Structurally confined influenza subunit vaccines in the prefusion conformation elicit a potent neutralizing antibody response

Effective vaccination against influenza viruses remains a significant global challenge. Despite ongoing efforts, continual antigenic changes in circulating viruses requires constant update of existing vaccine approaches. Furthermore, the majority of current licensed vaccines are derivatives of live virus and are inherently time consuming to produce and limit the potential response time to counter a new virus strain. However, the combined advances in subunit vaccine production and structural determination of critical neutralizing epitopes within influenza hemagglutinin (HA) provide the groundwork for the next generation of influenza vaccines which have the potential to overcome these limitations. In an effort to expand on these findings we have compared the effectiveness of both prefusion and postfusion forms of recombinant influenza hemagglutinin (rHA) as subunit vaccines. Using a novel stabilization tag to confine rHA in the prefusion conformation we demonstrated that while both HA conformations elicit anti-HA responses in mice, a neutralizing response (PRNT50 1:36000) is only observed for prefusion rHA. Using rHAs from a range of influenza subtypes and domain specific constructs together with a large panel of structurally defined antibodies we also examined the epitope specificity and cross-reactivity of the prefusion specific neutralizing response. Interestingly, a similar conformation dependence has been reported for respiratory syncytial virus1, 2, suggesting a universal strategy for the generation of potent subunit vaccines to target enveloped viruses. 1. Magro, M. et al. Neutralizing antibodies against the preactive form of respiratory syncytial virus fusion protein offer unique possibilities for clinical intervention. Proc Natl Acad Sci U S A 109, 3089-3094 (2012). 2. McLellan, J.S. et al. Structure-Based Design of a Fusion Glycoprotein Vaccine for Respiratory Syncytial Virus. Science 342, 592-598 (2013)

Absolute spin-valve effect with superconducting proximity structures

We investigate spin dependent transport in hybrid superconductor(S)--normal-metal(N)--ferromagnet(F) structures under conditions of proximity effect. We demonstrate the feasibility of the absolute spin-valve effect for a certain interval of voltages in a system consisting of two coupled tri-layer structures. Our results are also valid for non-collinear magnetic configurations of the ferromagnets.Comment: 1 TEX file, 2 Postscript files. Accepted for publication in Physical Review Letter

Water Dynamics in Shewanella oneidensis at Ambient and High Pressure using Quasi-Elastic Neutron Scattering

Quasielastic neutron scattering (QENS) is an ideal technique for studying water transport and relaxation dynamics at pico-to nanosecond timescales and at length scales relevant to cellular dimensions. Studies of high pressure dynamic effects in live organisms are needed to understand Earth's deep biosphere and biotechnology applications. Here we applied QENS to study water transport in Shewanella oneidensis at ambient (0.1 MPa) and high (200 MPa) pressure using H/D isotopic contrast experiments for normal and perdeuterated bacteria and buffer solutions to distinguish intracellular and transmembrane processes. The results indicate that intracellular water dynamics are comparable with bulk diffusion rates in aqueous fluids at ambient conditions but a significant reduction occurs in high pressure mobility. We interpret this as due to enhanced interactions with macromolecules in the nanoconfined environment. Overall diffusion rates across the cell envelope also occur at similar rates but unexpected narrowing of the QENS signal appears between momentum transfer values Q = 0.7-1.1 Å-1 corresponding to real space dimensions of 6-9 Å. The relaxation time increase can be explained by correlated dynamics of molecules passing through Aquaporin water transport complexes located within the inner or outer membrane structures

Sloan Digital Sky Survey Multicolor Observations of GRB010222

The discovery of an optical counterpart to GRB010222 (detected by BeppoSAX; Piro 2001) was announced 4.4 hrs after the burst by Henden (2001a). The Sloan Digital Sky Survey's 0.5m photometric telescope (PT) and 2.5m survey telescope were used to observe the afterglow of GRB010222 starting 4.8 hours after the GRB. The 0.5m PT observed the afterglow in five, 300 sec g' band exposures over the course of half an hour, measuring a temporal decay rate in this short period of F_nu \propto t^{-1.0+/-0.5}. The 2.5m camera imaged the counterpart nearly simultaneously in five filters (u' g' r' i' z'), with r' = 18.74+/-0.02 at 12:10 UT. These multicolor observations, corrected for reddening and the afterglow's temporal decay, are well fit by the power-law F_nu \propto nu^{-0.90+/-0.03} with the exception of the u' band UV flux which is 20% below this slope. We examine possible interpretations of this spectral shape, including source extinction in a star forming region.Comment: 8 pages, 4 figures, accepted for publication in ApJ. Two figures added, minor changes to text in this draft. Related material can be found at: http://sdss.fnal.gov:8000/grb

Energy gap in superconducting fullerides: optical and tunneling studies

Tunneling and optical transmission studies have been performed on superconducting samples of Rb3C60. At temperatures much below the superconducting transition temperature Tc the energy gap is 2 Delta=5.2 +- 0.2meV, corresponding to 2 Delta/kB Tc = 4.2. The low temperature density of states, and the temperature dependence of the optical conductivity resembles the BCS behavior, although there is an enhanced ``normal state" contribution. The results indicate that this fulleride material is an s-wave superconductor, but the superconductivity cannot be described in the weak coupling limit.Comment: RevTex file with four .EPS figures. Prints to four pages. Also available at http://buckminster.physics.sunysb.edu/papers/pubrece.htm

