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Parkinson's disease (PD) involves both motor and non-motor disturbances. Non-motor features include alterations in sensory olfactory function which may constitute a viable biomarker for the disorder. It is not clear what causes olfactory dysfunction but it appears to coincide with the development of synucleopathy within the olfactory bulb (OB). Elevation in alpha-synuclein (a-syn) is indeed a risk factor for development of the sporadic disorder. The multifactorial nature of the idiopathic disease combined with variability in its presentation suggests that it is likely to be influenced by several factors and that in vivo models that explore the synergistic effect of alpha-synuclein elevation with other potential contributing factors are likely to be of importance in understanding the disease etiology. Using a dual transgenic (DTg) mouse model of dopaminergic alpha-synuclein overexpression coupled with doxycycline (Dox)-inducible glutathione (GSH) depletion in these same cells, we demonstrate an age-related loss in behavioral olfactory function coupled with a significant neurodegeneration of glomerular dopaminergic neurons. This is accompanied by increase in alpha-synuclein levels in non-dopaminergic cells in the granule cell layer (GCL). In addition, isolated olfactory bulb synaptosomes from dual transgenic lines with Dox consistently showed a slight but significant reduction in maximum mitochondrial respiration compared to controls. These results suggest that in the presence of increased oxidative stress, increased alpha-synuclein expression within dopaminergic OB neurons results in neurodegeneration in the glomerular layer (GL) and increased alpha-synuclein levels in the granular cell layer which coincide with olfactory dysfunction.

Models to predict the split growth in notched AS4/3501-6 graphite/epoxy quasi-isotropic laminates under tension-dominated fatigue are presented. First, a power law model and an artificial neural network (ANN) model are developed to describe the split growth under constant-amplitude fatigue. They are then applied in conjunction with a linear damage growth model to predict the split growth under spectrum fatigue. The ANN model is found to work better than the power law model as a predictive tool for split growth.

The subcritical damage growth in notched AS4/3501-6 graphite/epoxy quasi-isotropic laminates under compression–compression and compression-dominated spectrum fatigue was investigated using the longitudinal split length as a damage measure. A linear split growth model was successfully used to predict the split growth in spectrum fatigue using the corresponding data under constant-amplitude fatigue. However, a linear degradation assumption was found to be inappropriate as it overpredicted lifetime under spectrum fatigue. The residual compressive strength did not show any sign of gradual reduction. The damage mode near the hole changed from longitudinal splitting to transverse extension of fiber failure and delamination as the fatigue stress increased. Thus, while the longitudinal split may serve as a measure of damage in high-cycle fatigue, the extent of transverse fiber failure is a better indication of residual compressive strength. It was shown that a compression-dominated fatigue loading spectrum could be shortened substantially by omitting the two lowest load levels at which no significant damage growth was seen under constant-amplitude fatigue.