Biology-guided algorithms:Improved cardiovascular risk prediction and biomarker discovery

Medical research has seen a stark increase in the amount of available data. The sheer volume and complexity of measured variables challenge the use of traditional statistical methods and are beyond the ability of any human to comprehend. Solving this problem demands powerful models capable of capturing the variable interactions and how those are non-linearly related to the condition under study. In this thesis, we first use Machine Learning (ML) methods to achieve better cardiovascular risk prediction/disease biomarker identification and then describe novel bio-inspired algorithms to solve some of the challenges. On the clinical side, we demonstrate how combining targeted plasma proteomics with ML models outperforms traditional clinical risk factors in predicting first-time acute myocardial infarction as well as recurrent atherosclerotic cardiovascular disease. We then shed some light on the pathophysiological pathways involved in heart failure development using a multi-domain ML model. To improve prediction, we develop a novel graph kernel that incorporates protein-protein interaction information, and suggest a manifold mixing algorithm to increase inter-domain information flow in multi-domain models. Finally, we address global model interpretability to uncover the most important variables governing the prediction. Permutation importance is an intuitive and scalable method commonly used in practice, but it is biased in the presence of covariates. We propose a novel framework to disentangle the shared information between covariates, making permutation importance competitive against methodologies where all marginal contributions of a feature are considered, such as SHAP

Marketing persona formulation and content strategy analysis for PHC Software, SA

JEL Classification System: M15; M31The customer’s role has grown in importance through the years. In the current technological and information age, it is crucial for companies to understand the customer’s needs and motives, as well as ways to attract new customers (Derunova and Semenov, 2013). In this paper, the persona tool is created for each of the PHC Software SaaS Products, PHC Business FX, PHC Billing FX and the PHC POS FX. Personas are fictitious representations embodying behaviours, pain points, goals and characteristics of real customers or target audiences (Junior and Filgueiras, 2005) that can be used as a tool to better understand customers and from there develop strategies. After the analysis of the main target audiences for these products, this paper then, elaborates an analysis of the correspondent content marketing strategy. By analysing the current content and its communication channels, this paper aims to find gaps in the current strategy with the use of the persona’s tool and provide recommendations on how the company might minimize its distance to the customers and further improve its relationship.O papel do consumidor tem vindo a ganhar importância ao longo dos anos. No atual panorama tecnológico e informacional, compreender as atuais necessidades e motivações do consumidor, assim como, novas formas de atrair novos clientes é determinante para as empresas (Derunova e Semenov, 2013). Neste trabalho, a ferramenta ‘Persona’ é criada para cada um dos produtos SaaS da PHC Software: PHC Business FX, PHC Billing FX e o PHC POS FX. Personas são representações ficcionais que incorporam os comportamentos, adversidades, objetivos e características de consumidores reais ou públicos alvo (Junior e Filgueiras, 2005), que podem ser utilizados como uma ferramenta para melhor compreender os consumidores e a partir dai desenvolver estratégias. Após a análise do público-alvo destes produtos, é elaborada uma analise à correspondente estratégia de conteúdo da empresa. Ao analisar o conteúdo atual e os meios de comunicação utilizados, este trabalho tem por objetivo encontrar lacunas na atual estratégia, através do uso de personas, e fornecer recomendações de como a empresa poderá minimizar a distância e otimizar as relações para com os atuais consumidores e público-alvo

Olive mill wastewater: a suitable medium for lipase production by yeasts

Fundação para a Ciência e a Tecnologia (FCT

Comparison of batch and fed-batch lipase production from olive mill wastewater by Yarrowia lipolytica and Candida cilindracea

