instruction:
In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
question:
Context: Classical conditioning of the eyeblink reflex is a simple form of motor learning which depends on the integrity of the cerebellum. Acquisition of conditioned eyeblink responses is markedly reduced in patients with cerebellar disorders. Noninvasive transcranial direct current stimulation (tDCS) has been reported to modify the excitability of the cerebellar cortex.', 'The aim of the study was to assess whether acquisition of conditioned eyeblink responses (CR) is altered by cerebellar tDCS.', 'A standard delay conditioning paradigm with a 540 ms tone as conditioned stimulus (CS) coterminating with a 100 ms air puff as unconditioned stimulus (US) was used in a total of 30 healthy subjects (18 female, 12 male, mean age 23.4 ± 1.9 years). One hundred paired CS-US trials and 30 extinction CS alone trials were given. tDCS (2 mA intensity, ramp like onset) was applied over the right cerebellar hemisphere ipsilaterally to the US during the acquisition phase. Subjects were randomly assigned to three groups (n = 10) using anodal, cathodal or sham stimulation. The investigator as well as the participants was blinded to the stimulation modality.', 'CR acquisition was significantly enhanced by anodal tDCS (mean total CR incidence 73.4 ± 25.2%) and significantly reduced by cathodal stimulation (12.6 ± 17.2%) compared to sham stimulation (43.8 ± 24.1%). During anodal tDCS CR onset occurred significantly earlier, that is mean onset of responses was shifted closer to CS onset.\Question: Is acquisition of conditioned eyeblink responses modulated by cerebellar tDCS?
answer:
Acquisition and timing of conditioned eyeblink responses is modified by cerebellar tDCS in a polarity dependent manner.


question:
Context: To evaluate pazopanib eye drops in subjects with active subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD).', 'Multicountry, randomized, parallel-group, double-masked, active and placebo-controlled, dose-ranging study of eye drops.', 'A total of 510 subjects (93% white; 58% female; mean age, 75.3 years) whose AMD was previously managed by anti-vascular endothelial growth factor intravitreal injections.', 'Treatments administered for 52 weeks included placebo eye drops instilled 4 times daily (n=73); pazopanib 5 mg/ml instilled 3 (n=72) or 4 times daily (n=74); pazopanib 10 mg/ml instilled 2 (n=73), 3 (n=73), or 4 times daily (n=72); or ranibizumab injection administered once every 4 weeks (n=73). In addition, for all eye drop treatment groups, open-label ranibizumab was administered as needed.', 'The main outcome measures were best-corrected visual acuity (BCVA) and injection frequency assessed at week 52. Safety was assessed every 4 weeks and pazopanib plasma concentrations were determined at weeks 4 and 24.', 'At week 52, pazopanib, with allowance for as-needed ranibizumab injections, was noninferior to monthly ranibizumab as well as to as-needed ranibizumab administered with placebo eye drops in maintaining BCVA (estimated BCVA gains of 0.3-1.8 vs. 1.4 vs. 0.2 letters, respectively). Pazopanib treatment did not reduce as-needed ranibizumab injections by ≥50% (prespecified efficacy criterion). At week 52, there were no clinically meaningful changes from baseline in retinal thickness or morphology, CNV size, or lesion characteristics on optical coherence tomography or fluorescein angiography. Complement factor H genotype had no effect on the responses to pazopanib and/or ranibizumab (BCVA, injection rate, or optical coherence tomography/fluorescein angiography changes). Steady-state concentrations of pazopanib in plasma seemed to be reached by week 4. The most common ocular adverse events related to pazopanib and ranibizumab were application site pain (3%) and injection site hemorrhage (1%), respectively. No treatment-related serious adverse events were reported.\Question: Does clinical evaluation of pazopanib eye drop versus ranibizumab intravitreal injections in subjects with neovascular age-related macular degeneration?
answer:
Pazopanib was well tolerated. Daily pazopanib eye drops in neovascular AMD subjects did not result in therapeutic benefit beyond that obtained with ranibizumab alone.


question:
Context: The mitotic kinases, Cdk1, Aurora A/B, and Polo-like kinase 1 (Plk1) have been characterized extensively to further understanding of mitotic mechanisms and as potential targets for cancer therapy. Cdk1 and Aurora kinase studies have been facilitated by small-molecule inhibitors, but few if any potent Plk1 inhibitors have been identified.', "We describe the cellular effects of a novel compound, BI 2536, a potent and selective inhibitor of Plk1. The fact that BI 2536 blocks Plk1 activity fully and instantaneously enabled us to study controversial and unknown functions of Plk1. Cells treated with BI 2536 are delayed in prophase but eventually import Cdk1-cyclin B into the nucleus, enter prometaphase, and degrade cyclin A, although BI 2536 prevents degradation of the APC/C inhibitor Emi1. BI 2536-treated cells lack prophase microtubule asters and thus polymerize mitotic microtubules only after nuclear-envelope breakdown and form monopolar spindles that do not stably attach to kinetochores. Mad2 accumulates at kinetochores, and cells arrest with an activated spindle-assembly checkpoint. BI 2536 prevents Plk1's enrichment at kinetochores and centrosomes, and when added to metaphase cells, it induces detachment of microtubules from kinetochores and leads to spindle collapse.\Question: Does the small-molecule inhibitor BI 2536 reveal novel insights into mitotic roles of polo-like kinase 1?
answer:

Our results suggest that Plk1's accumulation at centrosomes and kinetochores depends on its own activity and that this activity is required for maintaining centrosome and kinetochore function. Our data also show that Plk1 is not required for prophase entry, but delays transition to prometaphase, and that Emi1 destruction in prometaphase is not essential for APC/C-mediated cyclin A degradation.