Structures of free and complexed forms of Escherichia coli xanthine-guanine phosphoribosyltransferase

Structures of free, substrate-bound and product-bound forms of Escherichia coli xanthine-guanine phosphoribosyltransferase (XGPRT) have been determined by X-ray crystallography. These are compared with the previously determined structure of magnesium and sulphate-bound XPRT. The structure of free XGPRT at 2.25 Angstrom resolution confirms the flexibility of residues in and around a mobile loop identified in other PRTases and shows that the cis-peptide conformation of Arg37 at the active site is maintained in the absence of bound ligands. The structures of XGPRT complexed with the purine base substrates guanine or xanthine in combination with cPRib-PP, an analog of the second substrate PRib-PP, have been solved to 2.0 Angstrom resolution. In these two structures the disordered phosphate-binding loop of uncomplexed XGPRT becomes ordered through interactions with the 5'-phosphate group of cPRib-PP. The cyclopentane ring of cPRib-PP has the C3 exo pucker conformation, stabilised by the cPRib-PP-bound Mg2+. The purine base specificity of XGPRT appears to be due to water-mediated interactions between the 2-exocyclic groups of guanine or xanthine and side-chains of Glu136 and Asp140, as well as the main-chain oxygen atom of Ile135. Asp92, together with Lys115, could help stabilise the N7-protonated tautomer of the incoming base and could act as a general base to remove the proton from N7 .when the nucleotide product is formed. The 2.6 Angstrom resolution structure of XGPRT complexed with product GMP is similar to the substrate-bound complexes. However, the ribose ring of GMP is rotated by similar to 24 degrees compared with the equivalent ring in cPRib-PP. This rotation results in the loss of all interactions between the ribosyl group and the enzyme in the product complex. (C) 1998 Academic Press.

Context-free and context-sensitive dynamics in recurrent neural networks

Continuous-valued recurrent neural networks can learn mechanisms for processing context-free languages. The dynamics of such networks is usually based on damped oscillation around fixed points in state space and requires that the dynamical components are arranged in certain ways. It is shown that qualitatively similar dynamics with similar constraints hold for a(n)b(n)c(n), a context-sensitive language. The additional difficulty with a(n)b(n)c(n), compared with the context-free language a(n)b(n), consists of 'counting up' and 'counting down' letters simultaneously. The network solution is to oscillate in two principal dimensions, one for counting up and one for counting down. This study focuses on the dynamics employed by the sequential cascaded network, in contrast to the simple recurrent network, and the use of backpropagation through time. Found solutions generalize well beyond training data, however, learning is not reliable. The contribution of this study lies in demonstrating how the dynamics in recurrent neural networks that process context-free languages can also be employed in processing some context-sensitive languages (traditionally thought of as requiring additional computation resources). This continuity of mechanism between language classes contributes to our understanding of neural networks in modelling language learning and processing.

Therapeutic evaluation of free and liposome-loaded furazolidone in experimental visceral leishmaniasis

Drug delivery systems are promising pharmaceutical formulations used to improve the therapeutic index of drugs. In this study, we developed a liposomal formulation of furazolidone that targets Leishmania (Leishmania) chagasi amastigotes in a hamster model. Using laser scanning confocal microscopy, it was demonstrated that the liposomal drug co-localised with L. (L.) chagasi amastigotes within macrophages. Liposomal furazolidone administered intraperitoneally at 0.5 mg/kg for 12 consecutive days reduced spleen (74%) and liver (32%) parasite burden at a 100-fold lower dose than the free drug. Free furazolidone (50 mg/kg) also effectively reduced spleen (82.5%) and liver (85%) parasites; its in vitro activity against promastigotes and intracellular amastigotes demonstrated a high degree of parasite selectivity. Thus, furazolidone, both in the free and liposome-loaded formulation, is an effective inhibitor of L. (L.) chagasi, representing a possible cost-effective drug candidate for the treatment of visceral leishmaniasis. (C) 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Protective effect of different tetrafluorides on erosion of pellicle-free and pellicle-covered enamel and dentine

