The purpose of this study was to examine the effects of cortical spreading depression on neuronal activity in the rat motor (M1) cortex. It is known that cortical spreading depression causes widespread neuronal and glial activity in the cortex, but the degree to which it exerts its effects is unclear. Cortical spreading depression was induced in eight Sprague-Dawley male rats. After two hours, animals were euthanized and immunohistochemistry was performed on the brain to stain for the presence of c-Fos, an immediate early gene that is a well-known marker of neuronal activity. Sections were counterstained for Nissl substance to reveal two populations of cells: Nissl-stained neurons that were c-Fos positive, activated cells and Nissl-stained neurons that were c-Fos negative, non-activated cells. Three sections for each animal were examined and 20-30% of the total M1 cortex was analyzed. Cells were counted using systematic random sampling for each of the six cortical layers. Our results show that the cortical spreading depression did not produce an activation of all neurons. When layers were individually examined, there was a main effect of layer on neuronal activation. This confirmed previous findings that cortical spreading depression had the strongest effect on superficial layers of the cortex

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The studies in this thesis research were conducted to investigate if sensitivity to induced cortical spread depression (CSD) or the consequence of a CSD event is affected by sumatriptan induced latent sensitization. Previous studies in our lab showed persistent exposure of sumatripan to rats produced a latent state of sensitization. Using persistent sumatripan exposed rats as a model for medication overuse headache, behavior, electrical stimulation threshold to provoke a CSD event and the immunoreactivity of c-Fos in the trigeminal nucleus caudalis (TNC) were characterized. Current results showed no statistical difference of electrically induced CSD thresholds in anesthetized rats measured at day 20 in sumatripan exposed rats compared with saline treated rats. Topiramate (80 mg/kg, i.p.) used clinically for prophylaxis of migraine headache significantly increased CSD threshold in both saline and sumatriptan infused rats. CSD events appear to be associated with trigeminal vascular system activation in TNC because c-Fos expression significantly enhanced in rats with electrically stimulated CSD events. As compared to saline treated rats, sumatriptan-exposed rats demonstrated a significantly higher number of c-Fos positive cells following the electrically stimulated CSD event. Under environmental stress (bright light), sumatripan exposed rats demonstrated decreased response thresholds to periorbital and hindpaw tactile stimuli (i.e., allodynia) and enhanced c-Fos expression in TNC. A single dose of topiramate (80 mg/kg, i.p.) reversed environmental stress induced allodynia and c-Fos over-activity. Taken together, these results suggest that latent sensitization induced by persistent sumatripan exposure seems not correlated to the threshold of electrically stimulated CSD in current model. However, CSD enhanced the responses of trigeminal system in rats with sumatriptan-induced latent sensitization. The protective effects of topiramate shown in this model may be related to blocking the initiation of CSD events resulting from environmental stimulation as well as inhibiting the consequences of CSD events in primary afferents. These findings correlate with clinical observations of protective effects of topiramate for migraine prophylaxis.

M.Sc., Faculty of Science, University of the Witwatersrand, 2011 / Sea oor massive sulphides are deep sea mineral deposits currently being examined as a potential mining resource. Locating these deposits, which occur at depths in the order of 2km, is currently performed by expensive submersible sonar platforms as conventional sonar bathymetry products gathered by sea surface platforms do not achieve adequate spatial resolution. This document examines the use of so-called high resolution beamforming methods (such as MUSIC and ESPRIT) for sonar bathymetry, together with combinations of parameter estimation techniques, including techniques for full rank covariance matrix estimation and signal enumeration. These methods are tested for bathymetric pro le accuracy using simulated data, and compared to conventional bathymetric methods. It was found that high resolution methods achieved greater bathymetric accuracy and higher resolution than conventional beamforming. These methods were also robust in the presence of unwanted persistent signals and low signal to noise ratios.

