Prediction of anti-Alzheimer’s activity of flavonoids targeting acetylcholinesterase in silico

Introduction – Prenylated and pyrano-flavonoids of the genus Artocarpus J. R. Forster & G. Forster are well known for their acetylcholinesterase (AchE) inhibitory, anticholinergic, antiinflammatory, antimicrobial, antioxidant, antiproliferative and tyrosinase inhibitory activities. Some of these compounds have also been shown to be effective against Alzheimer’s disease. Objective – The aim of the in silico study was to establish protocols to predict the most effective flavonoid from prenylated and pyrano-flavonoid classes for AchE inhibition linking to the potential treatment of Alzheimer’s disease. Methodology – Three flavonoids isolated from Artocarpus anisophyllus Miq. were selected for the study. With these compounds, Lipinski filter, ADME/Tox screening, molecular docking and QSAR were performed in silico. In vitro activity was evaluated by bioactivity staining based on the Ellman’s method. Results – In the Lipinski filter and ADME/Tox screening, all test compounds produced positive results, but in the target fishing, only one flavonoid could successfully target AchE. Molecular docking was performed on this flavonoid, and this compound gained the score as -13.5762. From the QSAR analysis the IC50 was found to be 1659.59 nM. Again, 100 derivatives were generated from the parent compound and docking was performed. The derivative number 20 was the best scorer i.e., -31.6392 and IC50 was predicted as 6.025 nM. Conclusion – Results indicated that flavonoids could be efficient inhibitors of AchE and thus, could be useful in the management of Alzheimer’s disease

LHC Predictions from a Tevatron Anomaly in the Top Quark Forward-Backward Asymmetry

We examine the implications of the recent CDF measurement of the top-quark forward-backward asymmetry, focusing on a scenario with a new color octet vector boson at 1-3 TeV. We study several models, as well as a general effective field theory, and determine the parameter space which provides the best simultaneous fit to the CDF asymmetry, the Tevatron top pair production cross section, and the exclusion regions from LHC dijet resonance and contact interaction searches. Flavor constraints on these models are more subtle and less severe than the literature indicates. We find a large region of allowed parameter space at high axigluon mass and a smaller region at low mass; we match the latter to an SU(3)xSU(3)/SU(3) coset model with a heavy vector-like fermion. Our scenario produces discoverable effects at the LHC with only 1-2 inverse femtobarns of luminosity at 7-8 TeV. Lastly, we point out that a Tevatron measurement of the b-quark forward-backward asymmetry would be very helpful in characterizing the physics underlying the top-quark asymmetry.Comment: 35 pages, 10 figures, 4 table

Deuteron and antideuteron production in Au+Au collisions at sqrt(s_NN)=200 GeV

The production of deuterons and antideuterons in the transverse momentum range 1.1 < p_T < 4.3 GeV/c at mid-rapidity in Au + Au collisions at sqrt(s_NN)=200 GeV has been studied by the PHENIX experiment at RHIC. A coalescence analysis comparing the deuteron and antideuteron spectra with those of protons and antiprotons, has been performed. The coalescence probability is equal for both deuterons and antideuterons and increases as a function of p_T, which is consistent with an expanding collision zone. Comparing (anti)proton yields p_bar/p = 0.73 +/- 0.01, with (anti)deuteron yields: d_bar/d = 0.47 +/- 0.03, we estimate that n_bar/n = 0.64 +/- 0.04.Comment: 326 authors, 6 pages text, 5 figures, 1 Table. Submitted to PRL. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Single Electrons from Heavy Flavor Decays in p+p Collisions at sqrt(s) = 200 GeV

The invariant differential cross section for inclusive electron production in p+p collisions at sqrt(s) = 200 GeV has been measured by the PHENIX experiment at the Relativistic Heavy Ion Collider over the transverse momentum range $0.4 <= p_T <= 5.0 GeV/c at midrapidity (eta <= 0.35). The contribution to the inclusive electron spectrum from semileptonic decays of hadrons carrying heavy flavor, i.e. charm quarks or, at high p_T, bottom quarks, is determined via three independent methods. The resulting electron spectrum from heavy flavor decays is compared to recent leading and next-to-leading order perturbative QCD calculations. The total cross section of charm quark-antiquark pair production is determined as sigma_(c c^bar) = 0.92 +/- 0.15 (stat.) +- 0.54 (sys.) mb.Comment: 329 authors, 6 pages text, 3 figures. Submitted to Phys. Rev. Lett. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Sexual Size Dimorphism and Body Condition in the Australasian Gannet

