An Attenuated Zika Virus Encoding Non-Glycosylated Envelope (E) and Non-Structural Protein 1 (NS1) Confers Complete Protection against Lethal Challenge in a Mouse Model

Zika virus (ZIKV), a mosquito-transmitted flavivirus, emerged in the last decade causing serious human diseases, including congenital microcephaly in newborns and Guillain-Barré syndrome in adults. Although many vaccine platforms are at various stages of development, no licensed vaccines are currently available. Previously, we described a mutant MR766 ZIKV (m2MR) bearing an E protein mutation (N154A) that prevented its glycosylation, resulting in attenuation and defective neuroinvasion. To further attenuate m2MR for its potential use as a live viral vaccine, we incorporated additional mutations into m2MR by substituting the asparagine residues in the glycosylation sites (N130 and N207) of NS1 with alanine residues. Examination of pathogenic properties revealed that the virus (m5MR) carrying mutations in E (N154A) and NS1 (N130A and N207A) was fully attenuated with no disease signs in infected mice, inducing high levels of humoral and cell-mediated immune responses, and protecting mice from subsequent lethal virus challenge. Furthermore, passive transfer of sera from m5MR-infected mice into naïve animals resulted in complete protection from lethal challenge. The immune sera from m5MR-infected animals neutralized both African and Asian lineage viruses equally well, suggesting that m5MR virus could be developed as a potentially broad live virus vaccine candidate

An Attenuated Zika Virus Encoding Non-Glycosylated Envelope (E) and Non-Structural Protein 1 (NS1) Confers Complete Protection against Lethal Challenge in a Mouse Model

Zika virus (ZIKV), a mosquito-transmitted flavivirus, emerged in the last decade causing serious human diseases, including congenital microcephaly in newborns and Guillain-Barré syndrome in adults. Although many vaccine platforms are at various stages of development, no licensed vaccines are currently available. Previously, we described a mutant MR766 ZIKV (m2MR) bearing an E protein mutation (N154A) that prevented its glycosylation, resulting in attenuation and defective neuroinvasion. To further attenuate m2MR for its potential use as a live viral vaccine, we incorporated additional mutations into m2MR by substituting the asparagine residues in the glycosylation sites (N130 and N207) of NS1 with alanine residues. Examination of pathogenic properties revealed that the virus (m5MR) carrying mutations in E (N154A) and NS1 (N130A and N207A) was fully attenuated with no disease signs in infected mice, inducing high levels of humoral and cell-mediated immune responses, and protecting mice from subsequent lethal virus challenge. Furthermore, passive transfer of sera from m5MR-infected mice into naïve animals resulted in complete protection from lethal challenge. The immune sera from m5MR-infected animals neutralized both African and Asian lineage viruses equally well, suggesting that m5MR virus could be developed as a potentially broad live virus vaccine candidate

Quantum Monte Carlo Evidence for d-wave Pairing in the 2D Hubbard Model at a van Hove Singularity

We implement a Quantum Monte Carlo calculation for a repulsive Hubbard model with nearest and next-nearest neighbor hopping interactions on clusters up to 12x12. A parameter region where the Fermi level lies close to the van Hove singularity at the Saddle Points in the bulk band structure is investigated. A pairing tendency in the $d_{x^2-y^2}$ symmetry channel, but no other channel, is found. Estimates of the effective pairing interaction show that it is close to the value required for a 40 K superconductor. Finite-size scaling compares with the attractive Hubbard model.Comment: 11 pages, REVTex, 4 figures, postscrip

Instability of Anisotropic Fermi Surfaces in Two Dimensions

The effect of strong anisotropy on the Fermi line of a system of correlated electrons is studied in two space dimensions, using renormalization group techniques. Inflection points change the scaling exponents of the couplings, enhancing the instabilities of the system. They increase the critical dimension for non Fermi liquid behavior, from 1 to 3/2. Assuming that, in the absence of nesting, the dominant instability is towards a superconducting ground state, simple rules to discern between d-wave and extended s-wave symmetry of the order parameter are given.Comment: 5 pages, revte

Multilevel information storage using magnetoelastic layer stacks

The use of voltages to control magnetisation via the inverse magnetostriction effect in piezoelectric/ferromagnet heterostructures holds promise for ultra-low energy information storage technologies. Epitaxial galfenol, an alloy of iron and gallium, has been shown to be a highly suitable material for such devices because it possesses biaxial anisotropy and large magnetostriction. Here we experimentally investigate the properties of galfenol/spacer/galfenol structures in which the compositions of the galfenol layers are varied in order to produce different strengths of the magnetic anisotropy and magnetostriction constants. Based upon these layers, we propose and simulate the operation of an information storage device that can operate as an energy efficient multilevel memory cell

Density of States of Disordered Two-Dimensional Crystals with Half-Filled Band

A diagrammatic method is applied to study the effects of commensurability in two-dimensional disordered crystalline metals by using the particle-hole symmetry with respect to the nesting vector P_0={\pm{\pi}/a, {\pi}/a} for a half-filled electronic band. The density of electronic states (DoS) is shown to have nontrivial quantum corrections due to both nesting and elastic impurity scattering processes, as a result the van Hove singularity is preserved in the center of the band. However, the energy dependence of the DoS is strongly changed. A small offset from the middle of the band gives rise to disappearence of quantum corrections to the DoS .Comment: to be published in Physical Review Letter

