Testosterone Induces Vascular Smooth Muscle Cell Migration by NADPH Oxidase and c-Src-Dependent Pathways

Testosterone has been implicated in vascular remodeling associated with hypertension. Molecular mechanisms underlying this are elusive, but oxidative stress may be important. We hypothesized that testosterone stimulates generation of reactive oxygen species (ROS) and migration of vascular smooth muscle cells (VSMCs), with enhanced effects in cells from spontaneously hypertensive rats (SHRs). The mechanisms (genomic and nongenomic) whereby testosterone induces ROS generation and the role of c-Src, a regulator of redox-sensitive migration, were determined. VSMCs from male Wistar-Kyoto rats and SHRs were stimulated with testosterone (10(-7) mol/L, 0-120 minutes). Testosterone increased ROS generation, assessed by dihydroethidium fluorescence and lucigenin-enhanced chemiluminescence (30 minutes [SHR] and 60 minutes [both strains]). Flutamide (androgen receptor antagonist) and actinomycin D (gene transcription inhibitor) diminished ROS production (60 minutes). Testosterone increased Nox1 and Nox4 mRNA levels and p47phox protein expression, determined by real-time PCR and immunoblotting, respectively. Flutamide, actinomycin D, and cycloheximide (protein synthesis inhibitor) diminished testosterone effects on p47phox. c-Src phosphorylation was observed at 30 minutes (SHR) and 120 minutes (Wistar-Kyoto rat). Testosterone-induced ROS generation was repressed by 3-(4-chlorophenyl) 1-(1,1-dimethylethyl)-1H-pyrazolo[3,4-day]pyrimidin-4-amine (c-Src inhibitor) in SHRs and reduced by apocynin (antioxidant/NADPH oxidase inhibitor) in both strains. Testosterone stimulated VSMCs migration, assessed by the wound healing technique, with greater effects in SHRs. Flutamide, apocynin, and 3-(4-chlorophenyl) 1-(1,1-dimethylethyl)-1H-pyrazolo[3,4-day] pyrimidin-4-amine blocked testosterone-induced VSMCs migration in both strains. Our study demonstrates that testosterone induces VSMCs migration via NADPH oxidase-derived ROS and c-Src-dependent pathways by genomic and nongenomic mechanisms, which are differentially regulated in VSMCs from Wistar-Kyoto rats and SHRs. (Hypertension. 2012; 59: 1263-1271.). Online Data Supplement

Cash balance management: A comparison between genetic algorithms and particle swarm optimization

This work aimed to apply genetic algorithms (GA) and particle swarm optimization (PSO) in cash balance management using Miller-Orr model, which consists in a stochastic model that does not define a single ideal point for cash balance, but an oscillation range between a lower bound, an ideal balance and an upper bound. Thus, this paper proposes the application of GA and PSO to minimize the Total Cost of cash maintenance, obtaining the parameter of the lower bound of the Miller-Orr model, using for this the assumptions presented in literature. Computational experiments were applied in the development and validation of the models. The results indicated that both the GA and PSO are applicable in determining the cash level from the lower limit, with best results of PSO model, which had not yet been applied in this type of problem.

Increased fibroblast telomerase expression precedes myofibroblast alpha-smooth muscle actin expression in idiopathic pulmonary fibrosis

OBJECTIVE: This study sought to identify the relationship between fibroblast telomerase expression, myofibroblasts, and telomerase-mediated regulatory signals in idiopathic pulmonary fibrosis. METHODS: Thirty-four surgical lung biopsies, which had been obtained from patients with idiopathic pulmonary fibrosis and histologically classified as usual interstitial pneumonia, were examined. Immunohistochemistry was used to evaluate fibroblast telomerase expression, myofibroblast alpha-smooth muscle actin expression and the tissue expression of interleukin-4, transforming growth factor-beta, and basic fibroblast growth factor. The point-counting technique was used to quantify the expression of these markers in unaffected, collapsed, mural fibrosis, and honeycombing areas. The results were correlated to patient survival. RESULTS: Fibroblast telomerase expression and basic fibroblast growth factor tissue expression were higher in collapsed areas, whereas myofibroblast expression and interleukine-4 tissue expression were higher in areas of mural fibrosis. Transforming growth factor-beta expression was higher in collapsed, mural fibrosis and honeycombing areas in comparison to unaffected areas. Positive correlations were found between basic fibroblast growth factor tissue expression and fibroblast telomerase expression and between interleukin-4 tissue expression and myofibroblast alpha-smooth muscle actin expression. Negative correlations were observed between interleukin-4 expression and basic fibroblast growth factor tissue expression in areas of mural fibrosis. Myofibroblast alpha-smooth muscle actin expression and interleukin-4 tissue expression in areas of mural fibrosis were negatively associated with patient survival. CONCLUSION: Fibroblast telomerase expression is higher in areas of early remodeling in lung tissues demonstrating typical interstitial pneumonia, whereas myofibroblast alpha-smooth muscle actin expression predominates in areas of late remodeling. These events seem to be regulated by basic fibroblast growth factor and interleukin-4 tissue expression, respectively.

