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Analysis of physical constraints in an optical burst switching networkBuchta, Hao. Unknown Date (has links) (PDF)
Techn. University, Diss., 2005--Berlin.
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L’Eclat du voyage : Blaise Cendrars, Victor Segalen, Albert Londres / A Burst of Travel : Blaise Cendrars, Victor Segalen, Albert LondresPoizat-Amar, Mathilde 06 November 2015 (has links)
La thèse explore les œuvres de Blaise Cendrars, de Victor Segalen et d’Albert Londres sous l’angle de « l’éclat du voyage » et se propose d’analyser les effets produits par la présence du voyage sur un plan diégétique, métadiégétique et stylistique. Chez ces trois auteurs, la notion de voyage dépasse en effet sa vocation thématique pour se faire véritable matière à travailler le langage et atteindre la sphère de la littérarité en exerçant sur le texte une menace d’éclatement, et contribue à l’instauration d’une littérature moderne. Cette étude interroge les premiers écrits de Cendrars (1912-1938) en explorant par quelles voies la présence conjointe du motif du voyage et de l’éclatement conduit à la création d’une représentation fractale du monde. L’examen du cycle polynésien de Segalen met en évidence la présence du voyage comme le résultat d’un écart désirant qui aboutit à la formation d’une poétique littéraire de la diffraction. Enfin, à travers l’étude des reportages d’Albert Londres, la thèse montre comment l’écriture du voyage trouve un regain de force par le détour du reportage. / This thesis explores the bursting effect of travel in the works of Blaise Cendrars, Victor Segalen and Albert Londres in their diegetic, metadiegetic and stylistic aspects. The notion of travel goes beyond a mere theme discussed in those texts and affects their very language, challenges their literarity by issuing a bursting threat on them, and contributes to their modernity.This study examines the first works of Blaise Cendrars (1912-1938) and explores the ways in which the joined presence of travel and bursting phenomenon leads to a literary creation of a fractal world. The study of Segalen’s Polynesian period reveals that travel exists as an outcome of a distance invested by desire, and results in a poetic of diffraction in his texts. Finally, the investigation of the role of travel in Albert Londres’ reportages illuminates how travel writing and reportage can work together towards a modern literature.
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A Targeted LIGO-Virgo Search for Gravitational Waves Associated with Gamma-Ray Bursts Using Low-Threshold Swift GRB TriggersHarstad, Emelie 11 July 2013 (has links)
Gamma-ray bursts (GRBs) are short, intense flashes of 0.1-1 MeV electromagnetic radiation that are routinely observed by Earth orbiting satellites. The sources of GRBs are known to be extragalacitic and located at cosmological distances. Due to the extremely high isotropic equivalent energies of GRBs, which are on the order of Eiso~1054 erg, the gamma-ray emission is believed to be collimated, making them observable only when they are directed towards Earth. The favored progenitor models of GRBs are also believed to emit gravitational waves that would be observable by the current generation of ground-based interferometric gravitational wave detectors. The LIGO (Laser Interferometer Gravitational-Wave Observatory) and Virgo instruments operated near design sensitivity and collected more than a year of triple coincident data during the S5/VSR1 science run, which spanned the two year interval between November 2005 and October 2007. During this time, GRB detections were being made by the NASA/Goddard Swift Burst Alert Telescope at a rate of approximately 0.3 per day, producing a collection of triggers that has since been used in a coincident GRB-GW burst search with data from the LIGO-Virgo interferometer network. This dissertation describes the search for gravitational waves using the times and locations of 123 below-threshold potential GRB triggers from Swift over the same time period. Although most of the below-threshold triggers are likely false alarms, there is reason to believe that some are the result of actual faintly-observed GRB events. Recent GRB observations indicate that the local rate of low-luminosity GRBs is much higher than previously believed. This result, combined with the possibility of discovering a rare nearby GRB event accompanied by gravitational waves, is what motivates this search. The analysis results indicate no evidence for gravitational waves associated with any of the below-threshold triggers. A median distance lower limit of ~16 Mpc was derived for a typical neutron star-black hole coalescence progenitor assumption.
