Dissertations / Theses on the topic 'Curves of progress of the disease'

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Dentre as doenças causadoras de manchas foliares em algodoeiro, a mancha de ramulária tem se tornado importante em virtude das condições climáticas favoráveis para o desenvolvimento do patógeno, aliadas ao uso de cultivares suscetíveis, plantio consecutivo e extenso. Neste trabalho avaliaram-se as cultivares BRS Antares, BRS Araçá, BRS Aroeira, BRS Buriti, BRS Cedro, BRS Facual, BRS Ipê, BRS Sucupira, BRS 11612, Campo Verde 02, Campo Verde 05, Coodetec 409, Delta Opal, Deltapine Acala 90, Fiber Max 966, FMT 501, FMT 701, CNPA Ita 90, BRS Ita 96 e SL 502, quanto a resistência a Ramularia areola, em condições de campo na FCAV-UNESP no ano de 2006/2007. A severidade da doença, que ocorreu por infecção natural das plantas pelo fungo, foi avaliada semanalmente em trinta plantas previamente marcadas, utilizando uma escala descritiva de notas: 1 = 0%, 2 = Até 5%, 3 = de 5,1 a 25%, 4 = de 25,1 a 50% e 5 = Acima de 50% de área foliar com sintomas. O modelo de Gompertz foi o que melhor se ajustou aos dados de severidade de mancha de Ramulária em algodoeiro nas condições climáticas de Jaboticabal – SP no ano 2007. As cultivares Campo Verde 05, BRS 11612 e Deltapine Acala 90 foram as mais resistentes à doença. As cultivares BRS Ita 96, Campo Verde 02, BRS Facual, CNPA Ita 90 e BRS Buriti que apresentaram uma suscetibilidade intermediária à doença. As cultivares BRS Antares, BRS Aroeira, Delta Opal, SL 502, BRS Araçá, Coodetec 409, BRS Ipê, FMT 701, BRS Sucupira, BRS Cedro, Fiber Max 966 e FMT 501, mostraram – se mais suscetíveis.
Among the disease causing leaves spots in cotton plant, the gray mildew (Ramularia areola Atk.) has become important an disease in virtue of the environmental conditions favorable for development of the pathogens allread to the use of susceptible cultivars, consecutive and extensive plantation In this work the following cultivars were evaluated for the resistence to R. areola: BRS Antares, BRS Araçá, BRS Aroeira, BRS Buriti, BRS Cedro, BRS Facual, BRS Ipê, BRS Sucupira, BRS 11612, Campo Verde 02, Campo Verde 05, Coodetec 409, Delta Opal, Deltapine Acala 90, Fiber Max 966, FMT 501, FMT 701, CNPA Ita 90, BRS Ita 96 e SL 502. The experiment was carried out at the UNESP/FCAV experimental area in field conditions during 2006/2007. The disease severity occurred for natural infection and, the evolutions were made weekly in thirty marked plants using the scale: 1 = 0%, 2 = up to 5%, 3 = 5,1 to 25%, 4 = 25,1 to 50% and 5 = over of 50% of foliar area with symptoms. The Gompertz model was the better for the adjustment of the data of disease severity related to environmental conditions of Jaboticabal for 2006/2007. The cultivars Campo Verde 05, BRS 11612 and Deltapine Acala 90 were the most resistant to the disease. The cultivars BRS Ita 96, Campo Verde 02, BRS Facual, CNPA Ita 90 and BRS Buriti were moderately susceptible, while BRS Antares, BRS Aroeira, Delta Opal, SL 502, BRS Araçá, Coodetec 409, BRS Ipê, FMT 701, BRS Sucupira, BRS Cedro, Fiber Max 966 and FMT 501 were the most susceptible.

Orientador: Modesto Barreto
Banca: Margarete Camargo
Banca: Érika Auxiliadora Giacheto Scaloppi
Resumo: Dentre as doenças causadoras de manchas foliares em algodoeiro, a mancha de ramulária tem se tornado importante em virtude das condições climáticas favoráveis para o desenvolvimento do patógeno, aliadas ao uso de cultivares suscetíveis, plantio consecutivo e extenso. Neste trabalho avaliaram-se as cultivares BRS Antares, BRS Araçá, BRS Aroeira, BRS Buriti, BRS Cedro, BRS Facual, BRS Ipê, BRS Sucupira, BRS 11612, Campo Verde 02, Campo Verde 05, Coodetec 409, Delta Opal, Deltapine Acala 90, Fiber Max 966, FMT 501, FMT 701, CNPA Ita 90, BRS Ita 96 e SL 502, quanto a resistência a Ramularia areola, em condições de campo na FCAV-UNESP no ano de 2006/2007. A severidade da doença, que ocorreu por infecção natural das plantas pelo fungo, foi avaliada semanalmente em trinta plantas previamente marcadas, utilizando uma escala descritiva de notas: 1 = 0%, 2 = Até 5%, 3 = de 5,1 a 25%, 4 = de 25,1 a 50% e 5 = Acima de 50% de área foliar com sintomas. O modelo de Gompertz foi o que melhor se ajustou aos dados de severidade de mancha de Ramulária em algodoeiro nas condições climáticas de Jaboticabal - SP no ano 2007. As cultivares Campo Verde 05, BRS 11612 e Deltapine Acala 90 foram as mais resistentes à doença. As cultivares BRS Ita 96, Campo Verde 02, BRS Facual, CNPA Ita 90 e BRS Buriti que apresentaram uma suscetibilidade intermediária à doença. As cultivares BRS Antares, BRS Aroeira, Delta Opal, SL 502, BRS Araçá, Coodetec 409, BRS Ipê, FMT 701, BRS Sucupira, BRS Cedro, Fiber Max 966 e FMT 501, mostraram - se mais suscetíveis.
Abstract: Among the disease causing leaves spots in cotton plant, the gray mildew (Ramularia areola Atk.) has become important an disease in virtue of the environmental conditions favorable for development of the pathogens allread to the use of susceptible cultivars, consecutive and extensive plantation In this work the following cultivars were evaluated for the resistence to R. areola: BRS Antares, BRS Araçá, BRS Aroeira, BRS Buriti, BRS Cedro, BRS Facual, BRS Ipê, BRS Sucupira, BRS 11612, Campo Verde 02, Campo Verde 05, Coodetec 409, Delta Opal, Deltapine Acala 90, Fiber Max 966, FMT 501, FMT 701, CNPA Ita 90, BRS Ita 96 e SL 502. The experiment was carried out at the UNESP/FCAV experimental area in field conditions during 2006/2007. The disease severity occurred for natural infection and, the evolutions were made weekly in thirty marked plants using the scale: 1 = 0%, 2 = up to 5%, 3 = 5,1 to 25%, 4 = 25,1 to 50% and 5 = over of 50% of foliar area with symptoms. The Gompertz model was the better for the adjustment of the data of disease severity related to environmental conditions of Jaboticabal for 2006/2007. The cultivars Campo Verde 05, BRS 11612 and Deltapine Acala 90 were the most resistant to the disease. The cultivars BRS Ita 96, Campo Verde 02, BRS Facual, CNPA Ita 90 and BRS Buriti were moderately susceptible, while BRS Antares, BRS Aroeira, Delta Opal, SL 502, BRS Araçá, Coodetec 409, BRS Ipê, FMT 701, BRS Sucupira, BRS Cedro, Fiber Max 966 and FMT 501 were the most susceptible.
Mestre

A mancha preta dos citros (MPC), incitada pelo fungo Guignardia citricarpa, causa lesões em frutos depreciando-os para a comercialização no mercado interno de fruta fresca, restringindo-os para a exportação e pode causar queda prematura. Para auxiliar nos estudos epidemiológicos, foi desenvolvida uma escala diagramática para a severidade da MPC que contempla os dois tipos de sintomas usualmente observados no campo, “mancha dura”, cujos valores variam entre 0,5 e 49,0%, e “falsa melanose”, cujos valores variam entre 1,1 e 68%. O grau de suscetibilidade das variedades cítricas ‘Hamlin’, ‘Pera’ e ‘Valência’ à MPC foi avaliado em pomar comercial, sob infecção natural. O modelo monomolecular ajustou-se às curvas de progresso da incidência e da severidade da doença para as três variedades. Não houve diferença estatística significativa entre as taxas de progresso da MPC, concluindo-se que as três variedades possuem o mesmo grau de suscetibilidade à doença. O agente causal da MPC em sua fase epidêmica forma ascósporos e conídios. Os ascósporos, formados em folhas em decomposição no solo, são disseminados a curtas e longas distâncias pela ação do vento. Os conídios, formados em ramos e frutos fixados à planta, são disseminados a curtas distâncias pela ação da água. O padrão de distribuição espacial de plantas com MPC foi avaliado pelo índice de dispersão e pela função K de Ripley. As plantas doentes mostraram-se agregadas independentemente da incidência da doença, indicando elevada importância da dispersão do inóculo a curtas distâncias. Avaliou-se, também, o padrão de distribuição de frutos sintomáticos dentro da planta, pelo índice de dispersão e pela forma binária da lei de Taylor. Pelo índice de dispersão 84% das plantas avaliadas mostraram agregação de frutos sintomáticos. Pela lei de Taylor concluiu-se que a agregação de frutos sintomáticos independe da incidência da doença na planta, sugerindo a participação dos conídios no incremento da doença em condições de campo. Estudou-se o efeito da supressão de ascósporos, pela retirada periódica de folhas cítricas em decomposição do campo e o de conídios, pela colheita antecipada de frutos de maturação tardia, na intensidade da MPC, por dois anos, em área com alta pressão de inóculo. Esses tratamentos reduziram a severidade da doença, no segundo ano de avaliação, entretanto não foram suficientes para controlá-la adequadamente. Estas medidas de sanitização são importantes no controle da MPC, devendo ser adotadas em conjunto com o controle químico. Danos causados pela redução na produtividade e perdas medidas pelo retorno financeiro foram avaliados em dois experimentos. Tratamentos cujo incremento na produção por hectare que, em comparação com a isenção de tratamento, excederam 100 caixas de 40,8 kg, foram rentáveis. A amostragem de áreas para diagnosticar a presença da MPC depende da finalidade da produção. Em áreas para exportação e mercado interno de fruta fresca deve-se avaliar todas as plant as do talhão, uma vez que esta doença é quarentenária e causa danos qualitativos. Em áreas para a indústria de suco cítrico concentrado, 285 plantas são suficientes para amostrar incidências superiores a 15% de MPC, em pomares médios de 2200 plantas.
The fungus Guignardia citricarpa is the causal agent of citrus black spot (CBS), which is a disease that become the fruits unsightly and unsuitable for the fresh fruit market. Besides, premature fruit drop may occur, reducing the productivity. A diagrammatic scale for the two symptoms of CBS (hard spot and false melanose) was developed to evaluate the severity and help in epidemiological studies of this disease. The susceptibility level of ‘Hamlin’, ‘Pera’ and ‘Valência’ sweet orange to CBS was evaluated in commercial orchard, under natural infection. The monomolecular model was fitted to the incidence and severity progress curves of the disease for the three sweet oranges. According to the progress curves, there was not significant difference among cultivars, showing that ‘Hamlin’, ‘Pera’ and ‘Valência’ sweet orange have similar susceptibility level to CBS. G. citricarpa in the epidemic phase produce ascospores and conidia. The ascospores, produced in leaves on soil, are disseminated by wind, while conidia, produced in plant twigs and fruits, are disseminated by water. The pattern of spatial distribution of CBS plants was evaluated by dispersion index and Ripley K function. The groups of symptomatic plants were distributed independently of disease incidence, suggesting that short distance dispersion of the inocullum could be the most important factor in distribution of the disease. The binary form of Taylor´s power law and dispersion index were used to evaluate the distribution of symptomatic fruits in the plant. According to dispersion index 84% o f the evaluated plants showed aggregation of symptomatic fruits, while by the Taylor´s power law the symptomatic fruits aggregation occurred independently of the incidence of plant disease, suggesting that the increase of disease in field conditions is related to conidia production. The effect of ascospore suppression on intensity of CBS was evaluated by removing citrus leaves from the orchard soil surface, while the conidia suppression was evaluated by early harvesting of late maturation fruits. These treatments, carried out during two years in a high inocullum incidence area, reduced the disease severity in the second year, but the satisfactory control was not observed. However, these treatments could be important in CBS control whether used in association with chemical control. Damages caused by yield reduction and losses of financial return were evaluated in two experiments. In relation to non-treated orchards, those treated orchards where the production/ha increased more than hundred boxes (40.8 kg each box) were considered profitable. The destination of the orange production (juice of fresh fruit market) are important for determine the size of samples to assess the CBS incidence. Since the G. citricarpa fungus is considered a quarentine organism that causes qualitative losses, in areas used for production of fresh fruit market whole orchard has to be evaluated. However, in areas used for production of fruits to concentrated orange juice, 285 plants sampled are enough to determinate the CBS incidence superior to 15%, in average orchards containing 2200 plants.

