Bacterial Toxin Fusion Proteins Elicit Mucosal Immunity against a Foot-and-Mouth Disease Virus Antigen When Administered Intranasally to Guinea Pigs

Peptides corresponding to the foot-and-mouth disease virus VP1 G-H loop are capable of inducing neutralizing antibodies in some species but are considered relatively poor immunogens, especially at mucosal surfaces. However, intranasal administration of antigens along with the appropriate delivery vehicle/adjuvant has been shown to induce mucosal immune responses, and bacterial enterotoxins have long been known to be effective in this regard. In the current study, two different carrier/adjuvant approaches were used to augment mucosal immunity to the FMDV O1 BFS G-H loop epitope, in which the G-H loop was genetically coupled to the E. coli LT-B subunit and coexpressed with the LTA2 fragment (LTA2B-GH), or the nontoxic pseudomonas exotoxin A (ntPE) was fused to LTA2B-GH at LT-A2 to enhance receptor targeting. Only guinea pigs that were inoculated intranasally with ntPE-LTA2B-GH and LTA2B-GH induced significant anti-G-H loop IgA antibodies in nasal washes at weeks 4 and 6 when compared to ovalbumin or G-H loop immunized animals. These were also the only groups that exhibited G-H loop-specific antigen-secreting cells in the nasal mucosa. These data demonstrate that fusion of nonreplicating antigens to LTA2B and ntPE-LTA2B has the potential to be used as carriers/adjuvants to induce mucosal immune responses against infectious diseases

Bromelain Inhibits Allergic Sensitization and Murine Asthma via Modulation of Dendritic Cells

The incidence of atopic conditions has increased in industrialized countries. Persisting symptoms and concern for drug side-effects lead patients toward adjunctive treatments such as phytotherapy. Previously, we have shown that Bromelain (sBr), a mixture of cysteine proteases from pineapple, Ananas comosus, inhibits ovalbumin (OVA)-induced murine model of allergic airway disease (AAD). However, sBr’s effect on development of AAD when treatment is administered throughout OVA-alum sensitization was unknown and is the aim of the present study. C57BL/6J mice were sensitized with OVA/alum and challenged with 7 days OVA aerosol. sBr 6 mg/kg/0.5 ml or PBS vehicle were administered throughout sensitization. Lung, bronchoalveolar lavage (BAL), spleen, and lymph nodes were processed for flow cytometry and OVA-specific IgE was determined via ELISA. sBr treatment throughout OVA-alum sensitization significantly reduced the development of AAD (BAL eosinophils and lymphocytes). OVA-specific IgE and OVA TET+ cells were decreased. sBr reduced CD11c+ dendritic cell subsets, and in vitro treatment of DCs significantly reduced CD44, a key receptor in both cell trafficking and activation. sBr was shown to reduce allergic sensitization and the generation of AAD upon antigen challenge. These results provide additional insight into sBr's anti-inflammatory and antiallergic properties and rationale for translation into the clinical arena

A matemática financeira no ensino médio : uma nova visão

Dissertação (mestrado)—Universidade de Brasília, Instituto de Ciências Exatas, Departamento de Matemática, Programa de Mestrado Profissional em Matemática em Rede Nacional, 2016.Nesse trabalho é apresentada uma proposta para o desenvolvimento da aprendizagem da Matemática Financeira no 3º ano do Ensino Médio por meio da Educação Financeira, utilizando situações cotidianas e focando num resultado mais significativo na vida do educando. O consumismo e a falta de planejamento se tornaram comum na realidade de grande parte da população. Com o advento da globalização e dos programas sociais do Governo Federal, criou-se a possibilidade de pessoas de quaisquer classes sociais terem acesso a bens de consumo, bem como obtenção de créditos com mais facilidade que outrora o teriam, criando um ciclo consumista. O principal objetivo é proporcionar uma nova visão sobre a matemática levando os alunos a refletirem sobre os diversos ângulos em que podem ser mostrados os assuntos de modo a desenvolver nos alunos uma vontade de aprender e avançar no estudo da Matemática Financeira que podem e devem ser aplicadas no dia-a-dia das pessoas.This work has as objective to present a proposal for the learning development of Financial Mathematics of the 3rd year of high school through Financial Education, using everyday situations and focusing in a more significant result in the student’s life. The consumerism and the lack of planning has become a usual reality of the majority of the population. With the advent of globalization and social programs of the Federal Government, it created the possibility of people from any social class to access consumer goods and to obtain credit more easily than before, creating a consumerist cycle. The main objective is to provide a new insight of mathematics leading students to reflect on the various angles that the subjects can be shown in order to develop in students a desire to learn and advance in Financial Mathematics study that can and should be applied on day-by-day lives

