Neural correlates of post-traumatic brain injury (TBI) attention deficits in children

Traumatic brain injury (TBI) in children is a major public health concern worldwide. Attention deficits are among the most common neurocognitive and behavioral consequences in children post-TBI which have significant negative impacts on their educational and social outcomes and compromise the quality of their lives. However, there is a paucity of evidence to guide the optimal treatment strategies of attention deficit related symptoms in children post-TBI due to the lack of understanding regarding its neurobiological substrate. Thus, it is critical to understand the neural mechanisms associated with TBI-induced attention deficits in children so that more refined and tailored strategies can be developed for diagnoses and long-term treatments and interventions. This dissertation is the first study to investigate neurobiological substrates associated with post-TBI attention deficits in children using both anatomical and functional neuroimaging data. The goals of this project are to discover the quantitatively measurable markers utilizing diffusion tensor imaging (DTI), structural magnetic resonance imaging (MRI), and functional MRI (fMRI) techniques, and to further identify the most robust neuroimaging features in predicting severe post-TBI attention deficits in children, by utilizing machine learning and deep learning techniques. A total of 53 children with TBI and 55 controls from age 9 to 17 are recruited. The results show that the systems-level topological properties in left frontal regions, parietal regions, and medial occipitotemporal regions in structural and functional brain network are significantly associated with inattentive and/or hyperactive/impulsive symptoms in children post-TBI. Semi-supervised deep learning modeling further confirms the significant contributions of these brain features in the prediction of elevated attention deficits in children post-TBI. The findings of this project provide valuable foundations for future research on developing neural markers for TBI-induced attention deficits in children, which may significantly assist the development of more effective and individualized diagnostic and treatment strategies

Nterleukin-4 responsive dendritic, macrophage/neutrophil cells are dispensable for host resistance against Leishmania Mexicana infection in mice

Studies have shown that the protection against L. mexicana infection is potentiated by a type 1 response, driven by IL-12 production by dendritic cells. In contrast, IL-4 and IL-13 cytokines are associated with susceptibility to L. mexicana causing cutaneous leishmaniasis. This has been demonstrated in studies involving BALB/c mice deficient in IL-4, IL-13, and IL-4Rα infected with L. mexicana. To determine the specific cell in IL-4Rα-/- BALB/c mice that contribute to the control of L. mexicana infections, studies on cell-specific IL-4Rα deficient mice need to be investigated. IL4Rα-CD4+T deficient mice revealed sex-dependent protection from L. mexicana infection, suggesting the critical role of non-lymphocyte cells in conferring protection against L. mexicana amastigote infection. Macrophage/neutrophil-specific IL-4Rα deficient mice are protected from L. major infection in the footpad. Surprisingly, this mouse strain infected in the base of the tail failed to control L. mexicana amastigote infection. Nonetheless, IL-4Rα-DC deficient mice were hyper-susceptible to L. major infection. This conundrum suggests that different Leishmania species, site of infection, and developmental stages of parasite dictate the outcome of the disease. Here, mice with a deficiency of IL-4Rα signaling on DCs and macrophage/ neutrophil cells were subcutaneously infected with L. mexicana promastigotes in the footpad, and skin lesion progression was measured, and the clinical phenotype was evaluated by investigating both humoral and cellular immune responses. Mouse strains had similar footpad lesion progression, parasite loads, humoral responses, expansion of CD4+ and CD8+ T cells, their activation, memory phenotypes, and infiltration of DCs, macrophages, and neutrophils into the lymph nodes compared to their littermate IL-4Rα-/lox controls. Interestingly, IL‐12p70 and IL‐10 produced by BMDCs and BMDMs were similar. Nevertheless, nitrite/urea production was not affected. Together, this study suggests that, unlike L. major, IL-4Rα signaling on DCs and macrophage/ neutrophil cells does not contribute to the susceptibility or resistance to BALB/c mice to infection with L. mexicana

Computational investigations of the spectroscopy, vibronic coupling, and photo(stereo)chemistry in inorganic systems

