Lopes, Marcel Adriano. Efeitos do clonazepam sobre as respostas defensivas medidas em ratos submetidos ao labirinto em T elevado. 2010. 83f. Dissertação (mestrado) - Faculdade de Medicina de Ribeirão Preto - Universidade de São Paulo - Ribeirão Preto, 2010. O labirinto em T elevado (LTE) é um modelo etológico, que evoca comportamentos defensivos correlacionados com o transtorno de ansiedade generalizada (esquiva inibitória) e o transtorno do pânico (fuga). Apesar da validação farmacológica da tarefa de esquiva inibitória deste modelo estar bem estabelecida, algumas questões em relação à tarefa de fuga não estão claras. Resultados prévios da literatura mostram que drogas clinicamente eficazes no tratamento do transtorno do pânico, como antidepressivos tricíclicos (ex: imipramina e clomipramina) e inibidores seletivos da recaptação de serotonina (ex: fluoxetina e escitalopram), aumentam a latência de fuga no LTE, sugerindo efeito do tipo panicolítico. Entretanto, em relação aos benzodiazepínicos de alta potência, também amplamente utilizados na clínica para o tratamento do transtorno do pânico, os dados em relação ao LTE permanecem desconhecidos. Sendo assim, o presente trabalho teve como objetivo investigar o efeito da administração aguda ou repetida (7 ou 14 dias) de clonazepam em ratos submetidos ao LTE. Dada a importância da substância cinzenta periaquedutal dorsal (SCPD) na gênese do transtorno do pânico, verificamos se o efeito da administração aguda de clonazepam no LTE era bloqueado pela administração prévia intra-SCPD do antagonista de receptores BZD flumazenil. Nossos resultados mostram que o tratamento agudo com clonazepam diminuiu as latências de esquiva inibitória e aumentou as latências de fuga do braço aberto, indicativo de efeito ansiolítico e panicolítico, respectivamente. Já a administração repetida deste mesmo benzodiazepínico, seja por 7 ou 14 dias, diminuiu as latências de esquiva inibitória, sem alterar as respostas de fuga. A administração intra-SCPD do antagonista de receptores benzodiazepínicos flumazenil não bloqueou o efeito da administração aguda de clonazepam sobre as respostas defensivas medidas no LTE. Os resultados do presente estudo mostram ainda que o efeito do clonazepam sobre a resposta de fuga é dependente da maneira pela qual a aquisição da resposta de esquiva inibitória é realizada, ou seja, o tratamento agudo com clonazepam foi capaz de alterar esta resposta somente quando a esquiva inibitória foi realizada com 6 tentativas. Em suma, nossos dados mostram que a administração aguda de clonazepam promove efeito panicolítico e ansiolítico no LTE. No entanto, deve ser ressaltado que o efeito panicolítico do clonazepam foi apenas observado após a introdução de uma mudança metodológica no teste do LTE. De uma maneira geral, os resultados obtidos sustentam a associação entre o comportamento de fuga e ataques de pânico. / Lopes, Marcel Adriano. Effect of clonazepam on the defensive responses measured in rats tested in the elevated T maze. 2010. 83f. Dissertação (mestrado) - Faculdade de Medicina de Ribeirão Preto - Universidade de São Paulo - Ribeirão Preto, 2010. The elevated T maze (ETM) is an ethological model that generates in rats defensive behaviors in rats which have been associated with generalized anxiety (inhibitory avoidance) and panic (escape) disorders. A wealth of evidence in the literature supports the validity of the ETM inhibitory avoidance task for detecting the effects of generalized anxiety-effective drugs. However, the effect of panic-effective drugs on escape performance has not been fully investigated yet. Previous studies showed that panic-ameliorating drugs such as tricyclic antidepressants (e.g. imipramine and clomipramine) and selective serotonin reuptake inhibitors (e.g. fluoxetine and escitalopram), increase escape latencies in the ETM, suggesting a panicolytic-like effect. The effect of high-potency benzodiazepines agonists such as clonazepam and alprazolam, also widely used for the treatment of panic disorder, remains unknown. In this study we investigated the effect of acute or repeated administration (7 or 14 days) of clonazepam in rats submitted to the ETM. Given the attributed importance of the dorsal periaqueductal gray matter (dPAG) in the genesis/regulation of panic disorder, we also investigated whether the effects caused by the acute administration of clonazepam in ETM can be blocked by prior intra-dPAG administration of the BZD receptor antagonist flumazenil. Our results showed that acute treatment with clonazepam impaired inhibitory avoidance acquisition and increased escape latencies, suggesting anxiolytic and panicolytic effects, respectively. Repeated administration of clonazepam, either for 7 or 14 days, also impaired inhibitory avoidance acquisition, but did affect escape expression. Intra-dPAG injection of flumazenil did not block the effect of clonazepam on the defensive responses measured in ETM. Our results also showed that the effect of clonazepam on the escape response is dependent on the way inhibitory avoidance acquisition is measured, i.e. the drug anti-escape effect was only observed in group of animals that had 6 but not 3 trials to acquire inhibitory avoidance. Altogether, our data show that clonazepam causes both anxiolytic and panicolytic effects on ETM, in accordance to its therapeutic profile. However, it should be emphasized that the panicolytic effect of clonazepam was only observed after the introduction of a methodological modification in the ETM test protocol. Overall, our findings support the proposed association between escape behavior and panic attacks.

