Kaurenoic Acid from Sphagneticola trilobata Inhibits Inflammatory Pain: Effect on Cytokine Production and Activation of the NO-Cyclic GMP-Protein Kinase G-ATP-Sensitive Potassium Channel Signaling Pathway

Kaurenoic acid [ent-kaur-16-en-19-oic acid (1)] is a diterpene present in several plants including Sphagneticola trilobata. The only documented evidence for its antinociceptive effect is that it inhibits the writhing response induced by acetic acid in mice. Therefore, the analgesic effect of 1 in different models of pain and its mechanisms in mice were investigated further. Intraperitoneal and oral treatment with 1 dose-dependently inhibited inflammatory nociception induced by acetic acid. Oral treatment with 1 also inhibited overt nociception-like behavior induced by phenyl-p-benzoquinone, complete Freund's adjuvant (CFA), and both phases of the formalin test. Compound 1 also inhibited acute carrageenin- and PGE(2)-induced and chronic CFA-induced inflammatory mechanical hyperalgesia. Mechanistically, 1 inhibited the production of the hyperalgesic cytokines TNF-alpha and IL-1 beta. Furthermore, the analgesic effect of 1 was inhibited by L-NAME, ODQ, KT5823, and glybenclamide treatment, demonstrating that such activity also depends on activation of the NO-cyclic GMP-protein kinase G-ATP-sensitive potassium channel signaling pathway, respectively. These results demonstrate that 1 exhibits an analgesic effect in a consistent manner and that its mechanisms involve the inhibition of cytokine production and activation of the NO-cyclic GMP-protein lcinase G-ATP-sensitive potassium channel signaling pathway.

Characterization of selectivity and pharmacophores of type 1 sea anemone toxins by screening seven Na-v sodium channel isoforms

During their evolution, animals have developed a set of cysteine-rich peptides capable of binding various extracellular sites of voltage-gated sodium channels (VGSC). Sea anemone toxins that target VGSCs delay their inactivation process, but little is known about their selectivities. Here we report the investigation of three native type 1 toxins (CGTX-II, delta-AITX-Bcg1a and delta-AITX-Bcg1b) purified from the venom of Bunodosoma cangicum. Both delta-AITX-Bcg1a and delta-AITX-Bcg1b toxins were fully sequenced. The three peptides were evaluated by patch-clamp technique among Nav1.1-1.7 isoforms expressed in mammalian cell lines, and their preferential targets are Na(v)1.5 > 1.6 > 1.1. We also evaluated the role of some supposedly critical residues in the toxins which would interact with the channels, and observed that some substitutions are not critical as expected. In addition, CGTX-II and delta-AITX-Bcg1a evoke different shifts in activation/inactivation Boltzmann curves in Nav1.1 and 1.6. Moreover, our results suggest that the interaction region between toxins and VGSCs is not restricted to the supposed site 3 (S3-54 linker of domain IV), and this may be a consequence of distinct surface of contact of each peptide vs. targeted channel. Our data suggest that the contact surfaces of each peptide may be related to their surface charges, as CGTX-II is more positive than delta-AITX-Bcg1a and delta-AITX-Bcg1b. (C) 2011 Elsevier Inc. All rights reserved.

Anomalous centrality evolution of two-particle angular correlations from Au-Au collisions at root s(NN)=62 and 200 GeV

We present two-dimensional (2D) two-particle angular correlations measured with the STAR detector on relative pseudorapidity eta and azimuth phi for charged particles from Au-Au collisions at root s(NN) = 62 and 200 GeV with transverse momentum p(t) >= 0.15 GeV/c, vertical bar eta vertical bar <= 1, and 2 pi in azimuth. Observed correlations include a same-side (relative azimuth <pi/2) 2D peak, a closely related away-side azimuth dipole, and an azimuth quadrupole conventionally associated with elliptic flow. The same-side 2D peak and away-side dipole are explained by semihard parton scattering and fragmentation (minijets) in proton-proton and peripheral nucleus-nucleus collisions. Those structures follow N-N binary-collision scaling in Au-Au collisions until midcentrality, where a transition to a qualitatively different centrality trend occurs within one 10% centrality bin. Above the transition point the number of same-side and away-side correlated pairs increases rapidly relative to binary-collision scaling, the eta width of the same-side 2D peak also increases rapidly (eta elongation), and the phi width actually decreases significantly. Those centrality trends are in marked contrast with conventional expectations for jet quenching in a dense medium. The observed centrality trends are compared to perturbative QCD predictions computed in HIJING, which serve as a theoretical baseline, and to the expected trends for semihard parton scattering and fragmentation in a thermalized opaque medium predicted by theoretical calculations and phenomenological models. We are unable to reconcile a semihard parton scattering and fragmentation origin for the observed correlation structure and centrality trends with heavy-ion collision scenarios that invoke rapid parton thermalization. If the collision system turns out to be effectively opaque to few-GeV partons the present observations would be inconsistent with the minijet picture discussed here. DOI: 10.1103/PhysRevC.86.064902

