionable theories such as ANT that have contributed to this deficit of understanding and dialogue. / This same trend is then traced to the work of Thomas Kuhn. He is credited with moderate achievements but recent re-evaluations of his work point to his culpability in closing the field to critical possibilities, stifling the sociological side and giving rise to a distorted view of the HPS-STS relationship as seen in SSK and ANT. Now that the origins of the confused and politically divided state of Science Studies is understood, there is the urgent task of re-establishing a balance and dialogue between the HPS and the STS sides. --I use two important theoretical threads in critical theory of science and technology to bring clarity to the study of these interrelated yet culturally distinct practices. Firstly I look at the solid line of research established by Andrew Feenberg in the critical theory of technology that uses social constructivism to subvert the embedded values in the technical code and hence democratize technology. --Secondly I look at the work of Jürgen Habermas's formidable Critical Theory of science that sheds light on the basic human interests inside science and technology and establishes both the limits and extent to which social constructivism can be used to study them. --Together Feenberg and Habermas show the way forward for Science Studies, a way to establish a common ground that enables close scholarly dialogue between HPS and STS yet understands and maintains the critical difference between the philosophical and the sociological approaches that prevents them from being collapsed into one indistinguishable entity. Together they can restore the HPS-STS balance and through their shared emancipatory vision for society facilitate the bringing of science and technology into a democratic societal oversight, correcting the deficits and shortcomings of recent theories in the field of Science Studies. / Mode of access: World Wide Web. / vii, 248 p

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Ma recherche a pour but de faire le point sur les derniers développements de l’historical epistemology, modalité d’enquête de la connaissance qui a émergée au cours du XX siècle au sein de l’épistémologie française et qui reste actuellement active dans une variété de formes. En dépit de son succès auprès de nombreux auteurs contemporains, l’épistémologie historique ne bénéficie encore d’aucune systématisation ni d’aucune liste d’auteurs et d’ouvrages canoniques. Mon travail de thèse se propose de traiter directement la question même de la légitimité et de l’originalité de ce type d’épistémologie en discutant sa nature, sa méthodologie et son unité. En analysant les ouvrages les plus importants dans ce domaine, j’accorderai un rôle central d’un coté à Michel Foucault et de l’autre à Ian Hacking, qui, à maintes égards, ont entretenu des rapports complexes, controversés, et pourtant révélateurs, avec l’épistémologie historique. Les deux phases de l’épistémologie historique, l’une « originaire » et l’autre « contemporaine », seront analysées dans un rapport biunivoque, dans un souci de clarification réciproque. Le développement à l’étranger de l’épistémologie historique dans sa phase contemporaine a créé une sorte de vide et une perte d’intérêt étonnante dans son lieu de naissance. La reconnexion de ce type d’épistémologie au cadre philosophique originel de son émergence représente l’occasion de ré-ouvrir le débat en France. / What is historical epistemology? Why does this field, despite its current proliferation,seem to be permanently haunted by questions relative to its nature, limits and ultimatetasks? What kind of historicization is at stake in this sort of inquiry? What is the relationbetween contemporary historical epistemology, as it is practiced by a growing number ofEnglish-speaking historians and philosophers of science, and the French “tradition” ofépistémologie historique? To address these questions, my research aims to provide arecursive analysis demonstrating how the two phases of historical epistemology, the“classical” and the “contemporary”, can clarify each other. In this process, the“archaeological method” of Michel Foucault, which draws on and transforms fundamentalinsights by Gaston Bachelard and Georges Canguilhem, will be shown to exert an enduringinfluence on the field, especially through Ian Hacking and his philosophical cum historicalanalyses of probability. / Che cos’è l’epistemologia storica? Perchè questo campo, nonostante la sua proliferazione attuale, sembra essere permanentemente minacciato da questioni relative alla sua natura, ai suoi limiti e ai suoi obiettivi ultimi? Che tipo di storicizzazione caratterizza questo tipo di indagine? Qual è la relazione tra l’epistemologia storica contemporanea, come è praticata da un numero crescente di storici e filosofi della scienza di lingua inglese, e la tradizione francese dell’épistémologie historique? Per affrontare tali questioni, la mia ricerca intende fornire un’analisi ricorsiva che dimostri come le due fasi dell’epistemologia storica, quella “classica” e quella “contemporanea”, possono chiarificarsi reciprocamente. In questo processo, il “metodo archeologico” di Foucault, che trae spunto da e trasforma intuizioni fondamentali di Gaston Bachelard e Georges Canguilhem, sarà mostrato nella sua influenza su questo campo di indagine, specialmente attraverso Ian Hacking e le sue analisi storico-filosofiche della probabilità.

