TASK DEFINITION: Given a question and a context passage, generate the answer having the word or phrase from the context passage. Here, the answer should be a shortest continous span from the passage.
PROBLEM: Context: Ca2+ is a ubiquitous intracellular messenger responsible for controlling numerous cellular processes including fertilization, mitosis, neuronal transmission, contraction and relaxation of muscles, gene transcription, and cell death. At rest, the cytoplasmic Ca2+ concentration [Ca2+]i is approximately 100 nM, but this level rises to 500-1,000 nM upon activation. In osteoblasts, the elevation of [Ca2+]i is a result of an increase in the release of Ca2+ from endoplasmic reticulum and/or extracellular Ca2+ influx through voltage gated Ca2+ channels. Many of the cellular effects of Ca2+ are mediated by the Ca2+ binding protein, calmodulin (CaM). Upon binding up to four calcium ions, CaM undergoes a conformational change, which enables it to bind to specific proteins eliciting a specific response. Calmodulin kinase II (CaMKII) is a major target of the Ca(2+)/CaM second messenger system. Once bound to Ca(2+)/CaM, the multimeric CaMKII is released from its autoinhibitory status and maximally activated, which then leads to an intraholoenzyme autophosphorylation reaction. Calcineurin (Cn) is another major target protein that is activated by Ca(2+)/CaM. Cn is a serine-threonine phosphatase that consists of a heterodimeric protein complex composed of a catalytic subunit (CnA) and a regulatory subunit (CnB). Upon activation, Cn directly binds to, and dephosphorylates nuclear factor of activated T cells (NFAT) transcription factors within the cytoplasm allowing them to translocate to the nucleus and participate in the regulation of gene expression. This review will examine the potential mechanisms by which calcium, CaM, CaMKII, and Cn/NFAT control osteoblast proliferation and differentiation.
Question: Which calcium/calmodulin dependent protein phosphatase is involved in the activation of the family of NFAT transcription factors (Nuclear Factors of Activated T cells)?

SOLUTION: can

PROBLEM: Context: Imatinib mesylate is a new drug that can inhibit the tyrosine kinase activity of Bcr-Abl, the receptors for platelet-derived growth factor receptor(PDGF) and stem cell factor, or c-kit. Chronic myeloid leukemia (CML) is distinguished by the presence of a reciprocal translocation between chromosomes 9 and 22 that results in a shortened chromosome 22, termed the Philadelphia(Ph) chromosome. As a result of the translocation, a fusion gene called the Bcr-Abl gene is created from two normal cellular genes, encoding a chimeric Bcr-Abl protein with a deregulated tyrosine kinase activity. The expression of Bcr-Abl tyrosine kinase has been shown to be necessary and sufficient for the transformed phenotype of CML cells. Imatinib can block the kinase activity of Bcr-Abl, thus inhibiting the proliferation of Ph-positive progenitors, and has shown activity against all phases of CML, though responses are most substantial and durable in patients in the chronic phase. An international phase III study which compared the efficacy of imatinib with that of interferon alpha combined with low-dose cytarabine in newly diagnosed chronic-phase CML showed the rate of major cytogenetic response at 24 months was 90%, including 82% of complete cytogenetic response. These results indicated that imatinib was superior to interferon-containing treatment as a first-line therapy. More than 10,000 patients worldwide, including those in Japan, have been treated with imatinib in clinical trials, and a lot of information has been accumulated on the use of this drug. The aim of this article is to review the use of this drug and the practical management of patients with chronic myeloid leukemia.
Question: What tyrosine kinase, involved in a Philadelphia- chromosome positive chronic myelogenous leukemia, is the target of Imatinib (Gleevec)?

SOLUTION: bcr-abl

PROBLEM: Context: To compare the change of urethral mobility after midurethral sling procedures in stress urinary incontinence with hypermobile urethra and assess these findings with surgical outcomes. 141 women who agreed to undergo midurethral sling operations due to stress urinary incontinence with hypermobile urethra were enrolled in this non-randomized prospective observational study. Preoperatively, urethral mobility was measured by Q tip test. All women were asked to complete Urogenital Distress Inventory Short Form (UDI-6) and Incontinence Impact Questionnaire Short Form (IIQ-7) to assess the quality of life. Six months postoperatively, Q tip test and quality of life assessment were repeated. The primary surgical outcomes were classified as cure, improvement and failure. Transient urinary obstruction, de novo urgency, voiding dysfunction were secondary surgical outcomes. Of 141 women, 50 (35. 5%) women underwent TOT, 91 (64.5%) underwent TVT. In both TOT and TVT groups, postoperative Q tip test values, IIQ-7 and UDI-6 scores were statistically reduced when compared with preoperative values. Postoperative Q tip test value in TVT group was significantly smaller than in TOT group [25(15-45) and 20 (15-45), respectively]. When we compared the Q-tip test value, IIQ-7 and UDI-6 scores changes, there were no statistically significant changes between the groups. Postoperative urethral mobility was more frequent in TOT group than in TVT group (40% vs 23.1%, respectively). Postoperative primary and secondary outcomes were similar in both groups. Although midurethral slings decrease the urethtal hypermobility, postoperative mobility status of urethra does not effect surgical outcomes of midurethral slings in women with preoperative urethral hypermobility.
Question: Which type of urinary incontinence is diagnosed with the Q tip test?

SOLUTION:
stress urinary incontinence