Differential expression of CDC25 phosphatases splice variants in human breast cancer cells

Background: CDC25 phosphatases control cell cycle progression by activating cyclin dependent kinases. The three CDC25 isoforms encoding genes are submitted to alternative splicing events which generate at least two variants for CDC25A and five for both CDC25B and CDC25C. An over-expression of CDC25 was reported in several types of cancer, including breast cancer, and is often associated with a poor prognosis. Nevertheless, most of the previous studies did not address the expression of CDC25 splice variants. Here, we evaluated CDC25 spliced transcripts expression in anti-cancerous drug-sensitive and resistant breast cancer cell lines in order to identify potential breast cancer biomarkers. Methods: CDC25 splice variants mRNA levels were evaluated by semi-quantitative RT-PCR and by an original real-time RT-PCR assay. Results: CDC25 spliced transcripts are differentially expres-sed in the breast cancer cell lines studied. An up-regulation of CDC25A2 variant and an increase of the CDC25C5/C1 ratio are associated to the multidrug-resistance in VCREMS and DOXOR breast cancer cells, compared to their sensitive counterpart cell line MCF-7. Additionally, CDC25B2 tran-script is exclusively over-expressed in VCREMS resistant cells and could therefore be involved in the development of certain type of drug resistance. Conclusions: CDC25 splice variants could represent interesting potential breast cancer prognostic biomarkers.

Differential expression of GSPT1 GGCn alleles in cancer

The human eukaryotic release factor 3a (eRF3a), encoded by the G1 to S phase transition 1 gene (GSPT1; alias eRF3a), is upregulated in various human cancers. GSPT1 contains a GGCn polymorphism in exon 1, encoding a polyglycine expansion in the N-terminal of the protein. The longer allele, GGC12, was previously shown to be associated to cancer. The GGC12 allele was present in 2.2% of colorectal cancer patients but was absent in Crohn disease patients and in the control group. Real-time quantitative RT-PCR analysis showed that the GGC12 allele was present at up to 10-fold higher transcription levels than the GGC10 allele (P < 0.001). No GSPT1 amplifications were detected, and there was no correlation between the length of the alleles and methylation levels of the CpG sites inside the GGC expansion. Using flow cytometry, we compared the levels of apoptosis and proliferation rates between cell lines with different genotypes, but detected no significant differences. Finally, we used a cytokinesis-block micronucleus assay to evaluate the frequency of micronuclei in the same cell lines. Cell lines with the longer alleles had higher frequencies of micronuclei in binucleated cells, which is probably a result of defects in mitotic spindle formation. Altogether, these findings indicate that GSPT1 should be considered a potential proto-oncogene.

Actuador linear para teste de teclas na indústria automóvel

As indústrias de componentes e acessórios automóveis são um elo fundamental no processo produtivo da indústria automóvel. Neste leque industrial encontra-se a Preh Portugal, Lda, como empresa fornecedora de componentes electrónicos, mais concretamente, painéis de controlo de climatização. Os painéis fornecidos pela Preh aos seus clientes encontram-se sujeitos a rigorosos testes de qualidade e funcionalidade. Neste sentido o teste funcional das teclas surge, relacionando o curso da tecla em função de uma força actuante. Esta relação está comprometida com uma curva característica padrão para o tipo de tecla. Para além destes compromissos, também é necessário que a tecla feche e abra o seu contacto eléctrico. Esta tese foca-se no desenvolvimento do teste de teclas, apresentando uma alteração ao sistema actual com a introdução de um sistema embebido, no intuito de flexibilizar o sistema de teste e reduzindo custos. O sistema embebido pretende dar capacidade de processamento ao teste e, desta forma, substituir o actual computador como elemento de processamento. A solução implementada consistiu numa mudança estrutural, através da inclusão do sistema embebido entre o computador e o sistema de deslocamento. Passando o foco central do processo de teste a residir no sistema embebido, este tem de estabelecer comunicações com os restantes elementos intervenientes no teste. Estabelece comunicações série RS-232 com o sistema de deslocamento (leitura do curso e força na tecla), Ethernet com o computador (comandos, parâmetros e resultados) e CAN com o painel de controlo de climatização (fecho/abertura do contacto eléctrico). A concretização deste projecto resultou numa nova estrutura e aplicação, a qual é facilmente integrada na linha de produção com as vantagens de ser menos onerosa e mais flexível, conforme o pretendido.