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico
O cajueiro (Anacardium occidentale) no nordeste brasileiro caracterizando-se como uma das mais importantes fontes de emprego e renda das populaÃÃes. O lanÃamento de clones de cajueiro tipo anÃo-precoce aumentou a produtividade e qualidade das castanhas e pendÃculos, permitindo uma exploraÃÃo comercial mais vantajosa aos produtores, porem a uniformidade genÃtica deixou os pomares mais vulnerÃveis. A resinose hoje à considerada a principal doenÃa do cajueiro no semiÃrido nordestino. Esse estudo teve por objetivo avaliar a reaÃÃo de genÃtipos de cajueiro do tipo comum à resinose sob condiÃÃes de elevada incidÃncia no semiÃrido. Vinte clones de cajueiro-comum previamente selecionados pelo programa de melhoramento genÃtico da Embrapa AgroindÃstria Tropical foram usados no estudo e dessa forma foi possÃvel concluir que hà fontes de resistÃncia para uso em programas de melhoramento. Os clones CNPAT 06, CNPAT 08, CNPAT 11, CNPAT 12 e CNPAT 13 se apresentara como os mais resistentes a resinose, enquanto que os clones CNPAT 07, CNPAT 09, CNPAT 14, COMUM 05 e COMUM 31 forma os que obtiveram maiores notas de severidade de resinose. Outro importante resultado obtido foi que os clones CNPAT 08, CNPAT 11 e CNPAT 15 apresentaram capacidade de recuperaÃÃo da resinose. Por fim, sugere-se que com a avaliaÃÃo da incidÃncia à possÃvel estimar a severidade de resinose em pomares de cajueiro.
The cashew nut (Anacardium occidentale) represents a social and economic tradition in Brazilian northeastern as one of the most important source of income and labor for its people. The releasing of early-dwarf clones contributed to increase yield and nut and apple quality, allowing gain in profit by small growers, in spite of increase genetic vulnerability of orchards. Cashew gummosis is presently the most important disease of this species in semi-arid regions of northeast. This study aimed to evaluate reactions of common selected clones of cashew to gummosis under high disease pressure of semi-arid region. Twenty clones selected by the cashew breeding program of Embrapa AgroindÃstria Tropical were evaluated for three consecutive years. Clones named CNPAT 06, CNPAT 08, CNPAT 11, CNPAT 12 and CNPAT 13 attained the highest levels of resistance, while CNPAT 07, CNPAT 09, CNPAT 14, COMUM 05 and COMUM 31 otherwise were the most susceptible ones. It was also found that clones CNPAT 08, CNPAT 11 and CNPAT 15 are able to heal gummosis cankers, which points to a new kind of resistance to be considered. Finally, it was shown that monitoring gummosis incidence it is possible to estimate disease severity.

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Reburning caused by Phytophthora infestansis is characterized as an aggressive disease of great destructive impact, capable of limiting or even hindering the economic cultivation of the tomato plant under conditions of high humidity and low temperatures. In view of the problems reburning can cause to tomato plant crops, this work aimed to: 1) fit models to describe the progress of the disease and form groups of tomato accesses with similar curves; 2) estimate data referring to the number of days to reach 5% severity of the disease, by means of inverse regression; 3) fit survival curves by means of the Kaplan-Meier estimator for the access groups and compare them by means of the Logrank test;4)fit survival curves by means of probabilistic models and compare these curves with Kaplan Meir´s non-parametric technique. Using tomato reburning real data, it was possible to fit the exponential model (Y = y0 exp (rX)) to describe the disease s progress. The means of the parameter estimates were submitted to grouping analysis using the centroid method, generating 10 access groups. Time up to 5% of the disease was calculated via inverse regression. Non-parametric techniques were used to estimate survival function by means of the Kaplan-Meier´s estimator to compare the survival curves by the Logrank test .The survival function was also fit using the probabilistic models, exponential Weibull and Log-normal, respectively, which were compared by means of the verisimilitude ratio test (VRT), considering the generalized Gamma model, as a general case for these models. The methodology applied allowed fitting the exponential model to describe tomato plant reburning progress and to regroup the accesses studied in the 10 groups. The access BGH-6 obtained a smaller disease progress than the others, thus characterizing its higher resistance to the disease; An inverse regression allowed time estimation up to the occurrence of 5% of the severity of the tomato plant reburning. The Kaplan-Meier ´s non-parametric technique allowed estimating the survival curves of the tomato plant accesses belonging to the groups 1, 2, 4, 6 and 8. Utilizing the Logrank test, it could be concluded that most two-by-two comparisons were significant (p<0.05), except in the comparisons of groups 2x4, 4x8 and 6x8. The use of the probabilistic models, exponential Weibull and Log-normal allowed estimating the survival curves of groups 2, 4, 6 and 8, except for group 4, to which the Weibull model was not adequate. Comparing the probabilistic models with the non-parametric technique, the curves of the probabilistic models of groups 2 and 4 presented satisfactory results, compared to the curve estimated by Kaplan-Meier.
A requeima causada por Phytophthora infestans caracteriza-se por ser uma doença agressiva e de grande impacto destrutivo, podendo limitar ou até mesmo impedir o cultivo econômico do tomateiro sob condições de alta umidade e baixas temperaturas. Diante dos problemas que a requeima pode provocar às lavouras de tomate, este trabalho teve por objetivos: 1) ajustar modelos para descrever o progresso da doença e formar grupos de acessos de tomateiro com curvas semelhantes; 2) estimar dados referentes ao número de dias até atingir 5% de severidade da doença, por meio de regressão inversa; 3) ajustar curvas de sobrevivência por meio do estimador de Kaplan-Meier para grupos de acessos e compará-las mediante o uso do teste Logrank; 4) ajustar curvas de sobrevivência por meio de modelos probabilísticos e compará-las com a técnica não-paramétrica de Kaplan-Meier. Utilizando dados reais sobre a requeima do tomateiro, foi possível ajustar o modelo exponencial (Y = y0 exp (rX)) para descrever o progresso da doença. As médias das estimativas dos parâmetros foram submetidas à análise de agrupamento pelo método Centróide, o que gerou 10 grupos de acessos, sendo o tempo até a incidência de 5% da doença calculado via regressão inversa. Foram utilizadas técnicas não-paramétricas para estimar a função de sobrevivência por meio do estimador de Kaplan-Meier e para comparar as curvas de sobrevivência pelo teste Logrank. Foi também ajustada a função de sobrevivência, empregando-se os modelos probabilísticos Exponencial, Weibull e Log-normal, os quais foram comparados por meio do Teste da Razão da Verossimilhança (TRV), considerando-se o modelo Gama generalizado por ser caso geral para esses modelos. A metodologia utilizada permitiu ajustar o modelo Exponencial para descrever o progresso da requeima do tomateiro e agrupar os acessos estudados em 10 grupos. O acesso BGH-6 sofreu um progresso de doença menor que os demais, caracterizando-se, assim, sua maior resistência à enfermidade. A regressão inversa possibilitou estimar o tempo até a ocorrência de 5% da severidade da requeima do tomateiro. Pela técnica não-paramétrica de Kaplan-Meier, foi possível estimar as curvas de sobrevivência dos acessos de tomateiro pertencentes aos grupos 1, 2, 4, 6 e 8. Utilizando o teste Logrank, pode-se concluir que a maioria das comparações duas a duas foi significativa (p<0,05), exceto nas comparações dos grupos 2x4, 4x8 e 6x8. O uso dos modelos probabilísticos Exponencial, Weibull e Log-normal possibilitou a estimação das curvas de sobrevivência nos grupos 2, 4, 6 e 8, exceto no grupo 4, em que o modelo Weibull não foi adequado. Comparando os modelos probabilísticos com a técnica não-paramétrica, as curvas dos modelos probabilísticos dos grupos 2 e 4 apresentaram ajustes satisfatórios com relação à curva estimada por Kaplan-Meier.

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Brazil ranks ninth in the world production of tomato (Solanum esculentum L.), while much of this production is destined for processing industries. The added value obtained with the fruit processing endorses this species as the vegetable with the greatest economic importance in the Cerrado region of Brazil, where the State of Goiás stands out as the largest producer. Despite the favorable soil and climatic conditions, several factors have hindered its production, especially diseases caused by soilborne pathogens, which had increased their importance with the adoption of intensive production systems. Among them, white mold caused by Sclerotinia sclerotiorum (Lib.) De Bary has caused serious problems in infested soils, under mild temperatures and high humidity. Concerning the large number of S. sclerotiorum hosts and the lack of resistant hybrids, chemical control has been chosen as the most common method for disease management, despite not always efficient, due to the difficulties to reach the pathogen s resistance structures in the soil. Therefore, the study aimed to evaluate the disease escape on different tomato hybrids, to compare the effectiveness of synthetic fungicides mixed or not to potassium silicate; evaluate the biological control of white mold, with different commercial products based on Trichoderma spp. associated or not to a synthetic fungicide, and to evaluate the biological control with or without chemical fungicides, applied through chemigation. Tests were carried out in soil of medium texture at Unilever experimental farm, in Goiânia (GO), from 2008 to 2010. The experimental area was previously infested with sclerotia of the pathogen, obtained in pre-cleaning wastes of soybean. Drip irrigation was used in all tests, which had 4 plants m-1 with 1.5 meters between rows. The hybrids used in the disease escape tests were: U232, U2006 (Unilever), H9992, H7155 (Heinz), N877 (Nunhems) and H108 (Hypeel). In all other essays, Heinz 9780 was the chosen hybrid. All experiments were conducted under randomized blocks design with three replications, and had weekly assessments of disease incidence to estimate the area under the disease progress curve (AUDPC). We also evaluated the productivity and its components, as well as acidity, soluble solids content and industrial yield. The results were submitted to ANOVA and to the Scott Knott or Tukey tests at 5%, using the statistical program Sisvar. It was shown that: Hybrids H9992 and Hp108 had lower AUDPCs, suggesting a partial escape to white mold and that hybrid choice can be added to the disease management cultural practices, despite there was no difference on their yield. In 2008, under higher disease pressure, potassium silicate in plots without fungicide application showed disease incidence, AUDPC, productivity and industrial yield equivalent to treatments with fluazinam and procymidone, and superior to results with benzalkonium chloride. There was no difference between treatments with Trichoderma spp. associated or not to fluazinam, in any of the assessed traits. Regarding industrial yield, there was an interaction between Trichoderma, fluazinam and years, with higher pulp yield under higher disease incidence and fluazinam sprayed alone. It was found that biological control with Trichoderma spp. via chemigation as a single measure or in mixture with the synthetic fungicides procymidone fluazinam reduced the AUDPC and increased the productivity of processing tomatoes in 25 tons on average, compared to the control. Therefore, this study showed new options for the integrated management of white mold in processing tomatoes.
O Brasil ocupa o nono lugar na produção mundial de tomate (Solanum esculentum L.), sendo que grande parte desta produção é destinada a indústrias de processamento. A agregação de valor obtida com o processamento torna esta espécie a hortaliça de maior importância econômica na região do Cerrado do Brasil, onde o Estado de Goiás se destaca como maior produtor. Apesar das condições edafo-climáticas favoráveis, vários fatores têm dificultado sua produção, principalmente as doenças provocadas por patógenos habitantes do solo, que tem aumentado sua importância em sistemas de produção intensivos. Dentre elas, o mofo branco provocado por Sclerotinia sclerotiorum (Lib.) De Bary causa sérios problemas em solos infestados, sob condições de temperatura amena e alta umidade. Por ser um patógeno polífago e não existirem híbridos resistentes, o controle químico tem sido o método mais utilizado no manejo da doença, apesar de nem sempre ser eficiente pela dificuldade de atingir as estruturas de resistência do patógeno no solo. Dessa forma, este trabalho teve como objetivo avaliar diferentes híbridos quanto à arquitetura da planta para escape da doença; comparar a aplicação de fungicidas sintéticos com e sem a utilização de silício; avaliar o controle biológico do mofo branco por meio de diferentes produtos comerciais elaborados a partir de isolados do fungo Trichoderma spp., associados ou não com a aplicação de fungicida sintético, via barra de pulverização ou via fungigação. Foram conduzidos ensaios na fazenda experimental da Unilever, em Goiânia (GO), nos anos de 2008 a 2010, em solo de textura média. A área experimental foi previamente infestada com escleródios do patógeno, obtidos em resíduos de pré-limpeza de soja. A irrigação em todos os experimentos foi realizada por gotejamento em parcelas com estande de 4 plantas m-1 com 1,5 metro entre linhas. Os híbridos utilizados para avaliação quanto à arquitetura da planta foram: U232, U2006 (Unilever), H9992, H7155 (Heinz), N877 (Nunhems) e Hp108 (Hypeel). Já o híbrido utilizado nos demais ensaios foi o Heinz 9780. Todos os experimentos foram conduzidos sob delineamento experimental de blocos ao acaso, com três repetições, e tiveram avaliações semanais da incidência da doença para obtenção da área abaixo da curva de progresso da doença (AACPD). Avaliou-se ainda a produtividade e seus componentes, além de pH, teor de sólidos solúveis e rendimento de polpa. Os resultados foram submetidos à ANOVA e ao teste de Scott-Knott ou Tukey (5%) com auxílio do programa estatístico Sisvar. Verificou-se que: Em ambos os anos, a menor AACPD nos híbridos H9992 e Hp108 (Scott-Knott 5%), é creditada ao escape parcial da doença, devido ao porte das plantas e concentração de maturação, demonstrando que a escolha do híbrido pode ser adicionada às práticas culturais já utilizadas para o manejo da doença. Apesar de não ter havido diferenças entre os híbridos quanto à sua produtividade, as perdas na produção foram correlacionadas à incidência da doença e à AACPD. Em ano com elevada incidência os fungicidas (fluazinam e procimidona) são eficientes e silicato de potássio, sem aplicação de fluazinam ou procimidona, foi igualmente eficiente, podendo ser utilizado na agricultura orgânica. No controle do mofo branco, via barra de pulverização, na cultura do tomate para processamento industrial, o uso do Trichodermax e Trichodermil não diferiram do padrão de controle em relação a incidência da doença, produtividades e rendimentos. Não há influência do fluazinam via barra de pulverização no controle do mofo branco. Já para o rendimento de polpa há interação entre Trichoderma, ano e fluazinam, sendo que ocorreu um maior rendimento de polpa no ano de maior incidência com o uso do fluazinam. Verificou-se que o controle biológico com utilização do Trichoderma sp., via fungigação, para o mofo branco, isolado ou em combinação com os fungicidas sintéticos fluazinam e procimidona, reduz a AACPD e incrementa a produtividade do tomate para processamento industrial em até 25 toneladas ha-1 em média. O rendimento de polpa nos tratamentos com controle biológico foi aumentado em cerca de 1,0 e 7,0 t ha-1, respectivamente, em 2009 e 2010.

