ProbFAST: Probabilistic Functional Analysis System Tool

Background: The post-genomic era has brought new challenges regarding the understanding of the organization and function of the human genome. Many of these challenges are centered on the meaning of differential gene regulation under distinct biological conditions and can be performed by analyzing the Multiple Differential Expression (MDE) of genes associated with normal and abnormal biological processes. Currently MDE analyses are limited to usual methods of differential expression initially designed for paired analysis. Results: We proposed a web platform named ProbFAST for MDE analysis which uses Bayesian inference to identify key genes that are intuitively prioritized by means of probabilities. A simulated study revealed that our method gives a better performance when compared to other approaches and when applied to public expression data, we demonstrated its flexibility to obtain relevant genes biologically associated with normal and abnormal biological processes. Conclusions: ProbFAST is a free accessible web-based application that enables MDE analysis on a global scale. It offers an efficient methodological approach for MDE analysis of a set of genes that are turned on and off related to functional information during the evolution of a tumor or tissue differentiation. ProbFAST server can be accessed at http://gdm.fmrp.usp.br/probfast.

EXISTENCE RESULTS FOR ABSTRACT NEUTRAL FUNCTIONAL DIFFERENTIAL EQUATIONS

In this paper we discuss the existence of solutions for a class of abstract partial neutral functional differential equations.

Functional characterization of the sciarid BhC4-1 core promoter in transgenic Drosophila

Background: Core promoters are cis-regulatory modules to which bind the basal transcriptional machinery and which participate in the regulation of transcription initiation. Although core promoters have not been extensively investigated through functional assays in a chromosomal context, the available data suggested that the response of a given core promoter might vary depending on the promoter context. Previous studies suggest that a (-57/+40) fragment constitutes the core promoter of the BhC4-1 gene which is located in DNA puff C4 of the sciarid fly Bradysia hygida. Here we tested this (-57/+40) fragment in distinct regulatory contexts in order to verify if promoter context affects its core promoter activity. Results: Consistent with the activity of a core promoter, we showed that in the absence of upstream regulatory sequences the (-57/+40) fragment drives low levels of reporter gene mRNA expression throughout development in transgenic Drosophila. By assaying the (-57/+40) fragment in two distinct regulatory contexts, either downstream of the previously characterized Fbp1 enhancer or downstream of the UAS element, we showed that the BhC4-1 core promoter drives regulated transcription in both the germline and in various tissues throughout development. Furthermore, the use of the BhC4-1 core promoter in a UAS construct significantly reduced salivary gland ectopic expression in third instar larvae, which was previously described to occur in the context of the GAL4/UAS system. Conclusions: Our results from functional analysis in transgenic Drosophila show that the BhC4-1 core promoter drives gene expression regardless of the promoter context that was assayed. New insights into the functioning of the GAL4/UAS system in Drosophila were obtained, indicating that the presence of the SV40 sequence in the 3' UTR of a UAS construct does not preclude expression in the germline. Furthermore, our analysis indicated that ectopic salivary gland expression in the GAL4/UAS system does not depend only on sequences present in the GAL4 construct, but can also be affected by the core promoter sequences in the UAS construct. In this context, we propose that the sciarid BhC4-1 core promoter constitutes a valuable core promoter which can be employed in functional assays in insects.

Deep sequencing of New World screw-worm transcripts to discover genes involved in insecticide resistance

Background: The New World screw-worm (NWS), Cochliomyia hominivorax, is one of the most important myiasis-causing flies, causing severe losses to the livestock industry. In its current geographical distribution, this species has been controlled by the application of insecticides, mainly organophosphate (OP) compounds, but a number of lineages have been identified that are resistant to such chemicals. Despite its economic importance, only limited genetic information is available for the NWS. Here, as a part of an effort to characterize the C. hominivorax genome and identify putative genes involved in insecticide resistance, we sampled its transcriptome by deep sequencing of polyadenylated transcripts using the 454 sequencing technology. Results: Deep sequencing on the 454 platform of three normalized libraries (larval, adult male and adult female) generated a total of 548,940 reads. Eighteen candidate genes coding for three metabolic detoxification enzyme families, cytochrome P450 monooxygenases, glutathione S transferases and carboxyl/cholinesterases were selected and gene expression levels were measured using quantitative real-time polymerase chain reaction (qRT-PCR). Of the investigated candidates, only one gene was expressed differently between control and resistant larvae with, at least, a 10-fold down-regulation in the resistant larvae. The presence of mutations in the acetylcholinesterase (target site) and carboxylesterase E3 genes was investigated and all of the resistant flies presented E3 mutations previously associated with insecticide resistance. Conclusions: Here, we provided the largest database of NWS expressed sequence tags that is an important resource, not only for further studies on the molecular basis of the OP resistance in NWS fly, but also for functional and comparative studies among Calliphoridae flies. Among our candidates, only one gene was found differentially expressed in resistant individuals, and its role on insecticide resistance should be further investigated. Furthermore, the absence of mutations in the OP target site and the high frequency of mutant carboxylesterase E3 indicate that metabolic resistance mechanisms have evolved predominantly in this species.