Funding: The research was financially supported by the Holsworth Wildlife Research Endowment. Acknowledgments We thank the Victorian Marine Science Consortium, Sea All Dolphin Swim, Parks Victoria, and the Point Danger Management Committee for logistical support. We are grateful for the assistance of the many field volunteers involved in the study.Peer reviewedPublisher PD

Production of phi mesons at mid-rapidity in sqrt(s_NN) = 200 GeV Au+Au collisions at RHIC

We present the first results of meson production in the K^+K^- decay channel from Au+Au collisions at sqrt(s_NN) = 200 GeV as measured at mid-rapidity by the PHENIX detector at RHIC. Precision resonance centroid and width values are extracted as a function of collision centrality. No significant variation from the PDG accepted values is observed. The transverse mass spectra are fitted with a linear exponential function for which the derived inverse slope parameter is seen to be constant as a function of centrality. These data are also fitted by a hydrodynamic model with the result that the freeze-out temperature and the expansion velocity values are consistent with the values previously derived from fitting single hadron inclusive data. As a function of transverse momentum the collisions scaled peripheral.to.central yield ratio RCP for the is comparable to that of pions rather than that of protons. This result lends support to theoretical models which distinguish between baryons and mesons instead of particle mass for explaining the anomalous proton yield.Comment: 326 authors, 24 pages text, 23 figures, 6 tables, RevTeX 4. To be submitted to Physical Review C as a regular article. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Measurement of Transverse Single-Spin Asymmetries for Mid-rapidity Production of Neutral Pions and Charged Hadrons in Polarized p+p Collisions at sqrt(s) = 200 GeV

The transverse single-spin asymmetries of neutral pions and non-identified charged hadrons have been measured at mid-rapidity in polarized proton-proton collisions at sqrt(s) = 200 GeV. The data cover a transverse momentum (p_T) range 0.5-5.0 GeV/c for charged hadrons and 1.0-5.0 GeV/c for neutral pions, at a Feynman-x (x_F) value of approximately zero. The asymmetries seen in this previously unexplored kinematic region are consistent with zero within statistical errors of a few percent. In addition, the inclusive charged hadron cross section at mid-rapidity from 0.5 < p_T < 7.0 GeV/c is presented and compared to NLO pQCD calculations. Successful description of the unpolarized cross section above ~2 GeV/c using NLO pQCD suggests that pQCD is applicable in the interpretation of the asymmetry results in the relevant kinematic range.Comment: 331 authors, 6 pages text, 2 figures, 3 tables. Submitted to Phys. Rev. Lett. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Self-oligomerization regulates stability of survival motor neuron protein isoforms by sequestering an SCF^Slmb degron

Spinal muscular atrophy (SMA) is caused by homozygous mutations in human SMN1. Expression of a duplicate gene (SMN2) primarily results in skipping of exon 7 and production of an unstable protein isoform, SMNΔ7. Although SMN2 exon skipping is the principal contributor to SMA severity, mechanisms governing stability of survival motor neuron (SMN) isoforms are poorly understood. We used a Drosophila model system and label-free proteomics to identify the SCFSlmb ubiquitin E3 ligase complex as a novel SMN binding partner. SCFSlmb interacts with a phosphor degron embedded within the human and fruitfly SMN YG-box oligomerization domains. Substitution of a conserved serine (S270A) interferes with SCFSlmb binding and stabilizes SMNΔ7. SMA-causing missense mutations that block multimerization of full-length SMN are also stabilized in the degron mutant background. Overexpression of SMNΔ7S270A, but not wild-type (WT) SMNΔ7, provides a protective effect in SMA model mice and human motor neuron cell culture systems. Our findings support a model wherein the degron is exposed when SMN is monomeric and sequestered when SMN forms higher-order multimers

Isgur-Wise function in a QCD inspired potential model with confinement as parent in the Variationally Improved Perturbation Theory (VIPT)

We have recently reported the calculation of slope and curvature of Isgur-Wise function based on Variationally Improved Perturbation Theory (VIPT) in a QCD inspired potential model. In that work, Coulombic potential was taken as the parent while the linear one as the perturbation.In this work, we choose the linear one as the parent with Coulombic one as the perturbation and see the consequences. Keywords: VIPT,Isgur-Wise function, charge radii and convexity pa- rameter