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: Redirecting the splicing machinery through the hybridization of high affinity, RNase H-incompetent oligonucleotide analogs such as phosphoramidate morpholino oligonucleotides (PMO) might lead to important clinical applications. Chemical conjugation of PMO to arginine-rich cell penetrating peptides (CPP) such as (R-Ahx-R) 4 (with Ahx standing for 6-aminohexanoic acid) leads to sequencespecific splicing correction in the absence of endosomolytic agents in cell culture at variance with most conventional CPPs. Importantly, (R-Ahx-R) 4 -PMO conjugates are effective in mouse models of various viral infections and Duchenne muscular dystrophy. Unfortunately, active doses in some applications might be close to cytotoxic ones thus presenting challenge for systemic administration of the conjugates in those clinical settings. Structureactivity relationship studies have thus been undertaken to unravel CPP structural features important for the efficient nuclear delivery of the conjugated PMO and limiting steps in their internalization pathway. Affinity for heparin (taken as a model heparan sulfate), hydrophobicity, cellular uptake, intracellular distribution and splicing correction have been monitored. Spacing between the charges, hydrophobicity of the linker between the Arg-groups and Arg-stereochemistry influence splicing correction efficiency. A significant correlation between splicing correction efficiency, affinity for heparin and ability to destabilize model synthetic vesicles has been observed but no correlation with cellular uptake has been found. Efforts will have to focus on endosomal escape since it appears to remain the limiting factor for the delivery of these splice-redirecting ON analogs.

SOLUTION: Delivery of steric block morpholino oligomers by (R-X-R) 4 peptides: structure-activity studies

PROBLEM: Bovine renal brush-border membrane vesicle aminopeptidase N at various stages of purity was treated with two bifunctional cross-linking agents. A pattern of emergence of higher molecular weight forms was observed. By using a cleavable cross-linker, aminopeptidase N was shown to cross-link both to itself and to its breakdown products as well as to dipeptidyl peptidase IV. Using this technique it was possible to identify three of the breakdown products as 45 kDa, 66 kDa and 95 kDa peptides. N-terminal amino acid sequence analysis was used to define the precise cleavage points for the bovine renal aminopeptidase N breakdown products. The short amino acid sequences obtained show strong sequence similarity with the human intestinal and rat kidney aminopeptidase N.

SOLUTION: The oligomeric structure of renal aminopeptidase N from bovine brush-border membrane vesicles

PROBLEM: Objectives The common cold is the main cause of medical time loss in elite sport. Rapid diagnosis has been a challenge that may be amenable to molecular point-ofcare testing (POCT). Methods We performed a prospective observational study of the common cold in Team Finland during the 2018 Winter Olympic Games. There were 44 elite athletes and 68 staff members. The chief physician recorded the symptoms of the common cold daily on a standardised form. Two nasal swabs were taken at the onset of symptoms. One swab was analysed within 45 min using a molecular POCT for respiratory syncytial virus and influenza A and B viruses. After the Games, the other swab was tested for 16 possible causative respiratory viruses using PCR in laboratory-based testing. Results 20 out of 44 (45%) athletes and 22 out of 68 (32%) staff members experienced symptoms of the common cold during a median stay of 21 days. Eleven (26%) samples tested virus-positive using POCT. All subjects with influenza (n=6) and 32 close contacts were treated with oseltamivir. The aetiology of the common cold was finally detected in 75% of the athletes and 68 % of the staff members. Seven virus clusters were identified. They were caused by coronaviruses 229E, NL63 and OC43, influenza B virus, respiratory syncytial virus A, rhinovirus and human metapneumovirus. The virus infections spread readily within the team, most commonly within the same sport discipline. Conclusions The cold was indeed a common illness in Team Finland during the Winter Olympic Games. POCT proved to be clinically valuable, especially for influenza. The aetiology of the common cold was identified in most cases.

SOLUTION:
Common cold in Team Finland during 2018 Winter Olympic Games (PyeongChang): epidemiology, diagnosis including molecular point-of-care testing (POCT) and treatment