Olive mill wastewater (OMW) is a liquid waste that results in large amounts from the olive oil manufacturing industry. The quality and quantity of OMW constituents are dependent of many factors, such as olives type and maturity, climatic conditions and region of origin, cultivation methods, and technology used for oil extraction1. From the 3-phases centrifugation process around 1.6 cubic meters of OMW per ton of olives processed are generated. These liquid wastes present an environmental problem and many solutions have been proposed for it, such as its use as culture medium for different lipolytic yeast strains (Gonçalves et al, 2009; Lopes et al, 2009). The aim of this work is the comparison of batch and fed-batch mode of operation for the lipase production and the OMW degradation by two strains, Yarrowia lipolytica W29 and Candida cylindracea CBS 7869. OMW collected from 3-phase continuous olive mills were used (COD of 30 to 261 g/L). OMW used without dilution was supplemented with ammonium chloride and yeast extract proportionally to the COD values. Batch and fed-batch cultures were conducted in a fermenter of 2 L of capacity at pH 7.2, 500 rpm, with constant or variable aeration rate for batch or fed-batch operation, respectively. Batch operation was more adequate to lipase production than fed-batch for both strains but the difference was more significant for Candida cylindracea that revealed to be the most efficient strain for lipase production. However, the final media of the fed-batch cultures presented lower values of COD and sugars indicating a higher level of organic matter degradation

Special issue on Big Data and digital transformation

[Excerpt] The world we live in is more and more of a digital nature. Nowadays, more than ever, we are witnessing a fundamental trend - technological innovations are continuously appearing and rapidly made available to everyone. These have a huge impact on people, who, for the most, easily adhere to and use them, not only in their personal lives, but also at work. At the enterprise level, easy access to global markets and new ways of working and conducting business becomes possible due to technological innovations, leading to innovative business models. Similarly, governments, municipalities and public organizations are developing new ways to reach the citizens and interact with them, in manners that were impossible to foresee a few years ago. All these changes, fueled by the continuous stream of technological innovations, are widely known as Digital Transformation. [...]- (undefined

Application of non-conventional yeasts for olive mill wastewaters valorization

The olive oil consumed worldwide is mainly produced in Mediterranean countries. Portugal is one of the ten major producers. Pressing and continuous (three- or two-phase) are the most important extraction processes used in olive oil production. A large amount of a liquid waste, called Olive Mill Wastewater (OMW), is generated to a three-phase decanter extraction process. This effluent causes serious environmental problems due to its high lipid content, chemical oxygen demand (COD) and dark colour. Moreover the phytotoxicity of the OMW can be attributed to the phenolic compounds [1]. In fact, the olive pulp is very rich in phenolic compounds and approximately 53 % is lost in the OMW [2]. Due to the seasonality of olive oil production the OMW treatment process should be flexible enough to operate in a non-continuous mode. Besides, the olive mills are small enterprises, scattered around the olive production areas, making individual on-site treatment options unaffordable [3]. The OMW use as a resource to be valorised is an approach of great interest. It is widely posited that several lipolytic yeast species are able to grow in OMW media, consume the organic material and, simultaneously, produce biomass and other valuable products. The aim of the present study is the valorisation of distinct OMW by producing high-value compounds (such as biomass and lipase), while degrading this waste. The OMW were collected from different olive mills from the north of Portugal and 6 yeasts of Candida rugosa, Candida cylindracea and Yarrowia lipolytica were used. All strains were capable to grow on OMW based medium, without dilution, despite the low effectiveness of phenolic compounds degradation. Furthermore the yeast cells were able to consume almost all the sugars present in the media and significantly reduce COD. The process conditions were optimized in order to achieve the highest values of lipase activity. The strains were also selected according to its efficiency, and three of six strains were chosen: C. cylindracea CBS 7869, Y. lipolytica W29 (ATCC 20460) and C. rugosa CBS 2275. [1] Lanciotti, R. et al., Bioresour. Technol. (2005) 96:317 [2] Rodis, P.S. et al., J. Agric. Food. Chem. (2002) 50:596 [3] Paraskeva, P., Diamadopoulos, E., J. Chem. Technol. Biotechnol. (2006) 81:1475.Fundação para a Ciência e a Tecnologia (FCT) - SFRH/BD/27915/200

