Computational design of dynamic receptor-peptide signaling complexes applied to chemotaxis.

Engineering protein biosensors that sensitively respond to specific biomolecules by triggering precise cellular responses is a major goal of diagnostics and synthetic cell biology. Previous biosensor designs have largely relied on binding structurally well-defined molecules. In contrast, approaches that couple the sensing of flexible compounds to intended cellular responses would greatly expand potential biosensor applications. Here, to address these challenges, we develop a computational strategy for designing signaling complexes between conformationally dynamic proteins and peptides. To demonstrate the power of the approach, we create ultrasensitive chemotactic receptor-peptide pairs capable of eliciting potent signaling responses and strong chemotaxis in primary human T cells. Unlike traditional approaches that engineer static binding complexes, our dynamic structure design strategy optimizes contacts with multiple binding and allosteric sites accessible through dynamic conformational ensembles to achieve strongly enhanced signaling efficacy and potency. Our study suggests that a conformationally adaptable binding interface coupled to a robust allosteric transmission region is a key evolutionary determinant of peptidergic GPCR signaling systems. The approach lays a foundation for designing peptide-sensing receptors and signaling peptide ligands for basic and therapeutic applications

Evaluation of spatial data’s impact in mid-term room rent price through application of spatial econometrics and machine learning. Case study: Lisbon

Dissertation submitted in partial fulfilment of the requirements for the degree of Master of Science in Geospatial TechnologiesHousehold preferences is a topic whose relevance can be found to dominate the applied economics, but whereas urban economies view cities as production centers, this thesis aims to give importance to the role of consumption. Provision to PoIs might give explanation to what individuals value as an important asset for improvement of their quality of life in a chosen city. As such, understanding short-term rentals and real estate prices have induced various research to seek proof of impacting factors, but analysis of mid-term rent has faced the challenge of being an overlooked category. This thesis consists of an integrated three-steps approach to analyze spatial data’s impact over the mid-term room rent, choosing Lisbon as its case study. The proposed methodology constitutes use of traditional spatial econometric models and SVR, encompassing a large set of proxies for amenities that might be recognized to hold a possible impact over rent prices. The analytical frameworks’ first step is to create a suitable HPM model that captures the data well, so significant variables can be detected and analyzed as a discrete dataset. The second step applies subsets of the dataset in the creation of SVR models, in hopes of identifying the SVs influencing price variances. Finally, SOM clusters are chosen to address whether more natural order of data division exists. Results confirm the impact of proximity to various categories of amenities, but the enrichment of models with the proposed proxies of spatial data failed to corroborate attainment of model with a higher accuracy. (Nüst et al., 2018) provides a self-assessment of the reproducibility of research, and according to the criteria given, this dissertation is evaluated as: 0, 2, 1, 2, 2 (input data, preprocessing, methods, computational environment, results)

Machine Learning para deteção de padrões e previsão de ocorrências criminais

The increase of the world population, especially in large urban centers, has resulted in new challenges such as the management of natural resources and infrastructures as well as the optimization of services to promote the quality of citizens’ life. One of the biggest and most important challenges is the management of public safety, since, in addition to being a factor of interest to both the general population and the authorities, it is also an area that influences other essential indicators in a city such as tourism and employment. Public Safety has impact on the economic growth and social development of a community. This dissertation proposes a solution for the prediction of criminal occurrences in a city based on historical data of incidents and demographic data. The entire life cycle of the model’s learning process will be presented to provide an organization with predictive capability: start with the data collection from its original source, the treatment and transformations applied to them, the choice and the evaluation and implementation of the Machine Learning model up to the application layer. Classification models will be implemented to predict criminal risk for a given time interval and location, as well as regression models to predict the number of crimes. Machine Learning algorithms, such as Random Forest, Neural Networks, K-Nearest Neighbors and Logistic Regression will be used to predict occurrences, and their performance will be compared according to the data processing and transformation used. The results of the chosen model show that the use of Machine Learning techniques helps to anticipate criminal occurrences, which contributed to the reinforcement of public security. Finally, the models will be implemented on a platform that provides an API to enable other entities to request for predictions in real-time. An application will also be presented where it is possible to show criminal occurrences predictions visually.O aumento da população mundial, especialmente nos grandes centros urbanos, tem resultado em novos desafios tais como a gestão de recursos naturais, gestão de infraestruturas, bem como a otimização dos serviços para promover a qualidade de vida dos cidadãos. Um dos maiores e mais importantes desafios é a gestão da segurança pública. Para além de ser um fator de interesse quer da população em geral quer das autoridades, também é um domínio que influencia outros indicadores essenciais numa cidade como o turismo e o emprego. A segurança pública reflete-se no crescimento económico e no desenvolvimento social de uma comunidade. Nesta dissertação é proposta uma solução para previsão de ocorrências criminais numa cidade baseada em dados de histórico de incidentes e dados demográficos. Será apresentado todo o ciclo de vida do processo de aprendizagem do modelo para dotar uma organização da capacidade preditiva: desde a recolha dos dados da sua fonte de origem, o tratamento e transformações aplicadas aos mesmos, escolha, avaliação e implementação do modelo de Machine Learning até à camada de aplicação. Serão implementados modelos de classificação para previsão do risco criminal para um dado intervalo temporal e localização, e modelos de regressão para previsão do número de crimes. Irão ser utilizados algoritmos de Machine Learning como Random Forest, Redes Neuronais, K-Nearest Neighbors e Regressão Logística para a aprendizagem do modelo de previsão de ocorrências onde serão comparados os seus desempenhos de acordo com o tratamento e transformação dos dados utilizados. Os resultados do modelo escolhido evidenciam que a utilização de técnicas de Machine Learning auxiliam a antecipação de ocorrências criminais, o que contribuiu para o reforço da segurança pública. Por fim, irá ser procedida a implementação dos modelos numa plataforma que fornece uma API para que entidades externas possam solicitar previsões em tempo real. Será também apresentada a aplicação onde é possível mostrar visualmente as previsões de ocorrências criminais.Mestrado em Engenharia Informátic

The perceptual and cognitive roles of the motor system

The motor system in the brain is crucial in allowing us to successfully move aroundin our environment, interact with people and objects, and execute finely controlled motorcommands. While most of the early neuroscience research on these regions tends to focuson these “main” functions, over the last few decades evidence has been surfacing thatpoints to a more broadly integrated role for the motor system. Many recent findingssuggest that it is also of importance in many other aspects of human cognition, fromlanguage and thought to social cognition and, as I discuss in depth in the followingsections, many perceptual processes. In the following chapters, I outline and compareexisting prediction-based and simulation-based theories for motor system involvement inperception. I also describe experiments I completed investigating motor systeminvolvement in written language perception, music perception, and action observation.Furthermore, I discuss how these processes relate to conceptual learning and recall. Insummary, a vast literature points to the motor system proper not being a neural networkthat is only good for controlling and planning our actions. As we develop the vocabularyof the field to use terms like “action-perception loops” and discuss these processes as lessseparable than previously considered, perhaps we should also reconsider the term “motorsystem” to reflect its diverse roles in sensorimotor prediction

Bioinformatics

This book is divided into different research areas relevant in Bioinformatics such as biological networks, next generation sequencing, high performance computing, molecular modeling, structural bioinformatics, molecular modeling and intelligent data analysis. Each book section introduces the basic concepts and then explains its application to problems of great relevance, so both novice and expert readers can benefit from the information and research works presented here