Showing papers by "University of Lisbon published in 2002"

Multiscale entropy analysis of complex physiologic time series.

Abstract: There has been considerable interest in quantifying the complexity of physiologic time series, such as heart rate. However, traditional algorithms indicate higher complexity for certain pathologic processes associated with random outputs than for healthy dynamics exhibiting long-range correlations. This paradox may be due to the fact that conventional algorithms fail to account for the multiple time scales inherent in healthy physiologic dynamics. We introduce a method to calculate multiscale entropy (MSE) for complex time series. We find that MSE robustly separates healthy and pathologic groups and consistently yields higher values for simulated long-range correlated noise compared to uncorrelated noise.

Interactions of Flavonoids with Iron and Copper Ions: A Mechanism for their Antioxidant Activity

Abstract: The metal chelating properties of flavonoids suggest that they may play a role in metal-overload diseases and in all oxidative stress conditions involving a transition metal ion. A detailed study has been made of the ability of flavonoids to chelate iron (including Fe3+) and copper ions and its dependence of structure and pH. The acid medium may be important in some pathological conditions. In addition, the ability of flavonoids to reduce iron and copper ions and their activity-structure relationships were also investigated. To fulfill these objectives, flavones (apigenin, luteolin, kaempferol, quercetin, myricetin and rutin), isoflavones (daidzein and genistein), flavanones (taxifolin, naringenin and naringin) and a flavanol (catechin) were investigated. All flavonoids studied show higher reducing capacity for copper ions than for iron ions. The flavonoids with better Fe3+ reducing activity are those with a 2,3-double bond and possessing both the catechol group in the B-ring and the 3-hydroxyl group. The copper reducing activity seems to depend largely on the number of hydroxyl groups. The chelation studies were carried out by means of ultraviolet spectroscopy and electrospray ionisation mass spectrometry. Only flavones and the flavanol catechin interact with metal ions. At pH 7.4 and pH 5.5 all flavones studied appear to chelate Cu2+ at the same site, probably between the 5-hydroxyl and the 4-oxo groups. Myricetin and quercetin, however, at pH 7.4, appear to chelate Cu2+ additionally at the ortho-catechol group, the chelating site for catechin with Cu2+ at pH 7.4. Chelation studies of Fe3+ to flavonoids were investigated only at pH 5.5. Only myricetin and quercetin interact strongly with Fe3+, complexation probably occurring again between the 5-hydroxyl and the 4-oxo groups. Their behaviour can be explained by their ability to reduce Fe3+ at pH 5.5, suggesting that flavonoids reduce Fe3+ to Fe2+ before association.

The North Atlantic Oscillation influence on Europe: climate impacts and associated physical mechanisms

Abstract: A multivariable analysis of the influence of the North Atlantic Oscillation (NAO) on the climate of the North Atlantic and European sectors is presented using the 40 yr (1958-1997) consis- tent data set from NCEP. Using high and low NAO index composites, anomaly fields of climate vari- ables are then interpreted based on physical mechanisms associated with the anomalous mean flow (characterised by the surface wind field) and the anomalous eddy activity (characterised by the sur- face vorticity and the 500 hPa storm track fields). It is shown that NAO-related temperature patterns are mainly controlled by the advection of heat by the anomalous mean flow. However, large asym- metries between minimum and maximum temperatures, and more significantly, between positive and negative phases of NAO imply the importance of a different mechanism, namely, the modulation of short wave and long wave radiation by cloud cover variations associated with the NAO. Further- more, NAO influence on 2 different precipitation-related variables—precipitation rate and precip- itable water—displays different patterns. Precipitable water is shown to be strongly related to the corresponding anomaly fields of temperature while precipitation rate appears to be controlled by the surface vorticity field and associated strength of the tropospheric synoptic activity.

Evidence for active subduction beneath Gibraltar

Abstract: We report on a marine seismic survey that images an active accretionary wedge west of Gibraltar. Ramp thrusts offset the seafloor and sole out to an east-dipping decollement, indicating ongoing westward-vergent tectonic shortening. New traveltime tomographic re- sults image a slab of oceanic lithosphere descending from the Atlantic domain of the Gulf of Cadiz, passing through intermediate-depth (60-120 km) seismicity beneath the west- ernmost Alboran Sea, and merging with a region of deep-focus earthquakes 600-660 km below Granada, Spain. Together, these new data provide compelling evidence for an active east-dipping subduction zone.

