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  • Optimal Sizing of Renewable Energy Communities: A Multi-Objective Optimization Approach
    Publication . Marques, Carlos Pedro Tavares Freire; Pombo, José Álvaro Nunes
    Renewable energy communities (RECs) have gained popularity as a new mean of reducing carbon emissions and enhancing energy independence. However, determining the optimal sizing for each production and storage unit within RECs poses challenges due to conflicting objectives, such as minimizing costs while maximizing energy production. In an attempt to optimally address this issue, this paper proposes a new multi-objective optimization algorithm (MOA) denoted Multi-Objective Arithmetic & Differential Evolution Optimization (MOADEO). Nevertheless, to determine the optimal sizing of each of the production and storage units in RECs, this paper employs an existent and widely used MOA present in the literature, named Multi-Objective Particle Swarm Optimization (MOPSO), with multiple swarms. This multiple swarms approach aims to foster a broader diversity of solutions while concurrently ensuring a good plurality of nondominant solutions that define the Pareto Front. To evaluate the effectiveness and reliability of this approach, four case studies with different energy management strategies (EMSs) focused on real-world operations were evaluated, aiming to replicate the practical challenges encountered in actual RECs. The results demonstrate the effectiveness of the proposed approach in determining the optimal size of production and storage units, while simultaneously addressing multiple conflicting objectives, including economic and flexibility viability, specifically Levelized Cost of Energy (LCOE), SelfConsumption Ratio (SCR) and Self-Sufficiency Ratio (SSR). The findings also provide valuable insights that clarify which EMSs are most suitable for this type of communities.
    2024-03-21Master thesis Open access Show more
  • Immune dysfunction in obesity-associated hypertension and effects of vitamin D supplementation
    Publication . Santos, Catarina Cecília Pinheiro Reis dos; Sousa, Miguel Castelo Branco Craveiro de; Fonseca, Ana Mafalda Loureiro
    Arterial hypertension (HTN) is a systemic and chronic disease known for several decades but with a prognosis that as changed little since then. The high morbidity and mortality associated with high blood pressure have always been the thread to the development of new strategies and therapeutics but, even with noticeable scientific progress, the prognosis of HTN remains poor. In the last decade, multiple evidence as documented that immune cells may also contribute to the pathogenesis of HTN, underlining its role in the development of chronic and sustained inflammation. Given the close link between the innate and adaptive immune systems, it was not surprising that most immune cells were found to be implicated in the pathogenesis of hypertensive responses. In the case of obesity-related HTN, a growing epidemic in the nowadays, we must also consider the contribution of an already unbalanced immune system, supported by a powerful but also immunologically unbalanced endocrine organ, which is the adipose tissue. Counterbalancing this stormy environment is a difficult task and for which only some immunosuppressives have demonstrated efficacy. However, their applicability in clinical practice is limited and other alternatives should be searched. Vitamin D (VD) may represent one of such alternatives, since it has recognized immunomodulatory properties, being already used in the context of several auto-immune diseases like type 1 diabetes mellitus or multiple sclerosis. Aiming to explore the immune dysregulation that comes with obesity-related HTN, and the immunoregulatory role of VD in this setting, we developed an investigator-initiated trial. It was a phase-2, single-centre, randomised, open, 24-week study, where adults with obesity-associated HTN and VD deficiency were assigned to receive usual therapy plus 50 000 IU/week of cholecalciferol or usual therapy alone. Sampling of peripheral blood and subcutaneous abdominal adipose tissue ensued to evaluate for differences in immunological profiles. A control group of overweight normotensives was also evaluated at baseline. The primary endpoint was the percentual variation in peripheral TCD4+, TCD8+, T regulatory (Tregs), and T helper 17 (Th17) cells. Three additional secondary endpoints were defined: variation of peripheral T helper 1 (Th1), T cytotoxic 1 (Tc1) and Tc17 cells, and monocytes, variation in the number of adipose tissue perivascular and non-perivascular macrophages, TCD4+ and TCD8+ lymphocytes, and, lastly, the modifications in serum metabolome, with a special focus in glutamine. Modifications in the average values of insulin resistance indexes were also monitored and included HbA1c and visceral adiposity index. The trial recruited 36 