Submitted by Patrícia Valim Labres de Freitas (patricial) on 2016-04-05T18:36:31Z No. of bitstreams: 1 Mauricio Schafer_.pdf: 3502667 bytes, checksum: bef575d3f673b57858290149f4ca04ed (MD5) / Made available in DSpace on 2016-04-05T18:36:31Z (GMT). No. of bitstreams: 1 Mauricio Schafer_.pdf: 3502667 bytes, checksum: bef575d3f673b57858290149f4ca04ed (MD5) Previous issue date: 2015-10-28 / itt Performance - Instituto Tecnológico em Desempenho da Construção Civil / UNISINOS - Universidade do Vale do Rio dos Sinos / Uma solicitação extrema a que uma alvenaria pode ser submetida é a decorrente de incêndios, que se destacam pelo grande potencial de degradação. Os revestimentos de argamassa são normalmente aplicados sobre substratos e, por comporem a última camada da alvenaria, se tornam mais suscetíveis às elevadas temperaturas. O estudo das alterações macro e microestruturais das argamassas podem auxiliar na identificação dos níveis de temperatura a que a estrutura foi submetida ao longo de um incêndio, permitindo um melhor diagnóstico sobre o sinistro e uma melhor estimativa sobre o nível de danos da estrutura de concreto e demais componentes da edificação. Partindo deste contexto, esta pesquisa tem como objetivo a análise da influência de elevadas temperaturas em um revestimento de argamassa. O programa experimental desenvolvido possui duas etapas: a primeira utilizando-se argamassas de revestimento aplicadas sobre blocos cerâmicos submetidos, em uma mufla, a temperaturas de 100, 300, 500, 700, e 900ºC, e caracterizados com relação a sua macroestrutura (resistência de aderência, absorção de água e velocidade de propagação da onda) e microestrutura (microscopia eletrônica de varredura e porosimetria por intrusão de mercúrio). A segunda etapa consiste no ensaio de paredes de alvenaria, construídas com o mesmo bloco cerâmico e a mesma argamassa da etapa anterior, em um forno que simula a ação de incêndio, especificado pela NBR 10636 (ABNT, 1989). Nas temperaturas até 300ºC houve uma melhoria nas propriedades das argamassas, já a partir da temperatura de 500ºC ocorreu uma degradação das argamassas e do revestimento, com queda de revestimento a partir da temperatura de 700ºC. Embora os procedimentos utilizados para o aumento da temperatura em mufla e em forno tenham ciclos de aquecimento distintos, não foram constatadas diferenças expressivas entre os resultados de ensaios em revestimentos submetidos a aquecimento em mufla e os submetidos ao forno simulando o incêndio. / An extreme request that masonry can be submitted is the result of fires that stand out for great potential of degradation. The mortar coatings are typically applied to substrates, and compose the last layer of masonry, become more susceptible to elevated temperatures. The study of changes macro and microstructure of the mortars can help identify temperature levels to which the structure was subjected over a fire, enabling a better diagnosis of the accident and a better estimate of the level of damage of the concrete structure and other components of the building. From this context, this research aims to analyze the influence of high temperatures in a mortar coating. The experimental program has two steps: first using a mortar coating applied over subjected ceramic blocks in a muffle furnace at temperatures of 100, 300, 500, 700, and 900°C, and characterized with regard to its macrostructure (adhesion resistance, water absorption and speed wave propagation) and microstructure (scanning electron microscopy and mercury intrusion porosimetry). The second step consists in testing masonry walls built with the same ceramic block and the same mortar in an oven to simulate the action of fire, specified by NBR 10636 (ABNT, 1989). In temperatures to 300°C there was an improvement in the properties of mortars, already from 500°C temperature occurred the deterioration of the mortar and coating, coated drop from the temperature of 700°C. Although the procedures used for increasing the temperature in a muffle furnace and oven have separate heating cycles, no significant differences observed between the test results on coatings.

