1,868 research outputs found
The Long and Large Decline in U.S. Output Volatility
output volatility, macroeconomics, decline, U.S. output
Heterologous prime-boost-boost immunisation of Chinese cynomolgus macaques using DNA and recombinant poxvirus vectors expressing HIV-1 virus-like particles
Background: There is renewed interest in the development of poxvirus vector-based HIV vaccines due to the protective effect observed with repeated recombinant canarypox priming with gp120 boosting in the recent Thai placebo-controlled trial. This study sought to investigate whether a heterologous prime-boost-boost vaccine regimen in Chinese cynomolgus macaques with a DNA vaccine and recombinant poxviral vectors expressing HIV virus-like particles bearing envelopes derived from the most prevalent clades circulating in sub-Saharan Africa, focused the antibody response to shared neutralising epitopes.
Methods: Three Chinese cynomolgus macaques were immunised via intramuscular injections using a regimen composed of a prime with two DNA vaccines expressing clade A Env/clade B Gag followed by boosting with recombinant fowlpox virus expressing HIV-1 clade D Gag, Env and cholera toxin B subunit followed by the final boost with recombinant modified vaccinia virus Ankara expressing HIV-1 clade C Env, Gag and human complement protein C3d. We measured the macaque serum antibody responses by ELISA, enumerated T cell responses by IFN-gamma ELISpot and assessed seroneutralisation of HIV-1 using the TZM-bl beta-galactosidase assay with primary isolates of HIV-1.
Results: This study shows that large and complex synthetic DNA sequences can be successfully cloned in a single step into two poxvirus vectors: MVA and FPV and the recombinant poxviruses could be grown to high titres. The vaccine candidates showed appropriate expression of recombinant proteins with the formation of authentic HIV virus-like particles seen on transmission electron microscopy. In addition the b12 epitope was shown to be held in common by the vaccine candidates using confocal immunofluorescent microscopy. The vaccine candidates were safely administered to Chinese cynomolgus macaques which elicited modest T cell responses at the end of the study but only one out of the three macaques elicited an HIV-specific antibody response. However, the antibodies did not neutralise primary isolates of HIV-1 or the V3-sensitive isolate SF162 using the TZM-bl b-galactosidase assay.
Conclusions: MVA and FP9 are ideal replication-deficient viral vectors for HIV-1 vaccines due to their excellent safety profile for use in humans. This study shows this novel prime-boost-boost regimen was poorly immunogenic in Chinese cynomolgus macaques
Multi-physics Large-Eddy Simulation of methane oxy-combustion in Liquid Rocket Engines
Combustion in Liquid Rocket Engines (LRE) happens in extreme conditions which imply several multi-physics phenomena. For this reason, numerical simulation is used to predict and thus to optimize the engine performances and lifetime. In particular this thesis focuses on two main aspects: turbulent oxy-combustion in diffusion flames of methane at high pressure, and prediction of wall heat transfers. The Large Eddy Simulation (LES) code AVBP of CERFACS is used. Despite its lower performances, methane is now preferred to hydrogen for future LRE because of its reduced cost and its practicality both for in terms of usage and storage. For numerical simulation, this propellant raises new questions about how to ignite and stabilize the flame. To do so, developing realistic chemistry is a key step. Reduced finite rate chemistry schemes with about 15 species are derived and tested for high pressure and highly strained counterflow diffusion flames. However, even reduced kinetic schemes are still expensive in the context of industrial LES simulations. Therefore a new integration method for the chemical source terms is proposed in order to run reactive simulations closer to the flow time step. It is found that significant computational cost is spared, while keeping the same result accuracy compared to the classical integration. Finally, in order to develop future turbulent diffusion flame modeling, a study on how the mesh resolution impacts diffusion flames is also performed. The development of reduced chemistry allows to study precisely the influence of chemical reactions at the near-wall region in LRE conditions on the wall heat flux. Periodic turbulent channels are computed to compare the resolved and non-resolved turbulent boundary layer, with or without chemical reactions. Results show that the near-wall reactions may have a real impact on wall heat flux, and that wall models should take into account this effect in the context of wall-modeled LES. Another study is conducted to determine the impact of the coupling between the sub-grid scale model and the wall-law on the wall fluxes prediction. It is shown that the amount of turbulent viscosity at the near-wall region greatly changes the fluxes. A stochasticbased model is proposed in the case of isothermal simulations, in order to improve the results for two common LES sub-grid scale models, WALE and Sigma. The developed models and analyses of those test cases are then used for the LES simulation of two test rigs: the supercritical 5- injectors GCH4/GOx from ONERA and the subcritical single-injector GCH4/LOx from TUM. Their study particularly focuses on the flame behavior and the wall heat flux comparison with experiment
Existence results for a Cauchy-Dirichlet parabolic problem with a repulsive gradient term
We study the existence of solutions of a nonlinear parabolic problem of
Cauchy-Dirichlet type having a lower order term which depends on the gradient.
