In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.

Ex Input:
Context: Sleep disturbances have been thought to augment pain. Sleep deprivation has been proven to produce hyperalgesic effects. It is still unclear whether these changes are truly specific to pain and not related to general changes in somatosensory functions. The aim of the present study was to evaluate the effect of total sleep deprivation on thermal pain thresholds (heat, cold) and pain complaints. Thermal detection thresholds (warmth, cold) were included as covariates to determine the contribution of somatosensory functions to changes in pain processing.', 'Twenty healthy volunteers were randomly assigned either to two nights of total sleep deprivation or to two nights of undisturbed night sleep. Sleep deprivation nights were separated by two days with normal night sleep. Heat and cold pain thresholds as well as warmth and cold detection thresholds were measured by use of a peltier thermode in the evening before and the morning after each deprivation or control night. Pain complaints were examined by use of a questionnaire in parallel.', 'During treatment nights, sleep deprivation produced a significant overnight decrease in heat pain thresholds. Cold pain thresholds tended to decrease also during sleep deprivation, whereas the warmth and cold detection thresholds remained unaffected. Accordingly, no substantial contributions of the changes in thermal detection thresholds to the changes in thermal pain thresholds were determined by regression analyses. Pain complaints were not induced by sleep deprivation.\Question: Does sleep deprivation affect thermal pain thresholds but not somatosensory thresholds in healthy volunteers?

Ex Output:
The present findings suggest that sleep deprivation produces hyperalgesic changes that cannot be explained by nonspecific alterations in somatosensory functions.


Ex Input:
Context: To investigate the role of S100A3 and the effect of S100A3 inhibition on human castration-resistant prostate cancer (CRPC) cells by using in vitro and in vivo functional assays.', 'Using human CRPC cells (PC3 and DU145), S100A3 expression levels were assessed by reverse transcription-polymerase chain reaction and Western blot analysis. After S100A3-specific small interfering ribonucleic acid (RNA) treatment, cell viability was determined by Cell Counting Kit-8 assay, and apoptotic cell fractions were evaluated by flow cytometry. The invasive properties of these cells and the expression pattern of matrix metalloproteinases (MMPs) were assessed using transwell migration assays, reverse transcription-polymerase chain reaction, and gelatin zymography. Finally, the in vivo efficacy of S100A3 inhibition on human CRPC cells was investigated using human tumor xenograft models in nude mice.', 'Human CRPC cells showed overexpression of S100A3, and its suppression reduced cell viability owing to apoptotic cell death. Additionally, S100A3 inhibition decreased the invasiveness of human CRPC cells. Moreover, MMP-2 and MMP-9 were downregulated in PC3, whereas only MMP-9 was downregulated in D145 after S100A3 inhibition. In human CRPC xenograft models, we noted a marked reduction in tumor growth in mice injected with S100A3 short hairpin RNA-transfected PC3 and DU145 cells.\Question: Does s100A3 suppression inhibit in vitro and in vivo tumor growth and invasion of human castration-resistant prostate cancer cells?

Ex Output:
Human CRPC cells showed upregulation of S100A3 expression, and S100A3 inhibition reduced tumor cell viability. S100A3 inhibition reduced invasion capability with downregulation of MMP expression. More importantly, S100A3 inhibition resulted in tumor growth suppression in human CRPC xenograft models, suggesting S100A3 could serve as a novel therapeutic target for the treatment of human CRPC.


Ex Input:
Context: The proliferation of mural epithelial cells is a major cause of progressive cyst enlargement in autosomal-dominant polycystic kidney disease (ADPKD). Adenosine 3', 5' cyclic monophosphate (cAMP) stimulates the proliferation of cells from ADPKD cysts, but not cells from normal human kidney cortex (HKC), through the activation of protein kinase A (PKA), mitogen-activated protein kinase kinase (MEK), and extracellular signal-regulated kinase (ERK/MAPK). In the current study, we examined the signaling pathway between PKA and MEK in ADPKD and HKC cells.", 'Primary cultures of human ADPKD and HKC cells were prepared from nephrectomy specimens. We determined the effects of cAMP and epidermal growth factor (EGF) on the activation of ERK, B-Raf and Raf-1 in ADPKD and HKC cells by immune kinase assay and Western blot.', '8-Br-cAMP increased phosphorylated ERK (2.7- +/- 0.6-fold, N = 7), and B-Raf kinase activity (3.6- +/- 1.1-fold, N = 5) in cells from ADPKD kidneys; levels of phosphorylated Raf-1 were not changed. Inhibition of PKA by H89 strikingly decreased cAMP-stimulated phosphorylation of ERK and B-Raf, and MAPK inhibition by PD98059 blocked the effect of the nucleotide to activate ERK. By contrast, in HKC cells 8-Br-cAMP did not activate B-Raf and ERK. EGF stimulated the phosphorylation of ERK and Raf-1 in both ADPKD and HKC cells, but had no effect on B-Raf. 8-Br-cAMP and EGF conjointly increased ERK activation above that of either agonist alone in ADPKD cells, and this combined effect was abolished by PD98059, indicating that ERK was activated by EGF- and cAMP-responsive cascades that converge at MAPK.\Question: Does cyclic AMP activate B-Raf and ERK in cyst epithelial cells from autosomal-dominant polycystic kidneys?

Ex Output:

cAMP activates ERK and increases proliferation of ADPKD epithelial cells, but not cells from normal human kidney cortex, through the sequential phosphorylation of PKA, B-Raf and MAPK in a pathway separate from, but complementary to, the classical receptor tyrosine kinase cascade. Consequently, cAMP and EGF have great potential to accelerate the progressive enlargement of renal cysts.