The increased production of amyloid beta-peptide (Abeta) in Alzheimer's disease is acknowledged to be a key pathogenic event. In this study, we examined the response of primary human and rat brain cortical cultures to Abeta administration and found a marked increase in the tyrosine phosphorylation content of numerous neuronal proteins, including tau and putative microtubule-associated protein 2c (MAP2c). We also found that paired helical filaments of aggregated and hyperphosphorylated tau are tyrosine phosphorylated, indicating that changes in the phosphotyrosine content of cytoplasmic proteins in response to Abeta are potentially an important process. Increased tyrosine phosphorylation of cytoskeletal and other neuronal proteins was specific to fibrillar Abeta(25-35) and Abeta(1-42). The tyrosine phosphorylation was blocked by addition of the Src family tyrosine kinase inhibitor 4-amino-5-(4-chlorophenyl)-7(t-butyl)pyrazol(3,4-d)pyramide (PP2) and the phosphatidylinositol 3-kinase inhibitor LY 294002. Tyrosine phosphorylation of tau and MAP2c was concomitant with an increase in the tyrosine phosphorylation and subsequent putative activation of the non-receptor kinase, focal adhesion kinase (FAK). Immunoprecipitation of Fyn, a member of the Src family, from Abeta(25-35)-treated neurons showed an increased association of Fyn with FAK. Abeta treatment of cells also stimulated the sustained activation of extracellular regulated kinase-2, which was blocked by addition of PP2 and LY 294002, suggesting that FAK/Fyn/PI3-kinase association is upstream of mitogen-activated protein (MAP) kinase signaling in Abeta-treated neurons. This cascade of signaling events contains the earliest biochemical changes in neurons to be described in response to Abeta exposure and may be critical for subsequent neurodegenerative changes.

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The flow law determined experimentally for solid CO2 establishes that a hypothesis of glacial flow of C02 at the Martian poles is not physically unrealistic. Compression experiments carried out under 1 atm pressure and constant strain rate demonstrate that the strength of COz near its sublimation point is considerably less than the strength of water ice near its melting point. The data fit a power law "creep" equation of the form d = (4 x 106)a a'° exp(-12 200/RT), where ~ is compressive strain rate (sec-t), a is compressive stress (bars), R is the gas constant in calories per mole, and T is absolute temperature. The exponent of a of 3.9 contrasts with a value near 3.1 for water ice, and indicates that the strain rate is somewhat more sensitive to stress for CO2 than for water. Like,rise, the low activation energy for creep, 12 200calmole-1, illustrates that COz is not highly sensitive to temperature and is thus likely to flow over a broad range of temperatures below its melting point. Strength values for CO2 are of the order of one-tenth to one-third the strength of ice under equivalent conditions. A plausible glacial model for the Martian polar caps can be constructed and is helpful in explaining the unique character of the polar regions. CO2-rich layers deposited near the pole would have flowed outward laterally to relieve high internal shear stresses. The topography of the polar caps, the uniform layering of the layered deposits, and the general extent of the polar "sediments" could all be explained using this model. Flow of C02 rather than water ice greatly reduces the problems with Martian glaciation. Nevertheless, problems do remain, in particular the large amounts of CO2 necessary, the need to increase vapor pressure and temperature with depth in the polar deposits, and the lack of good observational evidence of flow features. Within the limits of the present knowledge of surface conditions on Mars, CO z glaciation appears to be a realistic alternate working hypothesis for the origin of the polar features.

Single crystals and aggregates of natural chalcopyrite were deformed under controlled conditions of temperature (24 ø to 500øC), confining pressure (500 to 2,000 bars), and strain rate (constant 7.2 X 10 -5 sec -•) in several series of experiments designed to test the deformational properties of this mineral under shallow tectonic conditions. At low temperature, chalcopyrite deforms by cataclasis combined with translation gliding on (112) (510) and (112) (0:•1). Polysynthetic deformation twinning, also on (112), begins at 100øC (at 500 bars) and becomes increasingly abundant at higher temperatures with a consequent loss of strength, increase in ductility, and decrease in cataclasis. True kinking is very rare in chalcopyrite. Likewise, no new grains or subgrains were observed in any of these deformation experiments. At room temperature, the strength and ductility of chalcopyrite increase with confining pressure, but at elevated temperatures the effects of confining pressure are greatly subordinate to those of the temperature itself. At the constant strain rate employed, the britfie-ductil.e transition in chalcopyrite takes place between 1,000 and 1,500 bars confining pressure at room temperature and below 500 bars at 200øC. As temperature increases, the ductility of chalcopyrite is enhanced and its strength is greatly reduced. For example, at 1,000 bars confining pressure the strength drops from nearly 5,000 bars at room temperature to less than 1,000 bars at 500øC. Even further reductions in strength would accompany the slower strain rates that prevail in nature (see Roscoe, 1975).Originally undeformed chalcopyrites were studied by both optical and scanning electron microscopy before and after experimental deformation for unambiguous evidence of deformation features. Chalcopyrite deformed at room temperature shows various types of shear and extension fractures whose orientation reflects the known stress field and whose intensity is strongly controlled by original twin and grain orientations. These cataclastic features persist but become subdued at higher temperatures. No deformation twins were seen in any room temperature run. Abundant (112) slip lines can be seen in crystal faces deformed at 24øC but are not visible in these same faces after polishing and etching. At temperatures of 100øC and higher, chalcopyrite develops polysynthetic (112) deformation twins that are readily distinguished from original (110) and (102) twins of nondeformational origin. Complex patterns and sequences of intragranular features arise where the (112) deformation twinning is superposed on a fabric of original growth twins, lensatic twins, and exsolution intergrowths. These features and their age relations could be clearly observed, and easily applied, in the analysis of naturally deformed sulfide deposits. These and earlier experiments (Clark and Kelly, 1973; Salmon et al., 1974) demonstrate that the relative strengths of chalcopyrite, pyrrhotite, sphalerite, and galena are dependent upon the conditions under which these minerals are...