O aquecimento global e as alterações nos padrões de precipitação são algumas das mudanças observadas no clima do planeta nos últimos anos. Simultaneamente, observa-se o aumento da concentração de gás carbônico ([CO2]) na atmosfera, devido principalmente a ações antrópicas. A elevação da [CO2] e da temperatura atmosférica global podem intensificar o efeito estufa, alterar a dinâmica de trocas gasosas das plantas e o ciclo do carbono nos ecossistemas. Isso ocorre tanto por influencias na fotossíntese, quanto nas respirações auto e heterotrófica. Outros fatores, como a umidade do solo também podem interferir nestes processos. As pastagens são ecossistemas de relevante importância para o ser humano e impactantes na dinâmica global do ciclo do carbono. A agricultura é a mais ampla forma de uso antrópico do solo e estoca mais de 10% de todo carbono da biosfera. Com o intuito de investigar o impacto das mudanças climáticas na dinâmica do CO2 e no ciclo do carbono nos ecossistemas de pastagem, este trabalho teve como objetivo quantificar a produção de biomassa, o fluxo líquido de CO2 do ecossistema (NEE), a respiração do solo e o fluxo de metano em ecossistemas de pastagem tropical. Duas espécies forrageiras, Panicum maximum Jacq. Cv Mombaça (gramínea C4), e Stylosanthes capitata Vogel (Leguminosa C3), foram cultivadas sob elevada concentração de CO2 (600 mol mol-1), elevada temperatura atmosférica (+2 ºC) e restrição hídrica em sistema combinado FACE (Free-air carbon dioxide enrichment) e T-FACE (Temperature free-air controlled enhancement). A quantificação do NEE foi realizada por câmaras de topo aberto desenvolvidas pelo grupo de pesquisa especificamente para o estudo ecofisiológico integrado de todo o dossel e não apenas de uma fração da área foliar ou pela biomassa, que são atualmente as técnicas mais utilizadas. No experimento utilizando a leguminosa C3 foi observado diminuição na biomassa total acima do solo, pela diminuição da quantidade de folhas, em tratamento com elevada temperatura (eT) e um aumento na biomassa de caules em tratamento combinado de elevada [CO2] e temperatura (eC+eT). O NEE diurno aumentou sob tratamento de elevada [CO2] (eC). A respiração do solo no período noturno foi aumentada em todos os tratamentos. Não houve mudança no fluxo de metano. No segundo experimento, utilizando a gramínea C4, a biomassa de folhas sofreu aumento no tratamento combinado eC+eT, o NEE diurno aumentou sob eC e a respiração do solo noturno aumentou sob eC+eT. No terceiro experimento, também utilizando a gramínea C4, porém, com tratamentos de restrição hídrica e elevada temperatura, não foram observadas diferenças nos dados coletados. De maneira geral, as mudanças climáticas trarão alterações no ciclo do carbono dos ecossistemas de pastagem, sendo que a utilização da leguminosa C3 S. capitata pode acarretar em perdas de produtividade de folhagem e aceleração da fenologia. Já a gramínea C4 P. maximum se mostrou resistente a um clima futuro de seca e temperatura elevada e se beneficiou da maior [CO2], com maior fixação de carbono pelo ecossistema e produção de biomassa de folhas, sendo assim uma boa opção para a produção de forragem em pastagens tropicais. / Global warming and changes in the rain patterns are some of the changes observed in the weather of the planet in the last years. Simultaneously, it has been observed increases in the atmospheres concentration of carbon dioxide ([CO2]), mainly by anthropic actions. The rising [CO2] and atmospheric temperature may intensify the greenhouse effect, modify the dynamic of plant gas exchange and the carbon cycle in the ecosystems. These changes occur by effects in the photosynthesis and respiration (auto and heterotrophic). Other factors, as soil moisture, may also affect these processes. Grasslands are ecosystems of importance to the humanity and of impact to the global carbon circle dynamic. Agriculture is the main anthropic land use and stores more than 10% of all carbon in the biosphere. With the aim of investigate the impact of climate changes in the dynamic of CO2 and carbon cycle in tropical grassland ecosystems, this work had as objective to quantify the production of biomass, the net flux of CO2 of the ecosystem (NEE), the soil respiration and methane flux in tropical grassland ecosystems. Two forage plant species, Panicum maximum Jacq. Cv Mombaça (C4 grass), and Stylosanthes capitata Vogel (C3 legume), were cultivated under elevated CO2 concentration (600 mol mol-1), elevated atmospheric temperature (+2 °C) and water