O que se desejou apresentar neste trabalho é se a aplicação da medida de complexidade LMC no estudo do fenômeno da depressão alastrante mostra-se eficiente na perspectiva de contribuir para uma melhor compreensão do fenômeno. Para isso, usou-se como modelo experimental a retina de pintinho in vitro. Na tentativa de obter informações sobre estados de equilíbrio entre a ordem e desordem, propõe-se as análises dos registros de dois dos concomitantes do fenômeno: a alteração lenta do potencial extracelular e do sinal intrínseco óptico. Para isso, avaliou-se o efeito de manipulações fármaco-química sobre esses dois concomitantes do fenômeno e através de análises comparativas entre as ondas de controle e as ondas obtidas em presença das diversas substâncias foram discutidas a aplicabilidade do método proposto, mostrando que a medida de complexidade trouxe novas informações sobre a depressão alastrante contribuindo para um entendimento melhor do fenômeno. / What we wanted to present in this work is the application of the LMC measure of complexity in the study of the phenomenon of spreading depression proves efficient in order to contribute to a better understanding of the phenomenon. For this, we used as an experimental model of the chick retina in vitro. In an attempt to obtain information about equilibrium states between order and disorder, it is proposed that the analysis of the records of two of the concomitant phenomena: a slowly changing the extracellular potential and intrinsic optical signal. For this, we evaluated the effect of pharmaco-chemical manipulations on these two concomitant phenomenon and by comparative analyzes of the control waves and the waves obtained in the presence of various substances discussed the applicability of the proposed method, the measure complexity brought new information on the spreading depression to a better understanding of the phenomenon.

Esta tese versa sobre as potencialidades da divulgação científica como literatura para o ensino de ciências. Fundamenta-se em autores que contribuem para problematizar a divulgação científica, como Ana Maria Sanchéz Mora, José Reis, João Zanetic, Mônica Teixeira e Ângelo Machado. Fundamenta-se, também, nos pressupostos de uma educação humanizadora e ancora-se, quanto a esse aspecto, nas contribuições de Paulo Freire. Para reflexão sobre o resgate do sentido do trabalho escolar, foram fundamentais as contribuições de Bernard Charlot. A partir das reflexões geradas pelo diálogo com a bibliografia consultada, a discussão prioriza obras que têm como centralidade uma concepção de ciência pautada pela presença de contradições e conflitos, uma ciência inserida no plano da cultura e compreendida como processo vivenciado por cientistas - sujeitos também inseridos em contextos - uma ciência, portanto, marcada por dilemas humanos. Diferenciando a divulgação científica canônica da divulgação científica não canônica, este trabalho realiza uma análise de narrativas presentes em obras não canônicas de literatura, a saber, 2001- odisséia no espaço, de Arthur Clarke, O dilema do bicho-pau, de Ângelo Machado, Contato, de Carl Sagan e Os meninos da Planície, de Cástor Cartelle. Na análise das obras foram priorizadas as contribuições específicas para a compreensão da ciência como produção cultural e das potencialidades humanizadoras que tem o ensino de ciências voltado para compreensão de aspectos da subjetividade humana e dos conflitos da existência. Nas obras analisadas, foi possível perceber uma ênfase narrativa tipicamente mitológica, marcada por situações conflitantes, em, por exemplo, se realiza a polarização entre medo e encanto, desejo e possibilidade, sonho e experiência. Foi possível localizar também uma opção narrativa pela imaginação criadora, pela capacidade humana e por sua potencialidade criativa, elementos que são, nesse caso, motes fundamentais para reflexão sobre a vida humana e também sobre a ciência; uma ciência produzida a partir de injunções sociais e contextuais, levada a cabo por pessoas reais, também, portadoras de uma dimensão humana e subjetiva. Nas obras selecionadas, foi possível perceber uma provável contribuição para renovação do ensino de ciências, pois sua centralidade recai sobre a reflexão acerca da humanização dos sujeitos e não sobre a transmissão de conteúdos da ciência, embora essa dimensão, a da formação científica, esteja inequivocamente presente em todas elas, sem prejuízos. / This study is about scientific spreading potentiality as literature for science teaching. It is based on authors who have contributed to discuss the scientific spreading, such as Ana Maria Sanchéz Mora, José Reis, João Zanetic, Mônica Teixeira, and Ângelo Machado. It is also based on the presupposition of a humanizing education, and is anchored, in relation to this aspect, in Paulo Freire\'s contributions. From the reflections which have arisen through the dialogue with the consulted bibliography, it prioritizes the ones which have as centrality a conception of science related to the presence of contradictions and conflicts, a science inserted in the culture plan and understood as a process lived by scientists - also subjects inserted in contexts - a science, therefore, marked by human dilemma. Differing the canonical scientific spreading from the non-canonical scientific spreading, this study makes analysis of the narratives present in non-canonical works of literature, to know, 2001: A space odyssey, by Arthur Clarke, Os meninos da planície, by Cástor Cartelle, O dilema do bicho-pau, by Ângelo Machado, and Contact, by Carl Sagan. In the analysis of the works, specific contributions were prioritized in order to understand science as cultural production and the humanizing potentialities which have science teaching turned to the comprehension of human subjectivity aspects and of existence conflicts. It was possible to notice a typically mythological narrative emphasis in the analyzed works, marked by conflicting situations, as, for example, where the polarization between fear and enchant, desire and possibility, and dream and experience are carried out. It was also possible to localize one narrative option through the creative imagination, the human capacity and its creative potentiality, elements which are, in this case, fundamental motivations for the reflection about human life and also about science, a science produced from the social and contextual injunctions on, carried out by real people; these ones also having a human and subjective dimension. It was possible to suppose a likely contribution to the renewal of science teaching in the selected works, because its centrality remains over the reflection about the humanizing of the subjects and not over the transmission of science contents, although such dimension, the one of scientific formation, is undoubtedly present in all of them, without any harm.