Análise de vida à fadiga sob carregamentos não proporcionais através de modelo de dano contínuo

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Tecnologia, Departamento de Engenharia Mecânica, 2016.Neste trabalho, busca-se utilizar o modelo de dano contínuo de Lemaitre como uma ferramenta de obtenção de vida em fadiga multiaxial para carregamentos proporcionais e não proporcionais. Primeiramente é apresentado o modelo matemático de Lemaitre, em que são formuladas as relações constitutivas necessárias à elaboração do modelo. O modelo de Chaboche foi escolhido para descrever a lei de evolução da tensão de endurecimento cinemático. Em seguida, é desenvolvido o modelo numérico para a solução das equações constitutivas, utilizando a lei de Chaboche com três termos e discretização implícita de Euler. Após, é feita a identificação dos parâmetros constitutivos do modelo para os aços 304 e S460N e para a liga de alumínio 6061-T6. É feita a implementação do modelo em uma rotina em linguagem FORTRAN, a qual é submetida a carregamentos uniaxiais e multiaxiais proporcionais e não proporcionais para cada material. Os dados de vida em fadiga obtidos pelo modelo de Lemaitre são, então, comparados com os dados experimentais disponíveis na literatura. É feita, em seguida, uma análise das amplitudes de tensão obtidas pelo modelo, as quais são comparadas com os dados experimentais. São obtidas, também, curvas de evolução do dano para cada carregamento e material. Os resultados obtidos mostram que o modelo de dano de Lemaitre descreve de maneira adequada o comportamento dos materiais analisados em fadiga de baixo ciclo, quando altas amplitudes de deformação são aplicadas.This project seeks to use Lemaitre’s Continuous Damage Model to obtain fatigue life estimates under multiaxial proportional and non-proportional loadings. Initially, the Lemaitre’s mathematical model is presented, by formulating the necessary constitutive relations. Chaboche’s model was chosen to describe the kinematic hardening law. Then, the numerical model necessary to solve the constitutive relations is developed, utilizing the Chaboche’s law with 3 terms and Euler’s implicit discretization. Then, the material parameters are identified for 304 and S460N steels and 6061-T6 aluminum alloy. The model is implemented in a FORTRAN routine, which is submitted to uniaxial and proportional and non-proportional multiaxial loading histories. The fatigue life data obtained from Lemaitre’s damage model is compared to experimental data. Then, a stress amplitude analysis is conducted and the numerical stresses are compared to experimental data. Damage evolution curves are also obtained for each material and loading. The results show that Lemaitre’s damage model describes adequately the behavior of the analyzed materials under low cycle fatigue, when low strain amplitudes are being applied to the specimen