Starting with the development of an enzymatic assay, where an enzyme in solution hydrolysed a solid-phase bound peptide, a model for the kinetics of enzyme action was introduced. This model allowed the estimation of kinetic parameters and enzyme activity for a system that has the peculiarity of not being saturable with the substrate, but with the enzyme. In a derivation of the model, it was found that the sensitivity of the signal to variations in the enzyme concentration had a transient increase along the reaction progress with a maximum at high substrate conversion levels.

The same behaviour was derived for the sensitivity in classical homogeneous enzymatic assays and experimental evidence of this was obtained. The impact of the transient increase of the sensitivity on the error structure, and on the ability of homogeneous end-point enzymatic assays to detect competitive inhibition, came into focus. First, a non-monotonous shape in the standard deviation of progress curve data was found and it was attributed to the random dispersion in the enzyme concentration operating through the transient increase in the sensitivity. Second, a model for the detection limit of the quantity Ki/[I] (the IDL-factor) as a function of the substrate conversion level was developed for homogeneous end-point enzymatic assays.

It was found that the substrate conversion level where the IDL-factor reached an optimum was beyond the initial velocity range. Moreover, at this optimal point not only the ability to detect inhibitors but also the robustness of the assays was maximized. These results may prove to be relevant in drug discovery for optimising end point homogeneous enzymatic assays that are used to find inhibitors against a target enzyme in compound libraries, which are usually big (>10000) and crowded with irrelevant compounds.

Starting with the development of an enzymatic assay, where an enzyme in solution hydrolysed a solid-phase bound peptide, a model for the kinetics of enzyme action was introduced. This model allowed the estimation of kinetic parameters and enzyme activity for a system that has the peculiarity of not being saturable with the substrate, but with the enzyme. In a derivation of the model, it was found that the sensitivity of the signal to variations in the enzyme concentration had a transient increase along the reaction progress with a maximum at high substrate conversion levels. The same behaviour was derived for the sensitivity in classical homogeneous enzymatic assays and experimental evidence of this was obtained. The impact of the transient increase of the sensitivity on the error structure, and on the ability of homogeneous end-point enzymatic assays to detect competitive inhibition, came into focus. First, a non-monotonous shape in the standard deviation of progress curve data was found and it was attributed to the random dispersion in the enzyme concentration operating through the transient increase in the sensitivity. Second, a model for the detection limit of the quantity Ki/[I] (the IDL-factor) as a function of the substrate conversion level was developed for homogeneous end-point enzymatic assays. It was found that the substrate conversion level where the IDL-factor reached an optimum was beyond the initial velocity range. Moreover, at this optimal point not only the ability to detect inhibitors but also the robustness of the assays was maximized. These results may prove to be relevant in drug discovery for optimising end point homogeneous enzymatic assays that are used to find inhibitors against a target enzyme in compound libraries, which are usually big (>10000) and crowded with irrelevant compounds.

Background: Community acquired pneumonia (CAP) is a high incidence disease resulting in about 260,000 hospital admissions per year in Germany, more than myocardial infarction or stroke. Worldwide, CAP is the most frequent infectious disease with high lethality ranging from 1.2 % in those 20–29 years old to over 10 % in patients older than 70 years, even in industrial nations. CAP poses numerous medical challenges, which the PROGRESS (Pneumonia Research Network on Genetic Resistance and Susceptibility for the Evolution of Severe Sepsis) network aims to tackle: Operationalization of disease severity throughout the course of disease, outcome prediction for hospitalized patients and prediction of transitions from uncomplicated CAP to severe CAP, and finally, to CAP with sepsis and organ failure as a life-threatening condition. It is a major aim of PROGRESS to understand and predict patient heterogeneity regarding outcome in the hospital and to develop novel treatment concepts. Methods: PROGRESS was designed as a clinical, observational, multi-center study of patients with CAP requiring hospitalization. More than 1600 patients selected for low burden of co-morbidities have been enrolled, aiming at a total of 3000. Course of disease, along with therapy, was closely monitored by daily assessments and long-term follow-up. Daily blood samples allow in depth molecular-genetic characterization of patients. We established a well-organized workflow for sample logistics and a comprehensive data management system to collect and manage data from more than 50 study centers in Germany and Austria. Samples are stored in a central biobank and clinical data are stored in a central data base which also integrates all data from molecular assessments. Discussion: With the PROGRESS study, we established a comprehensive data base of high quality clinical and molecular data allowing investigation of pressing research questions regarding CAP. In-depth molecular characterization will contribute to the discovery of disease mechanisms and establishment of diagnostic and predictive biomarkers. A strength of PROGRESS is the focus on younger patients with low burden of co-morbidities, allowing a more direct look at host biology with less confounding. As a resulting limitation, insights from PROGRESS will require validation in representative patient cohorts to assess clinical utility. Trial registration: The PROGRESS study was retrospectively registered on May 24th, 2016 with ClinicalTrials.gov: NCT02782013

A coluna vertebral desempenha um papel importante no dia a dia oferecendo suporte necessário à movimentação do tronco além da locomoção do ser humano, sendo o seu funcionamento diretamente relacionado com a qualidade de vida; sua disposição e articulação das vértebras proporcionam estabilidade e flexibilidade à coluna vertebral, atributos necessários para o equilíbrio do ser humano. A hipercifose torácica, hiperlordose lombar e escoliose são as patologias posturais mais comuns e podem ser diagnosticadas pela mensuração do ângulo da curvatura da coluna vertebral. Comumente a radiografia é utilizada como método para a mensuração de tais ângulos, porém, além de ser um método caro, é altamente invasivo por causa da exposição à radiação, por isso não é aconselhado praticá-lo muitas vezes, sendo o acompanhamento do tratamento difícil de ser feito. Há diversos métodos não invasivos, porém não combinam praticidade, baixo custo e análise tridimensional da curvatura, sendo eficazes em mensurar apenas a coluna no plano sagital. Por esses motivos, para o uso clínico, o profissional de saúde necessita de um método barato, confiável, prático, que atenda suas necessidades e não invasivo para a mensuração da curvatura da coluna vertebral. O objetivo desse trabalho foi desenvolver e validar com a Cinemetria composto de cinco câmeras infravermelhas uma ferramenta computacional (LoB Analytics) para mensurar esse ângulos, o software terá código aberto e uso gratuito. A média de todos os ângulos obtida pela Cinemetria foi de 43,4±18,5º e pelo LoB Analytics foi de 43,9±17,7º, com uma correlação muito forte de 0,98. Foram feitas regressões lineares que confirmaram que ângulos calculados pelo LoB Analytics são tão confiáveis quanto os calculados pela Cinemetria, que é um método bastante utilizado hoje em dia. Os grandes diferenciais do LoB Analytics sobre a Cinemetria são: o seu baixo custo e a praticidade de usá-lo em laboratórios e clínicas.
The spine has an important role day by day offering the necessary flexibility for movement of the trunk besides support and locomotion of humans and being is directly related to the quality of life. The provision and articulation of the vertebrae are responsible for the stability and flexibility of spine attributes necessary for the balance. The thoracic hiper and hypo kyphosis, lumbar hiper and hypo lordosis and scoliosis are the most common postural pathologies and can be diagnosed by measuring the angle of the curvature of the spine. The radiographic method has been the most popular method for such measurement, however, it is an expensive method and also invasive (because its exposure to radiation), it is not the method more indicated to be used repeatedly, being the monitoring of treatment difficult to be done. There are several noninvasive methods but they do not combine practicality, low cost and three-dimensional analysis of the spine curvature, and they are effective in measuring the spine only in the sagittal plane. For these reasons, the health professional needs a method that has low cost, reliable, practical and noninvasive methods for measurement of the curvature of the spine. The goal of this work was develop and validate, with motion capture system (Cinemetria), a computational tool for this measurement (LoB Analytics), which will be free and open source. The mean of all Cinemetria angles was 43,9±18,5º and LoB Analytics angles was 43,9±17,7, with a very strong correlation coefficient of 0,98. Linear regressions confirmed that LoB Analytics angles are as reliable as those calculated by Cinemetria, which is a method widely used today. The differentials of LoB Analytics on Cinemetria are: low cost and practicality of using it in laboratories and clinics.

