Assessment of a novel Cu (II) complex as a potential anticancer agent

Widely used in cancer treatment, chemotherapy still faces hindering challenges, ranging from severe induced toxicity to drug resistance acquisition. As means to overcome these setbacks, newly synthetized compounds have recently come into play with the basis of improved pharmacokinetic/pharmacodynamic properties. With this mind-set, this project aimed towards the antiproliferative potential characterization of a group of metallic compounds. Additionally the incorporation of the compounds within a nanoformulation and within new combination strategies with commercial chemotherapeutic drugs was also envisaged. Cell viability assays presented copper (II) compound (K4) as the most promising, presenting an IC50 of 6.10 μM and 19.09 μM for HCT116 and A549 cell line respectively. Exposure in fibroblasts revealed a 9.18 μM IC50. Hoechst staining assays further revealed the compound’s predisposition to induce chromatin condensation and nuclear fragmentation in HCT116 upon exposure to K4 which was later demonstrated by flow cytometry and annexin V-FITC/propidium iodide double staining analysis (under 50 % cell death induction). The compound further revealed the ability to interact with major macromolecules such as DNA (Kb = 2.17x105 M-1), inducing structural brakes and retardation, and further affecting cell cycle progression revealing delay in S-phase. Moreover BSA interactions were also visible however not conclusive. Proteome profiling revealed overexpression of proteins involved in metabolic activity and underexpression of proteins involved in apoptosis thus corroborating Hoechst and apoptosis flow cytometry data. K4 nanoformulation suffered from several hindrances and was ill succeeded in part due to K4’s poor solubility in aqueous buffers. Other approaches were considered in this regard. Combined chemotherapy assays revealed high cytotoxicity for afatinib and lapatinib strategies. Lapatinib and K4 proteome profiling further revealed high apoptosis rates, high metabolic activity and activation of redundant proteins as part of compensatory mechanisms.

Predição precoce de risco de Pré-eclâmpsia na doença hipertensiva e diabetes na gravidez: Papel de fatores angiogénicos

