Generation of CTL responses using Kunjin replicon RNA

The Kunjin replicon was used to express a polytope that consisted of seven hepatitis C virus cytotoxic T lymphocyte epitopes and one influenza cytotoxic T lymphocyte epitope for vaccination studies. The self-replicating nature of, and expression from, the ribonucleic acid was confirmed in vitro . Initial vaccinations with one dose of Kun-Poly ribonucleic acid showed that an influenza-specific cytotoxic T lymphocyte response was elicited more efficiently by intradermal inoculation compared with intramuscular delivery. Two micrograms of ribonucleic acid delivered in the ear pinnae of mice was sufficient to elicit a detectable cytotoxic T lymphocyte response 10 days post-vaccination. Further vaccination studies showed that four of the seven hepatitis C virus cytotoxic T lymphocyte epitopes were able to elicit weak cytotoxic T lymphocyte responses whereas the influenza epitope was able to elicit strong, specific cytotoxic T lymphocyte responses following three doses of Kun-Poly ribonucleic acid. These studies vindicate the use of the Kunjin replicon as a vector to deliver encoded proteins for the development of cell-mediated immune responses.

Discrete element modelling of power draw of tumbling mills

The power required to operate large mills is typically 5-10 MW. Hence, optimisation of power consumption will have a significant impact on overall economic performance and environmental impact. Power draw modelling results using the discrete element code PFC3D have been compared with results derived from the widely used empirical Model of Morrell. This is achieved by calculating the power draw for a range of operating conditions for constant mill size and fill factor using two modelling approaches. fThe discrete element modelling results show that, apart from density, selection of the appropriate material damping ratio is critical for the accuracy of modelling of the mill power draw. The relative insensitivity of the power draw to the material stiffness allows selection of moderate stiffness values, which result in acceptable computation time. The results obtained confirm that modelling of the power draw for a vertical slice of the mill, of thickness 20% of the mill length, is a reliable substitute for modelling the full mill. The power draw predictions from PFC3D show good agreement with those obtained using the empirical model. Due to its inherent flexibility, power draw modelling using PFC3D appears to be a viable and attractive alternative to empirical models where necessary code and computer power are available.

Provision of 4-1BB ligand enhances effector and memory CTL responses generated by immunization with dendritic cells expressing a human tumor-associated antigen

Up-regulation of receptor-ligand pairs during interaction of an MHC-presented epitope on dendritic cells (DCs) with cognate TCR may amplify, sustain, and drive diversity in the ensuing T cell immune response. Members of the TNF ligand superfamily and the TNFR superfamily contribute to this costimulatory molecule signaling. In this study, we used replication deficient adenoviruses to introduce a model tumor-associated Ag (the E7 oncoprotein of human papillomavirus 16) and the T cell costimulatory molecule 4-IBBL into murine DCs, and monitored the ability of these recombinant DO to elicit E7-directed T cell responses following immunization. Splenocytes from mice immunized with DCs expressing E7 alone elicited E7-directed effector and memory CTL responses. Coexpression of 4-1BBL in these E7-expressing DO increased effector and memory CTL responses when they were used for immunization. 4-1BBL expression up-regulated CD80 and CD86 second signaling molecules in DO. We also report an additive effect of 4-IBBL and receptor activator of NF-kappaB/receptor activator of NF-kappaB ligand coexpression in E7-transduced DC inummogens on E7-directed effector and memory CTL responses and on MHC class II and CD80/86 expression in DCs. Additionally, expression of 4-1BBL in E7-transduced DCs reduced nonspecific T cell activation characteristic of adenovirus vector-associated immunization. The results have generic implications for improved or tumor Ag-expressing DC vaccines by incorporation of exogenous 4-1BBL. There are also specific implications for an improved DC-based vaccine for human papillomavirus 16-associated cervical carcinoma.

Clinicians' attitudes to clinical practice guidelines

To the Editor: In their systematic review of clinicians' attitudes to clinical practice guidelines, Farquhar et al1 found that, although healthcare providers reported high satisfaction with guidelines, a significant number also expressed concerns about their practicality, their role in cost-cutting and their potential for increasing litigation. The review, however, did not address other potentially significant concerns of clinicians regarding the perceived validity of guidelines and the influence of external agencies (such as the pharmaceutical industry) on treatment recommendations.

