Browsing by Issue Date, starting with "2024-03-25"
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- Teaching Operational Research using Games and Simulation: a case studyPublication . Lopes, Cristina; Costa e Silva, ElianaThe use of gamification in teaching is not a novelty. It has been recognized as an effective method for fostering academic and practical skills, while simultaneously enhancing student engagement and motivation. In this work, we report on the use of web-based apps in classroom for introducing concepts and methods of Operational Research (OR) to students of Logistics and Business. Specifically, the Burrito Optimization game, available by Gurobi, and the TSP DYI app, developed by William Cook of the University of Waterloo, are employed to introduce mathematical optimization. The Burrito Optimization game simulates the facility location problem, challenging students to strategically position food trucks to optimize costs and profits, thereby acquainting them with linear programming models. Similarly, the TSP DYI app gamifies the TSP, encouraging student participation and competition while acquainting them with heuristic algorithms and optimization techniques. Through student feedback analysis, this study explores the efficacy of these gamified approaches in enhancing student engagement with OR concepts and motivating further exploration of complex topics. These web-based apps serve as entry points for aspiring data scientists and problem solvers, teaching why optimization is valuable and important, why it is difficult and why solvers and other optimization algorithms are essential.
- Cardiovascular pharmacogenomics-related genetic biomarkers: electrochemical genosensors for personalized medicinePublication . Barbosa, Tiago Manuel Moreira; Barroso, M. Fátima; Santos, Marlene; Vieira, MónicaCardiovascular diseases (CVDs) are one of the leading causes of death worldwide, and the anticoagulant warfarin is routinely used to treat and control CVDs. However, due to several individual factors, including genetic variations, as singles nucleotide polymorphisms (SNPs), drug’s efficacy varies between individuals. Moreover, given warfarin’s narrow therapeutic index, genotype-guided approaches have become critical in establishing personalized doses. Since conventional technologies for SNP detection such as Polymerase Chain Reaction or Real-Time Polymerase Chain Reaction (PCR or RT-PCR) are costly, time-consuming and demand skilled specialists, novel disposable electrochemical genosensors have been developed and optimized to facilitate SNP detection. In this project, two electrochemical genosensors were designed to detect both the -1639 G>ASNP in the vitamin K epoxide reductase complex (VKORC1) gene, important in the anticoagulant effect, and the CYP2C9 g.9133C>T gene variation involved in the metabolization of warfarin. The construction of these genosensors employed the formation of binary mixed self-assembled monolayers (SAMs) composed by DNA capture probes and mercaptohexanol (MCH), immobilized onto gold screen-printed electrodes (AuSPE). Furthermore, these genosensors employed a sandwich format hybridization technique (to increase sensitivity) that included the use of a fluorescein-labeled signaling probe and the enzymatic amplification of the electrochemical signal, measured via chronoamperometry. To obtain genomic DNA useful to be used in the genosensors, PCR technique was used to amplify genomic DNA from biological samples. Then, these samples were tested in the genosensors. The genosensors were able to detect genomic DNA associated to the CYP2C9 and VKORC1 genes, but only distinguished SNPs existent in the CYP2C9 gene displaying the ability to help in establishing the optimal warfarin dosage, providing a cost-effective alternative to the conventional procedures. This technique has the potential to improve patient care in cardiovascular medicine by tackling the problems associated with CVD therapy and the genetic heterogeneity of medication response.
- The impact of IFN-y-mediated endothelial cell activation for the progression of the mycobacterial granulomaPublication . Ribeiro, Nuno Miguel Pimenta; Resende, Mariana; Nova, Manuel Vila; Ferraz, RicardoMycobacterial infections, specifically those caused by Mycobacterium tuberculosis and Mycobacterium avium, continue to pose a challenge to public health. Understanding the genesis of granulomas brings u sone step further in understanding how to modulate the imune response to achive better disease outcomes. IFN-ɤ-mediated endotelial cell activation has been linked with increased permeability of the endothelium, enhancing leukocyte extravasation into the affected tissues. In this work we aimed to establish the role of IFN-ɤ signaling on endotelial cells (ECs) in promoting celular recruitment and in driving not only granuloma formation, but also central necrosis (a direct consequence of sever inflammation during mycobacterial infections). For that we used na inducible endotelial-specific IFN-ɤR1-KO mouse model (VE-Cadherin-CreERT2xifngR1fl/fl), intravenouslu infected with a low dose of Mycobacterium avium 25291, a strain known to induce prominente pathology with granulomas developing central necrosis. Ablation of IFNgR1 on ECs majorly impacted the histology of the livers and spleens, at 120 days post infection, displaying a significant reduction in inflammation. Compared to control mice, animals with impaired IFN-ɤ signaling on ECs exhibited reduced granuloma formation and a substantial decrease in necrotic lesions in the liver, along with complete abrogation of necrotic features and lower bacterial burdens in the spleen. These results suggest that IFN-ɤ signaling on ECs is an important mechanism to control inflammation on M. avium infected animals. Modulation of IFN-ɤ signaling on ECs might open up new avenues to manipulate inflammation and devise new therapies to control pathology by promoting disease tolerance.