Centralized Consensus Hemagglutinin Genes Induce Protective Immunity against H1, H3 and H5 Influenza Viruses

With the exception of the live attenuated influenza vaccine there have been no substantial changes in influenza vaccine strategies since the 1940’s. Here we report an alternative vaccine approach that uses Adenovirus-vectored centralized hemagglutinin (HA) genes as vaccine antigens. Consensus H1-Con, H3-Con and H5-Con HA genes were computationally derived. Mice were immunized with Ad vaccines expressing the centralized genes individually. Groups of mice were vaccinated with 1 X 1010, 5 X 107 and 1 X 107 virus particles per mouse to represent high, intermediate and low doses, respectively. 100% of the mice that were vaccinated with the high dose vaccine were protected from heterologous lethal challenges within each subtype. In addition to 100% survival, there were no signs of weight loss and disease in 7 out of 8 groups of high dose vaccinated mice. Lower doses of vaccine showed a reduction of protection in a dose-dependent manner. However, even the lowest dose of vaccine provided significant levels of protection against the divergent influenza strains, especially considering the stringency of the challenge virus. In addition, we found that all doses of H5-Con vaccine were capable of providing complete protection against mortality when challenged with lethal doses of all 3 H5N1 influenza strains. This data demonstrates that centralized H1-Con, H3-Con and H5-Con genes can be effectively used to completely protect mice against many diverse strains of influenza. Therefore, we believe that these Ad-vectored centralized genes could be easily translated into new human vaccines

Energy Spectrum Evolution of a Diffuse Field in Elastic Body Caused by Weak Nonlinearity

We study the evolution of diffuse elastodynamic spectral energy density under the influence of weak nonlinearity. It is shown that the rate of change of this quantity is given by a convolution of the linear energy at two frequencies. Quantitative estimates are given for sample aluminum and fused silica blocks of experimental interest.Comment: 9 pages, 3 figures; revised for better presentatio

Environmental Water Quality - a guide to sampling and measurement

The guide covers the problems associated with sampling water in the field and suggestions to overcome them. The main types of water pollution that potentially occur in the south west of Western Australia are discussed and for each contaminant, the origins and environmental effects are briefly described and where available, water quality guidelines are provided for major water uses. This is followed by specific requirements of the collection, storage and analysis of samples. The guide also includes further reading and details on suppliers, analytical costs and web resources

Expanding Mouse-Adapted Yamagata-like Influenza B Viruses in Eggs Enhances In Vivo Lethality in BALB/c Mice

Despite the yearly global impact of influenza B viruses (IBVs), limited host range has been a hurdle to developing a readily accessible small animal disease model for vaccine studies. Mouseadapting IBV can produce highly pathogenic viruses through serial lung passaging in mice. Previous studies have highlighted amino acid changes throughout the viral genome correlating with increased pathogenicity, but no consensus mutations have been determined. We aimed to show that growth system can play a role in mouse-adapted IBV lethality. Two Yamagata-lineage IBVs were serially passaged 10 times in mouse lungs before expansion in embryonated eggs or Madin–Darby canine kidney cells (London line) for use in challenge studies. We observed that virus grown in embryonated eggs was significantly more lethal in mice than the same virus grown in cell culture. Ten additional serial lung passages of one strain again showed virus grown in eggs was more lethal than virus grown in cells. Additionally, no mutations in the surface glycoprotein amino acid sequences correlated to differences in lethality. Our results suggest growth system can influence lethality of mouse-adapted IBVs after serial lung passaging. Further research can highlight improved mechanisms for developing animal disease models for IBV vaccine research

Interdecadal variability and oceanic thermohaline adjustment

Changes in the strength of the thermohaline overturning circulation are associated, by geostrophy, with changes in the east-west pressure difference across an ocean basin. The tropical-polar density contrast and the east-west pressure difference are connected by an adjustment process. In flat-bottomed ocean models the adjustment is associated with viscous, baroclinic Kelvin wave propagation. Weak-high latitude stratification leads to the adjustment having an interdecadal timescale. We reexamine model interdecadal oscillations in the context of the adjustment process, for both constant flux and mixed surface boundary conditions. Under constant surface flux, interdecadal oscillations are associated with the passage of a viscous Kelvin wave around the model domain. Our results suggest the oscillations can be self-sustained by perturbations to the western boundary current arising from the southward boundary wave propagation. Mixed boundary condition oscillations are characterized by the eastward, cross-basin movement of salinity-dominated density anomalies, and the westward return of these anomalies along the northern boundary. We suggest the latter is associated with viscous Kelvin wave propagation. Under both types of boundary conditions, the strength of the thermohaline overturning and the tropical-polar density contrast vary out of phase. We show how the phase relationship is related to the boundary wave propagation. The importance of boundary regions indicates an urgent need to examine the robustness of interdecadal variability in models as the resolution is increased, and as the representation of the coastal, shelf/slope wave guide is improved. (Abriged abstract)Comment: 20 pages, AGU LaTeX, 12 figures included using epsfig, to appear in JGR, complete manuscript also available at ftp://crosby.physics.mun.ca/pub/drew/papers/gp1.ps.g

