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: Centrosome orientation toward the leading edge of migrating cells depends on dynein and microtubules (MTs), as well as a number of signaling factors at the leading edge. However, centrosomes are maintained at the cell center during orientation in fibroblasts, suggesting that factors working at sites other than the leading edge may also be involved.', 'In a search for factors that function with dynein in centrosome orientation, we found that the polarity protein Par3 associated with dynein and that knockdown of Par3 inhibited centrosome orientation by disrupting the position of the centrosome at the cell center; this disrupted centrosome positioning is the same phenotype as that observed with dynein inhibition. Par3 associated with dynein through its N-terminal dimerization and PDZ1 domains and interacted specifically with dynein light intermediate chain 2 (LIC2). siRNA knockdown of LIC2, but not LIC1, or overexpression of LIC2 or the N-terminal domain of Par3, also inhibited centrosome orientation by disrupting centrosome position. In wound-edge fibroblasts, Par3 specifically localized to cell-cell contacts where it overlapped with MT ends and dynein puncta in a LIC2-dependent fashion. Live imaging showed that MTs exhibited increased pausing at cell-cell contacts compared to the leading edge and that this elevated pausing was dependent on Par3 and LIC2.

SOLUTION: 0

PROBLEM: Human inflammatory bowel disease (e.g., Crohn's disease and ulcerative colitis), is associated with leukocyte accumulation in the inflamed intestinal tissue. Recent studies strongly suggest a role of beta1 integrin receptors in regulating tissue damage and disease symptoms related to inflammatory bowel disease. The aim of this study was to investigate the role of the collagen-binding alpha2beta1 integrin (CD49b/CD29) in dextran sodium sulfate-induced colitis in mice.", 'Colitis was induced in mice through oral administration of 2% dextran sodium sulfate in drinking water. Rectal administration of anti-alpha2-monoclonal antibody (mAb) in 1 group was compared with oral treatment with betamethasone in another group and rectal administration of a control antibody in a third group. Clinical and histological signs of colitis, neutrophil infiltration into the colon mucosa, and gene expression of metalloproteinases were assessed.', 'Rectal administration of anti-alpha2-mAb was found to significantly reduce weight loss from 13.5% +/- 6.5% to 2.2% +/- 0.2% (P = 0.013 versus control mAb) and mucosal neutrophil infiltration from 47.2 +/- 10.0 to 6.6 +/- 8.0 neutrophils per counted area (P < 0.05 versus control mAb). Metalloproteinase gene expression was suppressed through anti-alpha2-mAb treatment. The protective effect against colitis seen after anti-alpha2beta1 integrin treatment was found to be favorable to the effect seen after high-dose oral betamethasone.

SOLUTION: 0

PROBLEM: To define the predictive capability of serum C-reactive protein for a contemporary patient collective undergoing metastasectomy for metastatic renal cell carcinoma with access to modern targeted therapies.', 'A total of 88 patients treated with metastasectomy for metastatic renal cell carcinoma from 2003 to 2014 were evaluated for putative clinicopathological risk factors and survival. Kaplan-Meier analyses, univariate and multivariate testing were carried out. Receiver operating characteristic curve analysis was applied to evaluate available risk stratification instruments for patients undergoing metastasectomy.', 'Median overall survival for the collective was 66.31 months (95% confidence interval 50.67-135.47; 5-year overall survival 55%). The median preoperative C-reactive protein level was 6.7 mg/L (range 0.1-161.7). A C-reactive protein cut-off value of 5 mg/dL was significantly discriminative of survival (P = 0.029). Median survival in dependence of C-reactive protein accounted for 50.67 months (range 33.86-63.05 months) in the C-reactive protein >5 mg/L group, and 135.47 months in the C-reactive protein 5 mg/L group (range 66.31-135.47 months). C-reactive protein elevation >5 mg/L, anemia and surgical margin status were identified as significant predictors of overall survival in univariate analysis. In a multivariate model, resection margin status (P = 0.015) and C-reactive protein elevation (P = 0.038) were confirmed as independent predictive variables.

SOLUTION:
1