REPRODUCTIVE BIOLOGY AND FUNCTIONAL MATURITY IN FEMALES OF AEGLA FRANCA (DECAPODA: ANOMURA: AEGLIDAE)

We describe the reproductive period. fecundity, and average size at the onset of functional maturity of female Aegla franca, the northernmost distributed aeglid species. The reproductive period is markedly seasonal and takes place front May (austral mid-autumn) to August (late winter). Ovigerous females appear quite abruptly in the population by May, and this condition is observed in all adult females sampled regardless of their size. The average size at the onset of functional maturity in females, at which 50% of the females sampled during the reproductive period were considered adults, was 12.75 mm CL. The smallest post-ovigerous female measured 12.06 mm carapace length (CL). Mean fecundity (+/- S.D.) from 41 females bearing early and intermediate eggs was 129.1 +/- 32.2 and corresponded to a mean female CL of 14.11 mm. The elliptical-shaped eggs exhibited significant increase in size along the development stages. The third pair of pleopods bore higher number of eggs than the others. Compiled information regarding the reproductive period reported for aeglids revealed all increase in the breeding period length with latitude. The reproductive period tends to be shorter in localities under larger rainfall variation and smaller temperature variability than in sites with opposite climate conditions. Eggs tend to be fewer in number and larger in size towards lower latitudes. We present an hypothesis that stream water velocity might act as a major selective pressure during the early life history of fluvial aeglids with direct effect on the reproductive pattern.

Exogenous Cx43 expression decrease cell proliferation rate in rat hepatocarcinoma cells independently of functional gap junction

Background: Gap junction intercellular communication (GJIC) is considered to play a role in the regulation of homeostasis because it regulates important processes, such as cell proliferation and cell differentiation. A reduced or lost GJIC capacity has been observed in solid tumors and studies have demonstrated that GJIC restoration in tumor cells contribute to reversion of the transformed phenotype. This observation supports the idea that restoration of the functional channel is essential in this process. However, in the last years, reports have proposed that just the increase in the expression of specific connexins can contribute to reversion of the malign phenotype in some tumor cells. In the present work, we studied the effects of exogenous Connexin 43 (Cx43) expression on the proliferative behavior and phenotype of rat hepatocarcinoma cells. Results: The exogenous Cx43 did not increase GJIC capacity of transfected cells, but it was critical to decrease the cell proliferation rate as well as reorganization of the actin filaments and cell flattening. We also observed more adhesion capacity to substrate after Cx43 transfection. Conclusion: Cx43 expression leads to a decrease of the growth of the rat hepatocellular carcinoma cells and it contributes to the reversion of the transformed phenotype. These effects were independent of the GJIC and were probably associated with the phosphorylation pattern changes and redistribution of the Cx43 protein.

