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The main aim of structural safety control is the multiple assessments of the expected dam behaviour based on models and the measurements and parameters that characterise the dam’s response and condition. In recent years, there is an increase in the use of data-based models for the analysis and interpretation of the structural behaviour of dams. Multiple Linear Regression is the conventional, widely used approach in dam engineering, although interesting results have been published based on machine learning algorithms such as artificial neural networks, support vector machines, random forest, and boosted regression trees. However, these models need to be carefully developed and properly assessed before their application in practice. This is even more relevant when an increase in users of machine learning models is expected. For this reason, this paper presents extensive work regarding the verification and validation of data-based models for the analysis and interpretation of observed dam’s behaviour. This is presented by means of the development of several machine learning models to interpret horizontal displacements in an arch dam in operation. Several validation techniques are applied, including historical data validation, sensitivity analysis, and predictive validation. The results are discussed and conclusions are drawn regarding the practical application of data-based models.

Introdução: A quimioterapia com 5-fluorouracil (5-FU) promove diversos efeitos colaterais. Estudos anteriores demonstram que esse quimioterápico altera a morfologia dos túbulos seminíferos e possibilita a descamação do epitélio germinativo do testículo. Entretanto, há poucos dados sobre os impactos do 5-FU nesse órgão em dose e terapêutica semelhantes à prática clínica. Objetivo: Avaliar o impacto da administração de 5-FU na morfologia do testículo de ratos adultos. Material e métodos: O estudo foi aprovado pelo Comitê de Ética no Uso de Animais da Universidade Estadual de Maringá (protocolo: 4422140918). Foram utilizados 14 ratos Wistar machos, divididos em dois grupos (n=7): grupo controle (GC), administrado com solução fisiológica via intraperitoneal; grupo quimioterapia (G5-FU), administrado pela mesma via com 15 mg/kg de 5-FU por quatro dias consecutivos, 6 mg/kg por mais quatro dias alternados e dose final de 15 mg/kg. Esse esquema é semelhante ao utilizado para o tratamento dos cânceres: colorretal, mama, estômago, pâncreas, fígado, útero, ovário e bexiga. No 15° dia, todos os animais foram eutanasiados por superdosagem de Tiopental Sódico. O testículo foi dissecado, fixado em Methacarn e incluído em blocos de parafina. Cortes semi-seriados de 5 μm foram corados com Hematoxilina e Eosina para avaliação morfológica pelo método de Weibel. Por fim, realizou-se a estatística e os valores foram expressos em média (porcentagem) ± erro padrão. Resultados: Por análise comparativa, foi observado alteração significativa nos compartimentos epitelial (GC= 58,94 ± 0,52; G5-FU= 55,37 ± 0,52) e estromal (GC= 31,48 ± 0,60; G5-FU= 34,81 ± 0,63) do testículo após administração de 5-FU. Esses resultados sugerem a descamação epitelial dos túbulos seminíferos frente à quimioterapia. Apesar do modelo experimental diferente, nossos resultados corroboram com outros estudos na literatura. Conclusão: A quimioterapia com 5-FU em posologia semelhante à humana alterou a histoarquitetura testicular de ratos Wistar.