Form III-like conformation and Form I-like packing in a chloroform channel solvate of the diuretic drug chlortalidone

Chlortalidone (CTD) is an antihypertensive drug for which only two solid state phases have been structurally elucidated thus far. Here, we have prepared a chloroform solvate thereof, namely, CTD Form IV, and its structure was compared to those of Form I and Form III. Its two conformers exhibit a dual structural feature in relation to the antecedent polymorphs. Both CTD molecules of Form IV adopt a Form III-like conformation, which is featured, if the conformation of CTD Form I is used as a reference, by a rotation of about 90 degrees on the axis of the C-C bond bridging the substituted benzene and isoindolinyl rings. However, CTD Form IV assembles as in the Form I crystal packing despite the different stacking fashion of their centrosymmetric dimers. In contrast to Form I, there is no offset stacking in Form IV, which forces a bend of ca. 24 degrees between the planes passing through the isoindolinyl moieties of two [100]-stacked dimers. Chloroform molecules at a maximum stoichiometry of 0.25 mol per mol of the drug play a stabilizing role in the assembly of Form IV by filling the channels formed on the crystals.

Effect of sample pre-cracking method and notch geometry in plane strain fracture toughness tests as applied to a PMMA resin

The influence of test method factors (notch shape, square or angular, and pre-cracking method, by tapping onto or pressing a razor blade) on the results obtained in plane strain fracture toughness test according to standard ASTM D5045 using SENB specimens made of a commercial PMMA resin were investigated. Results were analyzed quantitatively by comparing the obtained K-IC values and qualitatively by observing their effect on the Moire fringes observed using photoelasticity, showing that, at 95% significance level, the K-IC values are affected by the pre-cracking method, with the most conservative value being obtained when natural pre-cracks were introduced by tapping onto a razor blade (K-IC = 1.15 +/- 0.11 MPa.m(0.5)). This correlates with a perturbation in the stress field close to the pre-crack tip observed in the photoelasticity test sample when it was introduced by pressing the razor blade. Surprisingly, notch geometry only slightly affects the results. (C) 2012 Elsevier Ltd. All rights reserved.

Impaired beta-adrenoceptor-induced relaxation in small mesenteric arteries from DOCA-salt hypertensive rats is due to reduced K-Ca channel activity

beta-Adrenoceptor (beta-AR)-mediated relaxation plays an important role in the regulation of vascular tone. beta-AR-mediated vascular relaxation is reduced in various disease states and aging. We hypothesized that beta-AR-mediated vasodilatation is impaired in DOCA-salt hypertension due to alterations in the cAMP pathway. beta-AR-mediated relaxation was determined in small mesenteric arteries from DOCA-salt hypertensive and control uninephrectomized (Uni) rats. To exclude nitric oxide (NO) and cyclooxygenase (COX) pathways, relaxation responses were determined in the presence of L-NNA and indomethacin, NO synthase inhibitor and COX inhibitors, respectively. Isoprenaline (ISO)-induced relaxation was reduced in arteries from DOCA-salt compared to Uni rats. Protein kinase A (PKA) inhibitors (H89 or Rp-cAMPS) or adenylyl cyclase inhibitor (SQ22536) did not abolish the difference in ISO-induced relaxation between the groups. Forskolin (adenylyl cyclase activator)-induced relaxation was similar between the groups. The inhibition of IKCa/SKCa channels (TRAM-34 plus UCL1684) or BKCa channels (iberiotoxin) reduced ISO-induced relaxation only in Uni rats and abolished the relaxation differences between the groups. The expression of SKCa channel was decreased in DOCA-salt arteries. The expression of BKCa channel a subunit was increased whereas the expression of BKCa channel p subunit was decreased in DOCA-salt arteries. The expression of receptor for activated C kinase 1 (RACK1), which is a binding protein for BKG, channel and negatively modulates its activity, was increased in DOCA-salt arteries. These results suggest that the impairment of beta-AR-mediated relaxation in DOCA-salt mesenteric arteries may be attributable to altered IKCa/SKCa and/or BKCa channels activities rather than cAMP/PKA pathway. Impaired beta-AR-stimulated BKCa channel activity may be due to the imbalance between its subunit expressions and RACK1 upregulation. (C) 2012 Elsevier Ltd. All rights reserved.

