Given a passage classify if the passage has a definite objective/aim/goal or not. Output '1' if the passage has a defininte objective/aim/goal and output '0' if the passage does not have a definite objective/aim/goal.

[EX Q]: FoxO transcription factors have been reported to play pivotal roles in tumorigenesis and drug resistance. The mechanisms underlying the tumor suppression function of FoxOs in human cancers remain largely unknown. Aberrant expression and activation of Nrf2 often correlate with chemoresistance and poor prognosis. Here, we report that FoxO3 directs the basal transcription of Kelch-like ECH-associated protein 1 (Keap1), an adaptor protein that bridges Nrf2 to Cul3 for degradation. FoxO3 depletion resulted in Keap1 down-regulation, thereby activating Nrf2 signaling. We further demonstrated that inhibition of the FoxO3-Keap1 axis accounts for Nrf2 induction and activation induced by constitutively active AKT signaling or tumor necrosis factor treatment. Unlike previous findings, FoxO3 silencing led to decreased reactive oxygen species production, therefore protecting cells from oxidative stress-induced killing in an Nrf2-dependent manner. Importantly, FoxO3 deficiency strongly potentiated tumor formation in nude mice and rendered cholangiocarcinoma xenografts resistant to cisplatin-induced cell death by activating Nrf2. Additionally, we found that clinical cholangiocarcinoma samples displayed FoxO3-Keap1 down-regulation and Nrf2 hyperactivation, underscoring the essential roles of these proteins in cholangiocarcinoma development.
[EX A]: 0

[EX Q]: B-type natriuretic peptide (BNP)-natriuretic peptide receptor A (NPR-A) receptor signalling inhibits cardiac sympathetic neurotransmission, although C-type natriuretic peptide (CNP) is the predominant neuropeptide of the nervous system with expression in the heart and vasculature. We hypothesized that CNP acts similarly to BNP, and that transgenic rats (TGRs) with neuron-specific overexpression of a dominant negative NPR-B receptor would develop heightened sympathetic drive.', 'Mean arterial pressure and heart rate (HR) were significantly (P<0.05) elevated in freely moving TGRs (n=9) compared with Sprague Dawley (SD) controls (n=10). TGR had impaired left ventricular systolic function and spectral analysis of HR variability suggested a shift towards sympathoexcitation. Immunohistochemistry demonstrated co-staining of NPR-B with tyrosine hydroxylase in stellate ganglia neurons. In SD rats, CNP (250nM, n=8) significantly reduced the tachycardia during right stellate ganglion stimulation (1-7Hz) in vitro whereas the response to bath-applied norepinephrine (NE, 1M, n=6) remained intact. CNP (250nM, n=8) significantly reduced the release of
[EX A]: 1

[EX Q]: In patients presenting with a breast lesion, when initial core biopsy histology falls into the category of "uncertain malignant potential" (i.e. a B3 lesion), the next line of investigation has traditionally been a surgical biopsy (SBx). Vacuum-assisted biopsy (VAB) may be a viable minimally invasive alternative to SBx for B3 lesions. The primary aims of this study were to establish whether VAB reduces the need for surgical biopsy and determine VAB sensitivity for carcinoma following initial B3 histology.', 'B3 lesion data was collected from 2004 to 2013 retrospectively, from a single institution that utilises both VAB and SBx.', 'A total of 413 lesions were categorised B3 on initial biopsy. Mean age was 61 years (range: 24-91 years). Mean follow up was 52 months (range: 19-60 months). 156 patients (38%) underwent VAB. Only 20% of patients underwent VAB in 2004, with an increase to 95% by 2013. VAB histology revealed twelve carcinomas, all of which progressed to surgical excision. In six cases, a SBx was required following VAB in order to provide further diagnostic information. In one case, carcinoma was missed on VAB.
[EX A]:
1