Solution structure of CnErg1 (Ergtoxin), a HERG specific scorpion toxin

The three-dimensional structure of chemically synthesized CnErg1 (Ergtoxin), which specifically blocks HERG (human ether-a-go-go-related gene) K+ channels, was determined by nuclear magnetic resonance spectroscopy. CnErg1 consists of a triple-stranded beta-sheet and an a-helix, as is typical of K+ channel scorpion toxins. The peptide structure differs from the canonical structures in that the first beta-strand is shorter and is nearer to the second beta-strand rather than to the third beta-strand on the C-terminus. There is also a large hydrophobic patch on the surface of the toxin, surrounding a central lysine residue, Lys13. We postulate that this hydrophobic patch is likely to form part of the binding surface of the toxin. (C) 2003 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.

Structural characterization of respiratory syncytial virus fusion inhibitor escape mutants: homology model of the F protein and a syncytium formation assay

Respiratory syncytial virus (RSV) is a ubiquitous human pathogen and the leading cause of lower respiratory tract infections in infants. Infection of cells and subsequent formation of syncytia occur through membrane fusion mediated by the RSV fusion protein (RSV-F). A novel in vitro assay of recombinant RSV-F function has been devised and used to characterize a number of escape mutants for three known inhibitors of RSV-F that have been isolated. Homology modeling of the RSV-F structure has been carried out on the basis of a chimera derived from the crystal structures of the RSV-F core and a fragment from the orthologous fusion protein from Newcastle disease virus (NDV). The structure correlates well with the appearance of RSV-F in electron micrographs, and the residues identified as contributing to specific binding sites for several monoclonal antibodies are arranged in appropriate solvent-accessible clusters. The positions of the characterized resistance mutants in the model structure identify two promising regions for the design of fusion inhibitors. (C) 2003 Elsevier Science (USA). All rights reserved.

Enhanced effector and memory CTL responses generated by incorporation of receptor activator of NF-kappa B(RANK)/RANK ligand costimulatory molecules into dendritic cell immunogens expressing a human tumor-specific antigen

The outcome of dendritic cell (DC) presentation of Ag to T cells via the TCR/MHC synapse is determined by second signaling through CD80/86 and, importantly, by ligation of costimulatory ligands and receptors located at the DC and T cell surfaces. Downstream signaling triggered by costimulatory molecule ligation results in reciprocal DC and T cell activation and survival, which predisposes to enhanced T cell-mediated immune responses. In this study, we used adenoviral vectors to express a model tumor Ag (the E7 oncoprotein of human papillomavirus 16) with or without coexpression of receptor activator of NF-kappaB (RANK)/RANK ligand (RANKL) or CD40/CD40L costimulatory molecules, and used these transgenic DCs to immunize mice for the generation of E7-directed CD8(+) T cell responses. We show that coexpression of RANK/RANKL, but not CD40/CD40L, in E7-expressing DCs augmented E7-specific IFN-gamma-secreting effector and memory T cells and E7-specific CTLs. These responses were also augmented by coexpression of T cell costimulatory molecules (RANKL and CD40L) or DC costimulatory molecules (RANK and CD40) in the E7-expressing DC immunogens. Augmentation of CTL responses correlated with up-regulation of CD80 and CD86 expression in DCs transduced with costimulatory molecules, suggesting a mechanism for enhanced T cell activation/survival. These results have generic implications for improved tumor Ag-expressing DC vaccines, and specific implications for a DC-based vaccine approach for human papillomavirus 16-associated cervical carcinoma.

A protective effect of early pregnancy factor on experimental autoimmune encephalomyelitis induced in Lewis rats by inoculation with myelin basic protein

Experimental antoimmune encephalomyelitis (EAE) is an organ-specific autoimmune disease characterised by inflammation and demyelination of the central nervous system and is the best available animal model of multiple sclerosis (MS). Since previous studies have shown that EAE is less severe or is delayed in onset during pregnancy and that administration of the pregnancy hormone early pregnancy factor (EPF) down-regulates EAE, experiments in the present study were designed to explore further the role of EPF in EAE. By using the rosette inhibition test, the standard bioassay for EPF and, by semi-quantitative RT-PCR techniques, we have now shown that inflammatory cells from the spinal cord of rats with EAE can produce and secrete EPF, with production being greatest during recovery from disease. Administration of EPF to rats with EAE resulted in a significant increase in the expression of IL-4 and IL-10 mRNA and a significant decrease in IFN-gamma mRNA expression in spinal cord inflammatory cells. Encephalitogenic MBP-specific T cell lines were prepared from popliteal lymph nodes of rats with EAE. Proliferation assays using these cells demonstrated the ability of exogenous EPF to down-regulate the responses of T lymphocytes to MBP. (C) 2003 Elsevier B.V. All rights reserved.