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Combinaison des aspects temps réel et sûreté de fonctionnement pour la conception des plateformes avioniques / Combination of real-time and safety aspects for the design of avionic platformsMany, Florian 18 February 2013 (has links)
La conception des plateformes aéronautiques s’effectue en tenant compte des aspects fonctionnels et dysfonctionnels prévus dans les scénarios d’emploi des aéronefs qui les embarquent. Ces plateformes aéronautiques sont composées de systèmes informatiques temps réel qui doivent à la fois être précises dans leurs calculs, exactes dans l’instant de délivrance des résultats des calculs, et robustes à tout évènement pouvant compromettre le bon fonctionnement de la plateforme.Dans ce contexte, ces travaux de thèse abordent les ordonnancements temps réel tolérants aux fautes. Partant du fait que les systèmes informatiques embarqués sont perturbés par les ondes électromagnétiques des radars, notamment dans la phase d’approche des aéronefs, ces travaux proposent une modélisation des effets des ondes, dite en rafales de fautes. Après avoir exploré le comportement de l’ordonnanceur à la détection d’erreurs au sein d’une tâche, une technique de validation, reposant sur le calcul de pire temps de réponse des tâches, est présentée. Il devient alors possible d’effectuer des analyses d’ordonnançabilité sous l’hypothèse de la présence de rafales de fautes. Ainsi, cette technique de validation permet de conclure sur la faisabilité d’un ensemble de tâches en tenant compte de la durée de la rafale de fautes et de la stratégie de gestion des erreurs détectées dans les tâches.Sur la base de ces résultats, les travaux décrits montre comment envisager l’analyse au niveau système. L’idée sous-jacente est de mettre en évidence le rôle des ordonnancements temps réel tolérants aux fautes dans la gestion des données erronées causées par des perturbations extérieures au système.Ainsi, le comportement de chaque équipement est modélisé, ainsi que les flots de données échangés et la dynamique du système. Le comportement de chaque équipement est fonction de la perturbation subie, et donne lieu à l’établissement de la perturbation résultante, véritable réponse dysfonctionnelle de l’équipement à une agression extérieure. / The design of avionic platforms takes into account the functional and dysfunctional aspects, which depend on the aircraft operation concept. These avionic platforms embed computer resources that must produce accurate results at the right time, and must be dependable whatever the disturbance.In this specific context, we address the topic of fault tolerant real time scheduling. Since the embedded computer resources are disturbed by electromagnetic waves produced by radar, especially during the aircraft approach, we suggest a model of these wave effects named fault bursts. Afterthe analysis of scheduler behaviour when an error is dectected inside a task, we present a validation technique based on the evaluation of the worst case response time. By this way, we are able to study the task set feasibility under fault burst assumption and according to the error recovery strategy.Then, based on these results, we show a way to analyse the effects of disturbances such as electromagnetic waves at system level. The underlining idea is to demonstrate the main role of fault tolerant real time scheduler in the management of erroneous data. To do that, we suggest an equipment model which integrates the behaviour of the equipement when a disturbance occurs. We also describe thedata flows in order to describe the avionics platform dynamics.