Energy and system-size dependence of two- and four-particle nu(2) measurements in heavy-ion collisions at root S-NN=62.4 and 200 GeV and their implications on flow fluctuations and nonflow

We present STAR measurements of azimuthal anisotropy by means of the two- and four-particle cumulants nu(2) (nu(2){2} and nu(2){4}) for Au + Au and Cu + Cu collisions at center-of-mass energies root S-NN = 62.4 and 200 GeV. The difference between nu(2){2}(2) and nu(2){4}(2) is related to nu(2) fluctuations (sigma(nu 2)) and nonflow (delta(2)). We present an upper limit to sigma(nu 2)/nu 2. Following the assumption that eccentricity fluctuations sigma(epsilon) dominate nu(2) fluctuations nu(2)/sigma nu(2) approximate to epsilon/sigma epsilon we deduce the nonflow implied for several models of eccentricity fluctuations that would be required for consistency with nu(2){2} and nu(2){4}. We also present results on the ratio of nu(2) to eccentricity.

Analog circuit synthesis performing fast Pareto frontier exploration and analysis through 3D graphs

This paper presents a technique for performing analog design synthesis at circuit level providing feedback to the designer through the exploration of the Pareto frontier. A modified simulated annealing which is able to perform crossover with past anchor points when a local minimum is found which is used as the optimization algorithm on the initial synthesis procedure. After all specifications are met, the algorithm searches for the extreme points of the Pareto frontier in order to obtain a non-exhaustive exploration of the Pareto front. Finally, multi-objective particle swarm optimization is used to spread the results and to find a more accurate frontier. Piecewise linear functions are used as single-objective cost functions to produce a smooth and equal convergence of all measurements to the desired specifications during the composition of the aggregate objective function. To verify the presented technique two circuits were designed, which are: a Miller amplifier with 96 dB Voltage gain, 15.48 MHz unity gain frequency, slew rate of 19.2 V/mu s with a current supply of 385.15 mu A, and a complementary folded cascode with 104.25 dB Voltage gain, 18.15 MHz of unity gain frequency and a slew rate of 13.370 MV/mu s. These circuits were synthesized using a 0.35 mu m technology. The results show that the method provides a fast approach for good solutions using the modified SA and further good Pareto front exploration through its connection to the particle swarm optimization algorithm.

J/psi production as a function of charged particle multiplicity in pp collisions at root s=7 TeV

The ALICE Collaboration reports the measurement of the relative J/psi yield as a function of charged particle pseudorapidity density dN(ch)/d eta in pp collisions at root s = 7 TeV at the LHC. J/psi particles are detected for p(t) > 0, in the rapidity interval vertical bar y vertical bar < 0.9 via decay into e(+)e(-), and in the interval 2.5 < y < 4.0 via decay into mu(+)/mu(-) pairs. An approximately linear increase of the J/psi yields normalized to their event average (dN(J/psi)/dy)/(dN(J/psi)/dy) with (dN(ch)/c eta)/(dN(ch)/d eta) is observed in both rapidity ranges, where dN(ch)/d eta is measured within vertical bar eta vertical bar < 1 and p(t) > 0. In the highest multiplicity interval with (dN(ch)/d eta)(bin)) = 24.1, corresponding to four times the minimum bias multiplicity density, an enhancement relative to the minimum bias J/psi yield by a factor of about 5 at 2.5 < y <4 (8 at vertical bar y vertical bar < 0.9) is observed. (C) 2012 CERN. Published by Elsevier B.V. All rights reserved.

Hydrodynamic analysis of particle collection efficiency: comparing downflow and upflow filtration

Models of the filtration phenomenon describe the mass balance in bed filtration in terms of particle removal mechanisms, and allow for the determination of global particle removal efficiencies. These models are defined in terms of the geometry and characteristic elements of granule collectors, particles and fluid, and also the composition of the balance of forces that act in the particle collector system. This work analyzes particles collection efficiency comparing downflow and upflow direct filtration, taking into account the contribution of the gravitational factor of the settling removal efficiency in future proposal of initial collection efficiency models for upflow filtration. A qualitative analysis is also made of the proposal for the collection efficiency models for particle removal in direct downflow and upflow filtration using a Computational Fluid Dynamics (CFD) tool. This analysis showed a strong influence of gravitational factor in initial collection efficiency (t = 0) of particles, as well as the reasons of their values to be smaller for upflow filtration in comparison with the downflow filtration.

