Independent beta-arrestin 2 and G protein-mediated pathways for angiotensin II activation of extracellular signal-regulated kinases 1 and 2.

Stimulation of a mutant angiotensin type 1A receptor (DRY/AAY) with angiotensin II (Ang II) or of a wild-type receptor with an Ang II analog ([sarcosine1,Ile4,Ile8]Ang II) fails to activate classical heterotrimeric G protein signaling but does lead to recruitment of beta-arrestin 2-GFP and activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) (maximum stimulation approximately 50% of wild type). This G protein-independent activation of mitogen-activated protein kinase is abolished by depletion of cellular beta-arrestin 2 but is unaffected by the PKC inhibitor Ro-31-8425. In parallel, stimulation of the wild-type angiotensin type 1A receptor with Ang II robustly stimulates ERK1/2 activation with approximately 60% of the response blocked by the PKC inhibitor (G protein dependent) and the rest of the response blocked by depletion of cellular beta-arrestin 2 by small interfering RNA (beta-arrestin dependent). These findings imply the existence of independent G protein- and beta-arrestin 2-mediated pathways leading to ERK1/2 activation and the existence of distinct "active" conformations of a seven-membrane-spanning receptor coupled to each

Serration phenomena occurring during tensile tests of three high-manganese TWinning Induced Plasticity (TWIP) steels

In this study, the serration phenomena of two high-Mn TWIP steels and an Al-added TWIP steel were examined by tensile tests, and were explained by the microstructural evolution including formation of localized Portevin-Le Chatelier deformation bands and twins. In stress-strain curves of the high-Mn steels, serrations started in a fine and short shape, and their height and periodic interval increased with increasing strain, whereas the Al-added steel did not show any serrations. According to digital images of strain rate and strain obtained from a vision strain gage system, deformation bands were initially formed at the upper region of the gage section, and moved downward along the tensile loading direction. The time when the band formation started was matched with the time when one serration occurred in the stress-time curve. This serration behavior was generally explained by dynamic strain aging, which was closely related with the formation of deformation bands. (C) The Minerals, Metals & Materials Society and ASM International 2013ope

Probing the Neutrino Mass Hierarchy with Super-Kamiokande

We show that for recently discovered large values of theta(13), a superbeam with an average neutrino energy of ~ 5 GeV, such as those being proposed at CERN, if pointing to Super-Kamiokande (L = 8770 km), could reveal the neutrino mass hierarchy at 5 sigma in less than two years irrespective of the true hierarchy and CP phase. The measurement relies on the near resonant matter effect in the numu to nue oscillation channel, and can be done counting the total number of appearance events with just a neutrino beam.Comment: 16 pages, 7 pdf figures, 2 tables. Format changed and text extended. Four new pdf figures added. Dependency of the result on 1-3 mixing angle discussed. Conclusions unchanged. Accepted in JHE

Potential of optimized NOvA for large theta(13) & combined performance with a LArTPC & T2K

NOvA experiment has reoptimized its event selection criteria in light of the recently measured moderately large value of theta(13). We study the improvement in the sensitivity to the neutrino mass hierarchy and to leptonic CP violation due to these new features. For favourable values of deltacp, NOvA sensitivity to mass hierarchy and leptonic CP violation is increased by 20%. Addition of 5 years of neutrino data from T2K to NOvA more than doubles the range of deltacp for which the leptonic CP violation can be discovered, compared to stand alone NOvA. But for unfavourable values of deltacp, the combination of NOvA and T2K are not enough to provide even a 90% C.L. hint of hierarchy discovery. Therefore, we further explore the improvement in the hierarchy and CP violation sensitivities due to the addition of a 10 kt liquid argon detector placed close to NOvA site. The capabilities of such a detector are equivalent to those of NOvA in all respects. We find that combined data from 10 kt liquid argon detector (3 years of nu + 3 years of nubar run), NOvA (6 years of nu + 6 years of nubar run) and T2K (5 years of nu run) can give a close to 2 sigma hint of hierarchy discovery for all values of deltacp. With this combined data, we can achieve CP violation discovery at 95% C.L. for roughly 60% values of deltacp.Comment: 22 pages, 24 pdf figures, 5 tables. In the appendix, new results are presented with conservative choices of central values of oscillation parameters. New references are added. Accepted in JHE

Associations of vitamin D pathway genes with circulating 25-hydroxyvitamin-D, 1,25-dihydroxyvitamin-D, and prostate cancer:a nested case-control study

Vitamin D pathway single nucleotide polymorphisms (SNPs) are potentially useful proxies for investigating whether circulating vitamin D metabolites [total 25-hydroxyvitamin-D, 25(OH)D; 1,25-dihydroxyvitamin, 1,25(OH)2D] are causally related to prostate cancer. We investigated associations of sixteen SNPs across seven genes with prostate-specific antigen-detected prostate cancer

Mass hierarchy discrimination with atmospheric neutrinos in large volume ice/water Cherenkov detectors

