Zygmunt Gloger in his Encyklopedia staropolska mentions that the Polish plait (plica polonica) hairstyle was worn by some people in the Pinsk region and the Masovia region at the beginning of the 19th century. The Polish plait can vary between one large plait and multiple plaits that resemble dreadlocks. Dreadlocks are also worn by some Rastafarians, who believe they represent a biblical hair style worn as a symbol of devotion by the Nazirites, as described in Numbers 6:1–21. By culture
Locks have been worn for various reasons in each culture. Their use has also been raised in debates about cultural appropriation. Africa
Maasai warriors are known for their long, thin, red dreadlocks, dyed with red root extracts or red ochre.In Nigeria, dreadlocks are viewed in a negative light due to their stereotypical association with gangs and criminal activity; men with dreadlocks face profiling from Nigerian police. Australia
Some Indigenous Australians of North West and North Central Australia, as well as the Gold Coast region of North East Australia, have historically worn their hair in a locked style, sometimes also having long beards that are fully or partially locked. Traditionally, some wear the dreadlocks loose, while others wrap the dreadlocks around their heads, or bind them at the back of the head. In North Central Australia, the tradition is for the dreadlocks to be greased with fat and coated with red ochre, which assists in their formation. Buddhism
Within Tibetan Buddhism and other more esoteric forms of Buddhism, locks have occasionally been substituted for the more traditional shaved head.
BCR-ABL is detected in 95% of patients with CML.Patients with CML currently receive front line therapies nilotinib and/or dasatinib though 22−33% of patients discontinue therapy by two years due to adverse events, treatment failure and other causes. Discovery and origin
Ponatinib was designed using ARIADs computational and structure-based drug design platform to inhibit the enzymatic activity of BCR-ABL with very high potency and broad specificity. Ponatinib was intended to target not only native BCR-ABL, but also its isoforms that carry mutations that confer resistance to treatment with existing tyrosine kinase inhibitors, including especially the T315I mutation for which no effective therapy exists.The road to discovery is linked to AP23464, one of the first of Ariads ATP competitive dual Src/Abl inhibitors. AP23464 was identified using structure base drug design and focused synthetic libraries of trisubstituted purine analogs. The substance potently inhibits Src and Bcr-Abl kinases including many common imatinib-resistant Bcr-Abl mutations. AP23464 does not inhibit the T315I mutation, however, whereas ponatinib does.