Ligand- and Structure-Based Drug Design Strategies and PPAR delta/alpha Selectivity

Peroxisome-proliferator-activated receptors are a class of nuclear receptors with three subtypes: a, ? and d. Their main function is regulating gene transcription related to lipid and carbohydrate metabolism. Currently, there are no peroxisome-proliferator-activated receptors d drugs being marketed. In this work, we studied a data set of 70 compounds with a and d activity. Three partial least square models were created, and molecular docking studies were performed to understand the main reasons for peroxisome-proliferator-activated receptors d selectivity. The obtained results showed that some molecular descriptors (log P, hydration energy, steric and polar properties) are related to the main interactions that can direct ligands to a particular peroxisome-proliferator-activated receptors subtype.

Study of the oxygen vacancy influence on magnetic properties of Fe- and Co-doped SnO2 diluted alloys

Transition-metal (TM)-doped diluted magnetic oxides (DMOs) have attracted attention from both experimental and theoretical points of view due to their potential use in spintronics towards new nanostructured devices and new technologies. In the present work, we study the magnetic properties of Sn0.96TM0.04O2 and Sn0.96TM0.04O1.98(V (O))(0.02), where TM = Fe and Co, focusing in particular in the role played by the presence of O vacancies nearby the TM. The calculated total energy as a function of the total magnetic moment per cell shows a magnetic metastability, corresponding to a ground state, respectively, with 2 and 1 mu(B)/cell, for Fe and Co. Two metastable states, with 0 and 4 mu(B)/cell were found for Fe, and a single value, 3 mu(B)/cell, for Co. The spin-crossover energies (E (S)) were calculated. The values are E (S) (0/2) = 107 meV and E (S) (4/2) = 25 meV for Fe. For Co, E (S) (3/1) = 36 meV. By creating O vacancies close to the TM site, we show that the metastablity and E (S) change. For iron, a new state appears, and the state with zero magnetic moment disappears. The ground state is 4 mu(B)/cell instead of 2 mu(B)/cell, and the energy E (S) (2/4) is 30 meV. For cobalt, the ground state is then found with 3 mu(B)/cell and the metastable state with 1 mu(B)/cell. The spin-crossover energy E (S) (1/3) is 21 meV. Our results suggest that these materials may be used in devices for spintronic applications that require different magnetization states.

Two-dimensional semimetal-insulator transition in HgTe-based quantum wells induced by a longitudinal magnetic field

A metal-insulator transition in a two-dimensional semimetal based on HgTe quantum wells is discovered. The transition is induced by a magnetic field applied parallel to the plane of the quantum well. The threshold behavior of the activation energy as a function of the magnetic-field strength and an abrupt reduction of the Hall resistance at the onset of the transition suggest that the observed effect originates from the formation of an excitonic insulator.

Spin accumulation encoded in electronic noise for mesoscopic billiards with finite tunneling rates

We study the effects of spin accumulation (inside reservoirs) on electronic transport with tunneling and reflections at the gates of a quantum dot. Within the stub model, the calculations focus on the current-current correlation function for the flux of electrons injected into the quantum dot. The linear response theory used allows us to obtain the noise power in the regime of thermal crossover as a function of parameters that reveal the spin polarization at the reservoirs. The calculation is performed employing diagrammatic integration within the universal groups (ensembles of Dyson) for a nonideal, nonequilibrium chaotic quantum dot. We show that changes in the spin distribution determine significant alterations in noise behavior at values of the tunneling rates close to zero, in the regime of strong reflection at the gates.

Desigualdade social no adoecimento e morte por câncer de boca e orofaríngeo no Município de São Paulo, Brasil: 1997 a 2008

A ocupação do espaço geográfico é determinada historicamente pelo modelo socioeconômico e pelo dinamismo de suas relações sociais, políticas e ideológicas. O objetivo deste trabalho é avaliar a distribuição espacial e o efeito de indicadores socioeconômicos no adoecimento e morte por câncer de boca e orofaríngeo no Município de São Paulo, Brasil, no período de 1997 a 2008. Os dados foram coletados no Registro de Câncer de Base Populacional e no Programa de Aprimoramento das Informações de Mortalidade - PRO-AIM e georreferenciados pelos softwares Terraview e GeoDa. O referencial teórico para avaliação dos resultados foi baseado na teoria de Milton Santos. As taxas de incidência apresentaram um índice de autocorrelação Global de Moran de 0,226 e as taxas de mortalidade de 0,337. A Incidência de câncer de boca e orofaríngeo não apresenta um padrão espacial bem definido no Município de São Paulo, mas é bastante desigual no que se refere à Mortalidade, concentrando as suas menores taxas na área central, mais rica e economicamente menos desigual.

