TASK DEFINITION: Given a context passage, generate a question from the passage such that its answer is shortest continous span from the passage.
PROBLEM: Throughout 1476, supporters of Joanna from the nobility continued to submit to Isabella and Ferdinand, particularly those from the Pacheco-Giron lineage: Juan Tellez-Giron and his brother Rodrigo; Luis de Portocarrero; and, in September, the Marquis of Villena. In November 1476, Isabella's troops captured the castle of Toro. In the following months, they took control of the last bordering localities controlled by the Portuguese and dealt with their adversaries in Extremadura. In July 1477, Isabella arrived in Seville, the most populous city of Castile, with the objective of asserting her power over the nobility of Andalusia. In April 1476, Isabella and Ferdinand gave their first exculpation to the Marquis of Cadiz. He had been regaining power while his rival, the Duke of Medina Sidonia, initially the main Isabella supporter in Andalusia, had been falling into dishonour. Through skilful negotiations, the Queen managed to take control of the main strongholds of Seville occupied by the Marquis and the Duke and, instead of returning them to their legitimate owners, named others as their heads. She prohibited both nobles from entering the city of Seville, under the pretext that their simultaneous presence there would risk violent conflicts. In this way the Duke's political dominance over Seville disappeared, and the city passed into the control of the Crown. One of the few nobles that refused to submit to the monarchs was Marshall Fernan Arias de Saavedra. Isabella's troops laid siege to his fortress at Utrera, and conquered it by assault in March 1478. The defeated suffered harsh repression. The first son of the monarchs, John of Aragon and Castile, was born in Seville on June 30, 1478, which opened new possibilities for dynastic stability of the Isabellian side.

SOLUTION: What event happened first, Isabella arriving in Seville or Isabella and Ferdinand giving their first exculpation to the Marquis of Cadiz?

PROBLEM: The overlap between symptoms of PTSD and MDD is substantial. PTSD symptoms arise after a traumatic experience and the trauma is present in all of the diagnostic clusters. In individuals who have experienced a trauma a long time before, it is difficult to establish the exact moment of onset of their symptoms in relation to the trauma suffered. We proposed to raise awareness among operators who may encounter this problem, with the aim of providing them with valuable help in order to achieve a correct differential diagnosis. A sample of subjects suffering from PTSD without comorbidity was assessed to confirm the diagnosis and the severity of post-traumatic symptoms. The Kruskal-Wallis test was used to compare any modifications in the parameters analyzed through the Davidson Trauma Scale with the presence and severity of depressive symptoms as evaluated by the Hamilton-D scale. Half of the PSTD patients recruited showed values of HAM-D > 18, although an active Major Depressive Episode was clinically excluded. Symptom of "numbing", despite being different from the apathy experienced in depression, is identified as a depressive symptom by the HAM-D. Giving prevalence to depressive symptoms may be misleading for diagnosis and may ultimately result in inappropriate treatment.

SOLUTION: Symptoms of which disorder are evaluated with the Davidson Trauma Scale?

PROBLEM: Imatinib was developed as the first molecularly targeted therapy to specifically inhibit the BCR-ABL kinase in Philadelphia chromosome (Ph)-positive chronic myeloid leukemia (CML). Because of the excellent hematologic and cytogenetic responses, imatinib has moved toward first-line treatment for newly diagnosed CML. However, the emergence of resistance to imatinib remains a major problem in the treatment of Ph-positive leukemia. Several mechanisms of imatinib resistance have been identified, including BCR-ABL gene amplification that leads to overexpression of the BCR-ABL protein, point mutations in the BCR-ABL kinase domain that interfere with imatinib binding, and point mutations outside of the kinase domain that allosterically inhibit imatinib binding to BCR-ABL. The need for alternative or additional treatment for imatinib-resistant BCR-ABL-positive leukemia has guided the way to the design of a second generation of targeted therapies, which has resulted mainly in the development of novel small-molecule inhibitors such as AMN107, dasatinib, NS-187, and ON012380. The major goal of these efforts is to create new compounds that are more potent than imatinib and/or more effective against imatinib-resistant BCR-ABL clones. In this review, we discuss the next generation of BCR-ABL kinase inhibitors for overcoming imatinib resistance.

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