All-electrical generation of spin-polarized currents in quantum spin Hall insulators

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The focusing effect of electron flow and negative refraction in three-dimensional topological insulators

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Comparable fitness and transmissibility between oseltamivir-resistant pandemic 2009 and seasonal H1N1 influenza viruses with the H275Y neuraminidase mutation

Limited antiviral compounds are available for the control of influenza, and the emergence of resistant variants would further narrow the options for defense. The H275Y neuraminidase (NA) mutation, which confers resistance to oseltamivir carboxylate, has been identified among the seasonal H1N1 and 2009 pandemic influenza viruses; however, those H275Y resistant variants demonstrated distinct epidemiological outcomes in humans. Specifically, dominance of the H275Y variant over the oseltamivir-sensitive viruses was only reported for a seasonal H1N1 variant during 2008-2009. Here, we systematically analyze the effect of the H275Y NA mutation on viral fitness and transmissibility of A(H1N1)pdm09 and seasonal H1N1 influenza viruses. The NA genes from A(H1N1)pdm09 A/California/04/09 (CA04), seasonal H1N1 A/New Caledonia/20/1999 (NewCal), and A/Brisbane/59/2007 (Brisbane) were individually introduced into the genetic background of CA04. The H275Y mutation led to reduced NA enzyme activity, an increased K(m) for 3'-sialylactose or 6'-sialylactose, and decreased infectivity in mucin-secreting human airway epithelial cells compared to the oseltamivir-sensitive wild-type counterparts. Attenuated pathogenicity in both RG-CA04(NA-H275Y) and RG-CA04 x Brisbane(NA-H275Y) viruses was observed in ferrets compared to RG-CA04 virus, although the transmissibility was minimally affected. In parallel experiments using recombinant Brisbane viruses differing by hemagglutinin and NA, comparable direct contact and respiratory droplet transmissibilities were observed among RG-NewCal(HA,NA), RG-NewCal(HA,NA-H275Y), RG-Brisbane(HA,NA-H275Y), and RG-NewCal(HA) x Brisbane(NA-H275Y) viruses. Our results demonstrate that, despite the H275Y mutation leading to a minor reduction in viral fitness, the transmission potentials of three different antigenic strains carrying this mutation were comparable in the naive ferret model.published_or_final_versio

Comparable fitness and transmissibility between Oseltamivir-Resistant Pandemic 2009 and seasonal H1N1 Influenza Viruses with the H275Y Neuraminidase Mutation

Conference Theme: Translating Health Research into Policy and Practice for Health of the PopulationPoster Presentations - Emerging / Infectious Diseases: no. P65-Ab0010INTRODUCTION: Neuraminidase (NA) inhibitors are one of the limited options for the control of influenza. The H275Y NA mutation, which confers resistance to oseltamivir carboxylate, was initially considered to be of little clinical consequence due to limited detection of this mutation in field isolates prior to 2007-2008, when a globally spreading H275Y variant emerged. Oseltamivir-resistant A(H1N1)pdm09 viruses with the H275Y NA mutation has been reported since 2009 but have not replaced the …published_or_final_versio

Role of AMPK signaling in mediating the anticancer effects of silibinin in esophageal squamous cell carcinoma

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Influence of magnetic disorders on quantum anomalous Hall effect in magnetic topological insulator films beyond the two-dimensional limit

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Competitive Binding Between Id1 and E2F1 to Cdc20 Regulates E2F1 Degradation and Thymidylate Synthase Expression to Promote Esophageal Cancer Chemoresistance

Purpose: Chemoresistance is a major obstacle in cancer therapy. We found that fluorouracil (5-FU)-resistant esophageal squamous cell carcinoma cell lines, established through exposure to increasing concentrations of 5-FU, showed upregulation of Id1, IGF2, and E2F1. We hypothesized that these genes may play an important role in cancer chemoresistance. Experimental Design: In vitro and in vivo functional assays were performed to study the effects of Id1–E2F1–IGF2 signaling in chemoresistance. Quantitative real-time PCR, Western blotting, immunoprecipitation, chromatin immunoprecipitation, and dual-luciferase reporter assays were used to investigate the molecular mechanisms by which Id1 regulates E2F1 and by which E2F1 regulates IGF2. Clinical specimens, tumor tissue microarray, and Gene Expression Omnibus datasets were used to analyze the correlations between gene expressions and the relationships between expression profiles and patient survival outcomes. Results: Id1 conferred 5-FU chemoresistance through E2F1-dependent induction of thymidylate synthase expression in esophageal cancer cells and tumor xenografts. Mechanistically, Id1 protects E2F1 protein from degradation and increases its expression by binding competitively to Cdc20, whereas E2F1 mediates Id1-induced upregulation of IGF2 by binding directly to the IGF2 promoter and activating its transcription. The expression level of E2F1 was positively correlated with that of Id1 and IGF2 in human cancers. More importantly, concurrent high expression of Id1 and IGF2 was associated with unfavorable patient survival in multiple cancer types. Conclusions: Our findings define an intricate E2F1-dependent mechanism by which Id1 increases thymidylate synthase and IGF2 expressions to promote cancer chemoresistance. The Id1–E2F1–IGF2 regulatory axis has important implications for cancer prognosis and treatment. ©2015 AACR.postprin

Evidence of a structural quantum critical point in (CaxSr1-x)3Rh4Sn13 from a lattice dynamics study

Approaching a quantum critical point (QCP) has been an effective route to stabilize superconductivity. While the role of magnetic QCPs has been extensively discussed, similar exploration of a structural QCP is scarce due to the lack of suitable systems with a continuous structural transition that can be conveniently tuned to 0~K. Using inelastic X-ray scattering, we examine the phonon spectrum of the nonmagnetic quasi-skutterudite (Ca$_{x}$Sr$_{1-x}$)$_3$Rh$_4$Sn$_{13}$, which represents a precious system to explore the interplay between structural instabilities and superconductivity by tuning the Ca concentration $x$. We unambiguously detect the softening of phonon modes around the M point on cooling towards the structural transition. Intriguingly, at $x=0.85$, the soft mode energy squared at the M point extrapolates to zero at $(-5.7 \pm 7.7)$~K, providing the first compelling microscopic evidence of a structural QCP in (Ca$_{x}$Sr$_{1-x}$)$_3$Rh$_4$Sn$_{13}$. The enhanced phonon density-of-states at low energy provides the essential ingredient for realizing strong-coupling superconductivity near the structural QCP

Cancer cell-secreted IGF2 instigates fibroblasts and bone marrow-derived vascular progenitor cells to promote cancer progression

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Long-Lived Neutralino NLSPs

We investigate the collider signatures of heavy, long-lived, neutral particles that decay to charged particles plus missing energy. Specifically, we focus on the case of a neutralino NLSP decaying to Z and gravitino within the context of General Gauge Mediation. We show that a combination of searches using the inner detector and the muon spectrometer yields a wide range of potential early LHC discoveries for NLSP lifetimes ranging from 10^(-1)-10^5 mm. We further show that events from Z(l+l-) can be used for detailed kinematic reconstruction, leading to accurate determinations of the neutralino mass and lifetime. In particular, we examine the prospects for detailed event study at ATLAS using the ECAL (making use of its timing and pointing capabilities) together with the TRT, or using the muon spectrometer alone. Finally, we also demonstrate that there is a region in parameter space where the Tevatron could potentially discover new physics in the delayed Z(l+l-)+MET channel. While our discussion centers on gauge mediation, many of the results apply to any scenario with a long-lived neutral particle decaying to charged particles.Comment: 31 pages, 12 figure