Arrow Plot: a new graphical tool for selecting up and down regulated genes and genes differentially expressed on samples subgroups

Background: A common task in analyzing microarray data is to determine which genes are differentially expressed across two (or more) kind of tissue samples or samples submitted under experimental conditions. Several statistical methods have been proposed to accomplish this goal, generally based on measures of distance between classes. It is well known that biological samples are heterogeneous because of factors such as molecular subtypes or genetic background that are often unknown to the experimenter. For instance, in experiments which involve molecular classification of tumors it is important to identify significant subtypes of cancer. Bimodal or multimodal distributions often reflect the presence of subsamples mixtures. Consequently, there can be genes differentially expressed on sample subgroups which are missed if usual statistical approaches are used. In this paper we propose a new graphical tool which not only identifies genes with up and down regulations, but also genes with differential expression in different subclasses, that are usually missed if current statistical methods are used. This tool is based on two measures of distance between samples, namely the overlapping coefficient (OVL) between two densities and the area under the receiver operating characteristic (ROC) curve. The methodology proposed here was implemented in the open-source R software. Results: This method was applied to a publicly available dataset, as well as to a simulated dataset. We compared our results with the ones obtained using some of the standard methods for detecting differentially expressed genes, namely Welch t-statistic, fold change (FC), rank products (RP), average difference (AD), weighted average difference (WAD), moderated t-statistic (modT), intensity-based moderated t-statistic (ibmT), significance analysis of microarrays (samT) and area under the ROC curve (AUC). On both datasets all differentially expressed genes with bimodal or multimodal distributions were not selected by all standard selection procedures. We also compared our results with (i) area between ROC curve and rising area (ABCR) and (ii) the test for not proper ROC curves (TNRC). We found our methodology more comprehensive, because it detects both bimodal and multimodal distributions and different variances can be considered on both samples. Another advantage of our method is that we can analyze graphically the behavior of different kinds of differentially expressed genes. Conclusion: Our results indicate that the arrow plot represents a new flexible and useful tool for the analysis of gene expression profiles from microarrays.

Tsunamigenic earthquakes in the Gulf of Cadiz: fault model and recurrence

The Gulf of Cadiz, as part of the Azores-Gibraltar plate boundary, is recognized as a potential source of big earthquakes and tsunamis that may affect the bordering countries, as occurred on 1 November 1755. Preparing for the future, Portugal is establishing a national tsunami warning system in which the threat caused by any large-magnitude earthquake in the area is estimated from a comprehensive database of scenarios. In this paper we summarize the knowledge about the active tectonics in the Gulf of Cadiz and integrate the available seismological information in order to propose the generation model of destructive tsunamis to be applied in tsunami warnings. The fault model derived is then used to estimate the recurrence of large earthquakes using the fault slip rates obtained by Cunha et al. (2012) from thin-sheet neotectonic modelling. Finally we evaluate the consistency of seismicity rates derived from historical and instrumental catalogues with the convergence rates between Eurasia and Nubia given by plate kinematic models.

Arrow plot and CA maps on microarray preprocessing methods

Microarray allow to monitoring simultaneously thousands of genes, where the abundance of the transcripts under a same experimental condition at the same time can be quantified. Among various available array technologies, double channel cDNA microarray experiments have arisen in numerous technical protocols associated to genomic studies, which is the focus of this work. Microarray experiments involve many steps and each one can affect the quality of raw data. Background correction and normalization are preprocessing techniques to clean and correct the raw data when undesirable fluctuations arise from technical factors. Several recent studies showed that there is no preprocessing strategy that outperforms others in all circumstances and thus it seems difficult to provide general recommendations. In this work, it is proposed to use exploratory techniques to visualize the effects of preprocessing methods on statistical analysis of cancer two-channel microarray data sets, where the cancer types (classes) are known. For selecting differential expressed genes the arrow plot was used and the graph of profiles resultant from the correspondence analysis for visualizing the results. It was used 6 background methods and 6 normalization methods, performing 36 pre-processing methods and it was analyzed in a published cDNA microarray database (Liver) available at http://genome-www5.stanford.edu/ which microarrays were already classified by cancer type. All statistical analyses were performed using the R statistical software.

