Tubulin cofactor A gene silencing in mammalian cells induces changes in microtubule cytoskeleton, cell cycle arrest and cell death

Microtubules are polymers of alpha/beta-tubulin participating in essential cell functions. A multistep process involving distinct molecular chaperones and cofactors produces new tubulin heterodimers competent to polymerise. In vitro cofactor A (TBCA) interacts with beta-tubulin in a quasi-native state behaving as a molecular chaperone. We have used siRNA to silence TBCA expression in HeLa and MCF-7 mammalian cell lines. TBCA is essential for cell viability and its knockdown produces a decrease in the amount of soluble tubulin, modifications in microtubules and G1 cell cycle arrest. In MCF-7 cells, cell death was preceded by a change in cell shape resembling differentiation.

Risk of colorectal cancer associated with the C677T polymorphism in 5,10-methylenetetrahydrofolate reductase in Portuguese patients depends on the intake of methyl-donor nutrients

Background: Polymorphisms located in genes involved in the metabolism of folate and some methyl-related nutrients are implicated in colorectal cancer (CRC). Objective: We evaluated the association of 3 genetic polymorphisms [C677T MTHFR (methylene tetrahydrofolate reductase), A2756G MTR (methionine synthase), and C1420T SHMT (serine hydroxymethyltransferase)] with the intake of methyl-donor nutrients in CRC risk. Design: Patients withCRC(n 196) and healthy controls (n 200) matched for age and sex were evaluated for intake of methyl-donor nutrients and the 3 polymorphisms. Results: Except for folate intake, which was significantly lower in patients (P 0.02), no differences were observed in the dietary intake of other methyl-donor nutrients between groups. High intake of folate ( 406.7 g/d) was associated with a significantly lower risk of CRC (odds ratio: 0.67; 95% CI: 0.45, 0.99). The A2756G MTR polymorphism was not associated with the risk of developing CRC. In contrast, homozygosity for the C677TMTHFRvariant (TT) presented a 3.0-fold increased risk of CRC (95% CI: 1.3, 6.7). Similarly, homozygosity for the C1420T SHMT polymorphism also had a 2.6-fold increased risk (95% CI: 1.1, 5.9) of developing CRC. When interactions between variables were studied, low intake of all methyl-donor nutrients was associated with an increased risk ofCRC in homozygous participants for the C677T MTHFR polymorphism, but a statistically significant interaction was only observed for folate (odds ratio: 14.0; 95% CI: 1.8, 108.5). No significant associations were seen for MTR or SHMT polymorphisms. Conclusion: These results show an association between the C677T MTHFR variant and different folate intakes on risk of CRC.

Identification of a 0.4 Kb deletion region in 10q26 associated with endometrial carcinoma

We have identified an allelic deletion common region in the q26 region of chromosome 10 in endometrial carcinomas, which has been reported previously as a potential target of genetic alterations related to this neoplasia. An allelotyping analysis of 19 pairs of tumoral and non-tumoral samples was accomplished using seven microsatellite polymorphic markers mapping in the 10q26 chromosomal region. Loss of heterozygosity for one or more loci was detected in 29% of the endometrial carcinoma samples. The observed pattern of loss enabled the identification of a 3.5 Mb common deleted region located between the D10S587 and D10S186 markers. An additional result from an endometrial sample with evidence of a RER phenotype may suggest a more centromeric region of loss within the above-mentioned interval. This 401.84 Kb interval flanked by the D10S587 and D10S216 markers may be a plausible location for a putative suppressor gene involved in early stage endometrial carcinogenesis.

Análise de risco em sequenciamento de actividades com restrições de recursos

Mestrado em Engenharia Electrotécnica e de Computadores. Área de Especialização em Sistemas e Planeamento Industrial.

