Given a context passage, generate a question from the passage such that its answer is shortest continous span from the passage.
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Question: The 1873 Victorian football season was an Australian rules football competition played during the winter of 1873.

Answer: What's 1873 Victorian football season sport?


Question: Imatinib was the first BCR-ABL tyrosine kinase inhibitor to become clinically available. In this study, we retrospectively evaluated the long-term efficacy of low-dose imatinib (final maintenance dose <300mg per day) due to intolerance, in comparison to optimal-dose imatinib (300mg per day) in patients with Philadelphia chromosome-positive chronic myeloid leukemia in the chronic phase. The Kaplan-Meier estimates of the median time to complete cytogenetic response, major molecular response, and complete molecular response were longer for 31 patients receiving low-dose imatinib (360, 1360, and 1420days, respectively) than 74 patients receiving optimal-dose imatinib (170, 420, and 720days, respectively). However, the differences in response shrank over time and progression-free survival were comparable between the two groups. These findings suggest that long-term treatment with low-dose imatinib is an acceptable alternative for patients with intolerance to the optimal dose.

Answer: What tyrosine kinase, involved in a Philadelphia- chromosome positive chronic myelogenous leukemia, is the target of Imatinib (Gleevec)?


Question: The major constituent of senile plaques in Alzheimer's disease is a 42-aa peptide, referred to as beta-amyloid (Abeta). Abeta is generated from a family of differentially spliced, type-1 transmembrane domain (TM)-containing proteins, called APP, by endoproteolytic processing. The major, relatively ubiquitous pathway of APP metabolism in cell culture involves cleavage by alpha-secretase, which cleaves within the Abeta sequence, thus precluding Abeta formation and deposition. An alternate secretory pathway, enriched in neurons and brain, leads to cleavage of APP at the N terminus of the Abeta peptide by beta-secretase, thus generating a cell-associated beta-C-terminal fragment (beta-CTF). A pathogenic mutation at codons 670/671 in APP (APP "Swedish") leads to enhanced cleavage at the beta-secretase scissile bond and increased Abeta formation. An inhibitor of vacuolar ATPases, bafilomycin, selectively inhibits the action of beta-secretase in cell culture, suggesting a requirement for an acidic intracellular compartment for effective beta-secretase cleavage of APP. beta-CTF is cleaved in the TM domain by gamma-secretase(s), generating both Abeta 1-40 (90%) and Abeta 1-42 (10%). Pathogenic mutations in APP at codon 717 (APP "London") lead to an increased proportion of Abeta 1-42 being produced and secreted. Missense mutations in PS-1, localized to chromosome 14, are pathogenic in the majority of familial Alzheimer's pedigrees. These mutations also lead to increased production of Abeta 1-42 over Abeta 1-40. Knockout of PS-1 in transgenic animals leads to significant inhibition of production of both Abeta 1-40 and Abeta 1-42 in primary cultures, indicating that PS-1 expression is important for gamma-secretase cleavages. Peptide aldehyde inhibitors that block Abeta production by inhibiting gamma-secretase cleavage of beta-CTF have been discovered.

Answer:
Which disease the London mutation involved in?