Monotherapy and combined therapy of new potential antitumor compounds: antiproliferative activities and biological targets

Review article Martins, P., Marques, M., Coito, L., Pombeiro, A.J.L., Baptista, P.V., Fernandes, A.R. 2014. Organometallic Compounds in Cancer Therapy: Past Lessons and Future Directions. Anti-cancer Agents in Medicinal Chemistry 14. PMID: 25173559

Earthen plasters: the potential of the clayey soils of barrocal region in Algarve

Due to their high adsorption capacity of water vapor, earthen plasters can act as a moisture buffer, contributing to balance the relative humidity of the indoor environment of buildings. As a consequence of this capacity earthen plasters may also contribute to the perception of thermal comfort, since a high relative humidity increases the thermal conductivity of air and restricts skin evaporation, increasing the discomfort associated with the perception of heat or cold. Simultaneously, earthen plasters may also contribute to the indoor air quality. In one hand, by mitigating health problems of the respiratory system associated with indoor environment with high relative humidity, in which increases the risk of development of microorganisms usually responsible for infections, allergies or asthma. In the other hand, by mitigating the probability of inflammation of the respiratory system airways associated to exceedingly dry indoor environments. Therefore it also becomes expectable that earthen plasters may contribute for reducing the needs for air conditioning and mechanical ventilation in buildings and, thereby, also allowing the reduction of the associated energy consumption. The «Barrocal» region, located in the sedimentary basin of Algarve, South Portugal, presents geomorphological characteristics that promote the occurrence of soils with a clay mineralogy dominated by illite, which is a clay mineral characterized by a high adsorption capacity of water vapor and low expansibility. This fact turns expectable that these soils have a high potential for interior plastering. In order to evaluate this potential four mortars were formulated with an increasing content of clayey soil extracted from a selected clay quarry from «Barrocal» region. The results from the preliminary characterization campaign confirmed the reduced linear shrinkage of these mortars, as well as their high adsorption-desorption capacity, that is positively correlated with the content of clayey soil present in mortar formulation. However, the mechanical tests showed that the mechanical resistance of these mortars should be improved, for instance through the addition of natural fibers for reinforcement, which will be investigated in future research. This research contributed to increase certainty regarding the potential of clayey soils of the «Barrocal» sub-region of Algarve to produce mortars suitable for eco-efficient interior plastering.

Evaporation from porous building materials and its cooling potential

Evaporative cooling is a traditional strategy to improve summer comfort, which has gained renewed relevance in the context of the transition to a greener economy. Here, the potential for evaporative cooling of two common porous building materials, natural stone and ceramic brick, was evaluated. The work has relevance also to the protection of built heritage becauseevaporation underlies the problems of dampness and salt crystallization, which are so harmful and frequent in this heritage. It was observed that the drying rate of the materials is, in some cases, higher than the evaporation rate of a free water surface. Surface area measurements by a three-dimensional optical technique suggested, as probable cause of this behavior, that surface irregularity gives rise to a large effective surface of evaporation in the material. Surface temperature measurements by infrared were performed afterward during evaporation experiments outside during a hot summer day in Lisbon. Their results indicate that ordinary building materials can be very efficient evaporative media and, thus, may help in achieving higher energy efficiency while maintaining a simultaneous constructive or architectural function.

Groundwater quality, vulnerability and potential assessment in Kobo Valley development project, Ethiopia

This study deals with investigating the groundwater quality for irrigation purpose, the vulnerability of the aquifer system to pollution and also the aquifer potential for sustainable water resources development in Kobo Valley development project. The groundwater quality is evaluated up on predicting the best possible distribution of hydrogeochemicals using geostatistical method and comparing them with the water quality guidelines given for the purpose of irrigation. The hydro geochemical parameters considered are SAR, EC, TDS, Cl-, Na+, Ca++, SO4 2- and HCO3 -. The spatial variability map reveals that these parameters falls under safe, moderate and severe or increasing problems. In order to present it clearly, the aggregated Water Quality Index (WQI) map is constructed using Weighted Arithmetic Mean method. It is found that Kobo-Gerbi sub basin is suffered from bad water quality for the irrigation purpose. Waja Golesha sub-basin has moderate and Hormat Golena is the better sub basin in terms of water quality. The groundwater vulnerability assessment of the study area is made using the GOD rating system. It is found that the whole area is experiencing moderate to high risk of vulnerability and it is a good warning for proper management of the resource. The high risks of vulnerability are noticed in Hormat Golena and Waja Golesha sub basins. The aquifer potential of the study area is obtained using weighted overlay analysis and 73.3% of the total area is a good site for future water well development. The rest 26.7% of the area is not considered as a good site for spotting groundwater wells. Most of this area fall under Kobo-Gerbi sub basin.