Factors associated with depression symptoms in high school students in São Paulo, Brazil

OBJECTIVE: To assess factors associated with depression symptoms in high school students. METHODS: A cross-sectional study involving high school students was conducted in the city of São Paulo, Brazil, 2001. A total of 724 students aged 14-18 years answered questionnaires on life and health conditions. Another questionnaire was applied to working (44.8%) and unemployed (22.9%) students to collect information on working conditions. Factors associated to depressive disorders were analyzed using multiple logistic regression controlled for occupational status. RESULTS: Overall prevalence rate of depression was 7.5%. Rates according to gender were 39 (10.3%) in females and 15 (4.3%) in males. The multiple logistic regression analysis showed that factors associated with depressive disorders were: poor self-perception of health (OR=5.78), being female (OR = 2.45), and alcohol consumption (OR=2.35). CONCLUSIONS: The study results showed that sociodemographic, lifestyle and health variables were associated with symptoms of depression in this population. These ndings suggest that it is important to have mental health professionals available in high schools for early detection of mental conditions and student counseling.

Use of analgesics in adults with pain complaints: prevalence and associated factors, Turkey

OBJECTIVE: Use of analgesics has been increasingly recognized as a major public health issue with important consequences in Turkey. The objective of the study was to determine the prevalence and patterns of analgesics usage and associated factors in adults with pain complaints. METHODS: A cross-sectional study was conducted in 15 cities selected from five demographic regions in Turkey. The study sample population comprised 1.909 adults 18-65 age groups suffering from pain. The sampling method was multi-step stratified weighted quota-adjusted sampling. Data were collected by face-to-face interviews using a semi-structured survey questionnaire consisting of 28 questions. Odds ratios were produced by logistic regression analyses. RESULTS: The prevalence of analgesic use was 73.1%, and it was higher in females (75.7%; p<0.05), in subjects 45-54 years (81.4%; p<0.05), in subjects in rural areas (74.6%; p<0.05), in subjects in northern region (84.3%; p<0.05), in illiterate subjects (79.1%; p>0.05), and in subjects of lower socioeconomic status (74.1%; p>0.05). One in ten of the participants used non-prescription analgesics. Non-prescription analgesics were more prevalent among the 55-65 age groups (18.1%; p<0.05), among female (11.6%; p>0.05), among the urban population (10.7%; p>0.05), and in subjects of lower middle socioeconomic status (13.2%; p<0.05). Logistic regression showed statistically significant ORs only for age groups, duration of education, socioeconomic status, and demographic regions (p<0.05). CONCLUSIONS: The results showed that the prevalence of analgesic use and prescription analgesic use is high in Turkey, and their use is related to sociodemographic characteristics.

Metabolic changes associated with antiretroviral therapy in HIV-positive patients

OBJECTIVE: To evaluate metabolic changes associated with highly active antiretroviral therapy (HAART) in HIV-positive patients, and to identify risk factors associated. METHODS: Retrospective study that included 110 HIV-positive patients who where on HAART in the city of Porto Alegre (Southern Brazil) between January 2003 and March 2004. Data on demographic variables, cigarette smoking, diabetes mellitus, cholesterol and triglyceride levels, stage of HIV infection, antiretroviral therapy and HCV coinfection were collected. General linear models procedure for repeated measures was used to test the interaction between HAART and HCV coinfection or protease inhibitor treatment. RESULTS: Total cholesterol, triglycerides, and glucose levels significantly increased after receiving HAART (p<0.001 for all variables), but no interaction with protease inhibitors was seen for total cholesterol, glucose and triglyceride levels (interaction treatment*protease inhibitors p=0.741, p=0.784, and p=0.081, respectively). An association between total cholesterol levels and HCV coinfection was found both at baseline and follow-up (effect of HCV coinfection, p=0.011). Glucose levels were increased by HAART (treatment effect, p=0.036), but the effect was associated to HCV coinfection (treatment*HCV effect, p=0.018). Gender, smoking habit, intravenous drug use and age were not significantly associated with cholesterol, triglyceride and glucose changes. CONCLUSIONS: HCV-infected patients at baseline were significantly less likely to develop hypercholesterolemia. The results provide further evidence of the role of HAART for the development of metabolic disturbances.

