Effects of the Nearest-Neighbour Coulomb Interactions on the Ground State of the Periodic Anderson Model

The magnetic and non-magnetic ground states of the periodic Anderson model with Coulomb interaction between $f$-electrons on the nearest-neighbour(NN) sites are investigated using a variational method, which gives exact calculation of the expectation values in the limit of infinite dimensions. It is shown that for a critical value of NN Coulomb interactions the magnetic ground state of the periodic Anderson model in the Kondo regime is unstable. Factors in terms of the physical processes responsible for instability of the magnetic ground state are also discussed. Our study indicates the importance of the NN Coulomb interactions for correlated two band models.Comment: RevTeX, 6 pages, 5 figures, to appear in Phys. Rev.

A tapered multi-gap multi-aperture pseudospark-sourced electron gun based X-band slow wave oscillator

The experimental study of a tapered, multi-gap, multi-aperture pseudospark-sourced electron gun based X-band plasma assisted slow wave oscillator is presented. The designed electron gun is based on the pseudospark discharge concept and has been used to generate a high current density and high energy electron beam simultaneously. The distribution of apertures has been arranged such that the field penetration potency inside the backspace of the hollow-cathode is different while passing through the tapered gap region. This leads to non-concurrent ignition of the discharge through all the channels which is, in general, quite challenging in the case of multi-aperture plasma cathode electron gun geometries. Multiple and successive hollow cathode phases are reported from this electron gun geometry, which have been confirmed using simulations. This geometry also has led to the achievement of ∼71% fill factor inside the slow wave oscillator for an electron beam of energy of 20 keV and a beam current density in the range of 115-190 A/cm2 at a working argon gas pressure of 18 Pa. The oscillator has generated broadband microwave output in the frequency range of 10-11.7 GHz with a peak power of ∼10 kW for ∼50 ns

A novel AhR ligand, 2AI, protects the retina from environmental stress.

Various retinal degenerative diseases including dry and neovascular age-related macular degeneration (AMD), retinitis pigmentosa, and diabetic retinopathy are associated with the degeneration of the retinal pigmented epithelial (RPE) layer of the retina. This consequently results in the death of rod and cone photoreceptors that they support, structurally and functionally leading to legal or complete blindness. Therefore, developing therapeutic strategies to preserve cellular homeostasis in the RPE would be a favorable asset in the clinic. The aryl hydrocarbon receptor (AhR) is a conserved, environmental ligand-dependent, per ARNT-sim (PAS) domain containing bHLH transcription factor that mediates adaptive response to stress via its downstream transcriptional targets. Using in silico, in vitro and in vivo assays, we identified 2,2'-aminophenyl indole (2AI) as a potent synthetic ligand of AhR that protects RPE cells in vitro from lipid peroxidation cytotoxicity mediated by 4-hydroxynonenal (4HNE) as well as the retina in vivo from light-damage. Additionally, metabolic characterization of this molecule by LC-MS suggests that 2AI alters the lipid metabolism of RPE cells, enhancing the intracellular levels of palmitoleic acid. Finally, we show that, as a downstream effector of 2AI-mediated AhR activation, palmitoleic acid protects RPE cells from 4HNE-mediated stress, and light mediated retinal degeneration in mice

On wealth and the diversity of friendships: high social class people around the world have fewer international friends

Having international social ties carries many potential advantages, including access to novel ideas and greater commercial opportunities. Yet little is known about who forms more international friendships. Here, we propose social class plays a key role in determining people's internationalism. We conducted two studies to test whether social class is related positively to internationalism (the building social class hypothesis) or negatively to internationalism (the restricting social class hypothesis). In Study 1, we found that among individuals in the United States, social class was negatively related to percentage of friends on Facebook that are outside the United States. In Study 2, we extended these findings to the global level by analyzing country-level data on Facebook friends formed in 2011 (nearly 50 billion friendships) across 187 countries. We found that people from higher social class countries (as indexed by GDP per capita) had lower levels of internationalism—that is, they made more friendships domestically than abroad

Pharmacokinetic and safety profile of raltegravir and ribavirin, when dosed separately and together, in healthy volunteers