The aim was to analyze the protective effects of titanium, zirconium and hafnium tetrafluorides on erosion of pellicle-free and pellicle-covered enamel and dentine in vitro. Eight groups of 20 specimens each of bovine enamel and bovine dentine were prepared. Half the specimens in each group were immersed in human saliva for 2 h for pellicle formation. Specimens were then left untreated (controls) or were treated for 120 s with TiF(4), ZrF(4) or HfF(4) solutions (0.4 or 1%) or 1.25% AmF/NaF gel. All specimens were eroded by exposure to hydrochloric acid, pH 2.6, for 25 min. Cumulative calcium release into the acid was monitored in consecutive 30-second intervals for 5 min, then at 2-min intervals up to a total erosion time of 25 min using the Arsenazo III procedure. Data were analyzed by ANOVA. 1% TiF(4) solution offered the best protective effect, especially in dentine (reduction of calcium loss about 50% at 25 min). 1% ZrF 4, 1% HfF 4 and 0.4% TiF(4) also reduced calcium loss, but to a lesser extent. Long-term effects were limited to dentine, while reduction of enamel erosion (about 25%) was restricted to 1-min erosion. The fluoride gel had a protective effect only in dentine. The efficacy of the tetrafluorides was influenced by the presence of the pellicle layer, in that the protection against dentine erosion by TiF(4) and ZrF(4) was greater on pellicle-covered specimens. Tetrafluoride solutions, especially 1% TiF(4), could decrease dental erosion, but were more effective on dentine than on enamel. Copyright (C) 2008 S. Karger AG, Basel.

Historical PCDD Inputs and Their Source Implications from Dated Sediment Cores in Queensland (Australia)

Recent investigations have demonstrated the presence of an unidentified source of polychlorinated dibenzo-p-dioxins (PCDDs) in the coastal zone of Queensland (Australia). The present study provides new information on the possible PCDD sources and their temporal input to this environment. Two estuarine sediment cores were collected in northern Queensland for which radiochemical chronologies were established. Core sections from different depositional ages, up to three centuries, have been analyzed for 2,3,7,8-substituted PCDDs and polychlorinated dibenzofurans (PCDFs). Variations of PCDD concentrations in the sediment cores over several centuries of depositional history were relatively small, and elevated PCDD levels were still present in sediment slices from the early 17th century. PCDD/F isomer patterns and congener profiles in sediments deposited during the last 350 years were almost identical and correlated well to the characteristic profiles observed in surface sediments and soils from the entire Queensland coastline. Profiles were dominated by higher chlorinated PCDDs, in particular octachlorodibenzodioxin (OCDD), whereas PCDF concentrations were below or near the limit of detection. These results indicate the presence of a PCDD source prior to industrialization and production of commercial organochlorine products. Further, the present study demonstrates that PCDD input patterns have been similar along an extensive but localized area over at least several centuries, contributing relatively high concentrations of PCDDs to the coastal system of Queensland.

On learning context-free and context-sensitive languages

The long short-term memory (LSTM) is not the only neural network which learns a context sensitive language. Second-order sequential cascaded networks (SCNs) are able to induce means from a finite fragment of a context-sensitive language for processing strings outside the training set. The dynamical behavior of the SCN is qualitatively distinct from that observed in LSTM networks. Differences in performance and dynamics are discussed.

Construção de websites com ferramentas open-source: duas experiências de implementação em bibliotecas de ensino superior

As Tecnologias da Informação e da Comunicação (TIC) têm influenciado de forma inequívoca o desenvolvimento das bibliotecas à escala global. Nas últimas décadas, as TIC mudaram a dinâmica das bibliotecas permitindo a sua modernização (pelo desenvolvimento da eficiência das tarefas já realizadas), favorecendo a inovação (pela utilização das tecnologias como base para o desenvolvimento de novos serviços/técnicas) e promovendo a sua transformação (ao nível do paradigma funcional, da disponibilização de conteúdos, etc.) – criando, em suma, uma nova relação com os seus públicos

Sistema de correlação de eventos e notificações - SCEN

Mestrado em Engenharia Electrotécnica e de Computadores

Machine Learning Algorithms at Myocardial Perfusion Imaging - a Preliminary Study