An electro-rheological study of the nematic liquid crystal 4-n-heptyl-4'-cyanobiphenyl

An experimental and theoretical study of the electro-rheological effects observed in the nematic phase of 4-n-heptyl-4'-cyanobiphenyl has been conducted. This liquid crystal appears to be a model system, in which the observed rheological behaviour can be interpreted by the Leslie-Ericksen continuum theory for low molecular weight liquid crystals. Flow curves are illustrated at different temperatures and under the influence of an external electric field ranging from 0 to 3 kV mm-1, applied perpendicular to the direction of flow. Also presented is the apparent viscosity as a function of temperature, over similar values of electric field, obtained at different shear rates. A master flow curve has been constructed for each temperature by dividing the shear rate by the square of the electric field and multiplying by the square of a reference value of electric field. In a log-log plot, two Newtonian plateaux are found to appear at low and high shear rates, connected by a shear-thinning region. We have applied the Leslie-Ericksen continuum theory, in which the director alignment angle is a function of the electric field and the flow field boundary conditions are neglected, to determine viscoelastic parameters and the dielectric anisotropy.

Extraction of hemoglobin with calixarenes and biocatalysis in organic media of the complex with pseudoactivity of peroxidase

The present work involves the use of p-tert-butylcalix[4,6,8]arene carboxylic acid derivatives ((t)Butyl[4,6,8]CH2COOH) for selective extraction of hemoglobin. All three calixarenes extracted hemoglobin into the organic phase, exhibiting extraction parameters higher than 0.90. Evaluation of the solvent accessible positively charged amino acid side chains of hemoglobin (PDB entry 1XZ2) revealed that there are 8 arginine, 44 lysine and 30 histidine residues on the protein surface which may be involved in the interactions with the calixarene molecules. The hemoglobin-(t)Butyl[6]CH2COOH complex had pseudoperoxidase activity which catalysed the oxidation of syringaldazine in the presence of hydrogen peroxide in organic medium containing chloroform. The effect of pH, protein and substrate concentrations on biocatalysis was investigated using the hemoglobin-(t)Butyl[6]CH2COOH complex. This complex exhibited the highest specific activity of 9.92 x 10(-2) U mg protein(-1) at an initial pH of 7.5 in organic medium. Apparent kinetic parameters (V'(max), K'(m), k'(cat) and k'(cat)/K'(m)) for the pseudoperoxidase activity were determined in organic media for different pH values from a Michaelis-Menten plot. Furthermore, the stability of the protein-calixarene complex was investigated for different initial pH values and half-life (t(1/2)) values were obtained in the range of 1.96 and 2.64 days. Hemoglobin-calixarene complex present in organic medium was recovered in fresh aqueous solutions at alkaline pH, with a recovery of pseudoperoxidase activity of over 100%. These results strongly suggest that the use of calixarene derivatives is an alternative technique for protein extraction and solubilisation in organic media for biocatalysis.

Mulheres em morte-cor: os objetos que fazem e desfazem corpos e cancros metastáticos

Este texto sintetiza o último capítulo da investigação de doutoramento – Objetos feitos de cancro: a cultura material como pedaço de doença em histórias de mulheres contadas pela arte. Através de uma reflexão em torno dos objetos e materialidades que ganham forma e relevo em projetos artísticos referentes à experiência feminina do cancro, esta tese propõe conceitos alternativos de cultura material e de doença oncológica. Rejeita-se uma separação ou diferenciação entre dimensões materiais e intangíveis na doença, entendendo-se os objetos de cultura material como pedaços de cancro, ou seja, enquanto partes constitutivas das ideias, sensações, emoções e gestos que fazem a experiência do corpo doente. Objetos hospitalares, domésticos e pessoais, de uso coletivo ou individual, onde se incluem materialidades descartáveis, vestuário, mobiliário, equipamento e máquinas, compõem uma lista de realidades que se encastram nas experiências do corpo em diagnóstico, internamento, tratamento, reconstrução, remissão, recorrência, metastização e morte. Dando nome a esta continuidade indivisa, propus os conceitos “objeto nosoencastrável” e “doença modular”, pretendendo, na forma como defino as coisas, os mesmos encaixes que existem na realidade vivida. Para compreender a ação, os usos e os sentidos dos objetos que fazem e são pedaços de cancro(s), o campo de trabalho desta investigação abrangeu as imagens e os textos explicativos de cento e cinquenta projetos artísticos produzidos por ou com mulheres que viveram a experiência desta doença. Expostos na Internet, os exercícios criativos, amadores ou profissionais, de fotografia comercial e artística, pintura, desenho, colagem, modelagem, escultura, costura e tricô serviram de terreno narrativo e visual, permitindo-me encontrar a versão émica dos encaixes entre cultura material e doença. Tocar a continuidade entre objetos e cancros, juntando os saberes do corpo, da arte e da antropologia, assentou numa abordagem teórica e metodológica onde ensaiei o potencial heurístico daquilo a que chamo a “terceira metade das coisas e do conhecimento”.