Background The UN's Sustainable Development Goals (SDGs) are grounded in the global ambition of "leaving no one behind". Understanding today's gains and gaps for the health-related SDGs is essential for decision makers as they aim to improve the health of populations. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016), we measured 37 of the 50 health-related SDG indicators over the period 1990-2016 for 188 countries, and then on the basis of these past trends, we projected indicators to 2030. Methods We used standardised GBD 2016 methods to measure 37 health-related indicators from 1990 to 2016, an increase of four indicators since GBD 2015. We substantially revised the universal health coverage (UHC) measure, which focuses on coverage of essential health services, to also represent personal health-care access and quality for several non-communicable diseases. We transformed each indicator on a scale of 0-100, with 0 as the 2.5th percentile estimated between 1990 and 2030, and 100 as the 97.5th percentile during that time. An index representing all 37 health-related SDG indicators was constructed by taking the geometric mean of scaled indicators by target. On the basis of past trends, we produced projections of indicator values, using a weighted average of the indicator and country-specific annualised rates of change from 1990 to 2016 with weights for each annual rate of change based on out-of-sample validity. 24 of the currently measured health-related SDG indicators have defined SDG targets, against which we assessed attainment. Findings Globally, the median health-related SDG index was 56.7 (IQR 31.9-66.8) in 2016 and country-level performance markedly varied, with Singapore (86.8, 95% uncertainty interval 84.6-88.9), Iceland (86.0, 84.1-87.6), and Sweden (85.6, 81.8-87.8) having the highest levels in 2016 and Afghanistan (10.9, 9.6-11.9), the Central African Republic (11.0, 8.8-13.8), and Somalia (11.3, 9.5-13.1) recording the lowest. Between 2000 and 2016, notable improvements in the UHC index were achieved by several countries, including Cambodia, Rwanda, Equatorial Guinea, Laos, Turkey, and China; however, a number of countries, such as Lesotho and the Central African Republic, but also high-income countries, such as the USA, showed minimal gains. Based on projections of past trends, the median number of SDG targets attained in 2030 was five (IQR 2-8) of the 24 defined targets currently measured. Globally, projected target attainment considerably varied by SDG indicator, ranging from more than 60% of countries projected to reach targets for under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria, to less than 5% of countries projected to achieve targets linked to 11 indicator targets, including those for childhood overweight, tuberculosis, and road injury mortality. For several of the health-related SDGs, meeting defined targets hinges upon substantially faster progress than what most countries have achieved in the past. Interpretation GBD 2016 provides an updated and expanded evidence base on where the world currently stands in terms of the health-related SDGs. Our improved measure of UHC offers a basis to monitor the expansion of health services necessary to meet the SDGs. Based on past rates of progress, many places are facing challenges in meeting defined health-related SDG targets, particularly among countries that are the worst off. In view of the early stages of SDG implementation, however, opportunity remains to take actions to accelerate progress, as shown by the catalytic effects of adopting the Millennium Development Goals after 2000. With the SDGs' broader, bolder development agenda, multisectoral commitments and investments are vital to make the health-related SDGs within reach of all populations. Copyright The Authors. Published by Elsevier Ltd. This is an Open Access article published under the CC BY 4.0 license.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES
The morphological and cultural characteristics of G. graminis var. graminis isolates from rice and grasses were studied. The fungus forms two types of mycelia, dark macrohyphae that join laterally to form runner hyphae or rhizomorphs and hyaline or infectious microhyphae, as well as fan shaped hyphae characteristic of the pathogen. Pigmented and lobed hyphopodia on lower leaf sheaths were formed both under natural conditions and artificial inoculations of plants. The perithecia containing asci and ascospores were found on leaf sheaths lesions on field samples. The perithecia were produced on leaf sheaths of inoculated plants as well as on detached sterilized leaf sheaths and on culture medium, potato-dextrose-agar (PDA). Hyphae and hyphopodia were formed from germination tubes of ascospores, and the hyphae under moist stress conditions produced chlamydospores which were initially hyaline and later attained dark color. The culture of Ggg, was characterized by fluffy aerial mycelium, white in the initial stages of growth and later with age, the colony color changed from dirty-white or mouse gray to almost black. The marked diagnostic colony characteristic of whorled appearance was the curling back of marginal hyphae. The amount and time of formation of perithecia varied among the isolates tested. The virulence test conduced with 20 isolates of rice and grasses, showed differences in aggressiveness both on rice seedlings and adult plants. In general, isolates from rice were more aggressive on rice than isolates from grasses. The test with four levels of inoculum (0, 5, 1.0, 2.0, 4.0 g per plant of autoclaved sorghum grains) and two plant ages showed that 60-day old were more susceptible than 35-day old plants. The spontaneous infection of healthy plants was observed in the greenhouse indicating the role of ascospores in the dissemination of black sheath rot in rice. Furthermore, the pathogenicity of ascospores of Ggg on rice plants was confirmed by inoculations tests. Six fields of upland rice were surveyed in the advanced stages of maturation for the incidence of black sheath rot. The disease incidence on tillers, under natural conditions of infection, ranged from 68 to 100%. The pathogenicity of 20 isolates retrieved from rice and grasses were studied. All isolates were pathogenic to rice and grasses such as baranyard grass (Echinochloa crusgalli), fountain grass (Pennisetum setosum) signal grass (Brachiaria sp), crab grass (Digitaria horizontalis), plantain signal grass (Brachiaria plantaginea), indian goose grass (Eleusine indica) and southern sandbur (Cenchrus echinatus). Winter cereals such as wheat, oat, rye, barley and triticale as well as sorghum, corn, and millet exhibited different degrees of susceptibility to the isolate Ggg-a 01. Significant differences were observed in relation to characteristic symptoms on the culm, lesion height, number of tillers or dead plants, presence of characteristic mycelium, fan shaped hyphae, production of hyphopodia and perithecia. The formation of perithecia was not observed on leaf sheaths of inoculated plants of millet, sorghum, southern sandbur and maize. All inoculated wheat plants were killed indicating more susceptibility than other cereals. The resistance of 58 upland rice genotypes were tested in the greenhouse, utilizing rice isolate Ggg-a 01. Of the genotypes assessed, the lesion height of SCIA16 and SCIA08 was significantly shorter compared to the highly susceptible genotype CNAS10351. The progress and dissemination of black sheath rot in rice was studied during two years under field conditions in savanna sensu lato ‘cerrado’. The central line of each plot was inoculated with isolate of Ggg to establish the infection foci. The soil was infested with four levels of inoculum (5.0, 10.0, 20.0 and 40.0 g of autoclaved sorghum grains containing mycelium / 40 cm) and main tiller of plants (4, 8, 16 and 32, tillers per plot/ 40 cm) were inoculated with 2.0 cm-long detached leaf sheaths containing perithecia by insertion between the culm and leaf sheath of the tiller. There was no significant effect of inoculum level on the disease severity obtained by soil infestation with mycelium as well as the plants infected with perithecia. However, the total area under disease progress curve was significantly smaller for plant infection with perithecia than for soil infestation by mycelium, during 2002/2003. The evaluation of disease incidence for the analysis of gradients was based on infected tillers in 1.6 square meter area, five lines on either side of the inoculated 40 cm-long central line. The analysis according models of Gregory (1968) and Kiyosawa & Shiyomi (1972) showed the existence of gradients in the first year, both for levels of inoculum of soil infection by mycelium and plant infection with perithecia. In the second year (2004/2005), there was no well defined gradient for all the treatments. The disease progress was not affected by inoculum levels on soil or plant infections. Monomolecular model was found more adequate in tests conduced under greenhouse conditions while the models of Gompertz and monomolecular, better described the disease progress under field conditions.
Foram estudadas características morfológicas e culturais de isolados de Gaeumannomyces graminis var. graminis provenientes de arroz e capins. O fungo se estabelece formando dois tipos de hifas: macrohifas, escuras, superficiais que se juntam lateralmente e formam cordões ou rizomorfas e microhifas, hialinas ou infecciosas, que penetram no hospedeiro. Forma também hifas em leque sobre as bainhas, a partir de macrohifas, que caracterizam o patógeno. Houve a formação de hifopódios lobados e pigmentados em bainhas, tanto em condições naturais como em inoculações. Observou-se peritécios contendo ascas e ascósporos, característicos do fungo, nas bainhas sobre as lesões em amostras coletadas no campo. Através de inoculação artificial, foram produzidos peritécios em bainhas de plantas, em bainhas destacadas e esterilizadas e em meio de cultura de batata-dextrose-ágar (BDA). Foram formadas hifas e hifopódios a partir de tubos germinativos dos ascósporos e as hifas crescidas em condições de estresse hídrico produziram clamidósporos, inicialmente hialinos e, posteriormente, de coloração escura. O micélio de Ggg, geralmente de aspecto aéreo fofo, é branco no início do crescimento, com variação de cor com a idade, do branco cinza ao marrom oliváceo e quase preto. Uma característica marcante é a aparência espiralada das macrohifas escuras nas bordas da colônia. Entre os isolados testados houve variação na quantidade de peritécios bem como na época de formação. Os testes de virulência realizados com vinte isolados provenientes de arroz e capins apresentaram diferenças em agressividade, tanto em plântulas quanto em plantas de arroz. Em geral, os isolados provenientes de arroz foram mais agressivos em arroz que os isolados de capins. O teste com quatro níveis de inóculo (0,5, 1,0, 2,0, e 4,0 g de inóculo por planta, multiplicado em grãos de sorgo autoclavados) e duas idades de plantas mostrou que as plantas inoculadas aos 60 dias após o plantio foram mais suscetíveis do que aquelas inoculadas aos 35 dias, requerendo menor nível de inóculo para a infecção. A patogenicidade de ascósporos de Ggg em plantas de arroz foi comprovada, bem como o papel dos ascósporos na disseminação do mal-do-pé do arroz. A incidência de mal-do-pé em lavouras de arroz de terras altas nas condições naturais de infecção variou de 68 a 100% de perfilhos infectados, entre seis lavouras avaliadas em fase avançada de maturação. Foi estudada também a patogenicidade dos vinte isolados de Ggg obtidos, provenientes de arroz e capins. Todos os isolados foram patogênicos a arroz e aos capins: capim arroz (Echinochloa crusgalli), capim avião (Pennisetum setosum), capim braquiária (Bachiaria sp.), capim digitaria (Digitaria horizontalis), capim marmelada (Brachiaria plantaginea), capim pé-degalinha (Eleusine indica) e capim timbete (Cenchrus echinatus). Os cereais de inverno, trigo, aveia, centeio, cevada e triticale, bem como sorgo, milho, e milheto apresentaram diferentes graus de suscetibilidade ao isolado Ggg-a 01. As diferenças foram significativas quanto a sintomas típicos na base do colmo, altura de lesão escura na bainha, número de perfilhos ou plantas mortas, presença de micélio característico, hifas em leque e produção de hifopódios e peritécios. Não foram observados peritécios em milheto, sorgo, timbete e milho e a maior suscetibilidade foi apresentada pelo trigo, com a morte de todas as plantas inoculadas. Foi testada a resistência de 58 genótipos de arroz de terras altas, utilizando o isolado Ggg-a 01 proveniente de arroz, em casa-de-vegetação. Entre os genótipos avaliados, SCIA16 e SCIA08 apresentaram altura de lesão significativamente menor, sendo considerados resistentes em relação ao genótipo CNAS10351, altamente suscetível. O progresso e disseminação do maldo- pé do arroz foram estudados durante dois anos, em condições de campo em solo de cerrado. Utilizou-se delineamento experimental de blocos completos ao acaso e quatro repetições. Cada parcela foi constituída de dezenove linhas de sete e cinco metros, respectivamente no primeiro e segundo ano, com espaçamento de quarenta centímetros. Foi inoculada a linha central de cada parcela com isolado de Ggg para estabelecer os focos de disseminação da doença. O solo foi infestado com micélio em quatro níveis de inóculo (5,0, 10,0, 20,0 e 40,0 gramas de grãos de sorgo autoclavados e colonizados com micélio / 40 cm da linha) e perfilhos foram inoculados (4, 8, 16 e 32 perfilhos / 40 cm da linha) com pedaços de bainhas de arroz de dois centímetros de comprimento, contendo peritécios e micélio, inseridos entre o colmo e a bainha. Não houve efeito de níveis de inóculo na severidade da doença, tanto para micélio no solo quanto para peritécios na planta, nos dois anos de experimento. Entretanto, a área total sob a curva de progresso da doença na safra 2002/2003 foi significativamente menor nas plantas infectadas com peritécios, do que nas plantas infectadas através de infestação do solo com micélio. A avaliação de incidência da doença para análise do gradiente foi baseada nos perfilhos contados em 1,6 metros quadrados, compostos de cinco linhas de quarenta centímetros de cada lado da fonte de inóculo, na linha central. A análise de gradiente, conforme modelos de Gregory (1968) e Kiyosawa & Shiyomi (1972) mostrou existência de gradiente no primeiro ano, tanto para níveis de inóculo quanto para os focos provenientes dos dois tipos de inóculo. No segundo ano (2004/2005), não houve gradiente definido para os tratamentos testados. O progresso da doença não foi afetado pelos níveis, tanto na infecção do solo com micélio, quanto na planta com peritécios. Em teste de ajuste de modelo matemático para estudos epidemiológicos, o modelo monomolecular foi o mais apropriado para estudos de mal-do-pé do arroz nas condições de casa-de-vegetação e os modelos de Gompertz e monomolecular são os que melhor descrevem o progresso da doença, nas condições de campo.

The major physiological function of hemoglobin (Hb) is to bind, transport and deliver oxygen to tissues; made efficient by endogenous effectors, such as protons and 2,3-diphosphoglycerate. Synthetic allosteric effectors of Hb (AEHs) are also known to modulate Hb oxygen affinity, showing potential for the treatment of sickle cell disease (SCD) and ischemic-related diseases. In this project, AEHs which increase Hb affinity for oxygen, including derivatives of the anti-sickling compounds, 5HMF and benzaldehydes, as well as an AEH that decreases Hb affinity for oxygen, RSR-13, were synthesized for their effects on Hb oxygen binding property and their capability to release NO from substituted nitrate ester moieties. Compounds that were found to increase Hb affinity for oxygen were further tested for their anti-sickling activities. Structural studies were carried out to gain insight into the compound’s mode of action. Development of these agents could be a therapeutic strategy for SCD or ischemic-related diseases.

This work deals with a design of hypokinetic dysarthria analysis system. Hypokinetic dysarthria is a speech motor dysfunction that is present in approx. 90 % of patients with Parkinson’s disease. Next there is described Parkinson's disease and change of the speech signal by this disability. The following describes the symptoms, which are used for the diagnosis of Parkinson's disease (FCR, VSA, VAI, etc.). The work is mainly focused on parameterization techniques that can be used to diagnose or monitor this disease as well as estimate its progress. A protocol of dysarthric speech acquisition is described in this work too. In combination with acoustic analysis it can be used to estimate a grade of hypokinetic dysarthria in fields of faciokinesis, phonorespiration and phonetics (correlation with 3F test). Regarding the parameterization, new features based on method RASTA. The analysis is based on parametrization sentences complicated for articulation. Experimental dataset consists of 101 PD patients with different disease progress and 53 healthy controls. For classification with feature selection have selected method mRMR.