Identifying Optimal Equivalent Area Changes to Reduce Sonic Boom Loudness

This work explores the design space created from modeling the effect of localized geometric changes on a supersonic aircraft’s near-field pressure signature. These geometric changes are used to alter the aircraft’s near-field pressure signature in a way that reduces its sonic boom loudness at the ground. The aircraft used in this work is the NASA 25D concept and its near-field pressure signature is modeled using two separate methods. The first method uses the PANAIR panel code to obtain a near-field pressure signature for an axisymmetric representation of the 25D. This near-field signature is propagated to the ground using the NASA sBOOM propagation code and the perceived level in decibels is calculated using an in-house loudness code called PyLdB. The second method uses the equivalent area distribution of the 25D which is passed directly to sBOOM and the perceived level is again found using PyLdB. To model the geometric changes, the axisymmetric geometry and the equivalent area distributions are independently modified with a parameterized Gaussian deformation. These methods are fast enough to quickly explore the design space and find the change in loudness for different deformation parameters. This design space exploration is used to study loudness changes for both on-design conditions and the effects of deviations from on-design angle of attack, Mach number, and azimuth angle. A genetic algorithm is used in subsequent studies to explore the effects of different atmospheric conditions. These results can be used to inform higher fidelity CFD studies and structural adaptation design on the aircraft

Three dimensional model calculations of the global dispersion of high speed aircraft exhaust and implications for stratospheric ozone loss

Two-dimensional (zonally averaged) photochemical models are commonly used for calculations of ozone changes due to various perturbations. These include calculating the ozone change expected as a result of change in the lower stratospheric composition due to the exhaust of a fleet of supersonic aircraft flying in the lower stratosphere. However, zonal asymmetries are anticipated to be important to this sort of calculation. The aircraft are expected to be restricted from flying over land at supersonic speed due to sonic booms, thus the pollutant source will not be zonally symmetric. There is loss of pollutant through stratosphere/troposphere exchange, but these processes are spatially and temporally inhomogeneous. Asymmetry in the pollutant distribution contributes to the uncertainty in the ozone changes calculated with two dimensional models. Pollutant distributions for integrations of at least 1 year of continuous pollutant emissions along flight corridors are calculated using a three dimensional chemistry and transport model. These distributions indicate the importance of asymmetry in the pollutant distributions to evaluation of the impact of stratospheric aircraft on ozone. The implications of such pollutant asymmetries to assessment calculations are discussed, considering both homogeneous and heterogeneous reactions

U.S. State‐Supported Dental Schools: Financial Projections and Implications

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153620/1/jddj002203372006703tb04080x.pd

ASCA Observations of the Starburst-Driven Superwind Galaxy NGC 2146: Broad Band (0.6 - 9 keV) Spectral Properties

We report ASCA GIS and SIS observations of the nearby (D = 11.6 Mpc), nearly edge-on, starburst galaxy NGC 2146. These X-ray spectral data complement ROSAT PSPC and HRI imaging discussed by Armus et al., 1995. The broad band (0.6-9 keV) X-ray spectrum of NGC 2146 is best described by a two component model: the soft X-ray emission with a Raymond-Smith thermal plasma model having a temperature of kT $\sim 0.8$ keV; the hard X-ray emission with a thermal plasma model having kT $\sim 8$ keV or a power-law model having a photon index of $\sim 1.7$. We do not find compelling evidence of substantial excess absorption above the Galactic value. The soft (hard) thermal component provides about 30% (70%) of the total luminosity in the 0.5 - 2.0 keV energy band, while in the 2-10 keV energy range only the hard component plays a major role. The spectral results allow us to set tighter constraints on the starburst-driven superwind model, which we show can satisfactorily account for the luminosity, mass, and energy content represented by the soft X-ray spectral component. We estimate that the mass outflow rate ($\sim$ 9 M$_{\odot}$ per year) is about an order of magnitude greater than the predicted rate at which supernovae and stellar winds return mass into the interstellar medium and, therefore, argue that the flow is strongly "mass-loaded" with material in and around the starburst. The estimated outflow velocity of the hot gas is close to the escape velocity from the galaxy, so the fate of the gas is not clear. We suggest that the hard X-ray spectral component is due to the combined emission of X-ray binaries and/or young supernovae remnants associated with the starburst.Comment: 26 pages plus 4 figures, LaTex manuscript, Accepted for publication in the Astrophysical Journa