Particle Acceleration in Turbulence and Weakly Stochastic Reconnection

In this Letter we analyze the energy distribution evolution of test particles injected in three dimensional (3D) magnetohydrodynamic (MHD) simulations of different magnetic reconnection configurations. When considering a single Sweet-Parker topology, the particles accelerate predominantly through a first-order Fermi process, as predicted in [3] and demonstrated numerically in [8]. When turbulence is included within the current sheet, the acceleration rate is highly enhanced, because reconnection becomes fast and independent of resistivity [4,11] and allows the formation of a thick volume filled with multiple simultaneously reconnecting magnetic fluxes. Charged particles trapped within this volume suffer several head-on scatterings with the contracting magnetic fluctuations, which significantly increase the acceleration rate and results in a first-order Fermi process. For comparison, we also tested acceleration in MHD turbulence, where particles suffer collisions with approaching and receding magnetic irregularities, resulting in a reduced acceleration rate. We argue that the dominant acceleration mechanism approaches a second order Fermi process in this case.

Roof modular system in wood and particle board (OSB) to rural construction

Wood is a material of great applicability in construction, with advantageous properties to form various structural systems, such as walls and roof. Most of the roof structural systems follow models that have remained unchanged for a long time. A roof modular system in distinguished materials is proposed: reforested wood (Pine), oriented strand board (OSB) and roof tiles made of recycled long-life packaging material in order to be applied in rural construction. In this alternative, besides the benefit of giving destination packages with long-life thermal comfort, it also highlights the use of reforestated wood being the cultivation of such species that provides incentive for agribusiness. The structural performance of this alternative was evaluated through computer modeling and test results of two modular panels. The analysis is based on the results of vertical displacements, deformations and stresses. A positive correlation between theoretical and experimental values was observed, indicating the model's feasibility for use in roof structures. Therefore, the modular system represents a solution to new architecture conceptions to rural construction, for example, storage construction, cattle handling and poultry, with benefits provided by prefabricated building systems.

Macroalgal composition and its association with local hydrodynamics in the Laje de Santos Marine State Park, southwestern Atlantic, São Paulo, Brazil

The Laje de Santos Marine State Park (LSMSP), located in southeastern Brazil, is the only marine park in São Paulo State. This conservation unit has been established as a protected area of high biological diversity. Despite its importance for the conservation of the marine biota, little is known about the park's seaweed flora. The objectives of this study were as follows: to furnish increased knowledge of the composition of the macroalgae in the Park area; to relate the area's macroalgal composition to the presence of an important water mass in the region, the South Atlantic Central Water (SACW); and to investigate the possible influence of the Port of Santos on the composition of the macroalgae of the LSMSP. This study registered 31 new records for the LSMSP, 11 for São Paulo State, four for Brazil, one for the western Atlantic and one for the South Atlantic Ocean, in addition to the possible occurrence of one new species of Osmundea (Rhodomelaceae) and one new genus belonging to Ceramiaceae. The taxonomic composition of the macroalgae had a direct correlation with the arrival of the SACW in the summer-fall season. The SACW generated a strong thermocline and increased the supply of nutrients in the water column. Hydrodynamic and dispersion modeling analyses suggested that the Port of Santos influenced the composition of the LSMSP phycoflora.

Increased fibroblast telomerase expression precedes myofibroblast α-smooth muscle actin expression in idiopathic pulmonary fibrosis