In today’s lighter vehicles, EPS has had smaller breakthroughs, but not in heavyduty due to its high initial cost and lack of research. Even though there ispotential in the future when trucks may go electric. In this report, the theoreticalrequirements to implement an EPS system will be determined and investigatedalong with an in depth analysis of the electrical motor and planetary gearbox used.A preferred EPS system will consist of a Permanent magnet electric motor and aplanetary gearbox with optimized characteristics regarding voltage, cost, shape,dimensions and layout. The results lead to a theoretical EPS system that can befitted into a heavy duty truck’s engine compartment. Problems with implementingEPS, such as cost, electrical issues and limited space as well as possibilities forfuture work are discussed.

Recycling embosoms (REs) are transient intermediates of endosomal network, constantly generated from early/sorting endosomes (EEs/SEs). Conventionally, these organelles function in recycling of many growth/nutrient/signalling receptors from SEs to the cell surface and maintain the cellular homeostasis in all cell types. Recent studies have shown that REs slightly diverted their function in specialized cells such as melanocytes for the delivery of melanogenic cargo to a set of lysosome-related organelles (LROs) called melanosomes. However, it is unknown how melanocytes modulate the trafficking routes of REs towards the biogenesis of melanosomes. Any alterations in this process result in occulocutaneous albinism, commonly observed in autosomal recessive disorder, Hermansky-Pudlak Syndrome (HPS). HPS is caused by mutations in nine genes in human and fifteen genes in mouse and the protein products of these genes were grouped in multiple endosomal protein complexes; BLOC (Biogenesis of Lysosome-related Organelles Complex)-1, -2, -3, AP (Adaptor Protein)-3 and HOPS (homotypic fusion and protein sorting). Studies from our laboratory and others have shown that REs deliver the melanin-synthesizing enzymes to melanosome in BLOC-1 and BLOC-2 dependent manner. On the other side, studies in fibroblasts have shown that the adaptor AP-1 and microtubule-dependent motor, KIF13A also regulates the formation of REs. In these studies, it was proposed that AP-1 binds to the cargo tails and interacts with motor KIF13A to generate the RE tubules, where BLOC-1 initiates the biogenesis. Nevertheless, the mechanism behind the biogenesis of REs and how these molecules synergistically control these processes is largely unknown. Additionally, the role of BLOC-2 in REs biogenesis never been implicated. Here we have attempted to study the mechanism of RE biogenesis and their role in pigment granule formation using HeLa and mouse melanocytes as model systems. In general, Rab GTPases (Rabs) regulate the several process of membrane trafficking including cargo sorting, membrane domain organization, tethering and fusion. We hypothesized that the biogenesis of RE is also regulated by one of the endosome localized Rab GTPases. Our RNAi screening against Rabs involved in regulating the RE length/number showed Rab22A as a potential candidate. Thus, we aim to study the role of Rab22A in RE biogenesis and its regulation in melanocyte pigmentation. The current study entitled as “Understanding the role of Rab22A in recycling endosome biogenesis and melanocyte pigmentation” is divided into five chapters. Chapter-I outlines the review of literature on cell biology of intracellular organelles such as endocytic network and melanosomes. Chapter-II details the experimental procedures used in the study. Chapter-III to Chapter-V describes the results and discussion. Chapter-III: Identification of endosomal Rab GTPases required for the dynamics of recycling endosomes Endosomal Rabs are known to regulate various functions such as vesicle biogenesis, transport, tethering and fusion, but their role in generation of tubulo-vesicular carriers of endocytic system, REs is unknown. It has been shown that REs possibly derived from EEs/SEs and characterized by the association/localization of multiple proteins such as transferrin receptor (TfR), SNARE STX13, Rab11 and motor KIF13A. In this study, we have used YFP-KIF13A as a marker to label the REs. YFP-KIF13A in HeLa cells localized