Interactions between physical and psychosocial demands of work associated to low back pain

OBJECTIVE: To examine the interaction between physical and psychosocial demands of work associated to low back pain. METHODS: Cross-sectional study carried out in a stratified proportional random sample of 577 plastic industry workers in the metropolitan area of the city of Salvador, Northeast Brazil in 2002. An anonymous standard questionnaire was administered in the workplace by trained interviewers. Physical demands at work were self-rated on a 6-point numeric scale, with anchors at each end of the scale. Factor analysis was carried out on 11 physical demand variables to identify underlying factors. Psychosocial work demands were measured by demand, control and social support questions. Multivariate analysis was performed using the likelihood ratio test. RESULTS: The factor analysis identified two physical work demand factors: material handling (factor 1) and repetitiveness (factor 2). The multiple logistic regression analysis showed that factor 1 was positively associated with low back pain (OR=2.35, 95% CI 1.50;3.66). No interaction was found between physical and psychosocial work demands but both were independently associated to low back pain. CONCLUSIONS: The study found independent effects of physical and psychosocial work demands on low back pain prevalence and emphasizes the importance of physical demands especially of material handling involving trunk bending forward and trunk rotation regardless of age, gender, and body fitness.

Controlo difuso de um AGV

Neste trabalho pretende-se introduzir os conceitos associados à lógica difusa no controlo de sistemas, neste caso na área da robótica autónoma, onde é feito um enquadramento da utilização de controladores difusos na mesma. Foi desenvolvido de raiz um AGV (Autonomous Guided Vehicle) de modo a se implementar o controlador difuso, e testar o desempenho do mesmo. Uma vez que se pretende de futuro realizar melhorias e/ou evoluções optou-se por um sistema modular em que cada módulo é responsável por uma determinada tarefa. Neste trabalho existem três módulos que são responsáveis pelo controlo de velocidade, pela aquisição dos dados dos sensores e, por último, pelo controlador difuso do sistema. Após a implementação do controlador difuso, procedeu-se a testes para validar o sistema onde foram recolhidos e registados os dados provenientes dos sensores durante o funcionamento normal do robô. Este dados permitiram uma melhor análise do desempenho do robô. Verifica-se que a lógica difusa permite obter uma maior suavidade na transição de decisões, e que com o aumento do número de regras é possível tornar o sistema ainda mais suave. Deste modo, verifica-se que a lógica difusa é uma ferramenta útil e funcional para o controlo de aplicações. Como desvantagem surge a quantidade de dados associados à implementação, tais como, os universos de discurso, as funções de pertença e as regras. Ao se aumentar o número de regras de controlo do sistema existe também um aumento das funções de pertença consideradas para cada variável linguística; este facto leva a um aumento da memória necessária e da complexidade na implementação pela quantidade de dados que têm de ser tratados. A maior dificuldade no projecto de um controlador difuso encontra-se na definição das variáveis linguísticas através dos seus universos de discurso e das suas funções de pertença, pois a definição destes pode não ser a mais adequada ao contexto de controlo e torna-se necessário efectuar testes e, consequentemente, modificações à definição das funções de pertença para melhorar o desempenho do sistema. Todos os aspectos referidos são endereçados no desenvolvimento do AGV e os respectivos resultados são apresentados e analisados.