CD4 + T-cell depletion in HIV infection: Are we closer to understanding the cause?

Abstract: Is CD4+ cell depletion due to rapid elimination by HIV and failure of the immune system to replace these cells at the required rate? Increasing evidence suggests that this is not the case, and that infection-induced immune activation drives both viral replication and CD4+ cell depletion

Systematics of basidiomycetous yeasts: a comparison of large subunit D1/D2 and internal transcribed spacer rDNA regions

Abstract: Basidiomycetous yeasts in the Urediniomycetes and Hymenomycetes were examined by sequence analysis in two ribosomal DNA regions: the D1/D2 variable domains at the 5' end of the large subunit rRNA gene (D1/D2) and the internal transcribed spacers (ITS) 1 and 2. Four major lineages were recognized in each class: Microbotryum, Sporidiobolus, Erythrobasidium and Agaricostilbum in the Urediniomycetes; Tremellales, Trichosporonales, Filobasidiales and Cystofilobasidiales in the Hymenomycetes. Bootstrap support for many of the clades within those lineages is weak; however, phylogenetic analysis provides a focal point for in-depth study of biological relationships. Combined sequence analysis of the D1/D2 and ITS regions is recommended for species identification, while species definition requires classical biological information such as life cycles and phenotypic characterization.

Prevalence of chronic heart failure in Southwestern Europe: the EPICA study.

Abstract: Aim To estimate the prevalence of chronic heart failure (CHF) in mainland Portugal in 1998. Methods and population A community-based epidemiological survey involving subjects attending primary care centres selected by a combined two-stage sampling and stratified procedure. General practitioners (GPs) randomly selected in proportion to the population of the District, evaluated subjects attending primary care centres aged over 25 years, recruited consecutively and stratified by age. CHF cases were identified according to the Guidelines of the European Society of Cardiology for CHF diagnosis. Results 5434 eligible subjects were evaluated by 365 GPs; 551 patients with CHF were identified. The overall prevalence and 95% CI of CHF in mainland Portugal is 4.36% (3.69–5.02%), 4.33% in males (3.19–5.46%), and 4.38% in females (3.64–5.13%). Age-specific CHF prevalence was as follows: 1.36% in the 25–49 years-old group (0.39–2.33%), 2.93% in the 50–59 years-old group (5.58–9.37%), 7.63% in the 60–69 years-old group (5.58–9.37%), 12.67% in the 70–79 years-old group (10.73–14.6%), and 16.14% in group over 80 years old (13.81–18.47%). The prevalence of CHF due to systolic dysfunction was 1.3% and the prevalence of CHF with normal systolic function was 1.7%. Conclusions The overall prevalence of CHF in Portugal was slightly higher than that of other European studies and increases sharply with age. The prevalence of CHF due to systolic dysfunction is very similar to that reported by other recent European studies. The differences found may correspond to differences in methodology rather than actual differences in the population.

Ligands of the peroxisome proliferator-activated receptors (PPAR-gamma and PPAR-alpha) reduce myocardial infarct size.