Orientador: Mário Noboru Tamashiro Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Física Gleb Wataghin Resumo: Neste trabalho investigamos o modelo de gás de rede de Doniach em redes bipartidas, considerando a divisão do sistema em duas sub-redes interpenetrantes, atra- vés da aproximação de campo médio. O gás de rede de Doniach consiste num modelo estatístico mapeável num modelo de Ising de spin-1 com estados de sítio único altamente degenerados e a inclusão de interações dipolo-quadrupolo, além das interações usuais dipolo-dipolo, de campo cristalino e de efeito Zeeman, utilizando a nomenclatura do mo- delo análogo magnético. A sua formulação foi motivada visando o estudo de transições de fase em estruturas supramoleculares de fosfolipídios zwitteriônicos, em particular, para permitir a introdução de flutuações de densidade no sistema, não incorporada, até então, em propostas anteriores. Esta análise do modelo em redes bipartidas permitiu a investi- gação de fases alternadas, que passaram despercebidas na primeira análise do modelo na aproximação de campo médio, justamente por ter-se considerado apenas a presença de fases uniformes, isto é, sem a divisão do sistema em duas sub-redes distintas. No entanto, tais fases alternadas foram observadas para este modelo na aproximação de pares em re- des bipartidas. Para complementar nossa análise, foi realizado um estudo comparativo entre resultados experimentais para o fosfolipídio zwitteriônico dimiristoilfosfatidilcolina (DMPC) e os obtidos teoricamente pelo modelo na aproximação de campo médio Abstract: In this work, we investigate the Doniach lattice gas (DLG) model, consider- ing the division of the system into two interpenetrating sublattices, under the framework of the mean-field approximation. The Doniach lattice gas consists of a statistic model mappable on a spin-1 Ising model with highly degenerate single-site states and the inclu- sion of dipole-quadrupole interactions, besides the usual dipole-dipole, crystal-field and Zeeman-effect interactions, using the nomenclature of the analogous magnetic model. Its formulation was motivated aiming at the study of phase transitions in supramolecular structures of zwitterionic phospholipids, in particular, to allow the introduction of den- sity fluctuations in the system, not considered so far in previous proposals. This analysis of the model on bipartite lattices allowed the investigation of staggered phases, which were overlooked in the first analysis of the model in the mean-field approach, precisely because it was only assumed the presence of uniform phases, i.e., without spliting the system into two distinct sublattices. However, such staggered phases were observed for this model in the pair approximation on bipartite lattices. To complement our analysis, a comparative study was carried out between experimental results for the zwitterionic phos- pholipid dimiristoylphosphatidylcholine (DMPC) and those theoretically obtained by the model in the mean-field approach Mestrado Física Mestra em Física CAPES 1765886/2018

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES A cobrança pelo uso da água bruta é um instrumento econômico inserido na política ambiental, que tem como objetivo induzir os usuários a um uso mais racional dos recursos hídricos, na medida em que se busca regular os múltiplos usos da água. A tarifa a ser cobrada pelo uso da água bruta deve ser suficiente para alcançar o objetivo da cobrança, porém, sem comprometer a viabilidade econômica do setor usuário. O objetivo deste trabalho é avaliar a precificação de água bruta para o setor de abastecimento urbano no estado do Rio Grande do Norte e analisar a sensibilidade deste setor a aplicação da cobrança, propondo uma tabela de preços unitários de tarifas, calculados com base no lucro líquido, decorrente da diferença entre a receita bruta e o custo total do setor, no período de 2015 a 2019. Para a obtenção dos valores de receita total a ser arrecadada com a cobrança e aplicada no Sistema Integrado de Gestão de Recursos Hídricos (SIGERH), multiplicou-se cada preço unitário pelo volume de água captado pelas empresas de saneamento, informado no Sistema Nacional de Informações Sobre Saneamento (SNIS). Como resultado, e considerando a variação de preço entre R$ 0,02 à R$ 0,07 por m³ de água captada, obteve-se uma receita média anual de R$ 4,5 a R$ 16 milhões, que corresponde a cerca de 12,6% a 44% dos custos de operação, administração e manutenção do SIGERH do Estado do RN. Esses valores equivalem a cerca de 10,5% a 36,8% do lucro médio anual do setor de saneamento no Estado. Espera-se que os valores apresentados neste estudo sirvam de referência para a cobrança pelo uso da água bruta e que esse instrumento econômico de gestão melhore o gerenciamento de recursos hídricos no estado do Rio Grande do Norte. The charge for the use of raw water is an economic instrument inserted in the environmental policy, which aims to induce users to a more rational use of water resources, as it seeks to regulate the multiple uses of water. The tariff to be charged for the use of raw water must be sufficient to achieve the objective of the charge, however, without compromising the economic viability of the user sector. The objective of this work is to evaluate the pricing of raw water for the urban supply sector in the state of Rio Grande do Norte and to analyze the sensitivity of this sector to the application of collection, proposing a table of unit tariff prices, calculated based on net profit., due to the difference between the gross revenue and the total cost of the sector, in the period from 2015 to 2019. To obtain the total revenue values to be collected with the collection and applied in the Integrated Water Resources Management System (SIGERH), each unit price was multiplied by the volume of water collected by the sanitation companies, as reported in the National Sanitation Information System (SNIS). As a result, and considering the price variation between R$ 0.02 to R$ 0.07 per m³ of water captured, an average annual revenue of R$ 4.5 to R$ 16 million was obtained, which corresponds to approximately from 12.6% to 44% of the operating, administration and maintenance costs of SIGERH in the State of RN. These values are equivalent to about 10.5% to 36.8% of the average annual profit of the sanitation sector in the State. It is hoped that the values presented in this study will serve as a reference for charging for the use of raw water and that this economic management instrument will improve the management of water resources in the state of Rio Grande do Norte.