Robôs quadrúpedes: geração de trajectórias em tempo real usando sistemas dinâmicos não-lineares

A geração de trajectórias de robôs em tempo real é uma tarefa muito complexa, não existindo ainda um algoritmo que a permita resolver de forma eficaz. De facto, há controladores eficientes para trajectórias previamente definidas, todavia, a adaptação a variações imprevisíveis, como sendo terrenos irregulares ou obstáculos, constitui ainda um problema em aberto na geração de trajectórias em tempo real de robôs. Neste trabalho apresentam-se modelos de geradores centrais de padrões de locomoção (CPGs), inspirados na biologia, que geram os ritmos locomotores num robô quadrúpede. Os CPGs são modelados matematicamente por sistemas acoplados de células (ou neurónios), sendo a dinâmica de cada célula dada por um sistema de equações diferenciais ordinárias não lineares. Assume-se que as trajectórias dos robôs são constituídas por esta parte rítmica e por uma parte discreta. A parte discreta pode ser embebida na parte rítmica, (a.1) como um offset ou (a.2) adicionada às expressões rítmicas, ou (b) pode ser calculada independentemente e adicionada exactamente antes do envio dos sinais para as articulações do robô. A parte discreta permite inserir no passo locomotor uma perturbação, que poderá estar associada à locomoção em terrenos irregulares ou à existência de obstáculos na trajectória do robô. Para se proceder á análise do sistema com parte discreta, será variado o parâmetro g. O parâmetro g, presente nas equações da parte discreta, representa o offset do sinal após a inclusão da parte discreta. Revê-se a teoria de bifurcação e simetria que permite a classificação das soluções periódicas produzidas pelos modelos de CPGs com passos locomotores quadrúpedes. Nas simulações numéricas, usam-se as equações de Morris-Lecar e o oscilador de Hopf como modelos da dinâmica interna de cada célula para a parte rítmica. A parte discreta é modelada por um sistema inspirado no modelo VITE. Medem-se a amplitude e a frequência de dois passos locomotores para variação do parâmetro g, no intervalo [-5;5]. Consideram-se duas formas distintas de incluir a parte discreta na parte rítmica: (a) como um (a.1) offset ou (a.2) somada nas expressões que modelam a parte rítmica, e (b) somada ao sinal da parte rítmica antes de ser enviado às articulações do robô. No caso (a.1), considerando o oscilador de Hopf como dinâmica interna das células, verifica-se que a amplitude e frequência se mantêm constantes para -50.2. A extensão do movimento varia de forma directamente proporcional à amplitude. No caso das equações de Morris-Lecar, quando a componente discreta é embebida (a.2), a amplitude e a frequência aumentam e depois diminuem para - 0.170.5 Pode concluir-se que: (1) a melhor forma de inserção da parte discreta que menos perturbação insere no robô é a inserção como offset; (2) a inserção da parte discreta parece ser independente do sistema de equações diferenciais ordinárias que modelam a dinâmica interna de cada célula. Como trabalho futuro, é importante prosseguir o estudo das diferentes formas de inserção da parte discreta na parte rítmica do movimento, para que se possa gerar uma locomoção quadrúpede, robusta, flexível, com objectivos, em terrenos irregulares, modelada por correcções discretas aos padrões rítmicos.

