Given a context passage, generate a question from the passage such that its answer is shortest continous span from the passage.
One example is below.
Q: In 1582 the united provinces invited francis, duke of anjou to lead them; but after a failed attempt to take antwerp in 1583, the duke left the netherlands again. after the assassination of william of orange (10 july 1584), both henry iii of france and elizabeth i of england declined the offer of sovereignty. however, the latter agreed to turn the united provinces into a protectorate of england (treaty of nonsuch, 1585), and sent the earl of leicester as governor-general. this was unsuccessful and in 1588 the provinces became a confederacy. the union of utrecht is regarded as the foundation of the republic of the seven united provinces, which was not recognized by the spanish empire until the peace of westphalia in 1648.
A: In what year did francis, duke of anjou leave the netherlands?
Rationale: The generated question is perfect. Because the question is based on second sentence of the input passage and its answer is 1583.
Q: In breast cancer the development of metastasis is a major turning point in the treatment and outcome of the disease. Throughout tumour development, and especially in the development of metastasis, epithelial mesenchymal transition takes place. During this transformation into a mesenchymal phenotype, the tumour cells undergo a series of structural changes. The loss of structural integrity and adoption of mesenchymal filaments enables cells to detach from the epithelial cell layer and metastasise. Keratins form the intermediate filaments of the cytoskeleton and provide scaffold structures within cells. During cancer progression the intermediate filaments are reorganised, and dramatic changes are seen in their protein components. Keratins K8, K18, K19 and vimentin are intermediate filament proteins with altered expression profiles during tumour development. We have used in vivo and in vitro models to analyse changes in intermediate filament proteins. Antibody-based methods were used to study K8 levels and proteomic analysis to profile the protein content of metastatic breast cancer cell variants. K8 expression declines as human breast tumours progress into an invasive phenotype. Analysis of IF proteins indicated altered expression profiles of K8, K18, K19 and vimentin, with K8, K18, K19 expressed in high levels in the T47D and MCF-7 cell lines, whereas the highly metastatic cell lines expressed lower levels of K8 and K18 and no detectable K19. Vimentin showed reverse expression profile with T47D and MCF-7 cells having no detectable vimentin expression whereas the highly metastatic MDA-MB-231 and MDA-MB-436 showed high levels. Analysis of acetylation status using specific antibodies suggested acetylation occurred within the central coiled domain in the MCF-7 and T47D cells. Inhibition of tumour growth by tissue factor (TF) shRNA resulted in a dramatic re-elevation of expression of K8 in xenographs of the highly metastatic MDA-MB-436 line. Intermediate filament expression alters during epithelial mesenchymal transition. Identified post translational modifications may play a role in alterations seen in the organisation, solubility and stability of these filaments. Epithelial mesenchymal transition can be reversed and an epithelial phenotype re-established.
A:
What are the structures formed when keratin molecules come together?