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Determinação dos genótipos para o polimorfismo dos receptores de IgG, FcγRlla (H/R131) e FcγRIIIb (NA1/NA2), e estudo do burst oxidativo dos neutrófilos em indivíduos infectados pelo HIV e/ou Mycobacterium tuberculosisFaria, Carolina Maria Quinello Gomes de [UNESP] 18 February 2011 (has links) (PDF)
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faria_cmqg_me_arafcf.pdf: 1839645 bytes, checksum: 622ea7e8a83cf33004224bc20f5561fb (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Universidade Estadual Paulista (UNESP) / A infecção pelo vírus da imunodeficiência humana (HIV) ocorre com aumento dos níveis de anticorpos séricos e com grande quantidade de imunocomplexos circulantes. A associação entre as disfunções da fagocitose mediadas por receptores do tipo FcR, na infecção pelo HIV e, principalmente, na co-infecção com o Mycobacterium tuberculosis, têm sido amplamente descrita na literatura científica. A tuberculose (TB) é a infecção oportunista mais comum entre pacientes infectados pelo HIV e a causa de morte mais frequente entre os pacientes com a síndrome da imunodeficiência adquirida (AIDS). Sabe-se que a infecção pelo HIV torna o paciente susceptível às infecções oportunistas, como a tuberculose, e, essas co-infecções aumentam o potencial de replicação viral. A ineficiência do mecanismo de clearance de imunocomplexo (IC) e de fagocitose pode contribuir para o aumento da suscetibilidade às infecções oportunistas em indivíduos infectados pelo HIV. Sendo assim, a determinação dos genótipos para as variantes polimórficas funcionais dos receptores para a porção Fc da imunoglobulina de classe G (FcR), bem como das combinações dos diferentes genótipos, pode constituir um marcador importante para a patogênese da infecção pelo HIV, na co-infecção pelo M. tuberculosis e em infecções pelo M. tuberculosis isoladamente, ou seja, independente da infecção pelo vírus da AIDS. Desta forma, o objetivo deste estudo foi determinar os genótipos para os polimorfismos dos receptores FcRIIa (CD32; H/R131) e FcRIIIb (CD16; NA1/NA2) em portadores da infecção pelo HIV-1, co-infectados pelo M. tuberculosis e infectados apenas pelo M. tuberculosis, assim como a avaliação da função fagocítica através do burst oxidativo (formação de espécies reativas de oxigênio - EROs) induzido por polissacarídeos... / Infection with human immunodeficiency virus (HIV) occurs along with increased levels of serum antibodies and a large amount of circulating immune complexes. The association between FcR-dependent phagocytosis dysfunction in HIV infection and, especially, when in co-infection with Mycobacterium tuberculosis, has been widely described in scientific literature. Tuberculosis (TB) is the most common opportunistic infection among HIV-infected patients and the most frequent cause of death among patients with acquired immunodeficiency syndrome (AIDS). It is known that HIV infection makes the patient susceptible to opportunistic infections such as tuberculosis, and these co-infections increase the potential for viral replication. The inefficiency of the immune complex (IC) clearance mechanism and phagocytosis may contribute to increased susceptibility to opportunistic infections in HIV-infected individuals. Thus, determination of the functional polymorphic variants‟ genotypes for class G immunoglobulin Fc receptors (FcR) as well as combinations of different genotypes may be an important marker for the pathogenesis of HIV infection, for co- infection with M. tuberculosis and for M. tuberculosis infection alone, i.e. independent of infection with AIDS virus. Thus, the aim of this study was to determine the genotypes for FcRIIa (CD32; H/R131) and FcRIIIb (CD16; NA1/NA2) polymorphisms in patients carrying HIV-1 infection, co-infected with M. tuberculosis and infected with M. tuberculosis alone, as well as evaluating the phagocytic function via oxidative burst (formation of reactive oxygen species - ROS) induced by cell wall polysaccharides from Saccharomyces cerevisiae, known as zymosan, in peripheral blood neutrophils from these patients. Our results demonstrated reduced capacity... (Complete abstract click electronic access below)
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Identifying Explosive Transients and Implications for Gravitational Wave FollowupJanuary 2017 (has links)
abstract: High-energy explosive phenomena, Gamma-Ray Bursts (GRBs) and Supernovae (SNe), provide unique laboratories to study extreme physics and potentially open up the new discovery window of Gravitational-wave astronomy.
