Hypometabolism as a therapeutic target in Alzheimer's disease

The pathology of Alzheimer's disease (AD) is characterized by cerebral atrophy in frontal, temporal, and parietal regions, with senile plaques, dystrophic neurites, and neurofibrillar tangles within defined areas of the brain. Another characteristic of AD is regional hypometabolism in the brain. This decline in cerebral glucose metabolism occurs before pathology and symptoms manifest, continues as symptoms progress, and is more severe than that of normal aging. Ketone bodies are an efficient alternative fuel for cells that are unable to metabolize glucose or are 'starved' of glucose. AC-1202 is designed to elevate serum ketone levels safely. We previously showed that treatment with AC-1202 in patients with mild-to-moderate AD improves memory and cognition. Treatment outcomes were influenced by apolipoprotein E genotype status. These data suggest that AC-1202 may be an effective treatment for cognitive dysfunction by providing an alternative substrate for use by glucose-compromised neurons

Fully developed flow of a viscoelastic film down a vertical cylindrical or planar wall

The one-dimensional, gravity-driven film flow of a linear (l) or exponential (e) Phan-Thien and Tanner (PTT) liquid, flowing either on the outer or on the inner surface of a vertical cylinder or over a planar wall, is analyzed. Numerical solution of the governing equations is generally possible. Analytical solutions are derived only for: (1) l-PTT model in cylindrical and planar geometries in the absence of solvent, ß = ¿~s(¿~s + ¿~p) = 0, where ¿~p and ¿~s are the zero-shear polymer and solvent viscosities, respectively, and the affinity parameter set at ¿ = 0; (2) l-PTT or e-PTT model in a planar geometry when ß = 0 and ¿ ¿ 0; (3) e-PTT model in planar geometry when ß = 0 and ¿ = 0. The effect of fluid properties, cylinder radius, R~, and flow rate on the velocity profile, the stress components, and the film thickness, H~, is determined. On the other hand, the relevant dimensionless numbers, which are the Deborah, De = ¿~U/H~, and Stokes, St = ¿~g~H~2/ (¿~p + ¿~s)U, numbers, depend on H~ and the average film velocity, U. This makes necessary a trial and error procedure to obtain H~ a posteriori. We find that increasing De, ¿, or the extensibility parameter e increases shear thinning resulting in a smaller St. The Stokes number decreases as R~/H~ decreases down to zero for a film on the outer cylindrical surface, while it asymptotes to very large values when R~/H~ decreases down to unity for a film on the inner surface. When ¿ ¿ 0, an upper limit in De exists above which a solution cannot be computed. This critical value increases with e and decreases with ¿. © Springer-Verlag 2009

The Free (Open) Boundary Condition at inflow boundaries

The Free (or Open) Boundary Condition (FBC, OBC) was proposed by Papanastasiou et al. (A new outflow boundary condition, Int. J. Numer. Meth. Fluids 14 (1992) 587-608) to handle truncated domains with synthetic boundaries where the outflow conditions are unknown. In the present work, implementation of the FBC has been tested also at inflow boundaries in several test problems of viscous or viscoelastic flow. The Finite Element Method (FEM) is used to provide numerical results for both cases of planar and axisymmetric domains under laminar, isothermal or non-isothermal, steady-state conditions for Newtonian and non-Newtonian fluids. The present results extend previous ones regarding the applicability of the FBC, since they convincingly show that the FBC can be used equally well at inflow boundaries, without having to resort to artificially set inlet profiles for a given flow rate. (C) 2012 Elsevier B.V. All rights reserved

Oscillations of small bubbles and medium yielding in elastoviscoplastic fluids

We investigate the radial oscillations of small gas bubbles trapped in yield-stress fluids and driven by an acoustic pressure field. We model the rheological behavior of the yield-stress fluid using the recently developed elastoviscoplastic constitutive equation that takes into account the elastic and viscoplastic deformations of the material [Saramito, J. Non-Newton. Fluid Mech. 158, 154 (2009)]. Assuming that the bubble remains spherical during the pressure driving, we reduce the problem to a set of ordinary differential equations and an integrodifferential equation, which we solve numerically for the case of two yield-stress fluids, i.e., a soft Carbopol gel and a stiffer kaolin suspension. We find that depending on the amplitude and frequency of the pressure field, the radial oscillations of the bubble produce elastic stresses that may or may not suffice to yield the surrounding material. We evaluate the critical amplitude of the acoustic pressure required to achieve yielding and we find a good agreement between numerical simulations and an analytical formula derived under the assumption of linear deformations. Finally, we examine the bubble oscillation amplitude for a very wide range of applied pressures both below and above the critical value to assess the impact of yielding on the bubble dynamics. This analysis could be used to identify a signature of yielding in experiments where the radial dynamics of a bubble is measured. More generally, these results can be used to rationalize the optimal conditions for pressure-induced bubble release from yield-stress fluids, which is relevant to various biomedical and industrial applications, including the oil industry and food processing