Results: No statistically significant differences in PK parameters were observed for raltegravir between phases 2 and 3. A statistically significant decrease in maximum plasma concentration (Cmax) and an increase in time to maximum plasma concentration (Tmax) were observed for ribavirin in phase 3 compared with phase 1 [GMR (95% confidence interval) 0.79 (0.62 –1.00) and 1.39 (1.08 –1.78), respectively], whereas no significant differences in other ribavirin PK parameters were observed between study phases. No clinically significant safety concerns were reported. Conclusions: The PK profile of ribavirin is altered when administered with raltegravir (reduced Cmax and increased Tmax), with no safety concerns identified. This is unlikely to be of clinical significance or have an impact on the antiviral effects of ribavirin in HIV-1- and HCV-co-infected subjects

Almost sure stability of the Euler-Maruyama method with random variable stepsize for stochastic differential equations

In this paper, the Euler–Maruyama (EM) method with random variable stepsize is studied to reproduce the almost sure stability of the true solutions of stochastic differential equations. Since the choice of the time step is based on the current state of the solution, the time variable is proved to be a stopping time. Then the semimartingale convergence theory is employed to obtain the almost sure stability of the random variable stepsize EM solution. To our best knowledge, this is the first paper to apply the random variable stepsize (with clear proof of the stopping time) to the analysis of the almost sure stability of the EM method

Mutational profiling of kinases in glioblastoma

Background: Glioblastoma is a highly malignant brain tumor for which no cure is available. To identify new therapeutic targets, we performed a mutation analysis of kinase genes in glioblastoma.Methods: Database mining and a literature search identified 76 kinases that have been found to be mutated at least twice in multiple cancer types before. Among those we selected 34 kinase genes for mutation analysis. We also included IDH1, IDH2, PTEN, TP53 and NRAS, genes that are known to be mutated at considerable frequencies in glioblastoma. In total, 174 exons of 39 genes in 113 glioblastoma samples from 109 patients and 16 high-grade glioma (HGG) cell lines were sequenced. Results: Our mutation analysis led to the identification of 148 non-synonymous somatic mutations, of which 25 have not been reported before in glioblastoma. Somatic mutations were found in TP53, PTEN, IDH1, PIK3CA, EGFR, BRAF, EPHA3, NRAS, TGFBR2, FLT3 and RPS6KC1. Mapping the mutated genes into known signaling pathways revealed that the large majority of them plays a central role in the PI3K-AKT pathway. Conclusions: The knowledge that at least 50% of glioblastoma tumors display mutational activation of the PI3K-AKT pathway should offer new opportunities for the rational development of therapeutic approaches for glioblastomas. However, due to the development of resistance mechanisms, kinase inhibition studies targeting the PI3K-AKT pathway for relapsing glioblastoma have mostly failed thus far. Other therapies should be investigated, targeting early events in gliomagenesis that involve both kinases and non-kinases

Transplantation of Adult Mouse iPS Cell-Derived Photoreceptor Precursors Restores Retinal Structure and Function in Degenerative Mice

This study was designed to determine whether adult mouse induced pluripotent stem cells (iPSCs), could be used to produce retinal precursors and subsequently photoreceptor cells for retinal transplantation to restore retinal function in degenerative hosts. iPSCs were generated using adult dsRed mouse dermal fibroblasts via retroviral induction of the transcription factors Oct4, Sox2, KLF4 and c-Myc. As with normal mouse ES cells, adult dsRed iPSCs expressed the pluripotency genes SSEA1, Oct4, Sox2, KLF4, c-Myc and Nanog. Following transplantation into the eye of immune-compromised retinal degenerative mice these cells proceeded to form teratomas containing tissue comprising all three germ layers. At 33 days post-differentiation a large proportion of the cells expressed the retinal progenitor cell marker Pax6 and went on to express the photoreceptor markers, CRX, recoverin, and rhodopsin. When tested using calcium imaging these cells were shown to exhibit characteristics of normal retinal physiology, responding to delivery of neurotransmitters. Following subretinal transplantation into degenerative hosts differentiated iPSCs took up residence in the retinal outer nuclear layer and gave rise to increased electro retinal function as determined by ERG and functional anatomy. As such, adult fibroblast-derived iPSCs provide a viable source for the production of retinal precursors to be used for transplantation and treatment of retinal degenerative disease