Mechanisms of Vascular Damage by Hemorrhagic Snake Venom Metalloproteinases: Tissue Distribution and In Situ Hydrolysis

Background: Envenoming by viper snakes constitutes an important public health problem in Brazil and other developing countries. Local hemorrhage is an important symptom of these accidents and is correlated with the action of snake venom metalloproteinases (SVMPs). The degradation of vascular basement membrane has been proposed as a key event for the capillary vessel disruption. However, SVMPs that present similar catalytic activity towards extracellular matrix proteins differ in their hemorrhagic activity, suggesting that other mechanisms might be contributing to the accumulation of SVMPs at the snakebite area allowing capillary disruption. Methodology/Principal Findings: In this work, we compared the tissue distribution and degradation of extracellular matrix proteins induced by jararhagin (highly hemorrhagic SVMP) and BnP1 (weakly hemorrhagic SVMP) using the mouse skin as experimental model. Jararhagin induced strong hemorrhage accompanied by hydrolysis of collagen fibers in the hypodermis and a marked degradation of type IV collagen at the vascular basement membrane. In contrast, BnP1 induced only a mild hemorrhage and did not disrupt collagen fibers or type IV collagen. Injection of Alexa488-labeled jararhagin revealed fluorescent staining around capillary vessels and co-localization with basement membrane type IV collagen. The same distribution pattern was detected with jararhagin-C (disintegrin-like/cysteine-rich domains of jararhagin). In opposition, BnP1 did not accumulate in the tissues. Conclusions/Significance: These results show a particular tissue distribution of hemorrhagic toxins accumulating at the basement membrane. This probably occurs through binding to collagens, which are drastically hydrolyzed at the sites of hemorrhagic lesions. Toxin accumulation near blood vessels explains enhanced catalysis of basement membrane components, resulting in the strong hemorrhagic activity of SVMPs. This is a novel mechanism that underlies the difference between hemorrhagic and non-hemorrhagic SVMPs, improving the understanding of snakebite pathology.

Characterization of subgraph relationships and distribution in complex networks

A network can be analyzed at different topological scales, ranging from single nodes to motifs, communities, up to the complete structure. We propose a novel approach which extends from single nodes to the whole network level by considering non-overlapping subgraphs (i.e. connected components) and their interrelationships and distribution through the network. Though such subgraphs can be completely general, our methodology focuses on the cases in which the nodes of these subgraphs share some special feature, such as being critical for the proper operation of the network. The methodology of subgraph characterization involves two main aspects: (i) the generation of histograms of subgraph sizes and distances between subgraphs and (ii) a merging algorithm, developed to assess the relevance of nodes outside subgraphs by progressively merging subgraphs until the whole network is covered. The latter procedure complements the histograms by taking into account the nodes lying between subgraphs, as well as the relevance of these nodes to the overall subgraph interconnectivity. Experiments were carried out using four types of network models and five instances of real-world networks, in order to illustrate how subgraph characterization can help complementing complex network-based studies.

Relationship Between Surface Topography and Energy Density Distribution of Er,Cr:YSGG Beam on Irradiated Dentin: An Atomic Force Microscopy Study

Objective: The aim of this study was to assess by atomic force microscopy (AFM) the effect of Er,Cr:YSGG laser application on the surface microtopography of radicular dentin. Background: Lasers have been used for various purposes in dentistry, where they are clinically effective when used in an appropriate manner. The Er, Cr: YSGG laser can be used for caries prevention when settings are below the ablation threshold. Materials and Methods: Four specimens of bovine dentin were irradiated using an Er, Cr:YSGG laser (lambda = 2.78 mu m), at a repetition rate of 20 Hz, with a 750-mu m-diameter sapphire tip and energy density of 2.8 J/cm(2) (12.5 mJ/pulse). After irradiation, surface topography was analyzed by AFM using a Si probe in tapping mode. Quantitative and qualitative information concerning the arithmetic average roughness (Ra) and power spectral density analyses were obtained from central, intermediate, and peripheral areas of laser pulses and compared with data from nonirradiated samples. Results: Dentin Ra for different areas were as follows: central, 261.26 (+/- 21.65) nm; intermediate, 83.48 (+/- 6.34) nm; peripheral, 45.8 (+/- 13.47) nm; and nonirradiated, 35.18 (+/- 2.9) nm. The central region of laser pulses presented higher ablation of intertubular dentin, with about 340-760 nm height, while intermediate, peripheral, and nonirradiated regions presented no difference in height of peritubular and interperitubular dentin. Conclusion: According to these results, we can assume that even when used at a low-energy density parameter, Er, Cr: YSGG laser can significantly alter the microtopography of radicular dentin, which is an important characteristic to be considered when laser is used for clinical applications.

