Characterization of the retinoid orphan-related receptor-alpha coactivator binding interface: A structural basis for ligand-independent transcription

The retinoid orphan-related receptor-alpha (RORalpha) is a member of the ROR subfamily of orphan receptors and acts as a constitutive activator of transcription in the absence of exogenous ligands. To understand the basis of this activity, we constructed a homology model of Rill using the closely related TRbeta as a template. Molecular modeling suggested that bulky hydrophobic side chains occupy the RORa ligand cavity leaving a small but distinct cavity that may be involved in receptor stabilization. This model was subject to docking simulation with a receptor-interacting peptide from the steroid receptor coactivator, GR-interacting protein-1, which delineated a coactivator binding surface consisting of the signature motif spanning helices 3-5 and helix 12 [activation function 2 (AF2)]. Probing this surface with scanning alanine mutagenesis showed structural and functional equivalence between homologous residues of RORalpha and TRbeta. This was surprising (given that Rill is a ligand-independent activator, whereas TRbeta has an absolute requirement for ligand) and prompted us to use molecular modeling to identify differences between Rill and TRbeta in the way that the All helix interacts with the rest of the receptor. Modeling highlighted a nonconserved amino acid in helix 11 of RORa (Phe491) and a short-length of 3.10 helix at the N terminus of AF2 which we suggest i) ensures that AF2 is locked permanently in the holoconformation described for other liganded receptors and thus 2) enables ligand-independent recruitment of coactivators. Consistent with this, mutation of RORa Phe491 to either methionine or alanine (methionine is the homologous residue in TRbeta), reduced and ablated transcriptional activation and recruitment of coactivators, respectively. Furthermore, we were able to reconstitute transcriptional activity for both a deletion mutant of Ill lacking All and Phe491 Met, by overexpression of a GAL-AF2 fusion protein, demonstrating ligand-independent recruitment of AF2 and a role for Phe491 in recruiting AF2.

Implicit vector equilibrium problems with applications

Let X and Y be Hausdorff topological vector spaces, K a nonempty, closed, and convex subset of X, C: K--> 2(Y) a point-to-set mapping such that for any x is an element of K, C(x) is a pointed, closed, and convex cone in Y and int C(x) not equal 0. Given a mapping g : K --> K and a vector valued bifunction f : K x K - Y, we consider the implicit vector equilibrium problem (IVEP) of finding x* is an element of K such that f (g(x*), y) is not an element of - int C(x) for all y is an element of K. This problem generalizes the (scalar) implicit equilibrium problem and implicit variational inequality problem. We propose the dual of the implicit vector equilibrium problem (DIVEP) and establish the equivalence between (IVEP) and (DIVEP) under certain assumptions. Also, we give characterizations of the set of solutions for (IVP) in case of nonmonotonicity, weak C-pseudomonotonicity, C-pseudomonotonicity, and strict C-pseudomonotonicity, respectively. Under these assumptions, we conclude that the sets of solutions are nonempty, closed, and convex. Finally, we give some applications of (IVEP) to vector variational inequality problems and vector optimization problems. (C) 2003 Elsevier Science Ltd. All rights reserved.

Selective entrainment of sediment graded by size and density under waves

The influence of near-bed sorting processes on heavy mineral content in suspension is discussed. Sediment concentrations above a rippled bed of mixed quartz and heavy mineral sand were measured under regular nonbreaking waves in the laboratory. Using the traditional gradient diffusion process, settling velocity would be expected to strongly affect sediment distribution. This was not observed during present trials. In fact, the vertical gradients of time-averaged suspension concentrations were found to be similar for the light and heavy minerals, despite their different settling velocities. This behavior implies a convective rather than diffusive distribution mechanism. Between the nonmoving bed and the lowest suspension sampling point, fight and heavy mineral concentration differs by two orders of magnitude. This discrimination against the heavy minerals in the pickup process is due largely to selective entrainment at the ripple face. Bed-form dynamics and the nature of quartz suspension profiles are found to be little affected by the trialed proportion of overall heavy minerals in the bed (3.8-22.1%).