shortage in a Free-air carbon dioxide enrichment (FACE) and Temperature free-air controlled enhancement (T-FACE) combined system. The NEE quantification was realized by open top chambers developed by the research group specifically for the integrated ecophysiological study of the whole canopy and not just a fraction of leaf area or the biomass, which are the most commonly used technics nowadays. In the experiment using the C3 legume was observed a decrease in total above-ground biomass, by the reduction of leaf biomass, in treatment with elevated temperature (eT) and an increase of stems biomass in the combined treatment of elevated [CO2] and temperature (eC+eT). The diurnal NEE increased under elevated [CO2] (eC). The night soil respiration was increased in all three treatments. There were no changes in the methane flux. In the second experiment, utilizing the C4 grass, the leaves biomass increased under eC+eT, the diurnal NEE increased in the eC treatment and the night soil respiration also increased under eC+eT. In the third experiment, with the same C4, however, with water shortage and elevated temperature treatments, there were no differences in the collected data. Overall, the climate changes will bring alterations in the carbon cycle of grassland ecosystems, therefore, the use of the C3 legume S. capitata might entail in losses in foliage productivity and phenology acceleration. On the other hand, the C4 grass P. maximum showed resistance to a future climate with drought and elevated temperature, and benefited from the higher [CO2], with greater carbon fixation by the ecosystem and production of leaf biomass, being a good option for forage production in tropical pastures.

Concrete is a strong material as to its compressive strength. However, it is a material with a low tensile and shear strength, and brittleness at failure. Concrete has to be reinforced with appropriate materials. Steel fibre is one of the most common materials currently being used to develop reinforced concrete, which may replace partially or completely conventional steel reinforcement. Successful reinforcement of concrete composite is closely related to the bond characteristics between the reinforcing fibre and matrix. The effective utilisation of steel fibre reinforced concrete (SFRC) requires in-depth and detailed understanding of bonding mechanisms governing the tensile behaviour. In response to this demand, this study embraced two main areas: understanding the reinforcing mechanisms of fibres in SFRC and material's post-cracking behaviour. Comprehensive experimental and theoretical programmes have therefore been developed: the experimental work is subdivided into three parts. The first part was to investigate the effect of various physical parameters, such as fibre characteristics (i.e. geometry, inclination angle, embedded length, diameter and tensile strength) and matrix strength which controls the pull-out behaviour of steel fibres. The second part is concerned with the assessment of the bond mechanisms of straight and hooked end fibres after exposure to elevated temperatures and varying matrix strength. The third part is devoted to gain further insight on the bond mechanisms governing the post-cracking behaviour through uniaxial and bending tests. It was found that the varying hook geometry and matrix strength each had a major influence on the pull-out response of hooked end fibres. As the number of the hook's bends increased, the mechanical anchorage provided by fibre resulted in significant improvement of mechanical properties of SFRC. The reduction in bond strength at elevated temperatures is found to be strongly related to the degradation in properties of the constituent materials, i.e. the fibre and concrete. The most effective combination of matrix strength and fibre geometry was found to be as follows: 3DH (single bend) fibre with normal-medium strength matrix, 4DH (double bend) fibre with high strength matrix and 5DH (triple bend) fibre with ultra-high performance matrix. Two analytical models to predict the pull-out behaviour of hooked end fibres were developed. Both models were able to predict the pull-out response of SFRC made from a variety of fibre and matrix characteristics at ambient temperature. This work has established a comprehensive database to illustrate the bonding mechanisms of SFRC and anchorage strengthening of various hooked end fibres, and this should contribute towards an increasing interest and growing number of structural applications of SFRC in construction.

