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(e)Tj
0.2697 Tc -0.4572 Tw 4.5 0 Td
(quences. )Tj
0.0106 Tc 1.0519 Tw -303.75 -12 Td
(Indeed, the multiple alignment problem is NP)Tj
-0.2467 Tc 0 Tw 185.25 0 Td
(-)Tj
0.09171 Tc 0.47079 Tw 3 0 Td
(complete; furthermore, a scoring sy)Tj
0.60519 Tc 0 Tw 144 0 Td
(s-)Tj
0.0117 Tc 1.3008 Tw -332.25 -12 Td
(tem is difficult to define)Tj
/TT1 6.75 Tf
0.375 Tc 0 Tw 99.75 4.5 Td
(6)Tj
/TT1 9.75 Tf
0.10989 Tc 0.9213 Tw 3.75 -4.5 Td
(. These facts gave rise to different suboptimal alg)Tj
0.375 Tc 0 Tw 206.25 0 Td
(o)Tj
-0.0285 Tc 0.591 Tw 5.25 0 Td
(rithms )Tj
0.17171 Tc 0.39079 Tw -315 -12 Td
(based on progressive alignments)Tj
/TT1 6.75 Tf
0.1875 Tc 0.375 Tw 134.25 4.5 Td
(7, 8)Tj
/TT1 9.75 Tf
0.0554 Tc -0.2429 Tw 11.25 -4.5 Td
(. Finally, there are sequence profiles)Tj
/TT1 6.75 Tf
0.375 Tc 0 Tw 143.25 4.5 Td
(9)Tj
/TT1 9.75 Tf
0.31709 Tc -0.50459 Tw 3.75 -4.5 Td
( and hi)Tj
0.375 Tc 0 Tw 27 0 Td
(d)Tj
0.30701 Tc 0.25549 Tw 5.25 0 Td
(den )Tj
-0.04469 Tc 1.35719 Tw -324.75 -12 Td
(Markov models)Tj
/TT1 6.75 Tf
0.375 Tc 0 Tw 63.75 4.5 Td
(10)Tj
/TT1 9.75 Tf
0.0345 Tc 0.528 Tw 7.5 -4.5 Td
(, which exploit position)Tj
-0.2467 Tc 0 Tw 94.5 0 Td
(-)Tj
0.1468 Tc 0.4157 Tw 3 0 Td
(specific dependencies within pr)Tj
0.375 Tc 0 Tw 128.25 0 Td
(o)Tj
0.0305 Tc 0.532 Tw 5.25 0 Td
(tein fam)Tj
-0.35361 Tc 0 Tw 32.25 0 Td
(i-)Tj
0.0508 Tc 0.8867 Tw -334.5 -12 Td
(lies. All alignment methods r)Tj
0.1261 Tc 0.4364 Tw 117.75 0 Td
(equire a scoring system, which is typically a)Tj
0.375 Tc 0 Tw 180.75 0 Td
(d)Tj
0.2652 Tc 0.2973 Tw 5.25 0 Td
(justed to )Tj
0.08521 Tc -0.27271 Tw -303.75 -12 Td
(optimize sensitivity and specificity.)Tj
0 Tc -0.1875 Tw 140.25 0 Td
( )Tj
0.1675 Tc 1.145 Tw -123 -12 Td
(In a given twenty)Tj
-0.2467 Tc 0 Tw 74.25 0 Td
(-)Tj
0.375 Tc 3 0 Td
(by)Tj
-0.2467 Tc 10.5 0 Td
(-)Tj
0.0592 Tc 0.95329 Tw 3 0 Td
(twenty scoring matrix, each entry, )Tj
/TT2 9.75 Tf
-0.0428 Tc 0 Tw 144 0 Td
(s)Tj
/TT2 6.75 Tf
0.3735 Tc 3.75 -1.5 Td
(ij)Tj
/TT1 9.75 Tf
0.1803 Tc 0.8322 Tw 4.5 1.5 Td
(, is the score when )Tj
0.0589 Tc 0.1286 Tw -260.25 -12 Td
(amino acids )Tj
/TT2 9.75 Tf
0.28951 Tc 0 Tw 49.5 0 Td
(i)Tj
/TT1 9.75 Tf
0.30701 Tc -0.11951 Tw 3 0 Td
( and )Tj
/TT2 9.75 Tf
0.28951 Tc 0 Tw 19.5 0 Td
(j)Tj
/TT1 9.75 Tf
0.129 Tc -0.3165 Tw 2.25 0 Td
( are aligned opposite one another. Typically, )Tj
/TT2 9.75 Tf
-0.0428 Tc 0 Tw 180 0 Td
(s)Tj
/TT2 6.75 Tf
0.3735 Tc 3.75 -1.5 Td
(ij)Tj
/TT1 9.75 Tf
0.1519 Tc -0.1519 Tw 4.5 1.5 Td
( is a function )Tj
0.4391 Tc 0 Tw 54 0 Td
(of)Tj
0 Tc -0.1875 Tw 8.25 0 Td
( )Tj
ET
0 0 0 RG
0.75 w 10 M 1 j 1 J []0 d
304.5 284.25 m
341.25 284.25 l
S
BT
/TT1 10 Tf
-0.33 Tc 0 Tw 336.75 273.75 Td
(\))Tj
-8.25 0 Td
(\()Tj
-10.5 0 Td
(\))Tj
-6 0 Td
(\()Tj
19.5 14.25 Td
(\))Tj
-0.25 Tc -8.25 0 Td
(,)Tj
-0.33 Tc -6 0 Td
(\()Tj
-0.00999 Tc -27 -6.75 Td
(log)Tj
/TT2 10 Tf
0.22 Tc 43.5 -7.5 Td
(j)Tj
0.25 Tc -10.5 0 Td
(p)Tj
0.22 Tc -8.25 0 Td
(i)Tj
0.25 Tc -8.25 0 Td
(p)Tj
0.22 Tc 21.75 14.25 Td
(j)Tj
-8.25 0 Td
(i)Tj
0.25 Tc -8.25 0 Td
(p)Tj
/TT1 9.75 Tf
-0.26401 Tc 0.07651 Tw 31.5 -6.75 Td
(, \(1\))Tj
0 Tc -0.1875 Tw 132 0 Td
( )Tj
0.03619 Tc -0.22369 Tw -339.75 -22.5 Td
(where )Tj
/TT2 9.75 Tf
0.375 Tc 0 Tw 27 0 Td
(p)Tj
/TT1 9.75 Tf
-0.2467 Tc 5.25 0 Td
(\()Tj
/TT2 9.75 Tf
0.28951 Tc 3 0 Td
(i)Tj
/TT1 9.75 Tf
-0.1875 Tc 3 0 Td
(,)Tj
0 Tc -0.1875 Tw 2.25 0 Td
( )Tj
/TT2 9.75 Tf
0.28951 Tc 0 Tw 2.25 0 Td
(j)Tj
/TT1 9.75 Tf
0.0755 Tc 0.487 Tw 2.25 0 Td
(\) is the joint probability)Tj
/TT1 6.75 Tf
0.0023 Tc 0 Tw 96 4.5 Td
(f)Tj
1.5 0 Td
(-)Tj
0.375 Tc 2.25 0 Td
(1)Tj
/TT1 9.75 Tf
0.12601 Tc 0.43649 Tw 3.75 -4.5 Td
( of the aligned pair of residues )Tj
/TT2 9.75 Tf
0.28951 Tc 0 Tw 128.25 0 Td
(i)Tj
/TT1 9.75 Tf
0.30701 Tc 0.25549 Tw 3 0 Td
( and )Tj
/TT2 9.75 Tf
0.28951 Tc 0 Tw 21 0 Td
(j)Tj
/TT1 9.75 Tf
0.1834 Tc 0.3791 Tw 2.25 0 Td
(, and )Tj
/TT2 9.75 Tf
0.375 Tc 0 Tw 22.5 0 Td
(p)Tj
/TT1 9.75 Tf
-0.2467 Tc 5.25 0 Td
(\()Tj
/TT2 9.75 Tf
0.28951 Tc 3 0 Td
(i)Tj
/TT1 9.75 Tf
-0.2467 Tc 0.0592 Tw 3 0 Td
(\) )Tj
0.12511 Tc 0.31239 Tw -336.75 -12 Td
(the probability of occurrence of residue )Tj
/TT2 9.75 Tf
0.28951 Tc 0 Tw 164.25 0 Td
(i)Tj
/TT1 9.75 Tf
0.0988 Tc 0.4637 Tw 3 0 Td
(. This expression is called the log)Tj
-0.2467 Tc 0 Tw 136.5 0 Td
(-)Tj
0.375 Tc 3 0 Td
(od)Tj
0.2785 Tc -0.466 Tw 10.5 0 Td
(ds r)Tj
0.3371 Tc 0 Tw 15 0 Td
(a-)Tj
0.0575 Tc 0.505 Tw -332.25 -12 Td
(tio \(mutual information\) and when the log)Tj
0.17101 Tc 0 Tw 169.5 0 Td
(a)Tj
0.0981 Tc -0.1356 Tw 4.5 0 Td
(rithm is to base two it is measured in bits. )Tj
0.15939 Tc -0.2063 Tw -174 -12 Td
(The total score of two aligned sequences is finally calculated as the su\
m of scores of )Tj
0.222 Tc 0 Tw T*
(each)Tj
/TT1 12 Tf
0 Tc 18.75 0 Td
( )Tj
/TT1 9.75 Tf
0.0088 Tc 1.58501 Tw 5.25 0 Td
(aligned amino acid pair, along with empirically determined gap)Tj
-0.2467 Tc 0 Tw 261 0 Td
(-)Tj
0.4071 Tc 0.9054 Tw 3 0 Td
(opening a)Tj
0.375 Tc 0.1875 Tw 41.25 0 Td
(nd )Tj
0.30701 Tc 0 Tw -329.25 -12 Td
(gap)Tj
-0.2467 Tc 15 0 Td
(-)Tj
0.1228 Tc -0.3103 Tw 3 0 Td
(extension penalties that provide the means to accommodate length variabi\
lity.)Tj
0 Tc -0.1875 Tw 309.75 0 Td
( )Tj
/TT1 12 Tf
0 Tw -327.75 -30.75 Td
( )Tj
90 0 Td
( )Tj
ET
135.75 170.25 144 0.75 re
f
BT
/TT1 12 Tf
279.75 168 Td
( )Tj
/TT1 6.75 Tf
0.0023 Tc -144 -7.5 Td
(f)Tj
1.5 0 Td
(-)Tj
0.375 Tc 2.25 0 Td
(1)Tj
/TT1 8.25 Tf
0.1537 Tc 0.1088 Tw 3.75 -4.5 Td
(The scoring function is defined in terms of probabilities that )Tj
-0.15041 Tc 0.0379 Tw 210.75 0 Td
(are approximated by observed relative )Tj
0.106 Tc 0.0815 Tw -218.25 -9.75 Td
(frequencies. We also use terms relative frequency and probability interc\
hangeably.)Tj
/TT1 9.75 Tf
0 Tc -0.1875 Tw 282.75 0 Td
( )Tj
ET
q
/GS0 gs
/Fm0 Do
Q
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BT
/TT0 1 Tf
0 Tc 0 Tw 0 Ts 100 Tz 0 Tr 8 0 0 8 208.40401 748 Tm
(Pacific Symposium on Biocomputing 7:589-600 \(2002\) )Tj
ET
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0 0 0 rg
1 i
BT
/TT0 12 Tf
0 Tc 0 Tw 0 Ts 100 Tz 0 Tr 135.75 131.25 Td
( )Tj
/TT0 9.75 Tf
0.1264 Tc 0.3736 Tw 18 506.25 Td
(Two important sets of scoring matrices are the PAM \(accepted point muta\
tion\) )Tj
0.0499 Tc 0 Tw -18 -12 Td
(series)Tj
/TT0 6.75 Tf
0.4375 Tc 23.25 4.5 Td
(11,)Tj
0 Tc -0.1875 Tw 9 0 Td
( )Tj
0.375 Tc 0 Tw 1.5 0 Td
(12)Tj
/TT0 9.75 Tf
0.088 Tc 1.5995 Tw 7.5 -4.5 Td
( and the BLOSUM \(block substitution\) series)Tj
/TT0 6.75 Tf
0.375 Tc 0 Tw 191.25 4.5 Td
(13)Tj
/TT0 9.75 Tf
-0.1095 Tc 0.972 Tw 7.5 -4.5 Td
(. The initial PAM matrix )Tj
0.3138 Tc -0.5013 Tw -240 -12 Td
(was based on)Tj
0.10001 Tc -0.28751 Tw 54.75 0 Td
( just 1,572 substitutions. Evolutionary mode)Tj
0.28951 Tc 0 Tw 175.5 0 Td
(l)Tj
0.2382 Tc -0.4257 Tw 2.25 0 Td
(ing was then used to boost )Tj
0.2558 Tc 1.0567 Tw -232.5 -12 Td
(the data and develop a series of m)Tj
0.17101 Tc 0 Tw 146.25 0 Td
(a)Tj
0.1378 Tc 1.1747 Tw 4.5 0 Td
(trices, but this mode)Tj
0.28951 Tc 0 Tw 85.5 0 Td
(l)Tj
0.0813 Tc 0.8562 Tw 2.25 0 Td
(ing was imprecise)Tj
/TT0 6.75 Tf
0.375 Tc 0 Tw 72.75 4.5 Td
(14)Tj
/TT0 9.75 Tf
0.1003 Tc 0.0872 Tw 7.5 -4.5 Td
(. The )Tj
-0.0081 Tc 0.5706 Tw -318.75 -12 Td
(BLOSUM series was based on 2,106 aligned multiple)Tj
-0.2467 Tc 0 Tw 214.5 0 Td
(-)Tj
0.1606 Tc 0.2144 Tw 3 0 Td
(sequence segments with more )Tj
-0.075 Tc 1.7625 Tw -217.5 -12 Td
(than 15 million amino ac)Tj
0.224 Tc 1.0885 Tw 102.75 0 Td
(id pairs and used only segments in highly conserved r)Tj
0.3371 Tc 0 Tw 229.5 0 Td
(e-)Tj
0.1794 Tc -0.2419 Tw -332.25 -12 Td
(gions between gaps \(e.g. blocks\) to ca)Tj
0.28951 Tc 0 Tw 153.75 0 Td
(l)Tj
0.1731 Tc -0.3606 Tw 2.25 0 Td
(culate substit)Tj
0.375 Tc 0 Tw 54 0 Td
(u)Tj
0.0726 Tc -0.2601 Tw 5.25 0 Td
(tion probabilities. Grouping the )Tj
0.24561 Tc 1.06689 Tw -215.25 -12 Td
(aligned sequences by sequence ide)Tj
0.375 Tc 0 Tw 147.75 0 Td
(n)Tj
0.07249 Tc 0.3828 Tw 5.25 0 Td
(tity gave the BLOSUM series. After extensive )Tj
0.2177 Tc -0.4052 Tw -153 -12 Td
(testing, the )Tj
/TT0 8.25 Tf
-0.1046 Tc 0 Tw 47.25 0 Td
(BLOSUM)Tj
/TT0 9.75 Tf
-0.1631 Tc -0.0244 Tw 33.75 0 Td
(62 matrix was ide)Tj
0.3322 Tc 0 Tw 66.75 0 Td
(nt)Tj
0.28951 Tc 8.25 0 Td
(i)Tj
0.1058 Tc -0.2932 Tw 2.25 0 Td
(fied as the best general scoring matrix)Tj
/TT0 6.75 Tf
0.375 Tc 0 Tw 150 4.5 Td
(13)Tj
/TT0 9.75 Tf
-0.1875 Tc 7.5 -4.5 Td
(. )Tj
0 Tc -0.1875 Tw 4.5 0 Td
( )Tj
0.1604 Tc -0.3479 Tw -302.25 -12 Td
(Many additional scoring matrices have been developed)Tj
/TT0 6.75 Tf
0.2625 Tc -0.45 Tw 221.25 4.5 Td
(15, 16)Tj
/TT0 9.75 Tf
0.2453 Tc -0.28281 Tw 18 -4.5 Td
(. These are based on )Tj
0.08211 Tc 1.60539 Tw -257.25 -12 Td
(various criteria such as amino acid properties, structural superposition\
, minimum )Tj
0.1718 Tc 1.8907 Tw 0 -12 TD
(number of base changes per codon, evolutio)Tj
0.375 Tc 0 Tw 191.25 0 Td
(n)Tj
0.54359 Tc 1.51891 Tw 5.25 0 Td
(ary p)Tj
0.1046 Tc 1.0204 Tw 22.5 0 Td
(roperties, etc. These matrices )Tj
0.1161 Tc -0.3036 Tw -219 -12 Td
(have idiotypic advantages, but PAM and BLOSUM remain the most widely use\
d. )Tj
0 Tc -0.1875 Tw 326.25 0 Td
( )Tj
0.16701 Tc 0.27049 Tw -309 -12 Td
(The development of scoring matrices has focused on ordered proteins that\
fold )Tj
0.1908 Tc 0.3717 Tw -17.25 -12 Td
(into 3)Tj
-0.2467 Tc 0 Tw 23.25 0 Td
(-)Tj
0.16451 Tc -0.16451 Tw 3 0 Td
(D structures. In contrast, many proteins have functional regions)Tj
0.14639 Tc -0.33389 Tw 257.25 0 Td
( that exist as a )Tj
0.0937 Tc 0 Tw -283.5 -12 Td
(stru)Tj
0.17101 Tc 15.75 0 Td
(c)Tj
0.14059 Tc -0.0602 Tw 4.5 0 Td
(tural ensemble at either the secondary or the tertiary level, that is, t\
hese regions )Tj
0.06171 Tc 1.25079 Tw -20.25 -12 Td
(are intrinsically disordered)Tj
/TT0 6.75 Tf
0.375 Tc 0 Tw 108.75 4.5 Td
(17)Tj
/TT0 9.75 Tf
0.11839 Tc 0.9691 Tw 7.5 -4.5 Td
(. The realization that such disorder is not uncommon )Tj
0.1571 Tc 0.54179 Tw -116.25 -12 Td
(and is important for the function of essential proteins has led t)Tj
0.052 Tc 0.5105 Tw 258 0 Td
(o a call for the rea)Tj
0.60519 Tc 0 Tw 74.25 0 Td
(s-)Tj
0.11031 Tc -0.29781 Tw -332.25 -12 Td
(sessment of the view that function always follows from a protein\222s 3)Tj
-0.2467 Tc 0 Tw 271.5 0 Td
(-)Tj
0.01711 Tc -0.20461 Tw 3 0 Td
(D stru)Tj
0.17101 Tc 0 Tw 24.75 0 Td
(c)Tj
-0.0403 Tc 4.5 0 Td
(ture)Tj
/TT0 6.75 Tf
0.375 Tc 15.75 4.5 Td
(18)Tj
/TT0 9.75 Tf
-0.1875 Tc 7.5 -4.5 Td
(. )Tj
0 Tc -0.1875 Tw 4.5 0 Td
( )Tj
0.0959 Tc 1.5166 Tw -314.25 -12 Td
(Amino acid compositions for ordered and intrinsically disordered protein\
are )Tj
-0.0062 Tc 0.5687 Tw -17.25 -12 Td
(clearly different)Tj
/TT0 6.75 Tf
0.375 Tc 0 Tw 63 4.5 Td
(19)Tj
/TT0 9.75 Tf
0.1059 Tc 0.4566 Tw 7.5 -4.5 Td
(. Also, insertions and deletions are more common in di)Tj
0.25591 Tc -0.06841 Tw 222.75 0 Td
(sordered as )Tj
0.1454 Tc 0.4171 Tw -293.25 -12 Td
(compared to ordered regions)Tj
/TT0 6.75 Tf
0.375 Tc 0 Tw 117 4.5 Td
(20)Tj
/TT0 9.75 Tf
0.1743 Tc 0.2944 Tw 7.5 -4.5 Td
(. Thus, the scoring matrices and gap penalties deve)Tj
-0.35361 Tc 0 Tw 210 0 Td
(l-)Tj
0.0918 Tc 1.7207 Tw -334.5 -12 Td
(oped from ordered proteins are likely to be inappropriate for disordered\
protein. )Tj
0.1463 Tc 0.6974 Tw T*
(Here we report the first attempts to develop disorder)Tj
-0.2467 Tc 0 Tw 216.75 0 Td
(-)Tj
0.0896 Tc 0.4729 Tw 3 0 Td
(specific scoring matrices w)Tj
0.06799 Tc 0.49451 Tw 109.5 0 Td
(ith )Tj
0.1329 Tc -0.3204 Tw -329.25 -12 Td
(appropriately weighted gap)Tj
-0.2467 Tc 0 Tw 109.5 0 Td
(-)Tj
0.2637 Tc -0.4512 Tw 3 0 Td
(opening and gap)Tj
-0.2467 Tc 0 Tw 67.5 0 Td
(-)Tj
0.1463 Tc -0.3338 Tw 3 0 Td
(extension penalties.)Tj
0 Tc -0.1875 Tw 78.75 0 Td
( )Tj
/TT1 9.75 Tf
-0.2352 Tc 0.0477 Tw -261.75 -31.5 Td
(2 Materials and Methods)Tj
0 Tc -0.1875 Tw 100.5 0 Td
( )Tj
/TT2 9.75 Tf
0.18221 Tc -0.36971 Tw -100.5 -26.25 Td
(2.1 Databases, hardware and software)Tj
0 Tc -0.1875 Tw 156.75 0 Td
( )Tj
/TT0 9.75 Tf
0.1302 Tc 0.8698 Tw -156.75 -24 Td
(A set of proteins with structurally characterized regions of disorder of\
length )Tj
/TT3 9.75 Tf
-0.1028 Tc 0 Tw 322.5 0 Td
(\263)Tj
/TT0 9.75 Tf
-0.375 Tc 0.5625 Tw 5.25 0 Td
( 40 )Tj
0.1844 Tc -0.3719 Tw -327.75 -12 Td
(consecutive residues was identified by dat)Tj
0.1413 Tc -0.3288 Tw 170.25 0 Td
(abase and literature searches. Homol)Tj
0.375 Tc 0 Tw 146.25 0 Td
(o)Tj
-0.1044 Tc -0.0831 Tw 5.25 0 Td
(gous )Tj
0.0836 Tc 0.4789 Tw -321.75 -12 Td
(proteins were compiled using the BLAST algorithm)Tj
/TT0 6.75 Tf
0.375 Tc 0 Tw 208.5 4.5 Td
(4)Tj
/TT0 9.75 Tf
0.1355 Tc -0.073 Tw 3.75 -4.5 Td
(. For proteins with both ordered )Tj
0.1635 Tc 0.22591 Tw -212.25 -12 Td
(and disordered regions, it was assumed that segments aligning to the dis\
order were )Tj
0.1302 Tc 0.64661 Tw T*
(also disordered. The result was the following dat)Tj
0.4691 Tc 0 Tw 201 0 Td
(abase)Tj
/TT0 6.75 Tf
0.0023 Tc 23.25 4.5 Td
(f)Tj
1.5 0 Td
(-)Tj
0.375 Tc 2.25 0 Td
(2)Tj
/TT0 9.75 Tf
-0.28239 Tc 0.84489 Tw 3.75 -4.5 Td
(: 1d1r \(10, 23, 32\), 4E bin)Tj
0.4391 Tc 0 Tw 99.75 0 Td
(d-)Tj
0.23351 Tc 1.07899 Tw -331.5 -12 Td
(ing pr)Tj
0.375 Tc 0 Tw 24.75 0 Td
(o)Tj
-0.06911 Tc 1.2316 Tw 5.25 0 Td
(tein \(7, 115, 58\), ssDNA binding protein \(15, 50, 49\), )Tj
/TT3 9.75 Tf
-0.1523 Tc 0 Tw 221.25 0 Td
(a)Tj
/TT0 9.75 Tf
-0.1086 Tc 0.4836 Tw 6 0 Td
(_tubulin \(54, 48, 84\), )Tj
-0.28951 Tc 0 Tw -257.25 -12 Td
(DNA)Tj
-0.2467 Tc 21 0 Td
(-)Tj
-0.11169 Tc 5.17419 Tw 3 0 Td
(lyase \(7, 40, 80\), Bcl)Tj
-0.2467 Tc 0 Tw 99 0 Td
(-)Tj
0.375 Tc 3 0 Td
(x)Tj
/TT0 6.75 Tf
-0.3743 Tc 3.75 -1.5 Td
(L)Tj
/TT0 9.75 Tf
-0.2157 Tc 4.90331 Tw 4.5 1.5 Td
( \(7, 50, 81\), ca)Tj
0.28951 Tc 0 Tw 72.75 0 Td
(l)Tj
-0.1523 Tc 4.4648 Tw 2.25 0 Td
(cineurin \(22, 164, 34\), cyclin)Tj
-0.2467 Tc 0 Tw 127.5 0 Td
(-)Tj
/TT0 12 Tf
0 Tc -336.75 -18 Td
( )Tj
90 0 Td
( )Tj
ET
135.75 180 144 0.75 re
f
BT
/TT0 12 Tf
279.75 177.75 Td
( )Tj
/TT0 6.75 Tf
0.0023 Tc -144 -6.75 Td
(f)Tj
1.5 0 Td
(-)Tj
0.375 Tc 2.25 0 Td
(2)Tj
/TT0 6 Tf
0 Tc 3.75 -4.5 Td
( )Tj
/TT0 8.25 Tf
-0.07001 Tc 0.0575 Tw 1.5 0 Td
(The database is presented in the format: family name \(number of sequenc\
es, average sequence length, )Tj
-0.03979 Tc 0.22729 Tw -9 -10.5 Td
(average sequence ide)Tj
0.375 Tc 0 Tw 70.5 0 Td
(n)Tj
0.25951 Tc -0.07201 Tw 4.5 0 Td
(tity with )Tj
-0.0645 Tc 0.002 Tw 32.25 0 Td
(all family proteins\). The latter two numbers were rounded to the neares\
t )Tj
-0.0636 Tc 0.078 Tw -107.25 -9.75 Td
(integer. For proteins containing both ordered and disordered regions, on\
ly disordered regions were used.)Tj
/TT0 9.75 Tf
0 Tc -0.1875 Tw 339.75 0 Td
( )Tj
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(Pacific Symposium on Biocomputing 7:589-600 \(2002\) )Tj
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/TT0 12 Tf
0 Tc 0 Tw 0 Ts 100 Tz 0 Tr 135.75 131.25 Td
( )Tj
/TT0 9.75 Tf
0.0117 Tc 1.50529 Tw 0 506.25 TD
(dependent kinase inhibitor \(4, 162, 80\), chloroperoxidase \(2, 41, 44\)\
, ubiquinol c)Tj
0.4391 Tc 0 Tw 331.5 0 Td
(y-)Tj
0.0361 Tc 1.7764 Tw -331.5 -12 Td
(tochrome C reductase \(5, 45, 73\), eukaryotic translation initiation fa\
ct)Tj
0.4178 Tc 0.89481 Tw 291 0 Td
(or 4)Tj
/TT1 9.75 Tf
-0.2572 Tc 0 Tw 16.5 0 Td
(g)Tj
/TT0 9.75 Tf
-0.29111 Tc 1.10361 Tw 3.75 0 Td
( \(4, 98, )Tj
-0.0791 Tc 2.2487 Tw -311.25 -12 Td
(68\), carrot embryonic protein 1 \(37, 96, 69\), epidermal growth factor\
\(8, 38, 78\), )Tj
0.125 Tc 0 Tw 0 -12 TD
(Phe)Tj
-0.2467 Tc 15 0 Td
(-)Tj
-0.04829 Tc 1.11079 Tw 3 0 Td
(tRNA synthetase \(14, 88, 34\), flagellin \(34, 102, 48\), negative regu\
lator of fla)Tj
0.4391 Tc 0 Tw 313.5 0 Td
(g-)Tj
0.0293 Tc 1.2832 Tw -331.5 -12 Td
(ellin synthesis \(8, 98, 45\), f)Tj
0.28951 Tc 0 Tw 112.5 0 Td
(i)Tj
0.0159 Tc 1.2966 Tw 2.25 0 Td
(bronectin binding protein C \(2, 129, 96\), o)Tj
0.2849 Tc 0.2776 Tw 174.75 0 Td
(ncogene fos )Tj
-0.37041 Tc 2.68291 Tw -289.5 -12 Td
(\(21, 145, 44\), Gly)Tj
-0.2467 Tc 0 Tw 72 0 Td
(-)Tj
0.17329 Tc 1.88921 Tw 3 0 Td
(tRNA sy)Tj
0.375 Tc 0 Tw 37.5 0 Td
(n)Tj
-0.00819 Tc 1.78951 Tw 5.25 0 Td
(thetase \(23, 52, 27\), glycine methyltransferase \(8, 40, )Tj
-0.04829 Tc 2.16431 Tw -117.75 -12 Td
(86\), gonadotropin \(7, 34, 51\), transcription factor VP16 \(3, 93, 83\)\
, histone 5 \(9, )Tj
-0.323 Tc 4.6355 Tw T*
(114, 67\), HMG14 \(6, 101, 64\), HMG17 \(14, 87, 75\), HMGI\(Y\) \(10, 1\
53, 39\),)Tj
0 Tc -0.1875 Tw ( )Tj
-0.42599 Tc 0 Tw T*
(HMGT)Tj
-0.18671 Tc 1.49921 Tw 27.75 0 Td
( \(43, 209, 71\), I)Tj
-0.2467 Tc 0 Tw 62.25 0 Td
(-)Tj
0.12061 Tc 0.549 Tw 3 0 Td
(tRNA synthetase \(23, 39, 33\), inosine monophosphate deh)Tj
0.4391 Tc 0 Tw 238.5 0 Td
(y-)Tj
-331.5 -12 Td
(dr)Tj
0.375 Tc 8.25 0 Td
(o)Tj
0.015 Tc 1.57021 Tw 5.25 0 Td
(genase \(52, 174, 40\), lactose operon repressor \(37, 61, 45\), metamin\
opeptidase )Tj
-0.1035 Tc 2.166 Tw -13.5 -12 Td
(\(3, 123, 86\), HIV1 negative factor \(3, 119, 25\), osteocalcin \(20, 4\
7, 61\), transcri)Tj
0.4391 Tc 0 Tw 331.5 0 Td
(p-)Tj
0.05521 Tc 1.25729 Tw -331.5 -12 Td
(tion factor p65 )Tj
-0.11819 Tc 1.99319 Tw 66.75 0 Td
(\(4, 127, 41\), prion \(55, 98, 75\), prothymosin )Tj
/TT1 9.75 Tf
-0.1523 Tc 0 Tw 186.75 0 Td
(a)Tj
/TT0 9.75 Tf
-0.30051 Tc 1.23801 Tw 6 0 Td
( \(4, 111, 96\), )Tj
/TT2 9.75 Tf
0.1963 Tc 0 Tw 54.75 0 Td
(Pvu)Tj
/TT0 9.75 Tf
-0.2467 Tc 0.8092 Tw 15.75 0 Td
( II )Tj
-0.08549 Tc 0 Tw -330 -12 Td
(m)Tj
0.17101 Tc 6.75 0 Td
(e)Tj
0.28951 Tc 4.5 0 Td
(t)Tj
0.375 Tc 3 0 Td
(h)Tj
-0.0087 Tc 2.0712 Tw 5.25 0 Td
(yltransferase \(12, 24, 22\), anti)Tj
-0.2467 Tc 0 Tw 124.5 0 Td
(-)Tj
-0.0425 Tc 1.44881 Tw 3 0 Td
(termination protein N \(3, 120, 47\), regulator of )Tj
-0.28951 Tc 0 Tw -147 -12 Td
(G)Tj
-0.2467 Tc 6 0 Td
(-)Tj
-0.03709 Tc 1.84959 Tw 3 0 Td
(protein signalling 4 \(17, 80, 38\), acidic ribosomal protein P2)Tj
/TT1 9.75 Tf
-0.1028 Tc 0 Tw 250.5 0 Td
(b)Tj
/TT0 9.75 Tf
-0.3219 Tc 1.6344 Tw 5.25 0 Td
( \(56, 117, 41\), re)Tj
0.4391 Tc 0 Tw 66.75 0 Td
(p-)Tj
0.05859 Tc 0.87891 Tw -331.5 -12 Td
(lication protein )Tj
0.04761 Tc 0.51489 Tw 65.25 0 Td
(A \(7, 61, 21\), southern bean mosaic virus capsid \(6, 64, 71\), transl\
)Tj
0.4391 Tc 0 Tw 266.25 0 Td
(o-)Tj
0.0061 Tc 0.7439 Tw -331.5 -12 Td
(case sec61 \(9, 44, 47\), sindbis virus capsid \(6, 101, 45\), small hea\
