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

Overcoming phonon-induced dephasing for indistinguishable photon sources

Reliable single photon sources constitute the basis of schemes for quantum communication and measurement based quantum computing. Solid state single photon sources based on quantum dots are convenient and versatile but the electronic transitions that generate the photons are subject to interactions with lattice vibrations. Using a microscopic model of electron-phonon interactions and a quantum master equation, we here examine phonon-induced decoherence and assess its impact on the rate of production, and indistinguishability, of single photons emitted from an optically driven quantum dot system. We find that, above a certain threshold of desired indistinguishability, it is possible to mitigate the deleterious effects of phonons by exploiting a three-level Raman process for photon production

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

Role of Motility and the \u3cem\u3eflhDC\u3c/em\u3e Operon in \u3cem\u3eEscherichia coli\u3c/em\u3e MG1655 Colonization of the Mouse Intestine

Previously, we reported that the mouse intestine selected mutants of Escherichia coli MG1655 that have improved colonizing ability (M. P. Leatham et al., Infect. Immun. 73:8039-8049, 2005). These mutants grew 10 to 20% faster than their parent in mouse cecal mucus in vitro and 15 to 30% faster on several sugars found in the mouse intestine. The mutants were nonmotile and had deletions of various lengths beginning immediately downstream of an IS1 element located within the regulatory region of the flhDC operon, which encodes the master regulator of flagellum biosynthesis, FlhD4C2. Here we show that during intestinal colonization by wild-type E. coli strain MG1655, 45 to 50% of the cells became nonmotile by day 3 after feeding of the strain to mice and between 80 and 90% of the cells were nonmotile by day 15 after feeding. Ten nonmotile mutants isolated from mice were sequenced, and all were found to have flhDC deletions of various lengths. Despite this strong selection, 10 to 20% of the E. coli MG1655 cells remained motile over a 15-day period, suggesting that there is an as-yet-undefined intestinal niche in which motility is an advantage. The deletions appear to be selected in the intestine for two reasons. First, genes unrelated to motility that are normally either directly or indirectly repressed by FlhD4C2 but can contribute to maximum colonizing ability are released from repression. Second, energy normally used to synthesize flagella and turn the flagellar motor is redirected to growth

Role of Motility and the \u3cem\u3eflhDC\u3c/em\u3e Operon in \u3cem\u3eEscherichia coli\u3c/em\u3e MG1655 Colonization of the Mouse Intestine

Previously, we reported that the mouse intestine selected mutants of Escherichia coli MG1655 that have improved colonizing ability (M. P. Leatham et al., Infect. Immun. 73:8039-8049, 2005). These mutants grew 10 to 20% faster than their parent in mouse cecal mucus in vitro and 15 to 30% faster on several sugars found in the mouse intestine. The mutants were nonmotile and had deletions of various lengths beginning immediately downstream of an IS1 element located within the regulatory region of the flhDC operon, which encodes the master regulator of flagellum biosynthesis, FlhD4C2. Here we show that during intestinal colonization by wild-type E. coli strain MG1655, 45 to 50% of the cells became nonmotile by day 3 after feeding of the strain to mice and between 80 and 90% of the cells were nonmotile by day 15 after feeding. Ten nonmotile mutants isolated from mice were sequenced, and all were found to have flhDC deletions of various lengths. Despite this strong selection, 10 to 20% of the E. coli MG1655 cells remained motile over a 15-day period, suggesting that there is an as-yet-undefined intestinal niche in which motility is an advantage. The deletions appear to be selected in the intestine for two reasons. First, genes unrelated to motility that are normally either directly or indirectly repressed by FlhD4C2 but can contribute to maximum colonizing ability are released from repression. Second, energy normally used to synthesize flagella and turn the flagellar motor is redirected to growth

