Responsible research and innovation: a global perspective

Based on the paper presented at the Doctorate Conference on Technologogy Assessment in July 2013 at the University Nova Lisboa, Caparica campus

Complexos Organometálicos: caracterização preliminar de compostos de vanádio e de moléculas libertadoras de CO como potenciais fármacos

Vários complexos metálicos têm sido explorados visando uma melhoria de atuais tratamentos das mais variadas doenças. Os compostos de vanádio apresentam uma capacidade de mimetizar a ação da insulina, insurgindo-se assim como uma aposta no tratamento da doença Diabetes mellitus. O monóxido de carbono (CO), outrora visto como apenas um agente tóxico, atualmente é explorado pelas suas capacidades anti-inflamatórias, tendo-se desenvolvido moléculas libertadoras de CO, os CORMs, de modo a tirar partido dos seus efeitos biológicos. Com vista a determinar a formação de aductos entre os complexos organometálicos de vanádio e diferentes proteínas e caracterizar o tipo de interação estabelecida recorreu-se à Cristalografia de raios-X. A estrutura cristalográfica do aducto VOIV(picolinato)2–tripsina bovina foi obtida a 1,09 Å de resolução, mostrando o complexo VOIV(pic)2 no centro ativo da enzima, coordenado à cadeia lateral da serina catalítica (Ser195), numa geometria octaédrica. Ensaios cinéticos preliminares realizados com o complexo VO(pic)2 foram efetuados para determinar potenciais efeitos inibitórios na atividade das enzimas lisozima da clara do ovo (HEWL) e tripsina. O potencial terapêutico dos CORMs associado à Nanotecnologia foi explorado para o [Ru(CO)3Cl(glicinato)] (CORM-3), visando desenvolver nanopartículas de ouro (AuNPs) funcionalizadas com o composto e diferentes proteínas. A toxicidade celular direta do CORM-3, bem como alguns potenciais efeitos biológicos de CORM-3–albumina de soro humano (BSA) e CORM-3–HEWL foram também avaliados, recorrendo a ensaios de viabilidade celular , riscados celulares, e RT-qPCR em várias linhas celulares tumorais e linha primária de fibroblastos humanos. Foi possível iniciar o desenvolvimento de nanosistemas de AuNPs@PEG@BSA e AuNPs@PEG@HEWL, seguindo-se futuramente a conjugação com o CORM-3. Não foi possível determinar o efeito anti-inflamatório do CORM-3 e seus conjugados através da análise dos genes de resposta por RT-qPCR em tempo real, no entanto determinou-se que o composto CORM-3 não possui toxicidade em linhas celulares tumorais, e que aparenta fomentar a regeneração celular em fibroblastos e células tumorais NINA, sendo este efeito potenciado aquando conjugação com BSA.

Spatial distribution of disseminated histoplasmosis and AIDS co-infection in an endemic area of Northeastern Brazil

Abstract: INTRODUCTION: The spatial distribution of disseminated histoplasmosis (DH) and acquired immunodeficiency syndrome (AIDS) co-infection in adult residents of Fortaleza, Ceará, Brazil was evaluated. METHODS: Socio-demographic data for the DH/AIDS cases were obtained from a reference hospital, and socio-environmental indicators were obtained from an official Brazilian institute. Kernel analysis and local indicators of spatial autocorrelation (LISA) cluster maps were used to estimate the case density within the city. RESULTS: DH/AIDS cases were concentrated in the Northwestern and Southwestern peripheral areas of the city, related with low human development indices, but different from AIDS cases distribution. CONCLUSION: Risk factors other than AIDS infection must affect histoplasmosis development in this area.

Evaluation of human T-lymphotropic virus prevalence/co-infection rates for a four-year period in a non-metropolitan blood center in Southeast Brazil

Abstract: INTRODUCTION: Human T-lymphotropic virus types 1/2 (HTLV-1/2) are distributed worldwide and are endemic in specific regions. METHODS: Serological evaluation of the HTLV-1/2 prevalence and co-infection rate [human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), Chagas disease, and syphilis)] for 2011-2014 was performed with volunteer blood donors from the western part of São Paulo State. RESULTS: Serrana and Araçatuba had higher HTLV seroprevalence rates (0.1%); while Franca, Olimpia, and Bebedouro had lower seroprevalences (0.04%). Co-infection (HBV and syphilis) was present in 12.3% of HTLV-infected blood donors. CONCLUSIONS: Our findings provide data for the prevalence of HTLV in Brazil and demonstrate the importance of regional and global hemovigilance.

