Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 1996. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (M. Sc.)--University of Hong Kong, 1998. / Includes bibliographical references (leaf 37-41).

<p>Denna studie syftar till att undersöka i vilka spontana lektyper inomhus, förskolebarn uttrycker matematiska begrepp. Bakgrunden till studien är att vi anser att matematikarbetet på förskolan ska utgå från barnens perspektiv och då har leken en viktig betydelse. Leken ses som en central del för matematiklärandet och begreppsbildningen och därför är förskolan en lämplig plats för denna studie. Om barnen redan på förskolan skapar ett intresse och börjar använda matematiska begrepp gynnar det även den begreppsanvändning som krävs i skolan. Med inspiration av ett etnografiskt förhållningssätt har det genomförts observationer på två förskoleavdelningar, vid sju tillfällen på varje avdelning. Avsikten har varit att observera barns matematiska begreppsanvändning i den spontana leken. Vid observationerna har ett särskilt framtaget observationsschema använts för att dokumentera vilka lektyper och matematiska begrepp som observerats. Resultatet visar att olika lektyper stimulerar olika begrepp och de begrepp som uttrycks mest är jämförelseord. De lektyper som framkom i resultatet är; rollek, bygglek, lego, spel, bilar, figurer, dockor och övrigt. Avslutningsvis diskuteras resultatet och metoden i förhållande till litteraturen och våra egna tankar. Tre teman är framtagna i resultatdiskussionen; språket, leken och miljön med utgångspunkt i barnens begreppsanvändning och lektyperna.</p> / <p>This study aims to examine in which spontaneous play indoors, children in preschool expresses mathematical concepts. The background to the study is our belief that the mathematics work in preschool should be assumed from the children's perspective and that play has an important role in that work. The spontaneous play are a central part of mathematics learning and conception and therefore is preschool an appropriate place for this study. If children in preschool at an early stage creates an interest and begin using mathematical concepts if also favors the concept of use, that required in school. Inspired by an ethnographic approach, there have been observations of two preschool departments, on seven occasions in each department. The intention has been to observe children's mathematical concepts used in the spontaneous play. At the observations, a designed observation chart has been used to record the play types and mathematical concepts observed. The result shows that different play types stimulate different concepts, and the concepts that are mostly expressed are comparison words. The play types that emerged in the result are; role play, construction play, lego, games, cars, figures, dolls and others. To sum up, we discuss the result and the method in relation to the literature and our own thoughts. Three themes are produced in the result discussion; language, play and the environment on the basis of children's concepts of use and play types.</p>

An important feature of Chinese industrial relations is the changing role of collective labour since the early 2000s. The authorities in Beijing have introduced substantial new legislation and policies aimed at strengthening the contractual basis of employment and encouraging the extension of trade union membership and collective bargaining. Meanwhile, unofficial strikes in non-state sectors have become increasingly severe in terms of their intensity and complexity. The Chinese trade unions, which in law protect workers’ rights, have encountered challenges from the increasing demands of these strikes. This thesis looks at how the Chinese trade unions have responded to pressures from rank-and-file workers in the private sector. The thesis starts with a review of the development of Chinese labour law relating to dispute resolution and trade unions in the transition from a command economy to a partial capitalist market economy. A literature review of the role of trade unions in industrial conflict indicates the limitations of recent research arising from looking at workplace disputes from the outside. The thesis then presents original case studies of six foreign-owned enterprises, including one joint-venture enterprise. It describes and analyses the process of dispute resolution or avoidance at these workplaces during the strike wave of 2010. The cases drew on a range of interviews and participant observations, and examined the ways in which the trade unions had been practically involved in managing strikes. The thesis suggests that strikes continue to be autonomously organised by workers, while trade unions generally pursue a role limited to resolving the dispute. The cases illustrate how union guidance in dispute resolution encourages concessions to workers’ demands by foreign employers. The operational forms and the effects of this union dominated approach are varied, reflecting the specific industrial relations context at different locations. The research suggests that this reactive union approach is likely to be unstable and conditional. In the reforms that have followed strike action, the status of trade unions is being enhanced as a result of a simultaneous strengthening of their links with both workers and the government authorities. There are mixed implications for the likelihood that the trade unions will become more responsive in character. The thesis provides insights on the potential and constraints of state-approved trade unions in channeling workers’ discontents into formal decision-making processes.