Polar organic marker compounds in atmospheric aerosols during the LBA-SMOCC 2002 biomass burning experiment in Rondonia, Brazil: sources and source processes, time series, diel variations and size distributions

Measurements of polar organic marker compounds were performed on aerosols that were collected at a pasture site in the Amazon basin (Rondonia, Brazil) using a high-volume dichotomous sampler (HVDS) and a Micro-Orifice Uniform Deposit Impactor (MOUDI) within the framework of the 2002 LBA-SMOCC (Large-Scale Biosphere Atmosphere Experiment in Amazonia - Smoke Aerosols, Clouds, Rainfall, and Climate: Aerosols From Biomass Burning Perturb Global and Regional Climate) campaign. The campaign spanned the late dry season (biomass burning), a transition period, and the onset of the wet season (clean conditions). In the present study a more detailed discussion is presented compared to previous reports on the behavior of selected polar marker compounds, including levoglucosan, malic acid, isoprene secondary organic aerosol (SOA) tracers and tracers for fungal spores. The tracer data are discussed taking into account new insights that recently became available into their stability and/or aerosol formation processes. During all three periods, levoglucosan was the most dominant identified organic species in the PM(2.5) size fraction of the HVDS samples. In the dry period levoglucosan reached concentrations of up to 7.5 mu g m(-3) and exhibited diel variations with a nighttime prevalence. It was closely associated with the PM mass in the size-segregated samples and was mainly present in the fine mode, except during the wet period where it peaked in the coarse mode. Isoprene SOA tracers showed an average concentration of 250 ng m(-3) during the dry period versus 157 ng m(-3) during the transition period and 52 ng m(-3) during the wet period. Malic acid and the 2-methyltetrols exhibited a different size distribution pattern, which is consistent with different aerosol formation processes (i.e., gas-to-particle partitioning in the case of malic acid and heterogeneous formation from gas-phase precursors in the case of the 2-methyltetrols). The 2-methyltetrols were mainly associated with the fine mode during all periods, while malic acid was prevalent in the fine mode only during the dry and transition periods, and dominant in the coarse mode during the wet period. The sum of the fungal spore tracers arabitol, mannitol, and erythritol in the PM(2.5) fraction of the HVDS samples during the dry, transition, and wet periods was, on average, 54 ng m(-3), 34 ng m(-3), and 27 ng m(-3), respectively, and revealed minor day/night variation. The mass size distributions of arabitol and mannitol during all periods showed similar patterns and an association with the coarse mode, consistent with their primary origin. The results show that even under the heavy smoke conditions of the dry period a natural background with contributions from bioaerosols and isoprene SOA can be revealed. The enhancement in isoprene SOA in the dry season is mainly attributed to an increased acidity of the aerosols, increased NO(x) concentrations and a decreased wet deposition.

Combining Monte Carlo simulation and density-functional theory to describe the spectral changes of Na(2) in liquid helium

Spectral changes of Na(2) in liquid helium were studied using the sequential Monte Carlo-quantum mechanics method. Configurations composed by Na(2) surrounded by explicit helium atoms sampled from the Monte Carlo simulation were submitted to time-dependent density-functional theory calculations of the electronic absorption spectrum using different functionals. Attention is given to both line shift and line broadening. The Perdew, Burke, and Ernzerhof (PBE1PBE, also known as PBE0) functional, with the PBE1PBE/6-311++G(2d,2p) basis set, gives the spectral shift, compared to gas phase, of 500 cm(-1) for the allowed X (1)Sigma(+)(g) -> B (1)Pi(u) transition, in very good agreement with the experimental value (700 cm(-1)). For comparison, cluster calculations were also performed and the first X (1)Sigma(+)(g) -> A (1)Sigma(+)(u) transition was also considered.

Mn-doped cubic BN as an atomiclike memory device: A density functional study

We investigate the electronic properties of Mn(B) substitutional doping in cubic boron nitride (BN), for different charge states, using density functional theory (DFT) calculations. We show that the neutral Mn has a nonmagnetic ground state (S=0). Upon charge injection, it is unambiguously shown that the Mn(B)(-) has a high-spin configuration with a strong, localized magnetic moment of 5 mu(Bohr). We developed a simple model, parameterized by the DFT results, that allows us to interpret the rules played by the crystal-field and exchange-correlation splitting in the magnetization process.