Colapsos de pontes: lições aprendidas

Trabalho Final de Mestrado para obtenção do grau de Mestre em Engenharia Civil na Área de Especialização em Estruturas

Convective patterns under the Indo-Atlantic << box >>

Using fluid mechanics, we reinterpret the mantle images obtained from global and regional tomography together with geochemical, geological and paleomagnetic observations, and attempt to unravel the pattern of convection in the Indo-Atlantic "box" and its temporal evolution over the last 260 Myr. The << box >> presently contains a) a broad slow seismic anomaly at the CMB which has a shape similar to Pangea 250 Myr ago, and which divides into several branches higher in the lower mantle, b) a "superswell, centered on the western edge of South Africa, c) at least 6 "primary hotspots" with long tracks related to traps, and d) numerous smaller hotspots. In the last 260 Myr, this mantle box has undergone 10 trap events, 7 of them related to continental breakup. Several of these past events are spatially correlated with present-day seismic anomalies and/or upwellings. Laboratory experiments show that superswells, long-lived hotspot tracks and traps may represent three evolutionary stages of the same phenomenon, i.e. episodic destabilization of a hot, chemically heterogeneous thermal boundary layer, close to the bottom of the mantle. When scaled to the Earth's mantle, its recurrence time is on the order of 100-200 Myr. At any given time, the Indo-Atlantic box should contain 3 to 9 of these instabilities at different stages of their development, in agreement with observations. The return flow of the downwelling slabs, although confined to two main << boxes >> (Indo-Atlantic and Pacific) by subduction zone geometry, may therefore not be passive, but rather take the form of active thermochemical instabilities. (c) 2005 Elsevier B.V. All rights reserved.

PET/CT com 18-fluor-fluorodeoxiglucose no seguimento do melanoma maligno cutâneo

Introdução – O melanoma maligno cutâneo (MMC) é considerado uma das mais letais neoplasias e no seu seguimento recorre-se, para além dos exames clínicos e da análise de marcadores tumorais, a diversos métodos imagiológicos, como é o exame Tomografia por Emissão de Positrões/Tomografia Computorizada (PET/CT, do acrónimo inglês Positron Emission Tomography/Computed Tomography) com 18fluor-fluorodeoxiglucose (18F-FDG). O presente estudo tem como objetivo avaliar a utilidade da PET/CT relativamente à análise da extensão e à suspeita de recidiva do MMC, comparando os achados imagiológicos com os descritos em estudos CT. Metodologia – Estudo retrospetivo de 62 estudos PET/CT realizados em 50 pacientes diagnosticados com MMC. Excluiu-se um estudo cujo resultado era duvidoso (nódulo pulmonar). As informações relativas aos resultados dos estudos anatomopatológicos e dos exames imagiológicos foram obtidas através da história clínica e dos relatórios médicos dos estudos CT e PET/CT. Foi criada uma base de dados com os dados recolhidos através do software Excel e foi efetuada uma análise estatística descritiva. Resultados – Dos estudos PET/CT analisados, 31 foram considerados verdadeiros positivos (VP), 28 verdadeiros negativos (VN), um falso positivo (FP) e um falso negativo (FN). A sensibilidade, especificidade, o valor preditivo positivo (VPP), o valor preditivo negativo (VPN) e a exatidão da PET/CT para o estadiamento e avaliação de suspeita de recidiva no MMC são, respetivamente, 96,9%, 96,6%, 96,9%, 96,6% e 96,7%. Dos resultados da CT considerados na análise estatística, 14 corresponderam a VP, 12 a VN, três a FP e cinco a FN. A sensibilidade, especificidade, o VPP e o VPN e a exatidão da CT para o estadiamento e avaliação de suspeita de recidiva no MMC são, respetivamente, 73,7%, 80,0%, 82,4%, 70,6% e 76,5%. Comparativamente aos resultados CT, a PET/CT permitiu uma mudança na atitude terapêutica em 23% dos estudos. Conclusão – A PET/CT é um exame útil na avaliação do MMC, caracterizando-se por uma maior acuidade diagnóstica no estadiamento e na avaliação de suspeita de recidiva do MMC comparativamente à CT isoladamente.