In the Czech Republic, as well as in other countries, there are cases of fires reported, where the thermal destruction of the body of the victim is not a result of thermal effects of a fire of the surrounding space. These fires are typical for the affected area that is limited to the body and the immediate surroundings only. Frequently the bodies show extensive and complete thermal destruction of tissues to high levels of carbonization. Human tissue combustion appears in foreign sources, especially popular science, described with the term "Spontaneous Human Combustion". In the Czech Republic the translation equivalent is "samovolné vzplanutí osob". The motivation for the choice of the topic "Special Cases of Human Combustion" was the lack of adequate fire origin investigation methodology to be used by the members of the Fire and Rescue Service of CR. The other reason for the choice of the topic was the misleading information published in popular science sources and alternative information sources. The first step of the research was the literature research of the available professional texts and specific fire reports. Based on information gathered was designed scope and conditions of a research experiment conducted on samples of the same type of animal tissue, which corresponds to the human tissue. For the samples the tissue of a domestic pig was used and the samples were prepared to contain uniform percentages of muscle, fat and bone, including skin. The experiment was carried out in an accredited laboratory owned by the company PAVÚS, a.s. - fire testing laboratory #1026 in Veselí nad Lužnicí. With each sample the influence of different flammable substances on the level of subsequent damage of the animal tissue was tested. The influence of typical layered clothing, flammable base and cover was evaluated. Different real environment conditions were simulated with each sample. The aim of the thesis was an evaluation of the possibility of a start and the process of combustion of animal tissue. It was confirmed that the combustion of animal tissue, including bone tissue, is possible in a regular fire. The flammable materials in the form of clothing and the presence and the characteristics of a flammable base are crucial for the start and process of the combustion. The experiment revealed the possibility of further independent combustion of the tissue when supplied with a certain amount of initial energy by burning of the surrounding materials. The combustion of animal tissue characterically takes predominantly the form of smouldering lasting several hours, where the maximal measured temperature of the surface of the sample was 644,50 oC. The experiment further revealed the temperatures of the human tissue combustion not to be high enough to cause an ignition of flammable materials within defined distance. The results of the thesis can be used to define the basic guidelines for the members of Fire and Rescue Service of CR and the criminal justice, who can provide support with investigation of the causes of these types of fires of persons.

Spontaneous restoration of wetlands on arable field was observed in the part of South Bohemia. The main aim of the study was to describe colonization of the newly formed wetlands by plants in relation to character of the site and its surroundings (age and size of the wetland, distance to the field margin and to a nearest permanent wetland). Data were collected during six seasons (2011, 2012, 2013, 2014, 2015, 2016) and analyzed using regression analyses, scatterplots and ordination analyses (DCA, CCA). There were found no significant effects of the distance to the permanent wetland and the distance to the edge of the field on species composition of the newly created wetlands. The effect of successional age of wetlands on their species composition was significant. Species with a higher colonization ability were relatively more frequent in those wetlands located in a longer distance form the edge of the field. Participation anemochorious and hydrochorious species increased during a succesional time on studied wetlands, the proportion zoochorious and hemerochorious species decreased. These conclusions, however, be taken with caution, because it captured with a relatively small margin successional age. In general, it was shown that spontaneous restoration of wetlands on arable land is possible and runs to (semi)natural wetland vegetation.

