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.

Ex Input:
Inhalation of nitric oxide (NO) and inhibition of phosphodiesterase type 5 (PDE5) selectively dilate the pulmonary circulation in patients with acute lung injury (ALI) associated with pulmonary hypertension. PDE5 inhibitors administered at doses that decrease pulmonary artery pressures have been shown to worsen arterial oxygenation. We investigated the efficacy of doses of PDE5 inhibitors that do not reduce pulmonary artery pressure alone (subthreshold doses) to improve the response to inhaled NO in an animal model of ALI.', 'Adult Sprague-Dawley rats were pre-treated with 0.5 mg/kg Escherichia coli 0111:B4 endotoxin and 16 to 18 h later, their lungs were isolated perfused and ventilated. The thromboxane mimetic U46619 was used to induce pulmonary hypertension. After the determination of subthreshold doses of two different PDE5 inhibitors, either 50 microg zaprinast or 10 ng sildenafil was added to the perfusate and the decrease of pulmonary artery pressure measured in the presence and absence of inhaled NO.', 'In the presence of 4 or 10 ppm NO, zaprinast (-1.6 +/- 0.4 and -2.9 +/- 0.6 mmHg, respectively) and sildenafil (-1.9 +/- 0.4 and -2.4 + 0.3 mmHg, respectively) improved responsiveness to inhaled NO compared to lungs from rats treated with LPS only (0.7 +/- 0.1 and -1.0 +/- 0.1 mmHg, respectively; P<0.05). Neither zaprinast nor sildenafil prolonged the pulmonary vasodilatory response to inhaled NO.

Ex Output:
0


Ex Input:
A growing body of evidence indicates a positive correlation between expression of human antimicrobial peptide leucin leucin 37 (LL-37) and progression of epithelial cancers, including prostate cancer (PCa). Although the molecular mechanisms for this correlation has not yet been elucidated, the primary function of LL-37 as a chemotactic molecule for innate immune effector cells suggests its possible association in coordinating protumorigenic mechanisms, mediated by tumor-infiltrating immune cells.', 'To investigate protumorigenic role(s) of cathelicidin-related antimicrobial peptide (CRAMP), a murine orthologue of LL-37, the present study compared tumor growth kinetics between mouse PCa cell lines with and without CRAMP expression (TRAMP-C1 and TRAMP-C1(CRAMP-sh) , respectively) in immunocompetent mice. CRAMP-mediated chemotaxis of different innate immune cell types to the tumor microenvironment (TME) was observed in vivo and confirmed by in vitro chemotaxis assay. The role of CRAMP in differentiation and polarization of immature myeloid progenitors (IMPs) to protumorigenic type 2 macrophages (M2) in TME was determined by adoptive transfer of IMPs into mice bearing CRAMP(+) and CRAMP(-) tumors. To differentiate protumorigenic events mediated by tumor-derived CRAMP from host immune cell-derived CRAMP, tumor challenge study was performed in CRAMP-deficient mice. To identify mechanisms of CRAMP function, macrophage colony stimulating factor (M-CSF) and monocyte chemoattractant protein 1 (MCP-1) gene expression was analyzed by QRT-PCR and STAT3 signaling was determined by immunoblotting.', 'Significantly delayed tumor growth was observed in wild-type (WT) mice implanted with TRAMP-C1(CRAMP-sh) cells compared to mice implanted with TRAMP-C1 cells. CRAMP(+) TME induced increased number of IMP differentiation into protumorigenic M2 macrophages compared to CRAMP(-) TME, indicating tumor-derived CRAMP facilitates differentiation and polarization of IMPs toward M2. Tumor challenge study in CRAMP deficient mice showed comparable tumor growth kinetics with WT mice, suggesting tumor-derived CRAMP plays a crucial role in PCa progression. In vitro study demonstrated that overexpressed M-CSF and MCP-1 in TRAMP-C1 cells through CRAMP-mediated autocrine signaling, involving p65, regulates IMP-to-M2 differentiation/polarization through STAT3 activation.

Ex Output:
0


Ex Input:
IL-17 is the defining cytokine of the Th17, Tc17, and γδ T cell populations that plays a critical role in mediating inflammation and autoimmunity. Psoriasis vulgaris is an inflammatory skin disease mediated by Th1 and Th17 cytokines with relevant contributions of IFN-γ, TNF-α, and IL-17. Despite the pivotal role IL-17 plays in psoriasis, and in contrast to the other key mediators involved in the psoriasis cytokine cascade that are capable of inducing broad effects on keratinocytes, IL-17 was demonstrated to regulate the expression of a limited number of genes in monolayer keratinocytes cultured in vitro.', 'Given the clinical efficacy of anti-IL-17 agents is associated with an impressive reduction in a large set of inflammatory genes, we sought a full-thickness skin model that more closely resemble in vivo epidermal architecture. Using a reconstructed human epidermis (RHE), IL-17 was able to upregulate 419 gene probes and downregulate 216 gene probes. As possible explanation for the increased gene induction in the RHE model is that C/CAAT-enhancer-binding proteins (C/EBP) -β, the transcription factor regulating IL-17-responsive genes, is expressed preferentially in differentiated keratinocytes.

Ex Output:

0