The effects of the pressing step on the microstructure and aging of NdFeB bonded magnets

The effects of the compaction step on the (micro)structural features and aging behavior of polymer coated NdFeB-based bonded magnets is reported. Due to the fracture of the material during pressing, it is estimated an increase of at least 14% in the particles' area which is not coated. Such uncoated surfaces, when exposed to the environment, reduce the magnetic performance of the magnets aged/cured in air by 19% in the conditions evaluated in this investigation. Furthermore, XRD results interpreted by Rietveld analyses show a lattice parameter change in the tetragonal structure of the hard magnetic phase after pressing. Such change varies as a function of the height of the compacted part and it is ascribed to macro-elastic stress arising from the pressure distribution in the magnet. An aging/curing step during 24 h is able to relief such macro-elastic stress. (C) 2012 Elsevier B.V. All rights reserved.

Beyond the diffraction limit of optical/IR interferometers I. Angular diameter and rotation parameters of Achernar from differential phases

Context. Spectrally resolved long-baseline optical/IR interferometry of rotating stars opens perspectives to investigate their fundamental parameters and the physical mechanisms that govern their interior, photosphere, and circumstellar envelope structures. Aims. Based on the signatures of stellar rotation on observed interferometric wavelength-differential phases, we aim to measure angular diameters, rotation velocities, and orientation of stellar rotation axes. Methods. We used the AMBER focal instrument at ESO-VLTI in its high-spectral resolution mode to record interferometric data on the fast rotator Achernar. Differential phases centered on the hydrogen Br gamma line (K band) were obtained during four almost consecutive nights with a continuous Earth-rotation synthesis during similar to 5h/night, corresponding to similar to 60 degrees position angle coverage per baseline. These observations were interpreted with our numerical code dedicated to long-baseline interferometry of rotating stars. Results. By fitting our model to Achernar's differential phases from AMBER, we could measure its equatorial radius R-eq = 11.6 +/- 0.3 R-circle dot, equatorial rotation velocity V-eq = 298 +/- 9 km s(-1), rotation axis inclination angle i = 101.5 +/- 5.2 degrees, and rotation axis position angle (from North to East) PA(rot) = 34.9 +/- 1.6 degrees. From these parameters and the stellar distance, the equatorial angular diameter circle divide(eq) of Achernar is found to be 2.45 +/- 0.09 mas, which is compatible with previous values derived from the commonly used visibility amplitude. In particular, circle divide(eq) and PA(rot) measured in this work with VLTI/AMBER are compatible with the values previously obtained with VLTI/VINCI. Conclusions. The present paper, based on real data, demonstrates the super-resolution potential of differential interferometry for measuring sizes, rotation velocities, and orientation of rotating stars in cases where visibility amplitudes are unavailable and/or when the star is partially or poorly resolved. In particular, we showed that differential phases allow the measurement of sizes up to similar to 4 times smaller than the diffraction-limited angular resolution of the interferometer.

THE UBV(RI)(C) COLORS OF THE SUN

Photometric data in the UBV(RI)(C) system have been acquired for 80 solar analog stars for which we have previously derived highly precise atmospheric parameters T-eff, log g, and [Fe/H] using high-resolution, high signal-to-noise ratio spectra. UBV and (RI)(C) data for 46 and 76 of these stars, respectively, are published for the first time. Combining our data with those from the literature, colors in the UBV(RI) C system, with similar or equal to 0.01 mag precision, are now available for 112 solar analogs. Multiple linear regression is used to derive the solar colors from these photometric data and the spectroscopically derived T-eff, log g, and [Fe/H] values. To minimize the impact of systematic errors in the model-dependent atmospheric parameters, we use only the data for the 10 stars that most closely resemble our Sun, i.e., the solar twins, and derive the following solar colors: (B - V)(circle dot) = 0.653 +/- 0.005, (U - B)(circle dot) = 0.166 +/- 0.022, (V - R)(circle dot) = 0.352 +/- 0.007, and (V - I)(circle dot) = 0.702 +/- 0.010. These colors are consistent, within the 1 sigma errors, with those derived using the entire sample of 112 solar analogs. We also derive the solar colors using the relation between spectral-line-depth ratios and observed stellar colors, i.e., with a completely model-independent approach, and without restricting the analysis to solar twins. We find (B - V)(circle dot) = 0.653 +/- 0.003, (U - B)(circle dot) = 0.158 +/- 0.009, (V - R)(circle dot) = 0.356 +/- 0.003, and (V - I)(circle dot) = 0.701 +/- 0.003, in excellent agreement with the model-dependent analysis.