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A Doença Renal Crônica (DRC) é caracterizada pela perda da capacidade de filtragem dos rins. O paciente com DRC tem diminuição dos níveis de força muscular e de condicionamento físico, os quais estão diretamente ligados à qualidade de vida e à realização das atividades da vida diária. A atividade física, especificamente o treinamento de força, pode ser utilizada como uma intervenção não farmacológica para o tratamento da doença. Para a realização desse tipo de programa há a necessidade da identificação do volume e intensidade do treinamento neuromuscular, através de testes de carga. No entanto, a aplicação dos testes de carga dinâmica máxima (uma repetição máxima ou de peso por repetição) não é adequada para pacientes com DRC em razão do seu baixo nível de força muscular. Antes de se definir qual o melhor teste para avaliação da carga de treinamento, é necessário, primeiramente, identificar as características da produção da força muscular nesses pacientes. Para tanto, os testes de esforço muscular isométrico parecem ser ideais para isso, em específico o da dinamometria computadorizada de preensão da mão que, além de fácil aplicação, possibilita a avaliação do comportamento da contração muscular através da análise da curva força-tempo. Neste estudo propõe-se uma técnica para análise das curvas, em sua fase de produção de força (fase rápida) através do ajuste, por quadrados mínimos, de um modelo matemático com quatro parâmetros (a,b,c,d). A amostra foi composta de 31 pacientes com DRC (51±15 anos, 69,94±13,34 kg e 1,65±0,08 m) e 4 sujeitos hipertensos (37 ± 14 anos, 75,1 ± 16,5 kg e 1,72 ± 0,12 m), como controle. Foram utilizados os dinamômetros JAMAR (referência) e o transdutor de preensão manual computadorizado, com empunhadura modificada. Não foram observadas diferenças significativas entre os valores de força máxima dos membros dominante e não dominante, e dos parâmetros b (p = 0,18), c (p = 0,35) e d (p = 0,05). Somente os valores da pré-carga (p < 0,001) e do parâmetro a (p < 0,001) foram significativamente diferentes, o que significa dizer que o paciente com DRC inicia o teste com força inicial maior do que o grupo controle e atinge mais lentamente o valor máximo de força. Novas pesquisas baseadas em diferentes protocolos de 6 testes de esforço muscular isométrico poderão confirmar as ações específicas das unidades motoras de contração lenta e rápida em cada fase da curva força-tempo.
The chronic kidney disease (CKD) is characterized by lost in kidney filtration capacity. These patients with CKD have decreased levels of muscle strength, physical functioning, which is connected with daily activities and quality of life. The physical activity can be employed as a non pharmacologic procedure, but to programming a physical training is necessary evaluated the features to be work. The standard of evaluations must be observed to ensure pureness of datum collected. The evaluation of strength-time curve can be one methodology used to clarify the muscle contraction behavior. So, we proposed a methodology of curve analysis of patients with CKD, using non linear and linear mathematic parameter mode, which when evaluated allow us make correspondence with muscle contraction physiology. The sample was determined by 31 patients (51±15 years old, 69,94±13,34 kg e 1,65±0,08 meters) with CKD and 4 individuals with high blood pressure (37 ± 14 years old, 75,1 ± 16,5 kg e 1,72 ± 0,12 meters), they were evaluated by handgrip test in 2 moments with 2 different dynamometers. Significative differences were not observe between values of maximal strength, between members and parameters [b] (p=0,18), [c] (p=0,35) e [d] (p=0,05). Merely the values of preload (p = 0,00000014),, of [a] parameter (p=0,00078), and the values of patients strength between dynamometers were significant different: right (p = 0,00003) and left (p = 0,0001). Using the parameters of strength-time curve become a methodology with good price, non-invasive and could be applied easily in the evaluations. The necessity of new instigations employed the analysis methods is evident.

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During the last crops, the soybean rust has been appeared as one of the most important problems in the national agriculture. The direct loses on the production and in the costs with fungicides have been increased the damages on this crop. Aiming to understand better the disease epidemiology, this work searched for answers by epidemic progress in two locations, the time of planting effect, the cycle of planting, the use of fungicide, and by different cultivars. The experiments were assembled in Experimental Stations from Agência Rural in Senador Canedo and in Anápolis. For each place were used three times of planting, six cultivars on the three crop cycles (Monsoy 6101 and BRSNina premature cycle; Emgopa 315 and BRSGO Santa Cruz middle cycle; Emgopa 313 and BRSGO Paraíso late cycle), with and without fungicide action, have been evaluated on the three parts of the plant (lower, middle and upper). Each time, to each one of the places, have been considered as an experiment with spli-split-plot. After the disease symptom observations, the split under chemical control were freaked each 21 days using pyraclostrobin+epoxiconazole on 66,5 g + 25 g a.i. ha-1. The evaluations, after the first symptom observation, have been done weekly up to the complete leaves took away. With the periodic severity data the Area Under Progress Disease Curve (AUPDC) and Relative Area Under Progress Disease Curve (RAUPDC), that is the area divided by the epidemic time duration, were calculated. The parameters were productivity, thousand-grains weight (TGW) and small grains percent (%SG). The delay on the start of the disease on Anápolis, comparing with Senador Canedo, increases the discussion on the results. The previous disease occurrence in Senador Canedo and the high level inoculate presented can be associated to the fact of experimental site in Senador Canedo has soybean cultivate all over the year. The delay on the start of the disease on Anápolis, compared to Senador Canedo has been resulted on productivity increase and fungicide effect decrease. Comparing the time of planting in both planting places, the second one presented the highest level of severity, but the highest level of productivity even. The use of fungicide decrease significantly the AUPDC, increase the productivity, the TGW and decrease the %SG. The premature cycle cultivars presented lowest disease severity. The cultivar Emgopa 315 although be a medium cycle presented results equals premature cycles cultivars. On each site the time of planting were differentiated. On high pressure inoculate condition the difference between evaluated factors was lower. On lower inoculate pressure the evaluated factors expressed better the changes. As conclusion we have: a) how early the disease appears higher is your effect on productivity; b) using premature cultivars the escape effect decrease the disease damages when compared to medium and late cycle; c) the disease decrease the soybean cycle by the defoliation; d) although all the cultivars presented susceptibility to rust, related to lower severity on partial resistance; e) the fungicide utilization pyraclostrobin+epoxiconazole on de 66,5 g + 25 g a.i. ha-1, used on first symptom and in 21 on 21 days decrease the disease progress and the effects on productivity; f) the disease progress decrease by fungicide utilization is better in late planting; g) under the fungicide effect pyraclostrobin+epoxiconazole with 66,5 g + 25 g a.i. ha-1 there s no variation time planting and site; h) under high inoculate pressure the variation between time planting on disease progress and productivity is lower; i) the time of planting must be considered but not lonely, always in association with others factors of fungus action; j) the use of RAUPDC is necessarily when there is variation the time of soybean cycle, affecting the rust epidemic duration; l) the highest disease level occurs on the part of the plant near the soil and the defoliation difficult the disease evaluation on this part of the plant; m) the most effective disease occurs on the highest parts of the plant.
Durante as últimas safras a ferrugem asiática da soja tem se apresentado como um dos maiores problemas na sojicultura nacional. Os prejuízos diretos pela queda da produção e os gastos com fungicidas têm acarretado prejuízos que vêm aumentando a cada safra. Objetivando compreender melhor a epidemiologia da doença, este estudo a buscou respostas para fatores como variação do progresso da epidemia em duas localidades, o efeito da época de semeadura, do ciclo da cultivar, do uso de fungicida e da resposta de diferentes cultivares. Os experimentos foram montados, nas Estações Experimentais da Agência Rural de Senador Canedo e de Anápolis. Para cada local foram utilizadas três épocas de semeadura, com seis cultivares nos três ciclos da cultura (Monsoy 6101 e BRSNina ciclo precoce; Emgopa 315 e BRSGO Santa Cruz ciclo médio; Emgopa 313 e BRSGO Paraíso ciclo tardio), com e sem a ação de fungicida, sendo avaliados os três terços da planta (inferior, médio e superior). Cada época, para cada um dos locais, foi considerada como um experimento com parcelas sub-sub-divididas. Após a observação dos sintomas da doença, as parcelas com controle químico foram pulverizadas a cada 21 dias com pyraclostrobin+epoxiconazole na dosagem 66,5 g + 25 g i.a. ha-1. As avaliações após o aparecimento da doença foram realizadas semanalmente até a queda completa das folhas. Com os dados de severidade periódicos calculou-se a Área Abaixo da Curva de Progresso da Doença (AACPD) e a Área Abaixo da Curva de Progresso da Doença Relativa (AACPDR), que consiste na divisão da área pelo período de duração da epidemia. As variáveis de rendimento obtidas foram: produtividade, massa de mil grãos (MMG) e porcentagem de grãos chumbinho (%CH). O atraso da entrada da doença em Anápolis, quando comparado a Senador Canedo, propiciou variações nos resultados que enriqueceram a discussão dos dados. A antecipação da ocorrência da doença em Senador Canedo e a alta pressão de inóculo apresentadas podem estar associadas ao fato da estação experimental em Senador Canedo possuir soja cultivada durante todo o ano. O atraso da entrada da doença em Anápolis, quando comparada a Senador Canedo, possibilitou um incremento na produtividade e menor efeito de fungicida. Entre as épocas avaliadas nos dois locais, a segunda apresentou os maiores índices de severidade, mas também os maiores índices de produtividade, fator relacionado às condições do ambiente. O efeito da utilização do fungicida diminuiu significativamente a AACPD, aumentou a produtividade, a MMG e diminuiu a %CH. Cultivares de ciclo precoce apresentaram menor severidade da doença, seguidos pelas cultivares de ciclo médio e tardio. A cultivar Emgopa 315 apesar de ser de ciclo médio apresentou resultados semelhantes às cultivares de ciclo precoce nas avaliações como um todo. Em cada local as épocas se comportaram de forma diferenciada. Em condições de alta pressão de inóculo a diferença entre os fatores estudados é menor. Para pressão de inóculo menor os fatores avaliados expressaram melhor suas variações. Como conclusões retiradas a partir dos resultados discutidos concluiu-se que: a) quanto mais cedo a ferrugem aparece durante o ciclo da cultura, maior é o seu efeito na produtividade da soja; b) a utilização de cultivares de soja de ciclo precoce propicia um efeito escape, que reduz os efeitos da ferrugem, quando comparado às cultivares de ciclo médio e tardio; c) a ocorrência da doença diminui o ciclo da cultura, antecipando seu término devido à desfolha prematura; d) apesar de todas as cultivares apresentarem suscetibilidade à ferrugem, algumas apresentam menor severidade relacionada a variações nos níveis de resistência parcial à doença; e) a utilização do fungicida pyraclostrobin+epoxiconazole na dosagem de 66,5 g + 25 g i.a. ha-1, aplicado a partir do aparecimento dos primeiros sintomas e posteriormente a intervalos de 21 dias diminuiu expressivamente o progresso da doença e seus efeitos nas variáveis de rendimento da soja; f) a redução do progresso da doença devido à aplicação do fungicida estudado é mais evidente com a semeadura tardia; g) sob o efeito da mistura pyraclostrobin+epoxiconazole na dosagem de 66,5 g + 25 g i.a. ha-1 não há variação entre época de semeadura e local; h) sob alta pressão de inóculo, as variações entre épocas de semeadura no progresso da ferrugem e no rendimento da cultura são menos explícitas; i) o fator época de semeadura não deve ser considerado isoladamente, mas sempre em associação a outros fatores que influenciam a ação do fungo como aplicação de fungicida, ciclo e resistência da cultivar; j) a utilização do parâmetro Área Abaixo da Curva de Progresso da Doença Relativa (AACPDR) é justificada para dados nos quais existe variação da duração do ciclo da soja, interferindo na duração da epidemia de ferrugem. Esta adequação se faz necessária para que os resultados de progresso da doença não sejam comprometidos; l) a parte da planta mais afetada pelos sintomas é o terço inferior e a desfolha dificulta a avaliação da doença nesta região; m) o controle mais efetivo da doença pelo fungicida ocorre nos terços superior e médio da planta

With pre-implantation genetic diagnosis (PGD), genetic testing and selective transfer of embryos is possible. In the future, germ-line gene therapy (GLGT) applied to embryos before implantation, in order to introduce missing genes or replace mutant ones, may be possible. The objective of this dissertation is to analyse moral aspects of these technologies, as described by eighteen British, Italian and Swedish gynaecologists and geneticists. The objective is systematised into three parts: research interviews and qualitative analysis, philosophical analysis, and elaboration of a framework that supports the combination of analytic methods. PGD was described as positive since it enabled some couples at risk for a genetic disease to have a child without the disease. PGD was described as in different senses ‘better’ than methods for prenatal diagnosis and selective termination of pregnancy. It was also described as positive since it provided couples at risk with one more option, even if it did not result in the birth of a healthy child. However, interviewees were concerned about the difficulty of defining and evaluating genetic disease. They were also concerned about patients’ choices, and about exaggerated use or misuse. Whereas PGD gave rise to ambivalence in terms of how to understand, describe and evaluate it, GLGT was often described as unrealistic or undesirable. The results of the qualitative analysis are used in a philosophical analysis of the concepts of choice, autonomous choice, ambivalence, trust and ambivalence in trust relations. A set of distinct characteristics of each concept are elaborated. The results of the philosophical analysis are used in the discussion of the results of the qualitative analysis. The study shows that the technologies imply both ‘new’ ways to perform ‘old’ medical practices and ‘new’ practices. Old moral questions are reformulated. New moral questions are added. Against the background of this, the concept of genetic identity is discussed. Key words: empirical ethics, pre-implantation genetic diagnosis, germ-line gene therapy, qualitative research, philosophical analysis, medical progress, genetic disease, choice, autonomous choice, ambivalence, trust, genetic identity.

