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I have also determined that negative elements interfere with the frozenset optimization described in issue6690. http://bugs.python.org/issue6690.
Here's an example program:
# test.py
from dis import dis
def x(var): return var in {1,2,3} # Note curly braces. These are sets.
def y(var): return var in {1,-2,3}
print ("dis x:")
dis(x)
print()
print("dis y:")
dis(y)
Running this produces:
C:\tmp>c:\Python32\python.exe test.py
dis x:
 3 0 LOAD_FAST 0 (var)
 3 LOAD_CONST 4 (frozenset({1, 2, 3}))
 6 COMPARE_OP 6 (in)
 9 RETURN_VALUE
dis y:
 4 0 LOAD_FAST 0 (var)
 3 LOAD_CONST 1 (1)
 6 LOAD_CONST 4 (-2)
 9 LOAD_CONST 3 (3)
 12 BUILD_SET 3
 15 COMPARE_OP 6 (in)
 18 RETURN_VALUE