Toxicological aspects of treatment to remove cyanobacterial toxins from drinking water determined using the heterozygous P53 transgenic mouse model

The presence of toxic cyanobacteria in drinking water reservoirs renders the need to develop treatment methods for the 'safe' removal of their associated toxins. Chlorine has been shown to successfully remove a range of cyanotoxins including microcystins, cylindrospermopsin and saxitoxins. Each cyanotoxin requires specific treatment parameters, particularly solution pH and free chlorine residual. However, currently there has not been any investigation into the toxicological effect of solutions treated for the removal of these cyanotoxins by chlorine. Using the P53(def) transgenic mouse model mate and female C57BL/6J hybrid mice were used to investigate potential cancer inducing effects from such oral dosing solutions. Both purified cyanotoxins and toxic cell-free extract cyanobacterial solutions were chlorinated and administered over 90 and 170 days (respectively) in drinking water. No increase in cancer was found in any treatment. The parent cyanotoxins, microcystins, cylindrospermopsin and saxitoxins were readily removed by chlorine. There was no significant increase in the disinfection byproducts trihalomethanes or haloacetic acids, levels found were well below guideline values. Histological examination identified no effect of treatment solutions except male mice treated with chlorinated cylindrospermopsin (as a cell free extract). In this instance 40% of males were found to have fatty vacuolation in their livers, cause unknown. It is recommended that further toxicology be undertaken on chlorinated cyanobacterial solutions, particularly for non-genotoxic carcinogenic compounds, for example the Tg. AC transgenic mouse model. (C) 2003 Elsevier Science Ltd. All rights reserved.

A yield architecture framework to explain adaptation of pearl millet to environmental stress

Functional knowledge of the physiological basis of crop adaptation to stress is a prerequisite for exploiting specific adaptation to stress environments in breeding programs. This paper presents an analysis of yield components for pearl millet, to explain the specific adaptation of local landraces to stress environments in Rajasthan, India. Six genotypes, ranging from high-tillering traditional landraces to low-tillering open-pollinated modern cultivars, were grown in 20 experiments, covering a range of nonstress and drought stress patterns. In each experiment, yield components (particle number, grain number, 100 grain mass) were measured separately for main shoots, basal tillers, and nodal tillers. Under optimum conditions, landraces had a significantly lower grain yield than the cultivars, but no significant differences were observed at yield levels around 1 ton ha(-1). This genotype x environment interaction for grain yield was due to a difference in yield strategy, where landraces aimed at minimising the risk of a crop failure under stress conditions, and modem cultivars aimed at maximising yield potential under optimum conditions. A key aspect of the adaptation of landraces was the small size of the main shoot panicle, as it minimised (1) the loss of productive tillers during stem elongation; (2) the delay in anthesis if mid-season drought occurs; and (3) the reduction in panicle productivity of the basal tillers under stress. In addition, a low investment in structural panicle weight, relative to vegetative crop growth rate, promoted the production of nodal tillers, providing a mechanism to compensate for reduced basal tiller productivity if stress occurred around anthesis. A low maximum 100 grain mass also ensured individual grain mass was little affected by environmental conditions. The strategy of the high-tillering landraces carries a yield penalty under optimum conditions, but is expected to minimise the risk of a crop failure, particularly if mid-season drought stress occurs. The yield architecture of low-tillering varieties, by contrast, will be suited to end-of-season drought stress, provided anthesis is early. Application of the above adaptation mechanisms into a breeding program could enable the identification of plant types that match the prevalent stress patterns in the target environments. (C) 2003 E.J. van Oosterom. Published by Elsevier Science B.V. All rights reserved.

