Parametrization and penalties in spline models with an application to survival analysis

In this paper we show how a simple parametrization, built from the definition of cubic splines, can aid in the implementation and interpretation of penalized spline models, whatever configuration of knots we choose to use. We call this parametrization value-first derivative parametrization. We perform Bayesian inference by exploring the natural link between quadratic penalties and Gaussian priors. However, a full Bayesian analysis seems feasible only for some penalty functionals. Alternatives include empirical Bayes methods involving model selection type criteria. The proposed methodology is illustrated by an application to survival analysis where the usual Cox model is extended to allow for time-varying regression coefficients

Biomarkers: a strategic tool in the assessment of environmental quality of coastal waters

Ecosystems are under the pressure of complex mixtures of contaminants whose effects are not always simple to assess. Biomarkers, acting as early warning signals of the presence of potentially toxic xenobiotics, are useful tools for assessing either exposure to, or the effects of these compounds providing information about the toxicant bioavailability. In fact, it has been argued that a full understanding of ecotoxicological processes must consider an integrated multi-level approach, in which molecular impact is related with higher-order biological consequences at the individual, population and community levels. Monitoring programs should make use of this tool to link contaminants and ecological responses fulfilling strategies like those launched by OSPAR (Commissions of Oslo and Paris) Convention on the protection of the marine environment of the North-East Atlantic and the International Council for the Exploration of the Sea (ICES). An overview of the work done in the past few years using biomarkers as in situ tools for pollution assessment in Portuguese coastal waters is presented as a contribution to the set up of a biomonitoring program for the Portuguese coastal zone. Considering the data set available the biomonitoring proposal should include the analysis of biomarkers and effects at individual levels. The aim of the program will include a spatial and temporal characterization of the biomarkers acetyl-cholinesterase, metallothioneins, DNA damage, adenylate energy charge and scope-for-growth levels. The investigation of the spatial variation of biomarkers is crucial to define sites for long term monitoring, which will be integrated with a chemical monitoring program. This framework will be a major contribution to the implementation of a national database for the use of biomarkers along the Portuguese coast.info:eu-repo/semantics/publishedVersio

Working Memory and Early Numeracy Training in Preschool Children

Many factors influence children\u2019s performance in mathematical achievement, including both domainspecific and domain-general factors. This study aimed to verify and compare the effects of two types of training on early numerical skills. One type of training focused on the enhancement of working memory, a domain-general precursor, while the other focused on the enhancement of early numeracy, a domain-specific precursor. The participants were 48 five-year-old preschool children. Both the working memory and early numeracy training programs were implemented for 5 weeks. The results showed that the early numeracy intervention specifically improved early numeracy abilities in preschool children, whereas working memory intervention improved not only working memory abilities but also early numeracy abilities. These findings stress the importance of performing activities designed to train working memory abilities, in addition to activities aimed to enhance more specific skills, in the early prevention of learning difficulties during preschool years

Stepwise implementation of high-throughput sequencing metabarcoding to estuarine macrobenthic communities

This work was supported by FEDER through POFC-COMPETE by national funds from ‘Fundação para a Ciência e a Tecnologia (FCT)’ in the scope of the grant FCOMP-01-0124-FEDER-015429 and also by the strategic programme UID/BIA/04050/2013 (POCI-01- 0145-FEDER-007569) also funded by national funds through the FCT I.P. and by the ERDF through the COMPETE2020 - Programa Operacional Competitividade e Internacionalização (POCI). Jorge Lobo was supported by a PhD fellowship (SFRH/BD/69750/2010) from FCT.info:eu-repo/semantics/publishedVersio

Glutaraldehyde-crosslinking chitosan scaffolds reinforced with calcium phosphate spray-dried granules for bone tissue applications

The clinical demand for bone scaffolds as an alternative strategy for bone grafting has increased exponentially and, up to date, numerous formulations have been proposed to regenerate the bone tissue. However, most of these structures lack at least one of the fundamental/ideal properties of these materials (e.g., mechanical resistance, interconnected porosity, bioactivity, biodegradability, etc.). In this work, we developed innovative composite scaffolds, based on crosslinked chitosan with glutaraldehyde (GA), combined with different atomized calcium phosphates (CaP) granules - hydroxyapatite (HA) or biphasic mixtures of HA and β - tricalcium phosphate (β-TCP), with improved biomechanical behavior and enhanced biological response. This innovative combination was designed to improve the scaffolds' functionality, in which GA improved chitosan mechanical strength and stability, whereas CaP granules enhanced the scaffolds' bioactivity and osteoblastic response, further reinforcing the scaffolds' structure. The biological assessment of the composite scaffolds showed that the specimens with 0.2% crosslinking were the ones with the best biological performance. In addition, the inclusion of biphasic granules induced a trend for increase osteogenic activation, as compared to the addition of HA granules. In conclusion, scaffolds produced in the present work, both with HA granules or the biphasic ones, and with low concentrations of GA, have shown adequate properties and enhanced biological performance, being potential candidates for application in bone tissue engineering.publishe

Adaptive response of single and binary biofilms formed in the presence of benzalkonium chloride

