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.
--------
Question: Trans-activation Response DNA-binding Protein-43 (TDP-43) lesions are observed in Amyotrophic Lateral Sclerosis (ALS), Frontotemporal Lobar Degeneration with ubiquitin inclusions (FTLD-TDP) and 25-50% of Alzheimer's Disease (AD) cases. These abnormal protein inclusions are composed of either amorphous TDP-43 aggregates or highly ordered filaments. The filamentous TDP-43 accumulations typically contain clean 10-12 nm filaments though wider 18-20 nm coated filaments may be observed. The TDP-43 present within these lesions is phosphorylated, truncated and ubiquitinated, and these modifications appear to be abnormal as they are linked to both a cellular heat shock response and microglial activation. The mechanisms associated with this abnormal TDP-43 accumulation are believed to result in a loss of TDP-43 function, perhaps due to the post-translational modifications or resulting from physical sequestration of the TDP-43. The formation of TDP-43 inclusions involves cellular translocation and conversion of TDP-43 into fibrillogenic forms, but the ability of these accumulations to sequester normal TDP-43 and propagate this behavior between neurons pathologically is mostly inferred. The lack of methodology to produce soluble full length TDP-43 and recapitulate this polymerization into filaments as observed in disease has limited our understanding of these pathogenic cascades.", 'The protocols described here generate soluble, full-length and untagged TDP-43 allowing for a direct assessment of the impact of various posttranslational modifications on TDP-43 function. We demonstrate that Casein Kinase II (CKII) promotes the polymerization of this soluble TDP-43 into 10 nm diameter filaments that resemble the most common TDP-43 structures observed in disease. Furthermore, these filaments are recognized as abnormal by Heat Shock Proteins (HSPs) which can inhibit TDP-43 polymerization or directly promote TDP-43 filament depolymerization.

Answer: 0

Question: 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.

Answer: 1

Question: Thallium-201 (201Tl) myocardial perfusion imaging has been widely used for evaluation of myocardial ischemia/viability after myocardial infarction. The 3- to 4-h early redistribution imaging has underestimated a considerable part of viable myocardium, while the 24-h late redistribution imaging may enhance the detection of myocardial ischemia/viability, but remains controversial.', 'Thirty-eighty patients with myocardial infarction underwent the initial, 3-h, and 24-h redistribution imaging after intravenous injection of 148-185 MBq 201Tl. Image quality analysis was performed using a four-grade model: excellent, good, moderate, and poor. The initial and 3-h images, the initial and 24-h images, and the 3- and 24-h images were compared double-blinded.', 'The 3- and 24-h images showed no significant differences in image quality according to the four-grade model (P=.3580). Out of the 194 abnormal segments based on the initial imaging, 60 (31%) segments improved by at least one grade on the 3-h imaging, while 86 (44%) segments improved by at least one grade on the 24-h imaging. The 24-h late imaging detected more viable myocardium than the 3-h imaging did, with a significant difference (chi2=7.4235, P=.0064). There were 164 abnormal segments on the 3-h imaging, with an average 30% (48) segments improved by at least one grade on the 24-h imaging. There were 134 initial abnormal segments without any improvement on the 3-h imaging. Out of these segments, the 24-h late redistribution imaging detected additional redistribution in 30 segments, taking up 22%. The mean global score on the 3-h imaging significantly decreased compared to that on the initial imaging (t=5.71, P<.0001), and the mean global score on the 24-h imaging further decreased significantly compared to that on the 3-h imaging (t=6.28, P<.0001).

Answer:
0