Robust relations between CCN and the vertical evolution of cloud drop size distribution in deep convective clouds

In-situ measurements in convective clouds (up to the freezing level) over the Amazon basin show that smoke from deforestation fires prevents clouds from precipitating until they acquire a vertical development of at least 4 km, compared to only 1-2 km in clean clouds. The average cloud depth required for the onset of warm rain increased by similar to 350 m for each additional 100 cloud condensation nuclei per cm(3) at a super-saturation of 0.5% (CCN0.5%). In polluted clouds, the diameter of modal liquid water content grows much slower with cloud depth (at least by a factor of similar to 2), due to the large number of droplets that compete for available water and to the suppressed coalescence processes. Contrary to what other studies have suggested, we did not observe this effect to reach saturation at 3000 or more accumulation mode particles per cm(3). The CCN0.5% concentration was found to be a very good predictor for the cloud depth required for the onset of warm precipitation and other microphysical factors, leaving only a secondary role for the updraft velocities in determining the cloud drop size distributions. The effective radius of the cloud droplets (r(e)) was found to be a quite robust parameter for a given environment and cloud depth, showing only a small effect of partial droplet evaporation from the cloud's mixing with its drier environment. This supports one of the basic assumptions of satellite analysis of cloud microphysical processes: the ability to look at different cloud top heights in the same region and regard their r(e) as if they had been measured inside one well developed cloud. The dependence of r(e) on the adiabatic fraction decreased higher in the clouds, especially for cleaner conditions, and disappeared at r(e)>=similar to 10 mu m. We propose that droplet coalescence, which is at its peak when warm rain is formed in the cloud at r(e)=similar to 10 mu m, continues to be significant during the cloud's mixing with the entrained air, cancelling out the decrease in r(e) due to evaporation.

Electronic properties of liquid ammonia: A sequential molecular dynamics/quantum mechanics approach

The electronic properties of liquid ammonia are investigated by a sequential molecular dynamics/quantum mechanics approach. Quantum mechanics calculations for the liquid phase are based on a reparametrized hybrid exchange-correlation functional that reproduces the electronic properties of ammonia clusters [(NH(3))(n); n=1-5]. For these small clusters, electron binding energies based on Green's function or electron propagator theory, coupled cluster with single, double, and perturbative triple excitations, and density functional theory (DFT) are compared. Reparametrized DFT results for the dipole moment, electron binding energies, and electronic density of states of liquid ammonia are reported. The calculated average dipole moment of liquid ammonia (2.05 +/- 0.09 D) corresponds to an increase of 27% compared to the gas phase value and it is 0.23 D above a prediction based on a polarizable model of liquid ammonia [Deng , J. Chem. Phys. 100, 7590 (1994)]. Our estimate for the ionization potential of liquid ammonia is 9.74 +/- 0.73 eV, which is approximately 1.0 eV below the gas phase value for the isolated molecule. The theoretical vertical electron affinity of liquid ammonia is predicted as 0.16 +/- 0.22 eV, in good agreement with the experimental result for the location of the bottom of the conduction band (-V(0)=0.2 eV). Vertical ionization potentials and electron affinities correlate with the total dipole moment of ammonia aggregates. (c) 2008 American Institute of Physics.

Deformations of the Tracy-Widom distribution

In random matrix theory, the Tracy-Widom (TW) distribution describes the behavior of the largest eigenvalue. We consider here two models in which TW undergoes transformations. In the first one disorder is introduced in the Gaussian ensembles by superimposing an external source of randomness. A competition between TW and a normal (Gaussian) distribution results, depending on the spreading of the disorder. The second model consists of removing at random a fraction of (correlated) eigenvalues of a random matrix. The usual formalism of Fredholm determinants extends naturally. A continuous transition from TW to the Weilbull distribution, characteristic of extreme values of an uncorrelated sequence, is obtained.

Evidence for zero-differential resistance states in electronic bilayers

We observe zero-differential resistance states at low temperatures and moderate direct currents in a bilayer electron system formed by a wide quantum well. Several regions of vanishing resistance evolve from the inverted peaks of magneto-intersubband oscillations as the current increases. The experiment, supported by a theoretical analysis, suggests that the origin of this phenomenon is based on instability of homogeneous current flow under conditions of negative differential resistivity, which leads to formation of current domains in our sample, similar to the case of single-layer systems.

