Characterisation of secondary metabolites associated with neutrophil apoptosis

We studied changes in secondary metabolites in human neutrophils undergoing constitutive or tumour necrosis factor (TNFalpha) stimulated apoptosis by a combination of high-performance liquid chromatography (HPLC) and NMR spectroscopy. Our results show that in contrast to freshly isolated neutrophils, neutrophil cells aged for 20 h in vitro had marked differences in the levels of a number of endogenous metabolites including lactate, amino acids and phosphocholine (PCho). There was no change in the concentration of taurine or glutamate and the ATP/ADP ratio was not affected. Levels of glutamine and lactate actually decreased. Identical changes were also observed in neutrophils stimulated to undergo apoptosis over a shorter time period (6 h) in the presence of TNFalpha and the phosphatidylinositol-3-kinase inhibitor wortmannin (WM). The changes in the concentration of PCho suggest possible activation of phospholipase associated with apoptosis or a selective failure of phosphatidycholine synthesis. The increased levels of apoptosis obtained with WM+TNFalpha, compared to TNFalpha by itself, suggest a synergistic effect by these compounds. The acceleration in rate of apoptosis probably arises from suppression by WM of pathway(s) that normally delay the onset of apoptosis. Changes in PCho and other endogenous metabolites, if proven to be characteristic of apoptosis in other cell systems, may permit non-invasive quantification of apoptosis. '

Coupling between gamma-band power and cerebral blood volume during recurrent acute neocortical seizures

Characterization of neural and hemodynamic biomarkers of epileptic activity that can be measured using noninvasive techniques is fundamental to the accurate identification of the epileptogenic zone (EZ) in the clinical setting. Recently, oscillations at gamma-band frequencies and above (N30 Hz) have been suggested to provide valuable localizing information of the EZ and track cortical activation associated with epileptogenic processes. Although a tight coupling between gamma-band activity and hemodynamic-based signals has been consistently demonstrated in non-pathological conditions, very little is known about whether such a relationship is maintained in epilepsy and the laminar etiology of these signals. Confirmation of this relationship may elucidate the underpinnings of perfusion-based signals in epilepsy and the potential value of localizing the EZ using hemodynamic correlates of pathological rhythms. Here, we use concurrent multi-depth electrophysiology and 2- dimensional optical imaging spectroscopy to examine the coupling between multi-band neural activity and cerebral blood volume (CBV) during recurrent acute focal neocortical seizures in the urethane-anesthetized rat. We show a powerful correlation between gamma-band power (25–90 Hz) and CBV across cortical laminae, in particular layer 5, and a close association between gamma measures and multi-unit activity (MUA). Our findings provide insights into the laminar electrophysiological basis of perfusion-based imaging signals in the epileptic state and may have implications for further research using non-invasive multi-modal techniques to localize epileptogenic tissue

Terahertz analysis of stratified wall plaster at buildings of cultural importance across Europe

Terahertz (THz) radiation is being developed as a tool for the analysis of cultural heritage, and due to recent advances in technology is now available commercially in systems which can be deployed for field analysis. The radiation is capable of penetrating up to one centimetre of wall plaster and is delivered in ultrafast pulses which are reflected from layers within this region. The technique is non-contact, non-invasive and non-destructive. While sub-surface radar is able to penetrate over a metre of wall plaster, producing details of internal structures, infrared and ultraviolet techniques produce information about the surface layers of wall plaster. THz radiation is able to provide information about the interim region of up to approximately one centimetre into the wall surface. Data from Chartres Cathedral, France, Riga Dome Cathedral, Latvia, and Chartreuse du Val de Bénédiction, France is presented each with different research questions. The presence of sub-surface paint layers was expected from documentary evidence, dating to the 13th Century, at Chartres Cathedral. In contrast, at the Riga Dome Cathedral surface painting had been obscured as recently as 1941 during the Russian occupation of Latvia using white lead-based paint. In the 13th Century, wall paintings at the Chapel of the Frescos, Chartreuse du Val de Benediction in Villeneuve les Avignon were constructed using sinopia under-painting on plaster covering uneven stonework.. This paper compares and contrasts the ability of THz radiation to provide information about sub-surface features in churches and Cathedrals across Europe by analysing depth based profiles gained from the reflected signal. © (2013) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

ESC Working Group on Myocardial Function Position Paper: how to study the right ventricle in experimental models

The right ventricle has become an increasing focus in cardiovascular research. In this position paper, we give a brief overview of the specific pathophysiological features of the right ventricle, with particular emphasis on functional and molecular modifications as well as therapeutic strategies in chronic overload, highlighting the differences from the left ventricle. Importantly, we put together recommendations on promising topics of research in the field, experimental study design, and functional evaluation of the right ventricle in experimental models, from non-invasive methodologies to haemodynamic evaluation and ex vivo set-ups.

