Papillomavirus virus-like particles can deliver defined CTL epitopes to the MHC class I pathway

To evaluate an antigen delivery system in which exogenous antigen can target the major histocompatibility complex (MHC) class I pathway, a single human papillomavirus (HPV) 16 E7 cytotoxic T lymphocyte (CTL) epitope and a single HIV gp160 CTL epitope were separately fused to the C-terminus or bovine papillomavirus 1 (BPV1) L1 sequence to form hybrid BPV1L1 VLPs. Mice immunized with these hybrid VLPs mounted strong CTL responses against the relevant target cells in the absence of any adjuvants. In addition, the CTL responses induced by immunization with BPV1L1/HPV16E7CTL VLPs protected mice against challenge with E7-transformed tumor cells. Furthermore, a high titer-specific antibody response against BPV1L1 VLPs was also induced, and this antiserum could inhibit papillomavirus-induced agglutination of mouse erythrocytes, suggesting that the antibody may recognize conformational determinates relevant to virus neutralization. These data demonstrate that hybrid BPV1L1 VLPs can be used as carriers to target antigenic epitopes to both the MHC class I and class II pathways, providing a promising strategy for the design of vaccines to prevent virus infection, with the potential to elicit therapeutic virus-specific CTL responses. (C) 1998 Academic Press.

Conformational selection of inhibitors and substrates by proteolytic enzymes: Implications for drug design and polypeptide processing

Inhibitors of proteolytic enzymes (proteases) are emerging as prospective treatments for diseases such as AIDS and viral infections, cancers, inflammatory disorders, and Alzheimer's disease. Generic approaches to the design of protease inhibitors are limited by the unpredictability of interactions between, and structural changes to, inhibitor and protease during binding. A computer analysis of superimposed crystal structures for 266 small molecule inhibitors bound to 48 proteases (16 aspartic, 17 serine, 8 cysteine, and 7 metallo) provides the first conclusive proof that inhibitors, including substrate analogues, commonly bind in an extended beta-strand conformation at the active sites of all these proteases. Representative superimposed structures are shown for (a) multiple inhibitors bound to a protease of each class, (b) single inhibitors each bound to multiple proteases, and (c) conformationally constrained inhibitors bound to proteases. Thus inhibitor/substrate conformation, rather than sequence/composition alone, influences protease recognition, and this has profound implications for inhibitor design. This conclusion is supported by NMR, CD, and binding studies for HIV-1 protease inhibitors/ substrates which, when preorganized in an extended conformation, have significantly higher protease affinity. Recognition is dependent upon conformational equilibria since helical and turn peptide conformations are not processed by proteases. Conformational selection explains the resistance of folded/structured regions of proteins to proteolytic degradation, the susceptibility of denatured proteins to processing, and the higher affinity of conformationally constrained 'extended' inhibitors/substrates for proteases. Other approaches to extended inhibitor conformations should similarly lead to high-affinity binding to a protease.

Virtual models of the HLA class I antigen processing pathway

Antigen recognition by cytotoxic CD8 T cells is dependent upon a number of critical steps in MHC class I antigen processing including proteosomal cleavage, TAP transport into the endoplasmic reticulum, and MHC class 1 binding. Based on extensive experimental data relating to each of these steps there is now the capacity to model individual antigen processing steps with a high degree of accuracy. This paper demonstrates the potential to bring together models of individual antigen processing steps, for example proteosome cleavage, TAP transport, and MHC binding, to build highly informative models of functional pathways. In particular, we demonstrate how an artificial neural network model of TAP transport was used to mine a HLA-binding database so as to identify H LA-binding peptides transported by TAP. This integrated model of antigen processing provided the unique insight that HLA class I alleles apparently constitute two separate classes: those that are TAP-efficient for peptide loading (HLA-B27, -A3, and -A24) and those that are TAP-inefficient (HLA-A2, -B7, and -B8). Hence, using this integrated model we were able to generate novel hypotheses regarding antigen processing, and these hypotheses are now capable of being tested experimentally. This model confirms the feasibility of constructing a virtual immune system, whereby each additional step in antigen processing is incorporated into a single modular model. Accurate models of antigen processing have implications for the study of basic immunology as well as for the design of peptide-based vaccines and other immunotherapies. (C) 2004 Elsevier Inc. All rights reserved.

