Malaria is a widespread parasitic disease, causing 300-500 million infections per year and resulting in over 1 million deaths. There is widespread resistance of the parasite to most of the antimalarial treatments available, indicating the need for a vaccine (http://www.rbm.who.int/wmr2005/). The translationally controlled tumour protein (TCTP) family are highly conserved eukaryotic proteins that have been assigned a variety of functions. While most studies have focused on the intracellular functions of TCTP, human, malarial and other parasitic TCTPs have also been reported to have extracellular functions in the induction of histamine release from immune cells (e.g. MacDonald et al., 2001; Rao et al., 2002). Malarial TCTP has been detected in the sera of malaria-infected individuals (MacDonald et al., 2001) and is also known to bind to the antimalarial drug artemisinin (Bhisutthibhan et al., 1998). In this study, TCTP was investigated as a malarial vaccine candidate due to a previously observed protective effect in mice infected with Plasmodium yoelii YM. In that study, PfTCTP immunisation conferred a significant delay in disease progression, as judged by reduced parasitemia and prolonged survival (Taylor, 2002). It was thought that the protective effect might have been due to the inhibition of the extracellular actions of malarial TCTP by the acquired host immune response. P. falciparum and P. yoelii TCTP were initially expressed in S. cerevisiae, as in the previous study. The recombinant proteins were used to vaccinate mice, which were then challenged with two strains of P. yoelii. No protective effect was observed for either vaccine, and so the previous results using PfTCTP could not be confirmed. The TCTP of P. yoelii and P. berghei were then expressed in E. coli, which increased yield and decreased proteolysis. The recombinant proteins were used as vaccines in mice challenged with P. yoelii YM, P. c. chabaudi AS, or P. berghei ANKA. A significant delay in disease progression was observed in PyTCTP-immunised mice challenged with the non-lethal P.c. chabaudi, as determined by a significantly reduced parasitemia at each day post-infection leading up to a delayed peak parasitemia. A significant reduction in parasitemia was also observed in the early stages of P. yoelii YM infection in PyTCTP-immunised mice. P. berghei ANKA was used to challenge C57BL/6 mice to determine whether PbTCTP immunisation could protect mice from cerebral malaria development, no protective effect was observed. P. berghei ANKA was also used as a second lethal malaria challenge model in BALB/c mice, no significant differences in disease progression were observed in immunised mice. To further assess the functions of malarial TCTP, several attempts were made to create a TCTP-knockout strain of P. berghei ANKA. A TCTP-knockout malaria strain could be assessed for alterations in morphology, infectivity and artemisinin sensitivity compared with wild-type parasites. Initial genotype analysis of parasites resulting from several transfection experiments indicated that TCTP disruption had been successful, however TCTP-disrupted parasites were strongly selected against, and stable knockout strains could not be obtained. This indicates that TCTP performs an important role within the malaria parasite.

