Reproducible research using biomodels

Like other types of computational research, modeling and simulation of biological processes (biomodels) is still largely communicated without sufficient detail to allow independent reproduction of results. But reproducibility in this area of research could easily be achieved by making use of existing resources, such as supplying models in standard formats and depositing code, models, and results in public repositories

Reproducibility and FAIR Principles: The Case of a Segment Polarity Network Model

The issue of reproducibility of computational models and the related FAIR principles (findable, accessible, interoperable, and reusable) are examined in a specific test case. I analyze a computational model of the segment polarity network in Drosophila embryos published in 2000. Despite the high number of citations to this publication, 23 years later the model is barely accessible, and consequently not interoperable. Following the text of the original publication allowed successfully encoding the model for the open source software COPASI. Subsequently saving the model in the SBML format allowed it to be reused in other open source software packages. Submission of this SBML encoding of the model to the BioModels database enables its findability and accessibility. This demonstrates how the FAIR principles can be successfully enabled by using open source software, widely adopted standards, and public repositories, facilitating reproducibility and reuse of computational cell biology models that will outlive the specific software used

Characterisation of multiple substrate-specific (d)ITP/(d)XTPase and modelling of deaminated purine nucleotide metabolism

To be viable, organisms possess a number of (deoxy)nucleotide phosphohydrolases, which hydrolyze these nucleotides removing them from the active NTP and dNTP pools. Deamination of purine bases can result in accumulation of such nucleotides as ITP, dITP, XTP and dXTP. E. coli RdgB has been characterised as a deoxyribonucleoside triphosphate pyrophosphohydrolase that can act on these nucleotides. S. cerevisiae homologue encoded by YJR069C was purified and its (d)NTPase activity was assayed using fifteen nucleotide substrates. ITP, dITP, and XTP were identified as major substrates and kinetic parameters measured. Inhibition by ATP, dATP and GTP were established. On the basis of experimental and published data, modelling and simulation of ITP, dITP, XTP and dXTP metabolism was performed. (d)ITP/(d)XTPase is a new example of enzyme with multiple substrate-specificity demonstrating that multispecificity is not a rare phenomenon

what can music tell about the history of a colonial city?

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Correction of spatial distortion in magnetic resonance imaging

Dissertation to Obtain the Degree of Master in Biomedical EngineeringMagnetic Resonance Imaging (MRI) has been a major investigation and research focus among scientific and medical communities. So, new hardware with superior magnetic fields and faster sequences has been developed. However, these improvements result in intensity and spatial distortions, particularly in fast sequences, as Echo Plana Imaging (EPI), used in functional and diffusion-weighed MRI (fMRI and DW-MRI). Therefore, correction of spatial distortion is useful to obtain a higher quality in this kind of images. This project contains two major parts. The first part consists in simulating MRI data required for assessing the performance of Registration methods and optimizing parameters. To assess the methods five evaluation metrics were calculated between the corrected data and an undistorted EPI, namely: Root Mean Square (RMS); Normalized Mutual Information (NMI), Squared Correlation Coefficient(SCC); Euclidean Distance of Centres of Mass (CM) and Dice Coefficient of segmented images. In brief, this part validates the applied Registration correction method. The project’s second part includes correction of real images, obtained at a Clinical Partner. Real images are diffusion weighted MRI data with different b-values (gradient strength coefficient), allowing performance assessment of different methods on images with increasing b-values and decreasing SNR. The methods tested on real data were Registration, Field Map correction and a new proposed pipeline, which consists in performing a Field Map correction after a registration process. To assess the accuracy of these methods on real data, we used the same evaluation metrics, as for simulated data, except RMS and Dice Coefficient. At the end, it was concluded that Registration-based methods are better than Field Map, and that the new proposed pipeline produces some improvements in the registration. Regarding the influence of b-value on the correction, it is important to say that the methods performed using images with higher b’s showed more improvements in regarding metric values, but the behaviour is similar for all b-values

Transition from endemic behavior to eradication of malaria due to combined drug therapies: an agent-model approach

