Constraining the dark energy and smoothness parameter with type Ia supernovae and gamma-ray bursts

The existence of inhomogeneities in the observed Universe modifies the distance-redshift relations thereby affecting the results of cosmological tests in comparison to the ones derived assuming spatially uniform models. By modeling the inhomogeneities through a Zeldovich-Kantowski-Dyer-Roeder approach which is phenomenologically characterized by a smoothness parameter alpha, we rediscuss the constraints on the cosmic parameters based on type Ia supernovae (SNe Ia) and gamma-ray bursts (GRBs) data. The present analysis is restricted to a flat Lambda CDM model with the reasonable assumption that Lambda does not clump. A chi(2) analysis using 557 SNe Ia data from the Union2 compilation data (R. Amanullah et al., Astrophys. J. 716, 712 (2010).) constrains the pair of parameters (Omega(m), alpha) to Omega(m) = 0.27(-0.03)(+0.08) (2 sigma) and alpha >= 0.25. A similar analysis based only on 59 Hymnium GRBs (H. Wei, J. Cosmol. Astropart. Phys. 08 (2010) 020.) constrains the matter density parameter to be Omega(m) = 0.35(-0.24)(+0.62) (2 sigma) while all values for the smoothness parameter are allowed. By performing a joint analysis, it is found that Omega(m) = 0.27(-0.06)(+0.06) and alpha >= 0.52. As a general result, although considering that current GRB data alone cannot constrain the smoothness alpha parameter, our analysis provides an interesting cosmological probe for dark energy even in the presence of inhomogeneities.

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.

Extracytoplasmic function (ECF) sigma factor sigma(F) is involved in Caulobacter crescentus response to heavy metal stress

Background: The alpha-proteobacterium Caulobacter crescentus inhabits low-nutrient environments and can tolerate certain levels of heavy metals in these sites. It has been reported that C. crescentus responds to exposure to various heavy metals by altering the expression of a large number of genes. Results: In this work, we show that the ECF sigma factor sigma(F) is one of the regulatory proteins involved in the control of the transcriptional response to chromium and cadmium. Microarray experiments indicate that sigma(F) controls eight genes during chromium stress, most of which were previously described as induced by heavy metals. Surprisingly, sigma(F) itself is not strongly auto-regulated under metal stress conditions. Interestingly, sigma(F)-dependent genes are not induced in the presence of agents that generate reactive oxygen species. Promoter analyses revealed that a conserved sigma(F)-dependent sequence is located upstream of all genes of the sigma(F) regulon. In addition, we show that the second gene in the sigF operon acts as a negative regulator of sigma(F) function, and the encoded protein has been named NrsF (Negative regulator of sigma F). Substitution of two conserved cysteine residues (C131 and C181) in NrsF affects its ability to maintain the expression of sigma(F)-dependent genes at basal levels. Furthermore, we show that sigma(F) is released into the cytoplasm during chromium stress and in cells carrying point mutations in both conserved cysteines of the protein NrsF. Conclusion: A possible mechanism for induction of the sigma(F)-dependent genes by chromium and cadmium is the inactivation of the putative anti-sigma factor NrsF, leading to the release of sigma(F) to bind RNA polymerase core and drive transcription of its regulon.

Flux-Line-Lattice Melting and Upper Critical Field of Bi1.65Pb0.35Sr2Ca2Cu3O10+delta Ceramic Samples

We have conducted magnetoresistance measurements rho(T,H) in applied magnetic fields up to 18 T in Bi1.65Pb0.35Sr2Ca2Cu3O10+delta ceramic samples which were subjected to different uniaxial compacting pressures. The anisotropic upper critical fields H (c2)(T) were extracted from the rho(T,H) data, yielding and the out-of-plane superconducting coherence length xi (c) (0)similar to 3 . We have also estimated and xi (ab) (0) similar to 90 . In addition to this, a flux-line-lattice (FLL) melting temperature T (m) has been identified as a second peak in the derivative of the magnetoresistance d rho/dT data close to the superconducting transition temperature. An H (m) vs. T phase diagram was constructed and the FLL boundary lines were found to obey a temperature dependence H (m) ae(T (c) /T-1) (alpha) , where alpha similar to 2 for the sample subjected to the higher compacting pressure. A reasonable value of the Lindemann parameter c (L) similar to 0.29 has been found for all samples studied.

Structural Insights into Human Peroxisome Proliferator Activated Receptor Delta (PPAR-Delta) Selective Ligand Binding

Peroxisome proliferator activated receptors (PPARs delta, alpha and gamma) are closely related transcription factors that exert distinct effects on fatty acid and glucose metabolism, cardiac disease, inflammatory response and other processes. Several groups developed PPAR subtype specific modulators to trigger desirable effects of particular PPARs without harmful side effects associated with activation of other subtypes. Presently, however, many compounds that bind to one of the PPARs cross-react with others and rational strategies to obtain highly selective PPAR modulators are far from clear. GW0742 is a synthetic ligand that binds PPAR delta more than 300-fold more tightly than PPAR alpha or PPAR gamma but the structural basis of PPAR delta: GW0742 interactions and reasons for strong selectivity are not clear. Here we report the crystal structure of the PPAR delta:GW0742 complex. Comparisons of the PPAR delta:GW0742 complex with published structures of PPARs in complex with alpha and gamma selective agonists and pan agonists suggests that two residues (Val312 and Ile328) in the buried hormone binding pocket play special roles in PPAR delta selective binding and experimental and computational analysis of effects of mutations in these residues confirms this and suggests that bulky substituents that line the PPAR alpha and gamma ligand binding pockets as structural barriers for GW0742 binding. This analysis suggests general strategies for selective PPAR delta ligand design.