participants with the simultaneous diagnosis of HTN and obesity or metabolic syndrome, 18 randomised to each group. Only one patient was non-compliant with trial medication. All the analyses were performed per protocol. In comparison with normotensive controls, hypertensives presented higher percentages of T lymphocytes (p = 0.016), Tregs (p = 0.014), and non-classical monocytes (p< 0.001). At week 24, Th17 cells increased in control group (p = 0.017) but remained stable in cholecalciferol group. For Tregs, downregulation towards the values of normotensive controls was observed (p = 0.003), and in multivariate analysis, an increased loading in the setting of the cells of adaptive immunity observed (Eigenvalue 1.78, p < 0.001). No changes were documented for peripheral TCD4+, TCD8+ or monocytes. In adipose tissue, a baseline negative correlation between VD and perivascular macrophages was observed (r = -0.387, p = 0.024) that persisted in the control group (r = -0.528, p = 0.024) but not in the cholecalciferol group, which presented an increase in non-perivascular macrophages (p = 0.029) at week 24. Serum metabolome of hypertensives compared to normotensives presented an overall decreased expression of several amino acids, including ketogenic (p< 0.05) and glucogenic (p< 0.0001) amino acids as well as aromatic amino acids (p < 0.001). Following cholecalciferol supplementation, notable increases were observed in glutamine (p< 0.001) and histidine (p< 0.05) levels, while several other amino acids remaining unaffected. Glucose (p< 0.05) and acetate (p< 0.05) decreased after the 24 weeks in the group taking cholecalciferol and changes in the saturation of fatty acids were also observed, suggesting a role of liposoluble VD in lipid metabolism. No changes in the average values of insulin-resistance indexes were observed. No serious adverse events were reported for all the participants. We concluded that VD may be a useful and safe drug in setting of obesity-related HTN. The shift towards a more anti-inflammatory state may be reached using standard doses of VD. Peripheral immune profile of hypertensives contrasted significantly with normotensives, being identified paradoxical increases in both pro- and anti-inflammatory cells. The statistically significant difference observed for Tregs, as seen in other chronic conditions, points to upregulation as a means of counterbalancing the inflammatory milieu. Under the effects of cholecalciferol, the percentage of TCD4+ and TCD8+ was unaffected but the unrestrained proliferation of Tregs and Th17 cells was limited, with the frequencies of some cells approaching those of normotensive controls. Th1 cells increased but this change is not necessarily linked to increased release of cytokines, and monocytes were unaffected by VD. A unique metabotype was identified for hypertensives, which is characterized by reduced levels of several amino acids, both gluco- and ketogenic, but also sub-products of glucose metabolism, like lactate and acetate. Together, these modifications suggest a high catabolic rate and protein wasting but also routing of energy production outside of the Krebs cycle. With VD supplementation modifications were seen for some metabolites, most notably glutamine and histidine, partially offsetting the disturbances observed at baseline. Glutamine is a fundamental substrate to fuel immune cells activity, and increased availability may route immune cells to Krebs cycle instead of aerobic glycolysis. In combination with the reduction in glucose levels, this new microenvironment that surrounded immune cells could have dampen the fast energy production through glycolysis and, hence, attenuate T cell activation and proliferation. At the level of the adipose tissue, VD also documented immunomodulatory potential. Correlating negatively with perivascular macrophages, important releasers of vasoconstrictors, increased levels in the peripheral blood may interfere with monocytes migration to perivascular adipose tissue. Above of all, increased frequencies of macrophages with non-perivascular distribution were seen after supplementation, but not in controls, in a picture that seems to mimic the modifications seen after bariatric surgery, and the increased cells contributing to enhanced phagocytosis of cellular debris in an involuting adipose tissue mass. Although some of our findings are not in line with other reports and several limitations should be addressed, we think our trial represents an important effort of translation of results to the patient level, where heterogeneity and a multiple array of factors disrupt the well-controlled conditions of the laboratory. Above of all, this trial allowed us to gain a more comprehensive understanding of the immune mechanisms underlying HTN in a specific context and to explore more deeply the well-known immunomodulatory actions of VD.
    2024-03-21Doctoral thesis Open access Show more