Uncovering the intrinsic variability of GRBs constrains the size of the GRB emission region, and ejecta velocity, in turn provides hints on the nature of GRBs and their progenitors. We develop a novel method which ties together wavelet and structure-function analyses to measure, for the first time, the actual minimum variability timescale, Delta t_min, of GRB light curves. Implementing our technique to the largest sample of GRBs collected by Swift and Fermi instruments reveals that only less than 10% of GRBs exhibit evidence for variability on timescales below 2 ms. Investigation on various energy bands of the Gamma-ray Burst Monitor (GBM) onboard Fermi shows that the tightest constraints on progenitor radii derive from timescales obtained from the hardest energy channel of light curves (299--1000 keV). Our derivations for the minimum Lorentz factor, Gamma_min, and the minimum emission radius, R = 2c Gamma_min^2 Delta t_min / (1+z), find Gamma < 400 which imply typical emission radii R ~ 1 X 10^14 cm for long-duration GRBs and R ~ 3 X 10^13 cm for short-duration GRBs (sGRBs).
I present the Reionization and Transients InfraRed (RATIR) followup of LIGO/Virgo Gravitational-wave events especially for the G194575 trigger. I show that expanding our pipeline to search for either optical riZ or near-infrared YJH detections (3 or more bands)
should result in a false-alarm-rate ~1% (one candidate in the vast 100 deg^2 LIGO error region) and an efficiency ~90%.
I also present the results of a 5-year comprehensive SN search by the Palomar Transient Factory aimed to measure the SN rates in the local Luminous Infrared Galaxies. We find that the SN rate of the sample, 0.05 +/- 0.02 1/yr (per galaxy), is consistent with that expected from the theoretical prediction, 0.060 +/- 0.002 1/yr (per galaxy). / Dissertation/Thesis / Doctoral Dissertation Astrophysics 2017
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Atividade funcional de polimorfonucleares do sangue de bezerros neonatos versus Escherichia coli \"in vitro\": influência do volume de colostro mamado e da idade / Neonatal calves blood polymorphonuclear activities versus Escherichia coli \"in vitro\": colostrum volume intake and calf age influencesElizabeth Bohland 30 May 2008 (has links)
O objetivo foi avaliar a atividade funcional dos polimorfonucleares (PMN) do sangue de bezerros neonatos \"in vitro\" - metabolismo oxidativo induzida por: S. aureus, E. coli e PMA e fagocitose para S. aureus e E. coli, em citômetro de fluxo. Quinze animais avaliados nos tempos: t0 (antes da ingestão de colostro/leite); t1(até 48 hs. p.n); t2 (48 - 96 hs. p.n.); t3 (96 - 144 hs. p.n.); t4 (144-192 hs. p.n.); t5 (192-240 hs.p.n.) receberam quatro litros (grupo 1 - G1), dois litros de colostro ( grupo 2 - G2) e somente leite (grupo 3 - G3). O metabolismo oxidativo basal não diferiu em nenhum dos grupos e idades. Entre os grupos este foi menor em G1 do que em G3 (t3). Induzido pela S. aureus foi maior entre t1 e t3 (grupo 1), entre t2 e t3 (grupo 2) e sem diferenças (grupo 3). Entre os grupos G1 foi maior que G3 (t1). Induzido pela E.coli foi maior entre t1 e t3 (grupo 1), maior em t2 (grupo 2) e sem diferenças (grupo 3). Entre os grupos G1 foi maior que G2 e G3 (t1). O PMA estimulou a explosão respiratória em G1, G2 e G3 entre t0 e t5. Entre os grupos G1 foi menor para do que G2 e G3. A comparação entre metabolismo basal e induzido para G1 foi maior para PMA e S. aureus entre t0 e t5 e para E. coli entre t1 e t5; para G2 foi maior para o PMA entre t0 e t5, para