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.

Input: Consider Input: Context: Living a purposeful life is associated with better mental and physical health, including longevity. Accumulating evidence shows that these associations might be explained by the association between life purpose and regulation of physiological systems involved in the stress response. The aim of this study was to investigate the prospective associations between life purpose and allostatic load over a 10-year period.', 'Analyses were conducted using data from the Midlife in the United States (MIDUS) survey. Assessment of life purpose, psychological covariates and demographics were obtained at baseline, while biomarkers of allostatic load were assessed at the 10-year follow-up.', 'We found that greater life purpose predicted lower levels of allostatic load at follow-up, even when controlling for other aspects of psychological well-being potentially associated with allostatic load. Further, life purpose was also a strong predictor of individual differences in self-health locus of control-i.e., beliefs about how much influence individuals can exert on their own health-which, in turn, partially mediated the association between purpose and allostatic load. Although life purpose was also negatively linked to other-health locus of control-i.e., the extent to which individuals believe their health is controlled by others/chance-this association did not mediate the impact of life purpose on allostatic load.\Question: Does purpose in life predict allostatic load ten years later?

Output: The current study provides the first empirical evidence for the long-term physiological correlates of life purpose and supports the hypothesis that self-health locus of control acts as one proximal psychological mechanism through which life purpose may be linked to positive biological outcomes.


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.\Question: Does purification of polyethylenimine polyplexes highlight the role of free polycations in gene transfer?

Output: 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.


Input: Consider Input: Context: Intracellular targets sensitive to oxidized damage generated by photodynamic therapy (PDT) utilizing N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-mesochlorin e6 monoethylenediamine (Mce6) conjugates was explored to aid in the design of second generation PDT delivery systems.', 'Low temperature, metabolic inhibitor, and nuclear localization sequences (NLS(FITC)) were used to achieve desired subcellular localization that was evaluated by confocal analysis and subcellular fractionation. Mce6 was bound to HPMA copolymer conjugates via non-degradable dipeptide linkers (P-GG-Mce6, P-NLS(FITC)-GG-Mce6) or lysosomally degradable tetrapeptide spacers (P-GFLG-Mce6, P-NLS(FITC)-GFLG-Mce6). Chemotherapeutic efficacy was assessed by the concentration that inhibited growth by 50% (IC50), cell associated drug concentration (CAD) and confocal microscopy.', 'P-GFLG-Mce6 possessed enhanced chemotherapeutic activ ity compared to P-GG-Mce6 indicating enzymatically released Mce6 was more active than copolymer-bound Mce6. Lysosomes appeared less sensitive to photodamage as observed by a higher IC50. Nuclear-directed HPMA copolymer-Mce6 conjugates (P-NLS(FITC)-GG-Mce6, P-NLS(FITC)-GFLG-Mce6) possessed enhanced chemotherapeutic activity. However, control cationic HPMA copolymer-Mce6 conjugates containing a scrambled NLS (P-scNLS(FITC)-GG-Mce6) or amino groups (P-NH2-GG-Mce6) also displayed increased chemotherapeutic activity.\Question: Does correlation of subcellular compartmentalization of HPMA copolymer-Mce6 conjugate with chemotherapeutic activity in human ovarian carcinoma cells?


Output: Nuclear delivery was observed for P-NLS(FITC)-GG-Mce6 and P-NLS(FITC)-GFLG-Mce6 indicating NLS was a feasible approach for nuclear delivery. Due to the cationic nature of NLS, increased membrane binding of PDT systems incorporating cationic nuclear targeting moieties must be addressed.