Tradução como ponte plástica : hibridismo e identidade em verbetes da Wikipédia

Este trabalho apresenta os conceitos de tradução de forma ampla, rompendo com a concepção de transformação de uma mensagem em um determinado código linguístico para outro, na qual busca-se apenas uma equivalência literal. Objetiva-se discutir a partir de teóricos em torno das teorias pós-coloniais e desconstrucionistas como Bhabha (2010), Hall (2006), Derrida (2006), Ottoni (2005), Orlandi (2008) e Niranjana (2011), a possibilidade de reposicionar a tradução, entendendo-a como ferramenta capaz de desconstruir paradigmas dominantes e, assim, recontar histórias, constituindo-se pontes plásticas. Assim, buscar-se-á pensar a tradução, na sua plasticidade, promovendo pontes que manifestam os cruzamentos existentes entre línguas, evidenciando o homem como cruzamento de diversos sujeitos. Como objeto empírico de análise, utilizaremos três verbetes presentes no site Wikipédia, nos quais traços da identidade brasileira estão envolvidos e investigar-se-á, a partir da leitura estereoscópica e da Teoria da Relevância proposta por Speber & Wilson (2001), os nuances nos processos tradutórios que podem contribuir para a forma como o Brasil é representado tanto pelas comunidades locais quanto estrangeiras, levando à constituição de estereótipos. A pesquisa aqui proposta se mostra relevante, uma vez que, objetiva estudar um corpus pouco explorado academicamente, mas em voga socialmente, já que o site Wikipédia se encontra entre os dez mais acessados da atualidade, com mais de 300 milhões de acessos únicos, além da importância de ser uma fonte de construção coletiva do pensamento, reinventando o conceito de enciclopédia. A pesquisa também se torna relevante sob a ótica dos estudos da tradução já que discorre sobre a importância do tradutor como ferramenta de formação de identidades sejam nacionais, culturais e sociais, além de propor o conceito híbrido de tradução-resenha, como uma tendência ao mundo multilingual contemporâneo

Uma aplicação de matemática financeira à análise de títulos de renda fixa

No dia a dia, as pessoas sabem que existem várias aplicações financeiras, mas a grande maioria não possui o conhecimento necessário para escolher qual o melhor investimento para o seu dinheiro. E assim, muitas vezes acabam investindo somente na poupança, talvez pela sua simplicidade ou por sua popularidade. Neste trabalho, buscamos mostrar a importância da Matemática Financeira para o entendimento de investimentos. Através de uma abordagem de Progressões Geométrica e Aritmética e, consequentemente, da Matemática Financeira, são apresentadas algumas aplicações financeiras, com seus conceitos, cálculos e atividades que mostram como compará-las. Assim, no trabalho são descritos conceitos e propriedades das Progressões Geométrica e Aritmética, e da Matemática Financeira e, como aplicação desse conteúdo, são apresentados o conceito e o cálculo de diversas taxas (equivalência de taxas, taxas efetiva e nominal, taxa pré e pós-fixada, taxas variáveis, taxa referencial), além de alguns investimentos financeiros (poupança, CDB, LCI). Buscando consolidar esse estudo desenvolvido, apresentamos no final do trabalho uma proposta de atividades a serem realizadas em sala de aula, que contemplam cálculos da rentabilidade dos investimentos, mostrando ao aluno como calcular e comparar esses rendimentos.

COORDINSPECTOR: a tool for extracting coordination data from legacy code

More and more current software systems rely on non trivial coordination logic for combining autonomous services typically running on different platforms and often owned by different organizations. Often, however, coordination data is deeply entangled in the code and, therefore, difficult to isolate and analyse separately. COORDINSPECTOR is a software tool which combines slicing and program analysis techniques to isolate all coordination elements from the source code of an existing application. Such a reverse engineering process provides a clear view of the actually invoked services as well as of the orchestration patterns which bind them together. The tool analyses Common Intermediate Language (CIL) code, the native language of Microsoft .Net Framework. Therefore, the scope of application of COORDINSPECTOR is quite large: potentially any piece of code developed in any of the programming languages which compiles to the .Net Framework. The tool generates graphical representations of the coordination layer together and identifies the underlying business process orchestrations, rendering them as Orc specifications

Agent Inferencing Meets the Semantic Web

We provide all agent; the capability to infer the relations (assertions) entailed by the rules that, describe the formal semantics of art RDFS knowledge-base. The proposed inferencing process formulates each semantic restriction as a rule implemented within a, SPARQL query statement. The process expands the original RDF graph into a fuller graph that. explicitly captures the rule's described semantics. The approach is currently being explored in order to support descriptions that follow the generic Semantic Web Rule Language. An experiment, using the Fire-Brigade domain, a small-scale knowledge-base, is adopted to illustrate the agent modeling method and the inferencing process.

Assessing morbidity in the paediatric community

INTRODUCTION: Morbidity information is easily available from medical records but its scope is limited to the population attended by the health services. Information on the prevalence of diseases requires community surveys, which are not always feasible. These two sources of information represent two alternative assessments of disease occurrence, namely demand morbidity and perceived morbidity. The present study was conceived so as to elicit a potential relationship between them so that the former could be used in the absence of the latter. METHODS: A community of 13,365 families on the outskirts of S. Paulo, Brazil, was studied during the period from 15/Nov/1994 to 15/Jan/1995. Data regarding children less than 5 years old were collected from a household survey and from the 2 basic health units in the area. Prevalence of diseases was ascertained from perceived morbidity and compared to estimates computed from demand morbidity. RESULTS: Data analysis distinguished 2 age groups, infants less than 1 year old and children 1 to less than 5. The most important groups of diseases were respiratory diseases, diarrhoea, skin problems and infectious & parasitical diseases. Basic health units presented a better coverage for infants. Though disease frequencies were not different within or outside these units, a better coverage was found for diarrhoea and infectious & parasitical diseases in the infant group, and for diarrhoea in the older age group. Equivalence between the two types of morbidity was found to be limited to the infant group and concerned only the best covered diseases. The odds of a disease being seen at the health service should be of at least 4:10 to ensure this equivalence. CONCLUSION: It was concluded that, provided that health service coverage is good, demand morbidity can be taken as a reliable estimate of community morbidity.