t shock protein \(6, )Tj
-0.07809 Tc 1.14059 Tw T*
(40, 42\), sulfotransferase \(12, 69, 32\), )Tj
/TT1 9.75 Tf
-0.1523 Tc 0 Tw 152.25 0 Td
(a)Tj
/TT0 9.75 Tf
0.07719 Tc 0.86031 Tw 6 0 Td
( synuclein \(22, 134, 62\), tomato bushy stunt )Tj
0.15601 Tc 1.15649 Tw -158.25 -12 Td
(virus ca)Tj
0.375 Tc 0 Tw 33 0 Td
(p)Tj
0.2072 Tc 0.3553 Tw 5.25 0 Td
(sid )Tj
-0.12621 Tc 1.43871 Tw 15.75 0 Td
(\(7, 58, 64\), T)Tj
-0.2467 Tc 0 Tw 52.5 0 Td
(-)Tj
0.03999 Tc 0.52251 Tw 3 0 Td
(cell receptor )Tj
/TT1 9.75 Tf
-0.1523 Tc 0 Tw 54 0 Td
(a)Tj
/TT0 9.75 Tf
-0.0817 Tc 0.8317 Tw 6 0 Td
( \(10, 112, 38\), telomere bindin gprotein \(5, )Tj
-0.0226 Tc 2.42599 Tw -169.5 -12 Td
(39, 61\), transcription initiation factor IID \(3, 59, 53\), thyroid tra\
nscription fa)Tj
0.17101 Tc 0 Tw 324 0 Td
(c)Tj
0.13921 Tc -0.32671 Tw 4.5 0 Td
(tor )Tj
-0.1028 Tc 1.6028 Tw -328.5 -12 Td
(\(10, 187, 47\), Topoisomerase II \(26, 99, 29\), T)Tj
-0.2467 Tc 0 Tw 189 0 Td
(-)Tj
0.0666 Tc 1.1209 Tw 3 0 Td
(tRNA synthetase \(24, 95, 28\), yeast )Tj
0.3344 Tc 0.9781 Tw -192 -12 Td
(heat shock)Tj
-0.022 Tc 0.87289 Tw 45 0 Td
( protein \(2, 195, 23\). Overall, this database contains 55 families wit\
h 828 )Tj
0.0107 Tc 1.57449 Tw -45 -12 Td
(segments of disorder containing 81,491 residues in total. Minimum and ma\
ximum )Tj
0.28481 Tc 1.77769 Tw T*
(observed sequence identities b)Tj
0.17101 Tc 0 Tw 131.25 0 Td
(e)Tj
0.1591 Tc 1.1534 Tw 4.5 0 Td
(tween any two aligned sequences were 10% and )Tj
-0.04739 Tc -0.14011 Tw -135.75 -12 Td
(99.53%, respe)Tj
0.17101 Tc 0 Tw 54.75 0 Td
(c)Tj
0.1217 Tc 4.5 0 Td
(tively.)Tj
/TT0 12 Tf
0 Tc 24.75 0 Td
( )Tj
/TT0 9.75 Tf
0.6963 Tc 0.6162 Tw -66.75 -12 Td
(A se)Tj
0.0928 Tc 0.64281 Tw 20.25 0 Td
(t of unrelated proteins was taken from reference 21. This set contains 1\
31 )Tj
0.4391 Tc 0 Tw -37.5 -12 Td
(pr)Tj
0.375 Tc 8.25 0 Td
(o)Tj
0.0675 Tc -0.255 Tw 5.25 0 Td
(teins and 26,692 residues. )Tj
0 Tc -0.1875 Tw 104.25 0 Td
( )Tj
0.0677 Tc 1.2448 Tw -100.5 -12 Td
(The various experiments were performed on a Windows based 800 MHz Pe)Tj
0.4391 Tc 0 Tw 314.25 0 Td
(n-)Tj
0.1017 Tc -0.2892 Tw -331.5 -12 Td
(tium computer using C++ and MATLAB software packages.)Tj
0 Tc -0.1875 Tw 240 0 Td
( )Tj
/TT2 9.75 Tf
0.2122 Tc -0.3997 Tw -240 -25.5 Td
(2.2 Scoring Matrices)Tj
0 Tc -0.1875 Tw 85.5 0 Td
( )Tj
/TT0 9.75 Tf
0.2915 Tc 1.021 Tw -68.25 -24 Td
(To bui)Tj
0.0731 Tc 0.4894 Tw 27.75 0 Td
(ld scoring matrices we applied a simple iterative algorithm consisting e\
)Tj
0.60519 Tc 0 Tw 287.25 0 Td
(s-)Tj
0.22501 Tc -0.41251 Tw -332.25 -12 Td
(sentially of two steps:)Tj
0 Tc -0.1875 Tw 87.75 0 Td
( )Tj
-0.3109 Tc 0 Tw -69.75 -12 Td
(1\))Tj
0 Tc -0.1875 Tw 8.25 0 Td
( )Tj
0.0257 Tc 1.98331 Tw 5.25 0 Td
(for a given scoring matrix, align every protein in every family to all t\
he )Tj
0.0961 Tc -0.2836 Tw T*
(other proteins belonging to the same family)Tj
0 Tc -0.1875 Tw 173.25 0 Td
( )Tj
-0.3109 Tc 0 Tw -186.75 -12 Td
(2\))Tj
0 Tc -0.1875 Tw 8.25 0 Td
( )Tj
0.1058 Tc -0.2933 Tw 5.25 0 Td
(for a given set of alignments calculate )Tj
0.0157 Tc -0.2032 Tw 153 0 Td
(a new scoring matrix)Tj
0 Tc -0.1875 Tw 81 0 Td
( )Tj
-265.5 -12 Td
( )Tj
0.14149 Tc 0.4211 Tw 17.25 -12 Td
(Using )Tj
/TT0 8.25 Tf
-0.1046 Tc 0 Tw 27.75 0 Td
(BLOSUM)Tj
/TT0 9.75 Tf
-0.375 Tc 33.75 0 Td
(62)Tj
0.09399 Tc 1.03101 Tw 9 0 Td
( as the initial matrix, these two steps were repeated until the )Tj
0.15199 Tc -0.33949 Tw -87.75 -12 Td
(scoring matrices in two successive iterations remained essentially uncha\
nged.)Tj
0 Tc -0.1875 Tw 311.25 0 Td
( )Tj
ET
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(Pacific Symposium on Biocomputing 7:589-600 \(2002\) )Tj
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/TT0 12 Tf
0 Tc 0 Tw 0 Ts 100 Tz 0 Tr 135.75 131.25 Td
( )Tj
/TT1 9.75 Tf
0.23489 Tc -0.42239 Tw 0 507 TD
(2.3 Aligning sequences)Tj
0 Tc -0.1875 Tw 94.5 0 Td
( )Tj
/TT0 9.75 Tf
0.09151 Tc 0.47099 Tw -94.5 -24.75 Td
(We use both multiple alignment)Tj
/TT0 6.75 Tf
0.375 Tc 0 Tw 129.75 4.5 Td
(7)Tj
/TT0 9.75 Tf
0.1469 Tc 0.2906 Tw 3.75 -4.5 Td
( and a series of global )Tj
-0.0042 Tc -0.1833 Tw 93.75 0 Td
(pairwise alignments)Tj
/TT0 6.75 Tf
0.375 Tc 0 Tw 78.75 4.5 Td
(1)Tj
/TT0 9.75 Tf
0.0965 Tc -0.034 Tw 3.75 -4.5 Td
( in Step )Tj
0.1125 Tc 0.02139 Tw -309.75 -12 Td
(1. Both methods result in aligning every residue of every sequence in a \
family opp)Tj
0.4391 Tc 0 Tw 331.5 0 Td
(o-)Tj
0.1263 Tc 1.04559 Tw -331.5 -12 Td
(site only one residue or gap of every other sequence in the same family.\
Pairs of )Tj
0.1293 Tc -0.3168 Tw 0 -12 TD
(aligned sequences are used for calculating the final entries i)Tj
0.1756 Tc -0.3632 Tw 237.75 0 Td
(n the scoring matr)Tj
0.28951 Tc 0 Tw 72 0 Td
(i)Tj
0.40289 Tc 2.25 0 Td
(ces.)Tj
0 Tc -0.1875 Tw 15.75 0 Td
( )Tj
/TT1 9.75 Tf
0.22301 Tc -0.41051 Tw -327.75 -25.5 Td
(2.4 Assigning weights to sequences)Tj
0 Tc -0.1875 Tw 143.25 0 Td
( )Tj
/TT0 9.75 Tf
0.15179 Tc 0.4108 Tw -143.25 -24 Td
(In a scheme that differs from previous approaches, we assign a weight to\
every s)Tj
0.3371 Tc 0 Tw 332.25 0 Td
(e-)Tj
0.1653 Tc 0.4472 Tw -332.25 -12 Td
(quence as an inverse of its average sequence identity with all proteins \
of the same )Tj
-0.0106 Tc 0.9481 Tw T*
(family \(including itself\). We ta)Tj
0.1468 Tc 0.4157 Tw 124.5 0 Td
(ke a soft approach \(without thres)Tj
0.375 Tc 0 Tw 135.75 0 Td
(h)Tj
0.1456 Tc 0.4169 Tw 5.25 0 Td
(olds\) as compared )Tj
0.0799 Tc 1.66119 Tw -265.5 -12 Td
(to reference 13. Note that this method reduces the influence of large fa\
milies of )Tj
-0.07491 Tc -0.11259 Tw T*
(highly similar s)Tj
0.17101 Tc 0 Tw 60 0 Td
(e)Tj
0.0826 Tc -0.2701 Tw 4.5 0 Td
(quences, and all families contribute according to their size.)Tj
0 Tc -0.1875 Tw 232.5 0 Td
( )Tj
/TT1 9.75 Tf
0.30251 Tc -0.49001 Tw -297 -25.5 Td
(2.5 Counting mutations)Tj
0 Tc -0.1875 Tw 96.75 0 Td
( )Tj
/TT0 9.75 Tf
0.0157 Tc -0.2032 Tw -96.75 -24.75 Td
(No matter which stra)Tj
0.19971 Tc -0.38721 Tw 82.5 0 Td
(tegy of alignment is used, substitutions are counted as shown in )Tj
0.07651 Tc 0 Tw -82.5 -12 Td
(Fig.)Tj
0 Tc -0.1875 Tw 15 0 Td
( )Tj
-0.2813 Tc 0 Tw 2.25 0 Td
(1.)Tj
0 Tc -0.1875 Tw 6.75 0 Td
( )Tj
0.13651 Tc 0 Tw 2.25 0 Td
(Note)Tj
0 Tc -0.1875 Tw 19.5 0 Td
( )Tj
0.2813 Tc 0 Tw 2.25 0 Td
(that)Tj
0 Tc -0.1875 Tw 15.75 0 Td
( )Tj
0.375 Tc 0 Tw 2.25 0 Td
(no)Tj
0 Tc -0.1875 Tw 10.5 0 Td
( )Tj
0.23441 Tc 0 Tw 2.25 0 Td
(counting)Tj
0 Tc -0.1875 Tw 36 0 Td
( )Tj
-0.6266 Tc 0 Tw 2.25 0 Td
(is)Tj
0 Tc -0.1875 Tw 6.75 0 Td
( )Tj
0.32401 Tc 0 Tw 2.25 0 Td
(done)Tj
0 Tc -0.1875 Tw 20.25 0 Td
( )Tj
0.1579 Tc 0 Tw 2.25 0 Td
(when)Tj
0 Tc -0.1875 Tw 21.75 0 Td
( )Tj
0.17101 Tc 0 Tw 2.25 0 Td
(a)Tj
0 Tc -0.1875 Tw 4.5 0 Td
( )Tj
0.15601 Tc 0 Tw 2.25 0 Td
(residue)Tj
0 Tc -0.1875 Tw 29.25 0 Td
( )Tj
-0.6266 Tc 0 Tw 2.25 0 Td
(is)Tj
0 Tc -0.1875 Tw 6.75 0 Td
( )Tj
0.078 Tc 0 Tw 2.25 0 Td
(aligned)Tj
0 Tc -0.1875 Tw 29.25 0 Td
( )Tj
0.2785 Tc -0.466 Tw 2.25 0 Td
(to a)Tj
0 Tc -0.1875 Tw 15 0 Td
( )Tj
0.3709 Tc 0 Tw 2.25 0 Td
(gap.)Tj
0 Tc -0.1875 Tw 17.25 0 Td
( )Tj
0.0666 Tc 1.0728 Tw -267.75 -12 Td
(This algorithm is applied to all families of disordered proteins and the\
overall )Tj
0.11369 Tc -0.55119 Tw -18 -12 Td
(substitution count matrix )Tj
/TT1 9.75 Tf
0.1282 Tc 0 Tw 102 0 Td
(M)Tj
/TT0 9.75 Tf
0.0963 Tc -0.2838 Tw 8.25 0 Td
( is calcu)Tj
0.06419 Tc -0.25169 Tw 32.25 0 Td
(lated as the sum of all family count m)Tj
0.17101 Tc 0 Tw 147 0 Td
(a)Tj
0.17059 Tc 4.5 0 Td
(trices.)Tj
0 Tc -0.1875 Tw 24 0 Td
( )Tj
-300 -12 Td
( )Tj
/TT2 8.25 Tf
0.25591 Tc 0 Tw 72 -13.5 Td
(Input:)Tj
0 Tc 0.1875 Tw 24 0 Td
( )Tj
/TT0 8.25 Tf
0.0349 Tc 0 Tw 2.25 0 Td
(family)Tj
0 Tc 0.1875 Tw 22.5 0 Td
( )Tj
/TT1 8.25 Tf
-0.0435 Tc 0 Tw 2.25 0 Td
(f)Tj
0 Tc 0.1875 Tw 2.25 0 Td
( )Tj
/TT0 8.25 Tf
0.3139 Tc 0 Tw 2.25 0 Td
(of)Tj
0 Tc 0.1875 Tw 7.5 0 Td
( )Tj
/TT1 8.25 Tf
0.375 Tc 0 Tw 2.25 0 Td
(n)Tj
0 Tc 0.1875 Tw 4.5 0 Td
( )Tj
/TT0 8.25 Tf
0.06599 Tc 0 Tw 2.25 0 Td
(aligned)Tj
0 Tc 0.1875 Tw 24 0 Td
( )Tj
0.3336 Tc 0 Tw 2.25 0 Td
(proteins)Tj
0 Tc 0.1875 Tw 28.5 0 Td
( )Tj
/TT1 8.25 Tf
-0.2092 Tc 0 Tw 2.25 0 Td
(s)Tj
/TT0 5.25 Tf
0.375 Tc 3 -0.75 Td
(1)Tj
/TT0 8.25 Tf
0.1875 Tc 3 0.75 Td
(,)Tj
0 Tc 0.1875 Tw 2.25 0 Td
( )Tj
/TT1 8.25 Tf
-0.2092 Tc 0 Tw 1.5 0 Td
(s)Tj
/TT0 5.25 Tf
0.375 Tc 2.25 -0.75 Td
(2)Tj
/TT0 8.25 Tf
0.1875 Tc 2.25 0.75 Td
(,)Tj
/TT3 8.25 Tf
0 Tc 1.5 0 Td
(\274)Tj
/TT0 8.25 Tf
0.1875 Tw 8.25 0 Td
( )Tj
/TT1 8.25 Tf
-0.2092 Tc 0 Tw 1.5 0 Td
(s)Tj
/TT1 5.25 Tf
0.375 Tc 2.25 -0.75 Td
(n)Tj
/TT0 8.25 Tf
0 Tc 0.1875 Tw 2.25 0.75 Td
( )Tj
ET
q
387 366 3.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
387 368.25 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
0.07159 Tc 0.0659 Tw 225.75 356.25 Td
( with corresponding weights )Tj
/TT1 8.25 Tf
-0.2527 Tc 0 Tw 123 0 Td
(w)Tj
/TT0 5.25 Tf
0.375 Tc 5.25 -0.75 Td
(1)Tj
/TT0 8.25 Tf
-0.5625 Tc 3 0.75 Td
(, )Tj
/TT1 8.25 Tf
-0.2527 Tc 3 0 Td
(w)Tj
/TT0 5.25 Tf
0.375 Tc 4.5 -0.75 Td
(2)Tj
/TT0 8.25 Tf
-0.5625 Tc 2.25 0.75 Td
(, )Tj
/TT3 8.25 Tf
0 Tc 3 0 Td
(\274)Tj
/TT1 8.25 Tf
-0.2527 Tc 8.25 0 Td
(w)Tj
/TT1 5.25 Tf
0.375 Tc 4.5 -0.75 Td
(n)Tj
/TT0 8.25 Tf
0 Tc 0.1875 Tw 2.25 0.75 Td
( )Tj
ET
0 0.502 0 rg
220.5 378 170.25 1.5 re
f
0 0 0 rg
BT
/TT2 8.25 Tf
0.4398 Tc 0 Tw 225.75 344.25 Td
(Output:)Tj
/TT0 8.25 Tf
0.22569 Tc -0.03819 Tw 31.5 0 Td
( family count matrix )Tj
/TT1 8.25 Tf
-0.1223 Tc 0 Tw 74.25 0 Td
(M)Tj
/TT1 5.25 Tf
0.0405 Tc 6.75 -0.75 Td
(f)Tj
/TT0 8.25 Tf
0 Tc 0.1875 Tw 1.5 0.75 Td
( )Tj
/TT1 8.25 Tf
-0.1223 Tc 0 Tw -114 -13.5 Td
(M)Tj
/TT1 5.25 Tf
0.0405 Tc 6.75 -0.75 Td
(f)Tj
/TT0 8.25 Tf
0 Tc 0.1875 Tw 1.5 0.75 Td
( )Tj
/TT3 8.25 Tf
0.10719 Tc 0 Tw 2.25 0 Td
(\254)Tj
/TT0 8.25 Tf
0.375 Tc -0.1875 Tw 8.25 0 Td
( 20)Tj
0 Tc 0.1875 Tw 11.25 0 Td
( )Tj
/TT3 8.25 Tf
-0.0293 Tc 0 Tw 2.25 0 Td
(\264)Tj
/TT0 8.25 Tf
0 Tc 0.1875 Tw 4.5 0 Td
( )Tj
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(, )Tj
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(y)Tj
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( )Tj
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( )Tj
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(y)Tj
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(\) )Tj
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(\254)Tj
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( )Tj
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(, )Tj
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(\327)Tj
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( )Tj
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(Figure 1. )Tj
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(Calculating family count matrix)Tj
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( )Tj
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(2.6 Constructing the scoring matrix)Tj
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( )Tj
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(T)Tj
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(S)Tj
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(M)Tj
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(int probability matrix )Tj
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(Q)Tj
/TT0 9.75 Tf
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(i)Tj
/TT0 9.75 Tf
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(p)Tj
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(posite )Tj
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(residue )Tj
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(j)Tj
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(j)Tj
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(\345)Tj
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(\345)Tj
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(+)Tj
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(j)Tj
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(ij)Tj
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(T)Tj
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(M)Tj
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(m)Tj
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0.3735 Tc 6.75 -1.5 Td
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(M)Tj
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(i)Tj
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(Q)Tj
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(u-)Tj
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(t)Tj
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(-)Tj
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( trans)Tj
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(i-)Tj
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( )Tj
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(P)Tj
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( = )Tj
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( )Tj
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(a)Tj
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( )Tj
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(a)Tj
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( )Tj
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(\316)Tj
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( )Tj
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(\(1, )Tj
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(\245)Tj
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(et)Tj
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( )Tj
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(.)Tj
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(11, 12)Tj
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(evolutionary times by extrap)Tj
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(o)Tj
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(lating from proteins with sh)Tj
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(orter distances. However, )Tj
-0.1524 Tc 0.3399 Tw -236.25 -12 Td
(the matrix )Tj
/TT1 9.75 Tf
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(P)Tj
/TT0 9.75 Tf
0.1127 Tc 0.7226 Tw 6 0 Td
( is already developed using the available spectrum of divergence from )Tj
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(the available data, thus r)Tj
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(e)Tj
0.1022 Tc 0.3353 Tw 4.5 0 Td
(flecting moderate evolutionary distances. Naturally, since )Tj
0.2393 Tc 0.0732 Tw -106.5 -12 Td
(the assumptions about underlying Markov processes do not hold )Tj
0.0551 Tc -0.2426 Tw 268.5 0 Td
(strictly, the model )Tj
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(becomes less accurate as )Tj
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(a)Tj
/TT0 9.75 Tf
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( increases.)Tj
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( )Tj
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(Even with all amino acid exchanges observed in the database, there is no\
gua)Tj
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(r-)Tj
0.2558 Tc 0.6817 Tw -333.75 -12 Td
(antee that )Tj
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(P)Tj
/TT0 9.75 Tf
0.0701 Tc 0.8138 Tw 6 0 Td
( is positive definite. As a result, in order for expression \(3\) to be \
well)Tj
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(-)Tj
0.375 Tc -336.75 -12 Td
(d)Tj
0.17101 Tc 5.25 0 Td
(e)Tj
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(fined, a test for all positive e)Tj
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(igenvalues is performed before raising )Tj
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(P)Tj
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( to a non)Tj
-0.2467 Tc 0 Tw 37.5 0 Td
(-)Tj
0.1459 Tc -0.1459 Tw -336.75 -12 Td
(integer power. Failing the test, although such never occurred, would can\
cel the po)Tj
-0.2681 Tc 0 Tw 330 0 Td
(w-)Tj
0.0359 Tc -0.07339 Tw -330 -12 Td
(ering step. Finally, all entries )Tj
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(s)Tj
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0.3735 Tc 3.75 -1.5 Td
(ij)Tj
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( of a scoring matrix are calculated as)Tj
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( )Tj
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371.25 387 l
S
BT
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(\))Tj
-4.5 -7.5 Td
(\))Tj
-9 0 Td
(\()Tj
-9.75 0 Td
(\))Tj
-6.75 0 Td
(\()Tj
21 14.25 Td
(\))Tj
-0.25 Tc -9.75 0 Td
(,)Tj
-0.33 Tc -6 0 Td
(\()Tj
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(log)Tj
-0.33 Tc -15 0 Td
(\()Tj
0.134 Tc -24 0 Td
(round)Tj
/TT0 6 Tf
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(2)Tj
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(j)Tj
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(p)Tj
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(i)Tj
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(p)Tj
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(j)Tj
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(i)Tj
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(p)Tj
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(C)Tj
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(s)Tj
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(ij)Tj
/TT2 10 Tf
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(\327)Tj
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(=)Tj
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(, )Tj
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( \(4\))Tj
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( )Tj
1.1244 Tw -339.75 -22.5 Td
(where we multiply by )Tj
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(C)Tj
/TT0 9.75 Tf
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( )Tj
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(=)Tj
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( )Tj
0.1633 Tc 0.33099 Tw 2.25 0 Td
(2 before rounding to the nearest integer in order to have )Tj
/TT1 9.75 Tf
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(s)Tj
/TT1 6.75 Tf
0.3735 Tc 3.75 -1.5 Td
(ij)Tj
/TT0 9.75 Tf
0.09441 Tc 0.3181 Tw 4.5 1.5 Td
