instruction:
Given a question and a context passage, generate the answer having the word or phrase from the context passage. Here, the answer should be a shortest continous span from the passage.
question:
Context: The war had three phases. Initially it was a localized feud between supporters of Gebhard and those of the Catholic core of the Cathedral Chapter. With the election of Ernst of Bavaria as a competing archbishop, what had been a local conflict expanded in scale: Ernst's election guaranteed the military, diplomatic, and financial interest of the Wittelsbach family in the Electorate of Cologne's local affairs. After the deaths of Louis VI, Elector Palatine in 1583and William the Silent in 1584, the conflict shifted gears again, as the two evenly matched combatants sought outside assistance to break the stalemate. Finally, the intervention of Alexander Farnese, Duke of Parma, who had at his command the Spanish Army of Flanders, threw the balance of power in favor of the Catholic side. By 1588, Spanish forces had pushed Gebhard from the Electorate. In 1588 he took refuge in Strassburg, and the remaining Protestant strongholds of the Electorate fell to Parma's forces in 1589.
Question: After Louis VI, Elector Palatine, and Williant the Silent died, what set into motion the third phase of the war?
answer:
the intervention of alexander farnese

question:
Context: Autosomal-recessive hereditary spastic paraplegias (AR-HSP) consist of a genetically diverse group of neurodegenerative diseases characterised by pyramidal tracts dysfunction. The causative genes for many types of AR-HSP remain elusive. We tried to identify the gene mutation for AR-HSP with cerebellar ataxia and neuropathy. This study included two patients in a Japanese family with their parents who are first cousins. Neurological examination and gene analysis were conducted in the two patients and two normal family members. We undertook genome-wide linkage analysis employing single nucleotide polymorphism arrays using the two patients' DNAs and exome sequencing using one patient's sample. We detected a homozygous missense mutation (c.4189T>G, p.F1397V) in the lysosomal trafficking regulator (LYST) gene, which is described as the causative gene for Chediak-Higashi syndrome (CHS). CHS is a rare autosomal-recessive syndrome characterised by hypopigmentation, severe immune deficiency, a bleeding tendency and progressive neurological dysfunction. This mutation was co-segregated with the disease in the family and was located at well-conserved amino acid. This LYST mutation was not found in 200 Japanese control DNAs. Microscopic observation of peripheral blood in the two patients disclosed large peroxidase-positive granules in both patients' granulocytes, although they had no symptoms of immune deficiency or bleeding tendency. We diagnosed these patients as having adult CHS presenting spastic paraplegia with cerebellar ataxia and neuropathy. The clinical spectrum of CHS is broader than previously recognised. Adult CHS must be considered in the differential diagnosis of AR-HSP.
Question: Which mutated gene causes the ChediakHigashi Syndrome?
answer:
lysosomal trafficking regulator gene

question:
Context: Current therapies for Alzheimer's disease only treat the symptoms of the disease. We have previously developed a novel monoclonal antibody, 2B3, which binds to the -secretase cleavage site in amyloid precursor protein (APP) and reduces the production of amyloid- (A) in human cell lines. To determine whether the antibody was likely to be effective in mouse models of amyloid pathology in vivo, we investigated whether 2B3 could also bind to APP in mouse primary cortical neurones. Primary cortical neurones were produced from E15.5-17.5 C57Bl/6 wild-type and transgenic APP/V717I (London mutation) embryos. The percentage of the neuronal population was determined by immunocytochemistry. Cells were treated with 10 g/ml 2B3 or an irrelevant IgG for 48 h and A40 levels determined by ELISA. The population of cells was found to contain over 75% neurones and 2B3 bound effectively to these cells. No differences in A40 were detected between wild-type and transgenic cells. Importantly, 2B3 significantly inhibited the production of A40 by 75.151.37% of the media control, whereas an irrelevant IgG only significantly reduced A40 levels by 23.355.55% of the media control. The reduction in A40 produced by 2B3 was significantly greater than that caused by the IgG. These data indicate that 2B3 binds to APP in mouse neurones and can inhibit A40, similar to our previous findings. The antibody is probably therefore acting by steric hindrance of -secretase and these data suggest that it will be effective in mice in vivo and could be an alternative potential therapy for Alzheimer's disease.
Question: Which disease the London mutation involved in?
answer:
alzheimer's disease