Submitted by Fabrizio Grandi (fgrandivet@gmail.com) on 2016-03-10T14:56:58Z No. of bitstreams: 1 Doutorado.pdf: 5138229 bytes, checksum: cf3859209f1985d48832ef7e89af5b94 (MD5) / Approved for entry into archive by Sandra Manzano de Almeida (smanzano@marilia.unesp.br) on 2016-03-10T17:08:07Z (GMT) No. of bitstreams: 1 grandi_f_dr_bot.pdf: 5138229 bytes, checksum: cf3859209f1985d48832ef7e89af5b94 (MD5) / Made available in DSpace on 2016-03-10T17:08:07Z (GMT). No. of bitstreams: 1 grandi_f_dr_bot.pdf: 5138229 bytes, checksum: cf3859209f1985d48832ef7e89af5b94 (MD5) Previous issue date: 2016-02-29 / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / O tumor venéreo transmissível (TVT) canino é uma neoplasia transplantável, considerada um alo-enxerto. Entretanto, pouco se sabe a respeito da origem e processo de cacinogênese. Atualmente, postula-se que alguns tumores originem-se de células iniciadoras tumorais, classicamente descritas nas leucemias mielóide humanas. As características intrínsecas do TVT fornecem indícios de uma possível participação de células iniciadores tumorais no processo de carcinogênese nesse tumor. Foi realizado estudo de fenotipagem do TVT canino para avaliar a marcação das proteínas CD44, CD133, CD90 e CD34, comumente associadas ao potencial iniciador tumoral. Para tanto utilizou-se a citometria de fluxo, imuno-histoquímica e RTq-PCR. Foram analisados também as frações de crescimento pelo Ki-67) e o número de células em apoptose pela caspase-3 clivada. Trinta e oito amostras de TVT foram obtidas de pacientes sem tratamento quimioterápico prévio. As amostras foram classificadas em plasmocitóide ou mistas, de acordo com o subtipo citológico; as células positivas na citometria de fluxo foram representadas em termos percentuais para os marcadores CD44, CD34, CD90 e CD133; a fração de crescimento foi representada pela técnica do H-Score; a quantidade de células apoptóticas foi representada pelo somatório de células positivas para a caspase-3 clivada; as imuno-marcações das proteínas CD44 e CD34 foram representadas por escores semi-quantitativos baseados na intensidade e percentual de células positivas; as expressões de RNAm foram calculadas em termos relativos; ainda, os pacientes foram divididos em grupos resistente e não resistente e comparados quanto a expressão dos marcadores de células iniciadoras supracitados. Não foram observadas diferenças significativas entre os marcadores e os grupos citológicos plasmocitóide e misto; o percentual de células CD44+ comumente foi superior a 90%, enquanto que o percentual de células CD34+, menor que 0,5%; o percentual de células CD90+ e CD133+ variou amplamente; houve uma tendência em termos de diferença estatística entre os grupos quimiorresistente e não resistente; houve correlação forte entre o percentual de células CD133+ e CD90+ na citometria de fluxo. O estudo permitiu verificar diferentes níveis de expressão protéica e gênica nas amostras de TVT canino; ainda, os grupos citológicos aparentam não possuir diferenças com relação a expressão dos marcadores CD44, CD90, CD133 e CD34; os grupos quimiorresistentes e não-resistentes parecem diferir com relação a expressão dos marcadores de células iniciadoras tumorais. / The canine transmissible venereal tumor (CTVT) is a transplantable neoplasia considered an allograft. Information about the origin and carcinogenesis process is scarcely known. Currently, some neoplasms are believed to arise from a tumor-initiating cell (TIC´s) classically described in human myeloid leukemia. TVT intrinsic characteristics provide evidence of a possible TIC´s participation in carcinogenesis process of this malignancy. Thus, a phenotyping study of CTVT was conducted to assess the immunophenotyping properties of the proteins CD44, CD133, CD90 and CD34, already known to be associated to tumor initiator potential. The use of flow cytometry and immunohistochemistry contributed to this purpose. In addition, growth fractions and cells undergoing apoptosis were examined by Ki-67 and caspase-3 cleaved, respectively. Thirty-eight samples were chosen from patients having no previous chemotherapy and cytological diagnosis of CTVT. Samples were classified into plasmacytoid or mixed according to cytological subtype. Positive cells in the flow cytometry were expressed in percentage for the markers CD44, CD34, CD90 and CD133. H-score technique helped to represent growth fractions. Apoptotic cell quantity was calculated by summing positive cells. Immunohistochemical marking of CD44 and CD34 proteins were determined by semiquantitative scores based on the intensity