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: 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: Contralateral groin exploration in children with unilateral inguinal hernia is still controversial, particularly in infants. The patency rate of processus vaginalis is highest in infants but there are few data on the subsequent risk of contralateral hernia development in infants. In this retrospective study, we aimed to find out the incidence of contralateral inguinal hernia following unilateral inguinal herniotomy in infants aged less than one year.', 'All infants who underwent a unilateral Inguinal herniotomy between January 1990 and December 1998 were studied retrospectively. Infants with bilateral hernia (n = 7) were excluded from the study.', 'One hundred and one infants (93 boys and 8 girls) were studied. Median age at operation was 23 (range 2-52) weeks. The herniotomy was right-sided in 75% of the infants. Follow-up ranged from three and a half years to 11 years. A contralateral hernia developed in nine infants (9.0%). One of the initial hernias was incarcerated. Median time from operation to occurrence of contralateral hernia was 18 (range 2-60) months. None of the contralateral hernia was incarcerated. Age, sex, incarceration and side of initial hernia did not influence the development of contralateral hernia.\Question: Is contralateral groin exploration justified in infants with a unilateral inguinal hernia?

Output: The low incidence and benign nature of contralateral hernia development in infants undergoing a unilateral inguinal herniotomy does not justify routine contralateral groin exploration.

Input: Consider Input: Context: Alternative splicing is important for increasing the complexity of the human proteome from a limited genome. Previous studies have shown that for some autoantigens, there is differential immunogenicity among alternatively spliced isoforms.', 'Herein, we tested the hypothesis that alternative splicing is a common feature for transcripts of autologous proteins that are autoantigens. The corollary hypothesis tested was that nonautoantigen transcripts have a lower frequency of alternative splicing.', 'The extent of alternative splicing within 45 randomly selected self-proteins associated with autoimmune diseases was compared with 9554 randomly selected proteins in the human genome by using bioinformatics analyses. Isoform-specific regions that resulted from alternative splicing were studied for their potential to be epitopes for antibodies or T-cell receptors.', 'Alternative splicing occurred in 100% of the autoantigen transcripts. This was significantly higher than the approximately 42% rate of alternative splicing observed in the 9554 randomly selected human gene transcripts ( P < .001). Within the isoform-specific regions of the autoantigens, 92% and 88% encoded MHC class I and class II-restricted T-cell antigen epitopes, respectively, and 70% encoded antibody binding domains. Furthermore, 80% of the autoantigen transcripts underwent noncanonical alternative splicing, which is also significantly higher than the less than 1% rate in randomly selected gene transcripts ( P < .001).\Question: Does increased noncanonical splicing of autoantigen transcripts provide the structural basis for expression of untolerized epitopes?
Output: These studies suggest that noncanonical alternative splicing may be an important mechanism for the generation of untolerized epitopes that may lead to autoimmunity. Furthermore, the product of a transcript that does not undergo alternative splicing is unlikely to be a target antigen in autoimmunity.