Apoptosis of neurones, macrophages, and microglia occurs in the brains of paediatric patients with human immunodeficiency virus (HIV) type 1 encephalitis, which is often associated with pre-mortem neurological disease (progressive encephalopathy). We have previously reported that TUNEL-positive neurones in brain tissue from paediatric patients with HIV type 1 encephalitis and progressive encephalopathy are strikingly devoid of the pro-apoptotic gene product Bax, in marked contrast to brain-resident macrophages and microglia. Using immunocytochemical methods, the present study demonstrate that neurones in patients with HIV type 1 encephalitis and progressive encephalopathy, as well as macrophages and microglia, but not astrocytes, overexpress caspase-3, a pro-apoptotic enzyme that is proteolytically activated downstream of Bax-Bcl-2 dysregulation. Co-localization of neuronal cytoplasmic caspase-3 and nuclear TUNEL staining, a marker for fragmented DNA, was also infrequently observed in brain tissue from patients with HIV type 1 encephalitis and progressive encephalopathy. These findings suggest that vulnerable neurones in brain tissue from patients with HIV virus type 1 encephalitis and progressive encephalopathy undergo apoptosis by a mechanism that involves upregulation of caspase-3 in a pathway that is independent of Bax-Bcl-2 dysregulation. Furthermore, caspase-3 upregulation in apoptotic neurones likely occurs prior to DNA fragmentation.
Nanoindentation tests and finite element analysis that considers elastic-mesoplastic deformation for single crystals were used to investigate the mechanical properties of CaF2 under spherical indentation. The goal was to gain a better understanding of microfractures and crystalline anisotropy and their effect on the surface quality of CaF2 during manufacturing. In this analysis, indentations of the three main crystallographic planes (100), (110), and (111) were studied and compared to examine the effects of crystalline anisotropy on the load–displacement curves, surface profiles, contact radius, spherical hardness, stress distributions, and cleavage at two stages, namely at the maximum indentation load and after the load had been removed. Our model results were compared with experimental observation of surface microroughness, subsurface damage, and material removal rate in grinding of CaF2.
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