Given a passage, 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.

Q: Although evidence suggests that antiretroviral (ARV) regimens containing nonnucleoside reverse transcriptase inhibitors (NNRTIs) are superior to single-protease inhibitor (PI)-based regimens at suppressing viral load, it is unclear how much of the improved viral suppression is due to intrinsic drug potency versus higher levels of adherence to simpler regimens. We therefore examined adherence and viral suppression in NNRTI and single-PI regimens in a cohort of largely ARV-experienced participants by using objective measures of adherence.', "Participants were recruited from the Research on Access to Care in the Homeless (REACH) Cohort and were included in the study if they were on single-PI-based or NNRTI-based highly active antiretroviral therapy (HAART) regimens for at least 3 months prior to study entry. Adherence was measured by unannounced pill counts at the participant's usual place of residence. The primary outcome was suppression of HIV viral RNA to <50 copies/mL.", 'Among 109 individuals who were followed for a median of 8.7 months, the odds of virologic suppression were approximately 8 times higher (p < .01) for participants on NNRTI-based regimens (n = 53) compared with those using single-PI-based regimens (n = 56) when controlling for adherence, as well as other potential confounders in a multivariable analysis. The only other independent predictors of viral suppression in multivariable modeling were ARV adherence (p < .01), CD4 nadir (p = .02), and continuous months on current regimen prior to the start of adherence monitoring (p < .01). There was no significant difference in adherence by unannounced pill counts in participants receiving NNRTI- versus single-PI-containing regimens.

A: Are higher rates of viral suppression with nonnucleoside reverse transcriptase inhibitors compared to single protease inhibitors explained by better adherence?
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Q: Wnt proteins are important for developmental processes and certain diseases. WNT5A is a non-canonical Wnt protein that previously has been shown to play a role in the progression of malignant melanoma. High expression of WNT5A in melanoma tumors correlates to formation of distant metastasis and poor prognosis. This has partly been described by the findings that WNT5A expression in melanoma cell lines increases migration and invasion.', 'Malignant melanoma cell lines were treated with rWNT5A or WNT5A siRNA, and mRNA versus protein levels of soluble mediators were measured using RT-PCR, cytokine bead array and ELISA. The induced signaling pathways were analyzed using inhibitors, Rho-GTPase pull down assays and western blot. Ultracentrifugation and electron microscopy was used to analyze microvesicles. Gene expression microarray data obtained from primary malignant melanomas was used to verify our data.', 'We show that WNT5A signaling induces a Ca2+-dependent release of exosomes containing the immunomodulatory and pro-angiogenic proteins IL-6, VEGF and MMP2 in melanoma cells. The process was independent of the transcriptional machinery and depletion of WNT5A reduced the levels of the exosome-derived proteins. The WNT5A induced exosomal secretion was neither affected by Tetanus toxin nor Brefeldin A, but was blocked by the calcium chelator Bapta, inhibited by a dominant negative version of the small Rho-GTPase Cdc42 and was accompanied by cytoskeletal reorganization. Co-cultures of melanoma/endothelial cells showed that depletion of WNT5A in melanoma cells decreased endothelial cell branching, while stimulation of endothelial cells with isolated rWNT5A-induced melanoma exosomes increased endothelial cell branching in vitro. Finally, gene expression data analysis of primary malignant melanomas revealed a correlation between WNT5A expression and the angiogenesis marker ESAM.

A: Does wNT5A induce release of exosomes containing pro-angiogenic and immunosuppressive factors from malignant melanoma cells?
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Q: Advanced gene therapy, tissue engineering and biopharmaceutical manufacturing require sophisticated and well-balanced multiregulated multigene interventions to reprogram desired mammalian cell phenotypes.', 'We have combined the streptogramin (PIP)- and tetracycline (TET)-responsive gene regulation systems for independent expression control of the differentiation determinants myoD and msx1 in C2C12-derived cells.', 'Different dual-regulated expression scenarios which induce either both, only one or none of the lineage control genes triggered differential differentiation and precise control of myogenic, osteogenic or adipogenic cell phenotypes.

A:
Do dual-regulated myoD- and msx1-based interventions in C2C12-derived cells enable precise myogenic/osteogenic/adipogenic lineage control?
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