23 resultados para FUNDAMENTAL FREQUENCY

em Repositório Científico do Instituto Politécnico de Lisboa - Portugal


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Trabalho Final de mestrado para obtenção do grau de Mestre em engenharia Mecância

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Genomic damage is probably the most important fundamental cause of development and degenerative disease. It is also well established that genomic damage is produced by environmental exposure to genotoxins, medical procedures (e.g. radiation and chemicals), micronutrient deficiency (e.g. folate), lifestyle factors (e.g. alcohol, smoking, drugs and stress), and genetic factors such as inherited defects in DNA metabolism and/or repair. Tobacco smoke has been associated to a higher risk of development of cancer, especially in the oral cavity, larynx and lungs, as these are places of direct contact with many carcinogenic tobacco’s compounds. Alcohol is definitely a recognized agent that influence cells in a genotoxic form, been citied as a strong agent with potential in the development of carcinogenic lesions. Epidemiological evidence points to a strong synergistic effect between cigarette smoking and alcohol consumption in the induction of cancers in the oral cavity. Approximately 90% of human cancers originate from epithelial cells. Therefore, it could be argued that oral epithelial cells represent a preferred target site for early genotoxic events induced by carcinogenic agents entering the body via inhalation and ingestion. The MN assay in buccal cells was also used to study cancerous and precancerous lesions and to monitor the effects of a number of chemopreventive agents.

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O projecto “Principais tendências no cinema português contemporâneo” nasceu no Departamento de Cinema da ESTC, com o objectivo de desenvolver investigação especializada a partir de um núcleo formado por alunos da Licenciatura em Cinema e do Mestrado em Desenvolvimento de Projecto Cinematográfico, a que se juntaram professores-investigadores membros do CIAC e convidados. O que agora se divulga corresponde a dois anos e meio de trabalho desenvolvido pela equipa de investigação, entre Abril de 2009 e Novembro de 2011. Dada a forma que ele foi adquirindo, preferimos renomeá-lo, para efeitos de divulgação, “Novas & velhas tendências no cinema português contemporâneo”.

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Formaldehyde (FA), also known as formalin, formal and methyl aldehydes, is a colorless, flammable, strong-smelling gas. It has an important application in embalming tissues and that result in exposures for workers in the pathology anatomy laboratories and mortuaries. Occupational exposure to FA has been shown to induce nasopharyngeal cancer and has been classified as carcinogenic to humans (group 1) on the basis of sufficient evidence in humans and sufficient evidence in experimental animals. Manifold in vitro studies clearly indicated that FA is genotoxic. FA induced various genotoxic effects in proliferating cultured mammalian cells. The cytokinesis-block micronucleus (CBMN) assay was originally developped as an ideal system form easuring micronucleus (MN), however it can also be used to measure nucleoplasmic bridges (NBP) and nuclear buds (NBUD). Over the past decade another unique mechanism of micronucleus formation, known as nuclear budding has emerged. NBUDS is considered as a marker of gene amplification and/or altered gene dosage because the nuclear budding process is the mechanism by which cells removed amplified and/excess DNA.

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O projecto “Principais tendências no cinema português contemporâneo” nasceu no Departamento de Cinema da ESTC, com o objectivo de desenvolver investigação especializada a partir de um núcleo formado por alunos da Licenciatura em Cinema e do Mestrado em Desenvolvimento de Projecto Cinematográfico, a que se juntaram professores-investigadores membros do CIAC e convidados. O que agora se divulga corresponde a dois anos e meio de trabalho desenvolvido pela equipa de investigação, entre Abril de 2009 e Novembro de 2011. Dada a forma que ele foi adquirindo, preferimos renomeá-lo, para efeitos de divulgação, “Novas & velhas tendências no cinema português contemporâneo”.