Catch-up growth in children after repair of Tetralogy of Fallot

Purpose: To evaluate the growth of children after repair of Tetralogy of Fallot, as well as the influence of residual lesions and socio-economic status. Methods: A total of 17 children, including 10 boys with a median age of 16 months at surgery, were enrolled in a retrospective cohort, in a tertiary care university hospital. Anthropometric (as z-scores), clinical, nutritional, and social data were collected. Results: Weight-for-age and weight-for-height z-scores decreased pre-operatively and recovered post-operatively in almost all patients, most markedly weight for age. Weight-for-height z-scores improved, but were still lower than birth values in the long term. Long-term height-for-age z-scores were higher than those at birth, surgery, and 3 months post-operatively. Most patients showed catch-up growth for height for age (70%), weight for age (82%), and weight for height (70%). Post-operative residual lesions (76%) influenced weight-for-age z-scores. Despite the fact that most patients (70%) were from low-income families, energy intake was above the estimated requirement for age and gender in all but one patient. There was no influence of socio-economic status on pre- and post-operative growth. Bone age was delayed and long-term-predicted height was within mid-parental height limits in 16 children (93%). Conclusion: Children submitted to Tetralogy of Fallot repair had pre-operative acute growth restriction and showed post-operative catch-up growth for weight and height. Acute growth restriction could still be present in the long term.

The gene transformer-2 of Anastrepha fruit flies (Diptera, Tephritidae) and its evolution in insects

Abstract Background In the tephritids Ceratitis, Bactrocera and Anastrepha, the gene transformer provides the memory device for sex determination via its auto-regulation; only in females is functional Tra protein produced. To date, the isolation and characterisation of the gene transformer-2 in the tephritids has only been undertaken in Ceratitis, and it has been shown that its function is required for the female-specific splicing of doublesex and transformer pre-mRNA. It therefore participates in transformer auto-regulatory function. In this work, the characterisation of this gene in eleven tephritid species belonging to the less extensively analysed genus Anastrepha was undertaken in order to throw light on the evolution of transformer-2. Results The gene transformer-2 produces a protein of 249 amino acids in both sexes, which shows the features of the SR protein family. No significant partially spliced mRNA isoform specific to the male germ line was detected, unlike in Drosophila. It is transcribed in both sexes during development and in adult life, in both the soma and germ line. The injection of Anastrepha transformer-2 dsRNA into Anastrepha embryos caused a change in the splicing pattern of the endogenous transformer and doublesex pre-mRNA of XX females from the female to the male mode. Consequently, these XX females were transformed into pseudomales. The comparison of the eleven Anastrepha Transformer-2 proteins among themselves, and with the Transformer-2 proteins of other insects, suggests the existence of negative selection acting at the protein level to maintain Transformer-2 structural features. Conclusions These results indicate that transformer-2 is required for sex determination in Anastrepha through its participation in the female-specific splicing of transformer and doublesex pre-mRNAs. It is therefore needed for the auto-regulation of the gene transformer. Thus, the transformer/transfomer-2 > doublesex elements at the bottom of the cascade, and their relationships, probably represent the ancestral state (which still exists in the Tephritidae, Calliphoridae and Muscidae lineages) of the extant cascade found in the Drosophilidae lineage (in which tra is just another component of the sex determination gene cascade regulated by Sex-lethal). In the phylogenetic lineage that gave rise to the drosophilids, evolution co-opted for Sex-lethal, modified it, and converted it into the key gene controlling sex determination.

3C 273 variability at 7 mm: evidence of shocks and precession in the jet

We report on four years of observations of 3C 273 at 7mm obtained with the Itapetinga radio telescope, in Brazil, between 2009 and 2013. We detected a flare in 2010 March, when the flux density increased by 50 per cent and reached 35 Jy. After the flare, the flux density started to decrease and reached values lower than 10 Jy. We suggest that the 7-mm flare is the radio counterpart of the γ -ray flare observed by the Fermi Large Area Telescope in 2009 September, in which the flux density at high energies reached a factor of 50 of its average value. A delay of 170 d between the radio and γ -ray flares was revealed using the discrete correlation function (DCF) that can be interpreted in the context of a shock model, in which each flare corresponds to the formation of a compact superluminal component that expands and becomes optically thin at radio frequencies at latter epochs. The differences in flare intensity between frequencies and at different times are explained as a consequence of an increase in the Doppler factor δ, as predicted by the 16-yr precession model proposed by Abraham & Romero. This increase has a large effect on boosting at high frequencies while it does not affect the observed optically thick radio emission too much. We discuss other observable effects of the variation in δ, such as the increase in the formation rate of superluminal components, the variations in the time delay between flares and the periodic behaviour of the radio light curve that we have found to be compatible with changes in the Doppler factor.