Introduction: A major focus of data mining process - especially machine learning researches - is to automatically learn to recognize complex patterns and help to take the adequate decisions strictly based on the acquired data. Since imaging techniques like MPI – Myocardial Perfusion Imaging on Nuclear Cardiology, can implicate a huge part of the daily workflow and generate gigabytes of data, there could be advantages on Computerized Analysis of data over Human Analysis: shorter time, homogeneity and consistency, automatic recording of analysis results, relatively inexpensive, etc.Objectives: The aim of this study relates with the evaluation of the efficacy of this methodology on the evaluation of MPI Stress studies and the process of decision taking concerning the continuation – or not – of the evaluation of each patient. It has been pursued has an objective to automatically classify a patient test in one of three groups: “Positive”, “Negative” and “Indeterminate”. “Positive” would directly follow to the Rest test part of the exam, the “Negative” would be directly exempted from continuation and only the “Indeterminate” group would deserve the clinician analysis, so allowing economy of clinician’s effort, increasing workflow fluidity at the technologist’s level and probably sparing time to patients. Methods: WEKA v3.6.2 open source software was used to make a comparative analysis of three WEKA algorithms (“OneR”, “J48” and “Naïve Bayes”) - on a retrospective study using the comparison with correspondent clinical results as reference, signed by nuclear cardiologist experts - on “SPECT Heart Dataset”, available on University of California – Irvine, at the Machine Learning Repository. For evaluation purposes, criteria as “Precision”, “Incorrectly Classified Instances” and “Receiver Operating Characteristics (ROC) Areas” were considered. Results: The interpretation of the data suggests that the Naïve Bayes algorithm has the best performance among the three previously selected algorithms. Conclusions: It is believed - and apparently supported by the findings - that machine learning algorithms could significantly assist, at an intermediary level, on the analysis of scintigraphic data obtained on MPI, namely after Stress acquisition, so eventually increasing efficiency of the entire system and potentially easing both roles of Technologists and Nuclear Cardiologists. In the actual continuation of this study, it is planned to use more patient information and significantly increase the population under study, in order to allow improving system accuracy.

Plataforma de gestão de incidentes

Mestrado em Engenharia Electrotécnica e de Computadores. Área de Especialização de Telecomunicações.

Acesso remoto via infra-estrutura de teste IEEE1149.1 a dispositivos lógicos programáveis

Actualmente verifica-se que a complexidade dos sistemas informáticos tem vindo a aumentar, fazendo parte das nossas ferramentas diárias de trabalho a utilização de sistemas informáticos e a utilização de serviços online. Neste âmbito, a internet obtém um papel de destaque junto das universidades, ao permitir que alunos e professores possam interagir mais facilmente. A internet e a educação baseada na Web vêm oferecer acesso remoto a qualquer informação independentemente da localização ou da hora. Como consequência, qualquer pessoa com uma ligação à internet, ao poder adquirir informações sobre um determinado tema junto dos maiores peritos, obtém vantagens significativas. Os laboratórios remotos são uma solução muito valorizada no que toca a interligar tecnologia e recursos humanos em ambientes que podem estar afastados no tempo ou no espaço. A criação deste tipo de laboratórios e a sua utilidade real só é possível porque as tecnologias de comunicação emergentes têm contribuído de uma forma muito relevante para melhorar a sua disponibilização à distância. A necessidade de criação de laboratórios remotos torna-se imprescindível para pesquisas relacionadas com engenharia que envolvam a utilização de recursos escassos ou de grandes dimensões. Apoiado neste conceito, desenvolveu-se um laboratório remoto para os alunos de engenharia que precisam de testar circuitos digitais numa carta de desenvolvimento de hardware configurável, permitindo a utilização deste recurso de uma forma mais eficiente. O trabalho consistiu na criação de um laboratório remoto de baixo custo, com base em linguagens de programação open source, sendo utilizado como unidade de processamento um router da ASUS com o firmware OpenWrt. Este firmware é uma distribuição Linux para sistemas embutidos. Este laboratório remoto permite o teste dos circuitos digitais numa carta de desenvolvimento de hardware configurável em tempo real, utilizando a interface JTAG. O laboratório desenvolvido tem a particularidade de ter como unidade de processamento um router. A utilização do router como servidor é uma solução muito pouco usual na implementação de laboratórios remotos. Este router, quando comparado com um computador normal, apresenta uma capacidade de processamento e memória muito inferior, embora os testes efectuados provassem que apresenta um desempenho muito adequado às expectativas.

Realization of fractional-order controllers: analysis, synthesis and application to the velocity control of a servo system

The synthesis and application of fractional-order controllers is now an active research field. This article investigates the use of fractional-order PID controllers in the velocity control of an experimental modular servo system. The systern consists of a digital servomechanism and open-architecture software environment for real-time control experiments using MATLAB/Simulink. Different tuning methods will be employed, such as heuristics based on the well-known Ziegler Nichols rules, techniques based on Bode’s ideal transfer function and optimization tuning methods. Experimental responses obtained from the application of the several fractional-order controllers are presented and analyzed. The effectiveness and superior performance of the proposed algorithms are also compared with classical integer-order PID controllers.