Os estímulos evento-relacionados (event-related functional magnetic resonance imaging - ER-fMRI) têm se tornado mais popular nos últimos anos. A maioria das análises das séries temporais geradas nesses exames é baseada em um modelo específico da função resposta hemodinâmica, hemodinamic response function (HRF). Contudo, a considerável variabilidade da HRF e a baixa relação sinal ruído das imagens, tem dificultado sua caracterização e localização. Neste sentido, recentemente foi proposto um método baseado na computação da entropia de Shannon, que não faz suposição sobre a forma da resposta. Desse modo, no presente trabalho, buscou-se, em um primeiro momento, avaliar alguns parâmetros do método proposto a fim de aumentar sua sensibilidade. Além disso, generalizou-se o método com a entropia de Tsallis, que introduz um novo parâmetro, q. Foi proposto, também, um novo método baseado no cálculo da distância de Kullback-Leibler (KL). Todos os métodos foram aplicados a dados simulados e dados reais. Curvas ROC (Receiver Operating Characteristic) foram usadas para estudar a dependência dos valores de corte e os diferentes parâmetros dos métodos em relação à sensibilidade e especificidade. A entropia de Tsallis apresentou maior poder de detecção nos intervalos de -1 < q < 1 (q diferente de 0) com dois níveis. O método de KL mostrou uma melhora significativa da sensibilidade em dados simulados e apresentou a habilidade em discriminar regiões funcionais ativas e em repouso, para um estímulo motor. Por fim, foi proposta uma primeira tentativa de identificar simultaneamente duas regiões cerebrais não correlacionadas no tempo e no espaço com os métodos de Tsallis e KL-fMRI em um experimento de estímulo duplo (visual e motor). Além disso, um novo método mostrou-se eficiente, ainda que de forma preliminar, para detectar o atraso temporal de duas HRFs. / Event-related functional magnetic resonance imaging (ER-fMRI) has become more popular in the last years. Most of analysis applied to such exams is based on a specific model of the hemodynamic response function (HRF). However, the variability of HRF and the low signal-to-noise ratio of such exams have imposed interesting challenges to both characterization and localization of the HRF. Recently, it was proposed a method based on computation of Shannon entropy, which makes no assumption about the shape of the response. We herein evaluated some parameters of the previous method in order to increase its sensibility. Moreover, this method was generalized with Tsallis entropy, which introduces a new parameter, q. Besides, a new method was proposed based on a distance of Kullback- Leibler (KL) measurement. Every method was applied to simulated and real data. Receiver Operating Characteristic curves were used to study the threshold dependence and the different methods parameters related to sensitivity and specificity. Tsallis entropy showed high detection power in the intervals -1 < q < 1 (q different from 0) with two bins. The KL method allowed significant improvement of sensibility in simulated data and reviewed the ability to discriminate regions of functional activity and rest in a motor stimulus. Finally, it was proposed a new technique to identify two brain regions without correlation in time and space through Tsallis and KL-fMRI methods, in a experiment of double stimuli (visual and motor). Furthermore, in a preliminary study, we developed a strategy to detect temporal delay between two HRFs.

Os estímulos evento-relacionados (event-related functional magnetic resonance imaging - ER-fMRI) têm se tornado mais popular nos últimos anos. A maioria das análises das séries temporais geradas nesses exames é baseada em um modelo específico da função resposta hemodinâmica, hemodinamic response function (HRF). Contudo, a considerável variabilidade da HRF e a baixa relação sinal ruído das imagens, tem dificultado sua caracterização e localização. Neste sentido, recentemente foi proposto um método baseado na computação da entropia de Shannon, que não faz suposição sobre a forma da resposta. Desse modo, no presente trabalho, buscou-se, em um primeiro momento, avaliar alguns parâmetros do método proposto a fim de aumentar sua sensibilidade. Além disso, generalizou-se o método com a entropia de Tsallis, que introduz um novo parâmetro, q. Foi proposto, também, um novo método baseado no cálculo da distância de Kullback-Leibler (KL). Todos os métodos foram aplicados a dados simulados e dados reais. Curvas ROC (Receiver Operating Characteristic) foram usadas para estudar a dependência dos valores de corte e os diferentes parâmetros dos métodos em relação à sensibilidade e especificidade. A entropia de Tsallis apresentou maior poder de detecção nos intervalos de -1 < q < 1 (q diferente de 0) com dois níveis. O método de KL mostrou uma melhora significativa da sensibilidade em dados simulados e apresentou a habilidade em discriminar regiões funcionais ativas e em repouso, para um estímulo motor. Por fim, foi proposta uma primeira tentativa de identificar simultaneamente duas regiões cerebrais não correlacionadas no tempo e no espaço com os métodos de Tsallis e KL-fMRI em um experimento de estímulo duplo (visual e motor). Além disso, um novo método mostrou-se eficiente, ainda que de forma preliminar, para detectar o atraso temporal de duas HRFs. / Event-related functional magnetic resonance imaging (ER-fMRI) has become more popular in the last years. Most of analysis applied to such exams is based on a specific model of the hemodynamic response function (HRF). However, the variability of HRF and the low signal-to-noise ratio of such exams have imposed interesting challenges to both characterization and localization of the HRF. Recently, it was proposed a method based on computation of Shannon entropy, which makes no assumption about the shape of the response. We herein evaluated some parameters of the previous method in order to increase its sensibility. Moreover, this method was generalized with Tsallis entropy, which introduces a new parameter, q. Besides, a new method was proposed based on a distance of Kullback- Leibler (KL) measurement. Every method was applied to simulated and real data. Receiver Operating Characteristic curves were used to study the threshold dependence and the different methods parameters related to sensitivity and specificity. Tsallis entropy showed high detection power in the intervals -1 < q < 1 (q different from 0) with two bins. The KL method allowed significant improvement of sensibility in simulated data and reviewed the ability to discriminate regions of functional activity and rest in a motor stimulus. Finally, it was proposed a new technique to identify two brain regions without correlation in time and space through Tsallis and KL-fMRI methods, in a experiment of double stimuli (visual and motor). Furthermore, in a preliminary study, we developed a strategy to detect temporal delay between two HRFs.