and percentage of positive cells. Moreover, specimens were divided into resistant and non-resistant groups and compared according cell marker expressions cited before. No significant differences appeared between the markers, and cytological plasmacytoid and mixed groups. The CD44 + cells and CD34 + percentages showed up high and low values, respectively. CD90 + and CD133 + cell percentages presented variable values. Amplitudes of the gene expression values among markers were similar to those observed in flow cytometry with a low expression of CD34, and a high expression of CD44. There was a positive statistical tendence between chemo-resistant and non-resistant groups, as well as a strong correlation between the percentage of CD133 + and CD90 + in flow cytometry. Besides, cytological groups apparently have no differences with the marker expression of CD44, CD90, CD133 and CD34. Resistant and non-resistant groups to chemotherapy seems to differ with respect to the marker expression of TIC´s.

As doenças crônicas não transmissíveis (DCNT) estão posicionadas no topo das enfermidades em termos de morbimortalidade, no Brasil e no mundo. Entre estas, as doenças cardiovasculares (DCV), e particularmente, as cerebrovasculares (DCbV), produzem um impacto significativo sobre a autonomia das pessoas, desfalcando a força de trabalho das nações e gerando um alto custo para a previdência social de todos os países. No Brasil, só muito recentemente as enfermidades circulatórias passaram a ser contempladas por políticas públicas formuladas pelo Ministério da Saúde (MS), não só pela manutenção destas doenças em altos patamares de morbimortalidade, mas também pelo crescimento exponencial de alguns dos seus fatores de risco. Partindo do pressuposto que as políticas e programas oficiais não estão sendo efetivamente implementados no âmbito da Atenção Primária à Saúde (APS), o objetivo do presente estudo foi investigar e analisar como estas iniciativas do MS vem sendo efetivamente executadas em Juiz de Fora-MG. A estratégia utilizada para essa investigação consistiu em uma pesquisa qualiquantitativa com base em observação, documentos e entrevistas semi-estruturadas com os diferentes componentes profissionais das Equipes de Saúde da Família de três unidades básicas de saúde do município citado. Foram entrevistados 40 profissionais de saúde, entre médicos, enfermeiros e agentes comunitários de saúde, buscando-se entender como os programas governamentais com interface com a prevenção das doenças cardiovasculares e, em especial, cerebrovasculares, vêm sendo implementados ao nível do Programa de Saúde da Família. Na comparação entre o que é recomendado nos programas governamentais e o que vem sendo executado nas UBS, concluiu-se que ainda há um longo caminho a ser percorrido para que estes programas sejam efetivamente implementados na porta de entrada do sistema de saúde. / Non-transmissible chronic diseases (NTCD) are top diseases in terms of morbimortality, in Brazil and the world. Among these ones, cardiovascular and mainly cerebrovascular diseases have a strong impact on peoples autonomy, reducing the labour force of nations and creating high costs to the Social Security of all countries. In Brazil, it was only very recently that circulatory diseases started to be considered by public policies developed by the Ministry for Health, not just because these diseases have reached high morbimortality taxes, but also because there has been a significant increase in their risk factors. Starting from the hypothesis that official policies and programs have not been implemented within Primary Health Care, this study aims at investigating and analyzing how these initiatives of the Ministry for Health have been effectively carried out in Juiz de Fora-MG. The strategy used to test the hypothesis above was a qualiquantitative research based on observation, documents and semi-structured interviews with the different professional components of the Family Health Teams of three Basic Units in the city mentioned. We have interviewed 40 health professionals, such as doctors, nurses and community agents, in order to understand how the government programs with an interface with prevention of cardiovascular and especially cerebrovascular diseases have been implemented at the level of the Family Health Program. By comparing what is recommended by the government programs and what has been really carried out in Basic Health Units, it was concluded that there is still a long way to walk so that these programs can be effectively implemented at the port of entry of our health system.