Inclusividade e efetividade no Conselho Estadual de Direitos Humanos do Espírito Santo (2009-2013)

Esta dissertação de mestrado trata de analisar os limites e possibilidades do Conselho Estadual de Direitos Humanos do Espírito Santo. Ao investigar as condições de inclusividade e efetividade das demandas da sociedade civil local, observa-se de que modo essas condições colaboram para o aprofundamento da democracia. A relevância do trabalho está na sua capacidade de colaborar na verificação das consequências da participação política dos atores da sociedade civil local na instituição participativa. No sentido de testar as hipóteses levantadas lançou-se mão de uma metodologia qualitativa e quantitativa. Destarte, os resultados alcançados evidenciam que há no interior do CEDH consideráveis condições de inclusividade de variedade de temas e atores. Entretanto, no que tange à efetividade, esta se refere mais expressivamente a uma efetividade participativa, na qual os ganhos se pulverizam no fortalecimento da sociedade civil e no atendimento a questões mais pontuais do que propriamente à implementação de políticas públicas. Ademais, constatou-se que a judicialização da política tem sido a estratégia encontrada para superar tais percalços encontrados no processo participativo de concretização da garantia de direitos humanos.

Por trás dos muros da universidade : representações de estudantes sobre o sistema de reserva de vagas (cotas) e sobre os estudantes cotistas da UFES

Analisa as representações de estudantes da Universidade Federal do Espírito Santo (Ufes) sobre o sistema de reserva de vagas (cotas) e sobre os estudantes cotistas. Desenvolve a análise a partir dos seguintes objetivos específicos: identificar os fatores que contribuem para a formação e a reformulação das representações sociais no que diz respeito ao ser estudante universitário; verificar se existem discrepâncias nas representações de cada grupo em relação aos itens abordados; caracterizar os componentes que constituem o sentimento de pertença ao grupo estudantes universitários e compreender como se desenvolvem as relações intra e inter grupos entre os estudantes cotistas e não cotistas da Ufes. Utiliza como metodologia estudo de caso único, com múltiplas unidades de análise, posto que participaram estudantes de diferentes cursos e centros de ensino. Realiza a coleta de dados por meio de entrevista em profundidade por ser consagrada para este tipo de pesquisa. O número de entrevistados baseou-se no critério de saturação. A sistematização dos dados se deu a partir da análise de conteúdo das entrevistas utilizando a Teoria das Representações Sociais. As categorias de análise foram criadas a partir de dois aspectos, os objetivos da pesquisa e as falas dos estudantes. Observa que o acolhimento dos estudantes cotistas bem como, do sistema de reserva de vagas, se deu inicialmente por meio da comparação entre as condições de concorrência no vestibular entre estudantes oriundos de escolas públicas e particulares; que o sentimento de pertença ao grupo estudantes universitários se concretiza mais em relação aos fazeres próprios da universidade do que em relação a qualquer outra condição vivida pelos estudantes, inclusive o ser ou não cotista. Aponta para novos temas a serem discutidos e modos de esclarecer os estudantes de escolas secundárias públicas sobre seus direitos em relação ao cumprimento da Lei nº 12.711, de 2012 que estabeleceu a reserva de vagas nas Instituições de Ensino Superior públicas no Brasil.

Os ‘intrusos’ e os ‘outros’ quebrando o aquário e mudando os horizontes: as relações de raça e classe na implementação das cotas sociais no processo seletivo para cursos de graduação da UFES