No description available.

Ingeniero Civil / Un problema que afecta al mejoramiento de la productividad en la construcción con hormigón armado convencional es la necesidad de contar con mano de obra especializada para la colocación de la armadura (enfierradores). Por este motivo el uso de fibras como reemplazo de armadura convencional se presenta como una muy buena alternativa en viviendas de baja altura. La construcción basada en muros de hormigón armado es actualmente una de las más usadas en viviendas. Estas estructuras se caracterizan por tener demandas relativamente bajas en cuanto a esfuerzos y desplazamientos, por lo que el refuerzo de los muros y losas queda controlado por las cuantías mínimas. Dadas las bajas solicitaciones a las que son sometidas estas estructuras, el material presenta una sobre resistencia. El objetivo de este trabajo es entregar recomendaciones para el reemplazo de refuerzo convencional (mallas y/o barras) por fibras de acero, vidrio o polipropileno en viviendas de hormigón armado. Este reemplazo se considera tanto para muros como para losas. Para ello, se realiza una revisión de la literatura (normativas, códigos de diseño e investigaciones del hormigón reforzado con fibras) para establecer las capacidades teóricas al corte y flexión del hormigón con fibras. Posteriormente, se realiza el diseño de los elementos de una vivienda prototipo y se dan recomendaciones constructivas para la solución de hormigón reforzado con fibras. Finalmente se realiza una comparación técnico-económica entre la vivienda reforzada con fibras y una vivienda con refuerzo convencional para concluir analizando los beneficios de esta solución.

Functional Magnetic Resonance Imaging (fMRI) is one of the most popular neuroimaging methods for investigating the activity of the human brain during cognitive tasks. The main objective of the thesis is to identify this underlying brain activation over time, using fMRI signal by detecting active and passive voxels. We performed two sub goals sequentially in order to realize the main objective. First, by using simple, data-driven Fourier Wavelet Regularized Deconvolution (ForWaRD) method, we extracted hemodynamic response function (HRF) which is the information that shows either a voxel is active or passive from fMRI signal. Second, the extracted HRFs of voxels are classified as active and passive using Laplacian Eigenmaps. By this, the active and passive voxels in the brain are identified, and so are the activation areas. The ForWaRD method is directly applied to fMRI signals for the first time. The extraction method is tested on simulated and real block design fMRI signals, contaminated with noise from a time series of real MR images. The output of ForWaRD contains the HRF for each voxel. After HRF extraction, using Laplacian Eigenmaps algorithm, active and passive voxels are classified according to their HRFs. Also with this study, Laplacian Eigenmaps are used for HRF clustering for the first time. With the parameters used in this thesis, the extraction and clustering methods presented here are found to be robust to changes in signal properties. Performance analyses of the underlying methods are explained in terms of sensitivity and specificity metrics. These measurements prove the strength of our presented methods against different kinds of noises and changing signal properties.

