Bostonia: 1999-2000, no. 1-4

Founded in 1900, Bostonia magazine is Boston University's main alumni publication, which covers alumni and student life, as well as university activities, events, and programs

HOW TO BUILD BETTER MODELS: APPLYING AGILE TECHNIQUES TO SIMULATION

For simulation practitioners, the common steps in a simulation modeling engagement are likely familiar: problem assessment, requirements specification, model building, verification, validation, and delivery of results. And for industrial engineers, it’s a well-known adage that paying careful attention to process can help achieve better results. In this paper, we’ll apply this philosophy to the process of model building as well. We’ll consider model building within the framework of a software development exercise, and discuss how best practices from the broader software community can be applied for process improvement. In particular, we’ll focus on the “Milestones Approach ” to simulation development – based on the popular “agile software ” philosophy and our own experiences in realworld simulation consulting practice. We’ll discuss how thinking agile can help minimize risk within the modelbuilding process, and help create a better simulation for your customers.

Hippocampal ProNGF Signaling Pathways and β-Amyloid Levels in Mild Cognitive Impairment and Alzheimer Disease

Hippocampal precursor of nerve growth factor (proNGF)/NGF signaling occurs in conjunction with β-amyloid (Aβ) accumulations in Alzheimer disease (AD). To assess the involvement of this pathway in AD progression, we quantified these proteins and their downstream pathway activators in postmortem tissues from the brains of subjects with no cognitive impairment (NCI), mild cognitive impairment (MCI), and AD using immunoblotting and enzyme-linked immunosorbent assay (ELISA). Hippocampal proNGF was significantly greater in AD compared to NCI and MCI cases. TrkA was significantly reduced in MCI compared to NCI and AD, whereas p75(NTR), sortilin, and neurotrophin receptor homolog-2 remained stable. Akt decreased from NCI to MCI to AD, whereas phospho-Akt and phosphor-Akt to Akt ratio were elevated in AD compared to MCI and NCI. No differences were found in phospho-Erk, Erk or their ratio across groups. c-jun kinase (JNK) remained stable across groups, while phospho-JNK and the phospho-JNK to JNK ratio increased significantly in AD compared to NCI and MCI. Expression levels of Aβ(1-40), Aβ(1-42) and Aβ(40/42) ratio were stable. Statistical analysis revealed a strong positive correlation between proNGF and phospho-JNK, though only proNGF was negatively correlated with cognitive function and only TrkA was negatively associated with pathologic criteria. These findings suggest that alterations in the hippocampal NGF signaling pathway in MCI and AD favor proNGF-mediated pro-apoptotic pathways, and that this is independent of Aβ accumulation during AD progression