RESUMO: A pré-eclâmpsia tem elevada morbi-mortalidade materna e perinatal. A sua etiologia multi-fatorial tem sido objeto de investigação, não sendo ainda totalmente conhecida. Não se conhece também a razão da diferente suscetibilidade individual e das diferentes expressões da doença. A hipertensão crónica e a diabetes são fatores de risco reconhecidos, e o adiamento da maternidade contribui para que estas duas patologias sejam atualmente mais prevalentes entre as mulheres grávidas. Uma vez que o seu quadro fisiopatológico precede em meses o quadro clínico, tem-se investigado a possibilidade de serem encontrados marcadores precoces e indicadores de risco. Em Portugal, os estudos relativos à hipertensão na gravidez são escassos, bem como a investigação sobre fatores de risco e marcadores para a mesma. No sentido de avaliar possíveis marcadores de risco para o desenvolvimento de préeclâmpsia ou complicações hipertensivas foi colhida, para esta dissertação, uma amostra de 1215 mulheres que frequentaram a consulta de Hipertensão ou de Diabetes na gravidez de um centro terciário, entre 2004 e 2013. Optou-se pela realização de três estudos independentes, abrangendo os dois primeiros um leque temporal de 9 e de 2 anos respetivamente. O primeiro, centrado na hipertensão, pesquisou, em 521 mulheres com hipertensão na presente ou em anterior gravidez, fatores de risco capazes de influenciar a progressão para pré-eclâmpsia. O segundo, direcionado para a diabetes gestacional, considerou uma amostra de 334 grávidas, parte das quais tinha também hipertensão crónica e procurou identificar fatores que contribuíram para o aparecimento de complicações hipertensivas. O terceiro estudo, realizado em 2012 e 2013, em três coortes de grávidas com hipertensão crónica, com diabetes gestacional, e sem estas patologias - procurou avaliar no 1º trimestre o comportamento de dois marcadores placentares obtidos no 1º trimestre - proteína plasmática A associada à gravidez (PAPP-A) e o fator de crescimento placentar (PlGF) - e o seu papel, quer como bio-marcadores isolados, quer em associação aos fatores de risco encontrados nos anteriores estudos, na construção de um modelo preditivo de préeclâmpsia. No primeiro estudo, a nuliparidade, a hipertensão gestacional, a fluxometria das artérias uterinas com IP superiores ao P95 entre as 20-22 semanas e a existência de restrição de crescimento fetal, foram os fatores que contribuíram para a construção de um modelo preditivo de pré-eclâmpsia. No segundo estudo, a coexistência de diabetes e hipertensão crónica agravou o prognóstico, associando-se as complicações hipertensivas à multiparidade, obesidade, idade materna e etnia negra. No terceiro estudo verificou-se uma redução da PlGf e da PAPP-A no 1º trimestre nas duas primeiras coortes, comparativamente à coorte sem patologia; na análise separada de cada coorte, quando se verificaram complicações hipertensivas ou pré-eclâmpsia, as concentrações de PlGf e PAPP-A também foram inferiores. Contudo, na elaboração de um modelo preditivo de pré-eclâmpsia, em conjunto com marcadores encontrados, apenas a PlGf pode ser integrada no modelo preditivo, o que se verificou na coorte com hipertensão crónica. Os marcadores bioquímicos em estudo tiveram valores inferiores nas coortes com patologia hipertensiva, demonstrando uma deficiente produção destas proteínas placentares nestas situações, podendo ser importante a sua pesquisa. Contudo, neste estudo, apenas na coorte de hipertensão crónica a PlGf teve participação como fator de risco, na construção de um modelo preditivo de pré-eclâmpsia.--------------------------------------------------------------------------------------------------ABSTRACT: Preeclampsia is associated with a great maternal and perinatal morbimortality. Its multifactorial etiology has been under investigation and is still insufficiently understood. The reason why there are differences in individual susceptibility and differences in expressions of the disease is still unknown. Chronic hypertension and diabetes are known risk factors for preeclampsia and maternity delay contributes to the great prevalence of these pathologies among pregnant women. As the physiopathological signs antedate by months the clinical course of the disease, early risk factors and biological markers are object of clinical research. In Portugal, scarce clinical studies were devoted to hypertension in pregnancy and to risk factors and markers of this pathology. This dissertation inquires 1215 pregnant women who were treated for hypertension or diabetes in a tertiary care center between 2004 and 2013, in order to find risk markers for hypertensive complications or preeclampsia. We conducted three independent studies for this purpose. In the first one we investigated which risk factors could influence the progression to preeclampsia in 521 pregnant women with present or past history of hypertension. The second one was conducted to find what factors were associated to hypertensive complications, with a sample of 334 pregnant women with gestational diabetes, some also with chronic hypertension, addressing the identification of the factors contributing to hypertensive complications. The third study was conducted between 2012 and 2013 with three cohorts of pregnant women, with chronic hypertension, gestational diabetes, and in the third one, pregnant women had a low risk pregnancy. The objective of the study was to evaluate the behavior of two placental markers – PAPP-A and PlGf – obtained in the first trimester, and the role of these markers as isolated biomarkers or in association with other risk factors, in order to define a predictive model of early preeclampsia. In the first study, nuliparity, gestational hypertension, uterine arteries doppler with PI above P95 between 20-22 weeks of gestation and the presence of fetal growth restriction were the markers involved in a predictive model for preeclampsia. In the second study the cohort with the coexistence of diabetes and hypertension had registered worse result and hypertensive complications were associated to multiparity, obesity, maternal age and black ethnicity. In the third study there was a reduction of the PlGf and a PAPP-A concentration for the first trimester in the two first cohorts comparatively to the low risk cohort; the separate analysis of each cohort showed that plGf and PAPP-A concentrations were reduced when hypertensive complications appeared. However, when trying to find a preeclampsia predictive model, only plGf gave significant results for being considered in the model and this was only possible in the chronic hypertension cohort. The biochemical markers investigated in this study were reduced in the cohorts when high blood pressure complications occurred, showing a defective production of these placenta proteins, and suggesting that they should be investigated as first trimester biomarkers. Nevertheless, for this research, in the cohort of chronic hypertension only PlGf had a significant result, when multivariate analysis of all the risk factors was considered for the construction of a preeclampsia predictive model.

Development of sandwich panels of customized functionalities for the rehabilitation of the built patrimony

Considering that the future of the construction sector in most European countries will mainly lie in the renovation of the existing building stock, in the next coming years thousands of energy inefficient buildings will need renovation to force EU member states to reach the EU 2020 targets and implement the Energy Performance of Buildings Directive (EPBD). Seeing the actual crisis in the construction sector as an opportunity, this work aims to develop a concept for prefabricated customizable sandwich panels for the multifunctional renovation of buildings, focusing also on technological innovation. More than a conventional solution, this proposal aims to combine sustainable and recycled building materials, available technologies and systems with advanced design and manufacturing tools within an integrated and mass-customizable approach of advanced building renovation prefabricated solutions. The adoption of these new proposed solutions would improve the living standards of the inhabitants of our cities, reducing energy inefficiency and other existing construction/renovation problems, while enabling some advanced features like the incorporation of technical modules that could even monitor the building performance during its full lifetime and the living conditions of its occupants.