Magnetic and plagioclase linear fabric discrepancy in dykes: a new way to define the flow vector using magnetic foliation

In basaltic dykes the magnetic lineation K1 (maximum magnetic susceptibility axis) is generally taken to indicate the flow direction during solidification of the magma. This assumption was tested in Tertiary basaltic dykes from Greenland displaying independent evidence of subhorizontal flow. The digital processing of microphotographs from thin sections cut in (K1, K2) planes yields the preferred linear orientation of plagioclase, which apparently marks the magma flow lineation. In up to 60% of cases, the angular separation between K1 and the assumed flow direction is greater than 45degrees. This suggests that the uncorroborated use of magnetic lineations in dykes is risky. A simple geometrical method is proposed to infer the flow vector from AMS in dykes based solely on magnetic foliations.

Signal Subspace Identification in Hyperspectral Linear Mixtures

Chpater in Book Proceedings with Peer Review Second Iberian Conference, IbPRIA 2005, Estoril, Portugal, June 7-9, 2005, Proceedings, Part II

Criticality of colloids with distinct interaction patches: The limits of linear chains, hyperbranched polymers, and dimers

We use a simple model of associating fluids which consists of spherical particles having a hard-core repulsion, complemented by three short-ranged attractive sites on the surface (sticky spots). Two of the spots are of type A and one is of type B; the bonding interactions between each pair of spots have strengths epsilon(AA), epsilon(BB), and epsilon(AB). The theory is applied over the whole range of bonding strengths and the results are interpreted in terms of the equilibrium cluster structures of the phases. In addition to our numerical results, we derive asymptotic expansions for the free energy in the limits for which there is no liquid-vapor critical point: linear chains (epsilon(AA)not equal 0, epsilon(AB)=epsilon(BB)=0), hyperbranched polymers (epsilon(AB)not equal 0, epsilon(AA)=epsilon(BB)=0), and dimers (epsilon(BB)not equal 0, epsilon(AA)=epsilon(AB)=0). These expansions also allow us to calculate the structure of the critical fluid by perturbing around the above limits, yielding three different types of condensation: of linear chains (AA clusters connected by a few AB or BB bonds); of hyperbranched polymers (AB clusters connected by AA bonds); or of dimers (BB clusters connected by AA bonds). Interestingly, there is no critical point when epsilon(AA) vanishes despite the fact that AA bonds alone cannot drive condensation.

A class of singular first order differential equations with applications in reaction-diffusion

Agências Financiadoras: FCT e MIUR

Economic, environmental and mixed objective functions in non-linear process optimization using simulated annealing and tabu search

Screening of topologies developed by hierarchical heuristic procedures can be carried out by comparing their optimal performance. In this work we will be exploiting mono-objective process optimization using two algorithms, simulated annealing and tabu search, and four different objective functions: two of the net present value type, one of them including environmental costs and two of the global potential impact type. The hydrodealkylation of toluene to produce benzene was used as case study, considering five topologies with different complexities mainly obtained by including or not liquid recycling and heat integration. The performance of the algorithms together with the objective functions was observed, analyzed and discussed from various perspectives: average deviation of results for each algorithm, capacity for producing high purity product, screening of topologies, objective functions robustness in screening of topologies, trade-offs between economic and environmental type objective functions and variability of optimum solutions.

Quantification of endocrine disruptors and pesticides in water by gas chromatography–tandem mass spectrometry. Method validation using weighted linear regression schemes

Amulti-residue methodology based on a solid phase extraction followed by gas chromatography–tandem mass spectrometry was developed for trace analysis of 32 compounds in water matrices, including estrogens and several pesticides from different chemical families, some of them with endocrine disrupting properties. Matrix standard calibration solutions were prepared by adding known amounts of the analytes to a residue-free sample to compensate matrix-induced chromatographic response enhancement observed for certain pesticides. Validation was done mainly according to the International Conference on Harmonisation recommendations, as well as some European and American validation guidelines with specifications for pesticides analysis and/or GC–MS methodology. As the assumption of homoscedasticity was not met for analytical data, weighted least squares linear regression procedure was applied as a simple and effective way to counteract the greater influence of the greater concentrations on the fitted regression line, improving accuracy at the lower end of the calibration curve. The method was considered validated for 31 compounds after consistent evaluation of the key analytical parameters: specificity, linearity, limit of detection and quantification, range, precision, accuracy, extraction efficiency, stability and robustness.