O Diabetes mellitus é uma das doenças crônicas não-transmissíveis mais prevalentes do mundo, com prevalência estimada para 2025 de 7,1% e 14,0% da população mundial e brasileira, respectivamente. Atualmente existe a necessidade de desenvolvimento de programas com ênfase na prevenção primária, controle da incidência e complicações do diabetes devido ao elevado índice de morbi-mortalidade, associação com comorbidades e custo social-econômico. Para isso, uma das possíveis estratégias seria avaliar a utilização de medicamentos antidiabéticos orais e insulina prescritos aos portadores de DM atendidos pelo Sistema Único de Saúde. No presente trabalho, os usuários diabéticos pertencentes à rede municipal de saúde do Distrito Sanitário Oeste de Ribeirão Preto-SP foram identificados pela retirada de medicamentos antidiabéticos orais ou insulina nas farmácias das Unidades de Saúde do Distrito através da base de dados da prefeitura, denominado sistema Hygia de informação. Dessa forma, foi possível avaliar a terapia farmacológica para o tratamento do diabetes, a freqüência de retirada dos antidiabéticos orais e insulina, análise da outras classes medicamentosas prescritas para o controle das outras enfermidades e acesso aos diversos níveis de atenção à saúde. Por meio do banco de dados Hygia foram identificados 3927 usuários portadores de diabetes pertencentes ao Distrito Oeste de Ribeirão Preto-SP no período de mar/2006 a fev/2007, sendo a média de idade de 60,4 anos e 60,8% dos usuários identificados pertencerem ao gênero feminino. A monoterapia (60,0%) foi o esquema terapêutico mais prescrito, sendo a metformina o medicamento mais utilizado (31,8%). Apenas 3,3% dos usuários utilizaram insulina de forma isolada. No geral, as doses dos medicamentos antidiabéticos orais foram mais elevadas em politerapia do que em monoterapia, sendo que a freqüência média de retirada foi superior a 70,0%. Aproximadamente 34,0% dos indivíduos apresentaram insucesso no tratamento farmacológico do diabetes, com adição de medicamentos e/ou aumento da dose. Medicamentos como hidroclorotiazida, cimetidina, diclofenaco, entre outros, devem ser administrados com cautela em pacientes portadores de diabetes devido à possibilidade de elevar o risco de alteração da glicemia. Em relação às comorbidades, 73,5% dos usuários identificados são hipertensos e 25,9% dislipidêmicos. O número médio de consultas durante o período de estudo foi de 7,0 para todos os Grupos Terapêuticos. Portanto, através do estudo do perfil epidemiológico do Diabetes mellitus, foi possível verificar que existe a necessidade de se conhecer a situação real do consumo de medicamentos e do perfil epidemiológico das populações, além de constatar que os estudos de utilização de medicamentos são uma ferramenta útil neste processo, contribuindo para o uso racional dos medicamentos, direcionamento da prática médica e formulação de políticas de saúde. / The Diabetes mellitus is one of the non-transmissible chronic diseases most prevalent in the world. It is estimated that diabetes affect more than 7.1% people worldwide and 14.0% people in Brazil by 2025. Currently, it is necessary to develop programs with emphasis in the primary prevention, incidence and complications diabetes control due to the high mortality and comorbities rate. Therefore, one of the possible strategies would be to evaluate the use of oral antidiabetic agents and insulin prescribed to the people with DM attends by brazilian public health system. In the present study, the diabetic patients belonging to the public health system of the West Sanitary District of Ribeirão Preto-SP were identified to receive orals agents or insulin from pharmacy of the units of public health system of the West District through the Hygia database record. So, it was possible to evaluate the pharmacological therapy