Submitted by Renata Alves De Paula (medvetrenata@hotmail.com) on 2018-07-12T10:32:49Z No. of bitstreams: 1 Texto completo .pdf: 1611384 bytes, checksum: f6e1b93fde62170229cda125f7fbea46 (MD5) / Approved for entry into archive by Luciana Pizzani null (luciana@btu.unesp.br) on 2018-07-13T18:50:06Z (GMT) No. of bitstreams: 1 paula_ra_me_bot.pdf: 1611384 bytes, checksum: f6e1b93fde62170229cda125f7fbea46 (MD5) / Made available in DSpace on 2018-07-13T18:50:06Z (GMT). No. of bitstreams: 1 paula_ra_me_bot.pdf: 1611384 bytes, checksum: f6e1b93fde62170229cda125f7fbea46 (MD5) Previous issue date: 2018-06-06 / A equinocultura encontra-se em constante crescimento e por isso há um maior interesse em estudos científicos que favoreçam a relação homem animal garantindo consequentemente o bem-estar animal. Discussões são cada vez mais frequentes, envolvendo não só as formas de criação como também as práticas as quais são submetidos. A feromonioterapia é uma nova alternativa que vem sendo estudada a fim de tranquilizar e reduzir os problemas relacionados ao medo, ansiedade e fobia e limitando as manifestações do sistema nervoso autônomo e consequentemente o estresse a esses animais. Para tanto, o objetivo deste estudo foi avaliar a variabilidade da frequência cardíaca (VFC) de equinos submetidos ao tratamento com Feromônio Materno Equino (FME) durante o procedimento de casqueamento. Foram avaliados 20 potros, com idade média de vinte e quatro meses, machos e fêmeas sem experiência prévia ao casqueamento que foram divididos em dois grupos (A e B) onde um deles recebeu tratamento com FME e o outro placebo (excipiente sem o princípio ativo), considerado randomizado e duplo-cego. Os parâmetros avaliados foram frequência cardíaca (FC), frequência respiratória (FR), glicemia, VFC e análise de reações comportamentais. O exame clínico foi avaliado em dois momentos sendo: M1 (20 minutos previamente ao casqueamento) e M2 (20 minutos após o casqueamento). Já a VFC, foi avaliada nos momentos pré, trans e pós casqueamento. Os resultados demonstraram que não houve diferenças estatísticas dos parâmetros clínicos avaliados (FC, FR e glicemia) em comparação com os grupos (FME e placebo) em relação aos momentos M1 e M2. A FC mínima, FC média e FC máxima e principalmente os índices da VFC (SDNN, SDANN e SDNNi, RMSSD e PNN50) também não diferiram quando se comparou os grupos nos momentos pré, trans e pós casqueamento. Embora não tenha ocorrido significância, observou-se tendência a diminuição dos parâmetros FC, glicemia e reatividade em um dos grupos, havendo percepção nítida de mudança no comportamento durante o casqueamento sugerindo maior tranquilidade dos equinos durante o procedimento, com a feromonioterapia. / The horse breeding is found in constant growth and then there is a greater interest in scientific studies that favor the animal man relationship therefore ensuring animal welfare. Discussions are increasingly frequent, involving not only the forms of creation but also the practices which are submitted. Pheromone therapy is a new alternative that has been studied in order to reassure and reduce the problems related to fear, anxiety and phobia and limiting the manifestations of the autonomic nervous system and consequently the stress to these animals. For this purpose, the aim of this study was to evaluate the heart rate variability (HRV) of horses submitted to treatment with Maternal Equine Pheromone (MEP) during the hoof trimming. We evaluated 20 foals, with an average age of twenty-four months, males and females without prior experience to the hoof trimming that were divided into two groups (A and B) where one received treatment wich MEP and and the other placebo (excipient without the active ingredient), considered randomized and double-blind. The parameters evaluated were heart rate (HR), respiratory rate (FR), blood glucose, HRV and analysis of behavioral reactions. The clinical examination was studied in two moments: M1 (20 minutes before the procedure hoof trimming) and M2 (20 minutes after the procedure hoof trimming). Already the HRV was evaluated in pre, trans and post procedure hoof trimming. The results showed that there was no statistical differences of clinical parameters evaluated (FC, FR and glucose) compared to the groups (MEP and placebo) in relation to the moments M1 and M2. Minimum FC, medium FC and maximum FC and especially the index of VFC (SDNN, SDANN e SDNNi, RMSSD e PNN50) also did not differ when compared the groups in moments pre, during and after procedure hoof trimming. Although there has not been significance there was a tendency to decrease the parameters FC, blood glucose and reactivity in one of the groups, there being clear perception of change in behavior during procedure hoof trimming with pheromone therapy suggesting greater tranquility of equines during the procedure.