Abstract: This study was designed to investigate the effects of various chemically distinct activators of PPAR-gamma and PPAR-alpha in a rat model of acute myocardial infarction. Using Northern blot analysis and RT-PCR in samples of rat heart, we document the expression of the mRNA for PPAR-gamma (isoform 1 but not isoform 2) as well as PPAR-beta and PPAR-alpha in freshly isolated cardiac myocytes and cardiac fibroblasts and in the left and right ventricles of the heart. Using a rat model of regional myocardial ischemia and reperfusion (in vivo), we have discovered that various chemically distinct ligands of PPAR-gamma (including the TZDs rosiglitazone, ciglitazone, and pioglitazone, as well as the cyclopentanone prostaglandins 15D-PGJ2 and PGA1) cause a substantial reduction of myocardial infarct size in the rat. We demonstrate that two distinct ligands of PPAR-alpha (including clofibrate and WY 14643) also cause a substantial reduction of myocardial infarct size in the rat. The most pronounced reduction in infarct size was observed with the endogenous PPAR-gamma ligand, 15-deoxyDelta12,14-prostagalndin J2 (15D-PGJ2). The mechanisms of the cardioprotective effects of 15D-PGJ2 may include 1) activation of PPAR-alpha, 2) activation of PPAR-gamma, 3) expression of HO-1, and 4) inhibition of the activation of NF-kappaB in the ischemic-reperfused heart. Inhibition by 15D-PGJ2 of the activation of NF-kappaB in turn results in a reduction of the 1) expression of inducible nitric oxide synthase and the nitration of proteins by peroxynitrite, 2) formation of the chemokine MCP-1, and 3) expression of the adhesion molecule ICAM-1. We speculate that ligands of PPAR-gamma and PPAR-alpha may be useful in the therapy of conditions associated with ischemia-reperfusion of the heart and other organs. Our findings also imply that TZDs and fibrates may help protect the heart against ischemia-reperfusion injury. This beneficial effect of 15D-PGJ2 was associated with a reduction in the expression of the 1) adhesion molecules ICAM-1 and P-selectin, 2) chemokine macrophage chemotactic protein 1, and 3) inducible isoform of nitric oxide synthase. 15D-PGJ2 reduced the nitration of proteins (immunohistological analysis of nitrotyrosine formation) caused by ischemia-reperfusion, likely due to the generation of peroxynitrite. Not all of the effects of 15D-PGJ2, however, are due to the activation of PPAR-gamma. For instance, exposure of rat cardiac myocytes to 15D-PGJ2, but not to rosiglitazone, results in an up-regulation of the expression of the mRNA for heme-oxygenase-1 (HO-1). Taken together, these results provide convincing evidence that several, chemically distinct ligands of PPAR-gamma reduce the tissue necrosis associated with acute myocardial infarction.

Structure-antioxidant activity relationships of flavonoids: a re-examination.

Abstract: The antioxidant and prooxidant activities of flavonoids belonging to several classes were studied to establish their structure-activity relationships against different oxidants. Special attention was paid to the flavonoids quercetin (flavone), taxifolin (flavanone) and catechin (flavanol), which possess different basic structures but the same hydroxylation pattern (3,5,7,3'4'-OH). It was found that these three flavonoids exhibited comparable antioxidant activities against different oxidants leading to the conclusion that the presence of ortho-catechol group (3',4'-OH) in the B-ring is determinant for a high antioxidant capacity. The flavone kaempferol (3,5,7,4'-OH), however, in spite of bearing no catechol group, also presents a high antioxidant activity against some oxidants. This fact can be attributed to the presence of both 2,3-double bond and the 3-hydroxyl group, meaning that the basic structure of flavonoids becomes important when the antioxidant activity of B-ring is small.

Tauroursodeoxycholic acid, a bile acid, is neuroprotective in a transgenic animal model of Huntington's disease

Abstract: Huntington's disease (HD) is an untreatable neurological disorder caused by selective and progressive degeneration of the caudate nucleus and putamen of the basal ganglia. Although the etiology of HD pathology is not fully understood, the observed loss of neuronal cells is thought to occur primarily through apoptosis. Furthermore, there is evidence in HD that cell death is mediated through mitochondrial pathways, and mitochondrial deficits are commonly associated with HD. We have previously reported that treatment with tauroursodeoxycholic acid (TUDCA), a hydrophilic bile acid, prevented neuropathology and associated behavioral deficits in the 3-nitropropionic acid rat model of HD. We therefore examined whether TUDCA would also be neuroprotective in a genetic mouse model of HD. Our results showed that systemically administered TUDCA led to a significant reduction in striatal neuropathology of the R6/2 transgenic HD mouse. Specifically, R6/2 mice began receiving TUDCA at 6 weeks of age and exhibited reduced striatal atrophy, decreased striatal apoptosis, as well as fewer and smaller size ubiquitinated neuronal intranuclear huntingtin inclusions. Moreover, locomotor and sensorimotor deficits were significantly improved in the TUDCA-treated mice. In conclusion, TUDCA is a nontoxic, endogenously produced hydrophilic bile acid that is neuroprotective in a transgenic mouse model of HD and, therefore, may provide a novel and effective treatment in patients with HD.

Quantiles for counts

Abstract: This article studies the estimation of conditional quantiles of counts Given the discreteness of the data, some smoothness must be artificially imposed on the problem We show that it is possible to smooth the data in a way that allows inference to be performed using standard quantile regression techniques The performance and implementation of the estimators are illustrated by simulations and an application

Modulational instability in Bose-Einstein condensates in optical lattices

Abstract: A self-consistent theory of a cylindrically shaped Bose-Einstein condensate (BEC) periodically modulated by a laser beam is presented. We show, both analytically and numerically, that modulational instability/stability is the mechanism by which wave functions of soliton type can be generated in a cylindrically shaped BEC subject to a one-dimensional optical lattice. The theory explains why bright solitons can exist in a BEC with positive scattering length and why condensates with negative scattering length can be stable and give rise to dark solitary pulses.