A pesquisa desta tese investiga as mediações das categorias de raça e de classe social no processo de implementação do modelo de cotas sociais da Ufes para ingresso nos cursos de graduação, entre 2006 a 2012, como parte das ações afirmativas dessa universidade. Tal modelo, para incluir a população afro-brasileira no ensino superior do Espírito Santo, respeitou estritamente os critérios de renda e de origem escolar pública, não adotando o critério étnico-racial que contemplaria especificamente os negros e os indígenas. Diante disso, o autor busca sustentar a tese de que, considerando o padrão das relações raciais brasileiras produtor de assimetrias entre grupos com marcas raciais distintas, no caso de negros e brancos, as desigualdades raciais têm na operacionalização do racismo seu mote ofensivo e poderoso, ao mesmo tempo em que a classe social isolada é insuficiente na compreensão e superação do problema racial do Brasil. Portanto, na adoção de políticas de combate às desigualdades raciais no ensino superior, caberia também a utilização de medidas etnicamente referenciadas. Autores como Hall (2008) e Fraser (2006), ao trazerem a dimensão articulada e bifocal das injustiças simbólicas e das injustiças econômicas, permitem entender a complementaridade e as dinâmicas entre ambas, deslocando-se de determinismos classistas que invisibilizam o racismo como instrumento opressor nas relações sociais. Como objetivos específicos, considera: compreender o processo de construção do modelo de cotas da Ufes, para ingresso nos cursos de graduação implementado em 2008, sob a perspectiva do debate da relação entre raça e classe; examinar as políticas de ações afirmativas como respostas às demandas históricas dos afro-brasileiros no contexto da sociedade brasileira; avaliar a posição de professores e alunos de cursos de graduação da Ufes diante do ingresso de alunos cotistas, sobretudo afro-brasileiros e pobres; e investigar a relação das políticas classistas, no caso específico das cotas sociais, na superação das assimetrias raciais. Adota como procedimentos metodológicos a metodologia dialética de pesquisa considerando todas as contradições entre raça e classe no processo de implementação de ações afirmativas na Ufes. Como instrumentos de pesquisa, utiliza entrevistas de professores e alunos cotistas e não cotistas de cursos variados da universidade, assim como documentos referentes à temática. Os resultados apontam para uma “oxigenação” da universidade depois de uma entrada maior de negros e pobres, principalmente nos cursos mais elitizados, pois as cotas operam uma dimensão pedagógica de ampliar a diversidade social na academia, trazendo outras demandas, outras 10 afetividades, outras lógicas de mundo e concepções de sociedade para a única universidade pública do Espírito Santo. Indica que os mecanismos discriminatórios e estigmatizantes interpessoais e institucionais, vividos no contexto das cotas sociais e explícitos na pesquisa, não inviabilizam a importância das ações afirmativas, pois apontam para a universidade repensar e ressignificar seus currículos e ações pedagógicas homogeneizantes no sentido de ampliar a ideia de inclusão e de democratização de seus espaços. Reitera que a raça, em seu viés político e cultural, é operante de forma relacional e independente com a classe social no contexto da produção das assimetrias raciais brasileiras, de maneira que a ação de uma não nega a ação da outra, mesmo na relação entre ambas. Enfatiza a importância do entendimento e da materialidade das ações afirmativas como políticas de reconhecimento que combateriam as desigualdades simbólicas na Ufes. Aponta a relevância das políticas de assistência estudantil, conjugadas às cotas, como políticas de redistribuição econômica, que lidariam com as dificuldades ou ausências materiais dos discentes, principalmente dos cotistas. Conclui que as cotas étnico-raciais nas universidades brasileiras são instrumentos legítimos de luta pela educação, um direito social de oportunidade dos grupos historicamente apartados de princípios constituidores da emancipação, da cidadania, dos direitos humanos, da justiça social, da igualdade e da diferença.

Uprootedness and the protection of migrants in the International Law of Human Rights

The article attempt to demonstrate the evolution of international law in connected to the subject of the forced immigrants'. The author supported by several texts, cases and resolutions of the regional level, through interamerican court and European court, and the global level, through the international court. It's shown the evolution that occurred in international law in millennium turn over, which recognize the immigrants' rights. However, it's stressed the necessity of the development of those laws connected to the theme e the recognition, from the States; the importance of law's that effort to ensure the respect to human rights relative to the immigrants and their families.

Human Rights promotion in Serbia: a difficult task for the European Union

This article explores the role of the European Union in the human rights protection, implementation and promotion in Serbia. It is clear that the EU demands on democratisation in the region of Western Balkans are crucial to achieve the respect for human rights. The human rights standards as part of the conditionality criteria of the EU is a clear message towards the countries aspiring membership. However, Serbia progress in the field has been difficult due to several internal constraints. This paper aims to uncover the democratisation process of Serbia on its path towards the EU, and its progress (or not) regarding human rights protection and implementation.

Economic sanctions and human rights: an analysis of competing enforcement strategies in Latin America

This article addresses the consequences of economic sanctions for the protection of human rights in Latin America. The literature on sanctions and compliance informs three hypotheses, which investigate the relationship between sanctions and the level of rights protection in two groups of countries: those that were targeted by sanctions and those that were not. Using data from the Political Terror Scale (PTS) and from Freedom House, I find empirical evidence that sanctions do improve the level of protection in countries that were not targeted. This finding can be explained by the deterrent effect attributed to sanctions by the compliance literature, broadly interpreted. The presence of economic sanctions in a given year increases the probability of observing better human rights practices by almost 50%. These results hold for the 12 Latin American countries that were not subject to economic sanctions for the period 1976-2004.

