Given a passage, 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.

[Q]: Alzheimer's disease (AD) is characterized by cerebral deposition of β-amyloid peptide (Aβ). Aβ is produced by sequential cleavage of the Amyloid Precursor Protein (APP) by β- and γ-secretases. Many studies have demonstrated that the internalization of APP from the cell surface can regulate Aβ production, although the exact organelle in which Aβ is produced remains contentious. A number of recent studies suggest that intracellular trafficking also plays a role in regulating Aβ production, but these pathways are relatively under-studied. The goal of this study was to elucidate the intracellular trafficking of APP, and to examine the site of intracellular APP processing.", 'We have tagged APP on its C-terminal cytoplasmic tail with photoactivatable Green Fluorescent Protein (paGFP). By photoactivating APP-paGFP in the Golgi, using the Golgi marker Galactosyltranferase fused to Cyan Fluorescent Protein (GalT-CFP) as a target, we are able to follow a population of nascent APP molecules from the Golgi to downstream compartments identified with compartment markers tagged with red fluorescent protein (mRFP or mCherry); including rab5 (early endosomes) rab9 (late endosomes) and LAMP1 (lysosomes). Because γ-cleavage of APP releases the cytoplasmic tail of APP including the photoactivated GFP, resulting in loss of fluorescence, we are able to visualize the cleavage of APP in these compartments. Using APP-paGFP, we show that APP is rapidly trafficked from the Golgi apparatus to the lysosome; where it is rapidly cleared. Chloroquine and the highly selective γ-secretase inhibitor, L685, 458, cause the accumulation of APP in lysosomes implying that APP is being cleaved by secretases in the lysosome. The Swedish mutation dramatically increases the rate of lysosomal APP processing, which is also inhibited by chloroquine and L685, 458. By knocking down adaptor protein 3 (AP-3; a heterotetrameric protein complex required for trafficking many proteins to the lysosome) using siRNA, we are able to reduce this lysosomal transport. Blocking lysosomal transport of APP reduces Aβ production by more than a third.
[A]: Is the Amyloid Precursor Protein rapidly transported from the Golgi apparatus to the lysosome and where it is processed into beta-amyloid?


[Q]: Leaks of the blood-brain barrier can be detected on postcontrast-enhanced T1-weighted MRIs. Although early disruptions of the blood-brain barrier appear to be an important risk factor for tissue plasminogen activator-related hemorrhages in rodents, little is known about their incidence and consequences in human stroke.', "This is a retrospective analysis of a prospectively collected stroke database over the past 6 years. In 52 patients, multimodal MRI (including diffusion-weighted, perfusion-weighted, and postcontrast-enhanced T1-weighted MRI to detect blood-brain barrier changes) had been performed immediately before systemic thrombolysis and in 48 patients within a median of 30 minutes (interquartile range: 30 to 60 minutes) after recombinant tissue plasminogen activator treatment. The incidence of symptomatic hemorrhage (SICH), defined as any parenchymal hemorrhage leading to deterioration in the patient's clinical condition, was related to several clinical and imaging variables, including early blood-brain barrier changes.", 'Overall, SICH was detected in 9 (9%) patients and among these, 2 died. Although no blood-brain barrier changes were detectable before thrombolysis, 3 of 48 patients (6.25%) had a parenchymal gadolinium enhancement in the areas of initial infarction after tissue plasminogen activator treatment. All 3 patients developed SICHs at sites corresponding to the areas of enhancement. The presence of a parenchymal enhancement was significantly associated with SICH (P<0.01), whereas other clinical and imaging variables did not predict SICH in this series.
[A]: Does early disruption of the blood-brain barrier after thrombolytic therapy predict hemorrhage in patients with acute stroke?


[Q]: Rush immunotherapy (RIT) presents an attractive alternative to standard immunotherapy. However, RIT carries a much greater risk of acute allergic reactions, including anaphylaxis.', 'We hypothesized that omalizumab, a humanized monoclonal anti-IgE antibody, would be effective in enhancing both safety and efficacy of RIT.', 'Adult patients with ragweed allergic rhinitis were enrolled in a 3-center, 4-arm, double-blind, parallel-group, placebo-controlled trial. Patients received either 9 weeks of omalizumab (0.016 mg/kg/IgE [IU/mL]/mo) or placebo, followed by 1-day rush (maximal dose 1.2-4.0 mug Amb a 1) or placebo immunotherapy, then 12 weeks of omalizumab or placebo plus immunotherapy.', 'Of the 159 patients enrolled, 123 completed all treatments. Ragweed-specific IgG levels increased >11-fold in immunotherapy patients, and free IgE levels declined >10-fold in omalizumab patients. Patients receiving omalizumab plus immunotherapy had fewer adverse events than those receiving immunotherapy alone. Post hoc analysis of groups receiving immunotherapy demonstrated that addition of omalizumab resulted in a 5-fold decrease in risk of anaphylaxis caused by RIT (odds ratio, 0.17; P = .026). On an intent-to-treat basis, patients receiving both omalizumab and immunotherapy showed a significant improvement in severity scores during the ragweed season compared with those receiving immunotherapy alone (0.69 vs 0.86; P = .044).
[A]:
Does omalizumab pretreatment decrease acute reactions after rush immunotherapy for ragweed-induced seasonal allergic rhinitis?