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Formaldehyde (FA) is ubiquitous in the environment and is a chemical agent that possesses high reactivity. Occupational exposure to FA has been shown to induce nasopharyngeal cancer and has been classified as carcinogenic to humans (group 1) on the basis of sufficient evidence in humans and sufficient evidence in experimental animals. The exposure to this substance is epidemiologically linked to cancer and nuclear changes detected by the cytokinesis-block micronucleus test (CBMN). This method is extensively used in molecular epidemiology, since it determines several biomarkers of genotoxicity, such as micronucleus (biomarkers of chromosomes breakage or loss), nucleoplasmic bridges (biomarker of chromosome rearrangement, poor repair and / or telomeres fusion) and nuclear buds (biomarker of elimination of amplified DNA). The gene X-ray repair cross-complementing group 3 (XRCC3) is involved in homologous recombination repair of cross-links and chromosomal double-strand breaks and at least one polymorphism has been reported in codon 241, a substitution of a methionine for a threonine.

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Formaldehyde (FA) is a colourless gas widely used in the industry and hospitals as an aqueous solution, formalin. It is extremely reactive and induces various genotoxic effects in proliferating cultured mammalian cells. Tobacco smoke has been epidemiologically associated to a higher risk of development of cancer, especially in the oral cavity, larynx and lungs, as these are places of direct contact with many carcinogenic tobacco’s compounds. Genetic polymorphisms in enzymes involved in the metabolism are very important and can make changes in the individual susceptibility to disease. Alcohol dehydrogenase class 3 (ADH3), also known as formaldehyde dehydrogenase dependent of glutathione, is the major enzyme involved in the formaldehyde oxidation, especially in the buccal mucosa. The polymorphism in study is a substitution of an isoleucine for a valine in codon 349. The cytokinesis-blocked micronucleus assay (CBMN) in human lymphocytes is one of the most commonly used methods for measuring DNA damage, namely the detection of micronucleus, nucleoplasmic bridges, and nuclear buds, classified as genotoxicity biomarkers.

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Formaldehyde: an important industrial compound used in the manufacture of synthetic resins and chemical compounds such as lubricants and adhesives; also applied as a disinfectant, preservative and in cosmetics productions; relevant workplace exposure to FA also occurs in anatomy, pathology and in mortuaries; classified by IARC as carcinogenic to humans (Group 1), based on sufficient evidence in humans and experimental animals; manifold in vitro studies indicated that FA can induce genotoxic effects in proliferating cultured mammalian cells. Aim of the study: to evaluate if years of exposure induced a genotoxic biomarkers increase, namely MN in lymphocytes and buccal cells, in workers occupationally exposed to FA (factory and pathology anatomy laboratory).

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Formaldehyde is classified by IARC as carcinogenic to humans (nasopharyngeal cancer). Tobacco smoke has been epidemiologically associated to a higher risk of development of cancer, especially in the oral cavity, larynx and lungs, as these are places of direct contact with many carcinogenic tobacco’s compounds. XRCC3 is involved in homologous recombination repair of cross-links and chromosomal double-strand breaks (Thr241Met polymorphism). The aim of the study is to determine whether there is an in vivo association between genetic polymorphism of the gene XRCC3 and the frequency of genotoxicity biomarkers in subjects exposed or not to formaldehyde and with or without tobacco consumption.

