A small-molecule lead compound for the treatment of Alzheimer's disease

At autopsy, Alzheimer's disease is characterised by the presence of amyloid plaques and neurofibrillary tangles, made up of two peptide sequences, amyloid-beta(1-40) (A beta 40) and amyloid-beta(1-42) (A beta 42). In Tyrode's solution (2 mM Ca2+), 10 mu M A beta 42 peptide almost immediately aggregates and eventually forms p-sheets. This aggregation can be inhibited with 4,5-dianilinophthalimide (DAPH). Ca2+-permeant AMPA receptors are involved in the neuronal Ca2+ influx (neurotoxicity) induced by the A beta 42 peptide in cultured neuronal cells. The Ca2+ influx observed with pre-incubated A beta 42 peptide was inhibited by DAPH. DAPH also inhibits epidermal growth factor receptor kinase, and this will prevent its development for use in Alzheimer's disease. The potential of DAPH as a small-molecule lead compound for the treatment of Alzheimer's disease next requires the separation of the structural requirements that reverse fibril formation and inhibit epidermal growth factor receptor kinase.

A comparison of surface brightness profiles for ultracompact dwarfs and dwarf elliptical nuclei: implications for the “threshing” scenario

Using imaging from the Hubble Space Telescope, we derive surface brightness profiles for ultracompact dwarfs in the Fornax Cluster and for the nuclei of dwarf elliptical galaxies in the Virgo Cluster. Ultracompact dwarfs are more extended and have higher surface brightnesses than typical dwarf nuclei, while the luminosities, colors, and sizes of the nuclei are closer to those of Galactic globular clusters. This calls into question the production of ultracompact dwarfs via threshing, whereby the lower surface brightness envelope of a dwarf elliptical galaxy is removed by tidal processes, leaving behind a bare nucleus. Threshing may still be a viable model if the relatively bright Fornax ultracompact dwarfs considered here are descended from dwarf elliptical galaxies whose nuclei are at the upper end of their luminosity and size distributions.

Electrophysiological evidence for linear polarization sensitivity in the compound eyes of the stomatopod crustacean Gonodactylus chiragra

Gonodactyloid stomatopod crustaceans possess polarization vision, which enables them to discriminate light of different e-vector angle. Their unusual apposition compound eyes are divided by an equatorial band of six rows of enlarged, structurally modified ommatidia, the mid-band (MB). The rhabdoms of the two most ventral MB rows 5 and 6 are structurally designed for polarization vision. Here we show, with electrophysiological recordings, that the photoreceptors R1-R7 within these two MB rows in Gonodactylus chiragra are highly sensitive to linear polarized light of two orthogonal directions (PS=6.1). They possess a narrow spectral sensitivity peaking at 565 nm. Unexpectedly, photoreceptors within the distal rhabdomal tier of MB row 2 also possess highly sensitive linear polarization receptors, which are in their spectral and polarization characteristics similar to the receptors of MB rows 5 and 6. Photoreceptors R1-R7 within the remainder of the MB exhibit low polarization sensitivity (PS=2.3). Outside the MB, in the two hemispheres, R1-R7 possess medium linear polarization sensitivity (PS=3.8) and a broad spectral sensitivity peaking at around 500 nm, typical for most crustaceans. Throughout the retina the most distally situated UV-sensitive R8 cells are not sensitive to linear polarized light.

Vibration of symmetrically laminated thick super elliptical plates

This paper reports a free vibration analysis of thick plates with rounded corners subject to a free, simply-supported or clamped boundary condition. The plate perimeter is defined by a super elliptic function with a power defining the shape ranging from an ellipse to a rectangle. To incorporate transverse shear deformation, the Reddy third-order plate theory is employed. The energy integrals incorporating shear deformation and rotary inertia are formulated and the p-Ritz procedures are used to derive the governing eigenvalue equation. Numerical examples for plates with different shapes and boundary conditions are solved and their frequency parameters, where possible, are compared with known results. Parametric studies are carried out to show the sensitivities of frequency parameters by varying the geometry, fibre stacking sequence, and boundary condition. (C) 1999 Academic Press.