This work deals with a design of hypokinetic dysarthria analysis system. Hypokinetic dysarthria is a speech motor dysfunction that is present in approx. 90 % of patients with Parkinson’s disease. The work is mainly focused on parameterization techniques that can be used to diagnose or monitor this disease as well as estimate its progress. Next, features that significantly correlate with subjective tests are found. These features can be used to estimate scores of different scales like Unified Parkinson’s Disease Rating Scale (UPDRS) or Mini–Mental State Examination (MMSE). A protocol of dysarthric speech acquisition is introduced in this work too. In combination with acoustic analysis it can be used to estimate a grade of hypokinetic dysarthria in fields of faciokinesis, phonorespiration and phonetics (correlation with 3F test). Regarding the parameterization, features based on modulation spectrum, inferior colliculus coefficients, bicepstrum, approximate and sample entropy, empirical mode decomposition and singular points are originally introduced in this work. All the designed techniques are integrated into the system concept in way that it can be implemented in a hospital and used for a research on Parkinson’s disease or its evaluation.

The goal of this investigation was to explore the efficacy of implementing a rehabilitation robot controlled by a noninvasive brain-computer interface (BCI) to influence brain plasticity and facilitate motor learning. The motivation of this project stemmed from the need to address the population of stroke survivors who have few or no options for therapy. A stroke occurs every 40 seconds in the United States and it is the leading cause of long-term disability [1-3]. In a country where the elderly population is growing at an astounding rate, one in six persons above the age of 55 is at risk of having a stroke. Internationally, the rates of strokes and stroke-induced disabilities are comparable to those of the United States [1, 4-6]. Approximately half of all stroke survivors suffer from immediate unilateral paralysis or weakness, 30-60% of which never regain function [1, 6-9]. Many individuals who survive stroke will be forced to seek institutional care or long-term assistance. Clinicians have typically implemented stroke rehabilitative treatment using active training techniques such as constraint induced movement therapy (CIMT) and robotic therapy [10-12]. Such techniques restore motor activity by forcing the movement of weakened limbs. That active engagement of the weakened limb movement stimulates neural pathways and activates the motor cortex, thus inducing brain plasticity and motor learning. Several studies have demonstrated that active training does in fact have an effect on the way the brain restores itself and leads to faster rehabilitation [10, 13-15]. In addition, studies involving mental practice, another form of rehabilitation, have shown that mental imagery directly stimulates the brain, but is not effective unless implemented as a supplemental to active training [16, 17]. Only stroke survivors retaining residual motor ability are able to undergo active rehabilitative training; the current selection of therapies has overlooked the significant population of stroke survivors suffering from severe control loss or complete paralysis [6, 10]. A BCI is a system or device that detects minute changes in brain signals to facilitate communication or control. In this investigation, the BCI was implemented through an electroencephalograph (EEG) device. EEG devices detect electrical brain signals transmitted through the scalp that corresponded with imagined motor activity. Within the BCI, a linear transformation algorithm converted EEG spectral features into control commands for an upper-limb rehabilitative robot, thus implementing a closed-looped feedback-control training system. The concept of the BCI-robot system implemented in this investigation may provide an alternative to current therapies by demonstrating the results of bypassing motor activity using brain signals to facilitate robotic therapy. In this study, 24 able-bodied volunteers were divided into two study groups; one group trained to use sensorimotor rhythms (SMRs) (produced by imagining motor activity) to control the movement of a robot and the other group performed the 'guided-imagery' task of watching the robot move without control. This investigation looked for contrasts between the two groups that showed that the training involved with controlling the BCI-robot system had an effect on brain plasticity and motor learning. To analyze brain plasticity and motor learning, EEG data corresponding to imagined arm movement and motor learning were acquired before, during, and after training. Features extracted from the EEG data consisted of frequencies in the 5-35Hz range, which produced amplitude fluctuations that were measurably significant during reaching. Motor learning data consisted of arm displacement measures (error) produced during an motor adaptation task performed daily by all subjects. The results of the brain plasticity analysis showed persistent reductions in beta activity for subjects in the BCI group. The analysis also showed that subjects in the Non-BCI group had significant reductions in mu activity; however, these results were likely due to the fact that different EEG caps were used in each stage of the study. These results were promising but require further investigation. The motor learning data showed that the BCI group out-performed non-BCI group in all measures of motor learning. These findings were significant because this was the first time a BCI had been applied to a motor learning protocol and the findings suggested that BCI had an influence on the speed at which subjects adapted to a motor learning task. Additional findings suggested that BCI subjects who were in the 40 and over age group had greater decreases in error after the learning phase of motor assessment. These finding suggests that BCI could have positive long term effects on individuals who are more likely to suffer from a stroke and possibly could be beneficial for chronic stroke patients. In addition to exploring the effects of BCI training on brain plasticity and motor learning this investigation sought to detect whether the EEG features produced during guided-imagery could differentiate between reaching direction. While the analysis presented in this project produced classification accuracies no greater than ~77%, it formed the basis of future studies that would incorporate different pattern recognition techniques. The results of this study show the potential for developing new rehabilitation therapies and motor learning protocols that incorporate BCI.

Cette thèse analyse les liens entre la naissance de la notion d’un progrès historique dans la deuxième moitié du dix-huitième siècle et la formation de l’économie politique en tant que science autonome. Contrairement à une idée reçue, l’économie classique post-smithienne et la théorie ricardienne en particulier n’apparaissent pas comme une «science lugubre», mais plutôt comme une théorie pure du progrès. Dans la première partie, nous dégageons les articulations entre conception de l’histoire et théorie économique à l’œuvre chez Richard Cantillon, François Quesnay et Adam Smith. Alors que la théorie de Cantillon exprime une conception cyclique de l’histoire tandis que la théorie physiocratique vise à la suppression de cette conception cyclique de l’histoire, la théorie smithienne se démarque de celles de Cantillon et Quesnay, en fondant une conception progressiste de l’histoire et en affirmant que le progrès est «naturel». Comme la conception progressiste de Smith repose sur une coordination, simple mais novatrice, du changement technique dans le temps et dans l’espace, la deuxième et la troisième partie étudie la théorie classique du progrès technique et du commerce international. C’est ici que Ricardo s’avère être l’économiste smithien le plus rigoureux, en ayant identifié la condition sous laquelle le progrès est, effectivement, «naturel», et en ayant insisté sur le fait que cette condition est approximativement satisfaite par les prix naturels. En conclusion, l’affirmation d’un progrès naturel est à la fois ce qui unit les économistes classiques (post-)smithiens, y compris Marx, et ce qui les distingue des représentants antérieurs de la même approche du « surplus »
This thesis analyzes the relations between the origin of the notion of historical progress in the second half of the eighteenth century and the formation of political economy as an autonomous science. In contrast to a traditional view, post-Smithian classical political economy and Ricardian economics in particular appear not as the ‘dismal science’, but rather as a pure theory of progress. The first part deals with the way in which conceptions of history and economic theory are articulated in the works of Richard Cantillon, François Quesnay et Adam Smith. Whereas Cantillon’s theory expresses a cyclical conception of history and physiocratic thought aims at the repression of this cyclical conception, Smith’s theory is opposed both to Cantillon and Quesnay, through its foundation of a progressive conception of history and the affirmation that progress is ‘natural’. Since Smith’s progressive conception of the historical process is based upon a simple, yet novel co-ordination of technical change in time and across space, the second and third parts study the classical theory of technical progress and the classical theory of international trade. It is in this context that Ricardo turns out to be the most radical of the ‘Smithian’ economists: Ricardo identified the condition under which progress is indeed ‘natural’ and insisted upon the fact that this condition is approximately satisfied by natural prices. In the final analysis, it is Smith’s affirmation of natural progress which provides the common framework for post-Smithian classical economists, Marx included, and distinguishes them from earlier exponents of the same ‘surplus approach’ to value and distribution

Alzheimer's disease (AD) is the commonest neurodegenerative disorder that has become increasingly prevalent in most countries. The chronic progressive deteriorating course is characterized by great variations in individual pathways of decline. This abstract summarizes the findings of a prospective study to examine the factors that affect clinical decline in a group of Chinese subjects with Alzheimer's disease (AD).
At the follow up, 19 (18.3%) subjects had died. 74 (71.2%) subjects were alive and were reassessed. Of the subjects reassessed, 49 (66.2%) remained stable at the same CDR, and 25 subjects (33.8%) had deteriorated to a more advanced stage of dementia. A significant deterioration in global cognitive scores (MMSE and DRS) was found (paired t-tests, p<.001). The estimated annual deterioration in MMSE and DRS scores was 1.34 and 4.93. There was a non-significant trend for overall reduction of NP symptoms at the follow up, but a sizable proportion of subjects still exhibited a variety of NP symptoms.
Development of research plan and study objectives is discussed in the third chapter. Due to escalating problem of care for dementia sufferers, a prospective study to examine the clinical factors that affect decline in Chinese elderly people with AD is needed. Four main research objectives are developed. The first objective is to examine the clinical profiles of Chinese subjects with AD. The second objective is to evaluate the relationships between different clinical dimensions of the dementia syndrome. Thirdly, the differences in clinical characteristics between mild and moderate AD would be examined. Finally, significant factors that affect the rate of clinical decline would be determined.
The baseline global cognitive performances were similar among different outcome groups. The 'deteriorated' group had a higher educational level (One way ANOVA, F=4.85, p=.01, Bonferroni comparisons). There was an excess of number of cerebrovascular risk factors (CVRF) in subjects who had deteriorated (Kruskal Wallis test, z=6.6, p=.04). For subjects with CDR 1 at baseline, a significant excess of Apo E4 allele was found in those who had deteriorated at follow up (Pearson chi square 5.72, p=.017; OR = 6.3, CI 1.3 to 30.53). The difference in Apo E4 allele frequency was not significant in subjects with CDR 2 at the baseline. The 'Deceased' group had more advanced age, lower scores in the recognition tests of the Hong Kong List Learning Test (HKLLT) (Kruskal Wallis test, z=8.06, p=.008) and significantly higher scores of 'Parkinsonian signs' (Mann-Whitney U, z=2.99, p=.003). Concerning baseline NP syndromes, 70% of subjects in the 'Affective' groups remained stable at follow up; 31.8% of subjects in the 'Disturbing' groups died, another 31.8% deteriorated at follow up. Logistic regression analysis revealed that a lower score of recognition test of HKLLT, a higher score of 'Parkinsonian signs' and old age were significant predictors for mortality at the 22-month follow up. No significant predictor, apart from a higher premorbid educational level, for the deterioration to a more advanced level of dementia could be identified.
The fifth chapter reports the main research findings. The mean (SD) age at the baseline assessment was 78.18 (5.97) years. The mean (SD) of the Chinese version of the Mini-Mental State Examination (MMSE) and Mattis Dementia Rating Scale (DRS) scores were 16.21(3.69) and 94.88(13.17) respectively. Subjects with moderate AD (Clinical Dementia Rating, CDR=2), compared to subjects with mild AD (CDR=1), performed worse across all cognitive tests. NP symptoms, as evaluated by the Chinese version of the Neuropsychiatric Inventory (NPI), were prevalent and could be classified into 3 subgroups using Latent Class Analysis (LCA): the 'non-disturbing', 'affective' and 'disturbing' groups. The severity of soft neurological signs (SNS) and NP symptoms was more prominent as dementia became more severe. Strong associations between 'Motor coordination' and Sensory integration' signs with cognitive functions were found. The association between NP syndromes and cognitive functions were not as significant.
The following chapter describes the methodology. A group of 104 Chinese subjects with NINCDS-ADRDA criteria for AD were assessed twice in a naturalistic observational study with an average duration of 22 months. Comprehensive evaluation of cognitive, neuropsychiatric (NP), neurological characteristics, cerebrovascular risk and Apolipoprotein E gene polymorphism status was performed at the baseline. The progression of cognitive and clinical decline was compared at the follow up assessment. Baseline and follow up characteristics of cognitive, neuropsychiatric (NP) symptoms and soft neurological signs (SNS) were compared with a group of normal control (NC-FU, CDR=0) and questionable dementia (QD-FU, CDR=0.5). Significant factors influencing progression to a more advanced dementia and mortality were determined.
The introductory chapter outlines the major findings of recent studies on the clinical aspects of AD. Clinical AD is found in 3.6 % of Hong Kong Chinese elders over 70 years old. Literature review suggested that it is a genetically predisposed complex disorder with disease manifestations strongly modulated by health and lifestyle factors.
The last chapter lays out the conclusions of this study. Careful characterization of clinical profile should be emphasized in the management of elderly suffering from AD. This information will be useful for the assessment of prognosis and the formulation of care plan for AD sufferers.
The second chapter focuses on review of recent literature concerning factors that affect cognitive deterioration and clinical decline in AD. The potential determinants of disease progression included genetic predispositions, cognitive and neuropsychiatric profiles, neurological deficits and medical comorbidity.
The sixth Chapter comprises the discussion. The findings of this study provided information about the rate of cognitive and clinical decline in Chinese subjects with AD. The performance characteristics in cognitive tests, inter-subject variations, prevalence of Apo E4 allele and NP symptoms are potential factors that would influence the assessment of cognitive function with time. The universal occurrence of NP symptoms in AD supported a biological explanation for this clinical dimension. The findings also support the notion that cognitive and NP symptoms are relatively independent dimensions of the clinical dementia syndrome. The association between SNS and severity of cognitive impairment suggests that bedside neurological assessment is a feasible way to detect subtle neurological deficits in subjects with very early AD. The presence of 'Parkinsonian signs' predicted mortality, which indicated that the presence of co-morbid subcortical pathology play a significant role in determining the overall outcome. It appeared that trait factors such as the presence of the Apo E4 allele, a higher educational level and pre-existing cerebrovascular diseases, are associated with a faster rate of disease progression, although individual factors may operate differently at different phase of illness.
Lam Chiu Wa.
Source: Dissertation Abstracts International, Volume: 67-11, Section: B, page: 6299.
Thesis (M.D.)--Chinese University of Hong Kong, 2005.
Includes bibliographical references (p. 150-185).
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Abstracts in English and Chinese.
School code: 1307.