( entries in half bit units. Multiplying by two increases the resolution \
of the matrix )Tj
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(elements before rounding, which is pe)Tj
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(r)Tj
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(formed for the convenience o)Tj
0.1384 Tc 0.1741 Tw 120 0 Td
(f using integer )Tj
0.05321 Tc 0.9593 Tw -280.5 -12 Td
(arithmetic during the course of alig)Tj
0.375 Tc 0 Tw 144.75 0 Td
(n)Tj
0.20979 Tc 0.35271 Tw 5.25 0 Td
(ment. We use the same gap penalty system as )Tj
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(for )Tj
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(BLOSUM)Tj
/TT0 9.75 Tf
-0.375 Tc 33.75 0 Td
(62)Tj
0.1882 Tc -0.42931 Tw 9 0 Td
(. Once chosen at the start, the gap penalties are not changed during the\
)Tj
-0.2316 Tc 0 Tw -56.25 -12 Td
(refin)Tj
0.17101 Tc 18 0 Td
(e)Tj
-0.17329 Tc -0.26421 Tw 4.5 0 Td
(ment of matrix )Tj
/TT1 9.75 Tf
0.375 Tc 0 Tw 57.75 0 Td
(S)Tj
/TT0 9.75 Tf
0.14481 Tc -0.33231 Tw 5.25 0 Td
(, making the construction process far less expensive)Tj
-0.1875 Tc 0 Tw 207.75 0 Td
(. )Tj
0 Tc -0.1875 Tw 6.75 0 Td
( )Tj
-300 -12 Td
( )Tj
/TT1 9.75 Tf
0.2198 Tc -0.4073 Tw T*
(2.7 Evaluating the matrices)Tj
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( )Tj
-112.5 -12 Td
( )Tj
/TT0 9.75 Tf
0.0197 Tc 0.9178 Tw T*
(Scoring matrices were evaluated by building family)Tj
-0.2467 Tc 0 Tw 209.25 0 Td
(-)Tj
0.10921 Tc 0.45329 Tw 3 0 Td
(specific hi)Tj
0.375 Tc 0 Tw 41.25 0 Td
(d)Tj
0.1256 Tc 0.4369 Tw 5.25 0 Td
(den Markov models )Tj
0.071 Tc 0.9915 Tw -258.75 -12 Td
(\(HMMs\) from a set of aligned training proteins as described in Fig. 2.\
Test family )Tj
0.1227 Tc 0.1398 Tw T*
(proteins as well as a number of unrelated proteins were al)Tj
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(n-)Tj
0.1796 Tc 1.24831 Tw -331.5 -12 Td
(struction. A sequence identity threshold of 50% was set to include a rea\
sonable )Tj
0.10429 Tc 1.95821 Tw T*
(number of proteins while emphasizing the more divergent ones. Furthermor\
e, a)Tj
-0.35361 Tc 0 Tw 334.5 0 Td
(l-)Tj
0.1402 Tc 1.1723 Tw -334.5 -12 Td
(though both multiple sequence alignments)Tj
/TT0 6.75 Tf
0.375 Tc 0 Tw 176.25 4.5 Td
(7)Tj
/TT0 9.75 Tf
0.4534 Tc 0.8591 Tw 3.75 -4.5 Td
( and a se)Tj
-0.0562 Tc 0.8062 Tw 39.75 0 Td
(ries of optimal pairwise alig)Tj
0.4391 Tc 0 Tw 111.75 0 Td
(n-)Tj
-0.00861 Tc -331.5 -12 Td
(ments)Tj
/TT0 6.75 Tf
0.375 Tc 24 4.5 Td
(1)Tj
/TT0 9.75 Tf
0.1254 Tc 0.3689 Tw 3.75 -4.5 Td
( were tried in step one of our iterative procedure \(section )Tj
/TT2 9.75 Tf
-0.0625 Tc 0 Tw 234.75 0 Td
(2.2)Tj
/TT0 9.75 Tf
0.1138 Tc -0.3013 Tw 12.75 0 Td
(\), the latter gave )Tj
0.21741 Tc -0.40491 Tw -275.25 -12 Td
(slightly better results so that only these results are pr)Tj
0.17101 Tc 0 Tw 213 0 Td
(e)Tj
0.27161 Tc -0.45911 Tw 4.5 0 Td
(sented. )Tj
0 Tc -0.1875 Tw 31.5 0 Td
( )Tj
-231.75 -12 Td
( )Tj
/TT0 8.25 Tf
0.1825 Tc 0.005 Tw -17.25 -10.5 Td
(Table 1. )Tj
/TT2 8.25 Tf
0.14639 Tc 0.04111 Tw 30.75 0 Td
(Comparative performance of different matrices with given gap )Tj
-0.15311 Tc -0.10941 Tw 218.25 0 Td
(penalties for all test proteins )Tj
0.13271 Tc 0.05479 Tw -209.25 -10.5 Td
(whose average sequence identity to the training sequences is less than 5\
0%)Tj
/TT0 8.25 Tf
0 Tc 0.1875 Tw 259.5 0 Td
( )Tj
0.1322 Tc 0 Tw -295.5 -15.75 Td
(Matrix)Tj
0 Tc 0.1875 Tw 24 0 Td
( )Tj
-0.0815 Tc 0 Tw 51.75 0 Td
(Gap)Tj
0.2527 Tc 13.5 0 Td
(-)Tj
0.27901 Tc 3 0 Td
(ope)Tj
0.375 Tc 12.75 0 Td
(n)Tj
0.08369 Tc 0.10381 Tw 4.5 0 Td
(ing pe)Tj
0.375 Tc 0 Tw 21 0 Td
(n)Tj
0.2813 Tc 4.5 0 Td
(alty)Tj
0 Tc 0.1875 Tw 12.75 0 Td
( )Tj
-0.0815 Tc 0 Tw 11.25 0 Td
(Gap)Tj
0.2527 Tc 13.5 0 Td
(-)Tj
0.5014 Tc 3 0 Td
(exte)Tj
0.375 Tc 15 0 Td
(n)Tj
0.2236 Tc -0.0361 Tw 4.5 0 Td
(sion penalty)Tj
0 Tc 0.1875 Tw 42.75 0 Td
( )Tj
0.07269 Tc 0.11481 Tw 23.25 0 Td
(Cumulative score)Tj
0 Tc 0.1875 Tw 59.25 0 Td
( )Tj
ET
0 0.502 0 rg
133.5 453 76.5 1.5 re
f
210 453 1.5 1.5 re
f
211.5 453 81.75 1.5 re
f
293.25 453 1.5 1.5 re
f
294.75 453 88.5 1.5 re
f
383.25 453 1.5 1.5 re
f
384.75 453 93 1.5 re
f
q
139.5 430.5 29.25 7.5 re
h
W n
0 0 0 rg
BT
/TT0 6.75 Tf
0.37621 Tc 0 Tw 139.5 430.5 Td
(GONNET)Tj
ET
Q
q
168.75 430.5 4.5 8.25 re
h
W n
0 0 0 rg
BT
/TT0 8.25 Tf
168.75 430.5 Td
( )Tj
ET
Q
q
249 430.5 4.5 8.25 re
h
W n
0 0 0 rg
BT
/TT0 8.25 Tf
0.375 Tc 0 Tw 249 430.5 Td
(6)Tj
ET
Q
q
253.5 430.5 4.5 8.25 re
h
W n
0 0 0 rg
BT
/TT0 8.25 Tf
253.5 430.5 Td
( )Tj
ET
Q
q
332.25 430.5 11.25 8.25 re
h
W n
0 0 0 rg
BT
/TT0 8.25 Tf
0.3125 Tc 0 Tw 332.25 430.5 Td
(0.8)Tj
ET
Q
q
343.5 430.5 4.5 8.25 re
h
W n
0 0 0 rg
BT
/TT0 8.25 Tf
343.5 430.5 Td
( )Tj
ET
Q
q
420 430.5 20.25 8.25 re
h
W n
0 0 0 rg
BT
/TT0 8.25 Tf
0.33749 Tc 0 Tw 420 430.5 Td
(55.54)Tj
ET
Q
q
440.25 430.5 4.5 8.25 re
h
W n
0 0 0 rg
BT
/TT0 8.25 Tf
440.25 430.5 Td
( )Tj
ET
Q
133.5 440.25 76.5 0.75 re
f
210 440.25 0.75 0.75 re
f
210.75 440.25 82.5 0.75 re
f
293.25 440.25 0.75 0.75 re
f
294 440.25 89.25 0.75 re
f
383.25 440.25 0.75 0.75 re
f
384 440.25 93.75 0.75 re
f
0 0 0 rg
BT
/TT0 6.75 Tf
0.3121 Tc 0 Tw 139.5 420 Td
(BLOSUM)Tj
ET
q
168.75 418.5 9 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.375 Tc 168.75 420 Td
(30)Tj
ET
Q
q
177.75 418.5 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 177.75 420 Td
( )Tj
ET
Q
q
249 418.5 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.375 Tc 249 420 Td
(9)Tj
ET
Q
q
253.5 418.5 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 253.5 420 Td
( )Tj
ET
Q
q
336 418.5 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.375 Tc 336 420 Td
(1)Tj
ET
Q
q
340.5 418.5 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 340.5 420 Td
( )Tj
ET
Q
q
420 418.5 20.25 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.33749 Tc 420 420 Td
(65.34)Tj
ET
Q
q
440.25 418.5 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 440.25 420 Td
( )Tj
ET
Q
BT
/TT0 6.75 Tf
0.62421 Tc 139.5 409.5 Td
(PAM)Tj
ET
q
155.25 408 13.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.375 Tc 155.25 409.5 Td
(250)Tj
ET
Q
q
168.75 408 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 168.75 409.5 Td
( )Tj
ET
Q
q
243 408 15.75 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.32809 Tc 243 409.5 Td
(12.5)Tj
ET
Q
q
258.75 408 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 258.75 409.5 Td
( )Tj
ET
Q
q
332.25 408 11.25 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.3125 Tc 332.25 409.5 Td
(0.1)Tj
ET
Q
q
343.5 408 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 343.5 409.5 Td
( )Tj
ET
Q
q
420 408 20.25 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.33749 Tc 420 409.5 Td
(68.76)Tj
ET
Q
q
440.25 408 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 440.25 409.5 Td
( )Tj
ET
Q
BT
/TT0 6.75 Tf
0.3121 Tc 139.5 398.25 Td
(BLOSUM)Tj
ET
q
168.75 396.75 9 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.375 Tc 168.75 398.25 Td
(62)Tj
ET
Q
q
177.75 396.75 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 177.75 398.25 Td
( )Tj
ET
Q
q
245.25 396.75 11.25 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.3125 Tc 245.25 398.25 Td
(7.5)Tj
ET
Q
q
256.5 396.75 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 256.5 398.25 Td
( )Tj
ET
Q
q
332.25 396.75 11.25 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.3125 Tc 332.25 398.25 Td
(0.9)Tj
ET
Q
q
343.5 396.75 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 343.5 398.25 Td
( )Tj
ET
Q
q
420 396.75 9 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.375 Tc 420 398.25 Td
(74)Tj
ET
Q
q
429 396.75 11.25 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.3125 Tc 429 398.25 Td
(.55)Tj
ET
Q
q
440.25 396.75 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 440.25 398.25 Td
( )Tj
ET
Q
BT
/TT0 6.75 Tf
139.5 387 Td
(BLOSUM)Tj
ET
q
168.75 385.5 9 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.375 Tc 168.75 387 Td
(62)Tj
ET
Q
q
177.75 385.5 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 177.75 387 Td
( )Tj
ET
Q
q
246.75 385.5 9 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.375 Tc 246.75 387 Td
(10)Tj
ET
Q
q
255.75 385.5 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 255.75 387 Td
( )Tj
ET
Q
q
332.25 385.5 11.25 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.3125 Tc 332.25 387 Td
(0.6)Tj
ET
Q
q
343.5 385.5 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 343.5 387 Td
( )Tj
ET
Q
q
420 385.5 20.25 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.33749 Tc 420 387 Td
(76.03)Tj
ET
Q
q
440.25 385.5 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 440.25 387 Td
( )Tj
ET
Q
BT
/TT0 6.75 Tf
0.375 Tc 139.5 376.5 Td
(BENNER)Tj
ET
q
168 375 9 9.75 re
h
W n
BT
/TT0 8.25 Tf
168 376.5 Td
(74)Tj
ET
Q
q
177 375 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 177 376.5 Td
( )Tj
ET
Q
q
249 375 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
249 376.5 Td
(7)Tj
ET
Q
q
253.5 375 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 253.5 376.5 Td
( )Tj
ET
Q
q
332.25 375 11.25 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.3125 Tc 332.25 376.5 Td
(0.8)Tj
ET
Q
q
343.5 375 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 343.5 376.5 Td
( )Tj
ET
Q
q
420 375 20.25 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.33749 Tc 420 376.5 Td
(77.83)Tj
ET
Q
q
440.25 375 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 440.25 376.5 Td
( )Tj
ET
Q
BT
/TT0 6.75 Tf
0.3121 Tc 139.5 365.25 Td
(BLOSUM)Tj
ET
q
168.75 363.75 9 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.375 Tc 168.75 365.25 Td
(30)Tj
ET
Q
q
177.75 363.75 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 177.75 365.25 Td
( )Tj
ET
Q
q
246.75 363.75 9 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.375 Tc 246.75 365.25 Td
(10)Tj
ET
Q
q
255.75 363.75 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 255.75 365.25 Td
( )Tj
ET
Q
q
332.25 363.75 11.25 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.3125 Tc 332.25 365.25 Td
(1.5)Tj
ET
Q
q
343.5 363.75 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 343.5 365.25 Td
( )Tj
ET
Q
q
420 363.75 20.25 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.33749 Tc 420 365.25 Td
(79.13)Tj
ET
Q
q
440.25 363.75 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 440.25 365.25 Td
( )Tj
ET
Q
BT
/TT0 6.75 Tf
0.375 Tc 139.5 354 Td
(BENNER)Tj
ET
q
168 352.5 9 9.75 re
h
W n
BT
/TT0 8.25 Tf
168 354 Td
(74)Tj
ET
Q
q
177 352.5 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 177 354 Td
( )Tj
ET
Q
q
245.25 352.5 11.25 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.3125 Tc 245.25 354 Td
(9.5)Tj
ET
Q
q
256.5 352.5 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 256.5 354 Td
( )Tj
ET
Q
q
332.25 352.5 11.25 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.3125 Tc 332.25 354 Td
(0.8)Tj
ET
Q
q
343.5 352.5 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 343.5 354 Td
( )Tj
ET
Q
q
420 352.5 20.25 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.33749 Tc 420 354 Td
(83.19)Tj
ET
Q
q
440.25 352.5 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 440.25 354 Td
( )Tj
ET
Q
BT
/TT0 6.75 Tf
0.3013 Tc 139.5 343.5 Td
(IDENT)Tj
ET
q
160.5 342 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 160.5 343.5 Td
( )Tj
ET
Q
q
246.75 342 9 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.375 Tc 246.75 343.5 Td
(12)Tj
ET
Q
q
255.75 342 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 255.75 343.5 Td
( )Tj
ET
Q
q
332.25 342 11.25 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.3125 Tc 332.25 343.5 Td
(0.5)Tj
ET
Q
q
343.5 342 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 343.5 343.5 Td
( )Tj
ET
Q
q
420 342 20.25 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.33749 Tc 420 343.5 Td
(83.82)Tj
ET
Q
q
440.25 342 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 440.25 343.5 Td
( )Tj
ET
Q
BT
/TT0 6.75 Tf
0.3121 Tc 139.5 332.25 Td
(BLOSUM)Tj
ET
q
168.75 330.75 9 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.375 Tc 168.75 332.25 Td
(80)Tj
ET
Q
q
177.75 330.75 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 177.75 332.25 Td
( )Tj
ET
Q
q
249 330.75 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.375 Tc 249 332.25 Td
(7)Tj
ET
Q
q
253.5 330.75 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 253.5 332.25 Td
( )Tj
ET
Q
q
332.25 330.75 11.25 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.3125 Tc 332.25 332.25 Td
(1.5)Tj
ET
Q
q
343.5 330.75 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 343.5 332.25 Td
( )Tj
ET
Q
q
420 330.75 20.25 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.33749 Tc 420 332.25 Td
(87.48)Tj
ET
Q
q
440.25 330.75 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 440.25 332.25 Td
( )Tj
ET
Q
BT
/TT0 6.75 Tf
0.62421 Tc 139.5 321 Td
(PAM)Tj
ET
q
155.25 319.5 13.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.375 Tc 155.25 321 Td
(300)Tj
ET
Q
q
168.75 319.5 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 168.75 321 Td
( )Tj
ET
Q
q
243 319.5 15.75 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.32809 Tc 243 321 Td
(12.5)Tj
ET
Q
q
258.75 319.5 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 258.75 321 Td
( )Tj
ET
Q
q
332.25 319.5 11.25 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.3125 Tc 332.25 321 Td
(0.4)Tj
ET
Q
q
343.5 319.5 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 343.5 321 Td
( )Tj
ET
Q
q
420 319.5 20.25 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.33749 Tc 420 321 Td
(90.78)Tj
ET
Q
q
440.25 319.5 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 440.25 321 Td
( )Tj
ET
Q
BT
/TT0 6.75 Tf
0.3013 Tc 139.5 310.5 Td
(IDENT)Tj
ET
q
160.5 309 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 160.5 310.5 Td
( )Tj
ET
Q
q
249 309 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.375 Tc 249 310.5 Td
(7)Tj
ET
Q
q
253.5 309 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 253.5 310.5 Td
( )Tj
ET
Q
q
332.25 309 11.25 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.3125 Tc 332.25 310.5 Td
(1.4)Tj
ET
Q
q
343.5 309 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 343.5 310.5 Td
( )Tj
ET
Q
q
420 309 20.25 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.33749 Tc 420 310.5 Td
(95.40)Tj
ET
Q
q
440.25 309 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 440.25 310.5 Td
( )Tj
ET
Q
BT
/TT0 6.75 Tf
0.62421 Tc 139.5 299.25 Td
(PAM)Tj
ET
q
155.25 297.75 13.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.375 Tc 155.25 299.25 Td
(250)Tj
ET
Q
q
168.75 297.75 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 168.75 299.25 Td
( )Tj
ET
Q
q
246.75 297.75 9 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.375 Tc 246.75 299.25 Td
(11)Tj
ET
Q
q
255.75 297.75 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 255.75 299.25 Td
( )Tj
ET
Q
q
332.25 297.75 11.25 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.3125 Tc 332.25 299.25 Td
(0.5)Tj
ET
Q
q
343.5 297.75 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 343.5 299.25 Td
( )Tj
ET
Q
q
420 297.75 20.25 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.33749 Tc 420 299.25 Td
(96.45)Tj
ET
Q
q
440.25 297.75 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 440.25 299.25 Td
( )Tj
ET
Q
BT
/TT0 6.75 Tf
139.5 288 Td
(PAM)Tj
ET
q
155.25 286.5 13.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.375 Tc 155.25 288 Td
(120)Tj
ET
Q
q
168.75 286.5 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 168.75 288 Td
( )Tj
ET
Q
q
249 286.5 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.375 Tc 249 288 Td
(6)Tj
ET
Q
q
253.5 286.5 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 253.5 288 Td
( )Tj
ET
Q
q
332.25 286.5 11.25 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.3125 Tc 332.25 288 Td
(1.4)Tj
ET
Q
q
343.5 286.5 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 343.5 288 Td
( )Tj
ET
Q
q
417.75 286.5 24.75 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.3438 Tc 417.75 288 Td
(100.29)Tj
ET
Q
q
442.5 286.5 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 442.5 288 Td
( )Tj
ET
Q
BT
/TT0 6.75 Tf
0.37621 Tc 139.5 277.5 Td
(GONNET)Tj
ET
q
168.75 276 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 168.75 277.5 Td
( )Tj
ET
Q
q
246.75 276 9 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.375 Tc 246.75 277.5 Td
(14)Tj
ET
Q
q
255.75 276 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 255.75 277.5 Td
( )Tj
ET
Q
q
332.25 276 11.25 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.3125 Tc 332.25 277.5 Td
(0.2)Tj
ET
Q
q
343.5 276 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 343.5 277.5 Td
( )Tj
ET
Q
q
417.75 276 24.75 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.3438 Tc 417.75 277.5 Td
(103.47)Tj
ET
Q
q
442.5 276 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 442.5 277.5 Td
( )Tj
ET
Q
BT
/TT0 6.75 Tf
0.62421 Tc 139.5 266.25 Td
(PAM)Tj
ET
q
155.25 264.75 13.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.375 Tc 155.25 266.25 Td
(300)Tj
ET
Q
q
168.75 264.75 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 168.75 266.25 Td
( )Tj
ET
Q
q
249 264.75 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.375 Tc 249 266.25 Td
(9)Tj
ET
Q
q
253.5 264.75 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 253.5 266.25 Td
( )Tj
ET
Q
q
336 264.75 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.375 Tc 336 266.25 Td
(2)Tj
ET
Q
q
340.5 264.75 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 340.5 266.25 Td
( )Tj
ET
Q
q
417.75 264.75 24.75 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.3438 Tc 417.75 266.25 Td
(119.52)Tj
ET
Q
q
442.5 264.75 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 442.5 266.25 Td
( )Tj
ET
Q
BT
/TT0 6.75 Tf
0.3121 Tc 139.5 255 Td
(BLOSUM)Tj
ET
q
168.75 253.5 9 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.375 Tc 168.75 255 Td
(80)Tj
ET
Q
q
177.75 253.5 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 177.75 255 Td
( )Tj
ET
Q
q
243 253.5 15.75 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.32809 Tc 243 255 Td
(14.5)Tj
ET
Q
q
258.75 253.5 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 258.75 255 Td
( )Tj
ET
Q
q
330 253.5 15.75 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.32809 Tc 330 255 Td