The Australian Universities Teaching Committee project in 'Learning Outcomes and Curriculum Development in Psychology'

The Australian Universities Teaching Committee (AUTC) funds projects intended to improve the quality of teaching and learning in specific disciplinary areas. The project brief for 'Learning Outcomes and Curriculum Development in Psychology' for 2004/2005 was to 'produce an evaluative overview of courses ... with a focus on the specification and assessment of learning outcomes and ... identify strategic directions for universities to enhance teaching and learning'. This project was awarded to a consortium from The University of Queensland, University of Tasmania, and Southern Cross University. The starting point for this project is an analysis of the scientist-practitioner model and its role in curriculum design, a review of current challenges at a conceptual level, and consideration of the implications of recent changes to universities relating to such things as intemationalisation of programs and technological advances. The project will seek to bring together stakeholders from around the country in order to survey the widest possible range of perspectives on the project brief requirements. It is hoped also to establish mechanisms for fiiture scholarly discussion of these issues, including the establishment of an Australian Society for the Teaching of Psychology and an annual conference.

Constructing a class of designs with proportional balance

Text serves as a sequel to 'Computational and Constructive Design Theory,' c1996; containing research papers and surveys of recent research work on design construction and computer-aided study of designs. For researchers in theory of computational designs.

Masseter muscle thickness three years after surgical correction of class III dentofacial deformity

Objective: To analyse the effect of integrated orthodontic treatment, orthognathic surgery and orofacial myofunctional therapy on masseter muscle thickness in patients with class III dentofacial deformity three years after orthognathic surgery. Design: A longitudinal study was conducted on 13 patients with class III dentofacial deformities, denoted here as group P1 (before surgery) and group P3 (same patients 3 years to 3 years and 8 months after surgery). Fifteen individuals with no changes in facial morphology or dental occlusion were assigned to the control group (CG). Masseter muscle ultrasonography was performed in the resting and biting situations in the three groups. Data were analysed statistically by a mixed-effects linear model considering a level of significance of P < 0.05. Results: Significantly higher values (P < 0.01) of masseter muscle thickness (cm) were detected in group P3 (right rest: 0.82 +/- 0.16, left rest: 0.87 +/- 0.21, right bite: 1 +/- 0.22, left bite: 1.04 +/- 0.28) compared to group P1 (right rest: 0.63 +/- 0.19, left rest: 0.64 +/- 0.15, right bite: 0.87 +/- 0.16, left bite: 0.88 +/- 0.14). Between P3 and CG (right rest: 1.02 +/- 0.19, left rest: 1 +/- 0.19, right bite: 1.18 +/- 0.22, left bite: 1.16 +/- 0.22) there was a significant difference on the right side of the muscle (P < 0.05) in both situations and on the left side at rest. Conclusion: The proposed treatment resulted in improved masseter muscle thickness in patients with class III dentofacial deformity. (C) 2011 Elsevier Ltd. All rights reserved.

The cyclotides: Novel macrocyclic peptides as scaffolds in drug design

Cyclotides are a novel class of circular, disulfide-rich peptides (similar to 30 amino acids) that display a broad range of bioactivities and have exceptionally high stability. Their physical properties, which include resistance to thermal and enzymatic degradation, can be attributed to their unique cyclic backbone and knotted arrangement of disulfide bonds. The applicability of linear peptides as drugs is potentially limited by their susceptibility to proteolytic cleavage and poor bioavailability. Such limitations may be overcome by using the cyclotide framework as a scaffold onto which new activities may be engineered. The potential use of cyclotides for drug design is evaluated here, with reference to rapidly increasing knowledge of natural cyclotides and the emergence of new techniques in peptide engineering.

Implications of missed opportunities for learning and assessment in design and technology education

Supporting student learning can be difficult, especially within open-ended or loosely structured activities, often seen as valuable for promoting student autonomy in many curriculum areas and contexts. This paper reports an investigation into the experiences of three teachers who implemented design and technology education ideas in their primary school classrooms for the first time. The teachers did not capitalise upon many of the opportunities for scaffolding their students' learning within the open-ended activities they implemented. Limitations of the teachers' conceptual and procedural knowledge of design and technology were elements that influenced their early experiences. The study has implications for professional developers planning programs in newly introduced areas of the curriculum to support teachers in supporting learning within open-ended and loosely structured problem solving activities. (C) 2001 Elsevier Science Ltd. All rights reserved.