Lag-user method: Using laggards to leverage user innovation

Laggards are the last users to adopt a product. Prior literature on user-led innovation ignores laggards’ impact on innovation. In this paper, we develop the Lag-User Method, through which laggards can generate new ideas. Through six studies with 62 teams in three countries, we apply the method to different technologies and services and present our findings to executives to get managerial insights. Findings reveal that laggards who generate new ideas (lag-users) have different perceptions of user-friendly products and different unfulfilled needs. They prefer simple products. We propose that by involving lag-users in NPD, firms can improve the effectiveness of NPD.

Decisions of technology innovation: the role of indicators

This work presents research conducted to understand the role of indicators in decisions of technology innovation. A gap was detected in the literature of innovation and technology assessment about the use and influence of indicators in this type of decision. It was important to address this gap because indicators are often frequent elements of innovation and technology assessment studies. The research was designed to determine the extent of the use and influence of indicators in decisions of technology innovation, to characterize the role of indicators in these decisions, and to understand how indicators are used in these decisions. The latter involved the test of four possible explanatory factors: the type and phase of decision, and the context and process of construction of evidence. Furthermore, it focused on three Portuguese innovation groups: public researchers, business R&D&I leaders and policymakers. The research used a combination of methods to collect quantitative and qualitative information, such as surveys, case studies and social network analysis. This research concluded that the use of indicators is different from their influence in decisions of technology innovation. In fact, there is a high use of indicators in these decisions, but lower and differentiated differences in their influence in each innovation group. This suggests that political-behavioural methods are also involved in the decisions to different degrees. The main social influences in the decisions came mostly from hierarchies, knowledge-based contacts and users. Furthermore, the research established that indicators played mostly symbolic roles in decisions of policymakers and business R&D&I leaders, although their role with researchers was more differentiated. Indicators were also described as helpful instruments to conduct a reasonable interpretation of data and to balance options in innovation and technology assessments studies, in particular when contextualised, described in detail and with discussion upon the options made. Results suggest that there are four main explanatory factors for the role of indicators in these decisions: First, the type of decision appears to be a factor to consider when explaining the role of indicators. In fact, each type of decision had different influences on the way indicators are used, and each type of decision used different types of indicators. Results for policy-making were particularly different from decisions of acquisition and development of products/technology. Second, the phase of the decision can help to understand the role indicators play in these decisions. Results distinguished between two phases detected in all decisions – before and after the decision – as well as two other phases that can be used to complement the decision process and where indicators can be involved. Third, the context of decision is an important factor to consider when explaining the way indicators are taken into consideration in policy decisions. In fact, the role of indicators can be influenced by the particular context of the decision maker, in which all types of evidence can be selected or downplayed. More importantly, the use of persuasive analytical evidence appears to be related with the dispute existent in the policy context. Fourth and last, the process of construction of evidence is a factor to consider when explaining the way indicators are involved in these decisions. In fact, indicators and other evidence were brought to the decision processes according to their availability and capacity to support the different arguments and interests of the actors and stakeholders. In one case, an indicator lost much persuasion strength with the controversies that it went through during the decision process. Therefore, it can be argued that the use of indicators is high but not very influential; their role is mostly symbolic to policymakers and business decisions, but varies among researchers. The role of indicators in these decisions depends on the type and phase of the decision and the context and process of construction of evidence. The latter two are related to the particular context of each decision maker, the existence of elements of dispute and controversies that influence the way indicators are introduced in the decision-making process.

Santini ice creams: Co-Owning a tradition

The case studies the potential partnership between a small family business, rich in tradition, that sells ice cream in the Lisbon area and a recognized Portuguese family who runs a multinational business. The aim of this study is to address students to analyze the evolution of the small company by using the Agency and Resource-Based Theories and to outline a potentially successful co-ownership structure if the agreement were to take place. The particularity of the case regards considering and identifying the main Family Business issues to keep in mind when dealing with these types of firms.