Dentre a gama de estudos existentes acerca das respostas de plantas ao incremento de CO2 atmosférico associado às mudanças climáticas, são poucas as investigações que contemplam espécies amazônicas frente à relevância desse ecossistema, e se desconhecem estudos desse aspecto com palmeiras. O açaí (Euterpe oleracea Mart., Arecaceae) é uma espécie típica de planícies da Floresta Amazônica sujeitas ao regime anual de inundação e, além de ser extremamente tolerante à anóxia, apresenta elevado valor comercial e um potencial para a produção de energia a partir de biomassa, gerando uma exploração economicamente sustentável. Este trabalho buscou caracterizar o crescimento inicial de plântulas de açaí quanto à fotossíntese, crescimento e metabolismo de carboidratos e investigar as respostas desses parâmetros ao incremento de CO2 atmosférico (de 380ppm - ambiente para 760ppm - elevado) em duas escalas temporais: ao longo do desenvolvimento das plântulas (entre 105 e 195 dias após a germinação, período de desenvolvimento da segunda folha) e ao longo de 24 horas (aos 175 dias após a germinação). Foram analisadas medidas de altura, área foliar, acúmulo e alocação de biomassa, curvas de resposta da fotossíntese à luz, conteúdo de clorofila e concentração de carboidratos não-estruturais. Foi verificado que o período de estabelecimento das plântulas se estende até cerca de 150 dias após a germinação e se sobrepôs ao experimento com elevado CO2. A presença de outra via de entrada de carbono além da fotossíntese tamponou mas não inibiu os efeitos do aumento de CO2 atmosférico. Foram observadas ao longo do experimento reduções na área foliar, condutância estomática e respiração no escuro e aumentos na fotossíntese e eficiência de uso da água, além de aumento na concentração de carboidratos não-estruturais e na biomassa. Os dados obtidos após o esgotamento das reservas do endosperma não apresentaram sinais de que a planta aclimatará ao incremento de CO2, pois aos 90 dias de experimento foram observadas as maiores porcentagens de aumento na fotossíntese, 89%, e no teor de amido, 300%. Esses resultados indicam que essa espécie apresenta uma grande capacidade de aumento da força de dreno, o que diminui a sinalização por açúcares possibilitando a manutenção de uma resposta positiva ao incremento de CO2 atmosférico / Despite all knowledge available nowadays on plant responses to increasing atmospheric CO2, few are the studies that focus on Amazonian species in contrast to the biological relevance of this ecosystem, and no record has been found of Palm species analysis on this area of research. Açaí palm (Euterpe oleracea Mart., Arecaceae) is a typical species of Amazon plains subjected to annual periods of flooding. Apart from being extremely anoxia tolerant, this species presents high commercial value and a potential of energy production through biomass utilization, counting towards a sustainable economic exploitation. This study aimed to characterize the initial growth of açaí palm seedlings as for photosynthesis, growth and carbohydrate metabolism and to investigate these parameters\' responses to an increase on atmospheric CO2 (from 380ppm - ambient to 760ppm - elevated) on two temporal scales: throughout seedling development (from 105 to 195 days post germination, time span of second leaf development) and throughout 24 hours (at 175 days post germination). Analysis included: height, leaf area, biomass increase and allocation, light-response curves, chlorophyll content and non-structural carbohydrate concentration. It was observed that the seedling establishment period extends to 150 days post germination and overlapped the elevated CO2 experiment. The presence of another carbon entry pathway besides photosynthesis buffered the effects of elevated CO2, but did not inhibit them. Results observed were reductions on leaf area, stomatal conductance and dark respiration and increases on photosynthesis, water use efficiency, non-structural carbohydrate content and biomass. The results obtained after seed reserves were depleted did not seem to indicate that this species will present acclimation to elevated CO2, since the greater percentages of increase on photosynthesis (89%) and starch content (300%) occurred at the end of the experiment (90 days on elevated CO2). These results indicate that açaí palm seedlings have a large capacity of sink strenght increase, which reduces sugar signaling and maintains a positive response to the increase on atmospheric CO2