Domain-Specific Language for Coordination patterns

The integration and composition of software systems requires a good architectural design phase to speed up communications between (remote) components. However, during implementation phase, the code to coordinate such components often ends up mixed in the main business code. This leads to maintenance problems, raising the need for, on the one hand, separating the coordination code from the business code, and on the other hand, providing mechanisms for analysis and comprehension of the architectural decisions once made. In this context our aim is at developing a domain-specific language, CoordL, to describe typical coordination patterns. From our point of view, coordination patterns are abstractions, in a graph form, over the composition of coordination statements from the system code. These patterns would allow us to identify, by means of pattern-based graph search strategies, the code responsible for the coordination of the several components in a system. The recovering and separation of the architectural decisions for a better comprehension of the software is the main purpose of this pattern language

Do we need a “new” international convention that helps to avoid trafficking in organs? Some “criminal (and civil) law aspects” - Convention on Human Rights and Biomedicine – updated or outdated?

Abstract: § 1 «Do we need a “new” international convention that helps to avoid trafficking in organs? Some criminal (and civil) law aspects”» - «Convention on Human Rights and Biomedicine – updated or outdated?». § 2 Some important connections: on the one hand, between the 1997 Council of Europe Convention on Human Rights and Biomedicine; the 2002 Additional Protocol to the Convention on Human Rights and Biomedicine concerning Transplantation of Organs and Tissues of Human Origin; and, on the other hand, the problem of trafficking in organs, tissues and cells and trafficking in human beings for the purpose of the removal organs. Some connections. § 3 The «international undisputed principle». § 4 Trafficking in organs, tissues and cells; and trafficking in human beings for the purpose of the removal organs. Criminal Law and Civil Law. § 5 Promote organ donation. § 6 The necessity to collect reliable data on both trafficking cases. § 7 The necessity for an internationally agreed definition of trafficking in OTC: Convention on Human Rights and Biomedicine – updated or outdated? § 8 The (inter)national and (il)legal organ («tissue and cell») trade: some cases and some conclusions. § 9 Do we need a new international convention to prevent trafficking in organs, tissues and cells (OTC)? § 10 Of course we need a «new» international convention to prevent trafficking in organs, tissues and cells (OTC). § 11 At the present moment, we do not need a «new» international convention to prevent trafficking in human beings for the purpose of the removal organs. § 12 The Portuguese case. § 13 «Final conclusions.» § Resumo: § 1 «Precisamos de uma "nova" convenção internacional que ajude a evitar o tráfico de órgãos? Alguns aspectos de lei criminal (e civil)» - «Convenção sobre Direitos Humanos e Biomedicina - Actualizada ou desactualizada?». § 2 Algumas conexões importantes: por um lado, entre a Convenção do Conselho da Europa de 1997 sobre Direitos Humanos e Biomedicina; o Protocolo Adicional de 2002 à Convenção sobre os Direitos do Homem e da Biomedicina relativo ao transplante de órgãos e tecidos de origem humana, e, por outro lado, o problema do tráfico de órgãos, tecidos e células e tráfico de seres humanos para fins de remoção dos órgãos. § 3 O «indiscutível princípio internacional». § 4 O Tráfico de órgãos, tecidos e células; e o tráfico de seres humanos para fins de remoção dos órgãos. Direito Penal e Direito Civil. § 5 Promover a doação de órgãos. § 6 A necessidade de colectar dados fidedignos sobre os dois casos de tráfico. § 7 A necessidade de uma definição internacionalmente acordada de tráfico de OTC: Convenção sobre Direitos Humanos e Biomedicina - actualizada ou desactualizada? § 8 A (inter)nacional e (il)legal comercialização de órgãos («de tecidos e de células»): alguns casos e algumas conclusões. § 9 Será que precisamos de uma nova convenção internacional para prevenir o tráfico de órgãos, tecidos e células (OTC)? § 10 É claro que precisamos de uma «nova» convenção internacional para prevenir o tráfico de órgãos, tecidos e células (OTC). § 11 No presente momento, não precisamos de uma «nova» convenção internacional para impedir o tráfico de seres humanos para fins de remoção dos órgãos. § 12 O caso Português. § 13 «As conclusões finais.»

The rights approach to local public management: experiences from Brazil

The Fundação Getulio Vargas, São Paulo, Public Management and Citizenship Program was set up in 1996 with Ford Foundation support to identify and disseminate Brazilian subnational government initiatives in service provision that have a direct effect on citizenship. Already, the program has 2,500 different experiences in its data bank, the results of four annual cycles. The article draws some initial conclusions about the possibilities of a rights-based approach to public management and about the engagement of other agencies and civil society organizations.