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: Non-viral gene transfer efficiency is low as compared to viral vector systems. Here we describe the discovery of new drugs that are capable of enhancing non-viral gene transfer into mammalian cells using a novel two-stage screening procedure.', 'First, potential candidates are preselected from a molecular library at various concentrations by a semi-automated yeast transfection screen (YTS). The maximal transfection efficiency of every positive drug is subsequently determined in independent experiments at the optimal concentration and compared to the inhibitory effect of the drug on cell growth (IC50). In a subsequent mammalian cell transfection screen (MTS), the maximal transfection efficiency and the IC50 are determined for all preselected drugs using a human cell line and a luciferase reporter gene construct.', 'Employing our novel system we have been able to identify a new class of transfection enhancers, the tricyclic antidepressants (i.e. doxepin, maprotiline, desipramine and amoxapine). All positive drugs enhanced gene transfer in both yeast and human cell lines, but lower concentrations were sufficient for mammalian cells. With a triple combination of doxepin, amoxapine and chloroquine we obtained a transfection efficiency that exceeded that of chloroquine, one of the best-known transfection enhancers of mammalian cells, by nearly one order of magnitude.\Question: Does novel two-stage screening procedure lead to the identification of a new class of transfection enhancers?

Ex Output:
Non-viral gene transfer efficiency can be increased significantly using new transfection enhancers that are identified by a novel, semi-automated two-stage screening system employing yeast cells in the first and specific human target cells in the second round.


Ex Input:
Context: Secretory phospholipases A2 (sPLA2) initiate the biosynthesis of eicosanoids, are increased in the airways of people with severe asthma, and induce mucin hypersecretion. We used IL-13-transformed, highly enriched goblet cells and differentiated (ciliary cell-enriched) human bronchial epithelial cell culture to evaluate the relative contribution of ciliated and goblet cells to airway sPLA2 generation and response. We wished to determine the primary source(s) of sPLA2 and leukotrienes in human airway epithelial cells.', 'Human bronchial epithelial cells from subjects without lung disease were differentiated to a ciliated-enriched or goblet-enriched cell phenotype. Synthesis of sPLA2, cysteinyl leukotrienes (cysLTs), and airway mucin messenger RNA and protein was measured by real-time-polymerase chain reaction and an enzyme-linked immunosorbent assay, and the localization of mucin and sPLA2 to specific cells types was confirmed by confocal microscopy.', 'sPLA2 group IIa, V, and X messenger RNA expression was increased in ciliated-enriched cells (P < .001) but not in goblet-enriched cells. sPLA2 were secreted from the apical (air) side of ciliated-enriched cells but not goblet-enriched cells (P < .001). Immunostaining of sPLA2 V was strongly positive in ciliated-enriched cells but not in goblet-enriched cells. sPLA2 released cysLTs from goblet-enriched cells but not from ciliated-enriched cells, and this result was greatest with sPLA2 V (P < .05). sPLA2 V increased goblet-enriched cell mucin secretion, which was inhibited by inhibitors of lipoxygenase or cyclooxygenase (P < .02).\Question: Are secretory phospholipases A2 secreted from ciliated cells and increase mucin and eicosanoid secretion from goblet cells?

Ex Output:
sPLA2 are secreted from ciliated cells and appear to induce mucin and cysLT secretion from goblet cells, strongly suggesting that airway goblet cells are proinflammatory effector cells.


Ex Input:
Context: Genetic variability in hepatic uptake was recently shown to influence the disposition and cholesterol-lowering effects of statins. Ezetimibe, an inhibitor of the intestinal cholesterol uptake protein Niemann-Pick C 1 like 1, is another drug for which genetic polymorphisms of hepatic organic anion transporting polypeptides (OATPs) are expected to be of clinical relevance because ezetimibe undergoes intensive enterohepatic circulation for which hepatic uptake transporters may be rate-limiting determinants.', 'Using OATP1B3-, OATP2B1-, and OATP1B1-transfected HEK cells, including the OATP1B1 variants OATP1B1*1b and OATP1B1*5, we measured the uptake of ezetimibe and its glucuronide and we analyzed the competition with the common OATP-substrate bromosulfophthalein. Disposition and sterol-lowering effects of 20-mg ezetimibe were measured in 35 healthy participants genotyped for OATP1B1, ABCB1, ABCC2, and UGT1A1.', 'Ezetimibe glucuronide inhibited bromosulfophthalein uptake in all OATP-transfected cells (50% inhibitory concentration (IC50): 0.14-0.26 mumol/l) whereas ezetimibe was 30-100 times less potent. Only the glucuronide was accumulated significantly in cells expressing OATP1B1 and OATP2B1. Its uptake in cells expressing OATP1B1*1b and *5 was reduced. In-vivo studies showed there was a gene-dose-dependent decrease in the area under the curve of ezetimibe in participants with the OATP1B1*1b protein (*1a/*1a, N=12, 112+/-66 ngxh/ml vs. *1a/*1b, N=8, 88+/-39 ngxh/ml vs. *1b/*1b, N=5, 55+/-18 ngxh/ml; Jonkheere-Terpstra, P=0.041) and a tendency for increased glucuronide exposure (704+/-296 vs. 878+/-369 vs. 1059+/-363 ngxh/ml; P=0.092). Fecal ezetimibe excretion was significantly decreased whereas renal glucuronide excretion was increased in carriers of *1b/*1b. Fecal excretion was also diminished in carriers of OATP1B1*5 and *15. The sterol-lowering effect of ezetimibe was not influenced by OATP1B1 polymorphisms.\Question: Is disposition of ezetimibe influenced by polymorphisms of the hepatic uptake carrier OATP1B1?

Ex Output:

Pharmacokinetics of ezetimibe is influenced by OATP1B1 polymorphisms in healthy participants after single dose administration.