TASK DEFINITION: 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.
PROBLEM: Hydrocortisone therapy is based on a dosing regimen derived from estimates of cortisol secretion, but little is known of how the dose should be distributed throughout the 24 h. We have used deconvolution analysis of 24-h serum cortisol profiles to determine 24-h cortisol secretion and distribution to inform hydrocortisone dosing schedules in young children and older adults.', 'Twenty four hour serum cortisol profiles from 80 adults (41 men, aged 60-74 years) and 29 children (24 boys, aged 5-9 years) were subject to deconvolution analysis using an 80-min half-life to ascertain total cortisol secretion and distribution throughout the 24-h period.', 'Mean daily cortisol secretion was similar between adults (6.3 mg/m(2) body surface area/day, range 5.1-9.3) and children (8.0 mg/m(2) body surface area/day, range 5.3-12.0). Peak serum cortisol concentration was higher in children compared with adults, whereas nadir serum cortisol concentrations were similar. Timing of the peak serum cortisol concentration was similar (07.05-07.25), whereas that of the nadir concentration occurred later in adults (midnight) compared with children (22.48) (P = 0.003). Children had the highest percentage of cortisol secretion between 06.00 and 12.00 (38.4%), whereas in adults this took place between midnight and 06.00 (45.2%).

SOLUTION: 0

PROBLEM: Regulation of the cytoskeleton is a central feature of cell migration. The formin family of proteins controls the rate of actin nucleation at its barbed end. Thus, formins are predicted to contribute to several important cell processes such as locomotion, membrane ruffling, vesicle endocytosis, and stress fiber formation and disassociation.', 'In this study we investigated the functional role of Formin1-isoform4 (Fmn1-IV) by using genetically null primary cells that displayed augmented protrusive behaviour during wound healing and delayed cell spreading. Cells deficient of Fmn1-IV also showed reduced efficiency of focal adhesion formation. Additionally, we generated an enhanced green fluorescence protein (EGFP)-fused Fmn1-IV knock-in mouse to monitor the endogenous subcellular localization of Fmn1-IV. Its localization was found within the cytoplasm and along microtubules, yet it was largely excluded from adherens junctions.

SOLUTION: 0

PROBLEM: Zuo-Jin-Wan (ZJW), a traditional Chinese medicine formula, has been identified to be effective against drug resistance in cancer. In the present study, we investigated the effect of ZJW on acquired oxaliplatin-resistant and the PI3K/Akt/NF-κB pathway in vitro.', 'We tested the dose-response relationship of ZJW on reversing drug-resistance by CCK-8 assay and flow cytometry analysis in vitro. The protein expression of P-gp, MRP-2, LRP, and ABCB1 mRNA expression level were evaluated by Western blot and quantitative RT-PCR. The activities of PI3K/Akt/NF-κB pathway were also examined with or without ZJW, including Akt, IκB, p65 and their phosphorylation expression.', 'We found that ZJW significantly enhanced the sensitivity of chemotherapeutic drugs and increased oxaliplatin (L-OHP)-induced cell apoptosis in a time- and dose-dependent manner. Moreover, both ZJW and a PI3K specific inhibitor (LY294002) suppressed phosphorylation of Akt (Ser473) and NF-κB, which is necessary in the activation of the PI3K/Akt/NF-κB pathway. The effect of ZJW in reversing drug-resistance and suppressing phosphorylation of Akt (Ser473) and NF-κB were weakened after treatment with a PI3K/Akt activator in HCT116/L-OHP cells.

SOLUTION:
0