Knock-out of Arabidopsis metal transporter gene IRT1 results in iron deficiency accompanied by cell differentiation defects.

Abstract: IRT1 and IRT2 are members of the Arabidopsis ZIP metal transporter family that are specifically induced by iron deprivation in roots and act as heterologous suppressors of yeast mutations inhibiting iron and zinc uptake. Although IRT1 and IRT2 are thought to perform redundant functions as root-specific metal transporters, insertional inactivation of the IRT1 gene alone results in typical symptoms of iron deficiency causing severe leaf chlorosis and lethality in soil. The irt1 mutation is characterized by specific developmental defects, including a drastic reduction of chloroplast thylakoid stacking into grana and lack of palisade parenchyma differentiation in leaves, reduced number of vascular bundles in stems, and irregular patterns of enlarged endodermal and cortex cells in roots. Pulse labeling with 59Fe through the root system shows that the irt1 mutation reduces iron accumulation in the shoots. Short-term labeling with 65Zn reveals no alteration in spatial distribution of zinc, but indicates a lower level of zinc accumulation. In comparison to wild-type, the irt1 mutant responds to iron and zinc deprivation by altered expression of certain zinc and iron transporter genes, which results in the activation of ZIP1 in shoots, reduction of ZIP2 transcript levels in roots, and enhanced expression of IRT2 in roots. These data support the conclusion that IRT1 is an essential metal transporter required for proper development and regulation of iron and zinc homeostasis in Arabidopsis.

Dispersal, Genetic Differentiation and Speciation in Estuarine Organisms

Abstract: For some of their occupants, estuaries represent spatially discrete habitats, isolated from each other by barriers to dispersal or physiological tolerance. We present contrasting strategies for the retention or export of larvae from their estuary of origin, and consider the implications these have on population structure and divergence. Reported patterns of genetic differentiation and inferred gene flow in estuarine taxa (principally animals) are reviewed, and difficulties in the interpretation of existing genetic data discussed. Species concepts and models of speciation relevant to estuaries are outlined, and patterns of speciation of estuarine taxa reviewed. It is concluded that estuarine environments tend to restrict gene flow and impose distinct selective regimes, generating physiologically adapted populations divergent from their marine counterparts, and the potential for in situ speciation in complete or partial isolation. The resulting taxa may represent sibling or cryptic species groups of truly estuarine origin, rather than simply estuarine populations of marine eurytopes.

Lymphatic Uptake of Pulmonary Delivered Radiolabelled Solid Lipid Nanoparticles

Abstract: Lymphatic drainage plays an important role in the uptake of particulates in the respiratory system, being also associated to the spreading of lung cancer through metastasis development. In recent years solid lipid nanoparticles (SLN) have been proposed as carriers of anti-tumoural drugs, for their low toxicity and surface characteristics make them suitable for either imaging (gamma-scintigraphy) or therapy upon encapsulation of cytotoxic drugs. Assessment of inhaled radiolabelled SLN biodistribution is described in the present work. Methods : Nanoparticles (200 nm) were radiolabelled with 99m Tc using the lipophilic chelator d, l -hexamehylpropyleneamine oxime (HMPAO). Biodistribution studies were carried out following aerosolisation and administration of a 99m Tc-HMPAO-SLN suspension to a group of adult male Wistar rats. A 60 min dynamic image acquisition was performed in a gamma-camera, followed by static image collection at 30 min intervals up to 4 h postinhalation. Radiation counting was performed in ...

Exportin-5-mediated nuclear export of eukaryotic elongation factor 1A and tRNA

Abstract: Transport of proteins and RNA into and out of the cell nucleus is mediated largely by a family of RanGTP-binding transport receptors. Export receptors (exportins) need to bind RanGTP for efficient loading of their export cargo. We have identified eukaryotic elongation factor 1A (eEF1A) and tRNA as RanGTP-dependent binding partners of exportin-5 (Exp5). Exp5 stimulates nuclear export of eEF1A when microinjected into the nucleus of Xenopus laevis oocytes. Surprisingly, the interaction between eEF1A and Exp5 is dependent on tRNA that can interact directly with Exp5 and, if aminoacylated, recruits eEF1A into the export complex. These data suggested to us that Exp5 might support tRNA export. Indeed, not only the canonical tRNA export receptor, exportin-t, but also Exp5 can drive nuclear export of tRNA. Taken together, we show that there exists an alternative tRNA export pathway which can be exploited to keep eEF1A out of the cell nucleus.

