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: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. Current therapies confer partial benefits either by incompletely improving airflow limitation or by reducing acute exacerbations, hence new therapies are desirable. In the absence of robust early predictors of clinical efficacy, the potential success of novel therapeutic agents in COPD will not entirely be known until the drugs enter relatively large and costly clinical trials. New predictive models in humans, and new study designs are being sought to allow for confirmation of pharmacodynamic and potentially clinically meaningful effects in early development. This review focuses on human challenge models with lipopolysaccharide endotoxin, ozone, and rhinovirus, in the early clinical development phases of novel therapeutic agents for the treatment and reduction of exacerbations in COPD.

SOLUTION: Challenge models to assess new therapies in chronic obstructive pulmonary disease

PROBLEM: The dog is considered the main domestic reservoir for Trypanosoma cruzi infection and a suitable experimental animal model to study the pathological changes during the course of Chagas disease (CD). Vaccine development is one of CD prevention methods to protect people at risk. Two plasmids containing genes encoding a trans-sialidase protein (TcSP) and an amastigote-specific glycoprotein (TcSSP4) were used as DNA vaccines in a canine model. Splenomegaly was not found in either of the recombinant plasmid-immunized groups; however, cardiomegaly was absent in animals immunized only with the plasmid containing the TcSSP4 gene. The inflammation of subendocardial and myocardial tissues was prevented only with the immunization with TcSSP4 gene. In conclusion, the vaccination with these genes has a partial protective effect on the enlargement of splenic and cardiac tissues during the chronic CD and on microscopic hearth damage, since both plasmids prevented splenomegaly but only one avoided cardiomegaly, and the lesions in heart tissue of dog immunized with plasmid containing the TcSSP4 gene covered only subepicardial tissue.

SOLUTION: Effect of the Plasmid-DNA Vaccination on Macroscopic and Microscopic Damage Caused by the Experimental Chronic Trypanosoma cruzi Infection in the Canine Model

PROBLEM: required for defective interfering RNA replication, subgenomic RNA synthesis, and presumably also for virus genome replication. 1-3 For the BCoV 5' UTR, the minimum free energy structure is predicted to contain three stem-loops. 3 We have analyzed the entire 5' UTR sequences of nine group 1 and group 2 coronaviruses, including the newly discovered SARS and HKU1 coronaviruses, using consensus, covariation secondary structure predictions. Our analysis shows that the predicted secondary structures of all coronavirus 5' UTRs are strikingly similar and contain three or four stem-loops, including a previously unrecognized highly conserved UNR stem-loop. Computer-assisted modeling predicts an invariant and previously unrecognized UNR stem-loop among nine coronavirus UTR sequences, denoted SL2. This predicted conserved structure encompasses nucleotides 42-56 for both MHV and the SARScoronavirus. NMR spectroscopy of the 16-nt RNA SL2 sars reveals spectral features consistent with a UNR hairpin loop. Reverse genetics studies revealed that SL2 is required for MHV replication; MHV genomes containing a substitution of the required U48 with C in the UNR loop (U48C) were not viable. RT-PCR analysis of the U48C mutant indicated that negative sense genome sized RNAs were present in cells electroporated with this mutant; however, neither positive nor negative sense subgenomic RNAs were detected. Mutations that destabilized the stem of SL2 were viable but had moderately to severely impaired replication phenotypes. Mutants that maintained the stem-loop structure replicated similarly to wild-type MHV. These genetic data strongly support the existence of the predicted UNR stem loop and its functional importance in viral replication.

SOLUTION:
A PREVIOUSLY UNRECOGNIZED UNR STEM-LOOP STRUCTURE IN THE CORONAVIRUS 5' UNTRANSLATED REGION PLAYS A FUNCTIONAL ROLE IN REPLICATION