Given a context passage, generate a question from the passage such that its answer is shortest continous span from the passage.
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Question: Increased expression of nerve growth factor in injured or inflamed tissue is associated with increased pain. This proof-of-concept study was designed to investigate the safety and analgesic efficacy of tanezumab, a humanized monoclonal antibody that binds and inhibits nerve growth factor. We randomly assigned 450 patients with osteoarthritis of the knee to receive tanezumab (administered at a dose of 10, 25, 50, 100, or 200 g per kilogram of body weight) or placebo on days 1 and 56. The primary efficacy measures were knee pain while walking and the patient's global assessment of response to therapy. We also assessed pain, stiffness, and physical function using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC); the rate of response using the criteria of the Outcome Measures for Rheumatology Committee and Osteoarthritis Research Society International Standing Committee for Clinical Trials Response Criteria Initiative (OMERACT-OARSI); and safety. When averaged over weeks 1 through 16, the mean reductions from baseline in knee pain while walking ranged from 45 to 62% with various doses of tanezumab, as compared with 22% with placebo (P<0.001). Tanezumab, as compared with placebo, was also associated with significantly greater improvements in the response to therapy as assessed with the use of the patients' global assessment measure (mean increases in score of 29 to 47% with various doses of tanezumab, as compared with 19% with placebo; P0.001). The rate of response according to the OMERACT-OARSI criteria ranged from 74 to 93% with tanezumab treatment, as compared with 44% with placebo (P<0.001). The rates of adverse events were 68% and 55% in the tanezumab and placebo groups, respectively. The most common adverse events among tanezumab-treated patients were headache (9% of the patients), upper respiratory tract infection (7%), and paresthesia (7%). In this proof-of-concept study, treatment with tanezumab was associated with a reduction in joint pain and improvement in function, with mild and moderate adverse events, among patients with moderate-to-severe osteoarthritis of the knee. (Funded by Rinat Neuroscience; ClinicalTrials.gov number, NCT00394563.).

Answer: What is the target of tanezumab?

Question: Neurofibromatosis type 1 (NF1) is a neurocutaneous disorder resulting in the growth of a variety of tumours, and is inherited in an autosomal dominant pattern. Gastrointestinal stromal tumours (GISTs) are mesenchymal tumours that commonly harbour oncogenic mutations in KIT or PDGFRA and are thought to arise from the interstitial cells of Cajal (ICC; the pacemaker cells of the gut). To characterise two patients with NF1 and GISTs. Two patients were genotyped for germline mutations in NF1. GISTs from both patients were genotyped for somatic mutations in KIT and PDGFRA. Loss of heterozygosity (LOH) of NF1 in one GIST was assessed by genotyping seven microsatellite markers spanning 2.39 Mb of the NF1 locus in the tumour and in genomic DNA. The known germline mutation in NF1 was confirmed in GIST DNA by sequencing. The copy number of the mutated NF1 allele was determined by multiplex ligand-dependent probe amplification. GISTs from both patients were of wild type for mutations in KIT and PDGFRA. In the GIST with adequate DNA, all seven markers were informative and showed LOH at the NF1 locus; sequencing of NF1 from that GIST showed no wild-type sequence, suggesting that it was lost in the tumour. Multiplex ligand-dependent probe amplification analysis showed that two copies of all NF1 exons were present. This is the first evidence of mitotic recombination resulting in a reduction to homozygosity of a germline NF1 mutation in an NF1-associated GIST. We hypothesise that the LOH of NF1 and lack of KIT and PDGFRA mutations are evidence of an alternative pathogenesis in NF1-associated GISTs.

Answer: Which is the gene mutated in type 1 neurofibromatosis?

Question: A pulley is a simple machine that consists of a rope and grooved wheel. The rope fits into the groove in the wheel, and pulling on the rope turns the wheel. Pulleys are generally used to lift objects, especially heavy objects. The object lifted by a pulley is called the load. The force applied to the pulley is called the effort. Q: Can you guess what the pulley pictured above is used for? A: The pulley is used to lift heavy buckets full of water out of the well. Some pulleys are attached to a beam or other secure surface and remain fixed in place. They are called fixed pulleys. Other pulleys are attached to the object being moved and are moveable themselves. They are called moveable pulleys. Sometimes, fixed and moveable pulleys are used together. They make up a compound pulley. The three types of pulleys are compared in the Table 1.1. Q: Which type of pulley is the old pulley in the opening image? A: The old pulley is a single fixed pulley. It is securely attached to the beam above it. Type of Pulley How It Works Example Single fixed pul- ley Flagpole pulley No. of Rope Segments Pulling Up 1 Ideal Mechani- cal Advantage 1 Change Direction Force? yes Single moveable pulley Zip-line pulley 2 2 no Compound pulley (fixed & moveable pulleys) Crane pulley 2 2 varies in of The mechanical advantage of a simple machine such as a pulley is the factor by which the machine changes the force applied to it. The ideal mechanical advantage of a machine is its mechanical advantage in the absence of friction. All machines must overcome friction, so the ideal mechanical advantage is always somewhat greater than the actual mechanical advantage of the machine as it is used in the real world. In a pulley, the ideal mechanical advantage is equal to the number of rope segments pulling up on the object. The more rope segments that are helping to do the lifting work, the less force that is needed for the job. Look at the table of types of pulleys. It gives the ideal mechanical advantage of each type. In the single fixed pulley, only one rope segment pulls up on the load, so the ideal mechanical advantage is 1. In other words, this type of pulley doesnt increase the force that is applied to it. However, it does change the direction of the force. This allows you to use your weight to pull on one end of the rope and more easily raise the load attached to the other end. In the single moveable pulley, two rope segments pull up on the load, so the ideal mechanical advantage is 2. This type of pulley doesnt change the direction of the force applied to it, but it increases the force by a factor of 2. In a compound pulley, two or more rope segments pull up on the load, so the ideal mechanical advantage is 2 or greater than 2. This type of pulley may or may not change the direction of the force applied to itit depends on the number and arrangement of pulleysbut the increase in force may be great. Q: If a compound pulley has four rope segments pulling up on the load, by what factor does it multiply the force applied to the pulley? A: With four rope segments, the ideal mechanical advantage is 4. This means that the compound pulley multiplies the force applied to it by a factor of 4. For example if 400 Newtons of force were applied to the pulley, the pulley would apply 1600 Newtons of force to the load.

Answer:
a flagpole pulley is a