to long tubular structures throughout the cell and also to the clusters of peripheral endosomes. To identify the endosomal Rabs that regulate the RE dynamics (both length and number), we have transfected the HeLa cells with shRNA against endosomal Rabs such as Rab4A, Rab5A, Rab5B, Rab5C, Rab7A, Rab9A, Rab11A, Rab14A and Rab22A. Post transfection and shRNA selection, cells were transfected with YFP-KIF13A, analyzed and quantified the RE dynamics using ImageJ. Here, we have measured two parameters for the identification of Rab/s that potentially regulates the REs biogenesis: first, average number of tubules per cell and second, average length of tubules per cell. These studies identified Rab22A as a potential candidate, depletion of this Rab affects both number and average length of KIF13A-positive tubules. As described above, REs deliver several melanocyte specific cargoes to melanosomes in melanocytes. However, the function of Rab22A in controlling these transport steps to melanosome/its biogenesis or pigmentation has not been addressed. Thus, we have studied the mechanism of Rab22A in RE biogenesis and its role in pigmentation in the following sections. Chapter-IV: Characterization of Rab22A function in regulating the recycling endosomes Initially, we tested whether Rab22A localizes to the REs. Our co-expression studies show that Rab22A localizes to KIF13A- or STX13-positive RE compartments in HeLa or melanocytes, respectively. In general, Rab GTPases mediate their function through cycling between GTP (membrane bound) and GDP (cytosol) bound state. These states can be achieved by point mutation of active site residues in the protein. We have generated Rab22A constitutive active mutant (Rab22AQ64L, defective in GTP hydrolysis) and dominant negative mutant (Rab22AS19N, defective in GTP binding) to understand the role of Rab22A in regulating REs. Interestingly, overexpression of Rab22AQ64L mutant in HeLa cells increases the average number of KIF13A-positive REs relative to the wild-type Rab22A (Rab22AWT). As predicted, overexpression of Rab22AS19N mutant reduces the number as well as length of RE tubules relative to the control HeLa cells. Consistent to these studies, Rab22A-knockdown did not affect the endogenous KIF13A protein levels or its recruitment to endosomes, however recycling of TfR (measured through Tf-Alexa 594) was significantly affected in these cells. These studies suggest that Rab22A possibly regulates the formation or function of REs. Likewise, overexpression of Rab22AQ64L and Rab22AS19N mutants in melanocytes resulted in reduction of total melanin content in the cells. To confirm these results, we have performed immunofluorescence microscopy (IFM) analysis, which showed Rab22AQ64L localized to the enlarged vacuolar structures, positive for melanosomal cargo TYRP1 (tyrosinase-related protein 1), whereas Rab22AS19N localized to the cytosol. Further, Rab22A depletion in melanocytes causes the hypopigmentation in the cells concurrently reduces the stability of TYRP1 but not other melanocyte specific proteins, indicating a role for Rab22A in regulating TYRP1 transport to melanosomes. Altogether, our studies suggests that Rab22A regulates the TfR recycling in HeLa cells and TYRP1 transport in melanocytes by controlling the RE dynamics. Chapter-V: Molecular mechanism of recycling endosome biogenesis: a role for Rab22A Rabs perform their function by recruiting specific effector/s to the membrane upon Rab activation. It is unknown, how Rab22A regulates REs through its effectors. We hypothesize that Rab22A may regulate the recruitment and function of BLOC-1 and BLOC-2 complexes during RE formation. To validate these hypothesis, we carried out the knockdown of individual BLOC-1 and -2 subunits (destabilize the entire complex) separately in HeLa and studied the dynamics of RE through YFP-KIF13A expression. As expected, the length and number of KIF13A-postive tubules were significantly reduced in both BLOC-1- and BLOC-2-deficient HeLa cells and was phenocopying the Rab22A knockdown cells. Moreover, subcellular fractionation in HeLa, co-fractionated Rab22A with BLOC-1 (Muted) or BLOC-2 (HPS6) subunits along with KIF13A. Additionally, endogenous subunit levels of BLOC-1 and BLOC-2 were moderately reduced in Rab22A knockdown HeLa