(0.04)Tj
ET
Q
q
345.75 253.5 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 345.75 255 Td
( )Tj
ET
Q
q
417.75 253.5 24.75 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.3438 Tc 417.75 255 Td
(126.44)Tj
ET
Q
q
442.5 253.5 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 442.5 255 Td
( )Tj
ET
Q
BT
/TT0 6.75 Tf
0.62421 Tc 139.5 244.5 Td
(PAM)Tj
ET
q
155.25 243 13.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.375 Tc 155.25 244.5 Td
(120)Tj
ET
Q
q
168.75 243 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 168.75 244.5 Td
( )Tj
ET
Q
q
243 243 15.75 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.32809 Tc 243 244.5 Td
(12.5)Tj
ET
Q
q
258.75 243 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 258.75 244.5 Td
( )Tj
ET
Q
q
336 243 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.375 Tc 336 244.5 Td
(1)Tj
ET
Q
q
340.5 243 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 340.5 244.5 Td
( )Tj
ET
Q
q
417.75 243 24.75 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.3438 Tc 417.75 244.5 Td
(159.28)Tj
ET
Q
q
442.5 243 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 442.5 244.5 Td
( )Tj
ET
Q
BT
/TT0 6.75 Tf
0.1879 Tc 0.3746 Tw 139.5 233.25 Td
(OPTIMA )Tj
ET
q
168 231.75 5.25 9.75 re
h
W n
BT
/TT2 8.25 Tf
0.375 Tc 0 Tw 168 233.25 Td
(*)Tj
ET
Q
q
172.5 231.75 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 172.5 233.25 Td
( )Tj
ET
Q
q
244.5 231.75 13.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.375 Tc 0 Tw 244.5 233.25 Td
(120)Tj
ET
Q
q
258 231.75 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 258 233.25 Td
( )Tj
ET
Q
q
333.75 231.75 9 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.375 Tc 0 Tw 333.75 233.25 Td
(20)Tj
ET
Q
q
342.75 231.75 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 342.75 233.25 Td
( )Tj
ET
Q
q
417.75 231.75 24.75 9.75 re
h
W n
BT
/TT0 8.25 Tf
0.3438 Tc 0 Tw 417.75 233.25 Td
(276.57)Tj
ET
Q
q
442.5 231.75 4.5 9.75 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 442.5 233.25 Td
( )Tj
ET
Q
0 0.502 0 rg
133.5 230.25 76.5 1.5 re
f
210 230.25 1.5 1.5 re
f
211.5 230.25 81.75 1.5 re
f
293.25 230.25 1.5 1.5 re
f
294.75 230.25 88.5 1.5 re
f
383.25 230.25 1.5 1.5 re
f
384.75 230.25 93 1.5 re
f
0 0 0 rg
BT
/TT0 8.25 Tf
0.1552 Tc 0.0323 Tw 135.75 222 Td
(*The scale difference in gap penalties for )Tj
/TT0 6.75 Tf
0.0629 Tc 0 Tw 145.5 0 Td
(OPTIMA)Tj
/TT0 8.25 Tf
-0.3031 Tc 0.1156 Tw 27 0 Td
( arises from the ten times greater values used to i)Tj
0.375 Tc 0 Tw 147 0 Td
(n)Tj
-0.68471 Tc 0.12219 Tw 3.75 0 Td
(crease )Tj
0.1788 Tc 0.0087 Tw -323.25 -9.75 Td
(alignment sensitivity)Tj
0 Tc 0.1875 Tw 72.75 0 Td
( )Tj
/TT0 9.75 Tf
-0.1875 Tw 105.75 -9.75 Td
( )Tj
0.0806 Tc 2.2319 Tw -160.5 -12 Td
(In addition to representatives from the BLOS)Tj
0.14861 Tc 1.66389 Tw 193.5 0 Td
(UM and PAM series, we also )Tj
0.2193 Tc 0.7182 Tw -211.5 -12 Td
(evaluated two updates of )Tj
/TT0 8.25 Tf
0.2907 Tc 0 Tw 109.5 0 Td
(PAM)Tj
/TT0 9.75 Tf
-0.375 Tc 18.75 0 Td
(250)Tj
0.05119 Tc 0.88631 Tw 13.5 0 Td
(, Gonnet )Tj
/TT2 9.75 Tf
0.2813 Tc 1.0313 Tw 39 0 Td
(et al)Tj
/TT0 9.75 Tf
-0.1875 Tc 0 Tw 19.5 0 Td
(.)Tj
/TT0 6.75 Tf
0.375 Tc 2.25 4.5 Td
(22)Tj
/TT0 9.75 Tf
0.1403 Tc 0.6722 Tw 7.5 -4.5 Td
( and Benner )Tj
/TT2 9.75 Tf
0.2303 Tc 0 Tw 54 0 Td
(et)Tj
/TT0 9.75 Tf
0 Tc -0.1875 Tw 7.5 0 Td
( )Tj
/TT2 9.75 Tf
0.409 Tc 0 Tw 3 0 Td
(al.)Tj
/TT0 6.75 Tf
0.375 Tc 10.5 4.5 Td
(23)Tj
/TT0 9.75 Tf
-0.1806 Tc 0.2431 Tw 7.5 -4.5 Td
(. The matrix )Tj
/TT0 8.25 Tf
0.1516 Tc 0 Tw -292.5 -12 Td
(IDENT)Tj
/TT0 9.75 Tf
0.14771 Tc 1.0576 Tw 26.25 0 Td
( assigns +6 for a match and )Tj
/TT3 9.75 Tf
-0.1028 Tc 0 Tw 121.5 0 Td
(-)Tj
/TT0 9.75 Tf
0.0414 Tc 0.7711 Tw 5.25 0 Td
(1 for a mismatch, and the )Tj
/TT0 8.25 Tf
0.3546 Tc 0 Tw 108 0 Td
(OPTIMA)Tj
/TT0 9.75 Tf
0.66451 Tc -0.10201 Tw 33.75 0 Td
( m)Tj
0.17101 Tc 0 Tw 9.75 0 Td
(a)Tj
-0.13631 Tc 0.69881 Tw 4.5 0 Td
(trix was )Tj
-0.0025 Tc 1.5025 Tw -309 -12 Td
(taken from reference 24. For each matrix we used gap penalties from re)Tj
-0.4129 Tc 0 Tw 297.75 0 Td
(fe)Tj
-0.2467 Tc 7.5 0 Td
(r)Tj
0.02299 Tc 0.53951 Tw 3 0 Td
(ence 15 )Tj
ET
q
/GS0 gs
/Fm0 Do
Q
endstream
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0 g
0 i
BT
/TT0 1 Tf
0 Tc 0 Tw 0 Ts 100 Tz 0 Tr 8 0 0 8 208.40401 748 Tm
(Pacific Symposium on Biocomputing 7:589-600 \(2002\) )Tj
ET
endstream
endobj
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endobj
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0 0 0 rg
1 i
BT
/TT0 12 Tf
0 Tc 0 Tw 0 Ts 100 Tz 0 Tr 135.75 131.25 Td
( )Tj
/TT0 9.75 Tf
0.0506 Tc 0.5119 Tw 0 506.25 TD
(and both original and modified all)Tj
-0.2467 Tc 0 Tw 137.25 0 Td
(-)Tj
0.13879 Tc 0.3166 Tw 3 0 Td
(positive scoring matrices. We also tried gap pe)Tj
0.4391 Tc 0 Tw 191.25 0 Td
(n-)Tj
0.04401 Tc 1.55701 Tw -331.5 -12 Td
(alties 12/2 exploited in reference 24 but they exhibited poor performanc\
e and are )Tj
-0.0127 Tc -0.1748 Tw 0 -12 TD
(excluded from Table 1, except for the )Tj
/TT0 8.25 Tf
0.3546 Tc 0 Tw 147.75 0 Td
(OPTIMA)Tj
/TT0 9.75 Tf
-0.08549 Tc -0.10201 Tw 33.75 0 Td
( m)Tj
0.17101 Tc 0 Tw 9 0 Td
(a)Tj
-0.034 Tc -0.1535 Tw 4.5 0 Td
(trix for which they are optimal.)Tj
0 Tc -0.1875 Tw 120 0 Td
( )Tj
0.1611 Tc 0.1129 Tw -297 -12 Td
(Overall, the results of Table 1 suggest that, of the previously publishe\
d scoring )Tj
-0.03529 Tc 0.7478 Tw -18 -12 Td
(matrices, the matrix of Gonnet )Tj
/TT1 9.75 Tf
0.2813 Tc 0.2813 Tw 124.5 0 Td
(et al)Tj
/TT0 9.75 Tf
-0.1875 Tc 0 Tw 18.75 0 Td
(.)Tj
/TT0 6.75 Tf
0.375 Tc 2.25 4.5 Td
(22)Tj
/TT0 9.75 Tf
0.15781 Tc 0.40469 Tw 7.5 -4.5 Td
( performed the best on our disordered protein )Tj
0.1062 Tc -0.2937 Tw -153 -12 Td
(families with less than 50% sequence identity.)Tj
0 Tc -0.1875 Tw 183 0 Td
( )Tj
-0.17979 Tc 0.36729 Tw -165 -12 Td
(The matrix )Tj
/TT0 8.25 Tf
0 Tc 0 Tw 46.5 0 Td
(DISORDER)Tj
/TT0 9.75 Tf
0.2029 Tc 1.1096 Tw 40.5 0 Td
( was obtained as descri)Tj
0.06619 Tc 1.0963 Tw 99 0 Td
(bed in Section 2 with )Tj
/TT2 9.75 Tf
-0.1523 Tc 0 Tw 92.25 0 Td
(a)Tj
/TT0 9.75 Tf
0 Tc -0.1875 Tw 6 0 Td
( )Tj
-0.24899 Tc 0 Tw 2.25 0 Td
(=)Tj
0 Tc -0.1875 Tw 5.25 0 Td
( )Tj
-0.1619 Tc 0.7243 Tw 2.25 0 Td
(1.75 \()Tj
/TT2 9.75 Tf
-0.1523 Tc 0 Tw 21.75 0 Td
(a)Tj
/TT0 9.75 Tf
0 Tc -0.1875 Tw 6 0 Td
( )Tj
0.0905 Tc 0.8002 Tw -339.75 -12 Td
(values were tested in steps of 0.25 in the interval from 1 to 2\). This \
new, disorder)Tj
-0.2467 Tc 0 Tw 336.75 0 Td
(-)Tj
0.0071 Tc 2.2429 Tw -336.75 -12 Td
(specific scoring matrix \(Fig. 3\) differs significantly from all of the\
other sco)Tj
-0.2467 Tc 0 Tw 324 0 Td
(r)Tj
0.0965 Tc 0.466 Tw 3 0 Td
(ing )Tj
-0.0766 Tc 2.3891 Tw -327 -12 Td
(matrices in Table 1. For example, )Tj
/TT0 8.25 Tf
0 Tc 0 Tw 148.5 0 Td
(DISORDER)Tj
/TT0 9.75 Tf
0.0403 Tc 1.8347 Tw 40.5 0 Td
( differs in 100 out of 210 positions )Tj
-0.3119 Tc 0 Tw -189 -12 Td
(\(47.6)Tj
-0.1788 Tc 0.7413 Tw 18.75 0 Td
(%\) from )Tj
/TT0 8.25 Tf
-0.1046 Tc 0 Tw 38.25 0 Td
(BLOSUM)Tj
/TT0 9.75 Tf
-0.3125 Tc 0.125 Tw 33.75 0 Td
(62, )Tj
0.0656 Tc 1.3219 Tw 15.75 0 Td
(which was used as the initial matrix in the development )Tj
0.13921 Tc 0.79829 Tw -106.5 -12 Td
(cycle \(section )Tj
/TT1 9.75 Tf
-0.0625 Tc 0 Tw 60.75 0 Td
(2.2)Tj
/TT0 9.75 Tf
0.0676 Tc 1.1199 Tw 12.75 0 Td
(\). Differences in values were between )Tj
/TT2 9.75 Tf
-0.1028 Tc 0 Tw 159 0 Td
(-)Tj
/TT0 9.75 Tf
0.05811 Tc 0.50439 Tw 5.25 0 Td
(3 and 3, and exhibited an )Tj
-0.0287 Tc -0.1588 Tw -237.75 -12 Td
(almost normal distrib)Tj
0.375 Tc 0 Tw 83.25 0 Td
(u)Tj
0.1653 Tc -0.35291 Tw 5.25 0 Td
(tion \(not shown\).)Tj
0 Tc -0.1875 Tw 69 0 Td
( )Tj
-139.5 -12 Td
( )Tj
/TT3 8.25 Tf
0.0435 Tc 0 Tw -16.5 -10.5 Td
(C)Tj
0 Tc 0.1875 Tw 6.75 0 Td
( )Tj
/TT0 8.25 Tf
0.375 Tc 0 Tw 13.5 0 Td
(10)Tj
ET
q
166.5 468.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 166.5 471 Td
( )Tj
ET
Q
q
183 468.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 183 471 Td
( )Tj
ET
Q
q
198.75 468.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 198.75 471 Td
( )Tj
ET
Q
q
215.25 468.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 215.25 471 Td
( )Tj
ET
Q
q
231.75 468.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 231.75 471 Td
( )Tj
ET
Q
q
248.25 468.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 248.25 471 Td
( )Tj
ET
Q
q
264.75 468.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 264.75 471 Td
( )Tj
ET
Q
q
281.25 468.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 281.25 471 Td
( )Tj
ET
Q
q
297.75 468.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 297.75 471 Td
( )Tj
ET
Q
q
314.25 468.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 314.25 471 Td
( )Tj
ET
Q
q
330.75 468.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 330.75 471 Td
( )Tj
ET
Q
q
347.25 468.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 347.25 471 Td
( )Tj
ET
Q
q
363.75 468.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 363.75 471 Td
( )Tj
ET
Q
q
380.25 468.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 380.25 471 Td
( )Tj
ET
Q
q
396.75 468.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 396.75 471 Td
( )Tj
ET
Q
q
412.5 468.75 1.5 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 412.5 471 Td
( )Tj
ET
Q
q
429 468.75 0.75 10.5 re
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0 Tc 0.1875 Tw 429 471 Td
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445.5 468.75 0.75 10.5 re
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458.25 468.75 0.75 10.5 re
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0 Tc 0.1875 Tw 458.25 471 Td
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474 468.75 0.75 10.5 re
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0 Tc 0.1875 Tw 474 471 Td
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150.75 469.5 0.75 9.75 re
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-0.08701 Tc 137.25 461.25 Td
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0 Tc 0.1875 Tw 5.25 0 Td
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166.5 459 0.75 10.5 re
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0 Tc 0.1875 Tw 166.5 461.25 Td
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183 459 0.75 10.5 re
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0 Tc 0.1875 Tw 183 461.25 Td
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198.75 459 0.75 10.5 re
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0 Tc 0.1875 Tw 198.75 461.25 Td
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215.25 459 0.75 10.5 re
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0 Tc 0.1875 Tw 215.25 461.25 Td
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231.75 459 0.75 10.5 re
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0 Tc 0.1875 Tw 231.75 461.25 Td
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248.25 459 0.75 10.5 re
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0 Tc 0.1875 Tw 248.25 461.25 Td
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264.75 459 0.75 10.5 re
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0 Tc 0.1875 Tw 264.75 461.25 Td
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281.25 459 0.75 10.5 re
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0 Tc 0.1875 Tw 281.25 461.25 Td
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297.75 459 0.75 10.5 re
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0 Tc 0.1875 Tw 297.75 461.25 Td
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314.25 459 0.75 10.5 re
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0 Tc 0.1875 Tw 314.25 461.25 Td
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330.75 459 0.75 10.5 re
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0 Tc 0.1875 Tw 330.75 461.25 Td
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347.25 459 0.75 10.5 re
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0 Tc 0.1875 Tw 347.25 461.25 Td
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363.75 459 0.75 10.5 re
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0 Tc 0.1875 Tw 363.75 461.25 Td
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380.25 459 0.75 10.5 re
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0 Tc 0.1875 Tw 380.25 461.25 Td
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396.75 459 0.75 10.5 re
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0 Tc 0.1875 Tw 396.75 461.25 Td
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412.5 459 1.5 10.5 re
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0 Tc 0.1875 Tw 412.5 461.25 Td
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429 459 0.75 10.5 re
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0 Tc 0.1875 Tw 429 461.25 Td
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445.5 459 0.75 10.5 re
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0 Tc 0.1875 Tw 445.5 461.25 Td
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458.25 459 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 458.25 461.25 Td
( )Tj
ET
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474 459 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 474 461.25 Td
( )Tj
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150.75 459.75 0.75 9.75 re
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BT
/TT3 8.25 Tf
-0.2527 Tc 137.25 451.5 Td
(T)Tj
0 Tc 0.1875 Tw 4.5 0 Td
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0.375 Tc 0 Tw 20.25 0 Td
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166.5 449.25 0.75 10.5 re
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0 Tc 0.1875 Tw 166.5 451.5 Td
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/TT0 8.25 Tf
178.5 451.5 Td
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183 449.25 0.75 10.5 re
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0 Tc 0.1875 Tw 183 451.5 Td
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/TT0 8.25 Tf
194.25 451.5 Td
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198.75 449.25 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 198.75 451.5 Td
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215.25 449.25 0.75 10.5 re
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0 Tc 0.1875 Tw 215.25 451.5 Td
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231.75 449.25 0.75 10.5 re
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0 Tc 0.1875 Tw 231.75 451.5 Td
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248.25 449.25 0.75 10.5 re
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0 Tc 0.1875 Tw 248.25 451.5 Td
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264.75 449.25 0.75 10.5 re
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0 Tc 0.1875 Tw 264.75 451.5 Td
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281.25 449.25 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 281.25 451.5 Td
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ET
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297.75 449.25 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 297.75 451.5 Td
( )Tj
ET
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314.25 449.25 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 314.25 451.5 Td
( )Tj
ET
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330.75 449.25 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 330.75 451.5 Td
( )Tj
ET
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347.25 449.25 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 347.25 451.5 Td
( )Tj
ET
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363.75 449.25 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 363.75 451.5 Td
( )Tj
ET
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380.25 449.25 0.75 10.5 re
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W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 380.25 451.5 Td
( )Tj
ET
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396.75 449.25 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 396.75 451.5 Td
( )Tj
ET
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412.5 449.25 1.5 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 412.5 451.5 Td
( )Tj
ET
Q
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429 449.25 0.75 10.5 re
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W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 429 451.5 Td
( )Tj
ET
Q
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445.5 449.25 0.75 10.5 re
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W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 445.5 451.5 Td
( )Tj
ET
Q
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458.25 449.25 0.75 10.5 re
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W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 458.25 451.5 Td
( )Tj
ET
Q
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474 449.25 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 474 451.5 Td
( )Tj
ET
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150.75 449.25 0.75 10.5 re
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BT
/TT3 8.25 Tf
0.2092 Tc 137.25 441 Td
(P)Tj
0 Tc 0.1875 Tw 5.25 0 Td
( )Tj
/TT2 8.25 Tf
-0.0293 Tc 0 Tw 15 0 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(2)Tj
ET
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166.5 438.75 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 166.5 441 Td
( )Tj
ET
Q
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178.5 438.75 5.25 10.5 re
h
W n
BT
/TT0 8.25 Tf
-0.1875 Tw 178.5 441 Td
(0 )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 189.75 441 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(1)Tj
ET
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198.75 438.75 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 198.75 441 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
210.75 441 Td
(6)Tj
ET
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215.25 438.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 215.25 441 Td
( )Tj
ET
Q
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231.75 438.75 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 231.75 441 Td
( )Tj
ET
Q