Large mass ice/water Cherenkov experiments, optimized to detect low energy (1-20 GeV) atmospheric neutrinos, have the potential to discriminate between normal and inverted neutrino mass hierarchies. The sensitivity depends on several model and detector parameters, such as the neutrino flux profile and normalization, the Earth density profile, the oscillation parameter uncertainties, and the detector effective mass and resolution. A proper evaluation of the mass hierarchy discrimination power requires a robust statistical approach. In this work, the Toy Monte Carlo, based on an extended unbinned likelihood ratio test statistic, was used. The effect of each model and detector parameter, as well as the required detector exposure, was then studied. While uncertainties on the Earth density and atmospheric neutrino flux profiles were found to have a minor impact on the mass hierarchy discrimination, the flux normalization, as well as some of the oscillation parameter (\Delta m^2_{31}, \theta_{13}, \theta_{23}, and \delta_{CP}) uncertainties and correlations resulted critical. Finally, the minimum required detector exposure, the optimization of the low energy threshold, and the detector resolutions were also investigated.Comment: 23 pages, 16 figure

Optimized intermolecular potential for nitriles based on Anisotropic United Atoms model

An extension of the Anisotropic United Atoms intermolecular potential model is proposed for nitriles. The electrostatic part of the intermolecular potential is calculated using atomic charges obtained by a simple Mulliken population analysis. The repulsion-dispersion interaction parameters for methyl and methylene groups are taken from transferable AUA4 literature parameters [Ungerer et al., J. Chem. Phys., 2000, 112, 5499]. Non-bonding Lennard-Jones intermolecular potential parameters are regressed for the carbon and nitrogen atoms of the nitrile group (–C≡N) from experimental vapor-liquid equilibrium data of acetonitrile. Gibbs Ensemble Monte Carlo simulations and experimental data agreement is very good for acetonitrile, and better than previous molecular potential proposed by Hloucha et al. [J. Chem. Phys., 2000, 113, 5401]. The transferability of the resulting potential is then successfully tested, without any further readjustment, to predict vapor-liquid phase equilibrium of propionitrile and n-butyronitrile

Repressing Anarchy in Neutrino Mass Textures

The recent results that $\theta_{13}$ is relatively large, of the order of the previous upper bound, and the indications of a sizable deviation of $\theta_{23}$ from the maximal value are in agreement with the predictions of Anarchy in the lepton sector. The quark and charged lepton hierarchies can then be reproduced in a SU(5) GUT context by attributing non-vanishing $U(1)_{FN}$ charges, different for each family, only to the SU(5) tenplet states. The fact that the observed mass hierarchies are stronger for up quarks than for down quarks and charged leptons supports this idea. As discussed in the past, in the flexible context of $SU(5)\otimes U(1)_{FN}$, different patterns of charges can be adopted going from Anarchy to various types of hierarchy. We revisit this approach by also considering new models and we compare all versions to the present data. As a result we confirm that, by relaxing the extreme ansatz of equal $U(1)_{FN}$ charges for all SU(5) pentaplets and singlets, better agreement with the data than for Anarchy is obtained without increasing the model complexity. We also present the distributions obtained in the different models for the Dirac CP-violating phase. Finally we discuss the relative merits of these simple models.Comment: v1: 12 pages, 3 figures; v2: 13 pages, 3 figures, text improved, matches version accepted for publication; v3: submitted to add an acknowledgment to a networ

Global analyses of TetR family transcriptional regulators in mycobacteria indicates conservation across species and diversity in regulated functions

BACKGROUND: Mycobacteria inhabit diverse niches and display high metabolic versatility. They can colonise both humans and animals and are also able to survive in the environment. In order to succeed, response to environmental cues via transcriptional regulation is required. In this study we focused on the TetR family of transcriptional regulators (TFTRs) in mycobacteria. RESULTS: We used InterPro to classify the entire complement of transcriptional regulators in 10 mycobacterial species and these analyses showed that TFTRs are the most abundant family of regulators in all species. We identified those TFTRs that are conserved across all species analysed and those that are unique to the pathogens included in the analysis. We examined genomic contexts of 663 of the conserved TFTRs and observed that the majority of TFTRs are separated by 200 bp or less from divergently oriented genes. Analyses of divergent genes indicated that the TFTRs control diverse biochemical functions not limited to efflux pumps. TFTRs typically bind to palindromic motifs and we identified 11 highly significant novel motifs in the upstream regions of divergently oriented TFTRs. The C-terminal ligand binding domain from the TFTR complement in M. tuberculosis showed great diversity in amino acid sequence but with an overall architecture common to other TFTRs. CONCLUSION: This study suggests that mycobacteria depend on TFTRs for the transcriptional control of a number of metabolic functions yet the physiological role of the majority of these regulators remain unknown. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1696-9) contains supplementary material, which is available to authorized users

Neutrino physics at accelerators

Present and future neutrino experiments at accelerators are mainly concerned with understanding the neutrino oscillation phenomenon and its implications. Here a brief account of neutrino oscillations is given together with a description of the supporting data. Some current and planned accelerator neutrino experiments are also explained.Comment: 23 pages, 24 figures. Talk given at the Corfu Summer Institute on Elementary Particle Physics 200