The experimental autoimmune encephalomyelitis (EAE) model is the most commonly used animal model of multiple sclerosis (MS). However, phenotypic characterization of mice based on the traditional 5-point clinical paralysis scale does not fully capture disease progression. The frailty index (FI) conceptualizes frailty as the accumulation of health deficits and it is widely used to assess overall health in aging humans and preclinical models. Here, we adapted an established mouse FI tool for use in EAE mice and determined whether this could evaluate general signs of health in variably aged female EAE mice. The EAE-Clinical FI included 34 items related to clinical signs and deficits characteristic of aging and MS. This tool clearly showed more detailed EAE progression and severity at all ages, highlighting changes in systems other than motor paralysis measured with the traditional 5-point paralysis scale. When we induced disease at 3 and 6 months of age, mice showed typical EAE clinical manifestations with peak disease severity between 17 and 19 days post-induction and mean frailty scores of 0.36 ± 0.04 (3-month-old) and 0.43 ± 0.05 (6-month-old). By contrast, disease severity peaked after 14 days in 12-month-old mice. They showed atypical signs including wobbling, early belly drag, and splayed hindlegs that were better captured with the EAE-Clinical FI. Peak frailty scores also were higher than those of younger animals (0.54 ± 0.04). As MS most often develops in young to middle-aged people, this new tool may have significant value for use in EAE animal studies as a first step toward translation to people with MS.