OBJECTIVE: This study sought to identify the relationship between fibroblast telomerase expression, myofibroblasts, and telomerase-mediated regulatory signals in idiopathic pulmonary fibrosis. METHODS: Thirty-four surgical lung biopsies, which had been obtained from patients with idiopathic pulmonary fibrosis and histologically classified as usual interstitial pneumonia, were examined. Immunohistochemistry was used to evaluate fibroblast telomerase expression, myofibroblast α-smooth muscle actin expression and the tissue expression of inter leu kin-4, transforming growth factor-β, and basic fibroblast growth factor. The point-counting technique was used to quantify the expression of these markers in unaffected, collapsed, mural fibrosis, and honeycombing areas. The results were correlated to patient survival. RESULTS: Fibroblast telomerase expression and basic fibroblast growth factor tissue expression were higher in collapsed areas, whereas myofibroblast expression and interleukine-4 tissue expression were higher in areas of mural fibrosis. Transforming growth factor-β expression was higher in collapsed, mural fibrosis and honeycombing areas in comparison to unaffected areas. Positive correlations were found between basic fibroblast growth factor tissue expression and fibroblast telomerase expression and between interleukin-4 tissue expression and myofibroblast α-smooth muscle actin expression. Negative correlations were observed between interleukin-4 expression and basic fibroblast growth factor tissue expression in areas of mural fibrosis. Myofibroblast α-smooth muscle actin expression and interleukin-4 tissue expression in areas of mural fibrosis were negatively associated with patient survival. CONCLUSION: Fibroblast telomerase expression is higher in areas of early remodeling in lung tissues demonstrating typical interstitial pneumonia, whereas myofibroblast α-smooth muscle actin expression predominates in areas of late remodeling. These events seem to be regulated by basic fibroblast growth factor and interleukin-4 tissue expression, respectively.

Chemically Resolved Particle Fluxes Over Tropical and Temperate Forests

Chemically resolved submicron (PM1) particlemass fluxes were measured by eddy covariance with a high resolution time-of-flight aerosolmass spectrometer over temperate and tropical forests during the BEARPEX-07 and AMAZE-08 campaigns. Fluxes during AMAZE-08 were small and close to the detection limit (<1 ng m−2 s−1) due to low particle mass concentrations (<1 μg m−3). During BEARPEX-07, concentrations were five times larger, with mean mid-day deposition fluxes of −4.8 ng m−2 s−1 for total nonrefractory PM1 (Vex,PM1 = −1 mm s−1) and emission fluxes of +2.6 ng m−2 s−1 for organic PM1 (Vex,org = +1 mm s−1). Biosphere–atmosphere fluxes of different chemical components are affected by in-canopy chemistry, vertical gradients in gas-particle partitioning due to canopy temperature gradients, emission of primary biological aerosol particles, and wet and dry deposition. As a result of these competing processes, individual chemical components had fluxes of varying magnitude and direction during both campaigns. Oxygenated organic components representing regionally aged aerosol deposited, while components of fresh secondary organic aerosol (SOA) emitted. During BEARPEX-07, rapid incanopy oxidation caused rapid SOA growth on the timescale of biosphere-atmosphere exchange. In-canopy SOA mass yields were 0.5–4%. During AMAZE-08, the net organic aerosol flux was influenced by deposition, in-canopy SOA formation, and thermal shifts in gas-particle partitioning.Wet deposition was estimated to be an order ofmagnitude larger than dry deposition during AMAZE-08. Small shifts in organic aerosol concentrations from anthropogenic sources such as urban pollution or biomass burning alters the balance between flux terms. The semivolatile nature of the Amazonian organic aerosol suggests a feedback in which warmer temperatures will partition SOA to the gas-phase, reducing their light scattering and thus potential to cool the region.

Anomalous diffusion evidenced by particle tracking at high frame rates.

Diffusion is a common phenomenon in nature and generally is associated with a system trying to reach a local or a global equilibrium state, as a result of highly irregular individual particle motion. Therefore it is of fundamental importance in physics, chemistry and biology. Particle tracking in complex fluids can reveal important characteristics of its properties. In living cells, we coat the microbead with a peptide (RGD) that binds to integrin receptors at the plasma membrane, which connects to the CSK. This procedure is based on the hypothesis that the microsphere can move only if the structure where it is attached move as well. Then, the observed trajectory of microbeads is a probe of the cytoskeleton (CSK), which is governed by several factors, including thermal diffusion, pressure gradients, and molecular motors. The possibility of separating the trajectories into passive and active diffusion may give information about the viscoelasticity of the cell structure and molecular motors activity. And also we could analyze the motion via generalized Stokes-Einstein relation, avoiding the use of any active techniques. Usually a 12 to 16 Frames Per Second (FPS) system is used to track the microbeads in cell for about 5 minutes. Several factors make this FPS limitation: camera computer communication, light, computer speed for online analysis among others. Here we used a high quality camera and our own software, developed in C++ and Linux, to reach high FPS. Measurements were conducted with samples for 10£ and 20£ objectives. We performed sequentially images with different intervals, all with 2 ¹s exposure. The sequences of intervals are in milliseconds: 4 5 ms (maximum speed) 14, 25, 50 and 100 FPS. Our preliminary results highlight the difference between passive and active diffusion, since the passive diffusion is represented by a Gaussian in the distribution of displacements of the center of mass of individual beads between consecutive frames. However, the active process, or anomalous diffusion, shows as long tails in the distribution of displacements.