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248.25 438.75 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 248.25 441 Td
( )Tj
ET
Q
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264.75 438.75 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 264.75 441 Td
( )Tj
ET
Q
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281.25 438.75 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 281.25 441 Td
( )Tj
ET
Q
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297.75 438.75 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 297.75 441 Td
( )Tj
ET
Q
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314.25 438.75 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 314.25 441 Td
( )Tj
ET
Q
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330.75 438.75 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 330.75 441 Td
( )Tj
ET
Q
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347.25 438.75 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 347.25 441 Td
( )Tj
ET
Q
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363.75 438.75 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 363.75 441 Td
( )Tj
ET
Q
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380.25 438.75 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 380.25 441 Td
( )Tj
ET
Q
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396.75 438.75 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 396.75 441 Td
( )Tj
ET
Q
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412.5 438.75 1.5 10.5 re
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W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 412.5 441 Td
( )Tj
ET
Q
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429 438.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 429 441 Td
( )Tj
ET
Q
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445.5 438.75 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 445.5 441 Td
( )Tj
ET
Q
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458.25 438.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 458.25 441 Td
( )Tj
ET
Q
q
474 438.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 474 441 Td
( )Tj
ET
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150.75 439.5 0.75 9.75 re
f
BT
/TT3 8.25 Tf
0.0435 Tc 137.25 431.25 Td
(A)Tj
0 Tc 0.1875 Tw 6 0 Td
( )Tj
/TT2 8.25 Tf
-0.0293 Tc 0 Tw 14.25 0 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
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ET
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166.5 429 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 166.5 431.25 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
178.5 431.25 Td
(1)Tj
ET
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183 429 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 183 431.25 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
194.25 431.25 Td
(0)Tj
ET
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198.75 429 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 198.75 431.25 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 206.25 431.25 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(1)Tj
ET
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215.25 429 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 215.25 431.25 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
227.25 431.25 Td
(3)Tj
ET
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231.75 429 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 231.75 431.25 Td
( )Tj
ET
Q
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248.25 429 0.75 10.5 re
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W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 248.25 431.25 Td
( )Tj
ET
Q
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264.75 429 0.75 10.5 re
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W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 264.75 431.25 Td
( )Tj
ET
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281.25 429 0.75 10.5 re
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W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 281.25 431.25 Td
( )Tj
ET
Q
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297.75 429 0.75 10.5 re
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W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 297.75 431.25 Td
( )Tj
ET
Q
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314.25 429 0.75 10.5 re
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W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 314.25 431.25 Td
( )Tj
ET
Q
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330.75 429 0.75 10.5 re
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W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 330.75 431.25 Td
( )Tj
ET
Q
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347.25 429 0.75 10.5 re
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W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 347.25 431.25 Td
( )Tj
ET
Q
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363.75 429 0.75 10.5 re
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W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 363.75 431.25 Td
( )Tj
ET
Q
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380.25 429 0.75 10.5 re
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W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 380.25 431.25 Td
( )Tj
ET
Q
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396.75 429 0.75 10.5 re
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W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 396.75 431.25 Td
( )Tj
ET
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412.5 429 1.5 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 412.5 431.25 Td
( )Tj
ET
Q
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429 429 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 429 431.25 Td
( )Tj
ET
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445.5 429 0.75 10.5 re
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W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 445.5 431.25 Td
( )Tj
ET
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458.25 429 0.75 10.5 re
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W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 458.25 431.25 Td
( )Tj
ET
Q
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474 429 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 474 431.25 Td
( )Tj
ET
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150.75 429.75 0.75 9.75 re
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BT
/TT3 8.25 Tf
0.3315 Tc 137.25 421.5 Td
(G)Tj
0 Tc 0.1875 Tw 6.75 0 Td
( )Tj
/TT2 8.25 Tf
-0.0293 Tc 0 Tw 13.5 0 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(3)Tj
ET
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166.5 419.25 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 166.5 421.5 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
178.5 421.5 Td
(0)Tj
ET
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183 419.25 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 183 421.5 Td
( )Tj
ET
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BT
/TT2 8.25 Tf
-0.0293 Tc 189.75 421.5 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(2)Tj
ET
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198.75 419.25 0.75 10.5 re
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W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 198.75 421.5 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 206.25 421.5 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(1)Tj
ET
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215.25 419.25 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 215.25 421.5 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
227.25 421.5 Td
(0)Tj
ET
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231.75 419.25 0.75 10.5 re
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W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 231.75 421.5 Td
( )Tj
ET
Q
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/TT0 8.25 Tf
243.75 421.5 Td
(5)Tj
ET
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248.25 419.25 0.75 10.5 re
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W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 248.25 421.5 Td
( )Tj
ET
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264.75 419.25 0.75 10.5 re
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W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 264.75 421.5 Td
( )Tj
ET
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281.25 419.25 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 281.25 421.5 Td
( )Tj
ET
Q
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297.75 419.25 0.75 10.5 re
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W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 297.75 421.5 Td
( )Tj
ET
Q
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314.25 419.25 0.75 10.5 re
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W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 314.25 421.5 Td
( )Tj
ET
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330.75 419.25 0.75 10.5 re
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W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 330.75 421.5 Td
( )Tj
ET
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347.25 419.25 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 347.25 421.5 Td
( )Tj
ET
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363.75 419.25 0.75 10.5 re
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W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 363.75 421.5 Td
( )Tj
ET
Q
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380.25 419.25 0.75 10.5 re
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W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 380.25 421.5 Td
( )Tj
ET
Q
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396.75 419.25 0.75 10.5 re
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W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 396.75 421.5 Td
( )Tj
ET
Q
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412.5 419.25 1.5 10.5 re
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W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 412.5 421.5 Td
( )Tj
ET
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429 419.25 0.75 10.5 re
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W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 429 421.5 Td
( )Tj
ET
Q
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445.5 419.25 0.75 10.5 re
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W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 445.5 421.5 Td
( )Tj
ET
Q
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458.25 419.25 0.75 10.5 re
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W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 458.25 421.5 Td
( )Tj
ET
Q
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474 419.25 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 474 421.5 Td
( )Tj
ET
Q
150.75 419.25 0.75 10.5 re
f
BT
/TT3 8.25 Tf
0.0435 Tc 137.25 411 Td
(N)Tj
0 Tc 0.1875 Tw 6 0 Td
( )Tj
/TT2 8.25 Tf
-0.0293 Tc 0 Tw 14.25 0 Td
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/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
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ET
q
166.5 408.75 0.75 10.5 re
h
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 166.5 411 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
178.5 411 Td
(1)Tj
ET
q
183 408.75 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 183 411 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
194.25 411 Td
(0)Tj
ET
q
198.75 408.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 198.75 411 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 206.25 411 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(1)Tj
ET
q
215.25 408.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 215.25 411 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 222.75 411 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(1)Tj
ET
q
231.75 408.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 231.75 411 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
243.75 411 Td
(0)Tj
ET
q
248.25 408.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 248.25 411 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
260.25 411 Td
(4)Tj
ET
q
264.75 408.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 264.75 411 Td
( )Tj
ET
Q
q
281.25 408.75 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 281.25 411 Td
( )Tj
ET
Q
q
297.75 408.75 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 297.75 411 Td
( )Tj
ET
Q
q
314.25 408.75 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 314.25 411 Td
( )Tj
ET
Q
q
330.75 408.75 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 330.75 411 Td
( )Tj
ET
Q
q
347.25 408.75 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 347.25 411 Td
( )Tj
ET
Q
q
363.75 408.75 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 363.75 411 Td
( )Tj
ET
Q
q
380.25 408.75 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 380.25 411 Td
( )Tj
ET
Q
q
396.75 408.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 396.75 411 Td
( )Tj
ET
Q
q
412.5 408.75 1.5 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 412.5 411 Td
( )Tj
ET
Q
q
429 408.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 429 411 Td
( )Tj
ET
Q
q
445.5 408.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 445.5 411 Td
( )Tj
ET
Q
q
458.25 408.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 458.25 411 Td
( )Tj
ET
Q
q
474 408.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 474 411 Td
( )Tj
ET
Q
150.75 409.5 0.75 9.75 re
f
BT
/TT3 8.25 Tf
0.0435 Tc 137.25 401.25 Td
(D)Tj
0 Tc 0.1875 Tw 6 0 Td
( )Tj
/TT2 8.25 Tf
-0.0293 Tc 0 Tw 14.25 0 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(3)Tj
ET
q
166.5 399 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 166.5 401.25 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
178.5 401.25 Td
(0)Tj
ET
q
183 399 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 183 401.25 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 189.75 401.25 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(1)Tj
ET
q
198.75 399 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 198.75 401.25 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 206.25 401.25 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(2)Tj
ET
q
215.25 399 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 215.25 401.25 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 222.75 401.25 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(1)Tj
ET
q
231.75 399 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 231.75 401.25 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 239.25 401.25 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(1)Tj
ET
q
248.25 399 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 248.25 401.25 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
260.25 401.25 Td
(1)Tj
ET
q
264.75 399 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 264.75 401.25 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
276.75 401.25 Td
(4)Tj
ET
q
281.25 399 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 281.25 401.25 Td
( )Tj
ET
Q
q
297.75 399 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 297.75 401.25 Td
( )Tj
ET
Q
q
314.25 399 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 314.25 401.25 Td
( )Tj
ET
Q
q
330.75 399 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 330.75 401.25 Td
( )Tj
ET
Q
q
347.25 399 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 347.25 401.25 Td
( )Tj
ET
Q
q
363.75 399 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 363.75 401.25 Td
( )Tj
ET
Q
q
380.25 399 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 380.25 401.25 Td
( )Tj
ET
Q
q
396.75 399 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 396.75 401.25 Td
( )Tj
ET
Q
q
412.5 399 1.5 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 412.5 401.25 Td
( )Tj
ET
Q
q
429 399 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 429 401.25 Td
( )Tj
ET
Q
q
445.5 399 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 445.5 401.25 Td
( )Tj
ET
Q
q
458.25 399 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 458.25 401.25 Td
( )Tj
ET
Q
q
474 399 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 474 401.25 Td
( )Tj
ET
Q
150.75 399.75 0.75 9.75 re
f
BT
/TT3 8.25 Tf
-0.2527 Tc 137.25 391.5 Td
(E)Tj
0 Tc 0.1875 Tw 4.5 0 Td
( )Tj
/TT2 8.25 Tf
-0.0293 Tc 0 Tw 15.75 0 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(4)Tj
ET
q
166.5 389.25 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 166.5 391.5 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 174 391.5 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(1)Tj
ET
q
183 389.25 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 183 391.5 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 189.75 391.5 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(1)Tj
ET
q
198.75 389.25 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 198.75 391.5 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 206.25 391.5 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(1)Tj
ET
q
215.25 389.25 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 215.25 391.5 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 222.75 391.5 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(1)Tj
ET
q
231.75 389.25 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 231.75 391.5 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 239.25 391.5 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(2)Tj
ET
q
248.25 389.25 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 248.25 391.5 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
260.25 391.5 Td
(0)Tj
ET
q
264.75 389.25 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 264.75 391.5 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
276.75 391.5 Td
(2)Tj
ET
q
281.25 389.25 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 281.25 391.5 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
