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.

Input: Consider Input: Context: Angiostatin is a potent angiogenesis inhibitor that has been identified as a cryptic fragment of plasminogen molecule containing the first four kringle domain. Angiogenin, a 14-kDa monomeric protein, a potent blood vessel inducer, is expressed in tumors and present in mammalian plasma. The purpose of this study was to determine whether recombinant kringle 1-3 (rKI-3) of human plasminogen could interfere with angiogenesis induced by angiogenin and to evaluate the role of angiogenin in corneal angiogenesis in rabbit.', 'A Hydron polymer pellet containing 2.0 microg of angiogenin was implanted intrastromally into the superior cornea of each of 44 rabbit eyes. All eyes received an intrastromal pellet and were randomized into either one group treated with 12.5 microg of rKI-3 (n = 25) or the other group treated with phosphate-buffered saline (PBS; n = 19). Both pellets were positioned in parallel at the site 1.2 mm from the superior limbus. Two masked observers kept the angiogenesis score daily, based on the number and the length of new vessels. The corneas with induced angiogenesis also were examined histologically.', 'On the third day of the angiogenin pellets implantation, the eye treated with rKI-3 had less angiogenesis (mean score, 4.2 +/- 6.6) than eye treated with PBS (mean score, 16.1 +/- 17.1; p < 0.05, Mann-Whitney U test). The cornea treated with PBS also showed much more leukocyte adhesion than the cornea treated with rKI-3.
Answer: Recombinant kringle 1-3 appears to inhibit angiogenin-induced angiogenesis in a rabbit corneal pocket assay. Recombinant kringle 1-3 may have therapeutic potential as an antiangiogenic agent.

Output: Does recombinant kringle 1-3 of plasminogen inhibit rabbit corneal angiogenesis induced by angiogenin?


Input: Consider Input: Context: Cerebral deposition of phospho-tau in Alzheimer's disease (AD) occurs with varying patterns within hippocampus. Lamina-specific tau changes in AD may reflect trans-synaptic propagation of phospho-tau along neuroanatomical pathways.", 'To study patterns of tau deposition within inner (IML) and outer (OML) molecular layers of dentate gyrus and their clinical and neuropathological correlates.', '98 consecutive autopsied brains from the Columbia University Brain Bank were stained for phospho-tau using AT-8. Staining density was rated as High versus Low within IML and OML. Four patterns were observed among the 98 brains: High IML&OML, n = 44; High OML Only (n = 35); High IML Only (n = 5); and Low IML&OML (n = 14). Demographic, clinical, and neuropathological characteristics of these four groups were compared.', 'High IML&OML subjects, versus High OML Only, were more likely to fulfill CERAD criteria for Definite AD (93% versus 66%, p < 0.01) and to have higher median Braak stage (6 versus 5, p < 0.01) and earlier mean age of onset (65.9 versus 73.7 y, p = 0.02), with similar symptom duration. Using logistic regression, the association between High IML&OML and AD remained significant after adjustment for demographics but not symptom duration. In the 70 subjects with Definite AD, High IML&OML was associated with younger age of onset (mean difference 3.7 years, 95%CI -6.7 to -0.7, p < 0.01), after adjustment for demographics and symptom duration.
Answer: Phospho-tau pathology, when prominent within both IML and OML, is associated with CERAD diagnosis of Definite AD and earlier age of onset in AD. Laminar patterns of tau deposition reflect regional involvements during disease course.

Output: Does hippocampal laminar distribution of tau relate to Alzheimer 's disease and age of onset?


Input: Consider Input: Context: To investigate the effect of high glucose on insulin-induced vascular endothelial growth factor (VEGF) expression in bovine retinal microvascular endothelial cells (BRECs) and to probe into related mechanisms.', 'BRECs were isolated as primary cultures and identified by immunostaining. Passage cells were initially exposed to normal (5 mM) or high glucose (30 mM) for 3 days, and equimolar L-glucose was supplemented for osmotic equation. BRECs were then treated with 100 nM insulin for 24 h or not, and cells were prepared for the determination of VEGF mRNA expression by real-time PCR. VEGF protein was determined by human umbilical vein endothelial cell proliferation assay, immunofluorescence, and ELISA. BRECs were treated with 5 or 30 mM glucose for 3 days and then cells cultured with 5 mM glucose were exposed to the PI3-K inhibitor wortmannin (100 nM), the P42/44 mitogen-activated protein kinase (MAPK) inhibitor U0126 (50 microM), or to the protein kinase C (PKC) inhibitor GF109203X (2 microM) 1 h before addition of 100 nM insulin. Twenty-four hours after incubation with insulin, the cells were subjected to real-time PCR and ELISA analyses.', 'Insulin or high glucose alone markedly increased VEGF mRNA and protein levels in BRECs (P<0.05, two-way ANOVA). However, the combination of insulin and high glucose displayed a weaker effect in promoting VEGF expression than did insulin alone (P<0.05, t-test). Pretreatment of cells with PI3-K inhibitor significantly (P<0.05, one-way ANOVA) suppressed the insulin-induced VEGF expression; neither pretreatment with the PKC inhibitor nor with the P42/p44 MAPK inhibitor showed an effect on the expression of VEGF at the mRNA or protein level (P>0.05, one-way ANOVA).
Answer: Both insulin and high glucose can markedly increase VEGF expression in BRECs at the mRNA and protein level. We propose that insulin may upregulate VEGF expression through the PI3-K signalling pathway in BRECs, and high glucose may attenuate insulin-induced VEGF expression by impairing PI3-K signalling pathways.


Output: Does high glucose attenuate insulin-induced VEGF expression in bovine retinal microvascular endothelial cells?