Mechanical Alterations in airway smooth muscle after interaction with indoor pollutant – A mathematical model.

The viscoelasticity of mammalian lung is determined by the mechanical properties and structural regulation of the airway smooth muscle (ASM). The exposure to polluted air may deteriorate these properties with harmful consequences to individual health. Formaldehyde (FA) is an important indoor pollutant found among volatile organic compounds. This pollutant permeates through the smooth muscle tissue forming covalent bonds between proteins in the extracellular matrix and intracellular protein structure changing mechanical properties of ASM and inducing asthma symptoms, such as airway hyperresponsiveness, even at low concentrations. In the experimental scenario, the mechanical effect of FA is the stiffening of the tissue, but the mechanism behind this effect is not fully understood. Thus, the aim of this study is to reproduce the mechanical behavior of the ASM, such as contraction and stretching, under FA action or not. For this, it was created a two-dimensional viscoelastic network model based on Voronoi tessellation solved using Runge-Kutta method of fourth order. The equilibrium configuration was reached when the forces in different parts of the network were equal. This model simulates the mechanical behavior of ASM through of a network of dashpots and springs. This dashpot-spring mechanical coupling mimics the composition of the actomyosin machinery of ASM through the contraction of springs to a minimum length. We hypothesized that formation of covalent bonds, due to the FA action, can be represented in the model by a simple change in the elastic constant of the springs, while the action of methacholine (MCh) reduce the equilibrium length of the spring. A sigmoid curve of tension as a function of MCh doses was obtained, showing increased tension when the muscle strip was exposed to FA. Our simulations suggest that FA, at a concentration of 0.1 ppm, can affect the elastic properties of the smooth muscle ¯bers by a factor of 120%. We also analyze the dynamic mechanical properties, observing the viscous and elastic behavior of the network. Finally, the proposed model, although simple, incorporates the phenomenology of both MCh and FA and reproduces experimental results observed with in vitro exposure of smooth muscle to FA. Thus, this new mechanical approach incorporates several well know features of the contractile system of the cells in a tissue level model. The model can also be used in different biological scales.

Currents controlling sedimentation, deposits recording palaeo-hydrodynamics – lessons from the continental shelf-slope system off SE South America

The continental margin off SE South America hosts one of the world’s most energetic hydrodynamic regimes but also the second largest drainage system of the continent. Both, the ocean current system as well as the fluvial runoff are strongly controlled by the atmospheric circulation modes over the region. The distribution pattern of particular types of sediments on shelf and slope and the long-term built-up of depositional elements within the overall margin architecture are, thus, the product of both, seasonal to millennial variability as well as long-term environmental trends. This talk presents how the combination of different methodological approaches can be used to obtain a comprehensive picture of the variability of a shelf and upper-slope hydrodynamic system during Holocene times. The particular methods applied are: (a) Margin-wide stratigraphic information to elucidate the role of sea level for the oceanographic and sedimentary systems since the last glacial maximum; (b) Palaeoceanographic sediment proxies combined with palaeo-temperature indicating isotopes of bivalve shells to trace lateral shifts in the coastal oceanography (particularly of the shelf front) during the Holocene; (c) Neodymium isotopes to identify the shelf sediment transport routes resulting from the current regime; (d) Sedimentological/geochemical data to show the efficient mechanism of sand export from the shelf to the open ocean; (e) Diatom assemblages and sediment element distributions indicating palaeo-salinity and the changing marine influence to illustrate the Plata runoff history. Sea level has not only controlled the overall configuration of the shelf but also the position of the main sediment routes from the continent towards the ocean. The shelf front has shifted frequently since the last glacial times probably resulting from both, changes in the Westerly Winds intensity and in the shelf width itself. Remarkable is a southward shift of this front during the past two centuries possibly related to anthropogenic influences on the atmosphere. The oceanographic regime with its prominent hydrographic boundaries led to a clear separation of sedimentary provinces since shelf drowning. It is especially the shelf front which enhances shelf sediment export through a continuous high sand supply to the uppermost slope. Finally, the Plata River does not continuously provide sediment to the shelf but shows significant climate-related changes in discharge during the past centuries. Starting from these findings, three major fields of research should, in general, be further developed in future: (i) The immediate interaction of the hydrodynamic and sedimentary systems to close the gaps between deposit information and modern oceanographic dynamics; (ii) Material budget calculations for the marginal ocean system in terms of material fluxes, storage/retention capacities, and critical thresholds; (iii) The role of human activity on the atmospheric, oceanographic and solid material systems to unravel natural vs. anthropogenic effects and feedback mechanisms