System size and energy dependence of near-side dihadron correlations

Two-particle azimuthal (Delta phi) and pseudorapidity (Delta eta) correlations using a trigger particle with large transverse momentum (p(T)) in d+Au, Cu+Cu, and Au+Au collisions at root s(NN) = 62.4 GeV and 200 GeV from the STAR experiment at the Relativistic Heavy Ion Collider are presented. The near-side correlation is separated into a jet-like component, narrow in both Delta phi and Delta eta, and the ridge, narrow in Delta phi but broad in Delta eta. Both components are studied as a function of collision centrality, and the jet-like correlation is studied as a function of the trigger and associated p(T). The behavior of the jet-like component is remarkably consistent for different collision systems, suggesting it is produced by fragmentation. The width of the jet-like correlation is found to increase with the system size. The ridge, previously observed in Au+Au collisions at root s(NN) = 200 GeV, is also found in Cu+Cu collisions and in collisions at root s(NN) = 62.4 GeV, but is found to be substantially smaller at root s(NN) = 62.4 GeV than at root s(NN) = 200 GeV for the same average number of participants (< N-part >). Measurements of the ridge are compared to models.

New cosmic accelerating scenario without dark energy

We propose an alternative, nonsingular, cosmic scenario based on gravitationally induced particle production. The model is an attempt to evade the coincidence and cosmological constant problems of the standard model (Lambda CDM) and also to connect the early and late time accelerating stages of the Universe. Our space-time emerges from a pure initial de Sitter stage thereby providing a natural solution to the horizon problem. Subsequently, due to an instability provoked by the production of massless particles, the Universe evolves smoothly to the standard radiation dominated era thereby ending the production of radiation as required by the conformal invariance. Next, the radiation becomes subdominant with the Universe entering in the cold dark matter dominated era. Finally, the negative pressure associated with the creation of cold dark matter (CCDM model) particles accelerates the expansion and drives the Universe to a final de Sitter stage. The late time cosmic expansion history of the CCDM model is exactly like in the standard Lambda CDM model; however, there is no dark energy. The model evolves between two limiting (early and late time) de Sitter regimes. All the stages are also discussed in terms of a scalar field description. This complete scenario is fully determined by two extreme energy densities, or equivalently, the associated de Sitter Hubble scales connected by rho(I)/rho(f) = (H-I/H-f)(2) similar to 10(122), a result that has no correlation with the cosmological constant problem. We also study the linear growth of matter perturbations at the final accelerating stage. It is found that the CCDM growth index can be written as a function of the Lambda growth index, gamma(Lambda) similar or equal to 6/11. In this framework, we also compare the observed growth rate of clustering with that predicted by the current CCDM model. Performing a chi(2) statistical test we show that the CCDM model provides growth rates that match sufficiently well with the observed growth rate of structure.

Atopic dermatitis: correlation between non-damaged skin barrier function and disease activity

Background Atopic dermatitis (AD) is a chronic dermatosis, predominant in childhood, characterized by pruritus and eczematous-type lesions with xerosis as the prominent clinical sign. Objectives To analyze the correlation between biophysical measurements of skin barrier function and other assessment criteria of clinical severity according to Rajka and Langelands criteria. Methods Biophysical measurements [transepidermal water loss (TEWL) and corneometry] were obtained from 120 patients with the diagnosis of AD. Serum levels of IgE were also evaluated. Results A significant correlation between corneometry, TEWL, and clinical severity of AD was found. Data showed an inverse correlation between corneometry, TEWL, and AD severity, and a significant difference (P < 0.001) between mean of corneometry and TEWL and AD severity (mild, moderate, and severe). As for IgE levels, corneometry had significant negative correlation, in contrast with TEWL, which showed a significant positive correlation (P < 0.001). Conclusion Biophysical measurements of skin barrier in non-lesional skin of AD may work as an evaluation factor for AD severity.

A snapshot of suspended sediment and fluid mud occurrence in a mixed-energy embayment, Tijucas Bay, Brazil

