Given a context passage, generate a question from the passage such that its answer is shortest continous span from the passage.

Input: Consider Input: Chronic myeloid leukemia (CML) is arguably the best understood of all human malignancies. Its origins in the hematopoietic stem cell can be traced to a reciprocal translocation involving chromosomes 9 and 22, dubbed the Philadelphia chromosome, which is observed in essentially all patients. The resulting fusion gene, BCR/ABL, encodes an activated tyrosine kinase that can act alone to induce a CML-like syndrome in mouse models. These animal models have validated BCR/ABL as a target for the development of specific pharmaceutical inhibitors. The kinase inhibitor imatinib mesylate (Gleevec) is highly specific, effective, and minimally toxic, but may not effect cures as a single agent, particularly in patients with accelerated and blast-phase disease. Resistance to imatinib can confound therapy. Surprisingly, a high percentage of resistant cases manifest intact or augmented BCR/ABL signaling, suggesting that this oncoprotein, or signaling pathways emanating from it, remain viable targets. Combination chemotherapy is under active investigation, and among the most compelling strategies is dual treatment with agents that both target BCR/ABL signal transduction. BCR/ABL activates Ras, and compounds designed to antagonize Ras function called farnesyl transferase inhibitors (FTIs) have shown potent activity in vitro and in animal models of BCR/ABL-induced leukemia. Initial clinical trials in patients with refractory acute myeloid leukemia and CML in blast crisis have shown significant activity, suggesting that trials combining imatinib and FTIs are warranted.

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


Input: Consider Input: Notting hill is a small town west of London. Here lives shy William, a divorced man, who owns a little travel-book store. It was a Wednesday, when the poor shop keeper happened to meet Anna Scott ,a movie star who walked into his shop. They ran across each other in the street again. And they found themselves falling in love. But how could a poor man keep the love of a famous star? Their lives and their worlds were so different. Six months later, Anna was in London again for her new film. She came to William's thought ... Length :110 minutes Director:David Duning Cast:Julia Roberts(actress), Hugh Grant(actor)

Output: What is the passage mainly discussing ?


Input: Consider Input: -Synuclein (Syn), which forms amyloid fibrils, is linked to the neuronal pathology of Parkinson's disease, as it is the major fibrillar component of Lewy bodies, the inclusions that are characteristic of the disease. Oligomeric structures, common to many neurodegenerative disease-related proteins, may in fact be the primary toxic species, while the amyloid fibrils exist either as a less toxic dead-end species or even as a beneficial mechanism for clearing damaged proteins. To alter the progression of the aggregation and gain insights into the prefibrillar structures, we determined the effect of heme on Syn oligomerization by several different techniques, including native (nondenaturing) polyacrylamide gel electrophoresis, thioflavin T fluorescence, transmission electron microscopy, atomic force microscopy, circular dichroism, and membrane permeation using a calcein release assay. During aggregation, heme is able to bind the Syn in a specific fashion, stabilizing distinct oligomeric conformations and promoting the formation of Syn into annular structures, thereby delaying and/or inhibiting the fibrillation process. These results indicate that heme may play a regulatory role in the progression of Parkinson's disease; in addition, they provide insights into how the aggregation process may be altered, which may be applicable to the understanding of many neurodegenerative diseases.


Output: Which is the primary protein component of Lewy bodies?