The oscillatory bioelectrical signal from plants explained by a simulated electrical model and tested using Lempel-Ziv complexity

This paper demonstrates the oscillatory characteristics of electrical signals acquired from two ornamental plant types (Epipremnum pinnatum and Philodendron scandens - Family Araceae), using a noninvasive acquisition system. The electrical signal was recorded using Ag/AgCl superficial electrodes inside a Faraday cage. The presence of the oscillatory electric generator was shown using a classical power spectral density. The Lempel and Ziv complexity measurement showed that the plant signal was not noise despite its nonlinear behavior. The oscillatory characteristics of the signal were explained using a simulated electrical model that establishes that for a frequency range from 5 to 15 Hz, the oscillatory characteristic is higher than for other frequency ranges. All results show that non-invasive electrical plant signals can be acquired with improvement of signal-to-noise ratio using a Faraday cage, and a simple electrical model is able to explain the electrical signal being generated. (C) 2010 Elsevier B.V. All rights reserved.

Expression of metallothionein in ameloblastoma. A regulatory molecule?

BACKGROUND: Ameloblastoma is a benign odontogenic tumor, exhibiting local invasiveness and high rate of recurrence. Metallothionein is a protein associated with tumorigenesis, serving as prognostic factor in different neoplasms. We are interested in mechanisms underlying ameloblastoma local invasiveness. Thus, we decided to analyze expression of metallothionein in this tumor. MATERIALS AND METHODS: An immunohistochemical evaluation of metallothionein in ameloblastoma was carried out. As control, we assessed expression of the same molecule in calcifying cystic odontogenic tumor (CCOT), a non-invasive odontogenic neoplasm with ameloblastomatous epithelium. RESULTS: We studied 12 cases of solid/multicystic ameloblastomas. Metallothionein was observed in all samples. This molecule was observed in columnar cells in the periphery and in central polyhedral cells. CCOT (four cases) also showed the presence of metallothionein. Morphometry of stained areas showed that expression of metallothionein in ameloblastoma was significantly higher compared to CCOT (P < 0.0001). CONCLUSIONS: This protein may have an impact on ameloblastoma behavior. Metallothionein would act as a zinc reservoir for important proteases related to ameloblastoma biology, such as MMPs. This protein could also display pro-mitotic and anti-apoptotic features in the tumor. J Oral Pathol Med (2011) 40: 516-519

Matrix metalloproteinases, TIMPs and growth factors regulating ameloblastoma behaviour

Aims: Ameloblastoma is an odontogenic neoplasm with local invasiveness and recurrence. We have previously suggested that growth factors and matrix metalloproteinases (MMPs) influence ameloblastoma invasiveness(1). The aim was to study expression of MMPs, tissue inhibitor of metalloproteinases (TIMPs) and growth factors in ameloblastoma. Methods and results: Thirteen cases of solid/multicystic ameloblastoma were examined. As a control, calcifying cystic odontogenic tumour (CCOT), a non-invasive odontogenic neoplasm with ameloblastomatous epithelium was also studied. Immunohistochemistry detected MMPs, TIMPs and growth factors in ameloblastoma and CCOT. The labelling index (LI) of MMP-9 and TIMP-2 was significantly higher in ameloblastoma compared with CCOT. The LI of epidermal growth factor (EGF), transforming growth factor (TGF)-alpha and epidermal growth factor receptor (EGFR) was also increased in ameloblastoma. This neoplasm showed greater expression of MMPs, TIMPs and growth factors compared with CCOT. We then analysed these molecules in ameloblastoma cells and stroma. Ameloblastoma cells exhibited increased LI of MMP-1, -2 and EGFR. We found a positive correlation between EGF and TIMP-1, and between TGF-alpha and TIMP-2. It is known that signals generated by growth factors are transduced by the ERK pathway. Ameloblastoma stroma exhibited the phosphorylated (activated) form of ERK. Conclusions: These results suggest an interplay involving growth factors MMPs and TIMPs that may contribute to ameloblastoma behaviour. Signals generated by this molecular network would be transduced by ERK 1/2 pathway.

