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.

Input: Consider Input: Context: Endoplasmic reticulum (ER) stress is induced in many forms of chronic liver disease and may promote the development of hepatocellular carcinoma. The activator protein 1 (AP-1) complex is a transcription factor that promotes hepatic carcinogenesis in response to cellular stress. The aim of this study was to determine the role of ER stress in the regulation of the hepatic AP-1 complex.', 'Human hepatocellular carcinoma (HepG2) cells and C57BL/6J mice were subjected to pharmacologic ER stress and the expression of AP-1-associated genes and proteins was assessed. To determine the role of MAPK signaling in ER stress-induced AP-1 activation, ER stress was induced in JNK- and ERK-inhibited HepG2 cells.', 'Induction of ER stress promoted the activation of both Jun- and Fos-related genes and proteins of the AP-1 complex in HepG2 cells and murine liver. Inhibition of ERK phosphorylation in HepG2 cells completely prevented ER stress-induced activation of the fos-related components of AP-1 whereas activation of Jun-related components was only partially attenuated. Conversely, inhibition of JNK phosphorylation in HepG2 cells reduced ER stress-induced activation of Jun-related components but did not prevent activation of fos-related components.
Answer: ER stress activates the hepatic AP-1 complex via MAPK-dependent signaling pathways. ER stress-induced activation of Fos-related components is dependent primarily on ERK activation whereas ER stress-induced activation of Jun-related components is dependent primarily on JNK activation, although there is interplay between these regulatory pathways. These data implicate a novel signaling pathway by which sustained ER stress, as observed in many chronic liver diseases, may promote hepatic carcinogenesis.

Output: Does endoplasmic reticulum stress activate the hepatic activator protein 1 complex via mitogen activated protein kinase-dependent signaling pathways?


Input: Consider Input: Context: Nonviral vectors based on polyethylenimine (PEI) usually contain an excess of PEI that is not complexed to DNA. Since unbound PEI contributes to cellular and systemic toxicity, purification of polyplexes from unbound PEI is desirable.', 'Size exclusion chromatography (SEC) was used to purify PEI polyplexes of free PEI. Transfection properties of purified polyplexes and the effect of free PEI on gene delivery were studied in vitro and in vivo after systemic application into mice.', 'SEC did not change the size and zeta-potential of polyplexes. Independent of the amount of PEI used for complex formation, purified PEI polyplexes had the same final PEI nitrogen/DNA phosphate ratio of 2.5. Notably, purified PEI polyplexes demonstrated low cellular and systemic toxicity. High transfection efficiency was achieved with purified polyplexes at high DNA concentrations (8-15 microg/ml). At low DNA concentrations (2-4 microg/ml) gene transfer with purified particles was less efficient than with polyplexes containing free PEI both in vitro and in vivo. Mechanistic studies showed that free PEI partly blocked cellular association of DNA complexes but was essential for the following intracellular gene delivery. Adding free PEI to cells treated with purified particles with a delay of up to 4 h resulted in significantly enhanced transfection efficiency compared with non-purified particles or purified particles without free PEI.
Answer: This study presents an efficient method to remove free PEI from PEI polyplexes by SEC. Our results from transfection experiments demonstrate that free PEI substantially contributes to efficient gene expression but also mediates toxic effects in a dose-dependent manner. Purified polyplexes without free PEI have to be applied at increased concentrations to achieve high transfection levels, but exhibit a greatly improved toxicity profile.

Output: Does purification of polyethylenimine polyplexes highlight the role of free polycations in gene transfer?


Input: Consider Input: Context: To examine the role of antiretroviral treatment related perceptions relative to other clinical and psychosocial factors associated with sexual risk taking in HIV positive men who have sex with men (MSM).', 'Participants were recruited from ambulatory HIV clinics in Montreal. Information on sociodemographic factors, health status, antiretroviral treatment related perceptions, and sexual behaviours was collected using a self administered questionnaire. At-risk sexual behaviour was defined as at least one occurrence of unprotected insertive or receptive anal intercourse in the past 6 months. Multivariate logistic regression was performed to evaluate the associations between at-risk sexual behaviour and covariates.', '346 subjects participated in the study. Overall, 34% of subjects were considered at risk; 43% of sexually active subjects (n=274). At-risk sexual behaviour was associated with two antiretroviral treatment related perceptions: (1) taking antiretroviral treatment reduces the risk of transmitting HIV (adjusted odds ratio (OR), 2.10; 95% confidence interval (CI), 1.16 to 3.80); and (2) there is less safer sex practised by MSM because of HIV treatment advances (OR, 1.82; CI, 1.14 to 2.90). Other factors, however, were more strongly associated with risk. These were: (1) safer sex fatigue (OR, 3.23; CI, 1.81 to 5.78); (2) use of "poppers" during sexual intercourse (OR, 6.28; CI, 2.43 to 16.21); and (3) reporting a greater proportion of HIV positive anal sex partners, compared with reporting no HIV positive anal sex partners: (a) <50% HIV positive (OR, 16.79; CI, 4.70 to 59.98); (b) > or =50% HIV positive (OR, 67.67; CI, 15.43 to 296.90).
Answer: Despite much emphasis on HIV treatment related beliefs as an explanation for sexual risk taking in MSM, this concern may play a relatively minor part in the negotiation of risk by HIV positive MSM. Serosorting, safer sex fatigue, and the use of poppers appear to be more important considerations in understanding the sexual risk behaviours of HIV positive MSM.


Output: Is hIV status of sexual partners more important than antiretroviral treatment related perceptions for risk taking by HIV positive MSM in Montreal , Canada?