Multiple Pathways Analysis of Brain Functional Networks from EEG Signals: An Application to Real Data

In the present study, we propose a theoretical graph procedure to investigate multiple pathways in brain functional networks. By taking into account all the possible paths consisting of h links between the nodes pairs of the network, we measured the global network redundancy R (h) as the number of parallel paths and the global network permeability P (h) as the probability to get connected. We used this procedure to investigate the structural and dynamical changes in the cortical networks estimated from a dataset of high-resolution EEG signals in a group of spinal cord injured (SCI) patients during the attempt of foot movement. In the light of a statistical contrast with a healthy population, the permeability index P (h) of the SCI networks increased significantly (P < 0.01) in the Theta frequency band (3-6 Hz) for distances h ranging from 2 to 4. On the contrary, no significant differences were found between the two populations for the redundancy index R (h) . The most significant changes in the brain functional network of SCI patients occurred mainly in the lower spectral contents. These changes were related to an improved propagation of communication between the closest cortical areas rather than to a different level of redundancy. This evidence strengthens the hypothesis of the need for a higher functional interaction among the closest ROIs as a mechanism to compensate the lack of feedback from the peripheral nerves to the sensomotor areas.

A Multitechnique Study of Structure and Dynamics of Polyfluorene Cast Films and the Influence on Their Photoluminescence

This article describes the microstructure and dynamics in the solid state of polyfluorene-based polymers, poly(9,)-dioctylfluorenyl-2,7-diyl) (PFO), a semicrystalline polymer, and poly [(9,9-dioctyl- 2,7-divinylene-fluorenylene)-alt-co-{2-methoxy-5-(2-ethyl-hexyloxy)- 1,4-phenylene vinylene}, a copolymer with mesomorphic phase properties. These Structures were determined by wide-angle X-ray scattering (WAXS) measurements, Assuming a packing model for the copolymer structure, where the planes of the phenyl rings are stacked and separated by an average distance of similar to 4.5 angstrom and laterally spaced by about similar to 16 angstrom, we followed the evolution of these distances as a function of temperature using WAXS and associated the changes observed to the polymer relaxation processes identified by dynamical mechanical thermal analysis. Specific molecular motions were studied by solid-state nuclear magnetic resonance. The onset of the side-chain motion at about 213 K (beta-relaxation) produced a small increase in the lateral spacing and in the stacking distance of the phenyl rings in them aggregated Structures, Besides, at about 383 K (alpha-relaxation) there occurs a significant increase in the amplitude of the torsion motion in the backbone, producing a greater increase in the stacking distance of the phenyl rings. Similar results were observed in the semicrystalline phase of PFO, but in this case the presence of the crystalline structure affects considerably the overall dynamics, which tends to be more hindered. Put together, Our data explain many features of the temperature dependence of the photoluminescence of these two polymers.

Structural and thermodynamic analysis of thrombin:suramin interaction in solution and crystal phases

Suramin is a hexasulfonated naphthylurea which has been recently characterized as a non-competitive inhibitor of human alpha-thrombin activity over fibrinogen, although its binding site and mode of interaction with the enzyme remain elusive. Here, we determined two X-ray structure of the thrombin: suramin complex, refined at 2.4 angstrom resolution. While a single thrombin: suramin complex was found in the asymmetric unit cell of the crystal, some of the crystallographic contacts with symmetrically related molecules are mediated by both the enzyme and the ligand. Molecular dynamics simulations with the 1:1 complex demonstrate a large rearrangement of suramin in the complex, but with the protein scaffold and the more extensive protein-ligand regions keep unchanged. Small-angle X-ray scattering measurements at high micromolar concentration demonstrate a suramin-induced dimerization of the enzyme. These data indicating a dissimilar binding mode in the monomeric and oligomeric states, with a monomeric, 1:1 complex to be more likely to exist at the thrombin physiological, nanomolar concentration range. Collectively, close understanding on the structural basis for interaction is given which might establish a basis for design of suramin analogues targeting thrombin. Crown Copyright (C) 2009 Published by Elsevier B.V. All rights reserved.