S. aureus entre t0 e t3 e para a E. coli entre t2 e t4; para G3 foi maior para o PMA e S.aureus entre t0 e t5 e para a E. coli entre t3 e t5. A fagocitose induzida pela S. aureus foi maior nos tempos t1, t2 e t4 (grupo1) e o percentual de fagocitose foi maior após t0; para o grupo 2, foi maior em t2 e t3 e o percentual foi maior após t0; para o grupo 3, não diferiram entre os tempos. Entre os grupos G1 foi maior que G2 e G3 (t4) e o percentual foi maior para G1 e G2 (t3) do que G3 e maior para G1 do que G2 (t5). A fagocitose induzida pela E. coli e o percentual de fagocitose não diferiram em nenhum grupo. Entre os grupos G1 foi maior do que G3 (t0) e o percentual foi maior para G1 do que G2 (t2). Conclusão: o colostro não interferiu no metabolismo oxidativo basal e estimulado pelo PMA, a S. aureus estimulou o metabolismo oxidativo e a fagocitose antes e após a ingestão de colostro. A E. coli não induziu o metabolismo oxidativo (G3) e não foi eficiente para estimular a fagocitose. Não ficou esclarecida a influência da idade sobre a atividade dos PMNs. O fornecimento de quatro litros de colostro melhora resposta funcional dos PMNs para as bactérias. / The aim of this study was to evaluate \"in vitro\" functional activities of neonatal calves blood polymorphonuclear leukocytes (PMNs) - respiratory burst and phagocytosis induced by S.aureus, E.coli and PMA, measured by flow cytometry. Fifteen calves were tested at times: t0 (before milk/colostrum ingestion); t1 (until 48 hours post partum); t2 (48-96 hrs p.p.); t3 (96 - 144 hrs. p.p.); t4 (144-192 hrs. p.p.); t5 (192-240 hrs. p.p.) and the groups intakes were 4 liters of colostrum (group 1), 2 liters of colostrum (group 2) and only milk (group 3). The basal respiratory burst did not differ among groups but it was lower in G1 than G3 (t3). The burst induced by S.aureus was higher between t1 and t3 (G1) and t2 and t3 (G2) and showed no difference (G3). The G1 values were higher than G3 (t1). E.coli induced higher values between t1 and t3 (G1), higher on t2 (G2) and showed no difference (G3). Among groups G1 was higher than G2 and G3 (t1). The PMA induced the respiratory burst in G1, G2 and G3 between t0 and t5. Among groups G1 was lower in G2 than G3. The induced basal metabolism was compared and G1 was higher to PMA and S.aureus between t0 and t5 and to E.coli between t1 and t5. The G2 showed higher values to PMA between t0 and t5, to S.aureus between t0 and t3 and E.coli between t2 and t4. The G3 showed higher values in PMA and S.aureus between t0 and t5 and E.coli between t3 and t5. The S.aureus induced phagocytosis was higher on t1, t2 and t4 (G1) and the phagocystosis percentage was higher after t0. G2 groups showed higher values on t2 and t3 and higher percentage after t0. G3 had no difference on times. G1 showed higher values than G2 and G3 (t4) and G1 and G2 (t3) had higher percentage than G3 with G1 higher than G2 (t5). The E.coli induced phagocytosis and its percentage did not differ among groups. G1 was higher than G3 (t0) and G1 showed higher phagocytosis percentage than G2 (t2). Conclusion: the colostrum did not affect either, the basal respiratory burst and the one stimulated by PMA. S. aureus stimulated the respiratory burst and phagocytosis before and after the colostrum intake. E.coli did not induce the respiratory burst (G3) and did not stimulate the phagocytosis. The age influence in PMNs activity was not totally clarified. The intake of 4 litters of colostrum increases the PMNs activity against the species of bacteria studied.
