instruction:
Given a passage with a context and an answer, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.
question:
Context: To test the hypothesis that pharmacological plasminogen activator inhibitor (PAI)-1 inhibition protects against renin-angiotensin-aldosterone system-induced cardiovascular injury, the effect of a novel orally active small-molecule PAI-1 inhibitor, PAI-039, was examined in a mouse model of angiotensin (Ang) II-induced vascular remodeling and cardiac fibrosis.', 'Uninephrectomized male C57BL/6J mice were randomized to vehicle subcutaneus, Ang II (1 mug/h) subcutaneous, vehicle+PAI-039 (1 mg/g chow), or Ang II+PAI-039 during high-salt intake for 8 weeks. Ang II caused significant medial, adventitial, and aortic wall thickening compared with vehicle. PAI-039 attenuated Ang II-induced aortic remodeling without altering the pressor response to Ang II. Ang II increased heart/body weight ratio and cardiac fibrosis. PAI-039 did not attenuate the effect of Ang II on cardiac hypertrophy and increased fibrosis. The effect of PAI-039 on Ang II/salt-induced aortic remodeling and cardiac fibrosis was comparable to the effect of genetic PAI-1 deficiency. Ang II increased aortic mRNA expression of PAI-1, collagen I, collagen III, fibronectin, osteopontin, monocyte chemoattractant protein-1, and F4/80; PAI-039 significantly decreased the Ang II-induced increase in aortic osteopontin expression at 8 weeks.
Answer: This study demonstrates that pharmacological inhibition of PAI-1 protects against Ang II-induced aortic remodeling. Future studies are needed to determine whether the interactive effect of Ang II/salt and reduced PAI-1 activity on cardiac fibrosis is species-specific. In this study, the effect of pharmacological PAI-1 inhibition in a mouse model of Ang II-induced vascular remodeling and cardiac fibrosis was examined. PAI-1 inhibition significantly attenuated Ang II-induced aortic medial and wall thickening, but not cardiac hypertrophy, and enhanced Ang II/salt-induced cardiac fibrosis.
answer:
Does pharmacological inhibition and genetic deficiency of plasminogen activator inhibitor-1 attenuate angiotensin II/salt-induced aortic remodeling?


question:
Context: Material loss at the taper junction of metal-on-metal total hip arthroplasties has been implicated in their early failure. The mechanisms of material loss are not fully understood; analysis of the patterns of damage at the taper can help us better understand why material loss occurs at this junction.', 'We mapped the patterns of material loss in a series of 155 metal-on-metal total hip arthroplasties received at our center by scanning the taper surface using a roundness-measuring machine. We examined these material loss maps to develop a 5-tier classification system based on visual differences between different patterns. We correlated these patterns to surgical, implant, and patient factors known to be important for head-stem taper damage.', 'We found that 63 implants had "minimal damage" at the taper (material loss <1 mm
Answer: These material loss maps allow us to suggest different mechanisms that dominate the cause of the material loss in each pattern: (1) corrosion, (2) mechanically assisted corrosion, or (3) intraoperative damage or poor size tolerances leading to toggling of trunnion in taper.
answer:
Does damage Patterns at the Head-Stem Taper Junction help Understand the Mechanisms of Material Loss?


question:
Context: Immune responses are tempered in immunologically privileged sites including the testis. Previous studies have shown that islet transplantation in the testis significantly prolongs islet allograft survival. However, mechanisms underlying testicular immune privilege and intratesticular allograft survival remain unclear.', 'Allogeneic murine islets were transplanted in the testis. Programmed death-1 ligand-1 (PD-L1) expression was detected by immunohistochemstry and real-time polymerase chain reaction. Infiltrating T-cell proliferation was measured by bromodeoxyuridine uptakes, whereas their apoptosis was quantified by terminal deoxynucleotide transferase-mediated dUTP nick-end labeling methods. Transgenic T cells were used to track allospecific memory T-cell generation.', 'We found that programmed death-1 (PD-1):PD-L1 negative costimulation is essential for prolonged survival of intratesticular islet allografts, as blocking PD-L1 or PD-1, but not PD-L2 and cytotoxic T-lymphocyte antigen 4, abrogated long-term survival of intratesticular islet allografts. As controls, blocking PD-1 or PD-L1 did not significantly accelerate the acute rejection of islet allografts transplanted under the renal capsule, a conventional islet-grafting site. We also found for the first time that PD-L1 is constitutively expressed mainly by spermatocytes and spermatids in seminiferous tubules of the testis. Moreover, infiltrating T cells underwent less vigorous proliferation but faster apoptosis in the testis than in the kidney. Blocking PD-1:PD-L1 costimulation largely abolished the suppression of T-cell proliferation and acceleration of T-cell apoptosis. Importantly, testicular immune privilege significantly suppressed the generation and proliferation of donor-specific memory CD8 T cells.
Answer: The constitutive expression of PD-L1 in the testis is an important mechanism underlying testicular immune privilege and long-term survival of intratesticular islet allografts.
answer:

Does interaction of programmed death-1 and programmed death-1 ligand-1 contribute to testicular immune privilege?