Analysis of Agonist and Antagonist Effects on Thyroid Hormone Receptor Conformation by Hydrogen/Deuterium Exchange

Thyroid hormone receptors (TRs) are ligand-gated transcription factors with critical roles in development and metabolism. Although x-ray structures of TR ligand-binding domains (LBDs) with agonists are available, comparable structures without ligand (apo-TR) or with antagonists are not. It remains important to understand apo-LBD conformation and the way that it rearranges with ligands to develop better TR pharmaceuticals. In this study, we conducted hydrogen/deuterium exchange on TR LBDs with or without agonist (T(3)) or antagonist (NH(3)). Both ligands reduce deuterium incorporation into LBD amide hydrogens, implying tighter overall folding of the domain. As predicted, mass spectroscopic analysis of individual proteolytic peptides after hydrogen/deuterium exchange reveals that ligand increases the degree of solvent protection of regions close to the buried ligand-binding pocket. However, there is also extensive ligand protection of other regions, including the dimer surface at H10-H11, providing evidence for allosteric communication between the ligand-binding pocket and distant interaction surfaces. Surprisingly, C-terminal activation helix H12, which is known to alter position with ligand, remains relatively protected from solvent in all conditions suggesting that it is packed against the LBD irrespective of the presence or type of ligand. T(3), but not NH(3), increases accessibility of the upper part of H3-H5 to solvent, and we propose that TR H12 interacts with this region in apo-TR and that this interaction is blocked by T(3) but not NH(3.) We present data from site-directed mutagenesis experiments and molecular dynamics simulations that lend support to this structural model of apo-TR and its ligand-dependent conformational changes. (Molecular Endocrinology 25: 15-31, 2011)

The effects of anticalcification treatments and hydration on the molecular dynamics of bovine pericardium collagen as revealed by (13)C solid-state NMR

This article describes a solid-state NMR (SSNMR) investigation of the influence of hydration and chemical cross-linking on the molecular dynamics of the constituents of the bovine pericardium (BP) tissues and its relation to the mechanical properties of the tissue. Samples of natural phenetylamine-diepoxide (DE)- and glutaraldehyde (GL)-fixed BP were investigated by (13)C cross-polarization SSNMR to probe the dynamics of the collagen, and the results were correlated to the mechanical properties of the tissues, probed by dynamical mechanical analysis. For samples of natural BP, the NMR results show that the higher the hydration level the more pronounced the molecular dynamics of the collagen backbone and sidechains, decreasing the tissue`s elastic modulus. In contrast, in DE- and GL-treated samples, the collagen molecules are more rigid, and the hydration seems to be less effective in increasing the collagen molecular dynamics and reducing the mechanical strength of the samples. This is mostly attributed to the presence of cross-links between the collagen plates, which renders the collagen mobility less dependent on the water absorption in chemically treated samples. Copyright (C) 2010 John Wiley & Sons, Ltd.

Neoproterozoic glacial dynamics revealed by provenance of diamictites of the Bebedouro Formation, Sao Francisco Craton, Central Eastern Brazil

One of the main questions on Neoproterozoic geology regards the extent and dynamics of the glacial systems that are recorded in all continents. We present evidence for short transport distances and localized sediment sources for the Bebedouro Formation, which records Neoproterozoic glaciomarine sedimentation in the central-eastern Sao Francisco Craton (SFC), Brazil. New data are presented on clast composition, based on point counting in thin section and SHRIMP dating of pebbles and detrital zircon. Cluster analysis of clast compositional data revealed a pronounced spatial variability of clast composition on diamictite indicating the presence of individual glaciers or ice streams feeding the basin. Detrital zircon ages reveal distinct populations of Archean and Palaeoproterozoic age. The youngest detrital zircon dated at 874 +/- 9 Ma constrains the maximum depositional age of these diamictites. We interpret the provenance of the glacial diamictites to be restricted to sources inside the SFC, suggesting deposition in an environment similar to ice streams from modern, high latitude glaciers.

Palaeodrainage on Marajo Island, northern Brazil, in relation to Holocene relative sea-level dynamics

A large area in northeastern Marajo Island, northern Brazil, has been characterized geomorphologically, applying information acquired from Landsat imagery. This study was combined with detailed sedimentologic analysis of continuous cores, which provided a record of depositional settings developed in this area through the Holocene. The results revealed well-preserved, meandering to anastomosed drainage networks of wide palaeochannels that were superimposed by a narrower palaeochannel system. In both cases, the sedimentary record consists of sands, heterolithic deposits and muds, locally rich in plant debris. The strata are organized into fining upward successions that reach approximately 18 m thick in the wide channels and 4 m thick in the narrow channels. Sedimentary features suggestive of a coastal location for the wider palaeochannels and reworking of sediments by tidal currents include the prevalence of well to moderately sorted, rounded to sub-rounded, fine- to medium-grained sands displaying foreset packages separated by mud couplets, suggestive of tidal cycles. The data presented herein point to a rise in relative sea level reaching the Lake Arari area during the early to late/mid Holocene. This event was followed by a relative sea level drop. Tectonics seem to have contributed to an overall lowering in relative sea level in the study area since the mid-Holocene, which does not follow the same pattern recorded in other areas along the northern Brazilian coast.