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Correlação entre viscosidade e propriedades mecânicas de polpas kraft em sequências de branqueamento livres de cloro elementar / Correlation between viscosity and mechanical properties of kraft pulps in elemental chlorine free bleaching sequencesFerraz, Ana Paula Almeida 27 February 2018 (has links)
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Previous issue date: 2018-02-27 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O presente estudo tem por objetivo elucidar sobre a correlação entre a viscosidade e as propriedades mecânicas da polpa. O material utilizado foi uma amostra de Eucalyptus grandis x Eucalyptus urophylla. Os cavacos foram submetidos a cozimentos com tempos de polpação de 90 e 120 minutos. Para as polpas produzidas com tempo de 90 minutos, realizou-se a deslignificação com oxigênio com temperatura de 95°C e para as polpas produzidas com o tempo de 120 minutos, a temperatura do estágio de deslignificação com oxigênio foi de 115°C, objetivando uma maior diferença de viscosidade entre as amostras. Ambas as polpas foram branqueadas a partir das sequências ECF OD(E+P)DD, OAHTD(E+P)DP e OD(E+P)(PO). Posteriormente as polpas foram refinadas em moinho PFI e avaliadas quanto ao índice de rasgo, tração e arrebentamento, segundo as normas da TAPPI (Technical Association of the Pulp and Paper Industry). Os resultados indicam que o aumento do tempo de cozimento em 30 minutos e aumento da temperatura da deslignificação com oxigênio de 95°C para 115°C afetam significativamente a viscosidade da polpa. O refino foi afetado pela diminuição da viscosidade das sequências produzidas com deslignificação com oxigênio à temperatura de 115°C. O índice de rasgo apresentou decréscimo quanto menor a viscosidade da polpa em todas as sequências de branqueamento deste estudo. Os índices de tração e arrebentamento apresentaram decréscimo de acordo com a diminuição da viscosidade em uma mesma sequência, entretanto, quando a comparação foi feita entre diferentes sequências de branqueamento, não houve relação entre os índices de tração e de arrebentamento com a viscosidade da polpa. / This study aims to elucidate the correlation between the viscosity and the mechanical properties of the pulp. The material used was a sample of Eucalyptus grandisx Eucalyptus urophylla. The chips were cooked with cooking times of 90 and 120 minutes. For the pulps produced in 90 minutes, the delignification with oxygen at temperature of 95ºC was performed and for the pulps produced in 120 minutes, the temperature of the oxygen delignification stage was 115ºC, aiming a greater difference of viscosity between the samples. Both pulps were bleached from the sequences ECF OD(E+P)DD, OD(E+P)(PO) and OAHTD(E+P)DP. Later, the pulps were refined in PFI mill and assessed for the tear, tensile and burst indexes, according to the TAPPI (Technical Association of the Pulp and Paper Industry) standards. The results indicate that the increase of cooking time in 30 minutes and the increase of temperature in oxygen delignification from 95°C to 115°C affect significantly the pulp viscosity. The refining was affected by the viscosity reduction of the sequences produced with delignification with oxygen at temperature of 115ºC. Tear index decreased as the pulp viscosity was lower, in all the bleaching sequences. Tensile and burst indexes presented decrease with the decrease of the viscosity in the same sequence, however, when comparing different bleaching sequences, there was no relation between the tensile and burst indexes with the pulp viscosity.
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Dinâmica da resposta imune inata do sistema respiratório de bezerros / Dynamic of the innate immune response of the respiratory system in calvesCamila Freitas Batista 08 July 2011 (has links)
As influências etárias do sistema imune de bezerros são descritas na primeira fase de vida desses animais e a hipótese de também ocorrerem ariações nos principais mecanismos de resposta inata do pulmão pode identificar períodos de maior suscetibilidade às principais doenças respiratórias que acometem os bezerros nesse período. Com a finalidade de minimizar os prejuízos econômicos associados às doenças respiratórias em bezerros, este estudo objetivou avaliar a dinâmica imunológica inata do sistema respiratório de bezerros sadios nos três primeiros meses de vida, no qual nove bezerros sadios foram acompanhados por três meses e submetidos a oito avaliações imunológicas. O material recuperado do lavado broncoalveolar colhido por broncoscopia foi