Given a passage, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.

Q: Angiotensin II (Ang II) signaling has been implicated in cardiac arrhythmogenesis, which involves induction of reactive oxygen species (ROS). It was shown that Ang II can activate Ca/Calmodulin kinase II (CaMKII) by oxidation via a NADPH oxidase 2 (NOX2)-dependent pathway leading to increased arrhythmic afterdepolarizations. Interestingly, cAMP-dependent protein kinase A (PKA) which regulates similar targets as CaMKII has recently been shown to be redox-sensitive as well.', 'This study aims to investigate the distinct molecular mechanisms underlying Ang II-related cardiac arrhythmias with an emphasis on the individual contribution of PKA vs. CaMKII.', 'Isolated ventricular cardiac myocytes from rats and mice were used. Ang II exposure resulted in increased NOX2-dependent ROS generation assessed by expression of redox-sensitive GFP and in myocytes loaded with ROS indicator MitoSOX. Whole cell patch clamp measurements showed that Ang II significantly increased peak Ca and Na current (ICa and INa) possibly by enhancing steady-state activation of ICa and INa. These effects were absent in myocytes lacking functional NOX2 (gp91phox(-/-)). In parallel experiments using PKA inhibitor H89, the Ang II effects on peak INa and ICa were also absent. In contrast, genetic knockout of CaMKIIδ (CaMKIIδ(-/-)) did not influence the Ang II-dependent increase in peak ICa and INa. On the other hand, Ang II enhanced INa inactivation, increased late INa and induced diastolic SR (sarcoplasmic reticulum) Ca leak (confocal Ca spark measurements) in a CaMKIIδ-, but not PKA-dependent manner. Surprisingly, only the increase in diastolic SR Ca leak was absent in gp91phox(-/-)myocytes suggesting that Ang II regulates INa inactivation in a manner dependent on CaMKII- but not on NOX2. Finally, we show that Ang II increased the propensity for cellular arrhythmias, for which PKA and CaMKII contribute, both dependent on NOX2.

A: Does nADPH oxidase 2 mediate angiotensin II-dependent cellular arrhythmias via PKA and CaMKII?
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Q: IQ-domain GTPase-activating protein 1 (IQGAP1) binds to Dishevelled (Dvl) and functions as a modulator of Dvl nuclear localization in Xenopus embryos. However, the relationship between IQGAP1 and Dvl in tumor tissues is unclear.', 'We used immunohistochemistry to assess the expressions of IQGAP1 and Dvl in a cohort of 111 non-small cell lung cancer (NSCLC) patients. Association of their localization expressions with clinicopathological factors was also analyzed.', 'The positive rate of IQGAP1 in primary tumors was 48.6% (54/111) for its cytoplamic expression, 9.0% (10/111) for nuclear expression and 31.5% (35/111) for membranous expression; the positive rate of Dvl was 65.8% (73/111) for cytoplamic expression, 9.9% (11/111) for nuclear expression and 10.8% (12/111) for membranous expression. Coexpression rate of IQGAP1 and Dvl was 77.8% (42/54) in the cytoplasm, 80.0% (8/10) in the nucleus and 8.6% (3/35) in the membrane. Coexpression of IQGAP1 and Dvl in the cytoplasm and nucleus were significantly correlated (P<0.05), but not in the membrane (P>0.05). The positive expression rates of cyclin D1 and c-myc were significantly higher in the group of IQGAP1 and Dvl coexpression in the nucleus than that in the cytoplasm. Coexpression rate of IQGAP1 and Dvl in the cytoplasm and nucleus was significantly higher in lymph nodal metastases (63.3%, 19/30) than in primary growths (38.3%, 31/81), correlating with poor prognosis. Five-year survival time after resection in the group with their coexpression in the cytoplasm and nucleus was significantly lower than that with no coexpression (44.705±3.355 vs 58.403±2.543 months, p<0.05).

A: Is coexpression of IQ-domain GTPase-activating protein 1 ( IQGAP1 ) and Dishevelled ( Dvl ) correlated with poor prognosis in non-small cell lung cancer?
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Q: The objective was to evaluate whether endobronchial ultrasonography (EBUS) or endoscopic ultrasonography (EUS) staging techniques of the mediastinum for lung cancer can change the treatment plan compared with the "gold standard" of surgical staging.', 'Patients were retrospectively identified from a prospectively collected database. Endoscopic staging was compared with the "gold standard" cervical mediastinoscopy (CM). In cases where mediastinoscopy was not performed, EBUS/EUS was compared with "ideal" CM, a virtual procedure, which was assumed to have 100% rates of sensitivity and specificity.', 'EBUS was performed in 324 patients (99%), EUS in 295 patients (90%), and CM in 101 patients (31%); 226 patients (69%) were assumed to have undergone a virtual ideal CM and a virtual surgical mediastinal staging; 108 positive biopsies (33.0%) with endosonography had sampling of targets that were out of the scope of CM. Distant metastatic disease was diagnosed by EBUS/EUS in 7 patients (2.1%); 22 patients (6.7%) had positive targets outside the reach of the CM or virtual CM. If the 14 patients who had positive stations 5, 6, 10, and 11 are excluded (accessible with anterior mediastinotomy or extended cervical mediastinoscopy), there were 6 patients (1.8%) in whom endosonography upstaged the patient over ideal surgical mediastinal staging. In 20 patients (6.1%), ultrasound-guided biopsy made the diagnoses, which changed the treatment plan over CM and ideal CM.

A:
Does endoscopic Mediastinal Staging in Lung Cancer be Superior to `` Gold Standard '' Surgical Staging?
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