Along the southern Brazilian coast, Tijucas Bay is known for its unique muddy tidal flats associated with chenier plains. Previous field observations pointed to very high suspended sediment concentrations (SSCs) in the inner parts of the bay, and in the estuary of the Tijucas River, suggesting the presence of fluid mud. In this study, the occurrences of suspended sediments and fluid mud were examined during a larger-scale, high-resolution 2-day field campaign on 1-2 May 2007, encompassing survey lines spanning nearly 80 km, 75 water sampling stations for near-bottom density estimates, and ten sediment sampling stations. Wave refraction modeling provided qualitative wave energy estimates as a function of different incidence directions. The results show that SSC increases toward the inner bay near the water surface, but seaward near the bottom. This suggests that suspended sediment is supplied by the local rivers, in particular the Tijucas. Near-surface SSCs were of the order of 50 mg l(-1) close to the shore, but exceeded 100 mg l(-1) near the bottom in the deeper parts of the bay. Fluid mud thickness and location given by densimetry and echo-sounding agreed in some places, although being mostly discordant. The best agreement was observed where wave energy was high during the campaign. The discrepancy between the two methods may be an indication for the existence of fluid mud, which is recorded by one method but not the other. Agreement is considered to be an indication of fluidization, whereas disagreement indicates more consolidation. Wave modeling suggests that waves from the ENE and SE are the most effective in supplying energy to the inner bay, which may induce the liquefaction of mud deposits to form fluid mud. Nearshore mud resuspension and weak horizontal currents result in sediment-laden offshore flow, which explains the higher SSCs measured in the deeper parts of the bay, besides providing a mechanism for fine-sediment export to the inner shelf.

Accurate ab initio potential energy surfaces for the (3)A '' and (3)A ' electronic states of the O(P-3) plus HBr system

In this work, we report the construction of potential energy surfaces for the (3)A '' and (3)A' states of the system O(P-3) + HBr. These surfaces are based on extensive ab initio calculations employing the MRCI+Q/CBS+SO level of theory. The complete basis set energies were estimated from extrapolation of MRCI+Q/aug-cc-VnZ(-PP) (n = Q, 5) results and corrections due to spin-orbit effects obtained at the CASSCF/aug-cc-pVTZ(-PP) level of theory. These energies, calculated over a region of the configuration space relevant to the study of the reaction O(P-3) + HBr -> OH + Br, were used to generate functions based on the many-body expansion. The three-body potentials were interpolated using the reproducing kernel Hilbert space method. The resulting surface for the (3)A '' electronic state contains van der Waals minima on the entrance and exit channels and a transition state 6.55 kcal/mol higher than the reactants. This barrier height was then scaled to reproduce the value of 5.01 kcal/mol, which was estimated from coupled cluster benchmark calculations performed to include high-order and core-valence correlation, as well as scalar relativistic effects. The (3)A' surface was also scaled, based on the fact that in the collinear saddle point geometry these two electronic states are degenerate. The vibrationally adiabatic barrier heights are 3.44 kcal/mol for the (3)A '' and 4.16 kcal/mol for the (3)A' state. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.4705428]

A search for anisotropy in the arrival directions of ultra high energy cosmic rays recorded at the Pierre Auger Observatory

Observations of cosmic rays arrival directions made with the Pierre Auger Observatory have previously provided evidence of anisotropy at the 99% CL using the correlation of ultra high energy cosmic rays (UHECRs) with objects drawn from the Veron-Cetty Veron catalog. In this paper we report on the use of three catalog independent methods to search for anisotropy. The 2pt-L, 2pt+ and 3pt methods, each giving a different measure of self-clustering in arrival directions, were tested on mock cosmic ray data sets to study the impacts of sample size and magnetic smearing on their results, accounting for both angular and energy resolutions. If the sources of UHECRs follow the same large scale structure as ordinary galaxies in the local Universe and if UHECRs are deflected no more than a few degrees, a study of mock maps suggests that these three method can efficiently respond to the resulting anisotropy with a P-value = 1.0% or smaller with data sets as few as 100 events. using data taken from January 1, 2004 to July 31, 2010 we examined the 20, 30, ... , 110 highest energy events with a corresponding minimum energy threshold of about 49.3 EeV. The minimum P-values found were 13.5% using the 2pt-L method, 1.0% using the 2pt+ method and 1.1% using the 3pt method for the highest 100 energy events. In view of the multiple (correlated) scans performed on the data set, these catalog-independent methods do not yield strong evidence of anisotropy in the highest energy cosmic rays.

On the energy conversion efficiency in magnetic hyperthermia applications: A new perspective to analyze the departure from the linear regime

The success of magnetic hyperthermia cancer treatments rely strongly on the magnetic properties of the nanoparticles and their intricate dependence on the externally applied field. This is particularly more so as the response departs from the low field linear regime. In this paper we introduce a new parameter, referred to as the efficiency in converting electromagnetic energy into thermal energy, which is shown to be remarkably useful in the analysis of the system response, especially when the power loss is investigated as a function of the applied field amplitude. Using numerical simulations of dynamic hysteresis, through the stochastic Landau-Lifshitz model, we map in detail the efficiency as a function of all relevant parameters of the system and compare the results with simple-yet powerful-predictions based on heuristic arguments about the relaxation time. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.4705392]