Made available in DSpace on 2015-07-22T20:50:12Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-08-25 / Os antígenos cancer/testículo (CTAs) são considerados promissores alvos para abordagens de imunoterapia em câncer devido à sua alta imunogenicidade e padrão de expressão praticamente restrito a tecidos tumorais (estão também expressos em células germinativas do testículo, placenta e ovário fetal). Apesar do padrão de expressão dos CTAs estar bem estabelecido em carcinomas, pouco se sabe sobre a expressão desses antígenos em neoplasias linfóides como Linfomas de Hodgkin (LH) e Linfomas não-Hodgkin (LNH). Objetivo: Avaliar o potencial desses antígenos específicos tumorais como candidatos à imunoterapia em linfomas, através da análise de expressão protéica dos CTAs e avaliação da resposta imune humoral espontânea contra esses antígenos, correlacionando os achados com os dados clínicos e prognóstico. Métodos: Três blocos de Tissue Microarray (TMA) foram construídos a partir de 38 amostras teciduais de LH clássico e 106 de LNH obtidos nos arquivos do Departamento de Anatomia Patológia da UNIFESP. As lâminas de TMA foram submetidas a um painel de imunohistoquímica para 9 CTAs, a saber: MAGE-A1, MAGE-A3, MAGE-A4, MAGE-A10, CT7, CT10, NY-ESO-1, LAGE e GAGE. A avaliação da imunidade humoral espontânea foi realizada em 97 amostras de soro de pacientes com LNH ao diagnóstico (59 dos quais foram incluídos na casuística do TMA), utilizando-se a técnica de ELISA em um painel mais amplo de CTAs (MAGEA1, MAGE-A3, MAGE-A4, MAGE-A10, NY-ESO-1, CT7, CT10, CT24, CT45, CT46, CT47, CT63, CT83, SSX-1, SSX-2, SSX-4, LAGE-1, GAGE-2, SAGE-1, XAGE-1). Resultados: De forma global, houve baixa expressão de CTAs nas amostras analisadas, visto que apenas 21,1% das amostras de LH e 11,3% das amostras de LNH apresentaram positividade para pelo menos 1 dos CTAs incluídos no painel de imunohistoquímica. MAGE-A (18,4%) e CT7 (13,2%) foram os CTAs mais frequentemente expressos em LH, enquanto MAGE-A (6,6%), GAGE (5,7%) e NY-ESO-1 (4,8%) foram os mais expressos em LNH. Apesar de não ter sido encontrada diferença estatisticamente significante na expressão de CTAs entre os subgrupos clínicos de LH, houve maior frequência de positividade nos pacientes com estadiamento avançado (28,6%), comparado àqueles com estadiamento inicial (11,8%). Nos subgrupos clínicos de LNH, a frequência de expressão de CTAs foi maior nos linfomas agressivos (14,9%) em relação aos indolentes (3,1%), nos linfomas difusos de grandes células B (LDGCB) (16,1%) comparado aos não-LDGCB (6,0%) e no subgrupo que não atingiu resposta completa (15,0%) comparado àqueles que obtiveram resposta completa (6,8%). Entretanto, as diferenças não foram estatisticamente significantes em nenhum desses subgrupos. Um achado inesperado no presente estudo foi a expressão mais frequente de CTAs no subgrupo de LNH com estadiamento inicial (I e II) comparado ao subgrupo com estadiamento avançado (III e IV). Apesar da diferença encontrada na análise de sobrevida entre o grupo de pacientes que não apresentaram expressão de CTA (sobrevida mediana de 65 meses) e aqueles que apresentaram expressão de pelo menos 1 CTA (sobrevida mediana de 11 meses), a diferença não foi estatisticamente significante (p=0.0947). A resposta humoral espontânea contra pelo menos 1 CTA do painel foi encontrada em 19,6% dos pacientes com LNH. CT47 foi o CTA mais frequentemente expresso (7.2%), seguido do CT45 (5.1%), NY-ESO-1 (5.1%) e MAGE-A4 (5.1%). Os CTAs foram mais frequentemente expressos em LNH de células B (21.2%) comparado aos LNH de células T (6.2%) (p=0.048). Não houve diferença estatisticamente significante na resposta humoral anti-CTAs em qualquer dos outros subgrupos clínicos de LNH. Conclusão: De forma geral, houve baixa expressão protéica de CTAs em nossa casuística de LH e LNH com o