Orientador: Simone Biagio Chiacchio / Resumo: A equinocultura encontra-se em constante crescimento e por isso há um maior interesse em estudos científicos que favoreçam a relação homem animal garantindo consequentemente o bem-estar animal. Discussões são cada vez mais frequentes, envolvendo não só as formas de criação como também as práticas as quais são submetidos. A feromonioterapia é uma nova alternativa que vem sendo estudada a fim de tranquilizar e reduzir os problemas relacionados ao medo, ansiedade e fobia e limitando as manifestações do sistema nervoso autônomo e consequentemente o estresse a esses animais. Para tanto, o objetivo deste estudo foi avaliar a variabilidade da frequência cardíaca (VFC) de equinos submetidos ao tratamento com Feromônio Materno Equino (FME) durante o procedimento de casqueamento. Foram avaliados 20 potros, com idade média de vinte e quatro meses, machos e fêmeas sem experiência prévia ao casqueamento que foram divididos em dois grupos (A e B) onde um deles recebeu tratamento com FME e o outro placebo (excipiente sem o princípio ativo), considerado randomizado e duplo-cego. Os parâmetros avaliados foram frequência cardíaca (FC), frequência respiratória (FR), glicemia, VFC e análise de reações comportamentais. O exame clínico foi avaliado em dois momentos sendo: M1 (20 minutos previamente ao casqueamento) e M2 (20 minutos após o casqueamento). Já a VFC, foi avaliada nos momentos pré, trans e pós casqueamento. Os resultados demonstraram que não houve diferenças estatísticas dos parâmetros... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The horse breeding is found in constant growth and then there is a greater interest in scientific studies that favor the animal man relationship therefore ensuring animal welfare. Discussions are increasingly frequent, involving not only the forms of creation but also the practices which are submitted. Pheromone therapy is a new alternative that has been studied in order to reassure and reduce the problems related to fear, anxiety and phobia and limiting the manifestations of the autonomic nervous system and consequently the stress to these animals. For this purpose, the aim of this study was to evaluate the heart rate variability (HRV) of horses submitted to treatment with Maternal Equine Pheromone (MEP) during the hoof trimming. We evaluated 20 foals, with an average age of twenty-four months, males and females without prior experience to the hoof trimming that were divided into two groups (A and B) where one received treatment wich MEP and and the other placebo (excipient without the active ingredient), considered randomized and double-blind. The parameters evaluated were heart rate (HR), respiratory rate (FR), blood glucose, HRV and analysis of behavioral reactions. The clinical examination was studied in two moments: M1 (20 minutes before the procedure hoof trimming) and M2 (20 minutes after the procedure hoof trimming). Already the HRV was evaluated in pre, trans and post procedure hoof trimming. The results showed that there was no statistical differences of clinical p... (Complete abstract click electronic access below) / Mestre

This paper deals with the variability of HRF, which may have crucial impact on outcomes of fMRI neuronal activation detection in some cases. There are three methods described - averaging, regression deconvolution and biconjugate gradient method - which provide HRF shape estimation. In frame of simulations regression method, which uses B-spline curves of 4-th order for window length of 30 s, was chosen as the most robust method. Deconvolution estimates was used as HRF models for classic analyse of fMRI data, concretely visual oddball paradigm, via general linear model. Enlargement of localizated areas was observed and after expert consultation with scientific employees from neurology clinic, outcomes was evaluated as relevant. Furthermore Matlab application, which provides confortable observation of HRF variability among brain areas, was made.

This master´s thesis deals with processing and analysis of data, acquired from experimental examination performed with functional magnetic resonance imaging technique. It is an oddball type experimental task and its goal is an examination of cognitive functions of the subject. The principles of functional magnetic resonance imaging, possibilities of experimental design, processing of acquired data, modeling of a response of organism and statistical analysis are described in this work. Furthermore, particular parts of preprocessing and analysis are carried out using real data set from experiment. The main goal of this work is suggestion and realization of model, which enables advanced categorization of stimuli, considering the type of previous rare stimulus and the number of frequent stimuli within them. With its in-depth categorization, this model enables detail exploration of cerebral processes, associated mainly with attention, memory, expectancy or cognitive closure. The second point of that work is an evaluation of models of hemodynamic response, which are applied in statistical analysis of data from fMRI experiment. Comparison of basis functions, the models of hemodynamic response to experimental stimulation used for general linear model, is performed in this work. The result of this comparison is an evaluation of detection efficiency of activated voxels, false positivity rate and computational and user difficulty.