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O presente estudo visou caraterizar as representações que técnicos de intervenção precoce têm sobre famílias que vivem em meio rural e em meio urbano que recebem apoio das equipas. Foram realizadas entrevistas semi-diretivas, os participantes e entrevistados foram dez docentes com intervenção educativa nas equipas, cinco em apoio direto a famílias de meio rural e cinco a realizar intervenções com famílias de meio urbano. Deste estudo resultaram vários dados qualitativos que depois de analisados e discutidos, levaram a diversas conclusões que vem dar respostas às questões e problemática iniciais. As famílias inseridas nestes contextos têm características que as diferenciam; habilitações, recursos, necessidades e comportamentos em comunidade. Tem aspetos culturais que influenciam as suas atitudes, participação e autonomia e são ou não decisivas no desenvolvimento da criança. Em contexto rural as famílias apresentam um maior número de necessidades comparativamente às famílias de meio urbano. As maiores necessidades das famílias em contexto rural situam-se nas questões financeiras, de formação e apoio técnico e especializado. As maiores necessidades das famílias de contexto urbano situam-se ao nível do fraco apoio familiar e das redes sociais. As necessidades comuns situam-se nas necessidades de informação e promoção da autonomia e competências parentais. As visitas e intervenções domiciliares podem permitir melhorar a identificação das necessidades e recursos das famílias e compreender melhor os critérios de referência de algumas crianças. As oportunidades de aprendizagem são maiores nestes encontros em domicílio, estão presentes em muitos casos, elementos da família alargada, que muitas vezes tem um papel fundamental na educação e estimulação destas crianças. Os docentes de IP em intervenção em contexto urbano, comparativamente com os docentes inseridos em contexto rural, apoiam famílias que na generalidade abrangem áreas profissionais mais vantajosas financeiramente. Estas famílias terão á partida melhores condições para aceder a mais recursos e apoios. Nos dois contextos existe uma necessidade comum, falta de informação e alguma autonomia e competências parentais em relação ao crescimento das crianças. A realização de iii encontros de pais ou criação de grupos de pais que tenham por base a partilha de experiencias e informação, estão planeadas mas não são uma realidade nestas equipas. Nas práticas de qualidade, o profissional deve atuar nos contextos naturais como, a família, ou a comunidade, mas pode incluir também rotinas, brincadeiras, festas etc. cenários que facilitem o dia-a-dia. As famílias têm contextos e rotinas próprias que os profissionais devem identificar, os dados que recolhemos indicam essa necessidade de proceder a avaliação mais atenta das necessidades das famílias. As práticas recomendadas e o enquadramento legislativo são tidos em conta pelos docentes e profissionais das equipas, os recursos documentais são na sua maioria comuns, a todas as equipas participantes, seguindo as orientações e documentos/minutas facultadas pela comissão coordenadora do SNIPI (Sistema Nacional de Intervenção Precoce na Infância) Apesar das recomendações teóricas para práticas de qualidade centradas na família, verificamos que estas fazem parte das preocupações destes docentes, mas nem sempre são implementadas. A problemática da criança parece ser ainda o ponto mais importante dos programas e planos de intervenção e mesmo o critério decisivo para delinear a duração e frequência das intervenções, seja em contexto urbano ou rural. - ABSTRACT This study aimed to characterize the families of rural and urban areas that receive support from Early Intervention Teams. It has been proposed yet whether professionals IP suit their practices to the characteristics of these families and communities integrated in different cultural contexts. Interviews were conducted semidirective, participants were ten respondents and teachers with educational intervention teams, five in direct support to families in rural areas and five interventions with families in urban areas. This study resulted in a number of qualitative data that then analyzed and discussed, led to several conclusions that comes to answer the questions and problems early. The families included in these contexts have characteristics that differentiate them; qualifications, resources, needs and behaviors in the community. Has cultural aspects that influence their attitudes, participation and autonomy and are not decisive in the development of the child. In the rural households have a greater number of needs compared to urban families. The greatest needs of families in rural settings are located in financial matters, training and technical support and expertise. The greatest needs of the urban households are located at the level of weak family support and social networks. Common needs lie in information needs and promoting autonomy and parenting skills. The home visits and interventions may allow improved identification of needs and resources of families and understand the benchmarks of some children. Learning opportunities are greater in these meetings at home, are present in many cases, elements of the extended family, which often plays a key role in education and stimulation of these children. Teachers IP intervention in the urban compared with rural teachers placed in context, support families in general include professional areas more financially advantageous. These families will have better starting conditions for access to more resources and support. In both contexts there is a common need, lack of information and some autonomy and parenting skills in relation to the growth of children. The meetings of parents or creating parent groups that are based on the sharing of information and experiences are planned but are not a reality in these teams. In quality practices, the professional must act in natural contexts like the family or the community, but may also include routines, jokes, and parties’ etc. scenarios that v facilitate the day-to-day. Families have their own contexts and routines that professionals should identify, collect the data indicate that the need for more careful assessment of the needs of families. Best practices and legislative environment are taken into account by teachers and professional teams, the documentary resources are mostly common to all participating teams, following the guidelines and documents / drafts provided by the coordinating committee SNIPI (National Intervention Early Childhood) Despite the theoretical recommendations for quality practices family-centered, we see that these are part of the concerns of teachers, but are not always implemented. The issue of child seems to be still the most important programs and plans and even the decisive criterion for delineating the duration and frequency of interventions whether in urban or rural.