Osteogenic differentiation of adipose stem cells by endothelial cells co-culture within liquified capsules

Inspired by the native co-existence of multiple cell types and from the concept of deconstructing the stem cell niche, we propose a co-encapsulation strategy within liquified capsules. The present team has already proven the application of liquified capsules as bioencapsulation systems1. Here, we intend to use the optimized system towards osteogenic differentiation. Capsules encapsulating adipose stem cells alone (MONO-capsules) or in co-culture with endothelial cells (CO-capsules) were maintained in endothelial medium with or without osteogenic differentiation factors. The suitability of the capsules for living stem and endothelial cells encapsulation was demonstrated by MTS and DNA assays. The osteogenic differentiation was assessed by quantifying the deposition of calcium and the activity of ALP up to 21 days. CO capsules had an enhanced osteogenic differentiation, even when cultured in the absence of osteogenic factors. Furthermore, osteopontin and CD31 could be detected, which respectively indicate that osteogenic differentiation had occurred and endothelial cells maintained their phenotype. An enhanced osteogenic differentiation by co-encapsulation was also confirmed by the upregulation of osteogenic markers (BMP-2, RUNX2, BSP) while the expression of angiogenic markers (VEGF, vWF, CD31) revealed the presence of endothelial cells. The proposed capsules can also act as a growth factor release system upon implantation, as showed by VEGF and BMP-2 quantification. These findings demonstrate that the co-encapsulation of stem and endothelial cells within liquified injectable capsules provides a promising strategy for bone tissue engineering.  

In vitro chondrogenic commitment of human Wharton's jelly stem cells by co-culture with human articular chondrocytes.

Wharton's jelly stem cells (WJSCs) are a potential source of transplantable stem cells in cartilage-regenerative strategies, due to their highly proliferative and multilineage differentiation capacity. We hypothesized that a non-direct co-culture system with human articular chondrocytes (hACs) could enhance the potential chondrogenic phenotype of hWJSCs during the expansion phase compared to those expanded in monoculture conditions. Primary hWJSCs were cultured in the bottom of a multiwell plate separated by a porous transwell membrane insert seeded with hACs. No statistically significant differences in hWJSCs duplication number were observed under either of the culture conditions during the expansion phase. hWJSCs under co-culture conditions show upregulations of collagen type I and II, COMP, TGFβ1 and aggrecan, as well as of the main cartilage transcription factor, SOX9, when compared to those cultured in the absence of chondrocytes. Chondrogenic differentiation of hWJSCs, previously expanded in co-culture and monoculture conditions, was evaluated for each cellular passage using the micromass culture model. Cells expanded in co-culture showed higher accumulation of glycosaminoglycans (GAGs) compared to cells in monoculture, and immunohistochemistry for localization of collagen type I revealed a strong detection signal when hWJSCs were expanded under monoculture conditions. In contrast, type II collagen was detected when cells were expanded under co-culture conditions, where numerous round-shaped cell clusters were observed. Using a micromass differentiation model, hWJSCs, previously exposed to soluble factors secreted by hACs, were able to express higher levels of chondrogenic genes with deposition of cartilage extracellular matrix components, suggesting their use as an alternative cell source for treating degenerated cartilage.

Determinação dos elementos-traço (Zn, Co e Ni) em sedimentos da Plataforma Continental Amazônica sob influência da descarga do rio Amazonas

Esta pesquisa foi desenvolvida na Plataforma Continental Amazônica (PCA) no trecho compreendido entre os cabos Orange (AP) e Maguari (PA), para determinar os teores de Zn, Co e Ni nos sedimentos superficiais, identificando o papel dos sedimentos como fonte ou reserva de elementos-traço. A concentração dos elementos metálicos apresentou a seguinte associação: Zn > Ni > Co. Os sedimentos localizados na PCA podem ser considerados como sítio de ocorrência natural dos elementos metálicos, não havendo influência de fontes poluidoras na liberação destes para o sistema.

Estudo de metais pesados (Co, Cu, Fe, Cr, Ni, Mn, Pb e Zn) na Bacia do Tarumã-Açu Manaus (AM)

Os resíduos gerados em domicílios incluem diversos produtos, como pesticidas, produtos farmacêuticos, detergentes, óleos de cozinha, metais pesados contidos em baterias e outros utensílios. Esses resíduos são lançados continuamente em aterro sanitário ou lixões em cidades como Manaus. O chorume produzido nesses aterros, quando não tratados, contamina recursos hídricos superficiais e subterrâneos. Neste estudo foi feita uma avaliação das conseqüências da liberação do chorume no sistema hídrico da bacia do Tarumã-Açu. Amostras de água e sedimento foram coletadas nos igarapés Matrinxã, Acará, Bolívia, bacia do Tarumã-Açu e dentro do aterro sanitário (Manaus - Amazonas - Brasil) em março 2001. As amostras de água foram filtradas em filtro Milipore (0,45 mm de poro) e, em seguida, tratadas com HNO3 concentrado. As amostras de sedimento foram peneiradas em malha de 0,053 mm e digeridas com HCl:HNO3 (1:3) a 150ºC. As concentrações de alguns metais pesados (Co, Cu, Fe, Cr, Ni, Mn, Pb e Zn) foram determinadas nas amostras de água e sedimento por espectrometria de absorção atômica de chama. Os resultados revelaram que a concentração dos metais pesados é muito acima dos permitidos pela resolução 357/2005 do CONAMA em praticamente todos os locais amostrados, mostrando que o Aterro Sanitário é um dos principais responsáveis pelo impacto ambiental observado nos corpos hídricos estudados. As análises dos componentes principais (PCA) e hierárquica de cluster (HCA), revelam que os pontos de coleta localizados dentro do aterro sanitário apresentam características diferentes dos outros locais amostrados. Além disso, o HCA e PCA mostraram que existe uma similaridade entre os pontos de coleta localizados fora do aterro o que permite afirmar que o chorume do aterro se dissolve por todo corpo hídrico estudado.