Quantifying interictal intracranial EEG to predict focal epilepsy

Intracranial EEG (IEEG) is used for 2 main purposes, to determine: (1) if epileptic networks are amenable to focal treatment and (2) where to intervene. Currently these questions are answered qualitatively and sometimes differently across centers. There is a need for objective, standardized methods to guide surgical decision making and to enable large scale data analysis across centers and prospective clinical trials. We analyzed interictal data from 101 patients with drug resistant epilepsy who underwent presurgical evaluation with IEEG. We chose interictal data because of its potential to reduce the morbidity and cost associated with ictal recording. 65 patients had unifocal seizure onset on IEEG, and 36 were non-focal or multi-focal. We quantified the spatial dispersion of implanted electrodes and interictal IEEG abnormalities for each patient. We compared these measures against the 5 Sense Score (5SS), a pre-implant estimate of the likelihood of focal seizure onset, and assessed their ability to predict the clinicians choice of therapeutic intervention and the patient outcome. The spatial dispersion of IEEG electrodes predicted network focality with precision similar to the 5SS (AUC = 0.67), indicating that electrode placement accurately reflected pre-implant information. A cross-validated model combining the 5SS and the spatial dispersion of interictal IEEG abnormalities significantly improved this prediction (AUC = 0.79; p<0.05). The combined model predicted ultimate treatment strategy (surgery vs. device) with an AUC of 0.81 and post-surgical outcome at 2 years with an AUC of 0.70. The 5SS, interictal IEEG, and electrode placement were not correlated and provided complementary information. Quantitative, interictal IEEG significantly improved upon pre-implant estimates of network focality and predicted treatment with precision approaching that of clinical experts.Comment: 25 pages, 4 Figures, 1 tabl

Effects of proximity to an electronic topological transition on normal state transport properties of the high-Tc superconductors

Within the time dependent Ginzburg-Landau theory, the effects of the superconducting fluctuations on the transport properties above the critical temperature are characterized by a non-zero imaginary part of the relaxation rate gamma of the order parameter. Here, we evaluate Im gamma for an anisotropic dispersion relation typical of the high-Tc cuprate superconductors (HTS), characterized by a proximity to an electronic topological transition (ETT). We find that Im gamma abruptly changes sign at the ETT as a function of doping, in agreement with the universal behavior of the HTS. We also find that an increase of the in-plane anisotropy, as is given by a non-zero value of the next-nearest to nearest hopping ratio r=t'/t, increases the value of | Im gamma | close to the ETT, as well as its singular behavior at low temperature, therefore enhancing the effect of superconducting fluctuations. Such a result is in qualitative agreement with the available data for the excess Hall conductivity for several cuprates and cuprate superlattices.Comment: to appear in Phys. Rev.

Effects of an electronic topological transition for anisotropic low-dimensional superconductors

We study the superconducting properties of a two-dimensional superconductor in the proximity to an electronic topological transition (ETT). In contrast to the 3D case, we find that the superconducting gap at T=0, the critical temperature Tc, and the impurity scattering rate are characterized by a nonmonotonic behavior, with maxima occurring close to the ETT. We derive analytical expressions for the value of such maxima both in the s-wave and in the d-wave case. Such expressions are in good qualitative agreement with the phenomenological trend recently observed for Tc^max as a function of the hopping ratio t'/t across several cuprate compounds. We further analyze the effect of an ETT on the Ginzburg-Landau stiffness eta. Instead of vanishing at the ETT, as could be expected, thus giving rise to an increase of the fluctuation effects, in the case of momentum-independent electron-electron interaction, we find eta different from 0, as a result of an integration over the whole Fermi surface.Comment: to be published in Phys. Rev.

Interaction of convective organisation with monsoon precipitation, atmosphere, surface and sea: the 2016 INCOMPASS field campaign in India

The INCOMPASS field campaign combines airborne and ground measurements of the 2016 Indian monsoon, towards the ultimate goal of better predicting monsoon rainfall. The monsoon supplies the majority of water in South Asia, but forecasting from days to the season ahead is limited by large, rapidly developing errors in model parametrizations. The lack of detailed observations prevents thorough understanding of the monsoon circulation and its interaction with the land surface: a process governed by boundary‐layer and convective‐cloud dynamics. INCOMPASS used the UK Facility for Airborne Atmospheric Measurements (FAAM) BAe‐146 aircraft for the first project of this scale in India, to accrue almost 100 h of observations in June and July 2016. Flights from Lucknow in the northern plains sampled the dramatic contrast in surface and boundary‐layer structures between dry desert air in the west and the humid environment over the northern Bay of Bengal. These flights were repeated in pre‐monsoon and monsoon conditions. Flights from a second base at Bengaluru in southern India measured atmospheric contrasts from the Arabian Sea, over the Western Ghats mountains, to the rain shadow of southeast India and the south Bay of Bengal. Flight planning was aided by forecasts from bespoke 4 km convection‐permitting limited‐area models at the Met Office and India's NCMRWF. On the ground, INCOMPASS installed eddy‐covariance flux towers on a range of surface types, to provide detailed measurements of surface fluxes and their modulation by diurnal and seasonal cycles. These data will be used to better quantify the impacts of the atmosphere on the land surface, and vice versa. INCOMPASS also installed ground instrumentation supersites at Kanpur and Bhubaneswar. Here we motivate and describe the INCOMPASS field campaign. We use examples from two flights to illustrate contrasts in atmospheric structure, in particular the retreating mid‐level dry intrusion during the monsoon onset