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: Recent randomized trials suggest that intensive glycaemic control fails to reduce heart failure-related events in patients with diabetes. The molecular cues underlying persistent myocardial damage despite normoglycaemia restoration remain elusive. MicroRNAs (miRNAs), a class of small non-coding RNAs, orchestrate transcriptional programs implicated in adverse cardiac remodelling. The present study investigates whether miRNAs participate to hyperglycaemic memory in the diabetic heart.', 'miRNA landscape was assessed by Mouse miRNome miRNA PCR Arrays in left ventricular specimens collected from 4-month-old streptozotocin-induced diabetic mice, with or without intensive glycaemic control by slow-release insulin implants. A dysregulation of 316 out of 1008 total miRNAs was observed in the diabetic hearts when compared with controls. Of these, 209 were up-regulated and 107 were down-regulated by >2.0-fold. Interestingly enough, the expression of 268 of those miRNAs remained significantly altered in diabetic mice even after subsequent normoglycaemia. Ingenuity pathway analysis revealed that dysregulated miRNAs were implicated in myocardial signalling networks triggering apoptosis (miR-320b, miR-378, miR-34a), fibrosis (miR-125b, miR-150, miR-199a, miR-29b, miR30a), hypertrophic growth (miR-1, miR-150, miR-199a, miR-133a, miR-214, miR-29a, miR-125b, miR-221, miR-212), autophagy (miR-133a, miR-221, miR-212, miR30a), oxidative stress (miR-221, miR-146a, miR-34a, miR-210, miR-19b, miR-125b, miR27a, miR-155), and heart failure (miR-423, miR-499, miR-199a), respectively.

SOLUTION: 1

PROBLEM: Gap junction channels provide for direct electrical coupling between cells, and play an important role in homeostasis and electrical coupling. One of the proteins that form gap junctions, Connexin40 (Cx40), shows restricted expression in the body, and is found in blood vessels and in the atrium and conduction system of the heart. We have investigated whether gap junction channels formed of Cx40 are modulated by protein-kinase-A-mediated phosphorylation.', 'A communication-deficient human hepatoma cell line (SKHep1) was stably transfected with human Cx40 cDNA and the properties of Cx40 gap junctions channels and their modulation by cAMP were analyzed using immunocytochemistry, Western blotting, dual patch clamp, and dye coupling.', 'Administration of 1 mM 8-Br-cAMP resulted in a mobility shift of Cx40 protein on western blot and increased macroscopic gap junctional conductance between cell pairs by 46.2 +/- 12.0% (mean +/- S.E.M., n = 8). Under control conditions, single channel experiments revealed three single channel conductances around 30, 80 and 120 pS. When cAMP was added, channel conductances of 46 and 120 pS were observed. In monolayers, cAMP also increased the permeability of Cx40 gap junction channels for Lucifer Yellow by 58%.

SOLUTION: 1

PROBLEM: Multi-atlas fusion is a promising approach for computer-assisted segmentation of anatomic structures. The purpose of this study was to evaluate the accuracy and time efficiency of multi-atlas segmentation for estimating spleen volumes on clinically acquired computed tomography (CT) scans.', 'Under an institutional review board approval, we obtained 294 de-identified (Health Insurance Portability and Accountability Act-compliant) abdominal CT scans on 78 subjects from a recent clinical trial. We compared five pipelines for obtaining splenic volumes: Pipeline 1 - manual segmentation of all scans, Pipeline 2 - automated segmentation of all scans, Pipeline 3 - automated segmentation of all scans with manual segmentation for outliers on a rudimentary visual quality check, and Pipelines 4 and 5 - volumes derived from a unidimensional measurement of craniocaudal spleen length and three-dimensional splenic index measurements, respectively. Using Pipeline 1 results as ground truth, the accuracies of Pipelines 2-5 (Dice similarity coefficient, Pearson correlation, R-squared, and percent and absolute deviation of volume from ground truth) were compared for point estimates of splenic volume and for change in splenic volume over time. Time cost was also compared for Pipelines 1-5.', 'Pipeline 3 was dominant in terms of both accuracy and time cost. With a Pearson correlation coefficient of 0.99, average absolute volume deviation of 23.7\u2009cm(3), and time cost of 1 minute per scan, Pipeline 3 yielded the best results. The second-best approach was Pipeline 5, with a Pearson correlation coefficient of 0.98, absolute deviation of 46.92\u2009cm(3), and time cost of 1 minute 30 seconds per scan. Manual segmentation (Pipeline 1) required 11 minutes per scan.

SOLUTION:
1