The first shi originally ran from 11 pm to 1 am but was reckoned as starting at midnight by the time of the History of Song, compiled during the early Yuan. These apparently began to be used during the Eastern Han that preceded the Three Kingdoms era, but the sections that would have covered them are missing from their official histories; they first appear in official use in the Tang-era Book of Sui. Variations of all these units were subsequently adopted by Japan and the other countries of the Sinosphere. The 12 shi supposedly began to be divided into 24 hours under the Tang, although they are first attested in the Ming-era Book of Yuan. In that work, the hours were known by the same earthly branches as the shi, with the first half noted as its "starting" and the second as "completed" or "proper" shi. In modern China, these are instead simply numbered and described as "little shi". The modern ke is now used to count quarter-hours, rather than a separate unit. As with the Egyptian night and daytime hours, the division of the day into twelve shi has been credited to the example set by the rough number of lunar cycles in a solar year, although the 12-year Jovian orbital cycle was more important to traditional Chinese and Babylonian reckoning of the zodiac. Southeast Asia
In Thailand, Laos, and Cambodia, the traditional system of noting hours is the six-hour clock.
Signs and symptoms
Genetics
Costello syndrome is caused by any of at least five different mutations in the HRAS gene on chromosome 11. This gene provides instructions for making a protein, H-Ras, that helps control cell growth and division. Mutations that cause Costello syndrome lead to the production of an H-Ras protein that is permanently active. Instead of triggering cell growth in response to particular signals from outside the cell, the overactive protein directs cells to grow and divide constantly. This unchecked cell division may predispose those affected to the development of benign and malignant tumors. It remains unclear how mutations in HRAS cause other features of Costello syndrome, but many of the signs and symptoms may result from cell overgrowth and abnormal cell division.HRAS is a proto-oncogene in which somatic mutations in healthy people can contribute to cancer. Whereas children with Costello syndrome typically have a mutation in HRAS in every cell of their bodies, an otherwise healthy person with a tumor caused in part by HRAS mutation will only have mutant HRAS within the tumor. The test for the mutation in cancer tumors can also be used to test children for Costello syndrome.Costello syndrome is inherited in an autosomal dominant manner, which means one copy of the altered gene is sufficient to cause the disorder. Almost all cases have resulted from new mutations, and occur in people with no history of the disorder in their family. This condition is rare; as of 20 April 2007, 200 to 300 cases have been reported worldwide.