Alkaline phosphatase as a reporter of sigma(S) levels and rpoS polymorphisms in different E-coli strains

sigma(S) is responsible for the transcriptional regulation of genes related to protection against stresses and bacterial survival and it accumulates in the cell under conditions of stress, such as nutrient limitation. An increase in the levels of sigma(S) causes a reduction in the expression of genes that are transcribed by RNA polymerase associated with the principal sigma factor, sigma(70). phoA, that encodes alkaline phosphatase (AP) is expressed under phosphate shortage conditions, and is also repressed by sigma(S). Here we show that in a Pi-limited chemostat, accumulation of rpoS mutations is proportional to the intrinsic level of sigma(S) in the cells. Acquisition of mutations in rpoS relieves repression of the PHO genes. We also devised a non-destructive method based on the rpoS effect on AP that differentiates between rpo(S+) and rpoS mutants, as well as between high and low-sigma(S) producers. Using this method, we provide evidence that sigma(S) contributes to the repression of AP under conditions of Pi excess and that AP variation among different strains is at least partly due to intrinsic variation in sigma(S) levels. Consequently, a simple and non-destructive AP assay can be employed to differentiate between strains expressing different levels of sigma(S) on agar plates.

Estimating complex cortical networks via surface recordings-A critical note

We discuss potential caveats when estimating topologies of 3D brain networks from surface recordings. It is virtually impossible to record activity from all single neurons in the brain and one has to rely on techniques that measure average activity at sparsely located (non-invasive) recording sites Effects of this spatial sampling in relation to structural network measures like centrality and assortativity were analyzed using multivariate classifiers A simplified model of 3D brain connectivity incorporating both short- and long-range connections served for testing. To mimic M/EEG recordings we sampled this model via non-overlapping regions and weighted nodes and connections according to their proximity to the recording sites We used various complex network models for reference and tried to classify sampled versions of the ""brain-like"" network as one of these archetypes It was found that sampled networks may substantially deviate in topology from the respective original networks for small sample sizes For experimental studies this may imply that surface recordings can yield network structures that might not agree with its generating 3D network. (C) 2010 Elsevier Inc All rights reserved

Comparing diagnostic tests with missing data

When missing data occur in studies designed to compare the accuracy of diagnostic tests, a common, though naive, practice is to base the comparison of sensitivity, specificity, as well as of positive and negative predictive values on some subset of the data that fits into methods implemented in standard statistical packages. Such methods are usually valid only under the strong missing completely at random (MCAR) assumption and may generate biased and less precise estimates. We review some models that use the dependence structure of the completely observed cases to incorporate the information of the partially categorized observations into the analysis and show how they may be fitted via a two-stage hybrid process involving maximum likelihood in the first stage and weighted least squares in the second. We indicate how computational subroutines written in R may be used to fit the proposed models and illustrate the different analysis strategies with observational data collected to compare the accuracy of three distinct non-invasive diagnostic methods for endometriosis. The results indicate that even when the MCAR assumption is plausible, the naive partial analyses should be avoided.

A study on time-varying quantile and its applications

This Thesis is the result of my Master Degree studies at the Graduate School of Economics, Getúlio Vargas Foundation, from January 2004 to August 2006. am indebted to my Thesis Advisor, Professor Luiz Renato Lima, who introduced me to the Econometrics' world. In this Thesis, we study time-varying quantile process and we develop two applications, which are presented here as Part and Part II. Each of these parts was transformed in paper. Both papers were submitted. Part shows that asymmetric persistence induces ARCH effects, but the LMARCH test has power against it. On the other hand, the test for asymmetric dynamics proposed by Koenker and Xiao (2004) has correct size under the presence of ARCH errors. These results suggest that the LM-ARCH and the Koenker-Xiao tests may be used in applied research as complementary tools. In the Part II, we compare four different Value-at-Risk (VaR) methodologies through Monte Cario experiments. Our results indicate that the method based on quantile regression with ARCH effect dominates other methods that require distributional assumption. In particular, we show that the non-robust method ologies have higher probability to predict VaRs with too many violations. We illustrate our findings with an empirical exercise in which we estimate VaR for returns of São Paulo stock exchange index, IBOVESPA, during periods of market turmoil. Our results indicate that the robust method based on quantile regression presents the least number of violations.