293.25 391.5 Td
(4)Tj
ET
q
297.75 389.25 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 297.75 391.5 Td
( )Tj
ET
Q
q
314.25 389.25 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 314.25 391.5 Td
( )Tj
ET
Q
q
330.75 389.25 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 330.75 391.5 Td
( )Tj
ET
Q
q
347.25 389.25 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 347.25 391.5 Td
( )Tj
ET
Q
q
363.75 389.25 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 363.75 391.5 Td
( )Tj
ET
Q
q
380.25 389.25 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 380.25 391.5 Td
( )Tj
ET
Q
q
396.75 389.25 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 396.75 391.5 Td
( )Tj
ET
Q
q
412.5 389.25 1.5 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 412.5 391.5 Td
( )Tj
ET
Q
q
429 389.25 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 429 391.5 Td
( )Tj
ET
Q
q
445.5 389.25 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 445.5 391.5 Td
( )Tj
ET
Q
q
458.25 389.25 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 458.25 391.5 Td
( )Tj
ET
Q
q
474 389.25 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 474 391.5 Td
( )Tj
ET
Q
150.75 389.25 0.75 10.5 re
f
BT
/TT3 8.25 Tf
0.3315 Tc 137.25 381 Td
(Q)Tj
0 Tc 0.1875 Tw 7.5 0 Td
( )Tj
/TT2 8.25 Tf
-0.0293 Tc 0 Tw 12.75 0 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(3)Tj
ET
q
166.5 378.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 166.5 381 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
178.5 381 Td
(0)Tj
ET
q
183 378.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 183 381 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
194.25 381 Td
(0)Tj
ET
q
198.75 378.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 198.75 381 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 206.25 381 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(1)Tj
ET
q
215.25 378.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 215.25 381 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 222.75 381 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(1)Tj
ET
q
231.75 378.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 231.75 381 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 239.25 381 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(2)Tj
ET
q
248.25 378.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 248.25 381 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
260.25 381 Td
(1)Tj
ET
q
264.75 378.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 264.75 381 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
276.75 381 Td
(0)Tj
ET
q
281.25 378.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 281.25 381 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
293.25 381 Td
(0)Tj
ET
q
297.75 378.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 297.75 381 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
309.75 381 Td
(5)Tj
ET
q
314.25 378.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 314.25 381 Td
( )Tj
ET
Q
q
330.75 378.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 330.75 381 Td
( )Tj
ET
Q
q
347.25 378.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 347.25 381 Td
( )Tj
ET
Q
q
363.75 378.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 363.75 381 Td
( )Tj
ET
Q
q
380.25 378.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 380.25 381 Td
( )Tj
ET
Q
q
396.75 378.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 396.75 381 Td
( )Tj
ET
Q
q
412.5 378.75 1.5 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 412.5 381 Td
( )Tj
ET
Q
q
429 378.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 429 381 Td
( )Tj
ET
Q
q
445.5 378.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 445.5 381 Td
( )Tj
ET
Q
q
458.25 378.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 458.25 381 Td
( )Tj
ET
Q
q
474 378.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 474 381 Td
( )Tj
ET
Q
150.75 379.5 0.75 9.75 re
f
BT
/TT3 8.25 Tf
0.3315 Tc 137.25 371.25 Td
(H)Tj
0 Tc 0.1875 Tw 6.75 0 Td
( )Tj
/TT2 8.25 Tf
-0.0293 Tc 0 Tw 13.5 0 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(1)Tj
ET
q
166.5 369 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 166.5 371.25 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 174 371.25 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(1)Tj
ET
q
183 369 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 183 371.25 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
194.25 371.25 Td
(0)Tj
ET
q
198.75 369 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 198.75 371.25 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 206.25 371.25 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(2)Tj
ET
q
215.25 369 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 215.25 371.25 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 222.75 371.25 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(2)Tj
ET
q
231.75 369 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 231.75 371.25 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 239.25 371.25 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(1)Tj
ET
q
248.25 369 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 248.25 371.25 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
260.25 371.25 Td
(2)Tj
ET
q
264.75 369 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
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281.25 369 0.75 10.5 re
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297.75 369 0.75 10.5 re
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314.25 369 0.75 10.5 re
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0 Tc 0.1875 Tw 314.25 371.25 Td
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330.75 369 0.75 10.5 re
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347.25 369 0.75 10.5 re
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363.75 369 0.75 10.5 re
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380.25 369 0.75 10.5 re
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396.75 369 0.75 10.5 re
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412.5 369 1.5 10.5 re
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429 369 0.75 10.5 re
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445.5 369 0.75 10.5 re
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458.25 369 0.75 10.5 re
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474 369 0.75 10.5 re
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150.75 369.75 0.75 9.75 re
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0.0435 Tc 137.25 361.5 Td
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166.5 359.25 0.75 10.5 re
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183 359.25 0.75 10.5 re
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198.75 359.25 0.75 10.5 re
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0 Tc 0.1875 Tw 198.75 361.5 Td
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215.25 359.25 0.75 10.5 re
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231.75 359.25 0.75 10.5 re
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248.25 359.25 0.75 10.5 re
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264.75 359.25 0.75 10.5 re
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0 Tc 0.1875 Tw 264.75 361.5 Td
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281.25 359.25 0.75 10.5 re
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0 Tc 0.1875 Tw 281.25 361.5 Td
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297.75 359.25 0.75 10.5 re
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0 Tc 0.1875 Tw 297.75 361.5 Td
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314.25 359.25 0.75 10.5 re
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0 Tc 0.1875 Tw 314.25 361.5 Td
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326.25 361.5 Td
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330.75 359.25 0.75 10.5 re
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0 Tc 0.1875 Tw 330.75 361.5 Td
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342.75 361.5 Td
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347.25 359.25 0.75 10.5 re
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0 Tc 0.1875 Tw 347.25 361.5 Td
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363.75 359.25 0.75 10.5 re
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0 Tc 0.1875 Tw 363.75 361.5 Td
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380.25 359.25 0.75 10.5 re
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0 Tc 0.1875 Tw 380.25 361.5 Td
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396.75 359.25 0.75 10.5 re
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0 Tc 0.1875 Tw 396.75 361.5 Td
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412.5 359.25 1.5 10.5 re
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0 Tc 0.1875 Tw 412.5 361.5 Td
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429 359.25 0.75 10.5 re
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0 Tc 0.1875 Tw 429 361.5 Td
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445.5 359.25 0.75 10.5 re
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0 Tc 0.1875 Tw 445.5 361.5 Td
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458.25 359.25 0.75 10.5 re
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0 Tc 0.1875 Tw 458.25 361.5 Td
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474 359.25 0.75 10.5 re
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0 Tc 0.1875 Tw 474 361.5 Td
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150.75 359.25 0.75 10.5 re
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0.3315 Tc 137.25 351 Td
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0 Tc 0.1875 Tw 6 0 Td
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-0.0293 Tc 0 Tw 14.25 0 Td
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166.5 348.75 0.75 10.5 re
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0 Tc 0.1875 Tw 166.5 351 Td
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/TT2 8.25 Tf
-0.0293 Tc 174 351 Td
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183 348.75 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 183 351 Td
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/TT0 8.25 Tf
194.25 351 Td
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198.75 348.75 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 198.75 351 Td
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/TT2 8.25 Tf
-0.0293 Tc 206.25 351 Td
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215.25 348.75 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 215.25 351 Td
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/TT2 8.25 Tf
-0.0293 Tc 222.75 351 Td
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231.75 348.75 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 231.75 351 Td
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/TT2 8.25 Tf
-0.0293 Tc 239.25 351 Td
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248.25 348.75 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 248.25 351 Td
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/TT0 8.25 Tf
260.25 351 Td
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264.75 348.75 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 264.75 351 Td
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/TT2 8.25 Tf
-0.0293 Tc 272.25 351 Td
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281.25 348.75 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 281.25 351 Td
( )Tj
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/TT0 8.25 Tf
293.25 351 Td
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297.75 348.75 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 297.75 351 Td
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/TT0 8.25 Tf
309.75 351 Td
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314.25 348.75 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 314.25 351 Td
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/TT2 8.25 Tf
-0.0293 Tc 321.75 351 Td
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ET
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330.75 348.75 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 330.75 351 Td
( )Tj
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/TT0 8.25 Tf
342.75 351 Td
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347.25 348.75 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 347.25 351 Td
( )Tj
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/TT0 8.25 Tf
359.25 351 Td
(4)Tj
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363.75 348.75 0.75 10.5 re
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0 Tc 0.1875 Tw 363.75 351 Td
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380.25 348.75 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 380.25 351 Td
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396.75 348.75 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 396.75 351 Td
( )Tj
ET
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412.5 348.75 1.5 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 412.5 351 Td
( )Tj
ET
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429 348.75 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 429 351 Td
( )Tj
ET
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445.5 348.75 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 445.5 351 Td
( )Tj
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458.25 348.75 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 458.25 351 Td
( )Tj
ET
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474 348.75 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 474 351 Td
( )Tj
ET
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150.75 349.5 0.75 9.75 re
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BT
/TT3 8.25 Tf
-0.28799 Tc 137.25 341.25 Td
(M)Tj
0 Tc 0.1875 Tw 7.5 0 Td
( )Tj
/TT0 8.25 Tf
0.375 Tc 0 Tw 17.25 0 Td
(0)Tj
ET
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166.5 339 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 166.5 341.25 Td
( )Tj
ET
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/TT2 8.25 Tf
-0.0293 Tc 174 341.25 Td
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0.375 Tc 4.5 0 Td
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ET
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183 339 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 183 341.25 Td
( )Tj
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BT
/TT2 8.25 Tf
-0.0293 Tc 189.75 341.25 Td
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ET
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198.75 339 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 198.75 341.25 Td
( )Tj
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/TT2 8.25 Tf
-0.0293 Tc 206.25 341.25 Td
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0.375 Tc 4.5 0 Td
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ET
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215.25 339 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 215.25 341.25 Td
( )Tj
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/TT2 8.25 Tf
-0.0293 Tc 222.75 341.25 Td
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0.375 Tc 4.5 0 Td
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ET
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231.75 339 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 231.75 341.25 Td
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ET
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/TT2 8.25 Tf
-0.0293 Tc 239.25 341.25 Td
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0.375 Tc 4.5 0 Td
(4)Tj
ET
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248.25 339 0.75 10.5 re
h
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 248.25 341.25 Td
( )Tj
ET
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/TT2 8.25 Tf
-0.0293 Tc 255.75 341.25 Td
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/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
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ET
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264.75 339 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 264.75 341.25 Td
( )Tj
ET
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/TT2 8.25 Tf
-0.0293 Tc 272.25 341.25 Td
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0.375 Tc 4.5 0 Td
(4)Tj
ET
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281.25 339 0.75 10.5 re
h
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 281.25 341.25 Td
( )Tj
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/TT2 8.25 Tf
-0.0293 Tc 288.75 341.25 Td
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ET
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297.75 339 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 297.75 341.25 Td
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/TT2 8.25 Tf
-0.0293 Tc 305.25 341.25 Td
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ET
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314.25 339 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 314.25 341.25 Td
( )Tj
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/TT2 8.25 Tf
-0.0293 Tc 321.75 341.25 Td
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ET
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330.75 339 0.75 10.5 re
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0 Tc 0.1875 Tw 330.75 341.25 Td
( )Tj
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/TT2 8.25 Tf
-0.0293 Tc 338.25 341.25 Td
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347.25 339 0.75 10.5 re
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0 Tc 0.1875 Tw 347.25 341.25 Td
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/TT2 8.25 Tf
-0.0293 Tc 354.75 341.25 Td
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ET
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363.75 339 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 363.75 341.25 Td
( )Tj
ET
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/TT0 8.25 Tf