High-quality biodiesel production from Yarrowia lipolytica NCYC 2904 bio-oil

Due to the global increase in energy demands, the depletion of fossil fuel reserves, and the increase in environmental pollution, upsurges the need to create renewable and environmentally friendly energy. Biodiesel, one of the most attractive alternatives for the replacement of conventional fossil fuels, can be produced from bio-oil accumulated by oleaginous yeast. The use of low-cost feedstocks for bio-oil production contributes to reducing global costs and enables the development of more sustainable processes. Thus, bio-oil production by Yarrowia lipolytica NCYC 2904 from crude glycerol (a by-product of the biodiesel industry) and volatile fatty acids (intermediates in the anaerobic fermentation of food wastes) was studied in a lab-scale stirred tank bioreactor using fed-batch and two-stage batch operation modes. The fed-batch culture with a crude glycerol feeding rate of 3.12 mL·h-1, followed by the addition of 18 g·L-1 VFAs mixture, was the best strategy to obtain the highest bio-oil production (6.1 g·L-1). Bio-oil of Y. lipolytica, rich in oleic acid, was successfully converted into biodiesel, which meets the criteria of the international biodiesel standards EN 14214 and is similar to biodiesel produced from vegetable oils. This demonstrates the potential of Y. lipolytica to convert low-cost substrates into feedstocks for high-quality biodiesel production, according to the biorefinery and bioeconomy circular guidelines.info:eu-repo/semantics/publishedVersio

Enhancing microbial lipids synthesis for biodiesel production by Y. lipolytica W29 from volatile fatty acids: two-stage batch strategies

Microbial lipids produced by Y. lipolytica have the potential to be used as feedstock for the biodiesel industry, but the high costs of pure substrates used for its production are limiting the potential of this application. Volatile fatty acids (VFAs), obtained in anaerobic fermentation of organic wastes, are inexpensive carbon sources for the cost-effective production of microbial lipids. In this work, two-stage batch cultures were tested as a strategy to improve lipids production by Y. lipolytica W29. The process consists of a first growth phase in glucose or glycerol, followed by a lipogenic phase in VFAs medium composed of a mixture of acetate, propionate, and butyrate. The addition of three pulses of 6 g·L−1 VFAs mixture, or a single pulse of 18 g·L−1 VFAs mixture, in the lipogenic phase boosted microbial lipids production (23–25%, w/w) and prevented lipids mobilization. Microbial lipids synthesized in such conditions are mainly composed of oleic acid (54%) with an unsaturated/saturated fraction above 78%. The main properties of biodiesel produced from Y. lipolytica W29 lipids are within the ranges of the EU biodiesel standard EN 14214.This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UIDB/04469/2020 unit and Doctoral grant (SFRH/BD/129592/2017).info:eu-repo/semantics/publishedVersio

Biobaterias de nanofibras celulósicas usando glucose como eletrólito para aplicações médicas

Com o avanço da tecnologia inerente aos equipamentos médicos implantáveis, caracterís-ticas como o tamanho, a independência energética e a flexibilidade têm sido melhoradas no sen-tido de promover uma melhor adaptação do dispositivo ao paciente. Este trabalho teve como principal objetivo criar uma biobateria capaz de gerar energia atra-vés da degradação da glucose presente no sangue, recorrendo principalmente a estruturas po-liméricas de baixo custo. Para a construção da biobateria é necessário um separador, dois elétro-dos (um ânodo e um cátodo) e o eletrólito. ` O separador da biobateria foi produzido através da eletrofiação de uma solução de acetato de celulose (AC) tendo-se obtido uma membrana porosa e flexível. De seguida, foi desenvolvido e otimizado um processo de revestimento por fase de vapor de poli(3,4-etilenodioxitiofeno) (PE-DOT), um polímero condutor, na superfície das fibras de acetato de celulose formando um dos elétrodos do dispositivo. Durante este processo, vários parâmetros como a concentração de agente oxidante e tempo de reação, foram estudados de modo a otimizar o revestimento e me-lhorar a condutividade elétrica das membranas sem comprometer a sua estrutura. Assim, con-clui-se que utilizando uma concentração de 40 g/L e um tempo de reação de 2 horas, obtiveram-se membranas de AC/PEDOT com valores médios de condutividade de 6 S/cm. Por fim, uma biobateria composta pelo elétrodo de PEDOT, uma membrana de AC (como separador) e um elétrodo comercial de ouro foi testada na presença de uma solução salina com diferentes concentrações de glucose. Este dispositivo, apresentou uma resposta elétrica distinta para cada uma das concentrações de glucose testadas atingindo-se um valor máximo de densi-dade de corrente de 4 mA/cm2 para uma concentração de glucose de 2 g/L. Desta forma, verifica-se que a biobateria estudada apresenta um elevado potencial para a alimentação de dispositivos médicos implantáveis e deteção dos níveis de glucose