A model to screen and improve business potential of micro and small enterprises in developing countries: Evidence from the Island of Mozambique

Programmes supporting micro and small enterprises in developing countries have been showing that capital is not enough to allow business success: survival and growth. Literature does not provide comprehensive and practical tool to support business development in this context, but allowed the collection of forty-nine success variables that were studied in a sample of successful and unsuccessful businesses in the Island of Mozambique to discover what were the key factors affecting those businesses’ performance. Empirical data gave the insights for the development of a model to screen and improve business potential of micro and small enterprises in this context.

Potential M&A between TIM Brazil and Oi S.A: The irreversible force of Telecommunications convergence

The intrinsic forces of market aiming for telecom industry convergence has arrived to Brazil. This case presents real characters, a sequence of events and other public information that has been impacting two corporations studied in this case. TIM Brazil and Oi S.A, two top players in the Brazilian telecom industry mobile and fixed segment respectively. While a merge between the two of them looks perfect and simple in an operational perspective due to its vertical complementarity, bring to them opportunities to win over a bundle offer (multi service package) that will consolidate their market predominance. Macroeconomic and internal corporate contrasts between these companies’ environment might signal that an impulsive could have a high price to pay in the future.

The financial system in Mozambique: Opportunities, barriers and market potential

This research is empirical and exploratory intending to analyse the attractiveness of banking in Mozambique, considering its positive outlook. To identify the opportunities and barriers, the methods adopted were elite interviews with banking executives, complemented by secondary data. The opportunities for new entrants seem to include bankarization and the emergence of micro and smallmedium enterprises; other avenues seem to include investment banking, support of mega-projects (e.g. energy, infrastructures) through syndicates and cooperation with multilaterals, and the participation in developing capital markets. Conversely, the main barriers include shortage of talent, inadequate infrastructures, poverty, unsophisticated entrepreneurial culture (e.g. informal economy, inadequate financial reporting), burdensome bureaucracy (e.g. visas), foreign exchange regulation, as well as low liquidity and high funding costs for banks. The key conclusions suggest a window of opportunity for niche markets, and new products and services in retail and investment banking.

Engineering of metal oxide nanoparticles for application in electrochemical devices

The growing demand for materials and devices with new functionalities led to the increased inter-est in the field of nanomaterials and nanotechnologies. Nanoparticles, not only present a reduced size as well as high reactivity, which allows the development of electronic and electrochemical devices with exclusive properties, when compared with thin films. This dissertation aims to explore the development of several nanostructured metal oxides by sol-vothermal synthesis and its application in different electrochemical devices. Within this broad theme, this study has a specific number of objectives: a) research of the influence of the synthesis parameters to the structure and morphology of the nanoparticles; b) improvement of the perfor-mance of the electrochromic devices with the application of the nanoparticles as electrode; c) application of the nanoparticles as probes to sensing devices; and d) production of solution-pro-cessed transistors with a nanostructured metal oxide semiconductor. Regarding the results, several conclusions can be exposed. Solvothermal synthesis shows to be a very versatile method to control the growth and morphology of the nanoparticles. The electrochromic device performance is influenced by the different structures and morphologies of WO3 nanoparticles, mainly due to the surface area and conductivity of the materials. The dep-osition of the electrochromic layer by inkjet printing allows the patterning of the electrodes without wasting material and without any additional steps. Nanostructured WO3 probes were produced by electrodeposition and drop casting and applied as pH sensor and biosensor, respectively. The good performance and sensitivity of the devices is explained by the high number of electrochemical reactions occurring at the surface of the na-noparticles. GIZO nanoparticles were deposited by spin coating and used in electrolyte-gated transistors, which promotes a good interface between the semiconductor and the dielectric. The produced transistors work at low potential and with improved ON-OFF current ratio, up to 6 orders of mag-nitude. To summarize, the low temperatures used in the production of the devices are compatible with flexible substrates and additionally, the low cost of the techniques involved can be adapted for disposable devices.