A vegetação ao longo do rio Amazonas é submetida a dois períodos muito bem marcados ao longo do ano: estação de cheia e estação seca. Características morfológicas e fisiológicas das espécies de várzea foram amplamente descritas, porém, uma das principais características é o metabolismo de carboidratos que tem sido muito pouco explorada. Com o objetivo de estudar a resiliência dos carboidratos não estruturais da árvore amazônica Senna reticulata (Leguminosae), a mesma foi cultivada sob diferentes estresses abióticos, como luz baixa combinada com elevada concentração de CO2 atmosférico, bem como disponibilidade hídricas distintas (alagamento das raízes e seca). Os resultados encontrados reforçam o papel do amido nas folhas como principal órgão armazenador desta espécie e também a alta resiliência desta reserva, que foi mantida mesmo em condições de baixa irradiância, em alagamento e em condições de seca. Estes resultados também destacam a forte ligação entre as reservas de amido e a manutenção do crescimento. Além disso, esta espécie mostrou estratégias ecofisiológicas distintas em relação a diferentes estresses hídricos (alagamento x seca) e uma alta capacidade de se recuperar depois de um período de seca, padrão este que pode estar diretamente relacionado à manutenção do crescimento durante o estabelecimento de plantas jovens no primeiro período de fase terrestre / The vegetation along the Amazon River is subjected to two markedly periods: flooded and drought seasons. Morphological and physiological traits for floodplain species have been largely described; however, one of the main features is the carbohydrate metabolism, which has been poorly explored. In order to study the resilience of non-structural carbohydrates of the Amazonian tree Senna reticulate (Leguminosae), this species was grown under different abiotic stresses such as low light combined with elevated CO2 and distinct water availabilities (waterlogging and drought). Results reinforce the role of starch in leaves as a main storage organ of this species and also the high resilience of this reserve under low light, waterlogging and drought conditions. These findings also highlight the tight connection between starch reserves and growth maintenance. Additionally, this species has shown very distinct eco physiological strategies to cope with different water availabilities and a high ability to recover after drought that might be strictly related to growth maintenance during seedling establishment in the first period of terrestrial phase

Liver cancer is the fourth leading cause of cancer-associated deaths globally, and among primary liver cancers, hepatocellular carcinoma (HCC) encompasses 75-85% of all cases. HCC is a highly lethal disease due to limited treatment options – only a small subset of patients qualify for surgical resection or transplantation; the remaining patients often display resistance to radiation therapy or chemotherapy. Overexpression of the oncogene astrocyte elevated gene-1 (AEG-1) is associated with poorer survival and increased tumor recurrence in HCC, and numerous studies show its role in initiation of hepatocarcinogenesis. A prior study also demonstrated AEG-1 expression inhibits senescence by diminishing the ATM/Chk1/Chk2/p53/p21 DNA damage response (DDR) pathway. The aim of this study is to understand if AEG-1 expression promotes radioresistance in HCC. A CRISPR/Cas9 plasmid system was used to delete AEG-1 in the QGY-7703, HuH7 and DihXY cell lines, which model HCC. The cell lines were then treated with ionizing radiation (IR). We find that knockout of AEG-1 in these cell lines induces sensitivity to IR at 2.5 Gy. In response to radiation, AEG-1 wildtype cells more profoundly upregulate ATR, Chk1, and Chk2 signaling; and also more rapidly induce γH2AX, ATM, and BRCA1 signaling, which sense dsDNA breaks to initiate homologous recombination repair. We conclude that AEG-1 expression protects HCC cells from IR through two mechanisms: 1) rapidly initiating the DNA damage response; and 2) increasing replication fork stabilization. These findings indicate AEG-1 can be a therapeutic target in combination with radiation treatment to improve outcomes for HCC patients who demonstrate radioresistance.