Reward-risk efficiency in proportional reinsurance with different risk measures

We have studied, in particular under normality of the implied random variables, the connections between different measures of risk such as the standard deviation, the W-ruin probability and the p-V@R. We discuss conditions granting the equivalence of these measures with respect to risk preference relations and the equivalence of dominance and efficiency of risk-reward criteria involving these measures. Then more specifically we applied these concepts to rigorously face the problem of finding the efficient set of de Finetti’s variable quota share proportional reinsurance.

PHYLOViZ: phylogenetic inference and data visualization for sequence based typing methods

Background: With the decrease of DNA sequencing costs, sequence-based typing methods are rapidly becoming the gold standard for epidemiological surveillance. These methods provide reproducible and comparable results needed for a global scale bacterial population analysis, while retaining their usefulness for local epidemiological surveys. Online databases that collect the generated allelic profiles and associated epidemiological data are available but this wealth of data remains underused and are frequently poorly annotated since no user-friendly tool exists to analyze and explore it. Results: PHYLOViZ is platform independent Java software that allows the integrated analysis of sequence-based typing methods, including SNP data generated from whole genome sequence approaches, and associated epidemiological data. goeBURST and its Minimum Spanning Tree expansion are used for visualizing the possible evolutionary relationships between isolates. The results can be displayed as an annotated graph overlaying the query results of any other epidemiological data available. Conclusions: PHYLOViZ is a user-friendly software that allows the combined analysis of multiple data sources for microbial epidemiological and population studies. It is freely available at http://www.phyloviz.net.

On the monoids of transformations that preserve the order and a uniform partition

In this article we consider the monoid O(mxn) of all order-preserving full transformations on a chain with mn elements that preserve a uniformm-partition and its submonoids O(mxn)(+) and O(mxn)(-) of all extensive transformations and of all co-extensive transformations, respectively. We determine their ranks and construct a bilateral semidirect product decomposition of O(mxn) in terms of O(mxn)(-) and O(mxn)(+).

Immunogenicity of WHO-17D and Brazilian 17DD yellow fever vaccines: a randomized trial

OBJECTIVE: To compare the immunogenicity of three yellow fever vaccines from WHO-17D and Brazilian 17DD substrains (different seed-lots). METHODS: An equivalence trial was carried out involving 1,087 adults in Rio de Janeiro. Vaccines produced by Bio-Manguinhos, Fiocruz (Rio de Janeiro, Brazil) were administered following standardized procedures adapted to allow blocked randomized allocation of participants to coded vaccine types (double-blind). Neutralizing yellow fever antibody titters were compared in pre- and post-immunization serum samples. Equivalence was defined as a difference of no more than five percentage points in seroconversion rates, and ratio between Geometric Mean Titters (GMT) higher than 0.67. RESULTS: Seroconversion rates were 98% or higher among subjects previously seronegative, and 90% or more of the total cohort of vaccinees, including those previously seropositive. Differences in seroconversion ranged from -0.05% to -3.02%. The intensity of the immune response was also very similar across vaccines: 14.5 to 18.6 IU/mL. GMT ratios ranged from 0.78 to 0.93. Taking the placebo group into account, the vaccines explained 93% of seroconversion. Viremia was detected in 2.7% of vaccinated subjects from Day 3 to Day 7. CONCLUSIONS: The equivalent immunogenicity of yellow fever vaccines from the 17D and 17DD substrains was demonstrated for the first time in placebo-controlled double-blind randomized trial. The study completed the clinical validation process of a new vaccine seed-lot, provided evidence for use of alternative attenuated virus substrains in vaccine production for a major manufacturer, and for the utilization of the 17DD vaccine in other countries.

Adequação da acústica e controlo do ruído em unidades de ressonância magnética: projeto de investigação

Mestrado em Segurança e Higiene do Trabalho.

Aplicação web para tratamento estatístico de dados de teste

Mestrado em Engenharia Electrotécnica e de Computadores

A similarity measure for music signals

One of the goals in the field of Music Information Retrieval is to obtain a measure of similarity between two musical recordings. Such a measure is at the core of automatic classification, query, and retrieval systems, which have become a necessity due to the ever increasing availability and size of musical databases. This paper proposes a method for calculating a similarity distance between two music signals. The method extracts a set of features from the audio recordings, models the features, and determines the distance between models. While further work is needed, preliminary results show that the proposed method has the potential to be used as a similarity measure for musical signals.