painel utilizado. Apesar dos limitados dados disponíveis na literatura, esses achados são concordantes com a maioria dos estudos realizados utilizando RT-PCR e/ou imunohistoquímica. Não houve correlações estatisticamente significantes entre expressão de CTAs e parâmetros clínicos ou prognósticos no presente estudo. A reatividade sérica contra os CTAs testados ocorreu em níveis semelhantes ao da expressão protéica em LNH, sugerindo que os pacientes com LNH são capazes de montar resposta imune humoral específica contra CTAs. / Cancer/testis antigens (CTAs) are expressed in a variety of malignant tumors but in normal adult tissues solely in testicular germ cells. Based on this tumor-associated expression pattern, these antigens are potential targets for immunotherapy. Though carcinomas have been extensively analyzed, less is known about lymphoid malignancies such as lymphomas. Aims: To evaluate the potential of tumor specific antigens as candidates for immunotherapy in lymphomas throughout CTA protein expression and spontaneous humoral immune response analyses. We also aim to investigate clinical correlations and prognostic impact of CTAs expression in lymphomas. Methods: Tissue microarray was generated from 38 Hodgkin´s lymphoma (HL) and 106 non- Hodgkin´s lymphoma (NHL) archival cases. Immunohistochemistry (IHC) was done using a panel of 9 monoclonal antibodies against CTAs. Spontaneous humoral immune response analysis against a larger CTA panel was performed in 97 untreated NHL patient samples, including 59 cases from the TMA cohort, using ELISA technique. Results: We found overall low expression of CTAs in our series of HL (21.1%) and NHL (11.3%) TMAs, being MAGE-A (18.4%) and CT7 (13.2%) the most frequently expressed CTAs in HL, and MAGE-A (6.6%), GAGE (5.7%), NY-ESO-1 (4.8%) and CT7 (4.8%) the most frequently expressed CTAs in NHL. Although we did not find statistically significant difference in CTA expression among the clinicopathological subgroups of HL, CTA positivity was higher in advanced stage (28.6%) compared to early stage patients (11.8%). Among NHL, we found higher CTA expression in aggressive lymphomas (14.9%) compared to indolent lymphomas (3.1%), DLBCL (16.1%) compared to non-DLBCL (6.0%) and in non-complete response group (15.0%) compared to those who achieved complete response (6.8%), but it was not statistically significant. Unexpectedly, early stage disease (19.5%) had higher CTA expression than advanced stage NHL (6.2%). Despite the difference found in survival analysis between NHL patients that presented no CTAs expression (median OS 65 months) and those who expressed at least one CTA (median OS 11 months), it did not reach statistically significant difference (p=0.0947). Serum reactivity against at least 1 CTA was observed in (19.6%) of NHL patients, being more frequent in B-cell lymphomas (21.2%) then T-cell lymphomas (6.2%) (p=0.048). CT47 was the most frequently expressed CTA (7.2%), followed by CT45 (5.1%), NY-ESO-1 (5.1%) and MAGE-A4 (5.1%). Grouping the MAGE-A family similarly to the TMA analysis, we found positivity in 8.2% of NHL serum samples. Among DLBCL, CT45 and NY-ESO-1 were the most frequently expressed CTAs, being positive in 4/50 (8.0%) and 3/50 (6.0%), respectively. Conclusion: We found overall low expression of CTAs in our series of HL and NHL TMAs, and low reactivity against CTA in our serum samples. Our results demonstrated a slightly higher frequency of humoral response against most CTAs included in both TMA and ELISA panel compared to their expression by TMA. Considering that generally a small proportion of patients expressing CTAs develop specific humoral response, it is possible that CTA expression by TMA could be underestimated due to the focal expression pattern in some patients. Therefore, using an extensive panel of antibodies and large TMA and serum cohorts of lymphoma patients, we could not identify CTA candidates for immunotherapy in HL and NHL. / TEDE / BV UNIFESP: Teses e dissertações

Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2012-07-23T21:20:51Z No. of bitstreams: 1 Lorena Pinto. Avaliação ex vivo da proliferação espontanea em PBMC de individuos infectados pelo HTLV-1 por citometria de fluxo.pdf: 1267124 bytes, checksum: 830b004821bb96ca261aed15410bcb82 (MD5) / Made available in DSpace on 2012-07-23T21:20:51Z (GMT). No. of bitstreams: 1 Lorena Pinto. Avaliação ex vivo da proliferação espontanea em PBMC de individuos infectados pelo HTLV-1 por citometria de fluxo.pdf: 1267124 bytes, checksum: 830b004821bb96ca261aed15410bcb82 (MD5) Previous issue date: 2010 / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, Bahia, Brasil / O vírus linfotrópico de células T humanas do tipo 1 (HTLV-1) infecta cerca de 2% da população de Salvador-Bahia. O HTLV-1 é o agente etiológico da ATLL, HAM/TSP e uveíte. Este vírus também está relacionado a outras doenças inflamatórias como artrites, dermatites infectivas, polimiosites, alveolites e Síndrome de Sjögren. Uma das características imunológicas mais marcantes da infecção pelo HTLV-1 é a proliferação espontânea dos linfócitos T induzida por proteínas transativadoras virais, como Tax e HBZ. O papel da proliferação na patogênese da infecção não é conhecido, porém alguns trabalhos indicam que sua intensidade é maior nos pacientes com HAM/TSP, além disso pode ser responsável pela manutenção da carga proviral do HTLV-1, uma vez que o vírus se replica por divisão da célula infectada. A dinâmica da proliferação ex vivo não é muito conhecida, sendo normalmente avaliada por adição de 3[H]-Timidina às culturas, que possui várias desvantagens, entre as quais a toxicidade. Este é um estudo piloto que objetivou padronizar um método para avaliação da dinâmica da proliferação espontânea de linfócitos T utilizando o marcador CarboxyFluorescein diacetate Succinimidyl Ester (CFSE), por citometria de fluxo. Além de quantificar os índices de proliferação celular de linfócitos T totais e das subpopulações linfocitárias T CD4+ e T CD8+, correlacionar proliferação celular com a carga proviral do HTLV-1 e a expressão da proteína viral TAX. Para tal, PBMC de 30 pacientes infectados pelo HTLV-1 (16 assintomáticos e 14 HAM/TSP) foram cultivados por 24, 48, 72, 96 e 120 horas, em presença de CFSE. As células foram adquiridas em citometro de fluxo e os resultados analisados pelo programa FlowJo, através da porcentagem de células divididas e do índice de divisão celular. Observou-se proliferação em 66,7% dos indivíduos infectados pelo HTLV-1. A proliferação espontânea de PBMC foi superior no grupo de pacientes com HAM/TSP (porcentagem de células divididas: 79%, índice de divisão celular: 79%), comparada aos assintomáticos (porcentagem de células divididas: 50%, índice de divisão celular: 56,3%), porém essa diferença não foi significante A proliferação espontânea pode ser detectada nas primeiras 24 horas de cultura. A intensidade de proliferação é semelhante para as subpopulações de linfócitos T CD4 e T CD8, tanto em indivíduos assintomáticos como naqueles com HAM/TSP. Não houve correlação entre a carga proviral e a porcentagem de células divididas (r= -0,009; p= 0,9) e índice de divisão celular (r=0,1; p=0,5). A média de expressão de TAX em linfócitos TCD4+ foi de 2,4±2,4 %. Houve correlação entre a expressão da proteína Tax e a porcentagem de células divididas (r=0,59; p =0,05) e o índice de divisão celular (r=0,60; p=0,05), porém sem significância estatística. No entanto, encontrou-se uma correlação positiva entre a porcentagem de células T CD4+ divididas e a expressão da proteína Tax (r=0,79; p<0,003), bem como entre o índice de divisão das células TCD4+ e a expressão da proteína Tax (r=0,75; p=0,008). Em