An agent-based model to assess the attractiveness of industrial estates

This article describes the main approaches adopted in a study focused on planning industrial estates on a sub-regional scale. The study was supported by an agent-based model, using firms as agents to assess the attractiveness of industrial estates. The simulation was made by the NetLogo toolkit and the environment represents a geographical space. Three scenarios and four hypotheses were used in the simulation to test the impact of different policies on the attractiveness of industrial estates. Policies were distinguished by the level of municipal coordination at which they were implemented and by the type of intervention. In the model, the attractiveness of industrial estates was based on the level of facilities, amenities, accessibility and on the price of land in each industrial estate. Firms are able to move and relocate whenever they find an attractive estate. The relocating firms were selected by their size, location and distance to an industrial estate. Results show that a coordinated policy among municipalities is the most efficient policy to promote advanced-qualified estates. In these scenarios, it was observed that more industrial estates became attractive, more firms were relocated and more vacant lots were occupied. Furthermore, the results also indicate that the promotion of widespread industrial estates with poor-quality infrastructures and amenities is an inefficient policy to attract firms.

Deploying public surface transit to forward messages in DTN

Delay Tolerant Network (DTN) is a communication architecture enabling connectivity in a topology with unregular end-to-end network connection. DTN enables communication in environments with cross-connectivity, large delays and delivery time variations, and a high error rate. DTN can be used in vehicular networks where public transport get involved. This research aims to analyze the role of public transit as a DTN routing infrastructure. The impact of using public transit as a relay router is investigated by referencing the network performance, defined by its delivery ratio, average delay and overhead. The results show that public transit can be used as a backbone for DTN in an urban scenario using existing protocols. This opens insights for future researches on routing algorithm and protocol design.

The role of ascorbate peroxidase, guaiacol peroxidase, and polysaccharides in cassava (Manihot esculenta Crantz) roots under postharvest physiological deterioration

Abstract This study aimed to investigate the role of ascorbate peroxidase (APX), guaiacol peroxidase (GPX), polysaccharides, and protein contents associated with the early events of postharvest physiological deterioration (PPD) in cassava roots. Increases in APX and GPX activity, as well as total protein contents occurred from 3 to 5 days of storage and were correlated with the delay of PPD. Cassava samples stained with periodic acid-Schiff (PAS) highlighted the presence of starch and cellulose. Degradation of starch granules during PPD was also detected. Slight metachromatic reaction with toluidine blue is indicative of increasing of acidic polysaccharides and may play an important role in PPD delay. Principal component analysis (PCA) classified samples according to their levels of enzymatic activity based on the decision tree model which showed GPX and total protein amounts to be correlated with PPD. The Oriental (ORI) cultivar was more susceptible to PPD.

Generating timed trajectories foran autonomous robot

Tese de Doutoramento Programa Doutoral em Engenharia Electrónica e Computadores

Triagem universal de alunos em risco de apresentarem dificuldades de aprendizagem específicas na leitura: um estudo quantitativo no 3º ano do 1º Ciclo do Ensino Básico

Doutoramento em Estudos da Criança (área de especialização em Educação Especial).

Attachment style impacts behavior and early oculomotor response to positive, but not negative, pictures

The present study investigated whether oculomotor behavior is influenced by attachment styles. The Relationship Scales Questionnaire was used to assess attachment styles of forty-eight voluntary university students and to classify them into attachment groups (secure, preoccupied, fearful, and dismissing). Eye-tracking was recorded while participants engaged in a 3-seconds free visual exploration of stimuli presenting either a positive or a negative picture together with a neutral picture, all depicting social interactions. The task consisted in identifying whether the two pictures depicted the same emotion. Results showed that the processing of negative pictures was impermeable to attachment style, while the processing of positive pictures was significantly influenced by individual differences in insecure attachment. The groups highly avoidant regarding to attachment (dismissing and fearful) showed reduced accuracy, suggesting a higher threshold for recognizing positive emotions compared to the secure group. The groups with higher attachment anxiety (preoccupied and fearful) showed differences in automatic capture of attention, in particular an increased delay preceding the first fixation to a picture of positive emotional valence. Despite lenient statistical thresholds induced by the limited sample size of some groups (p < 0.05 uncorrected for multiple comparisons), the current findings suggest that the processing of positive emotions is affected by attachment styles. These results are discussed within a broader evolutionary framework.