V??deo institucional ENAP: 1997

V??deo institucional sobre objetivos e atua????o da ENAP

A disciplina de história da educação em perspectiva histórica : da Faculdade de Filosofia, Ciências e Letras à Universidade Federal do Espírito Santo (1951-2000)

A pesquisa analisa da constituição histórica da disciplina História da Educação ministrada na Faculdade de Filosofia Ciências e Letras do Estado do Espírito Santo, posteriormente incorporada a Universidade Federal do Espírito Santo entre os anos de 1951 e 2000. Investiga a constituição histórica da disciplina, as transformações programáticas, legais e institucionais referentes à disciplina de História da Educação, como também as abordagens historiográficas, periodizações e os conceitos de tempo, história e educação. A fundamentação teórica e metodológica articula-se dialogicamente a partir das construções conceituais e metodológicas de Carlo Ginzburg e Mikhail Bakhtin. A partir dos conceitos de polifonia e dialogismo, comum a ambos, investigou-se as vozes e diálogos impressos nas narrativas da disciplina de História da Educação e seu ensino, sejam em camadas mais superficiais ou profundas, encontradas no corpus documental consultado e analisado, que correspondem a: programas de ensino, transparências, leis, estruturas curriculares, documentos de departamento; resenhas e fichamentos de textos, bibliografia obrigatória e complementar, avaliações e entrevistas. Procurou-se no corpus documental dados aparentemente negligenciáveis – pistas, indícios e sinais – remontar uma realidade histórica complexa e não experimentável diretamente. Ao investigar historicamente a trajetória da disciplina História da Educação e seu ensino a partir dos parâmetros legais, programáticos e institucionais, foi possível perceber que as mudanças mais profundas operadas na disciplina não se originam das legislações e reestruturações curriculares, mas dos locais de produção e socialização do conhecimento histórico. Durante o período analisado, as duas esferas de produção historiográficas que mais influenciaram nas abordagens, periodizações e conceitos de tempo, história e educação da disciplina História da Educação do curso de pedagogia pesquisado foram: a editora responsável pela publicação e divulgação dos Manuais de História da Educação da coleção Atualidades Pedagógicas (1951-1979) e os Programas de Pós-graduação em Educação e História (1980 - 2000). Entre 1951 e finais de 1970 observa-se a influência dos Manuais de História da Educação, na organização e programação do ensino de História da Educação e uma abordagem filosófica voltada para a história das ideias pedagógicas e análises do pensamento de filósofos e educadores sobre a educação e respectivas inserções em doutrinas filosóficas europeias. A partir de 1980 as abordagens de cunho econômico, político e ideológico dos contextos históricos educativos passaram a predominar nos programas de ensino das disciplinas de História da Educação I e II, e vigoraram até meados nos anos de 1990. Na disciplina de História da Educação I a abordagem é marcada por análises do contexto de produção e organização das classes sociais; com relação à disciplina História da Educação II, até meados de 1995, trata da educação brasileira. A partir da abordagem fundamentada na Teoria da Dependência após 1995, os documentos consultados começam a mostrar outras marcas que sugerem uma abordagem voltada para a dimensão política e social, abordando a História da Educação Brasileira, a partir dos movimentos sociais e seus respectivos projetos educacionais.

Neural Electrode Array Based on Aluminum: Fabrication and Characterization

A unique neural electrode design is proposed with 3 mm long shafts made from an aluminum-based substrate. The electrode is composed by 100 individualized shafts in a 10 × 10 matrix, in which each aluminum shafts are precisely machined via dicing-saw cutting programs. The result is a bulk structure of aluminum with 65 ° angle sharp tips. Each electrode tip is covered by an iridium oxide thin film layer (ionic transducer) via pulsed sputtering, that provides a stable and a reversible behavior for recording/stimulation purposes, a 40 mC/cm2 charge capacity and a 145 Ω impedance in a wide frequency range of interest (10 Hz-100 kHz). Because of the non-biocompatibility issue that characterizes aluminum, an anodization process is performed that forms an aluminum oxide layer around the aluminum substrate. The result is a passivation layer fully biocompatible that furthermore, enhances the mechanical properties by increasing the robustness of the electrode. For a successful electrode insertion, a 1.1 N load is required. The resultant electrode is a feasible alternative to silicon-based electrode solutions, avoiding the complexity of its fabrication methods and limitations, and increasing the electrode performance.

Metodologia de Suporte à Utilização de Sistemas Interativos

Interactive systems users still face several challenge. Besides current improvements in usability and intuitiveness users have to adapt to the systems proposed to satisfy their needs. For instance, they must learn how to achieve tasks, how to interact with the system, etc. This paper proposes a methodology to improve this situation supporting the use of interactive systems by users. To achieve this goal the approach is based on enriched task models and picture-driven computing. An example based on a text editor illustrates the approach.