submetido à avaliação funcional dos macrófagos alveolares utilizando as provas de fagocitose (SaPI e E.coli), burst oxidativo, quantificação de imunoglobulinas e expressão de CD14. Os dados foram avaliados pelo teste ANOVA oneway (unstacked) (paramétricos) e pelo teste Mann-Whitney (não paramétricos). Verificaramse alterações funcionais de fagócitos CD14+, que apesar de se manterem constantes em seus valores relativos durante todo o período, apresentou intensidade de fagocitose elevada pontual na terceira semana de vida e um aumento da fagocitose por mononucleares CD14+ aos 45 dias de idade com diminuição da intensidade da fagocitose por essas mesmas células a partir dessa idade. Conclui-se que a partir de 45 dias de vida os animais começam a montar uma resposta imune própria, porém pontual e que até os 90 dias não atingem a estabilidade necessária para atestar a conclusão do processo de maturação da resposta inata local. / The influences of age in calves\' immune system are described in their first phase of life. The hypothesis that variations occur in the main mechanisms of lung innate response can help to identify periods of greater susceptibility to the respiratory diseases that affect calves in the first stage of their life. With the purpose of minimizing the economic losses associated with respiratory disease in calves, this study aimed to evaluate the innate immune dynamics of the respiratory system of healthy calves in the first three months of life. Nine healthy calves were monitored for three months and eight immunologic evaluations were performed. Bronchoalveolar lavage samples were recovered by bronchoscopy. Then, the alveolar macrophages in samples were identified by protein expression of CD14 and undergone functional evaluation of phagocytosis (SAPI and E.coli) and oxidative burst. Immunoglobulin were also quantified in samples. Data was assessed by one-way ANOVA (unstacked) (parametric) and the Mann-Whitney test nonparametric). Functional alterations in phagocytes CD14 + were observed, and although their relative values were kept throughout the period, higher intensity of phagocytosis in the third week and increased phagocytosis by macrophages CD14 + at 45 days of life was observed. Decreased intensity of phagocytosis was observed after this age. It is concluded that from 45 days of life on, calves began to maintain their immune response, but until 90 days of life they did not achieve the stability to conclude the maturation of local innate response.
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Ativação dos neutrófilos de pacientes com lúpus eritematoso sistêmico sobre células endoteliais in vitro: implicações na lesão tecidual mediada por imunocomplexos / Activation of neutrophils from patients with systemic lupus erythematosus on endothelial cells in vitro: implications for tissue injury mediated by immune complexesLeandro Sobrinho Avila 15 December 2016 (has links)
O lúpus eritematoso sistêmico (LES) é uma doença autoimune e protótipo das doenças por imunocomplexos (IC). A deposição de IC em tecidos ou órgãos leva a um processo inflamatório crônico, que resulta em lesão tecidual. A fisiopatologia deste processo envolve principalmente o sistema do complemento (SC), receptores de IgG (Fc?R), neutrófilos e moléculas de adesão. Os produtos de ativação SC atraem os neutrófilos para o foco inflamatório e sua interação com os IC depositados resulta na liberação de espécies reativas de oxigênio (ERO) e das enzimas dos neutrófilos sobre os tecidos. As ERO podem levar a danos nas estruturas celulares devido ao estresse oxidativo, resultando na exposição de autoantígenos e sustentação da autoimunidade. Várias anormalidades envolvendo neutrófilos, função e expressão dos Fc?R e CR foram descritas no LES. O objetivo deste estudo foi avaliar se essas alterações podem ter implicações para o dano tecidual através do depósito de IC. Devido à importância das interações neutrófilo-endotélio-SC para a inflamação e lesão tecidual por IC no LES, este estudo propôs avaliar o efeito da ativação de neutrófilos e produtos do SC sobre as células endoteliais in vitro. Os resultados mostram que a exposição das células endoteliais aos neutrófilos/LES ativo, sem estímulo, resulta em maior peroxidação lipídica comparada com o controle espontâneo, o que não foi observado com neutrófilos/saudáveis. Contudo, na presença de IC/SHN, a peroxidação lipídica foi maior quando as células endoteliais foram expostas aos neutrófilos/LES inativo comparada ao controle espontâneo. O efeito da ativação dos neutrófilos, em todos os grupos, sobre a peroxidação