Controlador Boundary-Scan

A crescente complexidade dos sistemas electrónicos associada a um desenvolvimento nas tecnologias de encapsulamento levou à miniaturização dos circuitos integrados, provocando dificuldades e limitações no diagnóstico e detecção de falhas, diminuindo drasticamente a aplicabilidade dos equipamentos ICT. Como forma de lidar com este problema surgiu a infra-estrutura Boundary Scan descrita na norma IEEE1149.1 “Test Access Port and Boundary-Scan Architecture”, aprovada em 1990. Sendo esta solução tecnicamente viável e interessante economicamente para o diagnóstico de defeitos, efectua também outras aplicações. O SVF surgiu do desejo de incutir e fazer com que os fornecedores independentes incluíssem a norma IEEE 1149.1, é desenvolvido num formato ASCII, com o objectivo de enviar sinais, aguardar pela sua resposta, segundo a máscara de dados baseada na norma IEEE1149.1. Actualmente a incorporação do Boundary Scan nos circuitos integrados está em grande expansão e consequentemente usufrui de uma forte implementação no mercado. Neste contexto o objectivo da dissertação é o desenvolvimento de um controlador boundary scan que implemente uma interface com o PC e possibilite o controlo e monitorização da aplicação de teste ao PCB. A arquitectura do controlador desenvolvido contém um módulo de Memória de entrada, um Controlador TAP e uma Memória de saída. A implementação do controlador foi feita através da utilização de uma FPGA, é um dispositivo lógico reconfiguráveis constituído por blocos lógicos e por uma rede de interligações, ambos configuráveis, que permitem ao utilizador implementar as mais variadas funções digitais. A utilização de uma FPGA tem a vantagem de permitir a versatilidade do controlador, facilidade na alteração do seu código e possibilidade de inserir mais controladores dentro da FPGA. Foi desenvolvido o protocolo de comunicação e sincronização entre os vários módulos, permitindo o controlo e monitorização dos estímulos enviados e recebidos ao PCB, executados automaticamente através do software do Controlador TAP e de acordo com a norma IEEE 1149.1. A solução proposta foi validada por simulação utilizando o simulador da Xilinx. Foram analisados todos os sinais que constituem o controlador e verificado o correcto funcionamento de todos os seus módulos. Esta solução executa todas as sequências pretendidas e necessárias (envio de estímulos) à realização dos testes ao PCB. Recebe e armazena os dados obtidos, enviando-os posteriormente para a memória de saída. A execução do trabalho permitiu concluir que os projectos de componentes electrónicos tenderão a ser descritos num nível de abstracção mais elevado, recorrendo cada vez mais ao uso de linguagens de hardware, no qual o VHDL é uma excelente ferramenta de programação. O controlador desenvolvido será uma ferramenta bastante útil e versátil para o teste de PCBs e outras funcionalidades disponibilizadas pelas infra-estruturas BS.

Factors associated to quality of life in active elderly

OBJECTIVE: To analyze whether quality of life in active, healthy elderly individuals is influenced by functional status and sociodemographic characteristics, as well as psychological parameters. METHODS: Study conducted in a sample of 120 active elderly subjects recruited from two open universities of the third age in the cities of São Paulo and São José dos Campos (Southeastern Brazil) between May 2005 and April 2006. Quality of life was measured using the abbreviated Brazilian version of the World Health Organization Quality of Live (WHOQOL-bref) questionnaire. Sociodemographic, clinical and functional variables were measured through crossculturally validated assessments by the Mini Mental State Examination, Geriatric Depression Scale, Functional Reach, One-Leg Balance Test, Timed Up and Go Test, Six-Minute Walk Test, Human Activity Profile and a complementary questionnaire. Simple descriptive analyses, Pearson's correlation coefficient, Student's t-test for non-related samples, analyses of variance, linear regression analyses and variance inflation factor were performed. The significance level for all statistical tests was set at 0.05. RESULTS: Linear regression analysis showed an independent correlation without colinearity between depressive symptoms measured by the Geriatric Depression Scale and four domains of the WHOQOL-bref. Not having a conjugal life implied greater perception in the social domain; developing leisure activities and having an income over five minimum wages implied greater perception in the environment domain. CONCLUSIONS: Functional status had no influence on the Quality of Life variable in the analysis models in active elderly. In contrast, psychological factors, as assessed by the Geriatric Depression Scale, and sociodemographic characteristics, such as marital status, income and leisure activities, had an impact on quality of life.