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The International Agency for Research on Cancer classified formaldehyde as carcinogenic to humans because there is “sufficient epidemiological evidence that it causes nasopharyngeal cancer in humans”. Genes involved in DNA repair and maintenance of genome integrity are critically involved in protecting against mutations that lead to cancer and/or inherited genetic disease. Association studies have recently provided evidence for a link between DNA repair polymorphisms and micronucleus (MN) induction. We used the cytokinesis-block micronucleus (CBMN assay) in peripheral lymphocytes and MN test in buccal cells to investigate the effects of XRCC3 Thr241Met, ADH5 Val309Ile, and Asp353Glu polymorphisms on the frequency of genotoxicity biomarkers in individuals occupationally exposed to formaldehyde (n = 54) and unexposed workers (n = 82). XRCC3 participates in DNA double-strand break/recombination repair, while ADH5 is an important component of cellular metabolism for the elimination of formaldehyde. Exposed workers had significantly higher frequencies (P < 0.01) than controls for all genotoxicity biomarkers evaluated in this study. Moreover, there were significant associations between XRCC3 genotypes and nuclear buds, namely XRCC3 Met/Met (OR = 3.975, CI 1.053–14.998, P = 0.042) and XRCC3 Thr/Met (OR = 5.632, CI 1.673–18.961, P = 0.005) in comparison with XRCC3 Thr/Thr. ADH5 polymorphisms did not show significant effects. This study highlights the importance of integrating genotoxicity biomarkers and genetic polymorphisms in human biomonitoring studies.

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A replicate evaluation of increased micronucleus (MN) frequencies in peripheral lymphocytes of workers occupationally exposed to formaldehyde (FA) was undertaken to verify the observed effect and to determine scoring variability. May–Grünwald–Giemsa-stained slides were obtained from a previously performed cytokinesis-block micronucleus test (CBMNT) with 56 workers in anatomy and pathology laboratories and 85 controls. The first evaluation by one scorer (scorer 1) had led to a highly significant difference between workers and controls (3.96 vs 0.81 MN per 1000 cells). The slides were coded before re-evaluation and the code was broken after the complete re-evaluation of the study. A total of 1000 binucleated cells (BNC) were analysed per subject and the frequency of MN (in ‰) was determined. Slides were distributed equally and randomly between two scorers, so that the scorers had no knowledge of the exposure status. Scorer 2 (32 exposed, 36 controls) measured increased MN frequencies in exposed workers (9.88 vs 6.81). Statistical analysis with the two-sample Wilcoxon test indicated that this difference was not significant (p = 0.17). Scorer 3 (20 exposed, 46 controls) obtained a similar result, but slightly higher values for the comparison of exposed and controls (19.0 vs 12.89; p = 0.089). Combining the results of the two scorers (13.38 vs 10.22), a significant difference between exposed and controls (p = 0.028) was obtained when the stratified Wilcoxon test with the scorers as strata was applied. Interestingly, the re-evaluation of the slides led to clearly higher MN frequencies for exposed and controls compared with the first evaluation. Bland–Altman plots indicated that the agreement between the measurements of the different scorers was very poor, as shown by mean differences of 5.9 between scorer 1 and scorer 2 and 13.0 between scorer 1 and scorer 3. Calculation of the intra-class correlation coefficient (ICC) revealed that all scorer comparisons in this study were far from acceptable for the reliability of this assay. Possible implications for the use of the CBMNT in human biomonitoring studies are discussed.

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Trabalho de Projeto para obtenção do grau de Mestre em Engenharia Civil na Área de Especialização em Edificações

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Dissertação para obtenção do grau de Mestre em Engenharia Civil na Área de Especialização em Estruturas

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Mestrado em Contabilidade