cells. Consistent to these results, recycling kinetics of Transferrin (Tf) was altered in Rab22A depleted cells as similar to BLOC-1- or BLOC-2-deficient cells as reported earlier. Likewise, Rab22A knockdown in melanocytes affected STX13-positive tubules and also the stability of endogenous BLOC-1 subunit, Pallidin, suggesting that Rab22A possibly works with BLOC-1 and BLOC-2 independent of cell types. To understand the regulation among these molecules, we overexpressed Rab22A in BLOC-1-deficient cells and analyzed the cells for BLOC-1-deficient rescue phenotypes such as pigmentation and cargo localization. However, Rab22A could not compensate the BLOC-1 function, suggesting that Rab22A possibly functions upstream of BLOC-1. Our subcellular and membrane associated fractionation studies of homogenates depleted with Rab22A, BLOC-1 and BLOC-2 showed that subunit levels of BLOC-1 and BLOC-2 in the membrane pool were significantly reduced upon Rab22A depletion compared to control cells. However, membrane association of Rab22A in BLOC-1 deficient cells was not affected. Further, our biochemical interaction studies showed that Rab22A interacts physically with BLOC-1 and BLOC-2 subunits as well as with KIF13A. Thus, these studies indicate that Rab22A possibly recruits and interacts with BLOC-1 and BLOC-2 for the generation of REs. We have summarized the study by proposing a model wherein Rab22A localizes to the limiting membrane of endosomes that are positive for KIF13A and then recruits and associates with BLOC-1 and BLOC-2 complexes which subsequently pulled by KIF13A for the generation of RE tubules.

L'expérience HPS (Heavy Photon Search) au Jefferson Lab (USA)recherche un nouveau boson de jauge vecteur, nommé "photon lourd" ou "photon sombre", dans une fourchette de masse allant de 20 à 1000 MeV. Une telle particule couplerait avec le photon du modèle standard par effet de "kinetic mixing" et pourrait ainsi être émis par l'intermédiaire d'électrons. En utilisant un faisceau d'électron de haute intensité d’un à six GeV envoyé sur une cible de tungstène, HPS cherche à détecter une fine résonance dans le bruit de fond produit par les processus QED qui serait la signature d'un photon lourd. HPS exploitera aussi le fait qu'à très petit couplages, le photon lourd se désintègrera après une distance détectable, fournissant ainsi une seconde signature sous la forme d'un vertex éloigné de la cible. Dans cette thèse, je présente les motivations pour une telle recherche de photon lourd dans ce domaine spécifique de l'espace de phase, puis je présente le spectromètre HPS, en détaillant en particulier le calorimètre électromagnétique qui a été l'un de mes sujets d'étude. Ensuite, je présente mon travail utilisant une intégration Monte-Carlo pour calculer la section efficace des processus QED attendus dans l'expérience HPS. Finalement, je présente dans cette thèse mon analyse de donnée pour la recherche d'un pic sur le bruit de fond QED dans les données acquises au printemps 2015. / The heavy photon search (HPS) experiment in Jefferson Lab (USA) is looking for a new vector gauge boson, called "heavy photon" or "dark photon", in a mass range of 20 MeV to 1000 MeV. Such particle can couple to the standard model photon through kinetic mixing and therefore can be radiated in electron scatterings. Using a high intensity, one to six GeV electron beam sent onto a tungsten target, HPS will look for a narrow resonance above the QED background that would be a signature of a dark photon. HPS will also exploit the fact that for small couplings, this dark photon would also travel a detectable distance before decaying, providing a second signature in the form of a vertex away from the target. In this thesis, I will present the motivations to look for such a dark photon in this particular domain of phase space, then present the HPS spectrometer, with a particular focus on the electromagnetic calorimeter which was a focus of my work. Then, I will present my work using a Monte-Carlo integration to calculate the cross section of the expected background QED processes for the HPS experiment. The final part of my work presented in this thesis will be focused on my data analysis, looking for a bump on the QED background, I carried out using data taken in Spring 2015.