Mixed integer non linear programming and artificial neural network based approach to ancillary services dispatch in competitive electricity markets

Ancillary services represent a good business opportunity that must be considered by market players. This paper presents a new methodology for ancillary services market dispatch. The method considers the bids submitted to the market and includes a market clearing mechanism based on deterministic optimization. An Artificial Neural Network is used for day-ahead prediction of Regulation Down, regulation-up, Spin Reserve and Non-Spin Reserve requirements. Two test cases based on California Independent System Operator data concerning dispatch of Regulation Down, Regulation Up, Spin Reserve and Non-Spin Reserve services are included in this paper to illustrate the application of the proposed method: (1) dispatch considering simple bids; (2) dispatch considering complex bids.

Observability of nonlinear fractional dynamical systems

We study the observability of linear and nonlinear fractional differential systems of order 0 < α < 1 by using the Mittag-Leffler matrix function and the application of Banach’s contraction mapping theorem. Several examples illustrate the concepts.

Controllability results for impulsive mixed type functional integro-differential evolution equations with nonlocal conditions

In this paper, we establish the controllability for a class of abstract impulsive mixed-type functional integro-differential equations with finite delay in a Banach space. Some sufficient conditions for controllability are obtained by using the Mönch fixed point theorem via measures of noncompactness and semigroup theory. Particularly, we do not assume the compactness of the evolution system. An example is given to illustrate the effectiveness of our results.

Combined mutation differential evolution to solve systems of nonlinear equations

This paper presents a differential evolution heuristic to compute a solution of a system of nonlinear equations through the global optimization of an appropriate merit function. Three different mutation strategies are combined to generate mutant points. Preliminary numerical results show the effectiveness of the presented heuristic.

Constraint reasoning for differential models

The basic motivation of this work was the integration of biophysical models within the interval constraints framework for decision support. Comparing the major features of biophysical models with the expressive power of the existing interval constraints framework, it was clear that the most important inadequacy was related with the representation of differential equations. System dynamics is often modelled through differential equations but there was no way of expressing a differential equation as a constraint and integrate it within the constraints framework. Consequently, the goal of this work is focussed on the integration of ordinary differential equations within the interval constraints framework, which for this purpose is extended with the new formalism of Constraint Satisfaction Differential Problems. Such framework allows the specification of ordinary differential equations, together with related information, by means of constraints, and provides efficient propagation techniques for pruning the domains of their variables. This enabled the integration of all such information in a single constraint whose variables may subsequently be used in other constraints of the model. The specific method used for pruning its variable domains can then be combined with the pruning methods associated with the other constraints in an overall propagation algorithm for reducing the bounds of all model variables. The application of the constraint propagation algorithm for pruning the variable domains, that is, the enforcement of local-consistency, turned out to be insufficient to support decision in practical problems that include differential equations. The domain pruning achieved is not, in general, sufficient to allow safe decisions and the main reason derives from the non-linearity of the differential equations. Consequently, a complementary goal of this work proposes a new strong consistency criterion, Global Hull-consistency, particularly suited to decision support with differential models, by presenting an adequate trade-of between domain pruning and computational effort. Several alternative algorithms are proposed for enforcing Global Hull-consistency and, due to their complexity, an effort was made to provide implementations able to supply any-time pruning results. Since the consistency criterion is dependent on the existence of canonical solutions, it is proposed a local search approach that can be integrated with constraint propagation in continuous domains and, in particular, with the enforcing algorithms for anticipating the finding of canonical solutions. The last goal of this work is the validation of the approach as an important contribution for the integration of biophysical models within decision support. Consequently, a prototype application that integrated all the proposed extensions to the interval constraints framework is developed and used for solving problems in different biophysical domains.