This thesis focuses on the spectroscopy and photo-stereochemistry of relatively large closed-shell and open-shell transition metal complexes, investigated with an array of modern computational methodologies. The presence of the metal electrons/orbitals results in a greater number of low-lying excited states, and these states are vibronically coupled resulting in Jahn-Teller or pseudo-Jahn-Teller (pJT) effects, or general surface crossings. These features are very challenging to calculate but are vitally important to explain the observed behavior in such systems. Computational investigations using the multiconfigurational CASSCF method on the pJT effect occurring in ammonia, and Mo2(DXylF)2(O2CCH3)2(μ2-O)2 complex are presented. These definitively show that in the latter case the experimentally observed structure is due to a vibronic coupling of the ground electronic state with that of a nondegenerate 1πδ* state, resulting in a rhomboidal rather than square motif at the bimetallic centre. The (BQA)PtMe2I (BQA= bis(8-quinolinyl)amide) complex has been found to undergo unexpected meridial to facial isomerisation induced by light. The TD-DFT method was used to examine the spectroscopy of this system, and the CASSCF method was used to examine excited state relaxation pathways. The system relaxes on an excited state potential energy surface, of an essentially localised ππ* excited state of the BQA ligand, and reaches a facial excited minimum that is located adjacent to a sloped conical intersection connecting the excited and ground electronic states. Chromium (III) complexes have been investigated for many years and many aspects of their photochemistry are still not very well understood. The photochemistry of paradigm Cr (III) complexes, such as chromium oxalate [Cr(C2O4)3]3-, chromium tris- (1,3diaminopropane) [Cr(tn)3]3+ and Cr(tn)2(CN)2, have been investigated using TDDFT and CASSCF methods. Non-radiative relaxation pathways have been documented showing mechanism of both internal conversion in the quartet manifold, as well as inter-system crossing into the doublet manifold. The results explain photostereochemical features of the photo-induced racemization of [Cr(C2O4)3]3- and the photoaquation of [Cr(tn)3]3+ and Cr(tn)2(CN)2.Engineering and Physical Sciences Research Council (EPSRC) grant No. EP/F01709

Avaliação do ciclo de vida da rolha de cortiça natural

Tese de mestrado. Engenharia do Ambiente (Gestão e Tratamento de Resíduos Industriais). Faculdade de Engenharia. Universidade do Porto. 200

Proceedings of the European Conference on Agricultural Engineering AgEng2021

This proceedings book results from the AgEng2021 Agricultural Engineering Conference under auspices of the European Society of Agricultural Engineers, held in an online format based on the University of Évora, Portugal, from 4 to 8 July 2021. This book contains the full papers of a selection of abstracts that were the base for the oral presentations and posters presented at the conference. Presentations were distributed in eleven thematic areas: Artificial Intelligence, data processing and management; Automation, robotics and sensor technology; Circular Economy; Education and Rural development; Energy and bioenergy; Integrated and sustainable Farming systems; New application technologies and mechanisation; Post-harvest technologies; Smart farming / Precision agriculture; Soil, land and water engineering; Sustainable production in Farm buildings

The stratification potential of a novel epigenetic biomarker in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disease of the joints, that affects 0.5-1% of the population globally. While primarily affecting the joints, systemic inflammation impacts other organs and the disease has a significant socioeconomic burden. While there are a wide range of medications to pharmacologically manage RA, it is a largely heterogeneous disease and the current treatment strategy does not consider the heterogeneity between patients. As such, precision medicine approaches to treatment are desired. A 5-loop chromosome conformation signature (CCS) was identified that had 90% specificity at predicting non-response to methotrexate (MTX) in early RA. These epigenetic biomarkers offer a novel strategy for improving patient care, and provide insight into disease pathogenesis. The aim of the work presented in this thesis was to further characterise this novel epigenetic biomarker. Investigation of this biomarker also offered the opportunity to hypothesise about underlying pathogenesis. A combination of molecular analysis of patient samples, and in-silico methodologies were applied to investigate these aims. In the first instance, the CCS was validated as a biomarker for identifying MTX responders using bioinformatic tools. Preliminary work was also carried out to identify the optimal method for detecting chromosome loops from the signature in the lab. Quantitative PCR was thoroughly explored, but excluded as a reliable and robust method of loop detection for our signature of interest. It was also found that the CCS was MTX specific, and alternative signatures would be required for prediction of response to other csDMARDs. Further validation of the signature, using an independent clinical cohort, revealed that specific loops from the CCS held stratification potential while others did not. In-silico investigations revealed different epigenetic landscapes exist between loops associated with responders and non-responders to MTX. Specifically, data suggests loops associated with responders exist in an environment which enhances gene transcription, while loops associated with non-responders have an environment indicating potential for gene repression. Differences in chromatin architecture, revealed through a discovery microarray, have indicated that 3D epigenetic endotypes exist within the early RA population. Further investigations suggested each endotype have different, unique pathways that are highly regulated. Furthermore, results revealed that there is a stable RA chromatin signature that exists, which highlights the importance of the 3D epigenome underpinning disease. In summation, this body of work has shown CCS to be promising biomarker for the stratification of the early RA population. Furthermore, thorough investigation of this signature highlighted novel pathways that may be involved in disease pathogenesis. This work has exciting potential to contribute to improved RA treatment in the future