碩士
國立中央大學
營建管理研究所
91
Abstract The construction progress of a project is very often controlled by the S-curve indicating the relationship between the projects expenses vs. the time elapsed. If the actual progress curve falls below the forecasted curve, the progress is behind the schedule. Various factors, such as the accuracy of the forecasted curve, the reviewer’s experience, the climate condition, the topography of the site, etc. may affect the effectiveness of the evaluation of the progress. It is also wondered that if the percentage of the total budget spent will truly reflect the progress of a construction project. A more reasonable indicator is thus needed to distinguish those projects lag behind from the projects go ahead of schedule. In this study, the progress curves collected from 12 building projects are used to create an envelope of curves known as Banana Curves for evaluating the reasonable range of proper progress in a typical building project. The Banana Curves are also used to study the reasoning of: 1.Provision 111 of the Implementation Rules of Government Procurement Law for the punishment on the contractors if the progress falls behind more than 10%, 2.Administration Rules on the punishment on the contracting entity if the budget spent falls less than 90% in the fiscal year. It is concluded that: 1.The 10% threshold indicated in the Provision 111 of the Implementation Rules may be misleading sometimes, 2.The upper bound of the Banana Curves may be adopted as a criteria to allow insensitive to encourage the contractor to progress faster, and, 3.The Banana Curves are good indicators for a reasonable construction progress.

碩士
南華大學
生死學研究所
93
This narrative research aims at studying how a Machado-Joseph Disease patient faced her disease and daily life, and how she demonstrated her strength and regenerated her energy to live while her body kept degenerating. Therefore the objectives of this research are to investigate the following areas: 1) To understand the difference of the patient’s attitude before and after the awareness of her genetic disease; 2) To understand how genetic disease occurs from one generation to another, different mind set between different members of the family when they are informed of the disease, and different stages of the way family members take care of each other; 3) To understand the patient’s strength to stay alive in the knowledge of a currently incurable genetic disease. 　 　　The methodology in this research involves mainly with interviews, completed with literature review and data analyses. There are six chapters in this thesis, including Preface, Literature Review, Methodology, The Story of “One Rope,” Analysis and Discussion of the Story, and Introspection and Ideas of Further Research. 　 The findings in this research include: 1. In this research, the patient faced the unknown in life with hope. After the root of the disease was identified, this hope was then transformed into the basis of “no-despair.” 2. When the patient suffered the disease, she focused her attention totally on her own pain, whereas when it turned out that there were more family members suffering the same disease, they began to bear the disease with the love of a family. When the disease was still in obscurity, there were more complaints in the family. However, when the situation was cleared up, they became understanding and the whole family was in unity. 3. Facing the incurable genetic disease, the patients were not able to keep living solely with their own senses. The “love” from and to their family was the major strength that kept the patients to hang on. 　 　　The researcher makes some suggestions according to the process and results of this research, hoping that they might be helpful for the medical authority and workers.

博士
國立陽明大學
臨床醫學研究所
105
BACKGROUND. Fabry disease is an X-linked lysosomal storage disease results from mutation in the α-Galactosidase A gene (GLA) that cause deficient α-Galactosidase A (α-Gal A). The incidence of male patients with classic Fabry disease (FD) is about 1/50,000. Although the females were generally considered to be the carriers of FD due to the X-linked inheritance, there is increasing recognition that manifestations in heterozygous females can develop vital organ damage and cause severe morbidity and mortality, as severe as those in affected males. The Fabry disease has two major phenotypes: the type 1 classic FD and the type 2 later-onset FD. Affected males with the type 1 classic phenotype have little or no α-Gal A activity and have onset of acroparesthesias, hypohidrosis, angiokeratomas, and/or a characteristic corneal dystrophy in childhood or adolescence. Males with the type 2 later-onset phenotype have residual α-Gal A activity, little or no vascular endothelial Gb3 accumulation, and lack of the early clinical manifestations of patients with the type 1 classic phenotype. As the age, affected males with the type 2 phenotype develop progressive multi-systemic involvement leading to renal failure, hypertrophic cardiomyopathy, and/or cerebrovascular disease. Recently, several studies revealed that the prevalence of later-onset FD was much higher than previously expected. It suggested that the later-onset FD might present as an important hidden health issue in certain ethnic or demographic populations in the world. In Taiwan, we have a specific Fabry mutation, IVS4+919G>A (IVS4). The specific Fabry mutation has a very high prevalence about 1 in 1600. However, the natural history of its phenotype has not been systemically investigated, especially the cardiac involvement. The study was designed to analyze the results of a large-scale newborn screening program for Fabry disease and to understand the natural course of the Fabry disease with the specific IVS4 mutation. METHODS The α-Gal A activity in dried blood spot (DBS) of filter paper was determined for the newborn screening of FD since 2008. For the newborn who was screened with low α-Gal A activities initially, the secondary re-tested analysis was done. If the double DBS screening showed positive, then the newborn will be recalled and referred to Taipei Veterans General hospital for further confirmation. Genetic analysis for Fabry mutation was performed for the individuals with low α-Gal A activities. Complete pedigree study was important with detailed investigation of the whole family, including the grandmother and grandfather and even the great-grandmother and great-grandfather, who would be the key individuals effected by disease. The level of α-Gal A activity and genetic analysis could be done for the familial members who was suspected carrying the Fabry mutations. Furthermore, the clinical history and observation of each familial member, especially carring Fabry mutation, must be carefully evaluated. For the individuals who suspected with cardiac manifestations, we used EKG, echocardiography, and cardiac magnetic resonance imaging for detailed evaluation. Biomarkers including the Gb3, lysoGb3 and genetic confirmation studies were also performed. Some patients with Fabry mutations have received the cardiac catheterization and endomyocardial biopsies to confirm the pathogenesis and the severity of the disease. RESULTS To date, 916,383 newborns have been screened for FD in Taiwan since 2008 to December 2015. In our center, a total of 1,439 individuals carrying Fabry mutations have been found. Of these, 1,201 (83.5%) individuals have been identified with the later-onset mutation, IVS4+919G>A (IVS4). 620 IVS4 adults had undergone echocardiogram for the analysis of the prevalence of left ventricular hypertrophy (LVH) and 129 FD patients including 100 IVS4 adults had gadolinium-enhanced cardiac magnetic resonance imaging (GE-CMRI). LVH occurred in 67% of males and 32% of females over 40 years old. GE-CMRI evidenced significant late gadolinium enhancement (LGE) in 38.1% of IVS4 males and 16.7% of IVS4 females without LVH. Seventeen underwent endomyocardial biopsies, which revealed significant globotriaosylceramide (Gb3) substrate accumulation in their cardiomyocytes. CONCLUSION In Taiwan, we have a high prevalence of the specific Fabry IVS4+919G>A mutation. Significant cardiomyocyte substrate accumulation in IVS4 patients leads to severe and irreversible cardiac fibrosis before development of LVH or other significant cardiac manifestations. Thus, it might be too late to start ERT after hypertrophic cardiomyopathy or significant cardiac manifestations have occurred for later-onset Fabry patients. This study also indicates the importance of newborn screening for early detection of the insidious but ongoing irreversible cardiac damage in the patients with later-onset FD.

碩士
國立臺灣大學
職業醫學與工業衛生研究所
105
Many studies have shown that particulate matter (PM) may have adverse effects on the human body. PM has been associated with mortality and morbidity of cardiopulmonary diseases. PM may affect the CNS by two pathways, through the direct or peripheral way. In the peripheral way, systemic inflammation induced by PM and transfer inflammatory response to the brain by enhanced neuroinflammation and oxidative stress. PM might contribute to neurodegeneration diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease. Alzheimer’s disease is a progressive neurodegenerative disease and the most common form of dementia, which is pathologically characterized by the amyloid plaque of amyloid-beta (Aβ) , neurofibrillary tangles of hyperphosphorylated tau protein. However, few toxicology studies explored the association between PM exposure and the progress of AD. The objective of the study is to explore the ambient particulate matter induced pathological lesions and cognitive impairment of Alzheimer''s disease by using 3xTg-AD mice. In the experiment, we use 3xTg-AD mice contain three mutations associated with Alzheimer''s disease. This is the first transgenic model to develop both plaque and tangle pathology in AD- relevant brain regions. The pathology of Alzheimer''s disease is closely mimics the distribution pattern that occurs in human AD brains. Male 3xTg-AD mice (17 weeks old) were randomly divided into control (filtered air, n=5) and exposure group (ambient PM, n=6) for about 12 weeks whole body inhalation exposure. The ambient air exposure was conducted by using Taipei Air Pollution Exposure System for Health (TAPES). The system can introduce the ambient air outside and provides non-concentrated ambient air. After exposure, Morris water maze post-test were conducted. Aβ, hyperphosphorylated tau protein and oxidative, nitrative stress marker of 8-OHdG and 8-NO2Gua were determined. The mean mass concentration for exposure ambient PM2.5 was 7.6 μg/m3 during the exposure duration. In Morris water maze test, sub-chronic exposure to ambient PM2.5 may not impair spatial learning and memory in 3xTg-AD mice. 8-OHdG, 8-NO2Gua and Aβ42 were not significantly different between the control and the exposure group in hippocampus, cerebellum and cortex. Most of the 8-OHdG, 8-NO2Gua and Aβ42 levels also below the LOD (Limit of Detection). In the immunohistochemistry stain, Aβ1-16 were not detected and one of the 3xTg-AD mice in the exposure group had more phosphorylated tau protein. We found no significant differences between the control and the exposure group in histopathology of lung and brain. Further study should be conducted to explore the mechanism and toxicity of Alzheimer''s disease induced by PM in the older 3xTg-AD mice.