STABILITY ANALYSIS WITH APPLICATIONS OF A TWO-DIMENSIONAL DYNAMICAL SYSTEM ARISING FROM A STOCHASTIC MODEL FOR AN ASSET MARKET

We analyze the stability properties of equilibrium solutions and periodicity of orbits in a two-dimensional dynamical system whose orbits mimic the evolution of the price of an asset and the excess demand for that asset. The construction of the system is grounded upon a heterogeneous interacting agent model for a single risky asset market. An advantage of this construction procedure is that the resulting dynamical system becomes a macroscopic market model which mirrors the market quantities and qualities that would typically be taken into account solely at the microscopic level of modeling. The system`s parameters correspond to: (a) the proportion of speculators in a market; (b) the traders` speculative trend; (c) the degree of heterogeneity of idiosyncratic evaluations of the market agents with respect to the asset`s fundamental value; and (d) the strength of the feedback of the population excess demand on the asset price update increment. This correspondence allows us to employ our results in order to infer plausible causes for the emergence of price and demand fluctuations in a real asset market. The employment of dynamical systems for studying evolution of stochastic models of socio-economic phenomena is quite usual in the area of heterogeneous interacting agent models. However, in the vast majority of the cases present in the literature, these dynamical systems are one-dimensional. Our work is among the few in the area that construct and study analytically a two-dimensional dynamical system and apply it for explanation of socio-economic phenomena.

Dynamic Changes in the Mental Rotation Network Revealed by Pattern Recognition Analysis of fMRI Data

We investigated the temporal dynamics and changes in connectivity in the mental rotation network through the application of spatio-temporal support vector machines (SVMs). The spatio-temporal SVM [Mourao-Miranda, J., Friston, K. J., et al. (2007). Dynamic discrimination analysis: A spatial-temporal SVM. Neuroimage, 36, 88-99] is a pattern recognition approach that is suitable for investigating dynamic changes in the brain network during a complex mental task. It does not require a model describing each component of the task and the precise shape of the BOLD impulse response. By defining a time window including a cognitive event, one can use spatio-temporal fMRI observations from two cognitive states to train the SVM. During the training, the SVM finds the discriminating pattern between the two states and produces a discriminating weight vector encompassing both voxels and time (i.e., spatio-temporal maps). We showed that by applying spatio-temporal SVM to an event-related mental rotation experiment, it is possible to discriminate between different degrees of angular disparity (0 degrees vs. 20 degrees, 0 degrees vs. 60 degrees, and 0 degrees vs. 100 degrees), and the discrimination accuracy is correlated with the difference in angular disparity between the conditions. For the comparison with highest accuracy (08 vs. 1008), we evaluated how the most discriminating areas (visual regions, parietal regions, supplementary, and premotor areas) change their behavior over time. The frontal premotor regions became highly discriminating earlier than the superior parietal cortex. There seems to be a parcellation of the parietal regions with an earlier discrimination of the inferior parietal lobe in the mental rotation in relation to the superior parietal. The SVM also identified a network of regions that had a decrease in BOLD responses during the 100 degrees condition in relation to the 0 degrees condition (posterior cingulate, frontal, and superior temporal gyrus). This network was also highly discriminating between the two conditions. In addition, we investigated changes in functional connectivity between the most discriminating areas identified by the spatio-temporal SVM. We observed an increase in functional connectivity between almost all areas activated during the 100 degrees condition (bilateral inferior and superior parietal lobe, bilateral premotor area, and SMA) but not between the areas that showed a decrease in BOLD response during the 100 degrees condition.