conclusão, a avaliação da proliferação espontânea por citometria de fluxo, em culturas com CFSE avaliadas pelo programa FlowJo permite identificar a proliferação celular nas 24 horas inicias da cultura e quantificar a proporção de linfócitos T CD4 e TCD8 que proliferam. Este método pode ser útil na avaliação de drogas que modulam a proliferação espontânea em PBMC de indivíduos infectados pelo HTLV-1. / Around 2% of the population of Salvador-Bahia are infected by the Human-T Lymphocyte virus type I (HTLV-1). This virus is the etiologic agent of ATLL, HAM/TSP and uveitis. It is also related to inflammatory illness like arthritis, infective dermatitis, polymyositis, alveolitis and Sjorgen syndrom. The spontaneous proliferation of T-lymphocytes induced by viral transactivating proteins like Tax and HBZ is one of the most outstanding immunological characteristics of the infection. The role of the proliferation in the pathogenesis is still unknown though some studies have shown that it is higher among HAM/TSP patients. Moreover, it could be responsible for the HTLV-1 remaining proviral load since the virus replicate through division of infected cell. The dynamics of the proliferation ex-vivo is not well known and is usually assessed by incorporating 3[H]-Thymidine to the cultures. This method has several disadvantages one of them being the 3[H]-Thymidine toxicity. This pilot study was aimed at the standardization of a method that assesses the dynamics of the spontaneous T-lymphocytes proliferation using flow cytometry and CarboxyFluorescein diacetate Succinimidyl Ester (CFSE) as a marker. Other objectives were to assess the rates of celular proliferation of both total T lymphocytes and CD4+ and T CD8+ subpopulations; to correlate the celular proliferation with the HTLV-1 viral load and the expression of the viral TAX protein. PBMCs of 30 HTLV-1 infected patients (16 assymptomatic and 14 HAM/TSP) were cultivated for 24, 48, 72, 96 and 120 hours in the presence of CFSE. Cells were obtained by flow cytometry and the results were analysed with the software Flowjo through the percentage of divided cells and the rate of celular division. Cell proliferation was observed in 66.7% of the HTLV-1 infected people. The PBMC spontaneous proliferation was higher in the group of HAM/TSP patients (percentage of divided cells:79%, rate of cellular division79%) compared to the assymptomatic individuals (percentage of divided cells: 50%, rate of cellular division: 56,3%) though this difference was not significant. Spontaneous proliferation can be detected in the first 24 hours of cell cultivation. The intensity of proliferation is similar in T CD4 e T CD8 subpopulations of assympomatic individuals and HAM/TSP patients. There was no correlation between proviral load and percentage of divided cells (r= -0,009; p= 0,9) and the rate of cellular division (r=0,1; p=0,5). The average of the TAX expression in T CD4+ was 2,4±2,4 %. There was a correlation between the expression of TAX protein and the percentage of divided cells (r=0,59; p =0,05) and the rate of cellular division (r=0,60; p=0,05), although not statistically significant. Nevertheless, a positive correlation was found between the percentage of divided T CD4+ cells and the expression of TAX protein (r=0,79; p<0,003), as well as between the rate of cellular division of TCD4+ cells and the expression of TAX protein (r=0,75; p=0,008). As a conclusion, the assessment of spontaneous proliferation by flow cytometry in cultures with CFSE analysed with the FlowJo software allows to identify the cellular proliferation in the first 24 hours of cultivation and to quantify the proportion of T CD4 and TCD8 lymphocytes that proliferated. This method could be usefull to assess drugs that modulate the spontaneous proliferation in PBMCs from HTLV-1 infected individuals.

Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2015-03-19T17:17:11Z No. of bitstreams: 1 Lorena Ana Pinto Efeito...pdf: 4813973 bytes, checksum: 919ea1532d5e21e5ccc608fc3405b3fd (MD5) / Approved for entry into archive by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2015-03-19T17:17:33Z (GMT) No. of bitstreams: 1 Lorena Ana Pinto Efeito...pdf: 4813973 bytes, checksum: 919ea1532d5e21e5ccc608fc3405b3fd (MD5) / Made available in DSpace on 2015-03-19T17:17:33Z (GMT). No. of bitstreams: 1 Lorena Ana Pinto Efeito...pdf: 4813973 bytes, checksum: 919ea1532d5e21e5ccc608fc3405b3fd (MD5) Previous issue date: 2014 / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / A proliferação espontânea de linfócitos é um marcador da infecção pelo Vírus Linfotrópico de Célula T Humana do tipo 1 (HTL V -l)o Esta é mais elevada em pacientes com paraparesia espástica tropical/mielopatia associada ao HTL V (HAMJTSP) que em indivíduos assintomáticos. Embora o seu papel na patogênese da HAM/TSP ainda seja desconhecido, a identificação de drogas capazes de modular a proliferação espontânea pode ser relevante para o tratamento da HAM/TSP. Neste estudo nós avaliamos os efeitos dos derivados quinoIínicos BS373, Ql e Q2 e da fisalina F em culturas de células mononucleares do sangue periférico (PBMC) de indivíduos infectados pelo HTL V com HAM/TSP. Estes compostos inibiram, ex vivo, a proliferação espontânea em culturas de PBMC, conforme avaliado pela incorporação de 3H-timidina. Além disso, a produção espontânea, ex vivo, de citocinas inflamatórias foi significativamente inibida pelo composto BS373 (25 j.tM) e pela tlsahna F (10 j.tM). A expressão da proteína viral Tax foi reduzida cerca de 80% após incubação de PBMC com BS373 (25 uM). BS373 e fisalina F induziram um aumento na porcentagem de células em apoptose, como demonstrado por análise da marcação do PBMC com anexina V por citometri~ de fluxo. A análise ultraestrutural de células cultivadas na presença destes compostos mostrou vacúolos apresentando membranas de mielina, que se assemelham a compartimentos autofágicos. Em conclusão, as quinolinas e a fisalina F foram capaz de inibir a proliferação espontânea de células de indivíduos infectados pelo HTL V-I. Outros estudos são necessários para compreendermos os mecanismos pelos quais estes compostos agem no PBMC de indivíduos infectados pelo HTL V-I. / Spontaneous lymphocyte proliferation, a hallmark ofHuman- T Lymphocyte Virus Type 1 (HTL V -1) infection, is particular1y high in HTL V -associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients compared to asymptomatic carriers. Although its role in the pathogenesis of HAM/TSP is stiH unknown, the identification of drugs capable of modulating the spontaneous proliferation may be reievant for the treatment ofHAM/TSP. Here we evaluated the effects ofthe quinoline derivative BS373, Q1 and Q2 and physalin F in cultures of peripheral blood mononuclear ceHs (PBMC) obtained from HTL V-infected subjects with HAM/TSP. Compounds inhibited of spontaneous proliferation in PBMC cultures, as assessed by 3H-thymidine incorporation. Additionally, the spontaneous production of inflammatory cytokines by PBMC was significantly inhibited by BS373 (25 flM) and physalin F (10 flM). The expression of the viral transcription factor Tax was reduced about 80% after incubation of PBMC with 8S373 (25 I-tM). BS373 and physalin F induced an increase in the percentage of apoptotic cells, as shown by flow cytometry analysis of annexin V-stained PBMC. Ultrastructural analysis of cultured cells in the presence of compounds showed vacuoles presented with myelin-like membranes, resembling autophagic vacuole-like compartments. In conc1usion, quinolines and physalin F was able to inhibit the spontaneous proliferation of cells from HTL V -l-infected individuaIs. Further studies are required to understand the mechanisms by which the compounds affect HTL V -1 PBMC.

