instruction:
Given a context passage, generate a question from the passage such that its answer is shortest continous span from the passage.
question:
Spleen tyrosine kinase (Syk) is a cytoplasmic tyrosine kinase involved in signalling in many of the cells that drive immune inflammation. The development of small molecules that inhibit Syk kinase may change the way we treat disorders such as rheumatoid arthritis (RA), as well as a range of other inflammatory diseases. Fostamatinib (R-788) is an orally bioavailable small molecule. It is the prodrug of R406, which is a potent Syk inhibitor. Fostamatinib was developed because it has more favourable physiochemical properties. It is rapidly converted to R406 by intestinal enterocytes. It has been evaluated in experimental models of RA, such as collagen-induced arthritis. In these models, fostamatinib suppressed clinical arthritis, bone erosions, pannus formation and synovitis. A phase II programme with fostamatinib has largely been completed. Three key trials have been published, lasting 12-26 weeks and each enrolling 189-457 patients (875 in total). All these trials involved placebo therapy and patients continued to receive methotrexate in addition to active treatment with fostamatinib. The first dose-ranging trial evaluated three treatment doses in RA patients who had not fully responded to methotrexate therapy. The second trial compared two treatment doses in patients who had not responded to methotrexate therapy. The third trial compared a single treatment dose with placebo in patients who had not responded to biological therapy. The primary outcome measure was the number of patients achieving American College of Rheumatology (ACR) 20% (ACR20) responses. Placebo ACR20 response rates in all three trials were similar (35-38%). All three trials involved one treatment arm receiving fostamatinib 100 mg twice daily; ACR20 responses with this active treatment ranged from 38% to 67%. A meta-analysis of ACR responses in these trials, using responses to the highest dose in each trial for comparisons with placebo therapy in a random effects model, showed a borderline benefit with ACR20 responses. There were more significant differences with ACR50 and ACR70 responses. The reason that this meta-analysis was not more strongly positive is that the third trial, which evaluated patients who had failed to respond to biological treatments, gave negative results. Individual ACR response components, such as changes in swollen joint counts, showed significant differences in the first two trials, but there were no definite treatment benefits in the third trial. Overall, the differences were significant in a meta-analysis of all three trials. The most important adverse reactions were diarrhoea, neutropenia and raised ALT levels, which all showed significant excesses with active treatment compared with placebo. Too few patients have been studied for a definitive safety profile to be known. Overall, the results of the phase II trials were sufficiently encouraging for a phase III programme to be initiated. It will be some years before their definitive results are available.
answer:
Which enzyme is inhibited by a drug fostamatinib?


question:
Leke III Dukagjini (1410--1481), mostly known as Leke Dukagjini, was a mysterious member of the Dukagjini family about whom little is known and who is thought to have been a 15th-century Albanian nobleman.
answer:
What was the noble family that Lekë Dukagjini was from?


question:
Fossils are our best form of evidence about Earth history, including the history of life. Along with other geological evidence from rocks and structures, fossils even give us clues about past climates, the motions of plates, and other major geological events. Since the present is the key to the past, what we know about a type of organism that lives today can be applied to past environments. That life on Earth has changed over time is well illustrated by the fossil record. Fossils in relatively young rocks resemble animals and plants that are living today. In general, fossils in older rocks are less similar to modern organisms. We would know very little about the organisms that came before us if there were no fossils. Modern technology has allowed scientists to reconstruct images and learn about the biology of extinct animals like dinosaurs! By knowing something about the type of organism the fossil was, geologists can determine whether the region was terrestrial (on land) or marine (underwater) or even if the water was shallow or deep. The rock may give clues to whether the rate of sedimentation was slow or rapid. The amount of wear and fragmentation of a fossil allows scientists to learn about what happened to the region after the organism died; for example, whether it was exposed to wave action. The presence of marine organisms in a rock indicates that the region where the rock was deposited was once marine. Sometimes fossils of marine organisms are found on tall mountains indicating that rocks that formed on the seabed were uplifted. By knowing something about the climate a type of organism lives in now, geologists can use fossils to decipher the climate at the time the fossil was deposited. For example, coal beds form in tropical environments but ancient coal beds are found in Antarctica. Geologists know that at that time the climate on the Antarctic continent was much warmer. Recall from the chapter Plate Tectonics that Wegener used the presence of coal beds in Antarctica as one of the lines of evidence for continental drift. An index fossil can be used to identify a specific period of time. Organisms that make good index fossils are distinctive, widespread, and lived briefly. Their presence in a rock layer can be used to identify rocks that were deposited at that period of time over a large area. The fossil of a juvenile mammoth found near downtown San Jose California reveals an enormous amount about these majestic creatures: what they looked like, how they lived, and what the environment of the Bay Area was like so long ago.
answer:

compared with fossils in younger rocks, fossils in older rocks are