Background Malaria in Brazil represents one of the highest percentages of Latin America cases, where approximately 84% of infections are attributed to Plasmodium (P.) vivax. Despite the high incidence, many aspects of gestational malaria resulting from P. vivax infections remain poorly studied. As such, we aimed to evaluate the consequences of P. vivax infections during gestation on the health of mothers and their neonates in an endemic area of the Amazon. Methods and findings We have conducted an observational cohort study in Brazilian Amazon between January 2013 and April 2015. 600 pregnant women were enrolled and followed until delivery. After applying exclusion criteria, 329 mother-child pairs were included in the analysis. Clinical data regarding maternal infection, newborn’s anthropometric measures, placental histopathological characteristics, and angiogenic and inflammatory factors were evaluated. The presence of plasma IgG against the P. vivax (Pv) MSP119 protein was used as marker of exposure and possible associations with pregnancy outcomes were analyzed. Multivariate logistic regression analysis revealed that P. vivax infections during the first trimester of pregnancy are associated with adverse gestational outcomes such as premature birth (adjusted odds ratio [aOR] 8.12, 95% confidence interval [95%CI] 2.69–24.54, p < 0.0001) and reduced head circumference (aOR 3.58, 95%CI 1.29–9.97, p = 0.01). Histopathology analysis showed marked differences between placentas from P. vivax-infected and non-infected pregnant women, especially regarding placental monocytes infiltrate. Placental levels of vasomodulatory factors such as angiopoietin-2 (ANG-2) and complement proteins such as C5a were also altered at delivery. Plasma levels of anti-PvMSP119 IgG in infected pregnant women were shown to be a reliable exposure marker; yet, with no association with improved pregnancy outcomes. Conclusions This study indicates that P. vivax malaria during the first trimester of pregnancy represents a higher likelihood of subsequent poor pregnancy outcomes associated with marked placental histologic modification and angiogenic/inflammatory imbalance. Additionally, our findings support the idea that antibodies against PvMSP119 are not protective against poor pregnancy outcomes induced by P. vivax infections., Author summary Malaria during pregnancy is associated with adverse effects on the fetus and the newborn. As far as we know, no study has previously investigated in a single work, the link between Plasmodium vivax malaria in pregnancy and poor gestational outcomes, alteration of the newborn’s anthropometric profile, placental lesions, angiogenic and inflammatory factors, and humoral immunity against the parasite. For this purpose, we investigated the association between P. vivax malaria during pregnancy and newborn’s anthropometric profile, placental pathology, gestational outcomes, and the presence of IgG against P. vivax MSP119 that may confer protection against infection during pregnancy. We performed a large cohort study of malaria during pregnancy that analyzed data from mother-child pairs delivered between 2013 and 2015 in the Southwestern Brazilian Amazonian region. By evaluating data from 329 pregnancies, we found that P. vivax malaria during the first pregnancy trimester is significantly associated with the occurrence of preterm birth, low birth weight, and reduced newborn head circumference and body length. We also noted that P. vivax malaria in pregnancy promoted placental lesions and homeostasis imbalance, characterized by increased syncytial nuclear aggregates, fibrin deposition, and monocytes/leukocytes infiltrate, as well as imbalanced angiogenic factors, leptin, and cytokines. We observed that pregnant women with IgG against P. vivax MSP119 are not protected against poor pregnancy outcomes caused by P. vivax infections during pregnancy. Our observations improve our understanding of the disease and P. vivax burden during pregnancy, changing the current paradigm of the outcome of P. vivax malaria in pregnancy. That may represent a long-term severe consequence for the affected populations living in P. vivax-endemic regions. Our results also indicate that IgG against P. vivax MSP119 is not associated with protection from poor pregnancy outcomes, excluding this protein as a possible vaccination target that can prevent adverse outcomes caused by P. vivax infections during pregnancy.

Submitted by Maria Paula Simões (mpaulasimoes@ipcb.pt) on 2021-12-02T10:58:07Z No. of bitstreams: 1 PrunusFITO-livro GO de Fruticultura 2021.pdf: 1803113 bytes, checksum: 85b6893be551b148405a45917da18b29 (MD5) Approved for entry into archive by Maria Eduarda Pereira Rodrigues (erodrigues@ipcb.pt) on 2022-01-04T17:01:29Z (GMT) No. of bitstreams: 1 PrunusFITO-livro GO de Fruticultura 2021.pdf: 1803113 bytes, checksum: 85b6893be551b148405a45917da18b29 (MD5) Made available in DSpace on 2022-01-04T17:11:41Z (GMT). No. of bitstreams: 1 PrunusFITO-livro GO de Fruticultura 2021.pdf: 1803113 bytes, checksum: 85b6893be551b148405a45917da18b29 (MD5) Previous issue date: 2021 info:eu-repo/semantics/publishedVersion

Pregnancy-associated malaria is often associated with adverse pregnancy outcomes. Placental circulatory impairments are an intriguing and unsolved component of malaria pathophysiology. Here, we uncovered a Toll-like receptor 4 (TLR4)-TRIF-endothelin axis that controls trophoblast motility and is linked to fetal protection during Plasmodium infection. In a cohort of 401 pregnancies from northern Brazil, we found that infection during pregnancy reduced expression of endothelin receptor B in syncytiotrophoblasts, while endothelin expression was only affected during acute infection. We further show that quantitative expression of placental endothelin and endothelin receptor B proteins are differentially controlled by maternal and fetal TLR4 alleles. Using murine malaria models, we identified placental autonomous responses to malaria infection mediated by fetally encoded TLR4 that not only controlled placental endothelin gene expression but also correlated with fetal viability protection. In vitro assays showed that control of endothelin expression in fetal syncytiotrophoblasts exposed to Plasmodium-infected erythrocytes was dependent on TLR4 via the TRIF pathway but not MyD88 signaling. Time-lapse microscopy in syncytiotrophoblast primary cultures and cell invasion assays demonstrated that ablation of TLR4 or endothelin receptor blockade abrogates trophoblast collective motility and cell migration responses to infected erythrocytes. These results cohesively substantiate the hypothesis that fetal innate immune sensing, namely, the TRL4-TRIF pathway, exerts a fetal protective role during malaria infection by mediating syncytiotrophoblast vasoregulatory responses that counteract placental insufficiency.