Experimental Comparison of Two Degrees-of-Freedom Vortex-Induced Vibration on High and Low Aspect Ratio Cylinders with Small Mass Ratio

Vortex-induced motion (VIM) is a specific way for naming the vortex-induced vibration (VIV) acting on floating units. The VIM phenomenon can occur in monocolumn production, storage and offloading system (MPSO) and spar platforms, structures presenting aspect ratio lower than 4 and unity mass ratio, i.e., structural mass equal to the displaced fluid mass. These platforms can experience motion amplitudes of approximately their characteristic diameters, and therefore, the fatigue life of mooring lines and risers can be greatly affected. Two degrees-of-freedom VIV model tests based on cylinders with low aspect ratio and small mass ratio have been carried out at the recirculating water channel facility available at NDF-EPUSP in order to better understand this hydro-elastic phenomenon. The tests have considered three circular cylinders of mass ratio equal to one and different aspect ratios, respectively L/D = 1.0, 1.7, and 2.0, as well as a fourth cylinder of mass ratio equal to 2.62 and aspect ratio of 2.0. The Reynolds number covered the range from 10 000 to 50 000, corresponding to reduced velocities from 1 to approximately 12. The results of amplitude and frequency in the transverse and in-line directions were analyzed by means of the Hilbert-Huang transform method (HHT) and then compared to those obtained from works found in the literature. The comparisons have shown similar maxima amplitudes for all aspect ratios and small mass ratio, featuring a decrease as the aspect ratio decreases. Moreover, some changes in the Strouhal number have been indirectly observed as a consequence of the decrease in the aspect ratio. In conclusion, it is shown that comparing results of small-scale platforms with those from bare cylinders, all of them presenting low aspect ratio and small mass ratio, the laboratory experiments may well be used in practical investigation, including those concerning the VIM phenomenon acting on platforms. [DOI: 10.1115/1.4006755]

Chronic Stress Improves the Myocardial Function without Altering L-type Ca+2 Channel Activity in Rats

Background: Chronic stress is associated with cardiac remodeling; however the mechanisms have yet to be clarified. Objective: The purpose of this study was test the hypothesis that chronic stress promotes cardiac dysfunction associated to L-type calcium Ca2+ channel activity depression. Methods: Thirty-day-old male Wistar rats (70 - 100 g) were distributed into two groups: control (C) and chronic stress (St). The stress was consistently maintained at immobilization during 15 weeks, 5 times per week, 1h per day. The cardiac function was evaluated by left ventricular performance through echocardiography and by ventricular isolated papillary muscle. The myocardial papillary muscle activity was assessed at baseline conditions and with inotropic maneuvers such as: post-rest contraction and increases in extracellular Ca2+ concentration, in presence or absence of specific blockers L-type calcium channels. Results: The stress was characterized for adrenal glands hypertrophy, increase of systemic corticosterone level and arterial hypertension. The chronic stress provided left ventricular hypertrophy. The left ventricular and baseline myocardial function did not change with chronic stress. However, it improved the response of the papillary muscle in relation to positive inotropic stimulation. This function improvement was not associated with the L-type Ca2+ channel. Conclusion: Chronic stress produced cardiac hypertrophy; however, in the study of papillary muscle, the positive inotropic maneuvers potentiated cardiac function in stressed rats, without involvement of L-type Ca2+ channel. Thus, the responsible mechanisms remain unclear with respect to Ca2+ influx alterations. (Arq Bras Cardiol 2012;99(4):907-914)

Ether-A -go-go 1 (Eag1) Potassium Channel Expression in Dopaminergic Neurons of Basal Ganglia is Modulated by 6-Hydroxydopamine Lesion