for the treatment of the diabetes, the frequency of oral agents and insulin received, analysis of the other medicines classes prescribed to control comorbities and access at the public health system. In this study was identified 3927 patient with diabetes attend to the West District of Ribeirão Preto-SP in the period from March 2006 to February 2007. The mean age of the patient population was 60.4 years and 60.8% of patients were females. The most frequent treatment prescribed was monotherapy (60.0%) and the metformin was drug more prescribed (31.8%). Only 3.3% of the patients were treated with insulin in monotherapy. In general, the doses of the oral antidiabetic agents were higher in politherapy than monotherapy, and the mean frequency of drugs received was higher to 70.0%. Approximately 34.0% of the patients showed failure in the pharmacological treatment of the diabetes, with addition of drugs and/or dose increase. Medicines such as hydrochlorothiazide, cimetidine, diclofenac, and others, should be administered with caution in patient with diabetes due to the possibility of increasing the risk of glycemic alteration. In relation to comorbities, 73.5% of the identified patients are hypertensive and 25.9% dyslipidemic. The mean of consultations was 7.0 in all Therapeutic Groups. Therefore, through of the study of the epidemic Diabetes mellitus profile, it was possible to verify that it is necessary to know the real situation of the consumption of medicines and the epidemic population profile, besides to verify that the drug utilization studies are a useful tool in this process, contributing to the rational use of the medicines, direction of the medical practice and politics health formulation.

Made available in DSpace on 2016-01-26T18:55:27Z (GMT). No. of bitstreams: 1 DISSETACAO_COMPLETA__16_04_09.pdf: 1755631 bytes, checksum: da3df5aaf8868dbddec8a1a0b3481970 (MD5) Previous issue date: 2009-02-13 / The transmissible venereal tumor (TVT) is a contagious neoplasm of round cells of dogs of very frequent casuistry. The standard treatment consists of chemotherapy, and the most effective treatment is the vincristine sulphate alone, however the resistance emergence to this agent has been taking the association with other drugs. Recent studies demonstrated the antitumoral effect of the avermectins when associated to the vincristine in the treatment of some neoplasms. Therefore, the objective of this work was to compare the effectiveness of the standard protocol with vincristine only and the ivermectin + vincristine association through histopathologycal and cytological analysis of the tumor. The samples analyses reveal a more precocious cure of TVT in the associated protocol. These results suggest that the protocol of the vincristine associated to ivermectin can be an excellent therapeutic alternative for the treatment of TVT in the future. / O tumor venéreo transmissível (TVT) é uma neoplasia de células redondas que acomete cães de casuística muito freqüente. O tratamento padrão consiste no uso de antineoplásicos, sendo de eleição a vincristina como agente único, porém o aparecimento de resistência a este fármaco tem levado a associação com outras drogas. Estudos recentes demonstraram o efeito antitumoral das avermectinas quando associadas à vincristina no tratamento de alguns tipos de neoplasias. Portanto, o objetivo deste trabalho foi comparar a eficácia do protocolo padrão com o uso único de vincristina e o protocolo da associação de vincristina e ivermectina através da análise histopatológica e citológica do tumor. As análises histopatológicas e citológicas revelarem uma cura mais precoce do TVT no protocolo associado. Estes resultados sugerem que o protocolo vincristina associada à ivermectina pode ser no futuro uma excelente alternativa terapêutica para o tratamento do TVT.