The significant increase in world population and urbanisation has brought several important challenges, in particular regarding the sustainability, maintenance and planning of urban mobility. At the same time, the exponential increase of computing capability and of available sensor and location data have offered the potential for innovative solutions to these challenges. In this work, we focus on the challenge of traffic forecasting and review the recent development and application of graph neural networks (GNN) to this problem. GNNs are a class of deep learning methods that directly process the input as graph data. This leverages more directly the spatial dependencies of traffic data and makes use of the advantages of deep learning producing state-of-the-art results. We introduce and review the emerging topic of GNNs, including their most common variants, with a focus on its application to traffic forecasting. We address the different ways of modelling traffic forecasting as a (temporal) graph, the different approaches developed so far to combine the graph and temporal learning components, as well as current limitations and research opportunities.

IL-1 axis activation during placental malaria induces poor pregnancy outcomes that are obliterated after treatment with Anakinra., Placental malaria (PM) is associated with severe inflammation leading to abortion, preterm delivery, and intrauterine growth restriction. Innate immunity responses play critical roles, but the mechanisms underlying placental immunopathology are still unclear. Here, we investigated the role of inflammasome activation in PM by scrutinizing human placenta samples from an endemic area and ablating inflammasome components in a PM mouse model. The reduction in birth weight in babies from infected mothers is paralleled by increased placental expression of AIM2 and NLRP3 inflammasomes. Using genetic dissection, we reveal that inflammasome activation pathways are involved in the production and detrimental action of interleukin-1β (IL-1β) in the infected placenta. The IL-1R pharmacological antagonist Anakinra improved pregnancy outcomes by restoring fetal growth and reducing resorption in an experimental model. These findings unveil that IL-1β–mediated signaling is a determinant of PM pathogenesis, suggesting that IL-1R antagonists can improve clinical outcomes of malaria infection in pregnancy.

Submitted by Maria Paula Simões (mpaulasimoes@ipcb.pt) on 2020-04-06T16:06:09Z No. of bitstreams: 1 2020-Amaral et al. Época de floração pessegueiro.Atas de Hort 32.pdf: 2307617 bytes, checksum: 648604b0de6960220dfa6804c65910e6 (MD5) Approved for entry into archive by Maria Eduarda Pereira Rodrigues (erodrigues@ipcb.pt) on 2020-04-13T17:55:57Z (GMT) No. of bitstreams: 1 2020-Amaral et al. Época de floração pessegueiro.Atas de Hort 32.pdf: 2307617 bytes, checksum: 648604b0de6960220dfa6804c65910e6 (MD5) Made available in DSpace on 2020-04-13T17:59:55Z (GMT). No. of bitstreams: 1 2020-Amaral et al. Época de floração pessegueiro.Atas de Hort 32.pdf: 2307617 bytes, checksum: 648604b0de6960220dfa6804c65910e6 (MD5) Previous issue date: 2020 info:eu-repo/semantics/publishedVersion

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Submitted by Maria Paula Simões (mpaulasimoes@ipcb.pt) on 2020-09-28T14:28:50Z No. of bitstreams: 1 0-Condições climáticas e pessegueiro-ICEUBI2019-BookofProceedingsVol2_final.pdf: 1108352 bytes, checksum: 26dcbc6f93395951c2595b9206eeae3d (MD5) Approved for entry into archive by Maria Eduarda Pereira Rodrigues (erodrigues@ipcb.pt) on 2020-10-10T11:06:09Z (GMT) No. of bitstreams: 1 0-Condições climáticas e pessegueiro-ICEUBI2019-BookofProceedingsVol2_final.pdf: 1108352 bytes, checksum: 26dcbc6f93395951c2595b9206eeae3d (MD5) Made available in DSpace on 2020-10-10T11:10:59Z (GMT). No. of bitstreams: 1 0-Condições climáticas e pessegueiro-ICEUBI2019-BookofProceedingsVol2_final.pdf: 1108352 bytes, checksum: 26dcbc6f93395951c2595b9206eeae3d (MD5) Previous issue date: 2020 Agroi9 info:eu-repo/semantics/publishedVersion