Evaluating the potential of yeast strains to produce added value products for the food and/or pharmaceutical industries

This study focus in the valorization of the apple pomace with the main goal of obtaining added value products. For that, hot compressed water technology was used for the extraction of phenolic compounds and hydrolysis of polysaccharides presents in the lignocellulosic structure of apple pomace to obtain simple sugars. The sugars have been utilized as alternative carbon source for growth, lipid accumulation and carotenoids production by five different yeast Yarrowia lipolytica, Rhodotorula mucilaginosa, Rhodotorula glutinis, Rhodosporidium babjevae and Rhodosporidium toruloides. Hydrolysis experiments were carried out with constant pressure of 100 bar, flow rate of 2mL/min and temperatures between 50°C and 250°C. The amount of total sugars present in apple pomace hydrolysates showed maximum values for the hydrolysis temperatures of 110°C and 190°C. In fact, these temperatures revealed the best results regarding the monosaccharides quantities. The amount of 5-HMF and furfural in each hydrolysate varied through the different temperatures. Maximum values for 5-HMF were obtained with 170°C, while furfural showed to be maximum at 210°C. Extraction of phenolic compounds were performed in simultaneously with hydrolysis reactions. Total phenolic compounds (TPC) increased along the temperature, however with small variations between 170°C and 250°C. Hydrolysates were then used as alternative carbon source to yeast growth. R. mucilaginosa shows the highest optical density, with the hydrolysate obtained at 130°C. Carotenoids produced by these yeast scored a total of 7.02μg carotenoids/g cell dry weight, while for the control assay, the same yeast scored 9.31μg caratonoides/g cell dry weight. β-carotene was quantified by HPLC, were 33% of the carotenoid production by R. mucilaginosa with hydrolysate as carbon source, corresponded to β-caroteno.

How to take advantage of wine tourism: Creation of a new concept for central Alentejo based on its potential and worldwide success factors

Wine Tourism is gaining importance in today’s world and more destinations and establishments have been arising. After understanding the importance of this economic activity and the factors it must have to succeed, a new project was conceived for Central Alentejo taking into account its potential. This project is an example of how to take advantage of Wine Tourism in wine regions that are underexplored, such as Aldeias de Montoito, the village near Redondo to which a Business Plan will be created, explaining the strategies to pursue in order to have a successful Wine Tourism destination.

Is there a potential win for companies when women enrich their role of workers through the enrichement of their family lives?

While the work-family relation conflict literature has received much attention, there is a lack of empirical evidence towards work-family positive relation. Furthermore, there is a lack of understanding and recognition of possible benefits obtained by skills’ development during maternity. This study concludes that a family-work relation has a positive outcome, namely the enrichment. It was evident that there is a potential win when women enrich their role as workers through the enrichment of their family lives. Moreover, this enrichment is perceived by mothers along the development of their children; each age and phase have different challenges and enable different skills’ improvement. The findings support the notion that not all work and family experiences are negative and experiences from the work and home can improve outcomes both inside and outside the workplace.

Proteomic analysis of a neurodegeneration cell model, treated with plant extracts with potential neuroprotective activity

Nowadays, a significant increase in chronic diseases is observed. Epidemiological studies showed a consistent relationship between the consumption of fruits and vegetables and a reduced risk of certain chronic diseases, namely neurodegenerative disorders. One factor common to these diseases is oxidative stress, which is highly related with proteins, lipids, carbohydrates and nucleic acids damage, leading to cellular dysfunction. Polyphenols, highly abundant in berries and associated products, were described as having antioxidant properties, with beneficial effect in these pathologies. The aims of this study were to evaluate by proteomic analyses the effect of oxidative insult in a neuroblastoma cell line (SK-N-MC) and understand the mechanisms involved in the neuroprotective effects of digested extracts from commercial and wild blackberry (R. vagabundus Samp.). The analysis of the total proteome by two-dimensional electrophoresis revealed that oxidative stress in SK-N-MC cells resulted in altered expression of 12 protein spots from a total of 318. Regarding some redox proteomics alterations, particularly proteins carbonylation and glutathionylation, protein carbonyl alterations during stress suggest that cells produce an early and late response; on the other hand, no glutathionylated polypeptides were detected. Relatively to the incubation of SK-N-MC cells with digested berry extracts, commercial blackberry promotes more changes in protein pattern of these cells than R. vagabundus. From 9 statistically different protein spots of cells incubated with commercial blackberry, only β-tubulin and GRP 78 were until now identified by mass spectrometry. Further studies involving the selection of sub proteomes will be necessary to have a better understanding of the mechanisms underlying the neuroprotective effects of berries.