We introduce an agent-based model describing a susceptible-infectious-susceptible (SIS) system of humans and mosquitoes to predict malaria epidemiological scenarios in realistic biological conditions. Emphasis is given to the transition from endemic behavior to eradication of malaria transmission induced by combined drug therapies acting on both the gametocytemia reduction and on the selective mosquito mortality during parasite development in the mosquito. Our mathematical framework enables to uncover the critical values of the parameters characterizing the effect of each drug therapy. Moreover, our results provide quantitative evidence of what is empirically known: interventions combining gametocytemia reduction through the use of gametocidal drugs, with the selective action of ivermectin during parasite development in the mosquito, may actively promote disease eradication in the long run. In the agent model, the main properties of human-mosquito interactions are implemented as parameters and the model is validated by comparing simulations with real data of malaria incidence collected in the endemic malaria region of Chimoio in Mozambique. Finally, we discuss our findings in light of current drug administration strategies for malaria prevention, that may interfere with human-to-mosquito transmission process.Comment: 12 pages, 6 figure

Autonomous Assessment of Videogame Difficulty Using Physiological Signals

Given the well-explored relation between challenge and involvement in a task, (e.g., as described in Csikszentmihalyi’s theory of flow), it could be argued that the presence of challenge in videogames is a core element that shapes player experiences and should, therefore, be matched to the player’s skills and attitude towards the game. However, handling videogame difficulty, is a challenging problem in game design, as too easy a task can lead to boredom and too hard can lead to frustration. Thus, by exploring the relationship between difficulty and emotion, the current work intends to propose an artificial intelligence model that autonomously predicts difficulty according to the set of emotions elicited in the player. To test the validity of this approach, we developed a simple puzzle-based Virtual Reality (VR) videogame, based on the Trail Making Test (TMT), and whose objective was to elicit different emotions according to three levels of difficulty. A study was carried out in which physiological responses as well as player self- reports were collected during gameplay. Statistical analysis of the self-reports showed that different levels of experience with either VR or videogames didn’t have a measurable impact on how players performed during the three levels. Additionally, the self-assessed emotional ratings indicated that playing the game at different difficulty levels gave rise to different emotional states. Next, classification using a Support Vector Machine (SVM) was performed to verify if it was possible to detect difficulty considering the physiological responses associated with the elicited emotions. Results report an overall F1-score of 68% in detecting the three levels of difficulty, which verifies the effectiveness of the adopted methodology and encourages further research with a larger dataset.Dada a relação bem explorada entre desafio e envolvimento numa tarefa (p. ex., con- forme descrito na teoria do fluxo de Csikszentmihalyi), pode-se argumentar que a pre- sença de desafio em videojogos é um elemento central que molda a experiência do jogador e deve, portanto, ser compatível com as habilidades e a atitude que jogador exibe perante o jogo. No entanto, saber como lidar com a dificuldade de um videojogo é um problema desafiante no design de jogos, pois uma tarefa muito fácil pode gerar tédio e muito di- fícil pode levar à frustração. Assim, ao explorar a relação entre dificuldade e emoção, o presente trabalho pretende propor um modelo de inteligência artificial que preveja de forma autônoma a dificuldade de acordo com o conjunto de emoções elicitadas no jogador. Para testar a validade desta abordagem, desenvolveu-se um jogo de puzzle em Realidade Virtual (RV), baseado no Trail Making Test (TMT), e cujo objetivo era elicitar diferentes emoções tendo em conta três níveis de dificuldade. Foi realizado um estudo no qual se recolheram as respostas fisiológicas, juntamente com os autorrelatos dos jogado- res, durante o jogo. A análise estatística dos autorelatos mostrou que diferentes níveis de experiência com RV ou videojogos não tiveram um impacto mensurável no desempenho dos jogadores durante os três níveis. Além disso, as respostas emocionais auto-avaliadas indicaram que jogar o jogo em diferentes níveis de dificuldade deu origem a diferentes estados emocionais. Em seguida, foi realizada a classificação por intermédio de uma Má- quina de Vetores de Suporte (SVM) para verificar se era possível detectar dificuldade, considerando as respostas fisiológicas associadas às emoções elicitadas. Os resultados re- latam um F1-score geral de 68% na detecção dos três níveis de dificuldade, o que verifica a eficácia da metodologia adotada e incentiva novas pesquisas com um conjunto de dados maior