Abstract

Abstract
Understanding the consequences of individual transcriptome variation is fundamental to deciphering human biology and disease. We implement a statistical framework to quantify the contributions of 21 individual traits as drivers of gene expression and alternative splicing variation across 46 human tissues and 781 individuals from the Genotype-Tissue Expression project. We demonstrate that ancestry, sex, age, and BMI make additive and tissue-specific contributions to expression variability, whereas interactions are rare. Variation in splicing is dominated by ancestry and is under genetic control in most tissues, with ribosomal proteins showing a strong enrichment of tissue-shared splicing events. Our analyses reveal a systemic contribution of types 1 and 2 diabetes to tissue transcriptome variation with the strongest signal in the nerve, where histopathology image analysis identifies novel genes related to diabetic neuropathy. Our multi-tissue and multi-trait approach provides an extensive characterization of the main drivers of human transcriptome variation in health and disease. © 2022 The Authors

Abstract

Abstract
In a world facing unprecedented challenges, such as climate changes and growing social problems, the pharmaceutical industry must ensure that its supply chains are environmentally sustainable and resilient, guaranteeing access to key medications even when faced with unanticipated disruptions or crises. The core goal of this work is to develop an innovative simulation-based approach to support more informed and effective decision making, while establishing reasonable trade-offs between supply chain robustness and resiliency, operational efficiency, and environmental and social concerns. Such a decision-support system will contribute to the development of more resilient and sustainable pharmaceutical supply chains, which are, in general, critical for maintaining access to essential medicines, especially during times of crises or relevant disruptions. The system will help companies to better manage and design their supply chains, providing a valuable tool to achieve higher levels of resilience and sustainability. The study we conducted has two primary contributions that are noteworthy. Firstly, we present a new advanced approach that integrates multiple simulation techniques, allowing for the modeling of highly complex environments. Secondly, we introduce a new conceptual framework that helps to comprehend the interplay between resiliency and sustainability in decision-making processes. These two contributions provide valuable insights into understanding complex systems and can aid in designing more resilient and sustainable systems.

Abstract
We investigate the fuzzy clustering of interval time series using wavelet variances and covariances; in particular, we use a fuzzy c-medoids clustering algorithm. Traditional hierarchical and non-hierarchical clustering methods lead to the identification of mutually exclusive clusters whereas fuzzy clustering methods enable the identification of overlapping clusters, implying that one or more series could belong to more than one cluster simultaneously. An interval time series (ITS) which arises when interval-valued observa-tions are recorded over time is able to capture the variability of values within each interval at each time point. This is in contrast to single-point information available in a classical time series. Our main contribution is that by combining wavelet analysis, interval data analysis and fuzzy clustering, we are able to capture information which would otherwise have not been contemplated by the use of traditional crisp clustering methods on classical time series for which just a single value is recorded at each time point. Through simulation studies, we show that under some circumstances fuzzy c-medoids clustering performs better when applied to ITS than when it is applied to the corresponding traditional time series. Applications to exchange rates ITS and sea-level ITS show that the fuzzy clustering method reveals different and more meaningful results than when applied to associated single-point time series.

Abstract
This paper presents a study on the use of gamified educational escape rooms to foster the teaching-learning process of computer programming, based on an user type taxonomy. The ultimate goal of this work is to identify and validate the most suitable gamification elements and mechanics for each user profile, providing case studies that illustrate their implementation. The main contribution of this work is to guide the design process of educational escape rooms in any domain, by considering the needs, preferences, and motivations of different user types. © Ricardo Queirós, Carla Pinto, Mário Cruz, and Daniela Mascarenhas;