375.75 341.25 Td
(7)Tj
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380.25 339 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 380.25 341.25 Td
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ET
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396.75 339 0.75 10.5 re
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0 Tc 0.1875 Tw 396.75 341.25 Td
( )Tj
ET
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412.5 339 1.5 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 412.5 341.25 Td
( )Tj
ET
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429 339 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 429 341.25 Td
( )Tj
ET
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445.5 339 0.75 10.5 re
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0 Tc 0.1875 Tw 445.5 341.25 Td
( )Tj
ET
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458.25 339 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 458.25 341.25 Td
( )Tj
ET
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474 339 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 474 341.25 Td
( )Tj
ET
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150.75 339.75 0.75 9.75 re
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BT
/TT3 8.25 Tf
-0.2092 Tc 137.25 331.5 Td
(I)Tj
0 Tc 0.1875 Tw 3 0 Td
( )Tj
/TT0 8.25 Tf
0.375 Tc 0 Tw 21.75 0 Td
(0)Tj
ET
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166.5 329.25 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 166.5 331.5 Td
( )Tj
ET
Q
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/TT2 8.25 Tf
-0.0293 Tc 174 331.5 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(2)Tj
ET
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183 329.25 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 183 331.5 Td
( )Tj
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BT
/TT2 8.25 Tf
-0.0293 Tc 189.75 331.5 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
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ET
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198.75 329.25 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 198.75 331.5 Td
( )Tj
ET
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/TT2 8.25 Tf
-0.0293 Tc 206.25 331.5 Td
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/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(2)Tj
ET
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215.25 329.25 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 215.25 331.5 Td
( )Tj
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/TT2 8.25 Tf
-0.0293 Tc 222.75 331.5 Td
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0.375 Tc 4.5 0 Td
(1)Tj
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231.75 329.25 0.75 10.5 re
h
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248.25 329.25 0.75 10.5 re
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264.75 329.25 0.75 10.5 re
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0 Tc 0.1875 Tw 264.75 331.5 Td
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-0.0293 Tc 272.25 331.5 Td
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281.25 329.25 0.75 10.5 re
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0 Tc 0.1875 Tw 281.25 331.5 Td
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297.75 329.25 0.75 10.5 re
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314.25 329.25 0.75 10.5 re
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0 Tc 0.1875 Tw 314.25 331.5 Td
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-0.0293 Tc 321.75 331.5 Td
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330.75 329.25 0.75 10.5 re
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-0.0293 Tc 338.25 331.5 Td
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347.25 329.25 0.75 10.5 re
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363.75 329.25 0.75 10.5 re
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0 Tc 0.1875 Tw 363.75 331.5 Td
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380.25 329.25 0.75 10.5 re
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0 Tc 0.1875 Tw 380.25 331.5 Td
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392.25 331.5 Td
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396.75 329.25 0.75 10.5 re
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0 Tc 0.1875 Tw 396.75 331.5 Td
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412.5 329.25 1.5 10.5 re
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0 Tc 0.1875 Tw 412.5 331.5 Td
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429 329.25 0.75 10.5 re
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445.5 329.25 0.75 10.5 re
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0 Tc 0.1875 Tw 445.5 331.5 Td
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458.25 329.25 0.75 10.5 re
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0 Tc 0.1875 Tw 458.25 331.5 Td
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474 329.25 0.75 10.5 re
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150.75 329.25 0.75 10.5 re
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-0.2527 Tc 137.25 321 Td
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0 Tc 0.1875 Tw 5.25 0 Td
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166.5 318.75 0.75 10.5 re
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0 Tc 0.1875 Tw 166.5 321 Td
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-0.0293 Tc 174 321 Td
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183 318.75 0.75 10.5 re
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0 Tc 0.1875 Tw 183 321 Td
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-0.0293 Tc 189.75 321 Td
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198.75 318.75 0.75 10.5 re
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0 Tc 0.1875 Tw 198.75 321 Td
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-0.0293 Tc 206.25 321 Td
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215.25 318.75 0.75 10.5 re
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0 Tc 0.1875 Tw 215.25 321 Td
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/TT2 8.25 Tf
-0.0293 Tc 222.75 321 Td
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231.75 318.75 0.75 10.5 re
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0 Tc 0.1875 Tw 231.75 321 Td
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/TT2 8.25 Tf
-0.0293 Tc 239.25 321 Td
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248.25 318.75 0.75 10.5 re
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0 Tc 0.1875 Tw 248.25 321 Td
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/TT2 8.25 Tf
-0.0293 Tc 255.75 321 Td
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264.75 318.75 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 264.75 321 Td
( )Tj
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BT
/TT2 8.25 Tf
-0.0293 Tc 272.25 321 Td
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ET
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281.25 318.75 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 281.25 321 Td
( )Tj
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/TT2 8.25 Tf
-0.0293 Tc 288.75 321 Td
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297.75 318.75 0.75 10.5 re
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0 Tc 0.1875 Tw 297.75 321 Td
( )Tj
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/TT2 8.25 Tf
-0.0293 Tc 305.25 321 Td
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ET
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314.25 318.75 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 314.25 321 Td
( )Tj
ET
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/TT2 8.25 Tf
-0.0293 Tc 321.75 321 Td
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/TT0 8.25 Tf
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ET
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330.75 318.75 0.75 10.5 re
h
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 330.75 321 Td
( )Tj
ET
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BT
/TT2 8.25 Tf
-0.0293 Tc 338.25 321 Td
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ET
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347.25 318.75 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 347.25 321 Td
( )Tj
ET
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BT
/TT2 8.25 Tf
-0.0293 Tc 354.75 321 Td
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/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
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ET
q
363.75 318.75 0.75 10.5 re
h
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 363.75 321 Td
( )Tj
ET
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BT
/TT0 8.25 Tf
375.75 321 Td
(2)Tj
ET
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380.25 318.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 380.25 321 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
392.25 321 Td
(2)Tj
ET
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396.75 318.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 396.75 321 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
408 321 Td
(4)Tj
ET
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412.5 318.75 1.5 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 412.5 321 Td
( )Tj
ET
Q
q
429 318.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 429 321 Td
( )Tj
ET
Q
q
445.5 318.75 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 445.5 321 Td
( )Tj
ET
Q
q
458.25 318.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 458.25 321 Td
( )Tj
ET
Q
q
474 318.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 474 321 Td
( )Tj
ET
Q
150.75 319.5 0.75 9.75 re
f
BT
/TT3 8.25 Tf
0.0435 Tc 137.25 311.25 Td
(V)Tj
0 Tc 0.1875 Tw 6 0 Td
( )Tj
/TT0 8.25 Tf
0.375 Tc 0 Tw 18.75 0 Td
(1)Tj
ET
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166.5 309 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 166.5 311.25 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 174 311.25 Td
(-)Tj
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0.375 Tc 4.5 0 Td
(2)Tj
ET
q
183 309 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 183 311.25 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
194.25 311.25 Td
(0)Tj
ET
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198.75 309 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 198.75 311.25 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 206.25 311.25 Td
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0.375 Tc 4.5 0 Td
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ET
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215.25 309 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 215.25 311.25 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
227.25 311.25 Td
(0)Tj
ET
q
231.75 309 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 231.75 311.25 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 239.25 311.25 Td
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/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(4)Tj
ET
q
248.25 309 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 248.25 311.25 Td
( )Tj
ET
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BT
/TT2 8.25 Tf
-0.0293 Tc 255.75 311.25 Td
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/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
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ET
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264.75 309 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 264.75 311.25 Td
( )Tj
ET
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BT
/TT2 8.25 Tf
-0.0293 Tc 272.25 311.25 Td
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/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(4)Tj
ET
q
281.25 309 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 281.25 311.25 Td
( )Tj
ET
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BT
/TT2 8.25 Tf
-0.0293 Tc 288.75 311.25 Td
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0.375 Tc 4.5 0 Td
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ET
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297.75 309 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 297.75 311.25 Td
( )Tj
ET
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BT
/TT2 8.25 Tf
-0.0293 Tc 305.25 311.25 Td
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/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
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ET
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314.25 309 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 314.25 311.25 Td
( )Tj
ET
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BT
/TT2 8.25 Tf
-0.0293 Tc 321.75 311.25 Td
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/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
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ET
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330.75 309 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 330.75 311.25 Td
( )Tj
ET
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BT
/TT2 8.25 Tf
-0.0293 Tc 338.25 311.25 Td
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/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
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ET
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347.25 309 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 347.25 311.25 Td
( )Tj
ET
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/TT2 8.25 Tf
-0.0293 Tc 354.75 311.25 Td
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0.375 Tc 4.5 0 Td
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ET
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363.75 309 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 363.75 311.25 Td
( )Tj
ET
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BT
/TT0 8.25 Tf
375.75 311.25 Td
(1)Tj
ET
q
380.25 309 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 380.25 311.25 Td
( )Tj
ET
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BT
/TT0 8.25 Tf
392.25 311.25 Td
(3)Tj
ET
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396.75 309 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 396.75 311.25 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
408 311.25 Td
(1)Tj
ET
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412.5 309 1.5 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 412.5 311.25 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
424.5 311.25 Td
(4)Tj
ET
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429 309 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 429 311.25 Td
( )Tj
ET
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q
445.5 309 0.75 10.5 re
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 445.5 311.25 Td
( )Tj
ET
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458.25 309 0.75 10.5 re
h
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 458.25 311.25 Td
( )Tj
ET
Q
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474 309 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 474 311.25 Td
( )Tj
ET
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150.75 309.75 0.75 9.75 re
f
BT
/TT3 8.25 Tf
0.2092 Tc 137.25 301.5 Td
(F)Tj
0 Tc 0.1875 Tw 4.5 0 Td
( )Tj
/TT2 8.25 Tf
-0.0293 Tc 0 Tw 15.75 0 Td
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0.375 Tc 4.5 0 Td
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ET
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166.5 299.25 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 166.5 301.5 Td
( )Tj
ET
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BT
/TT2 8.25 Tf
-0.0293 Tc 174 301.5 Td
(-)Tj
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0.375 Tc 4.5 0 Td
(2)Tj
ET
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183 299.25 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 183 301.5 Td
( )Tj
ET
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BT
/TT2 8.25 Tf
-0.0293 Tc 189.75 301.5 Td
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/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(2)Tj
ET
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198.75 299.25 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 198.75 301.5 Td
( )Tj
ET
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/TT2 8.25 Tf
-0.0293 Tc 206.25 301.5 Td
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/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(3)Tj
ET
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215.25 299.25 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 215.25 301.5 Td
( )Tj
ET
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/TT2 8.25 Tf
-0.0293 Tc 222.75 301.5 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(2)Tj
ET
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231.75 299.25 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 231.75 301.5 Td
( )Tj
ET
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BT
/TT2 8.25 Tf
-0.0293 Tc 239.25 301.5 Td
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/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(4)Tj
ET
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248.25 299.25 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 248.25 301.5 Td
( )Tj
ET
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/TT2 8.25 Tf
-0.0293 Tc 255.75 301.5 Td
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/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(2)Tj
ET
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264.75 299.25 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 264.75 301.5 Td
( )Tj
ET
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BT
/TT2 8.25 Tf
-0.0293 Tc 272.25 301.5 Td
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/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(4)Tj
ET
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281.25 299.25 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 281.25 301.5 Td
( )Tj
ET
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BT
/TT2 8.25 Tf