Climate is changing and it is certain that this change is due to human activities. Atmospheric greenhouse gases have been rising in an unprecedented way during the last two centuries, although the land biosphere has dampened their increase by absorbing CO2 emitted by anthropogenic activities. However, it is unclear if this will continue in the future. This uncertainty makes it difficult to predict future climate changes and to determine how much greenhouse gas emissions must be reduced to protect climate. To understand the future role of plants in limiting the atmospheric CO2 level, the effect of increasing CO2 on plant photosynthesis and productivity has been studied. However, studies on trees showed contradictory results, which depended on the duration of the experiment. This revealed that an initial strong CO2 fertilization may be a transient response that disappears after a few years. Because climate changes over centuries, we must explore the response of vegetation to increasing CO2 on this time scale. Studying tree rings is a good alternative to impractical decade-long experiments, because trees have experienced the CO2 increase during the last 200 years and may already have responded to it. This thesis shows that the intramolecular distribution of the stable hydrogen isotope deuterium (deuterium isotopomer distribution, DID) of tree rings is a reliable tool to study long-term plant-climate adaptations. The premise for this is that the deuterium abundance in tree rings depends on environmental as well as physiological factors. Using newly developed methodology for DID measurements, the influences of both factors can be separated. Applied to tree rings, separating both factors opens a strategy for simultaneous reconstruction of climate and of physiological responses. The results presented show that DIDs are influenced by kinetic isotope effects of enzymes, allowing studies of metabolic regulation. We show that the abundances of specific D isotopomers in tree-ring cellulose indeed allow identifying environmental and physiological factors. For example, the D2 isotopomer is mostly influenced by environment, its abundance should allow better reconstruction of past temperature. On the other hand, the abundance ratio of two isotopomers (D6R and D6S) depends on atmospheric CO2, and might serve as a measure of the efficiency of photosynthesis (ratio of photorespiration to assimilation). The presence of this dependence in all species tested and in tree-ring cellulose allows studying adaptations of plants to increasing CO2 on long time scales, using tree-ring series or other remnant plant material. / Klimatet förändras och det är numera allmänt vedertaget att detta beror på människans aktiviteter. Halten av växthusgaser har stigit onormalt mycket under de senaste två århundradena och detta beror i största del på människans användning av fossila bränslen. Landbiosfären har hittills haft en buffrande effekt på klimatförändringen eftersom den tar upp och lagrar mycket av växthusgasen CO2. Det är dock osäkert om, och i så fall hur länge, denna effekt kvarstår. Detta gör det mycket svårt att förutsäga framtida klimatförändringar, och därmed hur mycket utsläppen av växthusgaser måste reduceras för att skydda klimatet. För att förstå växternas framtida förmåga att begränsa halten atmosfäriskt CO2 har man studerat effekten av förhöjda halter av CO2 på växters fotosyntes och produktivitet. Resultaten av dessa försök varierar i stor omfattning. Studier på träd odlade under höga halter CO2 indikerar att den initiala ökningen av en trädets produktivitet kan vara en temporär effekt som försvinner redan efter några år. Eftersom klimatförändringen sker under århundraden, måste även växternas anpassningar på förhöjd CO2 halt utforskas på denna tidsskala, men experiment som skulle ta tiotals år är opraktiska att utföra. Trädringar är ett bra sätt att studera sådana anpassningar, eftersom träd redan har upplevt de senaste två hundra årens ökning av koldioxid och dess trädringar därför kan innehålla information om en respons som redan skett. Denna avhandling visar att den intramolekylära fördelningen av den stabila väteisotopen deuterium i trädringar är en tillförlitlig metod för att studera växters anpassningsförmåga till långsiktiga klimatförändringar. Antagandet bakom denna strategi är att isotopfördelningen i trädringar beror på faktorer både från miljön och växtens fysiologi. Om båda faktorerna skulle kunna utvinnas från trädringar, skulle detta öppna en helt ny väg för parallell rekonstruktion av klimatet och växters anpassning till det. Avhandlingen presenterar den första tekniken för att mäta isotopfördelningen av deuterium i växtglukos. Resultaten visar att deuteriumfördelningen hos växtglukos påverkas av enzymers isotopeffekter, vilket möjliggör att regleringen av växternas metabolism kan kartläggas. I avhandlingen bevisas att halten deuterium i skilda intramolekylära positioner (isotopomerer) av glukos från trädringcellulosa bestäms av miljöfaktorer respektive trädets fysiologi. T.ex. påverkas deuteriumhalten i position 2 (D2 isotopomer) av glukosmolekylen huvudsakligen av miljön, vilket kan användas för att förbättra temperaturrekonstruktioner från trädringar. Å andra sidan är kvoten deuterium mellan två andra positioner (D6R och D6S) relaterat till halten atmosfäriskt koldioxid, och kvoten skulle kunna användas som mått för fotosyntesens effektivitet, dvs. förhållandet mellan fotorespiration och fotosyntes. Närvaron av denna relation i trädringar och annat växtmaterial i alla de växter vi hittills studerat, öppnar en helt ny möjlighet att studera växters anpassning till den ökande mängden CO2 i atmosfären under århundraden.