A política do ensino médio integrado no Espírito Santo e a experiência de sua implantação na Escola Estadual de Ensino Médio Arnulpho Mattos

Esta dissertação teve como objeto o Ensino Médio Integrado no Espírito Santo, sua trajetória e implantação a partir do Decreto 5.154/2004. O objetivo principal foi analisar a política do ensino médio integrado à educação profissional técnica de nível médio implementada no Espírito Santo. Investigar a educação pública pressupõe contextualizar a sociedade e as construções sociais que se projetam. O ensino médio no Brasil, enquanto etapa intermediária entre o ensino fundamental e a educação superior constitui-se de grande complexidade na estruturação de políticas públicas, no que tange à sua expansão qualitativa e quantitativa. Foram estabelecidos os seguintes objetivos específicos: identificar os pressupostos teóricos e pedagógicos contidos na Proposta Pedagógica da unidade escolar EEEFM Arnulpho Mattos; analisar a matriz curricular e a proposta pedagógica; relacionar o projeto pedagógico do curso com a prática educacional relatada nos encontros com os alunos; analisar a organização escolar e sua gestão política e pedagógica em face da proposta do EMI; relacionar a proposta do EMI, o princípio da politecnia e os relatos dos alunos; mapear a oferta do EMI no estado e o seu investimento financeiro. Nesse cenário, identificamos a relação entre trabalho e educação que contextualiza a relação da escola com a sociedade no sistema capitalista, em especial no ensino médio. Assim, nossa hipótese foi que esta política tem dificuldades de alcançar seus objetivos porque sua estrutura material segue a lógica da escola capitalista, assentada na perspectiva da Teoria do Capital Humano. A formação profissional no ensino médio é uma demanda social e histórica da classe trabalhadora, que necessita ingressar mais rápido no mercado de trabalho do que os filhos das elites brasileiras. A metodologia empregada foi uma pesquisa do tipo qualitativa, sendo um estudo de caso da EEEF Arnulpho Mattos. Os procedimentos metodológicos adotados para a investigação foram: observação, entrevistas semi-estruturadas, a análise documental, a revisão bibliográfica e os princípios metodológicos inscritos na sociologia da experiência (DUBET, 1994). Na articulação desses procedimentos, verificamos que a política do ensino médio integrado no ES teve, em seu início, um planejamento de implantação bem estruturado mas interrompido e, posteriormente, caracterizou-se pela descontinuidade das ações. Ademais, constatamos que os alunos ingressam e permanecem no curso sem compreenderem de fato o que significa a formação integrada entre a área geral e a técnica/profissional. Nos grupos de discussão percebemos que bastaram alguns encontros para que se pudesse estabelecer uma visão e relação diferenciadas com a experiência social do ensino médio integrado, principalmente por serem alunos trabalhadores. Acrescentamos às nossas conclusões que há iniciativas da escola acerca da integração entre as disciplinas de formação geral e técnicas, mas sem apoio ou orientação da unidade gestora, ou seja, a Sedu. A ampliação da oferta do EMI ocorreu no estado sem investimento na formação e valorização dos professores, sem concurso público e sem uma infra-estrutura necessária para a formação de jovens e adultos com capacidade de entender e de interferir no mundo do trabalho.

Contribution towards a reflection about methodological strategies in design education and the function of drawing in design

This work presents a reflection on Design education and specifically on the role of Drawing in this area. As a subject, Design has expanded its field of action expanding into new areas such as Experience Design or Service Design. It became necessary for the designer to have more than an education based on technological knowledge or know-how. Many authors like Meredith Davis, Don Norman or Jamie Hobson point out the urgency to review the curricula of Design courses because nowadays “… design is more than appearance, design is about interaction, about strategy and about services. Designers change social behavior” (Norman 2011). When shifting from a product-centered design to a person-centered design (in a structure, a service or in a relationship) what should the function of drawing in a design course be? What should its curriculum be? Our work methodology will be to confront today’s perspectives on design theory and practice in an attempt to add to the discussion on the methodological strategies in design teaching in the contemporary context.