Many neurological disorders are a result of widespread changes in the excitability of brain tissue. The specific changes in neuronal excitability produces or worsens many of the symptoms associated with these disorders. Pharmacological methods are effective, but their associated side-effects are substantial, and often approximate the severity of the symptoms of the original disorder. The ketogenic diet, a high-fat, low-carbohydrate diet, has been shown to improve many neurological diseases by reducing hyperexcitability without the aforementioned side effects. The current study tested the hypothesis that a ketogenic diet would be associated with alterations in cerebral excitability. Animals were fed either a control or ketogenic diet for at least 21 days prior to experimentation. Power spectral analysis was conducted using EEG data across frequency bands, and compared between diet groups. Current source density analysis was also performed to visualize potential alterations in cerebral excitability.. In the second part of the experiment, a non-invasive ischemic stroke was delivered, and the excitability of the contralateral cortex was monitored. No significant differences were observed between ketogenic and control experiments in regards to overall excitability, although ketogenic diet experiments showed a significantly higher number of acute EEG depressions. No cortical spreading depression events were observed in contralateral recordings. Our findings are in contrast with data showing that ketogenic diets change overall basal excitability, but are in concert with other studies that show that ketogenic diets may not be associated with changes in excitability, but in changes in neuroplasticity.

Esta tese versa sobre as potencialidades da divulgação científica como literatura para o ensino de ciências. Fundamenta-se em autores que contribuem para problematizar a divulgação científica, como Ana Maria Sanchéz Mora, José Reis, João Zanetic, Mônica Teixeira e Ângelo Machado. Fundamenta-se, também, nos pressupostos de uma educação humanizadora e ancora-se, quanto a esse aspecto, nas contribuições de Paulo Freire. Para reflexão sobre o resgate do sentido do trabalho escolar, foram fundamentais as contribuições de Bernard Charlot. A partir das reflexões geradas pelo diálogo com a bibliografia consultada, a discussão prioriza obras que têm como centralidade uma concepção de ciência pautada pela presença de contradições e conflitos, uma ciência inserida no plano da cultura e compreendida como processo vivenciado por cientistas - sujeitos também inseridos em contextos - uma ciência, portanto, marcada por dilemas humanos. Diferenciando a divulgação científica canônica da divulgação científica não canônica, este trabalho realiza uma análise de narrativas presentes em obras não canônicas de literatura, a saber, 2001- odisséia no espaço, de Arthur Clarke, O dilema do bicho-pau, de Ângelo Machado, Contato, de Carl Sagan e Os meninos da Planície, de Cástor Cartelle. Na análise das obras foram priorizadas as contribuições específicas para a compreensão da ciência como produção cultural e das potencialidades humanizadoras que tem o ensino de ciências voltado para compreensão de aspectos da subjetividade humana e dos conflitos da existência. Nas obras analisadas, foi possível perceber uma ênfase narrativa tipicamente mitológica, marcada por situações conflitantes, em, por exemplo, se realiza a polarização entre medo e encanto, desejo e possibilidade, sonho e experiência. Foi possível localizar também uma opção narrativa pela imaginação criadora, pela capacidade humana e por sua potencialidade criativa, elementos que são, nesse caso, motes fundamentais para reflexão sobre a vida humana e também sobre a ciência; uma ciência produzida a partir de injunções sociais e contextuais, levada a cabo por pessoas reais, também, portadoras de uma dimensão humana e subjetiva. Nas obras selecionadas, foi possível perceber uma provável contribuição para renovação do ensino de ciências, pois sua centralidade recai sobre a reflexão acerca da humanização dos sujeitos e não sobre a transmissão de conteúdos da ciência, embora essa dimensão, a da formação científica, esteja inequivocamente presente em todas elas, sem prejuízos. / This study is about scientific spreading potentiality as literature for science teaching. It is based on authors who have contributed to discuss the scientific spreading, such as Ana Maria Sanchéz Mora, José Reis, João Zanetic, Mônica Teixeira, and Ângelo Machado. It is also based on the presupposition of a humanizing education, and is anchored, in relation to this aspect, in Paulo Freire\'s contributions. From the reflections which have arisen through the dialogue with the consulted bibliography, it prioritizes the ones which have as centrality a conception of science related to the presence of contradictions and conflicts, a science inserted in the culture plan and understood as a process lived by scientists - also subjects inserted in contexts - a science, therefore, marked by human dilemma. Differing the canonical scientific spreading from the non-canonical scientific spreading, this study makes analysis of the narratives present in non-canonical works of literature, to know, 2001: A space odyssey, by Arthur Clarke, Os meninos da planície, by Cástor Cartelle, O dilema do bicho-pau, by Ângelo Machado, and Contact, by Carl Sagan. In the analysis of the works, specific contributions were prioritized in order to understand science as cultural production and the humanizing potentialities which have science teaching turned to the comprehension of human subjectivity aspects and of existence conflicts. It was possible to notice a typically mythological narrative emphasis in the analyzed works, marked by conflicting situations, as, for example, where the polarization between fear and enchant, desire and possibility, and dream and experience are carried out. It was also possible to localize one narrative option through the creative imagination, the human capacity and its creative potentiality, elements which are, in this case, fundamental motivations for the reflection about human life and also about science, a science produced from the social and contextual injunctions on, carried out by real people; these ones also having a human and subjective dimension. It was possible to suppose a likely contribution to the renewal of science teaching in the selected works, because its centrality remains over the reflection about the humanizing of the subjects and not over the transmission of science contents, although such dimension, the one of scientific formation, is undoubtedly present in all of them, without any harm.