Monitorization of alveolar deposited surface area of nanoparticles and ultrafine particles in different environments

Nanotechnology is an important emerging industry with a projected annual market of around one trillion dollars by 2015. It involves the control of atoms and molecules to create new materials with a variety of useful functions. Although there are advantages on the utilization of these nano-scale materials, questions related with its impact over the environment and human health must be addressed too, so that potential risks can be limited at early stages of development. At this time, occupational health risks associated with manufacturing and use of nanoparticles are not yet clearly understood. However, workers may be exposed to nanoparticles through inhalation at levels that can greatly exceed ambient concentrations. Current workplace exposure limits are based on particle mass, but this criteria could not be adequate in this case as nanoparticles are characterized by very large surface area, which has been pointed out as the distinctive characteristic that could even turn out an inert substance into another substance exhibiting very different interactions with biological fluids and cells. Therefore, it seems that, when assessing human exposure based on the mass concentration of particles, which is widely adopted for particles over 1 μm, would not work in this particular case. In fact, nanoparticles have far more surface area for the equivalent mass of larger particles, which increases the chance they may react with body tissues. Thus, it has been claimed that surface area should be used for nanoparticle exposure and dosing. As a result, assessing exposure based on the measurement of particle surface area is of increasing interest. It is well known that lung deposition is the most efficient way for airborne particles to enter the body and cause adverse health effects. If nanoparticles can deposit in the lung and remain there, have an active surface chemistry and interact with the body, then, there is potential for exposure. It was showed that surface area plays an important role in the toxicity of nanoparticles and this is the metric that best correlates with particle-induced adverse health effects. The potential for adverse health effects seems to be directly proportional to particle surface area. The objective of the study is to identify and validate methods and tools for measuring nanoparticles during production, manipulation and use of nanomaterials.

Direcção de obra – obras de arte auto-estrada Transmontana – área 3

Este relatório diz respeito ao trabalho desenvolvido em ambiente de estágio académico numa Empreitada compreendendo Obras de Arte Correntes e Obras de Arte Especiais inseridas em traçado actual do IP4 que está a ser transformado em Auto-Estrada. As Obras de Arte Correntes compreendem Passagens Superiores, Passagens Inferiores e Passagens superiores de Nó. As Obras de Arte Especiais compreendem duas Pontes com vãos distintos. Todas as Obras de Arte referidas neste relatório contemplam uma solução mista de betão armado “in situ” e tabuleiros com vigas e pré-lajes em betão pré-fabricado. Além da descrição de todas as actividades realizadas em betão armado “in situ”, desde as fundações até ao tabuleiro, descreve também a execução dos diversos tipos de trabalhos de acabamentos. Além das actividades de construção civil, é efectuada uma descrição das actividades a cujo processo de realização estão associados trabalhos de concepção e desenvolvimento, como é o caso dos cimbres. Este relatório faz uma descrição abrangente das funções da Direcção de Obra numa Empreitada de Obras de Arte, que para além da execução da obra, com todas as actividades que lhe são inerentes, compreende várias áreas funcionais que fazem parte de uma empresa de construção civil, como a área comercial, financeira, planeamento, aprovisionamento, controlo orçamental, gestão contratual, gestão de subempreitadas e gestão da qualidade, ambiente e segurança.

The three-loop SSM beta-functions

We present the supersymmetric standard model three-loop beta-functions for gauge and Yukawa couplings and consider the effect of three-loop corrections on the standard running coupling analyses.

Direct medical costs associated with schizophrenia relapses in health care services in the city of São Paulo

OBJECTIVE: To assess direct medical costs associated with schizophrenia relapses in mental health services. METHODS: The study was conducted in three health facilities in the city of São Paulo: a public state hospital; a Brazilian National Health System (SUS)-contracted hospital; and a community mental health center. Medical records of 90 patients with schizophrenia who received care in 2006 were reviewed. Information on inpatient expenditures was collected and used for cost estimates. RESULTS: Mean direct medical cost of schizophrenia relapses per patient was US$ 4,083.50 (R$ 8,167.58) in the public state hospital; US$ 2,302.76 (R$ 4,605.46) in the community mental health center; and US$ 1,198.50 (R$ 2,397.74) in the SUS-affiliated hospital. The main component was daily inpatient room rates (87% - 98%). Medication costs varied depending on the use of typical or atypical antipsychotic drugs. Atypical antipsychotic drugs were more often used in the community mental health center. CONCLUSIONS: Costs associated with schizophrenia relapses support investments in antipsychotic drugs and strategies to reduce disease relapse and the need for mental health inpatient services. Treating patients in a community mental health center was associated with medium costs and added the benefit of not depriving these patients from family life.