High levels of the inflammatory molecule S100B protein have been identified in sera from several perinatal inflammatory conditions involving myelin damage and associated with an adverse prognosis or the emergence of sequelea. S100B is essential for oligodendrocyte (OL) differentiation and maturation, but it remains to be established if excessive levels of released S100B upon early brain injury are deleterious in the neurodevelopmental period. Here, we investigated this possibility by evaluating how elevated S100B affects oligodendrogenesis during this period. First, using primary cultures of OL we observed that damage-induced micromolar levels of S100B impair OL differentiation process. S100B elevated concentrations reduced both transition from immature NG2+ oligodendrocyte precursor cells (OPC) to mature MBP+ OL, and morphological maturation of differentiated OL. Interestingly, these effects were abolished by the use of receptor for advanced glycation end-products (RAGE) antagonist FPS-ZM1, suggesting an involvement of the S100B-RAGE axis on oligodendrogenesis impairment. Next, we used organotypic cerebellar slice cultures to explore the role of S100B in a more complex multicellular environment. Also in this model excessive S100B levels impaired oligodendrogenesis resulting in a reduced myelination. Further, elevated S100B levels compromised neuronal and synaptic integrity, while inducing astrogliosis, nuclear factor (NF)-kB activation and inflammation. Again, the FPS-ZM1 co-treatment prevented S100B-induced damaging effects. Overall, our results indicate that persistently elevated S100B levels have deleterious effects during the neurodevelopmental period through RAGE-dependent processes. Thus, targeting high S100B levels and/or S100B-RAGE interaction may constitute good therapeutic strategies to reduce brain injury, including deficits in neuronal architecture, synaptogenesis and myelination associated with perinatal inflammatory conditions.

Road infrastructure asset management is rapidly transforming into a digital environment where data accessibility, effective integration and collaboration and accessibility from different sources and assets are key. However, current asset management processes are not yet fully integrated or linked, and there are incompatibilities between various systems and platforms that limit the ability to integrate asset management with BIM. The CoDEC project has sought to understand the current status of information management for assets, including inventory, condition and new data sources such as sensors and scanning systems, to identify the challenges and needs for linking and integrating different data sets to support effective asset management. As a result, CoDEC has developed a data dictionary framework to help link/integrate static and dynamic data for the “key” infrastructure assets (road pavements, bridges, tunnels). This will enable BIM and Asset Management Systems (AMS) to exchange data and help optimise and integrate data management across systems and throughout the different asset lifecycle phases, from build to operation. This work will be followed up with three pilot projects to demonstrate the feasibility of integrating asset data from various sources through linked data/semantic web technology to build the connection between AMS and BIM platforms.

The production and transport of liquid and gaseous hydrocarbons have always been the object of studies to improve technologies and procedures, as they involve large volumes and high-value goods. There are several procedures, rules and regulations applied to the measurement of fluid flow, but its applicability may involve significant operating costs. The balance between requirements and costs led to the use of gauge pressure transmitters instead of absolute pressure gauges and assuming a constant atmospheric pressure value for parameterization of compensation algorithms. This solution simplifies the calibration process but can potentially impact measurement uncertainties because atmospheric pressure is not constant. This work quantifies these impacts and concludes that, for gas systems operating below 2000 kPa, the use of absolute pressure transmitters or the incorporation of in-line atmospheric pressure gauges is recommended. Above this value, the effects of atmospheric pressure variation do not have as much impact, but even in these cases the final uncertainty estimate of the measured gas volume must consider this source of additional uncertainties.