Susceptibility of swine to H5 and H7 low pathogenic avian influenza viruses

Citation: Balzli, C., Lager, K., Vincent, A., Gauger, P., Brockmeier, S., Miller, L., . . . Swayne, D. E. (2016). Susceptibility of swine to H5 and H7 low pathogenic avian influenza viruses. Influenza and other Respiratory Viruses. doi:10.1111/irv.12386Background: The ability of pigs to become infected with low pathogenic avian influenza (LPAI) viruses and then generate mammalian adaptable influenza A viruses is difficult to determine. Yet, it is an important link to understanding any relationship between LPAI virus ecology and possible epidemics among swine and/or humans. Objectives: Assess susceptibility of pigs to LPAI viruses found within the United States and their direct contact transmission potential. Methods: Pigs were inoculated with one of ten H5 or H7 LPAI viruses selected from seven different bird species to test infectivity, virulence, pathogenesis, and potential to transmit virus to contact pigs through histological, RRT-PCR and seroconversion data. Results: Although pigs were susceptible to infection with each of the LPAI viruses, no clinical disease was recognized in any pig. During the acute phase of the infection, minor pulmonary lesions were found in some pigs and one or more pigs in each group were RRT-PCR-positive in the lower respiratory tract, but no virus was detected in upper respiratory tract (negative nasal swabs). Except for one group, one or more pigs in each LPAI group developed antibody. No LPAI viruses transmitted to contact pigs. Conclusions: LPAI strains from various bird populations within the United States are capable of infecting pigs. Although adaptability and transmission of individual strains seem unlikely, the subclinical nature of the infections demonstrates the need to improve sampling and testing methods to more accurately measure incidence of LPAI virus infection in pigs, and their potential role in human-zoonotic LPAI virus dynamics. © 2016 John Wiley & Sons Ltd

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

SFRP1 reduction results in an increased sensitivity to TGF-β signaling

Background Transforming growth factor (TGF)-β plays a dual role during mammary gland development and tumorigenesis and has been shown to stimulate epithelial-mesenchymal transition (EMT) as well as cellular migration. The Wnt/β-catenin pathway is also implicated in EMT and inappropriate activation of the Wnt/β-catenin signaling pathway leads to the development of several human cancers, including breast cancer. Secreted frizzled-related protein 1 (SFRP1) antagonizes this pathway and loss of SFRP1 expression is frequently observed in breast tumors and breast cancer cell lines. We previously showed that when SFRP1 is knocked down in immortalized non-malignant mammary epithelial cells, the cells (TERT-siSFRP1) acquire characteristics associated with breast tumor initiating cells. The phenotypic and genotypic changes that occur in response to SFRP1 loss are consistent with EMT, including a substantial increase in the expression of ZEB2. Considering that ZEB2 has been shown to interact with mediators of TGF-β signaling, we sought to determine whether TGF-β signaling is altered in TERT-siSFRP1 cells. Methods Luciferase reporter assays and real-time PCR analysis were employed to measure TGF-β transcriptional targets. Western blot analysis was used to evaluate TGF-β-mediated ERK1/2 phosphorylation. Migration chamber assays were utilized to quantify cellular migration. TERT-siSFRP1 cells were transfected with Stealth RNAi™ siRNA in order to knock-down the expression of ZEB2. Results TERT-siSFRP1 cells exhibit a significant increase in both TGF-β-mediated luciferase activity as well as TGF-β transcriptional targets, including Integrin β3 and PAI-1. Phosphorylation of ERK1/2 is increased in TERT-siSFRP1 cells in response to enhanced TGF-β signaling. Furthermore, when the TGF-β pathway is blocked with a TGF-βR antagonist (LY364947), cellular migration is significantly hindered. Finally, we found that when ZEB2 is knocked-down, there is a significant reduction in the expression of exogeneous and endogenous TGF-β transcriptional targets and cellular migration is impeded. Conclusions We demonstrate that down-regulation of SFRP1 renders mammary epithelial cells more sensitive to TGF-β signaling which can be partially ameliorated by blocking the expression of ZEB2

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