In actual situations bacteria can live nicely in hostile environments in part due to its ability to live in biofilms and to regulate gene expression as an adaptive response to a variety of stresses. This altered profile, compared to planktonic counterparts, as well as the interactions amongst the several strains existing within the biofilm seems to be responsible for the gradual loss of susceptibility to antimicrobials. The presence of biofilms on the surfaces of various types of medical surfaces and equipment can be the source of pathogens and contribute to biofilm-associated infections. The aim of this work was to examine whether exposure of P.aeruginosa and E.coli to an antimicrobial agent – benzalkoniun chloride (BC) – during single and binary biofilm formation could induce an adaptive response in bacteria and further evaluate the biofilm behaviour after aggression with the same agent. Biofilms were formed in microtiter plates for 5 days in presence of 0.9 mM of BC, being afterwards submitted to BC attack (1 mM). Biofilms were characterized by total mass, through crystal violet, metabolic activity, through XTT method, and number of cells. The data showed that both single and binary biofilms formed in the presence of BC have clearly more mass, less activity and slight less number of cells. These events could be sign of a different metabolic state of the cells entrapped in the biofilms previously exposed to the surfactant. The simultaneous growth of both species seems not prejudice or favour binary biofilm development. After BC attack, biofilms developed in the absence of the surfactant suffered mass and activity reduction and had fewer cells, probably due to the toxic effect of the product. Conversely, when the biofilms were developed in the presence of BC, the attack leads to biofilms with more mass and activity, being however the number of cells reduced. This discrepancy may be due to the loss of culturability of bacteria in solid media. These facts emphasise that BC is not effective against biofilms developed in its presence. It can be concluded that the presence of BC during single and binary sessile growth seems to induce an adaptive resistance of P. aeruginosa and E. coli biofilms. This biofilm features, resulting from an adverse situation, can play a significant role in the selection of resistant pathogenic bacteria and be on the basis of recalcitrant biofilms, contaminating medical surfaces and causing nosocomial infections.IBB-CEB and FCT, for the financial support (Project PTDC/SAU-ESA/64609/2006; PhD Grant SFRH/BD/31065/2006)

Targeting Lipid Peroxidation for Cancer Treatment

grant number RTI2018-093864-B-I00Cancer is one of the highest prevalent diseases in humans. The chances of surviving cancer and its prognosis are very dependent on the affected tissue, body location, and stage at which the disease is diagnosed. Researchers and pharmaceutical companies worldwide are pursuing many attempts to look for compounds to treat this malignancy. Most of the current strategies to fight cancer implicate the use of compounds acting on DNA damage checkpoints, non-receptor tyrosine kinases activities, regulators of the hedgehog signaling pathways, and metabolic adaptations placed in cancer. In the last decade, the finding of a lipid peroxidation increase linked to 15-lipoxygenases isoform 1 (15-LOX-1) activity stimulation has been found in specific successful treatments against cancer. This discovery contrasts with the production of other lipid oxidation signatures generated by stimulation of other lipoxygenases such as 5-LOX and 12-LOX, and cyclooxygenase (COX-2) activities, which have been suggested as cancer biomarkers and which inhibitors present anti-tumoral and antiproliferative activities. These findings support the previously proposed role of lipid hydroperoxides and their metabolites as cancer cell mediators. Depletion or promotion of lipid peroxidation is generally related to a specific production source associated with a cancer stage or tissue in which cancer originates. This review highlights the potential therapeutical use of chemical derivatives to stimulate or block specific cellular routes to generate lipid hydroperoxides to treat this disease.publishersversionpublishe

Exchange interactions in the coper(II)-N-benzoylglycine (hippuric acid) complex

O complexo CuII-N-benzoilglicina provê um sistema conveniente para se estudar interações de troca fracas entre elétrons desemparelhados que são transmitidas por caminhos químicos de interesse biológico. A molécula existe como um dímero onde cada CuII está coordenado a cinco ligantes, formando uma pirâmide de base quadrada distorcida. O único caminho químico entre íons CuII magneticamente não-equivalentes envolve 17 átomos diamagnéticos e uma fraca ligação de hidrogênio putativa. Esta interação foi estudada por Ressonância Paramagnética Eletrônica de amostras monocristalinas a 9,5 e 34,5 GHz, tendo sua magnitude sido calculada em 4(1) mK. Esse valor é discutido em termos de valores obtidos para caminhos similares em outros compostos-modelo e proteínas.The complex CuII-N-benzoylglycine provides a convenient system to study weak exchange interactions between unpaired spins transmitted through a biologically relevant long chemical bridge. The molecule exists as a dimer with each CuII ion coordinated to five ligands, forming a distorted square–based pyramid. The only chemical connection between magnetically non-equivalent copper ions is a very long path comprising 17 diamagnetic atoms and a weak putative hydrogen bond. This interaction was studied using Electron Paramagnetic Resonance in single-crystal samples at 9.5 and 34.5 GHz and its magnitude was calculated as 4(1) mK. This value is discussed in terms of values obtained for similar paths in other model compounds and in proteins.CNPq (307102/2006-8)FAPESPCAPESFINEPPRONEX/FAPESP/CNPq (03/09859-2

Overweight and Class I Obesity Are Associated with Lower 10-Year Risk of Mortality in Brazilian Older Adults: The Bambuí Cohort Study of Ageing

Background: Prospective studies mostly with European and North-American populations have shown inconsistent results r