-0.0293 Tc 288.75 301.5 Td
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/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(4)Tj
ET
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297.75 299.25 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 297.75 301.5 Td
( )Tj
ET
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BT
/TT2 8.25 Tf
-0.0293 Tc 305.25 301.5 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(2)Tj
ET
q
314.25 299.25 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 314.25 301.5 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
326.25 301.5 Td
(0)Tj
ET
q
330.75 299.25 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 330.75 301.5 Td
( )Tj
ET
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BT
/TT2 8.25 Tf
-0.0293 Tc 338.25 301.5 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(3)Tj
ET
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347.25 299.25 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 347.25 301.5 Td
( )Tj
ET
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BT
/TT2 8.25 Tf
-0.0293 Tc 354.75 301.5 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(3)Tj
ET
q
363.75 299.25 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 363.75 301.5 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
375.75 301.5 Td
(1)Tj
ET
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380.25 299.25 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 380.25 301.5 Td
( )Tj
ET
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/TT0 8.25 Tf
392.25 301.5 Td
(1)Tj
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q
396.75 299.25 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 396.75 301.5 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
408 301.5 Td
(1)Tj
ET
q
412.5 299.25 1.5 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 412.5 301.5 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
424.5 301.5 Td
(0)Tj
ET
q
429 299.25 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 429 301.5 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
441 301.5 Td
(7)Tj
ET
q
445.5 299.25 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 445.5 301.5 Td
( )Tj
ET
Q
q
458.25 299.25 0.75 10.5 re
h
W n
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/TT0 8.25 Tf
0 Tc 0.1875 Tw 458.25 301.5 Td
( )Tj
ET
Q
q
474 299.25 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 474 301.5 Td
( )Tj
ET
Q
150.75 299.25 0.75 10.5 re
f
BT
/TT3 8.25 Tf
0.0435 Tc 137.25 291 Td
(Y)Tj
0 Tc 0.1875 Tw 6 0 Td
( )Tj
/TT0 8.25 Tf
0.375 Tc 0 Tw 18.75 0 Td
(0)Tj
ET
q
166.5 288.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 166.5 291 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 174 291 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(2)Tj
ET
q
183 288.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 183 291 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 189.75 291 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(1)Tj
ET
q
198.75 288.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 198.75 291 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 206.25 291 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(3)Tj
ET
q
215.25 288.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 215.25 291 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 222.75 291 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(2)Tj
ET
q
231.75 288.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 231.75 291 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 239.25 291 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(3)Tj
ET
q
248.25 288.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 248.25 291 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 255.75 291 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(1)Tj
ET
q
264.75 288.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 264.75 291 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 272.25 291 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(4)Tj
ET
q
281.25 288.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 281.25 291 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 288.75 291 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(3)Tj
ET
q
297.75 288.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 297.75 291 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
309.75 291 Td
(0)Tj
ET
q
314.25 288.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 314.25 291 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
326.25 291 Td
(2)Tj
ET
q
330.75 288.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 330.75 291 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 338.25 291 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(2)Tj
ET
q
347.25 288.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 347.25 291 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 354.75 291 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(2)Tj
ET
q
363.75 288.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 363.75 291 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 371.25 291 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(1)Tj
ET
q
380.25 288.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 380.25 291 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
392.25 291 Td
(0)Tj
ET
q
396.75 288.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 396.75 291 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
408 291 Td
(0)Tj
ET
q
412.5 288.75 1.5 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 412.5 291 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 420 291 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(1)Tj
ET
q
429 288.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 429 291 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
441 291 Td
(4)Tj
ET
q
445.5 288.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 445.5 291 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
453.75 291 Td
(8)Tj
ET
q
458.25 288.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 458.25 291 Td
( )Tj
ET
Q
q
474 288.75 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 474 291 Td
( )Tj
ET
Q
150.75 289.5 0.75 9.75 re
f
BT
/TT3 8.25 Tf
0 Tc 137.25 281.25 Td
(W)Tj
0.1875 Tw 9 0 Td
( )Tj
/TT2 8.25 Tf
-0.0293 Tc 0 Tw 11.25 0 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(5)Tj
ET
q
166.5 279 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 166.5 281.25 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 174 281.25 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(3)Tj
ET
q
183 279 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 183 281.25 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 189.75 281.25 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(5)Tj
ET
q
198.75 279 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 198.75 281.25 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 206.25 281.25 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(1)Tj
ET
q
215.25 279 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 215.25 281.25 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 222.75 281.25 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(5)Tj
ET
q
231.75 279 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 231.75 281.25 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 239.25 281.25 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(4)Tj
ET
q
248.25 279 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 248.25 281.25 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 255.75 281.25 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(3)Tj
ET
q
264.75 279 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 264.75 281.25 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 272.25 281.25 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(4)Tj
ET
q
281.25 279 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 281.25 281.25 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 288.75 281.25 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(4)Tj
ET
q
297.75 279 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 297.75 281.25 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 305.25 281.25 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(1)Tj
ET
q
314.25 279 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 314.25 281.25 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 321.75 281.25 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(2)Tj
ET
q
330.75 279 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 330.75 281.25 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
342.75 281.25 Td
(0)Tj
ET
q
347.25 279 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 347.25 281.25 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 354.75 281.25 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(3)Tj
ET
q
363.75 279 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 363.75 281.25 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 371.25 281.25 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(1)Tj
ET
q
380.25 279 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 380.25 281.25 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 387.75 281.25 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(2)Tj
ET
q
396.75 279 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 396.75 281.25 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 403.5 281.25 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(2)Tj
ET
q
412.5 279 1.5 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 412.5 281.25 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 420 281.25 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(4)Tj
ET
q
429 279 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 429 281.25 Td
( )Tj
ET
Q
BT
/TT2 8.25 Tf
-0.0293 Tc 436.5 281.25 Td
(-)Tj
/TT0 8.25 Tf
0.375 Tc 4.5 0 Td
(1)Tj
ET
q
445.5 279 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 445.5 281.25 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
453.75 281.25 Td
(3)Tj
ET
q
458.25 279 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 458.25 281.25 Td
( )Tj
ET
Q
BT
/TT0 8.25 Tf
465 281.25 Td
(13)Tj
ET
q
474 279 0.75 10.5 re
h
W n
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 474 281.25 Td
( )Tj
ET
Q
150.75 279.75 0.75 9.75 re
f
BT
/TT0 8.25 Tf
0 Tc 0.1875 Tw 137.25 270.75 Td
( )Tj
/TT3 8.25 Tf
0.0435 Tc 0 Tw 22.5 0 Td
(C)Tj
ET
q
166.5 269.25 0.75 9.75 re
h
W n
BT
/TT3 8.25 Tf
0 Tc 0.1875 Tw 166.5 270.75 Td
( )Tj
ET
Q
BT
/TT3 8.25 Tf
-0.08701 Tc 177.75 270.75 Td
(S)Tj
ET
q
183 269.25 0.75 9.75 re
h
W n
BT
/TT3 8.25 Tf
0 Tc 0.1875 Tw 183 270.75 Td
( )Tj
ET
Q
BT
/TT3 8.25 Tf
-0.2527 Tc 194.25 270.75 Td
(T)Tj
ET
q
198.75 269.25 0.75 9.75 re
h
W n
BT
/TT3 8.25 Tf
0 Tc 0.1875 Tw 198.75 270.75 Td
( )Tj
ET
Q
BT
/TT3 8.25 Tf
0.2092 Tc 210 270.75 Td
(P)Tj
ET
q
215.25 269.25 0.75 9.75 re
h
W n
BT
/TT3 8.25 Tf
0 Tc 0.1875 Tw 215.25 270.75 Td
( )Tj
ET
Q
BT
/TT3 8.25 Tf
0.0435 Tc 225.75 270.75 Td
(A)Tj
ET
q
231.75 269.25 0.75 9.75 re
h
W n
BT
/TT3 8.25 Tf
0 Tc 0.1875 Tw 231.75 270.75 Td
( )Tj
ET
Q
BT
/TT3 8.25 Tf
0.3315 Tc 241.5 270.75 Td
(G)Tj
ET
q
248.25 269.25 0.75 9.75 re
h
W n
BT
/TT3 8.25 Tf
0 Tc 0.1875 Tw 248.25 270.75 Td
( )Tj
ET
Q
BT
/TT3 8.25 Tf
0.0435 Tc 258.75 270.75 Td
(N)Tj
ET
q
264.75 269.25 0.75 9.75 re
h
W n
BT
/TT3 8.25 Tf
0 Tc 0.1875 Tw 264.75 270.75 Td
( )Tj
ET
Q
BT
/TT3 8.25 Tf
275.25 270.75 Td
(D)Tj
ET
q
281.25 269.25 0.75 9.75 re
h
W n
BT
/TT3 8.25 Tf
0 Tc 0.1875 Tw 281.25 270.75 Td
( )Tj
ET
Q
BT
/TT3 8.25 Tf
-0.2527 Tc 293.25 270.75 Td
(E)Tj
ET
q
297.75 269.25 0.75 9.75 re
h
W n
BT
/TT3 8.25 Tf
0 Tc 0.1875 Tw 297.75 270.75 Td
( )Tj
ET
Q
BT
/TT3 8.25 Tf
0.3315 Tc 306.75 270.75 Td
(Q)Tj
ET
q
314.25 269.25 0.75 9.75 re
h
W n
BT
/TT3 8.25 Tf
0 Tc 0.1875 Tw 314.25 270.75 Td
( )Tj
ET
Q
BT
/TT3 8.25 Tf
324 270.75 Td
(H)Tj
ET
q
330.75 269.25 0.75 9.75 re
h
W n
BT
/TT3 8.25 Tf
0 Tc 0.1875 Tw 330.75 270.75 Td
( )Tj
ET
Q
BT
/TT3 8.25 Tf
0.0435 Tc 341.25 270.75 Td
(R)Tj
ET
q
347.25 269.25 0.75 9.75 re
h
W n
BT
/TT3 8.25 Tf
0 Tc 0.1875 Tw 347.25 270.75 Td
( )Tj
ET
Q
BT
/TT3 8.25 Tf
0.3315 Tc 357.75 270.75 Td
(K)Tj
ET
q
363.75 269.25 0.75 9.75 re
h
W n
BT
/TT3 8.25 Tf
0 Tc 0.1875 Tw 363.75 270.75 Td
( )Tj
ET
Q
BT
/TT3 8.25 Tf
-0.28799 Tc 372.75 270.75 Td
(M)Tj
ET
q
380.25 269.25 0.75 9.75 re
h
W n
BT
/TT3 8.25 Tf
0 Tc 0.1875 Tw 380.25 270.75 Td
( )Tj
ET
Q
BT
/TT3 8.25 Tf
-0.2092 Tc 393.75 270.75 Td
(I)Tj
ET
q
396.75 269.25 0.75 9.75 re
h
W n
BT
/TT3 8.25 Tf
0 Tc 0.1875 Tw 396.75 270.75 Td
( )Tj
ET
Q
BT
/TT3 8.25 Tf
-0.2527 Tc 407.25 270.75 Td
(L)Tj
ET
q
412.5 269.25 1.5 9.75 re
h
W n
BT
/TT3 8.25 Tf
0 Tc 0.1875 Tw 412.5 270.75 Td
( )Tj
ET
Q
BT
/TT3 8.25 Tf
0.0435 Tc 423 270.75 Td
(V)Tj
ET
q
429 269.25 0.75 9.75 re
h
W n
BT
/TT3 8.25 Tf
0 Tc 0.1875 Tw 429 270.75 Td
( )Tj
ET
Q
BT
/TT3 8.25 Tf
0.2092 Tc 441 270.75 Td
(F)Tj
ET
q
445.5 269.25 0.75 9.75 re
h
W n
BT
/TT3 8.25 Tf
0 Tc 0.1875 Tw 445.5 270.75 Td
( )Tj
ET
Q
BT
/TT3 8.25 Tf
0.0435 Tc 452.25 270.75 Td
(Y)Tj
ET
q
458.25 269.25 0.75 9.75 re
h
W n
BT
/TT3 8.25 Tf
0 Tc 0.1875 Tw 458.25 270.75 Td
( )Tj
ET
Q
BT
/TT3 8.25 Tf
0 Tc 465 270.75 Td
(W)Tj
ET
q
474 269.25 0.75 9.75 re
h
W n
BT
/TT3 8.25 Tf
0.1875 Tw 474 270.75 Td
( )Tj
ET
Q
135 279 15.75 0.75 re
f
150.75 279 0.75 0.75 re
f
151.5 279 15.75 0.75 re
f
167.25 279 0.75 0.75 re
f
168 279 15.75 0.75 re
f
183.75 279 0.75 0.75 re
f
184.5 279 15 0.75 re
f
199.5 279 0.75 0.75 re
f
200.25 279 15.75 0.75 re
f
216 279 0.75 0.75 re
f
216.75 279 15.75 0.75 re
f
232.5 279 0.75 0.75 re
f
233.25 279 15.75 0.75 re
f
249 279 0.75 0.75 re
f
249.75 279 15.75 0.75 re
f
265.5 279 0.75 0.75 re
f
266.25 279 15.75 0.75 re
f
282 279 0.75 0.75 re
f
282.75 279 15.75 0.75 re
f
298.5 279 0.75 0.75 re
f
299.25 279 15.75 0.75 re
f
315 279 0.75 0.75 re
f
315.75 279 15.75 0.75 re
f
331.5 279 0.75 0.75 re
f
332.25 279 15.75 0.75 re
f
348 279 0.75 0.75 re
f
348.75 279 15.75 0.75 re
f
364.5 279 0.75 0.75 re
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365.25 279 15.75 0.75 re
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381 279 0.75 0.75 re
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381.75 279 15.75 0.75 re
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397.5 279 0.75 0.75 re
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398.25 279 15.75 0.75 re
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429.75 279 0.75 0.75 re
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430.5 279 15.75 0.75 re
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( )Tj
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(Figure 3. )Tj
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(DISORDER)Tj
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0.1599 Tc 0.0276 Tw 35.25 0 Td
( matrix)Tj
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0 Tc 0 Tw 24.75 0 Td
( )Tj
/TT0 9.75 Tf
-0.1875 Tw -198 -12 Td
( )Tj
0.0665 Tc 0.871 Tw T*
(To compare )Tj
/TT0 8.25 Tf
0 Tc 0 Tw 53.25 0 Td
(DISORDER)Tj
/TT0 9.75 Tf
0.1149 Tc 1.1976 Tw 40.5 0 Td
( with the other scoring matrices, we measured the pe)Tj
-0.2467 Tc 0 Tw 222 0 Td
(r-)Tj
0.21049 Tc -333.75 -12 Td
(for)Tj
-0.08549 Tc 11.25 0 Td
(m)Tj
0.1268 Tc 0.1472 Tw 6.75 0 Td
(ance of each with varying gap penalties and saved the best performing ex\
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0.19679 Tc 0.36571 Tw -18 -12 Td
(in each case. The gap)Tj
-0.2467 Tc 0 Tw 89.25 0 Td
(-)Tj
0.1763 Tc 0.3862 Tw 3 0 Td
(opening penalty was varied o)Tj
0.0728 Tc -0.04601 Tw 120.75 0 Td
(ver the range from 1 through 14 )Tj
0.13969 Tc 1.17281 Tw -213 -12 Td
(\(in steps of 0.5\), and the gap)Tj
-0.2467 Tc 0 Tw 122.25 0 Td
(-)Tj
0.0574 Tc 1.0885 Tw 3 0 Td
(extension penalty was varied from 0.5 through 2 \(in )Tj
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efinition given )Tj
0.1714 Tc 0.3911 Tw T*
(in section )Tj
/TT1 9.75 Tf
-0.0625 Tc 0 Tw 42.75 0 Td
(2.7)Tj
/TT0 9.75 Tf
0.1537 Tc 0.4088 Tw 12.75 0 Td
(, it is evident that the cumulative scor)Tj
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(e depends on the set of matrices )Tj
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(being evaluated. Thus, the cumulative score values in Tables 1 and 2 ca)Tj
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(n)Tj
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(DISORDER)Tj
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(r-)Tj
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(a-)Tj
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(BLOSUM)Tj
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(62)Tj
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(DISORDER)Tj
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( only ma)Tj
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(r-)Tj
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(BLOSUM)Tj
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( )Tj
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( )Tj
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(Table 2. )Tj
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(with )Tj
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(e)Tj
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( )Tj
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( )Tj
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Shaded )Tj
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(m)Tj
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(o)Tj
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(e-)Tj
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240.75 372 l
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402.75 243.75 l
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240.75 243.75 m
240.75 372 l
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401.25 372 l
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402.75 372 l
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( )Tj
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(DISORDER )Tj
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(\()Tj
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(Vucetic is thanked for numerous helpful discussions.)Tj
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( )Tj
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