The type of adjuvant in whole inactivated influenza a virus vaccines impacts vaccine-associated enhanced respiratory disease

Influenza A virus (IAV) causes a disease burden in the swine industry in the US and is a challenge to prevent due to substantial genetic and antigenic diversity of IAV that circulate in pig populations. Whole inactivated virus (WIV) vaccines formulated with oil-in-water (OW) adjuvant are commonly used in swine. However, WIV-OW are associated with vaccine-associated enhanced respiratory disease (VAERD) when the hemagglutinin and neuraminidase of the vaccine strain are mismatched with the challenge virus. Here, we assessed if different types of adjuvant in WIV vaccine formulations impacted VAERD outcome. WIV vaccines with a swine δ1-H1N2 were formulated with different commercial adjuvants: OW1, OW2, nano-emulsion squalene-based (NE) and gel polymer (GP). Pigs were vaccinated twice by the intramuscular route, 3 weeks apart, then challenged with an H1N1pdm09 three weeks post-boost and necropsied at 5 days post infection. All WIV vaccines elicited antibodies detected using the hemagglutination inhibition (HI) assay against the homologous vaccine virus, but not against the heterologous challenge virus; in contrast, all vaccinated groups had cross-reactive IgG antibody and IFN-γ responses against H1N1pdm09, with a higher magnitude observed in OW groups. Both OW groups demonstrated robust homologous HI titers and cross-reactivity against heterologous H1 viruses in the same genetic lineage. However, both OW groups had severe immunopathology consistent with VAERD after challenge when compared to NE, GP, and non-vaccinated challenge controls. None of the WIV formulations protected pigs from heterologous virus replication in the lungs or nasal cavity. Thus, although the type of adjuvant in the WIV formulation played a significant role in the magnitude of immune response to homologous and antigenically similar H1, none tested here increased the breadth of protection against the antigenically-distinct challenge virus, and some impacted immunopathology after challenge

Screening nuclear field fluctuations in quantum dots for indistinguishable photon generation

A semiconductor quantum dot can generate highly coherent and indistinguishable single photons. However, intrinsic semiconductor dephasing mechanisms can reduce the visibility of two-photon interference. For an electron in a quantum dot, a fundamental dephasing process is the hyperfine interaction with the nuclear spin bath. Here we directly probe the consequence of the fluctuating nuclear spins on the elastic and inelastic scattered photon spectra from a resident electron in a single dot. We find the nuclear spin fluctuations lead to detuned Raman scattered photons which are distinguishable from both the elastic and incoherent components of the resonance fluorescence. This significantly reduces two-photon interference visibility. However, we demonstrate successful screening of the nuclear spin noise which enables the generation of coherent single photons that exhibit high visibility two-photon interference.Comment: 5 pages, 4 figures + Supplementary Informatio

Learning Quantum Systems

Quantum technologies hold the promise to revolutionise our society with ground-breaking applications in secure communication, high-performance computing and ultra-precise sensing. One of the main features in scaling up quantum technologies is that the complexity of quantum systems scales exponentially with their size. This poses severe challenges in the efficient calibration, benchmarking and validation of quantum states and their dynamical control. While the complete simulation of large-scale quantum systems may only be possible with a quantum computer, classical characterisation and optimisation methods (supported by cutting edge numerical techniques) can still play an important role. Here, we review classical approaches to learning quantum systems, their correlation properties, their dynamics and their interaction with the environment. We discuss theoretical proposals and successful implementations in different physical platforms such as spin qubits, trapped ions, photonic and atomic systems, and superconducting circuits. This review provides a brief background for key concepts recurring across many of these approaches, such as the Bayesian formalism or Neural Networks, and outlines open questions

Generic flow profiles induced by a beating cilium

We describe a multipole expansion for the low Reynolds number fluid flows generated by a localized source embedded in a plane with a no-slip boundary condition. It contains 3 independent terms that fall quadratically with the distance and 6 terms that fall with the third power. Within this framework we discuss the flows induced by a beating cilium described in different ways: a small particle circling on an elliptical trajectory, a thin rod and a general ciliary beating pattern. We identify the flow modes present based on the symmetry properties of the ciliary beat.Comment: 12 pages, 6 figures, to appear in EPJ

Fluid transport at low Reynolds number with magnetically actuated artificial cilia

By numerical modeling we investigate fluid transport in low-Reynolds-number flow achieved with a special elastic filament or artifical cilium attached to a planar surface. The filament is made of superparamagnetic particles linked together by DNA double strands. An external magnetic field induces dipolar interactions between the beads of the filament which provides a convenient way of actuating the cilium in a well-controlled manner. The filament has recently been used to successfully construct the first artificial micro-swimmer [R. Dreyfus at al., Nature 437, 862 (2005)]. In our numerical study we introduce a measure, which we call pumping performance, to quantify the fluid transport induced by the magnetically actuated cilium and identify an optimum stroke pattern of the filament. It consists of a slow transport stroke and a fast recovery stroke. Our detailed parameter study also reveals that for sufficiently large magnetic fields the artificial cilium is mainly governed by the Mason number that compares frictional to magnetic forces. Initial studies on multi-cilia systems show that the pumping performance is very sensitive to the imposed phase lag between neighboring cilia, i.e., to the details of the initiated metachronal wave.Comment: 12 pages, 10 figures. To appear in EPJE, available online at http://dx.doi.org/10.1140/epje/i2008-10388-