Contribution towards a reflection about methodological strategies in Design Education and the function of Drawing in Design

This work presents a reflection on Design education and specifically on the role of Drawing in this area. As a subject, Design has expanded its field of action expanding into new areas such as Experience Design or Service Design. It became necessary for the designer to have more than an education based on technological knowledge or know-how. Many authors like Meredith Davis, Don Norman or Jamie Hobson point out the urgency to review the curricula of Design courses because nowadays “ … design is more than appearance, design is about interaction, about strategy and about services. Designers change social behavior” (Norman, 2011) When shifting from a product-centered design to a person-centered design (in a structure, a service or in a relationship) what should the function of drawing in a design course be? What should its curriculum be? Our work methodology will be to confront today’s perspectives on design theory and practice in an attempt to add to the discussion on the methodological strategies in design teaching in the contemporary context.

O currículo e as necessidades educativas especiais : práticas de adequação curricular no terceiro ciclo

A responsabilidade da construção de uma escola para todos deve ser o grande objectivo de todo e qualquer professor, criando espaços de reflexão conjunta no sentido de serem traçados projectos curriculares diferenciados que dêem resposta a todos os alunos na sua diversidade plural. Assim, a concepção e construção da escola inclusiva implicam mudanças, quer nas atitudes e práticas dos agentes educativos, quer nas estruturas do sistema de ensino ao nível organizacional e da gestão curricular. Neste âmbito, a adequação do currículo às necessidades educativas especiais (NEE) dos alunos torna-se essencial na (re)construção e operacionalização dos diferentes processos curriculares. O trabalho que agora se apresenta foi desenvolvido através de um estudo de caso. Constitui uma tentativa de compreensão das percepções dos professores e das práticas pedagógicas que desenvolvem para efectuar adequações curriculares para alunos com NEE. Centrámo-nos nos professores de um conselho de turma do sétimo ano do terceiro ciclo do ensino básico (3º CEB) que inclui uma aluna com NEE, procurando saber o que pensam sobre o processo de adequação curricular, como o concebem e como o implementam. Como metodologia de recolha dos dados utilizamos as técnicas da entrevista, da análise documental e da observação naturalista. Concluímos que, apesar das dificuldades que expressam e demonstram, os professores assumem a necessidade de implementar adequações curriculares face às NEE dos alunos, como resposta às diferenças e particularidades de cada um, tendo em vista o desenvolvimento de competências essenciais e a conclusão da escolaridade obrigatória. As Adequações Curriculares são percepcionadas como muito vantajosas do ponto de vista da promoção do sucesso educativo para todos os alunos e em particular para os alunos com NEE, proporcionando a estes, acompanhar o currículo mais próximo do que é normal, sentirem-se como “iguais” aos seus colegas, melhorar a sua auto-estima, auto-confiança e motivação ABSTRACT The responsibility of building a school for all must be the ultimate goal of any teacher, creating spaces for joint reflection in order to draw differentiated curricular projects which respond to all students in their plural diversity. Thus, the design and construction of the inclusive school involve changes both in attitudes and practices of the educational agents, and in the structures of the education system regarding the organization and the curriculum management. In this context, the adequacy of the curriculum to students’ special educational needs (SEN) becomes essential in the (re) construction and operationalization of the different curriculum processes. The work now presented was developed through a case study. It attempts to understand the perceptions of teachers and the pedagogical practices they develop to make curricular adjustments for students with SEN. We focused on the teachers of a seventh year class of the third cycle of basic education (3rd CBE) which includes a pupil, a girl, with SEN, trying to find out what they think about the process of adapting the curriculum, how they conceive and implement it. As a methodology of data collection we used different techniques: the interview, the documentary analysis and the naturalistic observation. We concluded that, despite the difficulties that teachers express and demonstrate they assume the need to implement curricular adjustments in relation to pupils with SEN in response to the differences and particularities of each one in order to develop core competencies and to complete compulsory schooling. The Curriculum Adequacies are perceived as very advantageous from the standpoint of promoting educational success for all students and particularly for pupils with SEN, providing the latter the possibility of following the curriculum closer than usual, feeling as "equal" to their schoolmates, improving their self-esteem, self- confidence and motivation.

Studying the development of an online course on Curriculum : implications for the students' workload in light of the Bologna principles

ECER 2014 "The Past, the Present and Future of Educational Research in Europe" will take place at the University of Porto from 1 - 5 September 2014.

The emergence of a curriculum model for online learning in a context of late investment in distance education

ECER 2015 "Education and Transition - Contributions from Educational Research", Corvinus University of Budapest from 7 to 11 September 2015.