Mechanical behavior and localized failure modes in a porous basalt from the Azores

Basaltic rocks are the main component of the oceanic upper crust, thus of potential interest for water and geothermal resources, storage of CO2 and volcanic edifice stability. In this work, we investigated experimentally the mechanical behavior and the failure modes of a porous basalt, with an initial connected porosity of 18%. Results were acquired under triaxial compression experiments at confining pressure in the range of 25-200 MPa on water saturated samples. In addition, a purely hydrostatic test was also performed to reach the pore collapse critical pressure P*. During hydrostatic loading, our results show that the permeability is highly pressure dependent, which suggests that the permeability is mainly controlled by pre-existing cracks. When the sample is deformed at pressure higher than the pore collapse pressure P*, some very small dilatancy develops due to microcracking, and an increase in permeability is observed. Under triaxial loading, two modes of deformation can be highlighted. At low confining pressure (Pc < 50 MPa), the samples are brittle and shear localization occurs. For confining pressure > 50 MPa, the stress-strain curves are characterized by strain hardening and volumetric compaction. Stress drops are also observed, suggesting that compaction may be localized. The presence of compaction bands is confirmed by our microstructure analysis. In addition, the mechanical data allows us to plot the full yield surface for this porous basalt, which follows an elliptic cap as previously observed in high porosity sandstones and limestones.

Projecto de execução do centro comercial Mercado da Praia: Cidade da Praia: Cabo Verde

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

Grupos heterogéneos e a diferenciação pedagógica

Relatório de Prática Profissional Supervisionada, Mestrado em Educação Pré-Escolar

Probabilistic tsunami hazard in the Northeast Atlantic from near- and far-field tectonic sources

In this article, we present the first study on probabilistic tsunami hazard assessment for the Northeast (NE) Atlantic region related to earthquake sources. The methodology combines the probabilistic seismic hazard assessment, tsunami numerical modeling, and statistical approaches. We consider three main tsunamigenic areas, namely the Southwest Iberian Margin, the Gloria, and the Caribbean. For each tsunamigenic zone, we derive the annual recurrence rate for each magnitude range, from Mw 8.0 up to Mw 9.0, with a regular interval, using the Bayesian method, which incorporates seismic information from historical and instrumental catalogs. A numerical code, solving the shallow water equations, is employed to simulate the tsunami propagation and compute near shore wave heights. The probability of exceeding a specific tsunami hazard level during a given time period is calculated using the Poisson distribution. The results are presented in terms of the probability of exceedance of a given tsunami amplitude for 100- and 500-year return periods. The hazard level varies along the NE Atlantic coast, being maximum along the northern segment of the Morocco Atlantic coast, the southern Portuguese coast, and the Spanish coast of the Gulf of Cadiz. We find that the probability that a maximum wave height exceeds 1 m somewhere in the NE Atlantic region reaches 60 and 100 % for 100- and 500-year return periods, respectively. These probability values decrease, respectively, to about 15 and 50 % when considering the exceedance threshold of 5 m for the same return periods of 100 and 500 years.

Multi-strand narrative structures: a filmic game of multiple players

Session 7: Playing with Roles, images and improvising New States of Awareness, 3rd Global Conference, 1st November – 3rd November, 2014, Prague, Czech Republic.

Juggling time concepts: complex metanarrative in Alejandro González Iñárritu’s 21 Grams

ABSTRACT - Starting with the explanation of metanarrative as a sort of self-reflexive storytelling (as defended by Kenneth Weaver Hope in his unpublished PhD. thesis), I propose to talk about enunciative practices that stress the telling more than the told. In line with some metaficcional practices applied to cinema, such as the ‘mindfuck’ film (Jonathan Eig, 2003), the ‘psychological puzzle film’ (Elliot Panek, 2003) and the ‘mind-game film’ (Thomas Elsaesser, 2009), I will address the manipulations that a narrative film endures in order to produce a more fruitful and complex experience for the viewer. I will particularly concentrate on the misrepresentation of time as a way to produce a labyrinthine work of fiction where the linear description of events is replaced by a game of time disclosure. The viewer is thus called upon to reconstruct the order of the various situations portrayed in a process that I call ‘temporal mapping’. However, as the viewer attempts to do this, the film, ironically, because of the intricate nature of the plot and the uncertain status of the characters, resists the attempt. There is a sort of teasing taking place between the film and its spectator: an invitation of decoding that is half-denied until the end, where the puzzle is finally solved. I will use three of Alejandro Iñárritu’s films to better convey my point: Amores perros (2000), 21 Grams (2003) and Babel (2006). I will consider Iñárritu’s methods to produce a non-linear storytelling as a way to stress the importance of time and its validity as one of the elements that make up for a metanarrative experience in films. I will focus especially on 21 Grams, which I consider to be a paragon of the labyrinth.