Patients with inflammatory bowel disease have higher abdominal adiposity and less skeletal mass than healthy controls

Background Abdominal fat type and distribution have been associated with complicated Crohn’s disease and adverse postoperative outcomes. Few studies have assessed the abdominal distribution of fat and lean stores in patients with inflammatory bowel disease (IBD) and compared this with healthy controls. This retrospective study aimed to compare the abdominal body composition in IBD patients who failed medical treatment and who underwent computed tomography (CT) imaging prior to gastrointestinal surgery with healthy controls. Associations between preoperative abdominal body composition and postoperative outcomes within a year of surgery were explored. Methods Abdominal body composition was evaluated in 22 presurgical patients with medically refractory IBD (18 with Crohn’s disease) and 22 healthy controls, using routinely acquired CT. Total fat, subcutaneous fat, visceral fat, and skeletal muscle cross-sectional area were measured. Results An independent disease effect was observed, explaining a fat deposition excess of 38 cm2 and a skeletal muscle deficit of 15 cm2 in IBD. Abdominal skeletal muscle correlated with visceral fat for the control (rho=0.51, P=0.015), but not for the IBD group (rho=-0.13, P=0.553). A positive correlation observed between subcutaneous fat with skeletal muscle in the controls (rho=0.47, P=0.026) was inverted in the IBD group (rho=-0.43, P=0.045). Preoperative abdominal body composition was not predictive of postoperative outcomes. Conclusions A higher degree of abdominal adiposity, a lower skeletal mass and a larger body size for the same anthropometry can be expected in IBD patients. Preoperative abdominal body composition is not associated with surgical outcomes. Keywords Inflammatory bowel disease, computed tomography, body compositio

Disentangling water, ion and polymer dynamics in an anion exchange membrane

Semipermeable polymeric anion exchange membranes are essential for separation, filtration and energy conversion technologies including reverse electrodialysis systems that produce energy from salinity gradients, fuel cells to generate electrical power from the electrochemical reaction between hydrogen and oxygen, and water electrolyser systems that provide H2 fuel. Anion exchange membrane fuel cells and anion exchange membrane water electrolysers rely on the membrane to transport OH− ions between the cathode and anode in a process that involves cooperative interactions with H2O molecules and polymer dynamics. Understanding and controlling the interactions between the relaxation and diffusional processes pose a main scientific and critical membrane design challenge. Here quasi-elastic neutron scattering is applied over a wide range of timescales (100–103 ps) to disentangle the water, polymer relaxation and OH− diffusional dynamics in commercially available anion exchange membranes (Fumatech FAD-55) designed for selective anion transport across different technology platforms, using the concept of serial decoupling of relaxation and diffusional processes to analyse the data. Preliminary data are also reported for a laboratory-prepared anion exchange membrane especially designed for fuel cell applications

Quantum Collective Creep: a Quasiclassical Langevin Equation Approach

The dynamics of an elastic medium driven through a random medium by a small applied force is investigated in the low-temperature limit where quantum fluctuations dominate. The motion proceeds via tunneling of segments of the manifold through barriers whose size grows with decreasing driving force $f$. In the limit of small drive, at zero-temperature the average velocity has the form $v\propto\exp[-{\rm const.}/\hbar^{\alpha} f^{\mu}]$. For strongly dissipative dynamics, there is a wide range of forces where the dissipation dominates and the velocity--force characteristics takes the form $v\propto\exp[-S(f)/\hbar]$, with $S(f)\propto 1/ f^{(d+2\zeta)/(2-\zeta)}$ the action for a typical tunneling event, the force dependence being determined by the roughness exponent $\zeta$ of the $d$-dimensional manifold. This result agrees with the one obtained via simple scaling considerations. Surprisingly, for asymptotically low forces or for the case when the massive dynamics is dominant, the resulting quantum creep law is {\it not} of the usual form with a rate proportional to $\exp[-S(f)/\hbar]$; rather we find $v\propto \exp\{-[S(f)/\hbar]^2\}$ corresponding to $\alpha=2$ and $\mu= 2(d+2\zeta-1)/(2-\zeta)$, with $\mu/2$ the naive scaling exponent for massive dynamics. Our analysis is based on the quasi-classical Langevin approximation with a noise obeying the quantum fluctuation--dissipation theorem. The many space and time scales involved in the dynamics are treated via a functional renormalization group analysis related to that used previously to treat the classical dynamics of such systems. Various potential difficulties with these approaches to the multi-scale dynamics -- both classical and quantum -- are raised and questions about the validity of the results are discussed.Comment: RevTeX, 30 pages, 8 figures inserte

Symbolic Computation via Program Transformation

Symbolic computation is an important approach in automated program analysis. Most state-of-the-art tools perform symbolic computation as interpreters and directly maintain symbolic data. In this paper, we show that it is feasible, and in fact practical, to use a compiler-based strategy instead. Using compiler tooling, we propose and implement a transformation which takes a standard program and outputs a program that performs semantically equivalent, but partially symbolic, computation. The transformed program maintains symbolic values internally and operates directly on them hence the program can be processed by a tool without support for symbolic manipulation. The main motivation for the transformation is in symbolic verification, but there are many other possible use-cases, including test generation and concolic testing. Moreover using the transformation simplifies tools, since the symbolic computation is handled by the program directly. We have implemented the transformation at the level of LLVM bitcode. The paper includes an experimental evaluation, based on an explicit-state software model checker as a verification backend