Study of glycosidic changes in lung cancer: potential effectors in hematogenous metastasis

RESUMO: O cancro do pulmão (LC), uma das principais causas de mortalidade relacionada com cancro em Portugal, pode levar à formação de metástases hematogénicas. A adesão das células tumorais ao endotélio é considerada um dos passos fundamentais envolvidos na metástase. Em células sanguíneas, esta adesão é mediada por ligandos de E-selectina (E-SL), glicoproteínas ou glicolípidos decorados principalmente com sialyl-Lewis x (sLex) e sialyl-Lewis a (sLea). Tem sido descrito a expressão destes antigénios em LC, contudo o seu papel funcional em permitir a adesão das células de LC ao endotélio é ainda pouco compreendido. Foram analisadas amostras emparelhadas normais e tumorais de pacientes com cancro de pulmão de não-pequenas células (NSCLC) e três linhas celulares de LC. Immunoblotting assays com anti-sLex/sLea e molécula quimérica de E-selectina demonstraram que tecidos tumorais de LC sobreexpressam significativamente E-SL e resultados de citometria de fluxo demonstraram uma expressão elevada de E-SL nas linhas celulares. Para compreender o mecanismo da sobreexpressão de E-SL em tecidos tumorais e linhas celulares de LC, foi analisada a expressão de genes envolvidos na biossíntese de E-SL, nomeadamente FUT3, FUT4, FUT6, FUT7, ST3GAL3, ST3GAL4, ST3GAL6, β4GALT1, GCNT1 e GALNT3. Observou-se a sobreexpressão das fucosiltransferases FUT3, FUT6 e FUT7 em tecidos tumorais de LC e FUT3 em linhas celulares de LC, sendo que neste último, esta expressão é correlacionada com um aumento da adesão das células de LC às selectinas endoteliais. Foi observado que uma baixa expressão de FUT4 em tecidos tumorais está associada com estadios menos avançados de NSCLC. Foram analisadas ainda proteínas decoradas com sLex/sLea, tendo-se identificado como E-SL o antigénio carcinoembrionário em NSCLC. Em resumo, esta tese contribuiu para uma melhor compreensão das alterações glicosídicas e moléculas que podem influenciar a progressão tumoral do LC, podendo permitir identificar futuramente novos biomarcadores de diagnóstico/prognóstico e potenciais alvos terapêuticos para o NSCLC.--------------------------ABSTRACT: Lung cancer (LC), one of the major causes of mortality related to cancer in Portugal, may lead to hematogenous metastasis. Adhesion of cancer cells to endothelium is considered one of the crucial steps involved in metastasis. In blood cells, this adhesion is initiated by endothelial selectin ligands (E-SL) that are glycoproteins or glycolipids decorated mostly with sialyl-Lewis x (sLex) and sialyl-Lewis a (sLea). While LC has been described as expressing these sialyl Lewis antigens, its functional role in allowing LC adhesion to endothelium is still poorly understood. We analyzed paired tumor and normal tissues samples from non-small cell lung cancer (NSCLC) patients and three LC cell lines. Immunoblotting assays with anti-sLex/sLea and E-selectin chimera demonstrated that LC tumor tissues significantly overexpress E-SL and flow cytometry results indicated that E-SL are also abundantly expressed in LC cell lines. To understand the mechanism behind the overexpression of E-SL in LC tissues and cell lines, we analyzed the expression of genes involved in its biosynthesis, namely FUT3, FUT4, FUT6, FUT7, ST3GAL3, ST3GAL4, ST3GAL6, β4GALT1, GCNT1 and GALNT3. It was observed the overexpression of fucosyltransferases FUT3, FUT6 and FUT7 in LC tumor tissues and FUT3 in LC cell lines, being this last one correlated with an increased reactivity of the LC cells to endothelial selectins. It was described that low expression of FUT4 in tumor tissues is correlated with early stages of NSCLC. We also analyzed scaffolds proteins of sLex/sLea and it was identified the carcinoembryonic antigen as an E-SL in NSCLC. In summary, this thesis contributed to a better understanding of the glycosidic changes and molecules that can influence tumor progression of LC, allowing identifying in the future new diagnosis/prognosis biomarkers and potential therapeutic targets for NSCLC.

Historic and potential technology transition paths of grid battery storage: Co-evolution of energy grid, electric mobility and batteries

Scarcity of fuels, changes in environmental policy and in society increased the interest in generating electric energy from renewable energy sources (RES) for a sustainable energy supply in the future. The main problem of RES as solar and wind energy, which represent a main pillar of this transition, is that they cannot supply constant power output. This results inter alia in an increased demand of backup technologies as batteries to assure electricity system safety. The diffusion of energy storage technologies is highly dependent on the energy system and transport transition pathways which might lead to a replacement or reconfiguration of embedded socio-technical practices and regimes (by creating new standards or dominant designs, changing regulations, infrastructure and user patterns). The success of this technology is dependent on hardly predictable future technical advances, actor preferences, development of competing technologies and designs, diverging interests of actors, future cost efficiencies, environmental performance, the evolution of market demand and design and evolution of our society.