TASK DEFINITION: Given a passage classify if the passage has a definite objective/aim/goal or not. Output '1' if the passage has a defininte objective/aim/goal and output '0' if the passage does not have a definite objective/aim/goal.
PROBLEM: T-wave alternans (TWA) is an indicator of vulnerability to ventricular arrhythmias and is useful for predicting sudden cardiac death (SCD) in patients with various structural heart diseases. We evaluated whether high levels of time-domain TWA on ambulatory ECG (AECG) are associated with a history of ventricular fibrillation (VF) in Brugada syndrome (BrS) patients.', 'We examined the associations among VF history, family history of SCD, spontaneous type 1 electrocardiogram (ECG), late potentials, VF induction by programmed electrical stimulation, and TWA in 45 BrS patients (44 males; mean age, 45 ± 15 years). TWA analyzed from 24-h AECG recordings using the modified moving average method was positive in 13 of 43 patients (30%). Patients with a history of VF had a significantly higher incidence of a positive TWA test (82% vs. 13%; P < 0.001) and spontaneous type 1 ECG (92% vs. 38%; P = 0.007) than those without VF history. Multivariate analysis indicated that positive TWA (OR 7.217; 95% CI 2.503-35.504; P = 0.002) and spontaneous type 1 ECG (OR 5.530; 95% CI 1.651-34.337; P = 0.020) were closely associated with VF history. Spontaneous type 1 ECG had high sensitivity (92%) but low specificity (63%). Positive TWA was a reliable marker with high sensitivity and specificity (82% and 88%, respectively).

SOLUTION: 1

PROBLEM: Growth factor therapy provides a therapeutic alternative for "no option" patients with coronary disease. Fibroblast Growth Factor-2 (FGF-2) predominantly stimulates angiogenesis, the growth of new capillaries, whereas Monocyte Chemoattractant Protein-1 (MCP-1) is considered an arteriogenic agent. We hypothesised a synergetic effect of FGF-2 and MCP-1 in ischemic myocardium.', 'A severe coronary stenosis was created in pigs. After one week, chronic ischemia was confirmed by angiography, echocardiography, reduced ejection fraction, and increase of marker enzymes. FGF-2, MCP-1, both, or vector only were then injected intramyocardially as plasmid DNA in the impaired area. Regional contractility and number of capillaries and arterial vessels were evaluated after three months.', 'FGF-2, FGF-2+MCP-1, and vector, but not MCP-1 alone improved regional contractility at rest, whereas only FGF-2 alone ameliorated function under stress conditions. Angiogenesis in the ischemic area was stimulated by FGF-2 compared to MCP-1. In contrast, MCP-1 induced arteriogenesis relative to FGF-2.

SOLUTION: 0

PROBLEM: Cohesion between sister chromatids is fundamental to ensure faithful chromosome segregation during mitosis and accurate repair of DNA damage postreplication. At the molecular level, cohesion establishment involves two defined events, a chromatin binding step and a chromatid entrapment event driven by posttranslational modifications on cohesin subunits.', "Here, we show that modification by the small ubiquitin-like protein (SUMO) is required for sister chromatid tethering after DNA damage. We find that all subunits of cohesin become SUMOylated upon exposure to DNA damaging agents or presence of a DNA double-strand break. We have mapped all lysine residues on cohesin's α-kleisin subunit Mcd1 (Scc1) where SUMO can conjugate. We demonstrate that Mcd1 SUMOylation-deficient alleles are still recruited to DSB-proximal regions but are defective in tethering sister chromatids and consequently fail to establish damage-induced cohesion both at DSBs and undamaged chromosomes. Moreover, we demonstrate that the bulk of Mcd1 SUMOylation in response to damage is carried out by the SUMO E3 ligase Nse2, a subunit of the related Smc5-Smc6 complex. SUMOylation occurs in cells with compromised Chk1 kinase activity, necessary for known posttranslational modifications on Mcd1, required for damage-induced cohesion.

SOLUTION:
0