Increase in the magnitude of the energy barrier distribution in Ni nanoparticles due to dipolar interactions

The energy barrier distribution E(b) of five samples with different concentrations x of Ni nanoparticles using scaling plots from ac magnetic susceptibility data has been determined. The scaling of the imaginary part of the susceptibility chi""(v, T) versus T ln (iota t/tau(0)) remains valid for all samples, which display Ni nanoparticles with similar shape and size. The mean value < E(b)> increases appreciably with increasing x, or more appropriately with increasing dipolar interactions between Ni nanoparticles. We argue that such an increase in < E(b)> constitutes a powerful tool for quality control in magnetic recording media technology where the dipolar interaction plays an important role. (c) 2011 American Institute of Physics. [doi: 10.1063/1.3533911]

Unraveling effects of disorder on the electronic structure of SiO(2) from first principles

We present a first-principles systematic study of the electronic structure of SiO(2) including the crystalline polymorphs alpha quartz and beta cristobalite, and different types of disorder leading to the amorphous phase. We start from calculations within density functional theory and proceed to more sophisticated quasiparticle calculations according to the GW scheme. Our results show that different origins of disorder have also different impact on atomic and electronic-density fluctuations, which affect the electronic structure and, in particular, the size of the mobility gap in each case.

Electronic, structural, and transport properties of Ni-doped graphene nanoribbons

We have investigated the electronic and transport properties of zigzag Ni-adsorbed graphene nanoribbons (Ni/GNRs) using ab initio calculations. We find that the Ni adatoms lying along the edge of zigzag GNRs represent the energetically most stable configuration, with an energy difference of approximately 0.3 eV when compared to the adsorption in the middle of the ribbon. The carbon atoms at the ribbon edges still present nonzero magnetic moments as in the pristine GNR even though there is a quenching by a factor of almost five in the value of the local magnetic moments at the C atoms bonded to the Ni. This quenching decays relatively fast and at approximately 9 A from the Ni adsorption site the magnetic moments have already values close to the pristine ribbon. At the opposite edge and at the central carbon atoms the changes in the magnetic moments are negligible. The energetic preference for the antiparallel alignment between the magnetization at the opposite edges of the ribbon is still maintained upon Ni adsorption. We find many Ni d-related states within an energy window of 1 eV above and below the Fermi energy, which gives rise to a spin-dependent charge transport. These results suggest the possibility of manufacturing spin devices based on GNRs doped with Ni atoms.

Optical absorption and electronic band structure first-principles calculations of alpha-glycine crystals

Light absorption of alpha-glycine crystals grown by slow evaporation at room temperature was measured, indicating a 5.11 +/- 0.02 eV energy band gap. Structural, electronic, and optical absorption properties of alpha-glycine crystals were obtained by first-principles quantum mechanical calculations using density functional theory within the generalized gradient approximation in order to understand this result. To take into account the contribution of core electrons, ultrasoft and norm-conserving pseudopotentials, as well as an all electron approach were considered to compute the electronic density of states and band structure of alpha-glycine crystals. They exhibit three indirect energy band gaps and one direct Gamma-Gamma energy gap around 4.95 eV. The optical absorption related to transitions between the top of the valence band and the bottom of the conduction band involves O 2p valence states and C, O 2p conduction states, with the carboxyl group contributing significantly to the origin of the energy band gap. The calculated optical absorption is highly dependent on the polarization of the incident radiation due to the spatial arrangement of the dipolar glycine molecules; in the case of a polycrystalline sample, the first-principles calculated optical absorption is in good agreement with the measurement when a rigid energy shift is applied.

Quasi-elastic barrier distribution of the (17)O+(64)Zn system and the derivation of the (17)O nuclear matter diffuseness

The quasi-elastic excitation function for the (17)O+(64)Zn system was measured at energies near and below the Coulomb barrier, at the backward angle theta(lab) = 161 degrees. The corresponding quasi-elastic barrier distribution was derived. The excitation function for the neutron stripping reactions was also measured, at the same angle and energies, and the experimental values of the spectroscopic factors were deduced by fitting the data. A reasonably good agreement was obtained between the experimental quasi-elastic barrier distribution with the coupled-channel calculations including a very large number of channels. Of the channels investigated, three dominated the coupling matrix: two inelastic channels, (64)Zn(2(1)(+)) and (17)O(1/(+)(2)), and one-neutron transfer channel, particularly the first one. On the other hand, a very good agreement is obtained when we use a nuclear diffuseness for the (17)O nucleus larger than the one for (16)O. We verify that quasi-elastic barrier distribution is a sensitive tool for determining nuclear matter diffuseness.

