Incorporation of GM-CSF or CD40L Enhances the Immunogenicity of Hantaan Virus-Like Particles

A safe and effective Hantaan virus (HTNV) vaccine is highly desirable because HTNV causes an acute and often fatal disease (hemorrhagic fever with renal syndrome, HFRS). Since the immunity of the inactivated vaccine is weak and the safety is poor, HTNV virus-like particles (VLPs) offer an attractive and safe alternative. These particles lack the viral genome but are perceived by the immune system as virus particles. We hypothesized that adding immunostimulatory signals to VLPs would enhance their efficacy. To accomplish this enhancement, we generated chimeric HTNV VLPs containing glycosylphosphatidylinositol (GPI)-anchored granulocyte macrophage colony-stimulating factor (GM-CSF) or CD40 ligand (CD40L) and investigated their biological activity in vitro. The immunization of mice with chimeric HTNV VLPs containing GM-CSF or CD40L induced stronger humoral immune responses and cellular immune responses compared to the HTNV VLPs and Chinese commercial inactivated hantavirus vaccine. Chimeric HTNV VLPs containing GM-CSF or CD40L also protected mice from an HTNV challenge. Altogether, our results suggest that anchoring immunostimulatory molecules into HTNV VLPs can be a potential approach for the control and prevention of HFRS

Electronic properties of CVD graphene: The role of grain boundaries, atmospheric doping, and encapsulation by ALD

Grain boundaries and unintentional doping can have profound effects on graphene-based devices. Here we study these in detail for CVD grown poly-crystalline monolayer graphene with two significantly different grain size distributions centered around 10–25 mm and 100–400 mm. Although the two types of graphene are processed under identical conditions after growth, they show distinct transport properties in field effect transistor devices. While all asfabricated samples showed similar p-type doping, the smaller grain size type graphene with larger number of grain boundaries exhibit lower average mobility. In order to separate out the effects of grain boundaries and doping from ambient exposure on the transport properties, the devices were encapsulated with Al2O3 by atomic layer deposition. The encapsulation of large grain samples thereby showed drastic improvements in the performance with negligible doping while the small grain samples are largely intolerant to this process. We discuss the implications of our data for the integrated manufacturing of graphene-based device platforms.We acknowledge funding from EPSRC (grant EP/K016636/1, GRAPHTED). Z.A.V.V. acknowledges funding from ESPRC grant EP/L016087/1. J.A.A.-W. acknowledges a Research Fellowship from Churchill College, Cambridge.This is the final version of the article. It first appeared from Wiley at http://dx.doi.org/10.1002/pssb.201600255

Cover to Volume 3

The fibroblast mitogen platelet-derived growth factor -BB (PDGF-BB) induces a transient expression of the orphan nuclear receptor NR4A1 (also named Nur77, TR3 or NGFIB). The aim of the present study was to investigate the pathways through which NR4A1 is induced by PDGF-BB and its functional role. We demonstrate that in PDGF-BB stimulated NIH3T3 cells, the MEK1/2 inhibitor CI-1040 strongly represses NR4A1 expression, whereas Erk5 downregulation delays the expression, but does not block it. Moreover, we report that treatment with the NF-κB inhibitor BAY11-7082 suppresses NR4A1 mRNA and protein expression. The majority of NR4A1 in NIH3T3 was found to be localized in the cytoplasm and only a fraction was translocated to the nucleus after continued PDGF-BB treatment. Silencing NR4A1 slightly increased the proliferation rate of NIH3T3 cells; however, it did not affect the chemotactic or survival abilities conferred by PDGF-BB. Moreover, overexpression of NR4A1 promoted anchorage-independent growth of NIH3T3 cells and the glioblastoma cell lines U-105MG and U-251MG. Thus, whereas NR4A1, induced by PDGF-BB, suppresses cell growth on a solid surface, it increases anchorage-independent growth

Asymmetric Inelastic Inert Doublet Dark Matter from Triplet Scalar Leptogenesis

The nature of dark matter (DM) particles and the mechanism that provides their measured relic abundance are currently unknown. In this paper we investigate inert scalar and vector like fermion doublet DM candidates with a charge asymmetry in the dark sector, which is generated by the same mechanism that provides the baryon asymmetry, namely baryogenesis-via-leptogenesis induced by decays of scalar triplets. At the same time the model gives rise to neutrino masses in the ballpark of oscillation experiments via type II seesaw. We discuss possible sources of depletion of asymmetry in the DM and visible sectors and solve the relevant Boltzmann equations for quasi-equilibrium decay of triplet scalars. A Monte-Carlo-Markov-Chain analysis is performed for the whole parameter space. The survival of the asymmetry in the dark sector leads to inelastic scattering off nuclei. We then apply bayesian statistic to infer the model parameters favoured by the current experimental data, in particular the DAMA annual modulation and Xenon100 exclusion limit. The latter strongly disfavours asymmetric scalar doublet DM of mass \mathcal{O}(\TeV) as required by DM-$\bar{\rm DM}$ oscillations, while an asymmetric vector like fermion doublet DM with mass around 100 GeV is a good candidate for DAMA annual modulation yet satisfying the constraints from Xenon100 data.Comment: 35 pages and 15 figures, references adde

Improved Constraints on Sterile Neutrino Mixing from Disappearance Searches in the MINOS, MINOS+, Daya Bay, and Bugey-3 Experiments.

Searches for electron antineutrino, muon neutrino, and muon antineutrino disappearance driven by sterile neutrino mixing have been carried out by the Daya Bay and MINOS+ collaborations. This Letter presents the combined results of these searches, along with exclusion results from the Bugey-3 reactor experiment, framed in a minimally extended four-neutrino scenario. Significantly improved constraints on the θ_{μe} mixing angle are derived that constitute the most constraining limits to date over five orders of magnitude in the mass-squared splitting Δm_{41}^{2}, excluding the 90% C.L. sterile-neutrino parameter space allowed by the LSND and MiniBooNE observations at 90% CL_{s} for Δm_{41}^{2}<13  eV^{2}. Furthermore, the LSND and MiniBooNE 99% C.L. allowed regions are excluded at 99% CL_{s} for Δm_{41}^{2}<1.6 eV^{2}