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: To chemically identify and quantify glucose degradation products in heat sterilized fluids for peritoneal dialysis.', 'Three different brands of commercial PD-fluids and one laboratory made fluid, sterilized either by heat or filtration, were investigated for the presence of aldehydes.', 'Aldehydes were identified and quantified using high performance liquid chromatography and gas chromatography.', 'The tested brands of heat sterilized PD-fluids were found to contain several different aldehydes while the sterile filtered PD-fluid contained none. The highest concentrations in commercial PD-fluids of these aldehydes were: acetaldehyde (420 microns), glyoxal (14 microns), methylglyoxal (12 microns) and formaldehyde (11 microns). Valeraldehyde was also identified but not quantified. The presence of 5-HMF (15 microns) and 2-furaldehyde (2 microns), which has been identified by others, was confirmed.
Answer: The heat sterilization of commercial PD-fluids gives rise to several aldehydes which may contribute to adverse effects of PD-fluids on patients.

SOLUTION: Does heat sterilization of fluids for peritoneal dialysis give rise to aldehydes?

PROBLEM: Context: Frontotemporal dementia is a neurodegenerative disease affecting mostly the frontal and/or temporal lobes, with neuronal loss and intraneuronal and/or intraglial inclusions composed of hyperphosphorylated microtubule-associated protein tau and ubiquitin. Missense and splice site mutations in the TAU gene have been identified in approximately 15% of all frontotemporal dementia cases. In this study, we evaluated the involvement of mutations in the TAU gene in development of frontotemporal dementia phenotype in patients of French or English Canadian origins.', 'Fourteen patients with frontotemporal dementia phenotype and 98 normal controls were recruited for the study. The TAU gene was screened by sequencing and denaturing high performance liquid chromatography.', 'No mutations, except some new polymorphisms, were detected in the TAU gene of these patients. One polymorphism, however, may play a role in pathogenesis.
Answer: Our results agree with previous work suggesting that mutations in this gene are not a frequent cause of the frontotemporal dementia phenotype in Canadian patients.

SOLUTION: Are tAU mutations a predominant cause of frontotemporal dementia in Canadian patients?

PROBLEM: Context: To assess the activity of mTOR and downstream effector proteins in the mTOR pathway after treatment with a dual mTOR complex 1 and 2 (mTORC1/2) inhibitor (PP242) compared with that of mTOR complex 1 (mTORC1) inhibitor (rapamycin) using a xenograft tumor model.', 'Pheochromocytoma PC12 cell were xenografted into nude mice. Animals were treated with PP242 and rapamycin. Mean tumor volume was compared across groups. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining was used to detect apoptosis. Immunoblot analysis was performed to assess mTORC1/2 activity using p-Akt, p-S6, and p-4E-BP1. The expression of the antiapoptotic protein Bcl-2, pro-apoptotic protein Bax, and the mediator of angiogenesis vascular endothelial growth factor were also investigated.', 'The mean tumor volume of PP242 was significantly lower than in other groups. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling results showed that PP242 markedly increased cell apoptosis compared with other groups. Immunoblot analysis of tumor lysates treated with PP242 demonstrated inhibition of activated p-Akt. We also observed that only PP242, but not rapamycin, significantly reduced Bcl-2 expression and markedly increased Bax expression. Rapamycin decreased vascular endothelial growth factor expression, but not nearly as striking as seen in the PP242 group.
Answer: Our study showed that PP242 showed strong antitumor activity in a pheochromocytoma PC12 cell tumor model. Based on our study, dual mTORC1/2 kinase inhibitors warrant further investigation as a potential treatment for malignant pheochromocytomas or paragangliomas.

SOLUTION:
Does the dual mTORC1 and mTORC2 inhibitor PP242 show strong antitumor activity in a pheochromocytoma PC12 cell tumor model?