café é a segunda bebida mais consumida no mundo, ficando atrás apenas da água; o Brasil figura como o maior produtor e exportador desta commodity no cenário global. Apesar de possuir uma cadeia altamente consolidada em nível global, mudanças e refinamentos tecnológicos estão em constante evolução, visando melhoria ou elevação da qualidade final da bebida, para atender a mercados cada vez mais exigentes. As interações entre os fatores edafoclimáticos, as formas de processamento, secagem, armazenagem e torrefação, implicam nos resultados sensoriais, que são desempenhados pelos Q-Graders de café, consequentemente, afetam o preço final do produto. Pesquisas recentes vêm demonstrando, que mesmo por trás de toda complexidade, que envolve a descrição da qualidade do café, é possível modificar o perfil sensorial da bebida, com controles mais precisos no processamento da matéria após a colheita. Tais indicativos estão inerentes aos processos de fermentações que ocorrem nos frutos, sendo que as fermentações podem conferir notas especiais de aroma, fragrância e acidez, bem como prejudicar a qualidade, quando não bem controlada. Com objetivo de elevação, melhoria e maior controle de processo na fase via-úmida, esta tese aplicou quatro formas de processamento por via-úmida, em seis estratos de altitude distintos, visando potencializar a qualidade final da bebida e estimar melhores métodos para cada faixa de altitude, com base nos fatores edafoclimáticos e nos fatores de ordem de processamento (fermentações espontâneas e induzidas). A qualidade final dos cafés foi mensurada por meio de resultados sensoriais, físico-químicos e cromatográficos, para que fosse possível determinar os melhores métodos de processamento por via-úmida para zonas de produção montanhosas Além da relação do processamento, estudaram-se formas de se introduzir maior acurácia ao processo de análise sensorial, objetivando redução da subjetividade. Os resultados foram empreendidos mediante análise de variância conjunta de experimentos, para os resultados sensoriais e físico-químicos (compostos fenólicos, acidez titulável total e pH), sendo as médias comparadas pelo teste de Tukey, considerando o nível de significância de 5%, e os modelos de regressão foram testados pelo teste F e os parâmetros pelo teste t. Além das análises de variância, adotou-se o método de agrupamento hierárquico com ligação completa, para as análises multivariadas. Os resultados indicam que o uso de cultura de arranque na fase de fermentação por via-úmida constitui em uma alternativa relevante para zonas menos elevadas, onde naturalmente os cafés tendem a notas sensoriais mais baixas, quando aplicados métodos tradicionais, e que as fermentações espontâneas possuem maior potencial de entrega de resultados sensoriais em faixas acima dos 900 metros de altitude. Os resultados demonstram que o processamento adotado após a colheita pode ser determinante para a formação do perfil sensorial, físico-químico e cromatográfico que o café terá, indicando que o controle de processo constitui em uma fase indispensável no pós-colheita. Tais evidências indicam que a qualidade pode ser modificada, para atender determinados nichos de mercado, visando à produção de um produto mais consistente e que dependa menos dos fatores climáticos ou do acaso. / Coffee is the second most consumed drink in the world, behind only water, Brazil figures as the largest producer and exporter of this commodity in the global scenario. Despite having a highly consolidated chain globally, technological and refinements changes are constantly evolving, aimed at improving or raising the final quality of the drink, to meet increasingly demanding markets. The interactions between the edaphoclimatic factors, the forms of processing, drying, storage and roasting, imply in the sensorial results, which are performed by the coffee tasters, consequently affect the final price of the product. Recent researches have shown that even behind all complexity, which involves the description of the quality of the coffee, it is possible to modify the sensorial profile of the beverage, with more precise controls in the processing of the matter, after the harvest. Such indications are inherent to the fermentation processes that occur in the fruits, and the fermentations can confer special notes of aroma, fragrance and acidity, as well as impair quality, when not well controlled. With objective of elevation, improvement and greater process control in the wet phase. This thesis applied four forms of wet processing in six distinct altitude strata, aiming at enhancing the final quality of the beverage and estimating better methods for each altitude range, based on edaphoclimatic factors, and processing order factors (spontaneous and induced fermentations). The final quality of the coffees was measured by sensorial, physico-chemical and chromatographic results, to determine the best wet processing methods for mountainous production areas In addition to the processing relationship, we studied ways to introduce greater accuracy to the process of sensory analysis, aiming to reduce subjectivity. The results were carried out through the analysis of joint variance of experiments for the sensory and physicochemical results (phenolic compounds, total titratable acidity and pH). The averages were compared by Tukey's test, considering a significance level of 5% and the regression models were tested by the F test and the parameters by the t test. In addition to the variance analysis, the hierarchical grouping method with complete linkage was used for the multivariate analysis. The results indicate that the use of starter culture in the wet fermentation phase constitutes a relevant alternative for less elevated areas, where naturally the coffees tend to lower sensorial scores when traditional methods are applied and that spontaneous fermentations have greater potential for delivery of sensory results in bands above 900 meters altitude. The results show that the post-harvest processing can be determinant for the formation of the sensorial, physico-chemical and chromatographic profile that the coffee will have, indicating that the process control is an indispensable post-harvest phase. Such evidence indicates that quality can be modified to meet certain market niches, aiming at producing a product that is more consistent and less dependent on climatic or chance factors.