Effect of the acoustic impedance in ultrasonic emitter transducers using digital modulations

In an underwater environment it is difficult to implement solutions for wireless communications. The existing technologies using electromagnetic waves or lasers are not very efficient due to the large attenuation in the aquatic environment. Ultrasound reveals a lower attenuation, and thus has been used in underwater long-distance communications. The much slower speed of acoustic propagation in water (about 1500 m/s) compared with that of electromagnetic and optical waves, is another limiting factor for efficient communication and networking. For high data-rates and real-time applications it is necessary to use frequencies in the MHz range, allowing communication distances of hundreds of meters with a delay of milliseconds. To achieve this goal, it is necessary to develop ultrasound transducers able to work at high frequencies and wideband, with suitable responses to digital modulations. This work shows how the acoustic impedance influences the performance of an ultrasonic emitter transducer when digital modulations are used and operating at frequencies between 100 kHz and 1 MHz. The study includes a Finite Element Method (FEM) and a MATLAB/Simulink simulation with an experimental validation to evaluate two types of piezoelectric materials: one based on ceramics (high acoustic impedance) with a resonance design and the other based in polymer (low acoustic impedance) designed to optimize the performance when digital modulations are used. The transducers performance for Binary Amplitude Shift Keying (BASK), On-Off Keying (OOK), Binary Phase Shift Keying (BPSK) and Binary Frequency Shift Keying (BFSK) modulations with a 1 MHz carrier at 125 kbps baud rate are compared.

A soft computing approach to kidney diseases evaluation

Kidney renal failure means that one’s kidney have unexpectedly stopped functioning, i.e., once chronic disease is exposed, the presence or degree of kidney dysfunction and its progression must be assessed, and the underlying syndrome has to be diagnosed. Although the patient’s history and physical examination may denote good practice, some key information has to be obtained from valuation of the glomerular filtration rate, and the analysis of serum biomarkers. Indeed, chronic kidney sickness depicts anomalous kidney function and/or its makeup, i.e., there is evidence that treatment may avoid or delay its progression, either by reducing and prevent the development of some associated complications, namely hypertension, obesity, diabetes mellitus, and cardiovascular complications. Acute kidney injury appears abruptly, with a rapid deterioration of the renal function, but is often reversible if it is recognized early and treated promptly. In both situations, i.e., acute kidney injury and chronic kidney disease, an early intervention can significantly improve the prognosis.The assessment of these pathologies is therefore mandatory, although it is hard to do it with traditional methodologies and existing tools for problem solving. Hence, in this work, we will focus on the development of a hybrid decision support system, in terms of its knowledge representation and reasoning procedures based on Logic Programming, that will allow one to consider incomplete, unknown, and even contradictory information, complemented with an approach to computing centered on Artificial Neural Networks, in order to weigh the Degree-of-Confidence that one has on such a happening. The present study involved 558 patients with an age average of 51.7 years and the chronic kidney disease was observed in 175 cases. The dataset comprise twenty four variables, grouped into five main categories. The proposed model showed a good performance in the diagnosis of chronic kidney disease, since the sensitivity and the specificity exhibited values range between 93.1 and 94.9 and 91.9–94.2 %, respectively.

An assessment of chronic kidney diseases

Kidney renal failure means that one’s kidney have unexpectedlystoppedfunctioning,i.e.,oncechronicdiseaseis exposed, the presence or degree of kidney dysfunction and its progression must be assessed, and the underlying syndrome has to be diagnosed. Although the patient’s history and physical examination may denote good practice, some key information has to be obtained from valuation of the glomerular filtration rate, and the analysis of serum biomarkers. Indeed, chronic kidney sickness depicts anomalous kidney function and/or its makeup, i.e., there is evidence that treatment may avoid or delay its progression, either by reducing and prevent the development of some associated complications, namely hypertension, obesity, diabetes mellitus, and cardiovascular complications. Acute kidney injury appears abruptly, with a rapiddeteriorationoftherenalfunction,butisoftenreversible if it is recognized early and treated promptly. In both situations, i.e., acute kidney injury and chronic kidney disease, an early intervention can significantly improve the prognosis. The assessment of these pathologies is therefore mandatory, although it is hard to do it with traditional methodologies and existing tools for problem solving. Hence, in this work, we will focus on the development of a hybrid decision support system, in terms of its knowledge representation and reasoning procedures based on Logic Programming, that will allow onetoconsiderincomplete,unknown,and evencontradictory information, complemented with an approach to computing centered on Artificial Neural Networks, in order to weigh the Degree-of-Confidence that one has on such a happening. The present study involved 558 patients with an age average of 51.7 years and the chronic kidney disease was observed in 175 cases. The dataset comprise twenty four variables, grouped into five main categories. The proposed model showed a good performance in the diagnosis of chronic kidney disease, since the sensitivity and the specificity exhibited values range between 93.1 and 94.9 and 91.9–94.2 %, respectively.

Desenvolvimento de um concentrador solar com sistema de seguimento

Dissertação de mestrado em Engenharia Mecânica

Evaluating balance, stability and gait symmetry of stroke patients using kinematic and dynamic gait lab data

Dissertação de mestrado integrado em Engenharia Biomédica

Otimização do internamento no Hospital de Braga usando metodologia Kaizen

Dissertação de mestrado integrado em Engenharia Biomédica (área de especialização em Engenharia Clínica)