TASK DEFINITION: Given a passage with a context and an answer, 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.
PROBLEM: Context: The Notch signaling pathway is an evolutionary conserved signal transduction pathway involved in embryonic patterning and regulation of cell fates during development and self-renewal. Recent studies have demonstrated that this pathway is integral to a complex system of interactions, involving as well other signal transduction pathways, and implicated in distinct human diseases. Delta-like 1 (Dll1) is one of the known ligands of the Notch receptors. The role of the Notch ligands is less well understood. Loss-of-function of Dll1 leads to embryonic lethality, but reduction of Delta-like 1 protein levels has not been studied in adult stage.', 'Here we present the haploinsufficient phenotype of Dll1 and a missense mutant Dll1 allele (Dll1(C413Y)). Haploinsufficiency leads to a complex phenotype with several biological processes altered. These alterations reveal the importance of Dll1 mainly in metabolism, energy balance and in immunology. The animals are smaller, lighter, with altered fat to lean ratio and have increased blood pressure and a slight bradycardia. The animals have reduced cholesterol and triglyceride levels in blood. At the immunological level a subtle phenotype is observed due to the effect and fine-tuning of the signaling network at the different levels of differentiation, proliferation and function of lymphocytes. Moreover, the importance of the proteolytic regulation of the Notch signaling network emphasized.
Answer: In conclusion, slight alterations in one player of Notch signaling alter the entire organism, emphasizing the fine-tuning character of this pathway in a high number of processes.

SOLUTION: Does dll1 haploinsufficiency in adult mice lead to a complex phenotype affecting metabolic and immunological processes?

PROBLEM: Context: To investigate the differential expressions of nucleolin in invasive cervical squamous cell carcinoma, cervical intraepithelial neoplasms (CIN) and normal cervical epithelial tissues and explore the role of nucleolin in the carcinogenesis and progression of cervical squamous cell carcinoma.', 'Fifty specimens of invasive cervical squamous cell carcinoma, 65 specimens of CIN, and 60 adjacent normal cervical epithelial tissue specimens were examined immunohistochemically for nucleolin expression. The correlation of nucleolin expression levels with histological grades of invasive cervical squamous cell carcinoma and CIN were analyzed.', 'The specimens of invasive cervical squamous cell carcinoma showed a significantly higher positivity rate for nucleolin expression than CIN and normal cervical epithelial tissues, and the rate in CIN tissues was significantly higher than that in normal cervical epithelial tissues (P<0.01). The expression level of nucleolin was significantly higher in invasive cervical squamous cell carcinoma than in CIN and normal cervical epithelia tissues, and higher in CIN than in normal cervical epithelia tissues, whose immunostaining scores were 7.6±0.3, 6.1±0.2, and 3.0±0.2, respectively (P<0.01). The mean nucleolin immunostaining score was significantly higher in poorly and moderately differentiated than in highly differentiated cervical squamous cell carcinoma (7.9 vs 7.1, P<0.01), and higher in high grade CIN than in low grade CIN tissues (6.0 vs 4.0, P<0.01).
Answer: Overexpression of nucleolin plays an important role during carcinogenesis of cervical squamous cell carcinoma and is positively correlated with tumor progression of CIN and cervical squamous cell carcinoma.

SOLUTION: Is [ Nucleolin expression correlated with carcinogenesis and progression of cervical squamous cell carcinoma ]?

PROBLEM: Context: We sought to determine whether the flow-dependent changes in Doppler-derived valve effective orifice area (EOA) are real or due to artifact.', 'It has frequently been reported that the EOA may vary with transvalvular flow in patients with aortic stenosis. However, the explanation of the flow dependence of EOA remains controversial and some studies have suggested that the EOA estimated by Doppler-echocardiography (EOA(Dop)) may underestimate the actual EOA at low flow rates.', 'One bioprosthetic valve and three rigid orifices were tested in a mock flow circulation model over a wide range of flow rates. The EOA(Dop) was compared with reference values obtained using particle image velocimetry (EOA(PIV)).', 'There was excellent agreement between EOA(Dop) and EOA(PIV) (r2 = 0.94). For rigid orifices of 0.5 and 1.0 cm2, no significant change in the EOA was observed with increasing flow rate. However, substantial increases of both EOA(Dop) and EOA(PIV) were observed when stroke volume increased from 20 to 70 ml both in the 1.5 cm2 rigid orifice (+52% for EOA(Dop) and +54% for EOA(PIV)) and the bioprosthetic valve (+62% for EOA(Dop) and +63% for EOA(PIV)); such changes are explained either by the presence of unsteady effects at low flow rates and/or by an increase in valve leaflet opening.
Answer: The flow-dependent changes in EOA(Dop) are not artifacts but represent real changes in EOA attributable either to unsteady effects at low flow rates and/or to changes in valve leaflet opening. Such changes in EOA(Dop) can be relied on for clinical judgment making.

SOLUTION:
Are flow-dependent changes in Doppler-derived aortic valve effective orifice area real and not due to artifact?