Made available in DSpace on 2016-07-18T17:53:05Z (GMT). No. of bitstreams: 1 DISSETACAO_COMPLETA__16_04_09.pdf: 1755631 bytes, checksum: da3df5aaf8868dbddec8a1a0b3481970 (MD5) Previous issue date: 2009-02-13 / The transmissible venereal tumor (TVT) is a contagious neoplasm of round cells of dogs of very frequent casuistry. The standard treatment consists of chemotherapy, and the most effective treatment is the vincristine sulphate alone, however the resistance emergence to this agent has been taking the association with other drugs. Recent studies demonstrated the antitumoral effect of the avermectins when associated to the vincristine in the treatment of some neoplasms. Therefore, the objective of this work was to compare the effectiveness of the standard protocol with vincristine only and the ivermectin + vincristine association through histopathologycal and cytological analysis of the tumor. The samples analyses reveal a more precocious cure of TVT in the associated protocol. These results suggest that the protocol of the vincristine associated to ivermectin can be an excellent therapeutic alternative for the treatment of TVT in the future. / O tumor venéreo transmissível (TVT) é uma neoplasia de células redondas que acomete cães de casuística muito freqüente. O tratamento padrão consiste no uso de antineoplásicos, sendo de eleição a vincristina como agente único, porém o aparecimento de resistência a este fármaco tem levado a associação com outras drogas. Estudos recentes demonstraram o efeito antitumoral das avermectinas quando associadas à vincristina no tratamento de alguns tipos de neoplasias. Portanto, o objetivo deste trabalho foi comparar a eficácia do protocolo padrão com o uso único de vincristina e o protocolo da associação de vincristina e ivermectina através da análise histopatológica e citológica do tumor. As análises histopatológicas e citológicas revelarem uma cura mais precoce do TVT no protocolo associado. Estes resultados sugerem que o protocolo vincristina associada à ivermectina pode ser no futuro uma excelente alternativa terapêutica para o tratamento do TVT.

This thesis evaluates different controllers for traction control on an electric forklift truck and has been done in cooperation with Toyota Material Handling Manufacturing Sweden. The need for a traction control system has increased with the introduction of lithium-ion batteries replacing the older lead-acid batteries, reducing the battery weight and therefore the downward force on the driving wheel increasing the risk for slip. The forklift truck was modelled using Simulink and validated by experiment. Different possible control strategies were investigated and three were chosen for implementation in simulation. These were controllers based on Model Following Control, Maximum Transmissible Torque Estimation and Sliding Mode Control. Model Following Control makes use of a nominal model to compare actual wheel speed values with nominal wheel speed values to determine if slip is occurring, Maximum Transmissible Torque Estimation makes use of a closed-loop disturbance observer to compute the maximum transmissible torque possible without inducing slip and using it as a limitation on the input signal, and Sliding Mode Control uses different functions to \say{slide} along a sliding surface to stay around a specific slip value. All three controller types were developed both as speed controlled and torque controlled. All of the controllers could reduce slip heavily in simulation. The Maximum Transmissible Torque Estimation controller reduced slip the most and kept oscillations at a minimum, but was not as responsive as the others to driver commands. The conclusion was that the controller of choice would depend on the working environment of the forklift truck. In a low friction environment where slip is expected to occur often, the Maximum Transmissible Torque Estimation controller is advisable, while the other two would be a better choice for environment with low slip occurrence. The use of torque control, while often better with regards to decreasing slip, could not be advised due to a perceived increase in implementation cost.

No description available.

Transmissive spongiform encephalopathies (TSEs) are neurodegenerative diseases characterized by depositions of abnormally folded prion protein (PrPTSE ) in brain. PrPTSE is at present the only specific biochemical marker of human and animal TSEs. Diagnostic tests are based on the detection of PrPres after proteinase K digestion of brain homogenate using Western blot or on the immunohistochemistry of fixed brain tissue, which are both difficult and time consuming. In this work we focused on development of a new type of tests based on PrP detection without need of proteinase K digestion. As deposits of PrPTSE remain in the body for a long time, there is a substantial chance of them being nonenzymatically modified by glycation. The detection of glycated PrPTSE may have a potential to serve as a diagnostic marker. We prepared monoclonal antibodies specific for carboxymethyl lysine/arginine modified prion protein. Bacterially expressed and purified recombinant human prion protein (rhPrP) was modified by glyoxylic acid that introduces carboxymethyl groups on lysine and arginine residues present within the molecule of the protein. Modified rhPrP (rhPrP-CML) was used for immunization of laboratory mice and hybridoma cells were prepared. Screening of cell supernatants resulted in the selection of 4...