Excited-state dynamics of polyfluorene derivatives in solution

The excited-state dynamics of two polyfluorene copolymers, one fully conjugated containing phenylene vinylene units alternated with 9,9`-dihexylfluorenyl groups and the other segmented by -(CH2)(8)- spacer, were studied in dilute solution of different solvents using a picosecond single-photon timing technique. The excited-state dynamics of the segmented copolymer follows the Forster resonant energy-transfer model which describes intrachain energy-transfer kinetics among random oriented chromophores. Energy transfer is confirmed by analysis of fluorescence anisotropy relaxation with the measurement of a short decay component of about 60 ps. The fluorescence decay surface of the fully conjugated copolymer is biexponential with decay times of about 470 and 900 ps, ascribed to deactivation of chain moieties containing trans and cis isomers already in a photostationary condition. Thus, energy transfer is very fast due to the conjugated nature and rigid-rod-like structure of this copolymer chain.

Structural studies of prephenate dehydratase from Mycobacterium tuberculosis H37Rv by SAXS, ultracentrifugation, and computational analysis

Tuberculosis (TB) is one of the most common infectious diseases known to man and responsible for millions of human deaths in the world. The increasing incidence of TB in developing countries, the proliferation of multidrug resistant strains, and the absence of resources for treatment have highlighted the need of developing new drugs against TB. The shikimate pathway leads to the biosynthesis of chorismate, a precursor of aromatic amino acids. This pathway is absent from mammals and shown to be essential for the survival of Mycobacterium tuberculosis, the causative agent of TB. Accordingly, enzymes of aromatic amino acid biosynthesis pathway represent promising targets for structure-based drug design. The first reaction in phenylalanine biosynthesis involves the conversion of chorismate to prephenate, catalyzed by chorismate mutase. The second reaction is catalyzed by prephenate dehydratase (PDT) and involves decarboxylation and dehydratation of prephenate to form phenylpyruvate, the precursor of phenylalanine. Here, we describe utilization of different techniques to infer the structure of M. tuberculosis PDT (MtbPDT) in solution. Small angle X-ray scattering and ultracentrifugation analysis showed that the protein oligomeric state is a tetramer and MtbPDT is a flat disk protein. Bioinformatics tools were used to infer the structure of MtbPDT A molecular model for MtbPDT is presented and molecular dynamics simulations indicate that MtbPDT i.s stable. Experimental and molecular modeling results were in agreement and provide evidence for a tetrameric state of MtbPDT in solution.

Essays on firm dynamics in the Swedish wholesale trade sector

This thesis consists of a summary and five self-contained papers addressing dynamics of firms in the Swedish wholesale trade sector. Paper [1] focuses upon determinants of new firm formation in the Swedish wholesale trade sector, using two definitions of firms’ relevant markets, markets defined as administrative areas, and markets based on a cost minimizing behavior of retailers. The paper shows that new entering firms tend to avoid regions with already high concentration of other firms in the same branch of wholesaling, while right-of-the-center local government and quality of the infrastructure have positive impacts upon entry of new firms. The signs of the estimated coefficients remain the same regardless which definition of relevant market is used, while the size of the coefficients is generally higher once relevant markets delineated on the cost-minimizing assumption of retailers are used. Paper [2] analyses determinant of firm relocation, distinguishing between the role of the factors in in-migration municipalities and out-migration municipalities. The results of the analysis indicate that firm-specific factors, such as profits, age and size of the firm are negatively related to the firm’s decision to relocate. Furthermore, firms seems to be avoiding municipalities with already high concentration of firms operating in the same industrial branch of wholesaling and also to be more reluctant to leave municipalities governed by right-of-the- center parties. Lastly, firms seem to avoid moving to municipalities characterized with high population density. Paper [3] addresses determinants of firm growth, adopting OLS and a quantile regression technique. The results of this paper indicate that very little of the firm growth can be explained by the firm-, industry- and region-specific factors, controlled for in the estimated models. Instead, the firm growth seems to be driven by internal characteristics of firms, factors difficult to capture in conventional statistics. This result supports Penrose’s (1959) suggestion that internal resources such as firm culture, brand loyalty, entrepreneurial skills, and so on, are important determinants of firm growth rates. Paper [4] formulates a forecasting model for firm entry into local markets and tests this model using data from the Swedish wholesale industry. The empirical analysis is based on directly estimating the profit function of wholesale firms and identification of low- and high-return local markets. The results indicate that 19 of 30 estimated models have more net entry in high-return municipalities, but the estimated parameters is only statistically significant at conventional level in one of our estimated models, and then with unexpected negative sign. Paper [5] studies effects of firm relocation on firm profits of relocating firms, employing a difference-in-difference propensity score matching. Using propensity score matching, the pre-relocalization differences between relocating and non-relocating firms are balanced, while the difference-in-difference estimator controls for all time-invariant unobserved heterogeneity among firms. The results suggest that firms that relocate increase their profits significantly, in comparison to what the profits would be had the firms not relocated. This effect is estimated to vary between 3 to 11 percentage points, depending on the length of the analyzed period. 