Two-photon absorption spectra of carotenoids compounds

Carotenoids are biosynthetic organic pigments that constitute an important class of one-dimensional pi-conjugated organic molecules with enormous potential for application in biophotonic devices. In this context, we studied the degenerate two-photon absorption (2PA) cross-section spectra of two carotenoid compounds (beta-carotene and beta-apo-8'-carotenal) employing the conventional and white-light-continuum Z-scan techniques and quantum chemistry calculations. Because carotenoids coexist at room temperature as a mixture of isomers, the 2PA spectra reported here are due to samples containing a distribution of isomers, presenting distinct conjugation length and conformation. We show that these compounds present a defined structure on the 2PA spectra, that peaks at 650 nm with an absorption cross-section of approximately 5000 GM, for both compounds. In addition, we observed a 2PA band at 990 nm for beta-apo-8'-carotenal, which was attributed to a overlapping of I(I)B(u) +-like and 2(I)Ag(-)-like states, which are strongly one- and two-photon allowed, respectively. Spectroscopic parameters of the electronic transitions to singlet-excited states, which are directly related to photophysical properties of these compounds, were obtained by fitting the 2PA spectra using the sum-over-states approach. The analysis and interpretations of the 2PA spectra of the investigated carotenoids were supported by theoretical predictions of one- and two-photon transitions carried out using the response functions formalism within the density functional theory framework, using the long-range corrected CAM-B3LYP functional. (C) 2011 American Institute of Physics. [doi:10.1063/1.3590157]

Gene Expression Noise in Spatial Patterning: hunchback Promoter Structure Affects Noise Amplitude and Distribution in Drosophila Segmentation

Positional information in developing embryos is specified by spatial gradients of transcriptional regulators. One of the classic systems for studying this is the activation of the hunchback (hb) gene in early fruit fly (Drosophila) segmentation by the maternally-derived gradient of the Bicoid (Bcd) protein. Gene regulation is subject to intrinsic noise which can produce variable expression. This variability must be constrained in the highly reproducible and coordinated events of development. We identify means by which noise is controlled during gene expression by characterizing the dependence of hb mRNA and protein output noise on hb promoter structure and transcriptional dynamics. We use a stochastic model of the hb promoter in which the number and strength of Bcd and Hb (self-regulatory) binding sites can be varied. Model parameters are fit to data from WT embryos, the self-regulation mutant hb(14F), and lacZ reporter constructs using different portions of the hb promoter. We have corroborated model noise predictions experimentally. The results indicate that WT (self-regulatory) Hb output noise is predominantly dependent on the transcription and translation dynamics of its own expression, rather than on Bcd fluctuations. The constructs and mutant, which lack self-regulation, indicate that the multiple Bcd binding sites in the hb promoter (and their strengths) also play a role in buffering noise. The model is robust to the variation in Bcd binding site number across a number of fly species. This study identifies particular ways in which promoter structure and regulatory dynamics reduce hb output noise. Insofar as many of these are common features of genes (e. g. multiple regulatory sites, cooperativity, self-feedback), the current results contribute to the general understanding of the reproducibility and determinacy of spatial patterning in early development.

Anisotropic Confinement, Electronic Coupling and Strain Induced Effects Detected by Valence-Band Anisotropy in Self-Assembled Quantum Dots

A method to determine the effects of the geometry and lateral ordering on the electronic properties of an array of one-dimensional self-assembled quantum dots is discussed. A model that takes into account the valence-band anisotropic effective masses and strain effects must be used to describe the behavior of the photoluminescence emission, proposed as a clean tool for the characterization of dot anisotropy and/or inter-dot coupling. Under special growth conditions, such as substrate temperature and Arsenic background, 1D chains of In(0.4)Ga(0.6) As quantum dots were grown by molecular beam epitaxy. Grazing-incidence X-ray diffraction measurements directly evidence the strong strain anisotropy due to the formation of quantum dot chains, probed by polarization-resolved low-temperature photoluminescence. The results are in fair good agreement with the proposed model.