Bridging the gap between closed and open data. System proposal for the Portuguese Legislation

Esta dissertação apresenta uma proposta de sistema capaz de preencher a lacuna entre documentos legislativos em formato PDF e documentos legislativos em formato aberto. O objetivo principal é mapear o conhecimento presente nesses documentos de maneira a representar essa coleção como informação interligada. O sistema é composto por vários componentes responsáveis pela execução de três fases propostas: extração de dados, organização de conhecimento, acesso à informação. A primeira fase propõe uma abordagem à extração de estrutura, texto e entidades de documentos PDF de maneira a obter a informação desejada, de acordo com a parametrização do utilizador. Esta abordagem usa dois métodos de extração diferentes, de acordo com as duas fases de processamento de documentos – análise de documento e compreensão de documento. O critério utilizado para agrupar objetos de texto é a fonte usada nos objetos de texto de acordo com a sua definição no código de fonte (Content Stream) do PDF. A abordagem está dividida em três partes: análise de documento, compreensão de documento e conjunção. A primeira parte da abordagem trata da extração de segmentos de texto, adotando uma abordagem geométrica. O resultado é uma lista de linhas do texto do documento; a segunda parte trata de agrupar os objetos de texto de acordo com o critério estipulado, produzindo um documento XML com o resultado dessa extração; a terceira e última fase junta os resultados das duas fases anteriores e aplica regras estruturais e lógicas no sentido de obter o documento XML final. A segunda fase propõe uma ontologia no domínio legal capaz de organizar a informação extraída pelo processo de extração da primeira fase. Também é responsável pelo processo de indexação do texto dos documentos. A ontologia proposta apresenta três características: pequena, interoperável e partilhável. A primeira característica está relacionada com o facto da ontologia não estar focada na descrição pormenorizada dos conceitos presentes, propondo uma descrição mais abstrata das entidades presentes; a segunda característica é incorporada devido à necessidade de interoperabilidade com outras ontologias do domínio legal, mas também com as ontologias padrão que são utilizadas geralmente; a terceira característica é definida no sentido de permitir que o conhecimento traduzido, segundo a ontologia proposta, seja independente de vários fatores, tais como o país, a língua ou a jurisdição. A terceira fase corresponde a uma resposta à questão do acesso e reutilização do conhecimento por utilizadores externos ao sistema através do desenvolvimento dum Web Service. Este componente permite o acesso à informação através da disponibilização de um grupo de recursos disponíveis a atores externos que desejem aceder à informação. O Web Service desenvolvido utiliza a arquitetura REST. Uma aplicação móvel Android também foi desenvolvida de maneira a providenciar visualizações dos pedidos de informação. O resultado final é então o desenvolvimento de um sistema capaz de transformar coleções de documentos em formato PDF para coleções em formato aberto de maneira a permitir o acesso e reutilização por outros utilizadores. Este sistema responde diretamente às questões da comunidade de dados abertos e de Governos, que possuem muitas coleções deste tipo, para as quais não existe a capacidade de raciocinar sobre a informação contida, e transformá-la em dados que os cidadãos e os profissionais possam visualizar e utilizar.

Utilização de plataformas de fonte aberta no controlo de condição

Trabalho Final de Mestrado para obtenção do grau de Mestre em Engenharia Mecânica

A survey of wireless technologies coexistence in WBAN: analysis and open research issues

Wireless Body Area Network (WBAN) is the most convenient, cost-effective, accurate, and non-invasive technology for e-health monitoring. The performance of WBAN may be disturbed when coexisting with other wireless networks. Accordingly, this paper provides a comprehensive study and in-depth analysis of coexistence issues and interference mitigation solutions in WBAN technologies. A thorough survey of state-of-the art research in WBAN coexistence issues is conducted. The survey classified, discussed, and compared the studies according to the parameters used to analyze the coexistence problem. Solutions suggested by the studies are then classified according to the followed techniques and concomitant shortcomings are identified. Moreover, the coexistence problem in WBAN technologies is mathematically analyzed and formulas are derived for the probability of successful channel access for different wireless technologies with the coexistence of an interfering network. Finally, extensive simulations are conducted using OPNET with several real-life scenarios to evaluate the impact of coexistence interference on different WBAN technologies. In particular, three main WBAN wireless technologies are considered: IEEE 802.15.6, IEEE 802.15.4, and low-power WiFi. The mathematical analysis and the simulation results are discussed and the impact of interfering network on the different wireless technologies is compared and analyzed. The results show that an interfering network (e.g., standard WiFi) has an impact on the performance of WBAN and may disrupt its operation. In addition, using low-power WiFi for WBANs is investigated and proved to be a feasible option compared to other wireless technologies.