The structure and stability of molecular cloud cores in external radiation fields

Abstract: We have considered the thermal equilibrium in pre-protostellar cores in the approximation where the dust tempera- ture is independent of interactions with the gas and where the gas is heated both by collisions with dust grains and ionization by cosmic rays. We have then used these results to study the stability of cores in hydrostatic equilibrium in the limit where thermal pressure dominates over magnetic field and turbulence. We compare the density distribution derived in this manner with results obtained in the isothermal case. We find that for cores with characteristics similar to those observed in nearby molecular clouds, the gas and dust temperatures are coupled in the core interior with densities above ∼3×10 4 cm −3 . As a consequence, one expects that the gas temperature like the dust temperature decreases towards the center of these objects. However, the regime where gas and dust temperatures are coupled coincides approximately with that in which CO and many other molecular species deplete onto dust grain surfaces. At larger radii and lower densities, the gas and dust temperatures decouple and the gas temperature tends to the value expected for cosmic ray heating alone. The density structure which one computes taking into account such deviations from isothermality are not greatly different from that expected for an isothermal Bonnor-Ebert sphere. It is impossi- ble in the framework of these models to have a stable equilibrium core with mass above ∼5 Mand column density compatible with observed values (NH > 2 × 10 22 cm −2 or AV > 10 mag). We conclude from this that observed high mass cores are either supported by magnetic field or turbulence or are already in a state of collapse. Lower mass cores on the other hand have stable states where thermal pressure alone provides support against gravitation and we conclude that the much studied object B68 may be in a state of stable equilibrium if the internal gas temperature is computed in self-consistent fashion. Finally we note that in molecular clouds such as Ophiuchus and Orion with high radiation fields and pressures, gas and dust temperatures are expected to be well coupled and hence in the absence of an internal heat source, one expects temperatures to decrease towards core centers and to be relatively high as compared to low pressure clouds like Taurus.

Wannier functions analysis of the nonlinear Schrödinger equation with a periodic potential.

Abstract: In the present paper we use the Wannier function basis to construct lattice approximations of the nonlinear Schrodinger equation with a periodic potential. We show that the nonlinear Schrodinger equation with a periodic potential is equivalent to a vector lattice with long-range interactions. For the case-example of the cosine potential we study the validity of the so-called tight-binding approximation, i.e., the approximation when nearest neighbor interactions are dominant. The results are relevant to the Bose-Einstein condensate theory as well as to other physical systems, such as, for example, electromagnetic wave propagation in nonlinear photonic crystals.

Prospective Evaluation of the Peptide-Bound Collagen Type I Cross-Links N-Telopeptide and C-Telopeptide in Predicting Bone Metastases Status

Abstract: PURPOSE: The objective assessment of bone metastases is currently based on serial changes in skeletal survey. We performed a prospective study to determine whether a correlation exists between the ...

Asymptotically unbiased estimators of the tail index based on external estimation of the second order parameter

Abstract: In this paper we shall deal with the asymptotic and finite sample properties of “asymptotically unbiased” estimators of the tail index γ, based on “external” adequate estimators of the second order parameter ρ. The behavior of the ρ-estimator considered has indeed a high impact on the distributional properties of the final estimator of γ, and must be carefully chosen. As a by-product of the final study we present also the finite sample properties of a few ρ-estimators available in the literature.

Integrability of Poisson brackets

Abstract: We show that various notions of integrability for Poisson brackets are all equivalent, and we give the precise obstructions to integrating Poisson manifolds. We describe the integration as a symplectic quotient, in the spirit of the Poisson sigma-model of Cattaneo and Felder. For regular Poisson manifolds we express the obstructions in terms of variations of symplectic areas. As an application of these results, we show that a Poisson manifold admits a complete symplectic realization if, and only if, it is integrable. We discuss also the integration of submanifolds and Morita equivalence of Poisson manifolds.