Exchange rate dynamics in Brazil

The paper aims to investigate on empirical and theoretical grounds the Brazilian exchange rate dynamics under floating exchange rates. The empirical analysis examines the short and long term behavior of the exchange rate, interest rate (domestic and foreign) and country risk using econometric techniques such as variance decomposition, Granger causality, cointegration tests, error correction models, and a GARCH model to estimate the exchange rate volatility. The empirical findings suggest that one can argue in favor of a certain degree of endogeneity of the exchange rate and that flexible rates have not been able to insulate the Brazilian economy in the same patterns predicted by literature due to its own specificities (managed floating with the use of international reserves and domestic interest rates set according to inflation target) and to externally determined variables such as the country risk. Another important outcome is the lack of a closer association of domestic and foreign interest rates since the new exchange regime has been adopted. That is, from January 1999 to May 2004, the US monetary policy has no significant impact on the Brazilian exchange rate dynamics, which has been essentially endogenous primarily when we consider the fiscal dominance expressed by the probability of default.

Endogenous protection in Mercosul: an empirical analysis

This paper analyses the equilibrium structure of protection in Mercosul, developing empirical analyses based on the literature ensuing from the sequence of models set forth by Grossman and Helpman since 1994. Not only Mercosul’s common external tariff (CET) may be explained under a political economy perspective, but the existence of deviations, both at the level of the external tariffs and at that of the internal ones, make it interesting to contrast several structures under this approach. Different general equilibrium frameworks, in which governments are concerned with campaign contributions and with the welfare of the average voter, while organized special-interest groups care only about the welfare of their members, are used as the theoretical basis of the empirical tests. We build a single equation for explaining the CET and two fourequations systems (one equation for each member) for explaining deviations from the CET and from the internal free trade between members. The results (at the two-digit level) shed an interesting light on the sectoral dynamics of protection in each country; notably, Brazil seems to fit in better in the model framework, followed by Uruguay. In the case of the CET, and of deviations from it, the interaction between the domestic lobbies in the four countries plays a major role. There is also suggestion that the lobby structure that bid for deviations, be they internal or external, differs from the one which bid for the CET.

Dynamics of micro-entrepeneurial activities

This paper generates and organizes stylized facts related to the dynamics of selfemployment activities in Brazil. The final purpose is to help the design of policies to assist micro-entrepreneurial units. The 'first part of the paper uses as a main tool of analysis transitional data constructed from household surveys. The longitudinal information used covers three transition horizons: 1-month, 12-month and 5-year periods. Quantitative flows analysis assesses the main origins, destinies and various types of risks assumed by microentrepreneurial activities. Complementarily, logistic regressions provides evidence on the main characteristics and resources of micro-entrepreneurial units. In particular, we use the movements from self-employment to employer activities as measures of entrepreneurial success. We also use these transitions as measures of employment creation intensity within the self-employed segment.The second part of the paper explores various data sources. First, we attempt to analyze the life-cycle trajectories and determinants of self-employment. We use cohort data constructed from PME and qualitative data on financial and work history factors related to the opening of small bussiness from the informal firms survey implemented during 1994. Second, we apply a standart Mincerian wage equation approach to self-employment profits. This exerci se attempts to capture the correlation patterns between micro-entrepreneurial performance and a variety of firms leveI variables present in the 1994 Informal Survey. Finally, we use a a survey on the poor enterpreneurs of Rocinha favela as a laboratory to study poor entrepreneurs resources and behavior.In sum, the main questions pursued in the paper are: i) who are the Brazilian selfemployed?; ii) in particular: what is relative importance among the self-employed of subsistence activities versus those activities with growth and capital accumulation potential?; iii) what are the main static and dynamic determinants ofmicro-entrepreneurial success?; iv) what is the degree ofrisk associated with micro-entrepreneurial activities in Brazil?; v) What is the life-cycle profile of self-employment?; vi) what are the main constraints on poor entrepreneurs activities?.