La génomique des populations rend possible la mise en évidence de traces de sélection dans le génome. Les travaux effectués considèrent en général une échelle de temps longue (~ 10³ générations). En comparaison, peu d’intérêt a été porté aux études expérimentales de court terme (~ 10 générations). De telles expériences sont pourtant susceptibles de nous renseigner sur la base génétique de caractères complexes. Nous proposons une méthode de vraisemblance basée sur un modèle de Wright-Fisher pour détecter la sélection à partir d’échantillons génétiques temporels acquis sur une période de dix générations. Nous montrons par simulation que notre méthode permet de différencier les signaux dus à la combinaison de la sélection et de la dérive génétique de ceux dus à la dérive seule. Nous montrons également par simulation qu’il est possible d’estimer le coefficient de sélection appliqué à un locus testé. De plus, nous illustrons l’intérêt de notre méthode pour la détection de marqueurs candidats à la sélection au travers de deux études génomiques sur données réelles, chez le diable de Tasmanie (Sarcophilus harrisii) et chez la truite arc-en-ciel (Oncorhynchus mykiss). Ces applications mettent en évidence des régions génomiques candidates pour des phénotypes complexes dans des contextes différents. Dans l’ensemble, nos résultats montrent qu’il est possible de détecter des gènes sujets à une sélection directionnelle intense à partir d’échantillons génétiques temporels, même si la sélection est de courte durée et si les populations examinées ont un faible effectif. / Population genomics makes it possible to detect traces of selection in the genome. Studies in this field have mainly focused on long time scale (~ 10³ generations). In comparison, short-term experimental studies (~ 10 generations) have attracted much less interest. Such experiments are, however, likely to inform us about the genetic basis of complex characters. We propose a likelihood method based on a Wright-Fisher model to detect selection from genetic temporal samples collected over ten generations. We show through simulation that our method can disentangle signals due to the combination of genetic drift and selection to those due to drift alone. We also show through simulation that it is possible to estimate the selection coefficient applied to a tested locus. In addition, we illustrate the interest of our method for the detection of candidate markers for selection through two genome scans performed on real data, in the Tasmanian devil (Sarcophilus harrisii) and in the rainbow trout (Oncorhynchus mykiss). These practical applications highlight candidate genomic regions for complex phenotypes in different contexts. Collectively, our results show the possibility of detecting genes submitted to strong directional selection from genetic time-series, even if selection is applied on a short time period and if the examined populations are small.

Transmissive spongiform encephalopathies (TSEs) are neurodegenerative diseases characterized by depositions of abnormally folded prion protein (PrPTSE ) in brain. PrPTSE is at present the only specific biochemical marker of human and animal TSEs. Diagnostic tests are based on the detection of PrPres after proteinase K digestion of brain homogenate using Western blot or on the immunohistochemistry of fixed brain tissue, which are both difficult and time consuming. In this work we focused on development of a new type of tests based on PrP detection without need of proteinase K digestion. As deposits of PrPTSE remain in the body for a long time, there is a substantial chance of them being nonenzymatically modified by glycation. The detection of glycated PrPTSE may have a potential to serve as a diagnostic marker. We prepared monoclonal antibodies specific for carboxymethyl lysine/arginine modified prion protein. Bacterially expressed and purified recombinant human prion protein (rhPrP) was modified by glyoxylic acid that introduces carboxymethyl groups on lysine and arginine residues present within the molecule of the protein. Modified rhPrP (rhPrP-CML) was used for immunization of laboratory mice and hybridoma cells were prepared. Screening of cell supernatants resulted in the selection of 4...