Comparative genomics of Mycoplasma gallisepticum: Implications for pathogenesis

Mycoplasma gallisepticum causes a significant infectious disease of poultry, which accounts for great losses on commercial farms. Typically, M. gallisepticum induces lesions in the respiratory and reproductive tracts of poultry and is spread both horizontally and vertically. Producers often employ vaccination strategies to control infection, yet little is known about the mechanism(s) of attenuation of the live attenuated vaccines used on these farms. The F strain of M. gallisepticum is commonly used to eradicate field isolates from poultry facilities. To better understand its mechanism(s) of attenuation, we sequenced the complete genome of the F strain and compared it with the previously sequenced virulent Rlow strain to identify genes or loci that are different between these isolates. Among the changes observed, hypothetical gene MGA1107 was missing from the F strain genome. A previous study showed that MGA1107 is up-regulated when Rlow is attached to eukaryotic cells. Taken together, these data implicate MGA1107 as a potential virulence factor of M. gallisepticum. In vivo evaluation of a MGA1107 mutant demonstrated that this gene is essential for virulence in the tracheas of infected chickens, as lesions were similar to those observed in medium inoculated birds, and the organism was not recovered post-challenge. Further examination of the differences between Rlow and the F strain was conducted by comparing their transcriptomes using DNA microarrays. Among the differentially expressed features was hypothetical gene MGA0674. MGA0674 was also identified in previous proteomic studies where it was shown to be an immunogenic, detergent-phase protein which is proteolytically processed into two fragments. In silico analyses indicate that MGA0674 is a lipoprotein which shares conserved domains strictly with other members of the genus Mycoplasma thereby leading to the name Mycoplasma-specific lipoprotein A (mslA). In vivo evaluation of three mslA mutants resulted in reduced lesion scores in chickens compared to those induced by Rlow , indicating that mslA is a virulence factor of M. gallisepticum. These results demonstrate that genomic analyses, combined with virulence assessments in host animals, are useful in the study of Mycoplasma virulence.

Comparative genomics of Mycoplasma gallisepticum: Implications for pathogenesis

Mycoplasma gallisepticum causes a significant infectious disease of poultry, which accounts for great losses on commercial farms. Typically, M. gallisepticum induces lesions in the respiratory and reproductive tracts of poultry and is spread both horizontally and vertically. Producers often employ vaccination strategies to control infection, yet little is known about the mechanism(s) of attenuation of the live attenuated vaccines used on these farms. The F strain of M. gallisepticum is commonly used to eradicate field isolates from poultry facilities. To better understand its mechanism(s) of attenuation, we sequenced the complete genome of the F strain and compared it with the previously sequenced virulent Rlow strain to identify genes or loci that are different between these isolates. Among the changes observed, hypothetical gene MGA1107 was missing from the F strain genome. A previous study showed that MGA1107 is up-regulated when Rlow is attached to eukaryotic cells. Taken together, these data implicate MGA1107 as a potential virulence factor of M. gallisepticum. In vivo evaluation of a MGA1107 mutant demonstrated that this gene is essential for virulence in the tracheas of infected chickens, as lesions were similar to those observed in medium inoculated birds, and the organism was not recovered post-challenge. Further examination of the differences between Rlow and the F strain was conducted by comparing their transcriptomes using DNA microarrays. Among the differentially expressed features was hypothetical gene MGA0674. MGA0674 was also identified in previous proteomic studies where it was shown to be an immunogenic, detergent-phase protein which is proteolytically processed into two fragments. In silico analyses indicate that MGA0674 is a lipoprotein which shares conserved domains strictly with other members of the genus Mycoplasma thereby leading to the name Mycoplasma-specific lipoprotein A (mslA). In vivo evaluation of three mslA mutants resulted in reduced lesion scores in chickens compared to those induced by Rlow , indicating that mslA is a virulence factor of M. gallisepticum. These results demonstrate that genomic analyses, combined with virulence assessments in host animals, are useful in the study of Mycoplasma virulence.

Comparison of the <i>Mycoplasma gentialium model (i</i>PS189) [49] and the model presented in this paper for <i>Mycoplasma gallisepticum</i>.

<p>Comparison of the <i>Mycoplasma gentialium model (i</i>PS189) <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003208#pcbi.1003208-Suthers1" target="_blank">[49]</a> and the model presented in this paper for <i>Mycoplasma gallisepticum</i>.</p