Immune tolerance to self antigens prevents the onset of autoimmune diseases such as Multiple Sclerosis (MS). There are three branches of tolerance which allow the auto-aggressive potential of T lymphocytes to be limited; these are death, anergy-adaptation and regulation. The main body of this work attempts to clarify a role for adaptation in maintaining the sensitivity of the autoreactive T cell repertoire below a ‘threshold for harm’ in the mouse model of MS, experimental autoimmune encephalomyelitis (EAE). The well defined myelin basic protein (MBP) Ac1-9 epitope altered peptide ligand (APL) system has been used to develop a model allowing the examination of mechanisms underlying the adaptation of cells. Previous data showed immunisation with the 4Lys (wild-type) epitope mediated disease whereas a superagonist APL with a tyrosine substitution at position 4 (4Tyr) did not, despite showing potency in vitro. This was shown to be a result of both activation induced cell death and adaptation. Here an in vitro model was developed using MBP-reactive TCR transgenic cells to make predictions about the mechanisms underlying adaptation. These data lead to the conclusion that T cells can adapt (become less sensitive) either before or after encounter with the wild-type peptide, leading to a reversal of their pathogenic potential. The MBP APL system and MBP reactive transgenic cells were also used to assess the contribution of epitope spreading in a relapsing-remitting (RR) model of EAE induced with proteolipid protein. The cells were tracked and changes in phenotype and behaviour were monitored. The data show that disease induced with one antigen can be manipulated with cells relevant to a different antigen and that bystander suppression may be an effective weapon in controlling the progression to RR-EAE.

Impact of drops on a dry smooth surface was studied at elevated chamber pressures and low Reynold's numbers to characterize the effect of chamber pressure on drop splashing and spreading. Two drop sizes of methanol, ethanol, propanol, hexadecane and diesel were tested for impact speeds between 1.5 - 3.3 m/s and pressure of upto 12 bars. Splash ratio, unlike the results of Xu et al, increased sharply with decreasing impact speed suggesting that drop speed is a more critical parameter for splash. Drop splashing was also found to be affected by drop shape, with drop distortion having a significant impact on splash promotion or suppression. In accordance with existing theory, drop spreading and maximum spread factor were found to be independent of pressure in the regime tested. These observations provide new insights and comparison data for evaluating and modeling the behavior of alternate fuels like ethanol.