Logarithmic contribution to the electrical resistivity in (Ru(1-x)Ir(x))Sr(2)GdCu(2)O(8) compounds

A systematic study of magnetoresistance and dc magnetization was conducted in polycrystalline (Ru(1-x)Ir(x))Sr(2)GdCu(2)O(8) [(Ru,Ir)-1212] compounds, for 0 <= x <= 0.15. We found that a deviation from linearity in the normal-state electrical resistivity (rho) curves for temperatures below the magnetic transition temperature T(M) < 130 K can be properly described by a logarithmic term. The prefactor C(x, H) of this anomalous ln T contribution to rho(T) increases linearly with the Ir concentration, and diminishes rapidly with increasing applied magnetic field up to H approximate to 4 T, merging with the C(0,H) curve at higher magnetic fields. Correlation with magnetic susceptibility measurements supports a scenario of local perturbations in the orientation of Ru moments induced in the neighborhood of the Ir ions, therefore acting as scattering centers. The linear dependence of the prefactor C(x,H=0) and the superconducting transition temperature T(SC) on x points to a common source for the resistivity anomaly and the reduction in T(SC), suggesting that the CuO(2) and RuO(2) layers are not decoupled.

Accurate prediction of the Si/SiO(2) interface band offset using the self-consistent ab initio DFT/LDA-1/2 method

We use the density functional theory/local-density approximation (DFT/LDA)-1/2 method [L. G. Ferreira , Phys. Rev. B 78, 125116 (2008)], which attempts to fix the electron self-energy deficiency of DFT/LDA by half-ionizing the whole Bloch band of the crystal, to calculate the band offsets of two Si/SiO(2) interface models. Our results are similar to those obtained with a ""state-of-the-art"" GW approach [R. Shaltaf , Phys. Rev. Lett. 100, 186401 (2008)], with the advantage of being as computationally inexpensive as the usual DFT/LDA. Our band gap and band offset predictions are in excellent agreement with experiments.

Edge effects in bilayer graphene nanoribbons: Ab initio total-energy density functional theory calculations

We show that the ground state of zigzag bilayer graphene nanoribbons is nonmagnetic. It also possesses a finite gap, which has a nonmonotonic dependence with the width as a consequence of the competition between bulk and strongly attractive edge interactions. All results were obtained using ab initio total-energy density functional theory calculations with the inclusion of parametrized van der Waals interactions.

Barrier-free substitutional doping of graphene sheets with boron atoms: Ab initio calculations

Using ab initio methods, we propose a simple and effective way to substitutionally dope graphene sheets with boron. The method consists of selectively exposing each side of the graphene sheet to different elements. We first expose one side of the membrane to boron while the other side is exposed to nitrogen. Proceeding this way, the B atoms will be spontaneously incorporated into the graphene membrane without any activation barrier. In a second step, the system should be exposed to a H-rich environment, which will remove the CN radical from the layer and form HCN, leading to a perfect substitutional doping.

Approximation to density functional theory for the calculation of band gaps of semiconductors

The local-density approximation (LDA) together with the half occupation (transitionstate) is notoriously successful in the calculation of atomic ionization potentials. When it comes to extended systems, such as a semiconductor infinite system, it has been very difficult to find a way to half ionize because the hole tends to be infinitely extended (a Bloch wave). The answer to this problem lies in the LDA formalism itself. One proves that the half occupation is equivalent to introducing the hole self-energy (electrostatic and exchange correlation) into the Schrodinger equation. The argument then becomes simple: The eigenvalue minus the self-energy has to be minimized because the atom has a minimal energy. Then one simply proves that the hole is localized, not infinitely extended, because it must have maximal self-energy. Then one also arrives at an equation similar to the self- interaction correction equation, but corrected for the removal of just 1/2 electron. Applied to the calculation of band gaps and effective masses, we use the self- energy calculated in atoms and attain a precision similar to that of GW, but with the great advantage that it requires no more computational effort than standard LDA.

Short-range structure of Pb(1-x)Ba(x)Zr(0.65)Ti(0.35)O(3) ceramic compounds probed by XAS and Raman scattering techniques

Ti K-edge x-ray absorption near-edge spectroscopy (XANES) and Raman scattering were used to study the solid solution effects on the structural and vibrational properties of Pb(1-x)Ba(x)Zr(0.65)Ti(0.35)O(3) with 0.0 < x < 0.40. Compared with x-ray diffraction techniques, which indicates that the average crystal symmetry changes with the substitution of Pb by Ba ions or with temperature variations for samples with x=0.00, 0.10, and 0.20, local structural probes such as XANES and Raman scattering results demonstrate that at local level, the symmetry changes are much less prominent. Theoretical XANES spectra calculation corroborate with the interpretation of the XANES experimental data.