lipídica das células endoteliais foi dependente da opsonização dos IC pelo complemento (IC/SHN), uma vez que não foi observado quando as proteínas do complemento foram inativadas (IC/SHI). Não houve diferença na produção de ERO entre os neutrófilos dos grupos estudados. Observou-se menor expressão dos Fc?RIIa (CD32) e CR1 em neutrófilos/LES ativo, quando comparados com o grupo controle. Houve maior liberação de catalase pelos neutrófilos/LES, quando estes foram estimulados via Fc?R, e maior produção de glutationa por neutrófilos/LES inativo quando estas células foram estimuladas via Fc?R e CR. A expressão de ICAM-1 não foi diferente entre os grupos de neutrófilos, entretanto foi menor na ausência de complemento. Não houve diferença na medida da ativação da via clássica do complemento avaliada pelo fragmento C4d. Estes resultados mostram que as células endoteliais são mais suscetíveis à peroxidação lipídica na presença de neutrófilos/LES. Contudo, quando o complemento do soro é inativado, esta suscetibilidade desaparece, bem como há menor liberação de ICAM-1 por todos os grupos de neutrófilos e maior liberação de catalase por neutrófilos/LES. A interação dos neutrófilos/LES com células endoteliais pode ser deletéria para este último e depender da atividade das proteínas do sistema complemento. O modelo desenvolvido neste estudo pode contribuir para a compreensão do envolvimento dos neutrófilos e do SC nas lesões teciduais no LES. / Systemic lupus erythematosus (SLE) is an autoimmune disease and prototype of immune complex diseases (IC). The deposition of IC in tissues or organs leads to a chronic inflammatory process, which results in tissue injury. The pathophysiology of this process mainly involves the complement system (SC), IgG (Fc?R) receptors, neutrophils and adhesion molecules. SC activation products attract neutrophils to the inflammatory focus and their interaction with deposited IC results in the release of reactive oxygen species (ROS) and neutrophil enzymes into tissues. ROS can lead to damage to cell structures due to oxidative stress, resulting in the exposure of autoantigens and the support of autoimmunity. Several abnormalities involving neutrophils, function and expression of Fc?R and CR have been described in SLE. The aim of this study was to assess whether these changes may have implications for tissue damage through the deposition of IC. Due to the importance of neutrophil-endothelial-SC interactions for inflammation and tissue damage by IC in SLE, this study proposed to evaluate the effect of the activation of neutrophils and SC products on endothelial cells in vitro. The results show that exposure of endothelial cells to active neutrophils / SLE without stimulus results in higher lipid peroxidation compared to spontaneous control, which was not observed with neutrophils / healthy. However, in the presence of IC / complement from normal human serum (NHS), lipid peroxidation was greater when endothelial cells were exposed to inactive neutrophils / SLE compared to spontaneous control. The effect of neutrophil activation in all groups on endothelial cell lipid peroxidation was dependent on IC with complement (IC / NHS), as it was not observed when complement proteins were inactivated (IC / INHS). There was no difference in ROS production among the neutrophils of the studied groups. Lower expression of Fc?RIIa (CD32) and CR1 in active neutrophils / SLE, when compared with the control group, was observed. There was greater release of catalase by neutrophils / SLE, when they were stimulated via Fc?R, and increased production of glutathione by neutrophils / inactive SLE when these cells were stimulated via Fc?R and CR. There was no difference in expression of ICAM-1 between the neutrophil groups, however it was lower in the absence of complement. There was no difference in the extent of the activation of the classical complement pathway evaluated by the C4d fragment. These results show that endothelial cells are more susceptible to lipid peroxidation in the presence of neutrophils / SLE. However, when serum complement is inactivated, this susceptibility disappears, as well as there is a lower release of ICAM-1 by all neutrophil groups and greater release of catalase by neutrophils / SLE. The interaction of neutrophils / SLE with endothelial cells may be deleterious to the latter and depends on the activity of the complement system proteins. The model developed in this study may contribute to the understanding of neutrophil and SC involvement in tissue lesions in SLE.
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