The model we have in mind is the following: \begin{cases}\begin{split} &
u_t-\text{div}(A(t,x)\nabla u|\nabla u|^{p-2})=\gamma |\nabla u|^q+f(t,x)
&\qquad\text{in } Q_T,\\ & u=0 &\qquad\text{on }(0,T)\times \partial \Omega,\\
& u(0,x)=u_0(x) &\qquad\text{in } \Omega, \end{split}\end{cases} where
, is a bounded domain of , , , the matrix is coercive and with measurable bounded
coefficients, the r.h.s. growth rate satisfies the superlinearity condition and the initial
datum is an unbounded function belonging to a suitable Lebesgue space
. We point out that, once we have fixed , there exists a
link between this growth rate and exponent which allows
one to have (or not) an existence result. Moreover, the value of deeply
influences the notion of solution we can ask for. The sublinear growth case
with is dealt at the end of the paper for what concerns
small value of , namely
Constraints on CDM cosmology from galaxy power spectrum, CMB and SNIa evolution
We examine the constraints that can be obtained on standard cold dark matter
models from the most currently used data set: CMB anisotropies, type Ia
supernovae and the SDSS luminous red galaxies. We also examine how these
constraints are widened when the equation of state parameter and the
curvature parameter are left as free parameters. For the
CDM model, our 'vanilla' model, cosmological parameters are tightly
constrained and consistent with current estimates from various methods. When
the dark energy parameter is free we find that the constraints remain
mostly unchanged, i.e. changes are smaller than the 1 sigma uncertainties.
Similarly, relaxing the assumption of a flat universe leads to nearly identical
constraints on the dark energy density parameter of the universe
, baryon density of the universe , the optical
depth , the index of the power spectrum of primordial fluctuations ,
with most one sigma uncertainties better than 5%. More significant changes
appear on other parameters: while preferred values are almost unchanged,
uncertainties for the physical dark matter density , Hubble
constant and are typically twice as large. We found that
different methodological approaches on large scale structure estimates lead to
appreciable differences in preferred values and uncertainty widths. We also
found that possible evolution in SNIa intrinsic luminosity does not alter these
constraints by much, except for , for which the uncertainty is twice as
large. At the same time, this possible evolution is severely constrained. We
conclude that systematic uncertainties for some estimated quantities are
similar or larger than statistical ones.Comment: Revised version, 9 pages, 8 figures, accepted for publication in A&
Scaling and Universality in City Space Syntax: between Zipf and Matthew
We report about universality of rank-integration distributions of open spaces
in city space syntax similar to the famous rank-size distributions of cities
(Zipf's law). We also demonstrate that the degree of choice an open space
represents for other spaces directly linked to it in a city follows a power law
statistic. Universal statistical behavior of space syntax measures uncovers the
universality of the city creation mechanism. We suggest that the observed
universality may help to establish the international definition of a city as a
specific land use pattern.Comment: 24 pages, 5 *.eps figure
Expérimentation, en milieu contraint, d’une méthodologie de co-conception de produits innovants
Nous proposons un modèle de co-conception qui a été construit, testé puis appliqué à un exemple de développement de produit nouveau, en PME, par la combinaison d’une analyse de la valeur associée à des pratiques de co-design
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