The ether A go-go (Eag) gene encodes the voltage-gated potassium (K+) ion channel Kv10.1, whose function still remains unknown. As dopamine may directly affect K+ channels, we evaluated whether a nigrostriatal dopaminergic lesion induced by the neurotoxin 6-hydroxydopamine (6-OHDA) would alter Eag1-K+ channel expression in the rat basal ganglia and related brain regions. Male Wistar rats received a microinjection of either saline or 6-OHDA (unilaterally) into the medial forebrain bundle. The extent of the dopaminergic lesion induced by 6-OHDA was evaluated by apomorphine-induced rotational behavior and by tyrosine hydroxylase (TH) immunoreactivity. The 6-OHDA microinjection caused a partial or complete lesion of dopaminergic cells, as well as a reduction of Eag1+ cells in a manner proportional to the extent of the lesion. In addition, we observed a decrease in TH immunoreactivity in the ipsilateral striatum. In conclusion, the expression of the Eag1-K+-channel throughout the nigrostriatal pathway in the rat brain, its co-localization with dopaminergic cells and its reduction mirroring the extent of the lesion highlight a physiological circuitry where the functional role of this channel can be investigated. The Eag1-K+ channel expression in dopaminergic cells suggests that these channels are part of the diversified group of ion channels that generate and maintain the electrophysiological activity pattern of dopaminergic midbrain neurons.

Influence of 60-MeV Proton-Irradiation on Standard and Strained n- and p-Channel MuGFETs

In this work the proton irradiation influence on Multiple Gate MOSFETs (MuGFETs) performance is investigated. This analysis was performed through basic and analog parameters considering four different splits (unstrained, uniaxial, biaxial, uniaxial+biaxial). Although the influence of radiation is more pronounced for p-channel devices, in pMuGFETs devices, the radiation promotes a higher immunity to the back interface conduction resulting in the analog performance improvement. On the other hand, the proton irradiation results in a degradation of the post-irradiated n-channel transistors behavior. The unit gain frequency showed to be strongly dependent on stress efficiency and the radiation results in an increase of the unit gain frequency for splits with high stress effectiveness for both cases p- and nMuGFETs.

Quantum deformation of the angular distributions of synchrotron radiation. Emission from particles in the first excited state

The exact expressions for the characteristics of synchrotron radiation of charged particles in the first excited state are obtained in analytical form using quantum theory methods. We performed a detailed analysis of the angular distribution structure of radiation power and its polarization for particles with spin 0 and 1/2. It is shown that the exact quantum calculations lead to results that differ substantially from the predictions of classical theory.

CIRCULATION AND SALT INTRUSION IN THE PIACAGUERA CHANNEL, SANTOS (SP)

Analysis of thermohaline properties and currents sampled at an anchor station in the Piacaguera Channel (Santos Estuary) in the austral winter was made in terms of tidal (neap and spring tidal cycles) and non-tidal conditions, with the objective to characterize the stratification, circulation and salt transport due to the fortnightly tidal modulation. Classical methods of observational data analysis of hourly and nearly synoptic observations and analytical simulations of nearly steady-state salinity and longitudinal velocity profiles were used. During the neap tidal cycle the flood (v<0) and ebb (v>0) velocities varied in the range of -0.20 m/s to 0.30 m/s associated with a small salinity variation from surface to bottom (26.4 psu to 30.7 psu). In the spring tidal cycle the velocities increased and varied in the range of -0.40 m/s to 0.45 m/s, but the salinity stratification remained almost unaltered. The steady-state salinity and velocity profiles simulated with an analytical model presented good agreement (Skill near 1.0), in comparison with the observational profiles. During the transitional fortnightly tidal modulation period there was no changes in the channel classification (type 2a - partially mixed and weakly stratified), because the potential energy rate was to low to enhance the halocline erosion. These results, associated with the high water column vertical stability (RiL > 20) and the low estuarine Richardson number (RiE = 1.6), lead to the conclusions: i) the driving mechanism for the estuary circulation and mixing was mainly balanced by the fresh water discharge and the tidal forcing associated with the baroclinic component of the gradient pressure force; ii) there was no changes in the thermohaline and circulation characteristics due to the forthnigtly tidal modulation; and iii) the nearly steady-state of the vertical salinity and velocity profiles were well simulated with a theoretical classical analytical model.