O Conselho Municipal de Desenvolvimento Sustentável (CMDS) e a gestão de recursos hídricos: um estudo na Bacia do Rio Itabapoana (RJ)

O objetivo desta dissertação é analisar a forma de atuação do CMDS, e sua contribuição para a gestão dos recursos hídricos nos cinco municípios do Rio de Janeiro pertencentes à bacia do rio Itabapoana. O presente estudo foi conduzido a partir de uma discussão teórica sobre os temas: desenvolvimento local, cidadania, desenvolvimento local com cidadania e gestão social. Posteriormente, foram realizadas entrevistas temáticas, baseadas no método não probabilístico, com uma amostra composta por 38 pessoas, entre conselheiros do CMDS (membros do poder público e sociedade civil organizada), técnico, consultores e gestores do Sebrae/RJ. No tratamento dos dados foi utilizada a análise de discurso. Foram identificados aspectos negativos e positivos no que diz respeito à atuação e funcionamento do Conselho nos municípios analisados. Mesmo assim, pode-se verificar que grande parte dos conselheiros tem experiência anterior em Conselhos e movimentos sociais, e que o Projeto Managé, por meio da atuação dos CMDS, ajudou a construir uma identidade territorial para a bacia e também despertou a necessidade de maior conscientização e preservação do meio ambiente. Pode-se concluir que a forma de atuação do CMDS depende da interação e do nível de comprometimento do poder público e da sociedade civil organizada. Portanto, as condições institucionais locais exercem importante influência nas formas de mobilização social e participação dos indivíduos, visto que o processo de gerenciamento de recursos hídricos da bacia encontra-se ainda em fase de construção

A democratização da política pública e o fortalecimento da cidadania. Conhecendo o projeto Casa Brasil : unidades Vitória e Vila Velha

The purpose of this dissertation is to analyze the Casa Brasil Project and its contribution for promoting actions related to citizenship in Vitoria and Vila Velha cities. The essay was led through a theoretical discussion about citizenship, public space, social participation and public politics. Thereafter thematic interviews based on a non-probabilistic method were done with seventeen people such as public power representatives, organized civilian society and community. The speech analysis was used for data treatment. Some negative and positive aspects referred to citizenship and public power were identified. The aim of the research was checking if there is any encouragement to a genuine and consciousness participation of the society for the structure and continuous citizenship practice. The Casa Brasil Project experience in Vitoria and Vila Velha demonstrates that its sustainability and effectiveness depend on how interacted and committed the strategic stakeholders are, since the condition of local institutions influences the model of social mobilization and individual participation. Besides, this essay shows it is necessary: to improve the citizen involvement ¿ by implementing the board of directors, which assures public participation in order to stimulate the community to take the unity control ¿ to grant democratic feature to the public power, and to increase citizenship.

Life Cycle Models, Heterogeneity of Initial Assets,and Wealth Inequality

Life cycle general equilibrium models with heterogeneous agents have a very hard time reproducing the American wealth distribution. A common assumption made in this literature is that all young adults enter the economy with no initial assets. In this article, we relax this assumption – not supported by the data - and evaluate the ability of an otherwise standard life cycle model to account for the U.S. wealth inequality. The new feature of the model is that agents enter the economy with assets drawn from an initial distribution of assets, which is estimated using a non-parametric method applied to data from the Survey of Consumer Finances. We found that heterogeneity with respect to initial wealth is key for this class of models to replicate the data. According to our results, American inequality can be explained almost entirely by the fact that some individuals are lucky enough to be born into wealth, while others are born with few or no assets.

Análise de agrupamentos dos dados de DFA oriundos de perfis elétricos de indução de poços de petróleo

The main objective of this study is to apply recently developed methods of physical-statistic to time series analysis, particularly in electrical induction s profiles of oil wells data, to study the petrophysical similarity of those wells in a spatial distribution. For this, we used the DFA method in order to know if we can or not use this technique to characterize spatially the fields. After obtain the DFA values for all wells, we applied clustering analysis. To do these tests we used the non-hierarchical method called K-means. Usually based on the Euclidean distance, the K-means consists in dividing the elements of a data matrix N in k groups, so that the similarities among elements belonging to different groups are the smallest possible. In order to test if a dataset generated by the K-means method or randomly generated datasets form spatial patterns, we created the parameter Ω (index of neighborhood). High values of Ω reveals more aggregated data and low values of Ω show scattered data or data without spatial correlation. Thus we concluded that data from the DFA of 54 wells are grouped and can be used to characterize spatial fields. Applying contour level technique we confirm the results obtained by the K-means, confirming that DFA is effective to perform spatial analysis