碩士
國立中興大學
生命科學系所
107
Down’s syndrome (DS), caused by the duplication of chromosome 21, is the most common hereditary genetic disease of intellectual disability. Except face and morphological abnormality, DS patients suffer with Alzheimer’s disease (AD)-like mental retardation and dementia at their young age. Our previous evidence indicates that F127-encapsulating can reduce the cytotoxicity of N-butylidenephthalide (Bp), one of the main components of Angelica sinensis. Feeding F127-coated Bp at the dosage of 200 mg/kg for nineteen weeks showed the attenuation of memory/learning disabilities in SAMP8 mice. In this study, we used the mice model of DS to further evaluate the therapeutic effect of F127-Bp (200 mg/kg) on DS-like dementia for five months. We found that F127-Bp treatment significantly enhance the learning performance, determined by the Morris Water Maze and Barnes Maze test. This learning improvement was not caused by the motor advantage, evidenced by the similar scores of Rotarod and grip test between the non-treated and treated DS mice. Immunohistochemistry staining further demonstrated that F127-Bp treatment increased the number of astrocytes in the hippocampus, accompanied with the reduced Aβ content and hyperphosphorylation of Tau protein, the two hallmark of AD cytopathology. These results strongly indicated that F127-Bp compound is a potential drug for attenuating the mental retardation of Down’s syndrome patients.

越來越多的研究證據表明阿滋海默症（AD）相關的認知障礙並非僅限於記憶、注意、執行等功能，高級視覺功能也在疾病過程中受到影響。值得注意的是，高級視覺功能受損可能與疾病的發生和發展密切相關，並可能對病人的智力下降產生影響。為此，本研究基於多模態磁共振測量方法，對AD進展過程中高級視覺腦網絡的變化進行全面分析，並對維生素B12在減緩高級視覺皮層萎縮方面的作用進行探索性評估。
在本文第一部份，我們使用全腦逐體素腦連接分析方法在縱向和橫向靜息態功能磁力共振數據上比較了發展為AD的輕度認知障礙（MCI）病人與穩定MCI及正常人之間的腦連接差別。結果表明進展性MCI病人多個腦區的功能連接發生改變，其中包括了兩個重要的高級視覺皮層腦區。這為之後集中研究高級視覺皮層提供了依據。另外分析結果不支援橫向比較結果具有很好的預測MCI是否進展的價值。
第二部份，我們使用腦區啟動似然評估（activation likelihood estimation, ALE）的方法定位腦高級視覺皮層的位置。ALE分析根據高級視覺功能種類分類。結果給出了多套高級視覺皮層的腦空間坐標，即一系列按功能分類的高級視覺腦區圖。
第三部份，我們使用前一步中獲得的ALE坐標定位AD和MCI病人的高級視覺皮層，並進一步利用基於體素的形態學分析和靜息態功能連接的方法分析其在疾病中灰質萎縮和功能連接情況。此外我們還應用圖論分析方法評估了高級視覺網絡的拓撲學結構變化。結果發現AD病人的背側視覺網絡以特徵路徑長度變長和聚類係數升高為其主要特點。此外我們還觀察到AD病人的高級視覺皮層萎縮廣泛，而MCI病人的萎縮則相對局限。
第四部份，我們對維生素B12補充治療在有輕度B12缺乏的MCI病人中減緩高級視覺皮層萎縮和認知衰退的療效進行評估。我們分析了用藥組和安慰劑組縱向（27個月）視覺皮層體積和認知功能變化。結果表明治療有效改善B12缺乏，但是並不可以減緩MCI患者認知減退和腦萎縮。
最後，綜合多模態各項分析結果我們認為在AD發展過程中高級視覺皮層的損害可能是一個長期的過程，並與疾病的嚴重程度及進展的風險相一致。這些發現有望拓寬我們對AD/MCI疾病中高級視覺功能障礙的認識並有助於我們更加深入的瞭解AD的病理過程。
Increasing evidence has suggested that Alzheimer’s disease (AD) related cognitive dysfunctions were not limited to memory, attention, and executive processes, and the high-level visual (HLV) functions were also involved in AD progression. More importantly, the decline of HLV functions is possibly related to the pathogenesis or progression of the disease, and may contribute to the intellectual deterioration in AD. Therefore, based on the advance of multimodal neuroimaging probes, this study aimed to provide a comprehensive characterization of the neurobiological changes of brain HLV network during AD progression and to investigate the treatment effect of VB12 on HLV cortices atrophy.
In the first part, we performed a whole-brain voxel-wise connectivity analysis (i.e., voxel-wise degree analysis based on graph theory) on the cross-sectional and longitudinal resting-state fMRI data of mild cognitive impairment (MCI) patients who progress to AD (PMCI) by comparing with stable MCIs and control subjects. Several brain regions showed significantly altered connectivity in PMCI group, and several classical HLV regions were included. The results provided objective evidence that HLV cortices were involved in the AD-related progression, thus lead us with more confidence and interest to focus the subsequent analyses on HLV cortices in AD and MCI.
In the second part, to focus the subsequent analyses on HLV cortices, we used the activation likelihood estimation (ALE) to define the cortical location of HLV cortices. Several sets of brain coordinates of HLV cortices were successfully provided and sorted in accordance with their corresponding HLV function categories (i.e., a series of functionally sorted HLV maps of object, face, and motion perceptions, etc.).
In the third part, acquired HLV maps in previous part were applied to locate the HLV cortices in AD and MCI patients, and their gray matter atrophy and functional connectivity were respectively analyzed by voxel-based morphometry (VBM) and resting-state functional connectivity (RSFC). Furthermore, the topological alterations of HLV network were evaluated. We found impaired functional connectivity with prolonged characteristic path length and increased clustering coefficient in the “where” visual network of AD patients. Besides, three atrophied HLV regions in late MCI while extensive atrophied HLV cortices (i.e., 28 regions) in AD were found, and the observed atrophy was found to be correlated with the cognitive decline.
In the fourth part, the effect of VB12 supplementation on slowing the cognitive decline and HLV cortices atrophy was evaluated. The volume changes of whole-brain and HLV cortices and cognitive functions were evaluated in methylcobalamin supplement and placebo groups before and after a 27-month follow-up. The results indicated that methylcobalamin 1000 mcg daily could effectively treat the VB12 deficiency, while didn’t prevent cognitive decline or brain atrophy significantly in MCI patients.
In summary, the integrated findings suggest that the impairment of HLV cortices might be a long-term process along the AD continuum, and correspond with the disease severity and the risk of progression. We hope these findings could extend our knowledg
Deng, Yanjia.
Thesis Ph.D. Chinese University of Hong Kong 2016.
Includes bibliographical references (leaves ).
Abstracts also in Chinese.
Title from PDF title page (viewed on …).
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.

碩士
國立臺灣大學
農業化學系研究所
86
The MRL/lpr mice develop a syndrome that resembles human systemic lupus erythematosus ( SLE ), including production of autoantibodies and formation of immune complexes. They have a strikingly short life span and die at the age of 6~8 months secondary to renal failure. The purpose of this study was to investigate the effects of high levels of vitamin E supplementation on the autoimmune disease courses. Ninety weanling MRL/lpr female mice were randomly divided into three groups and respectively fed on an AIN-76 diet containing 5% fresh soybean oil ( Control ), control diet supplemented with vitamin E at 10 times levels of AIN-76 ( E10 ), or 20 times levels ( E20 ).After 14 weeks, half of the mice were killed for in vitro experiments at 5 months of age. The results showed that the relative weights of spleen and kidney were reduced in E10 and E20 groups. Supplementation with all-rac--tocopheryl acetate elevated the -tocopherol content and reduced TBARS in liver and kidney. With respect to the antioxidant enzyme activities, the hepatic SOD and GSH-Px activity were significantly ( p<0.05 ) higher in E20 group and the renal SOD activity was significantly higher in E10 group. The E10 and E20 groups had lower IL-6 and PGE2 secreted from peritoneal cells than the control group. PGE2 production by spleen cells was also reduced in E10 and E20 groups. But there were no effects on TNF-、IL-6 and IL-10 production. In conclusion, vitamin E supplementation decreases the oxidative stress and the PGE2 production from splenocytes and peritoneal macrophage, but it neither reduce the autoantibody production nor prolong the life span through the Th1、Th2 cells regulation in MRL/lpr mice.

BACKGROUND: Differences in disease-modifying therapy (DMT) prescribing patterns between different groups of neurologists have not been explored. HYPOTHESIS: MS-specialist neurologists use a broader range of DMTs in contrast to generalist neurologists who preferentially prescribe Avonex. METHODS: Ontario neurologist demographic and geographical characteristics were linked to 2009 DMT prescription data. Lorenz curves and Gini coefficients were constructed to examine prescribing patterns; separating neurologist characteristics dichotomously and separating Avonex from the other DMTs. Gini Coefficients were compared using jack-knife statistical techniques to derive 95% confidence intervals. RESULTS: Prescriptions are highly concentrated with 12% of Ontario neurologists prescribing 80% of DMTs. High-volume prescribers show a broader range of DMT use while low-volume prescribers tend to use a particular DMT. CONCLUSIONS: The majority of DMTs are prescribed by a small subset of neurologists. High-volume prescribers show more variability in DMT use while low-volume prescribers tend to individually focus on a narrower range of DMTs.

博士
國立臺灣大學
微生物與生化學研究所
93
The purpose of this study was to investigate the effect of vitamin E supplementation on the autoimmune disease in NZB/W F1 female mice. The animal model and cell culture experiments were conducted to extend the mechanism of vitamin E supplementation in different dietary condition. The mice were fed an AIN-76 diet containing either 10 % oxidized frying oil+5 % fresh oil (SF), SF supplemented with all-rac-alpha-tocopheryl acetate at a level of 550 mg/kg diet (SFE10), 5 % fresh oil (E1), E1 supplemented with all-rac-alpha-tocopheryl acetate at 500 mg/kg (E10) or vitamin E deficiency (E0) respectively. The results showed that both MRL/lpr and NZB/W F1 mice fed the SFE10 diet convalesced growth and food intake. NZB/W F1 mice fed the SFE10 diet had lower anti-dsDNA IgG antibody level and longer life span than those fed the SF diets. The vitamin E supplementation in the oxidized oil significantly decreased TBARS values in the kidney and spleen of NZB/W F1 mice. The RBC hemolysis and TBARS values were increase in mice fed the ED diet. IFN-gamma and IL-6 production by mitogen-stimulated splenocytes decreased in mice fed on the SFE10, E10 and E0 diets. The IL-2 secretion by PHA-stimulation significantly increased in the SFE10 and E0 groups. The splenocytes from mice fed on the E0 diet have lower proliferative responses by PHA and LPS stimulation. The percentage of T cells significantly increased while major histocompatibility complex (MHC) class II-bearing cells decresed in the spleens of the SFE10 and E0 groups. The SFE10 group had significantly higher LA composition and tended to have lower AA and urinary bicycle-PGE2 than those of the SF diet group. We previously demonstrated that high dose of alpha-tocopherol succinate inhibited IL-2 mRNA expression and production in PHA-activated splenocytes of MRL/lpr mice. The na��ve T helper cells differentiated to major distinct subsets, T helper 1 (Th1) and T helper 2 (Th2) from BALB/c TCR-transgenic mice. Th1 cell treated with 50 microM TOC increased the IL-2 secretion in splenocyte, but 1000 microM alpha-TOC decreased the IL-2 secretion. We examined the regulation of alpha-tocopherol (alpha-TOC) on IL-2 expression by investigating the gene expression of IL-2, I-kappa-B-alpha and PPARgamma in splenocytes from BALB/c mice. The results showed that low dose of alpha-TOC increased IL-2 gene expression, but high dose of alpha-TOC had opposite effects that might involve in upregulating the PPARgamma pathway, enhancing I-kappa-B-alpha expression, inducing apoptosis, and suppressing proliferative responses of splenocytes. Therefore, vitamin E supplementation in normal diet decreases IL-6 and IFN-γ secretion, but did not affect apoptosis and IL-2 secretion. The results suggest that high dose of vitamin E may not benefit Th2-prone autoimmune disease. Vitamin E supplementation in oxidized oil and vitamin E deficiency decrease oxidative stress, anti-dsDNA IgG antibody, regulate cytokines and subsequently alleviate the severity of autoimmune disease such as systemic lupus erythematosus.

Veterinarians often perform controlled experiments in which they inoculate animals with infectious diseases. They then monitor the transmission process in infected animals. The aim of such experiments can be to assess vaccine effects. The fitting of individual-level models (ILMs) to the infectious disease data, typically achieved by means of Markov Chain Monte Carlo (MCMC) methods, can be computationally burdensome. Here, we want to see if a vaccination effect can be identified using simpler regression-type models rather than the complex infectious disease models. We examine the use of various logistic growth curve models, via a series of simulated experiments in which the underlying true model is a mechanistic model of infectious disease spread. We want to investigate whether a vaccination effect can be identified when only partial epidemic curves are observed, and to assess the performance of these models when experiments are run with various sets of observational times.