Periodic and Quasiperiodic Motion of an Elongated Microswimmer in Poiseuille Flow

We study the dynamics of a prolate spheroidal microswimmer in Poiseuille flow for different flow geometries. When moving between two parallel plates or in a cylindrical microchannel, the swimmer performs either periodic swinging or periodic tumbling motion. Although the trajectories of spherical and elongated swimmers are qualitatively similar, the swinging and tumbling frequency strongly depends on the aspect ratio of the swimmer. In channels with reduced symmetry the swimmers perform quasiperiodic motion which we demonstrate explicitely for swimming in a channel with elliptical cross section

Substitutions near the hemagglutinin receptor-binding site determine the antigenic evolution of influenza A H3N2 viruses in U.S. swine

Swine influenza A virus is an endemic and economically important pathogen in pigs, with the potential to infect other host species. The hemagglutinin (HA) protein is the primary target of protective immune responses and the major component in swine influenza A vaccines. However, as a result of antigenic drift, vaccine strains must be regularly updated to reflect currently circulating strains. Characterizing the cross-reactivity between strains in pigs and seasonal influenza virus strains in humans is also important in assessing the relative risk of interspecies transmission of viruses from one host population to the other. Hemagglutination inhibition (HI) assay data for swine and human H3N2 viruses were used with antigenic cartography to quantify the antigenic differences among H3N2 viruses isolated from pigs in the United States from 1998 to 2013 and the relative cross-reactivity between these viruses and current human seasonal influenza A virus strains. Two primary antigenic clusters were found circulating in the pig population, but with enough diversity within and between the clusters to suggest updates in vaccine strains are needed. We identified single amino acid substitutions that are likely responsible for antigenic differences between the two primary antigenic clusters and between each antigenic cluster and outliers. The antigenic distance between current seasonal influenza virus H3 strains in humans and those endemic in swine suggests that population immunity may not prevent the introduction of human viruses into pigs, and possibly vice versa, reinforcing the need to monitor and prepare for potential incursions

Modern optical astronomy: technology and impact of interferometry

The present `state of the art' and the path to future progress in high spatial resolution imaging interferometry is reviewed. The review begins with a treatment of the fundamentals of stellar optical interferometry, the origin, properties, optical effects of turbulence in the Earth's atmosphere, the passive methods that are applied on a single telescope to overcome atmospheric image degradation such as speckle interferometry, and various other techniques. These topics include differential speckle interferometry, speckle spectroscopy and polarimetry, phase diversity, wavefront shearing interferometry, phase-closure methods, dark speckle imaging, as well as the limitations imposed by the detectors on the performance of speckle imaging. A brief account is given of the technological innovation of adaptive-optics (AO) to compensate such atmospheric effects on the image in real time. A major advancement involves the transition from single-aperture to the dilute-aperture interferometry using multiple telescopes. Therefore, the review deals with recent developments involving ground-based, and space-based optical arrays. Emphasis is placed on the problems specific to delay-lines, beam recombination, polarization, dispersion, fringe-tracking, bootstrapping, coherencing and cophasing, and recovery of the visibility functions. The role of AO in enhancing visibilities is also discussed. The applications of interferometry, such as imaging, astrometry, and nulling are described. The mathematical intricacies of the various `post-detection' image-processing techniques are examined critically. The review concludes with a discussion of the astrophysical importance and the perspectives of interferometry.Comment: 65 pages LaTeX file including 23 figures. Reviews of Modern Physics, 2002, to appear in April issu

High-resolution imaging of dust shells using Keck aperture masking and the IOTA Interferometer

We present first results of an experiment to combine data from Keck aperture masking and the Infrared-Optical Telescope Array (IOTA) to image the circumstellar environments of evolved stars with ~20 milliarcsecond resolution. The unique combination of excellent Fourier coverage at short baselines and high-quality long-baseline fringe data allows us to determine the location and clumpiness of the inner-most hot dust in the envelopes, and to measure the diameters of the underlying stars themselves. We find evidence for large-scale inhomogeneities in some dust shells and also significant deviations from uniform brightness for the photospheres of the most evolved M-stars. Deviations from spherically-symmetric mass loss in the red supergiant NML Cyg could be related to recent evidence for dynamically-important magnetic fields and/or stellar rotation. We point out that dust shell asymmetries, like those observed here, can qualitatively explain the difficulty recent workers have had in simultaneously fitting the broad-band spectral energy distributions and high-resolution spatial information, without invoking unusual dust properties or multiple distinct shells (from hypothetical ``superwinds''). This paper is the first to combine optical interferometry data from multiple facilities for imaging, and we discuss the challenges and potential for the future of this method, given current calibration and software limitations.Comment: To appear in ApJ (61 pages: 4 tables, 23 figures). Image resolution degrade