The anterior claustrum (CLA) has been implicated in epileptogenesis and epileptiform activity due to its abundant and widespread bilateral connections to some of the structures believed to play an important role in seizure generalization: the motor cortex, entorhinal cortex, limbic structures, and brainstem sites. Kindling in the CLA has been characterized as comprising two distinct phases: an early phase and a late phase. Early phase seizures progress quickly into generalized seizures, are short in duration, and resemble cortical seizures. Late phase seizures are characterized as being more severe in intensity, having longer durations, and resembling limbic-type seizures.<p>It is unknown whether kindling in the CLA will lead to changes in behaviour as seen after kindling of limbic sites. Thus, I measured the behavioural effects of kindling in the anterior CLA to investigate potential changes in learning, memory, and anxiety-related behaviours. I hypothesized that changes in behaviour would occur after kindling of late phase seizures, because of their close resemblance to limbic-type seizures, but not after kindling of early phase seizures. Anxiety-like behaviour was assessed in the elevated plus maze and open field. Object memory was assessed in an object recognition test, and spatial learning and memory were assessed in the water maze.<p>I found no significant changes in behaviour in the late phase group in comparison to the early phase and control groups. Thus, contrary to my hypothesis, late phase kindling of the CLA does not produce changes in learning and memory or alterations in anxiety-related behaviours.

A fundamental task in structural stability analysis is to ensure the safety of structures throughout their operational life so as to prevent catastrophic consequences either at ambient or elevated temperatures. This thesis concerns the stability of unbraced steel frames due to abnormal loadings or fire loads, and develops practical methods to evaluate the stability capacity of unbraced steel frames at ambient temperature or in fire. The problem of determining the elastic buckling strengths of unbraced steel frames subjected to variable loadings can be expressed as an optimization problem with stability constraints based on the concept of storey-based buckling. The optimization problem can be solved by the linear programming method, which is considerably simpler and more suitable for engineering practice than the nonlinear programming method. However, it was found that the frame buckling strength obtained from the linear programming method based on Taylor series approximation on column stiffness may be overestimated in some cases. Thus, a secant approximation of the column stiffness was introduced, and a modified linear programming method based on the secant approximation was proposed. Numerical examples show that the linear programming method in light of the secant approximation can yield conservative results and maintain simplicity. In spite of the convenience of the modified linear programming method, numerical examples show that the linear programming method cannot accurately detect the maximum and minimum frame buckling strengths in some cases. Therefore, an alternative method to assess the lateral stiffness of an axially loaded column derived by using two cubic Hermite elements to signify the column is proposed. Unlike the column stiffness obtained from the Euler-Bernoulli beam theory containing transcendental functions, the stiffness in the proposed method includes only polynomials. Thus, the column stiffness within the proposed method enables the minimization and maximization problems to be solved by efficient gradient-based nonlinear programming algorithms, which overcome the inability of linear programming algorithm to detect the minimum frame buckling strength in some cases. The accuracy of the column stiffness associated with the proposed method was compared with that of the Euler-Bernoulli beam theory. Four unbraced steel frames were investigated to demonstrate the efficiency of the proposed method. It is known that the evaluation of the lateral stability of steel frames subjected to elevated temperatures is different from that at ambient temperature due to the degradation of material strength. Thus, the storey-based buckling method at ambient temperature was extended to evaluating the stability of unbraced steel frames subjected to elevated temperature. To simulate a steel column exposed to the elevated temperature, an analytical model was proposed to examine the effects of axial loading, elevated temperature, and thermal boundary restraints on the lateral stiffness of steel columns in unbraced frames. The procedure of evaluating the stability capacity of unbraced steel frames at elevated temperature was then concluded. Numerical examples are presented to demonstrate the evaluation procedure of the proposed method. The column model was then refined to evaluate the lateral stiffness of steel column subjected to non-uniform elevated temperature distributions along the longitudinal direction. The lateral stiffness equation of the column model was derived based on the Euler-Bernoulli beam theory. The procedure to evaluate the stability capacity of unbraced steel frames subjected to non-uniform elevated temperature distributions was then concluded. The numerical examples were investigated with the proposed method for non-uniform elevated temperature distributions. Finally, initial attempts were made to evaluate the stability of unbraced steel frames with fire-protected columns at different fire scenarios. A degradation factor charactering the variation of the Young's Modulus of steel at elevated temperature was introduced. The objective and constraint functions were constructed, and optimal tools were used to determine the buckling strength of an unbraced steel frame at different fire scenarios.