TASK DEFINITION: In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.
PROBLEM: To elucidate the impact of a hepatitis B (HB) vaccination program on the prevalence of HB surface antigen (HBsAg) and HB envelope antigen (HBeAg) as well as the success rate of HBeAg clearance among parturients, we collected data on parturients who gave birth between 2000 and 2010, and recorded the HB status postpartum of those with positive HBeAg before birth. A total of 8696 parturients were enrolled, of whom 113 with prenatal positive HBeAg were invited back. The prevalence of HBsAg decreased over the study period, particularly in the vaccinated cohort, while there was no change in the prevalence of HBeAg. Foreign parturients had a higher HBeAg-positive rate and delayed HBeAg clearance, and those with a higher body mass index (>24 kg/m 2 ) had earlier HBeAg clearance (51.9% vs. 23.9%, p = 0.005). Only 30% of the subjects who were positive for HBeAg before birth became negative 5 years after delivery. In conclusion, the downward trend in HB infection with more significance among vaccinated parturients reflects effective prevention and the impact of universal HB immunization. Nonetheless, aggressive follow-up is necessary for parturients who are persistently positive for HBeAg postpartum, as well as developing different public health policies for foreign parturients from endemic areas. Published: xx xx xxxx OPEN www.nature.com/scientificreports/ 2 Scientific RepoRts | 7: 1212 |

SOLUTION: Changes in the Prevalence of HBsAg and HBeAg: a Study of 8696 Parturients in a Well Vaccinated Area OPEN

PROBLEM: Background: Nonadditivity in fitness effects from two or more mutations, termed epistasis, can result in compensation of deleterious mutations or negation of beneficial mutations. Recent evidence shows the importance of epistasis in individual evolutionary pathways. However, an unresolved question in molecular evolution is how often and how significantly fitness effects change in alternative genetic backgrounds. Results: To answer this question, we quantified the effects of all single mutations and double mutations between all positions in the IgG-binding domain of protein G (GB1). By observing the first two steps of all possible evolutionary pathways using this fitness profile, we were able to characterize the extent and magnitude of pairwise epistasis throughout an entire protein molecule. Furthermore, we developed a novel approach to quantitatively determine the effects of single mutations on structural stability (DDG U ). This enabled determination of the importance of stability effects in functional epistasis. Conclusions: Our results illustrate common biophysical mechanisms for occurrences of positive and negative epistasis. Our results show pervasive positive epistasis within a conformationally dynamic network of residues. The stability analysis shows that significant negative epistasis, which is more common than positive epistasis, mostly occurs between combinations of destabilizing mutations. Furthermore, we show that although significant positive epistasis is rare, many deleterious mutations are beneficial in at least one alternative mutational background. The distribution of conditionally beneficial mutations throughout the domain demonstrates that the functional portion of sequence space can be significantly expanded by epistasis.

SOLUTION: Article A Comprehensive Biophysical Description of Pairwise Epistasis throughout an Entire Protein Domain

PROBLEM: Introduction-Rapid transmission of norovirus often occurs due to its low infectious dosage, high genetic diversity and its short incubation time. The viruses cause acute gastroenteritis and may lead to death. Presently, no effective vaccine or selective drugs accepted by the United States Food and Drug Administration (FDA) are available for the treatment of norovirus. Advances in the development of norovirus replicon cell lines, GII.4-Sydney HuNoV strain human B cells, and murine and gnotobiotic pig norovirus models have facilitated the discovery of effective small molecule inhibitors in vitro and in vivo. Areas covered-This review gives a brief discussion of the biology and replication of norovirus before highlighting the discovery of anti-norovirus molecules. The article coverage includes: an overview of the current state of norovirus drug discovery, the targeting of the norovirus life cycle, the inhibition of structural and nonstructural proteins of norovirus such as proteases and polymerase, and the blockage of virus entry into host cells. Finally, anti-norovirus drugs in the clinical development stage are described. Expert opinion-The current approach for the counteraction of norovirus focuses on the inhibition of viral RNA polymerase, norovirus 3C-like protease and the structural proteins VP1 as well as the blockade of norovirus entry. Broad-spectrum anti-norovirus molecules, based on the inhibition of 3C-like protease, have been developed. Other host factors and ways to overcome the development of resistance through mutation are also being examined. A dual approach in targeting viral and host factors may lead to an effective counteraction of norovirus infection. Current successes in developing norovirus replicon harboring cells and norovirus infected human cells, as well as murine norovirus models and other animal models such as piglets have facilitated the discovery of effective drugs and helped our understanding of its mechanism of action.

SOLUTION:
Current Tools for Norovirus Drug Discovery HHS Public Access