Riscos da co-incineração ou co-incineração dos riscos? Análise das controvérsias sobre resíduos industriais perigosos

A co-incineração constitui um método de tratamento de resíduos industriais, introduzido em diversos países e proposto também em Portugal, como alternativa à construção de centrais de incineração “dedicada”. A co-incineração consiste na queima de resíduos, incluindo resíduos industriais perigosos, em fornos de fábricas cimenteiras, onde são utilizados como combustível. Motivos de ordem ambiental, assim como de ordem económica, têm sido invocados em defesa do recurso a esse método como parte de estratégias de gestão dos resíduos industriais.

Entre incertezas e divergências: a ciência e a avaliação do risco

O risco é uma das áreas em que é mais evidente a primazia dos sistemas periciais nas sociedades contemporâneas. Viver em “sociedades de risco” só é sustentável quando há confiança na competência dos peritos e na autenticidade do conhecimento especializado, como garantia de minimização do risco. Hoje em dia, as sociedades encontram-se, com efeito, na dependência dos peritos científicos e dos “órgãos sensórios” da ciência (instrumentos, técnicas) para a identificação dos riscos modernos, que são em grande parte inacessíveis à percepção humana.

Consumidores, pacientes, activistas, cidadãos: representação e participação do público na gestão do risco

Os riscos alimentares, ambientais e de saúde pública têm dado origem a polémicas públicas acesas que têm alimentado receios e movimentações sociais e levado mesmo à obstrução de decisões políticas e à paralisação de investimentos.

Informação ou dramatização do risco: os media e os novos riscos

Também transversal a todos os casos analisados é o importante papel desempenhado pelos meios de comunicação social. Nas sociedades contemporâneas, os conflitos sociais apenas adquirem existência na esfera pública quando recebem cobertura mediática. No caso particular das questões de risco, tal é especialmente verdade. Os mass media, por via do chamado efeito do Agenda Setting, conferem existência a problemas que de outra forma estariam ausentes da esfera pública. Ao divulgarem um caso de risco, pressionam o poder político para tomar medidas ou justificar as opções tomadas, assim como a comunidade científica para sustentar o aconselhamento prestado.

Exposure assessment: the influence of environmental monitoring methodology

Exposure assessment is an important step of risk assessment process and has evolved more quickly than perhaps any aspect of the four-step risk paradigm (hazard identification, exposure assessment, dose-response analysis, and risk characterization). Nevertheless, some epidemiological studies have associated adverse health effects to a chemical exposure with an inadequate or absent exposure quantification. In addition to the metric used, the truly representation of exposure by measurements depends on: the strategy of sampling, random collection of measurements, and similarity between the measured and unmeasured exposure groups. Two environmental monitoring methodologies for formaldehyde occupational exposure were used to assess the influence of metric selection in exposure assessment and, consequently, in risk assessment process.

Indoor air quality in primary schools

Clean air is a basic requirement of life. The Indoor Air Quality (IAQ) has been the object of several studies due to an increasing concern within the scientific community on the effects of indoor air quality upon health, especially as people tend to spend more time indoors than outdoors. The quality of air inside homes, offices, schools or other private and public buildings is an essential determinant of healthy life and people’s well-being. People can be exposed to contaminants by inhalation, ingestion and dermal contact. In the past, scientists have paid much attention to the study of exposure to outdoor air contaminants, because they have realised the seriousness of outdoor air pollution problems. However, each indoor microenvironment has unique characteristics, determined by the local outdoor air, specific building characteristics and indoor activities. Indeed, hazardous substances are emitted from buildings, construction materials and indoor equipment or due to human activities indoors.

Quality of life in dilated cardiomyopathy with refractory chronic heart failure undergoing devices implantation

Heart failure is the final stage of most of cardiac diseases. It is a complex syndrome in which the patients should have the following features: symptoms of heart failure, typically shortness of breath at rest or during exertion, and/or fatigue; signs of fluid retention such as pulmonary congestion or ankle swelling; and objective evidence of an abnormality of the structure or function of the heart at rest. This progressive syndrome as a high incidence and prevalence and poor prognosis: four-year mortality is around 50% with 40% of the patients admitted to hospital dying or readmitted within a year. With ageing, many patients will develop chronic heart failure, which, because of its symptoms, patient’s awareness of their risk of dying, and the effects of therapy, together with frequent hospitalizations, has considerable impact on patient’s health-related quality of life.