Structural, optical and magnetic properties of pulsed laser deposited Co-doped ZnO films

Zn1−xCoxO films with different Co concentrations (with x=0.00, 0.10, 0.15, and 0.30) were grown by pulsed laser deposition (PLD) technique. The structural and optical properties of the films were investigated by grazing incidence X-ray diffraction (GIXRD), Raman spectroscopy and photoluminescence (PL). The magnetic properties were measured by conventional magnetometry using a SQUID and simulated by ab-initio calculations using Korring–Khon–Rostoker (KKR) method combined with coherent potential approximation (CPA). The effect of Co-doping on the GIXRD and Raman peaks positions, shape and intensity is discussed. PL studies demonstrate that Co-doping induces a decrease of the bandgap energy and quenching of the UV emission. They also suggest the presence of Zn interstitials when x≥0.15. The 10% Co-doped ZnO film shows ferromagnetism at 390 K with a spontaneous magnetic moment ≈4×10−5 emu and coercive field ≈0.17 kOe. The origin of ferromagnetism is explained based on the calculations using KKR method.

Nonsolvent induced phase separation preparation of poly(vinylidene fluoride-co-chlorotrifluoroethylene) membranes with tailored morphology, piezoelectric phase content and mechanical properties

Poly(vinylidene fluoride-co-chlorotrifluoroethylene) – P(VDF-CTFE) membranes are increasingly interesting for a wide range of applications, including battery separators, filtration membranes and biomedical applications. This work reports on the morphology, hydrophobicity, thermal and mechanical properties variation of P(VDF-CTFE) membranes processed by nonsolvent induced phase separation technique (NIPS) as a function of the main processing parameters. All membranes show a porous structure composed of large spherulites, (interconnected) micropores and/or microvoids depending on the processing conditions used that in turn affect their hydrophobicity and mechanical properties. The degree of crystallinity of the membranes remains approximately constant with a value of about 15 %, except for the membranes immediately immersed in ethanol, which is of about 23 %. In turn, the crystalline phases present in the copolymer is mainly affected by the temperature and nonsolvent characteristics of the coagulation bath, the β-phase content ranging from 33 to 100 %, depending on those processing parameters. It was show that the temperature of water-based coagulation bath plays an important role in order to produce structurally uniform and homogeneous porous membranes, which is particularly important from the point of view of technological applications.

Poly(vinylidene fluoride-co-chlorotrifluoroethylene) (PVDF-CTFE) lithium-ion battery separator membranes prepared by phase inversion

Separator membranes based on poly(vinylidene fluoride-co-chlorotrifluoroethylene) (PVDF-CTFE) were prepared by solvent casting technique based on its phase diagram in N,Ndimethylformamide (DMF) solvent. The microstructure of the PVDF-CTFE separator membranes depends on the initial position (temperature and concentration) of the solution in the phase diagram of the PVDF-CTFE/DMF system. A porous microstructure is achieved for PVDF-CTFE membranes with solvent evaporation temperature up to 50 ºC for a polymer/solvent relative concentration of 20 wt%. The ionic conductivity of the separator depends on the degree of porosity and electrolyte uptake, the highest room temperature value being 1.5 mS.cm-1 for the sample with 20 wt% of polymer concentration and solvent evaporation temperature at 25 ºC saturated with 1 mol L-1 lithium bis (trifluoromethanesulfonyl) imide (LiTFSI) in propylene carbonate (PC). This PVDF-CTFE separator membrane in Li/C-LiFePO4 half-cell shows good cyclability and rate capability, showing a discharge value after 50 cycles of 92 mAh.g-1 at 2 C, which is still 55% of the theoretical value. PVDF-CTFE separators are thus excellent candidates for high-power and safety lithium-ion batteries applications.