Bacterial peptides for treatment of pneumococcal infection

Abstract

The invention relates to an isolated peptide five to eleven amino acids in length of the sequence B1X6X7X8X9B2, wherein B1 is selected from - X1X2X3TX5, - X2X3TX5, - X3TX5, - TX5, - X5 and - no amino acid, with X1 being V or A, X2 being N or Q, X3 being A or T, and X5 being D, E or A. - X6 is D, E and A; - X7 is D, E or A; - X8 is R, L or A; - X9 is W or A; and B2 is selected from f: - X10A, - X10 and - no amino acid with X10 being N or A, and wherein at most two of X5, X6, X7, X9 and X10 are A; and its use in treatment a bacterial infection. A particular advantage of the peptides disclosed herein is their ability to revert drug resistant strains, particularly pneumococcal strains, to susceptibility to antibacterial drugs.

Description

[0001]v r nmrr rmnrrnum n n rr ,n ., rnmrn, n w r ., rrn rn. nrr rrnnnvnnn. r nv n r rrmnrrvnn nrn r mn n r , w rrnr rr nn wn nn r rmn rr. . nmm rr n r rnznnnrnnn.mn r unumn nm . rm- n-nn- nn mnn,nmnn v rr rn r r rnn rn, m w nn mr n mr, m mmn m rn mmnmrm. nm rwnnrn mn- rnmn wn r n rrnvn,n nwrmnr r n . m .numn m nz mn n rn n n r rmru mvrru.nmrvmmn m mnrnn r r rnuumrum, numn,rxm, m n m nzn . r n..numn nn mmn rn r - r r n nvrnmn v rnrrm- n nmrn w , r nnnxr n m nn nnrnnmz,n.nnvnr rrmvnnxrrnnrnnrr'r rnwrm n rnr w. rn. nnn , n r ., , ,rn.r.:.:. m.. nr w. m :.:. m.. .m r n rrrr w r mrn nmn,nr rm .numn n nmn,n wr nn w rnnm- x, . n r , . nnwn , w r nrm r rnr r .numn rm rmn v wr r r.numn rm mnnn mv-mnrn rnr,n,rv. rnrmnnvnnnn.rv v wrvrvnn mm-mnrrnnnnnnmmrn n, n ,xm,rnr mnrvnmrr nrvn. n xr mrrmmr. vrwn.numnn - n wn rw w rn n n nv mn r n n , ,r nnnmn ,nn nvnr ’,n rnrmn n. mnrrn , r vnrrn’, m nnrnmrn rr mm nn r n rnxn r rr nn vv nm r n mr . wn v mrm, r . nvnnrrmnrm wr r nnm nznr nvnr r n mmnrm n . rmn nvnn rm rnnn m n r nnxrn numn rm, w mnnmr.nnuxn. nvnr n n. nwnr n n mn v m- rm. w r n nm rwrm,nr n n r n rnrmn r r , r nn n rmrrw n. r nm rn mn nvnrr nvrmnnzrn rr n,rrrnx, wn x. nr w r rw m n m,nn : r nnrnn r, w n nv vnn r vnvnm.n nn,nn wrnn167892-1r,m -122335,5, r nn - 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-12233mr nn: 5,5, - -3555,, - - nn 1 mn . .n3rmr nn n.2. rmr nn n.5rmrmrrnnnnn, -16789v rrmr22-110,n n , rmr nn: 0,n 10- nmn nr rmrmmr nn n. nr rmmn, mn nn. nr r n, vnmn nn. nr mmn, xmn nn. n rmmn, vmn nn. nr -nrmmn, n n rmr -122: 3355667788991010, - -1123567891,0-22356789,, - -33355678910, 5566677789108899110,, - - -5566789,0, -5677889910, w -rn6,78,9,10r 123,5,6,7,9n10v mnn n r vnv rmr,nrnm. rmmnnn r :-.nvnn, n6789wnr12356vr,nr1r n,2m,m3,m .5,n6,,7,9n10v n mnn nn r78v910, wnr2rnrnm2,r .3m,5,m6,n7,,9n10v mnnn nn3r567v8910,v, wrn1,2,356,79 10n n1235678vnr rmmn910, v,rnm,.,,,n v mnn n r v wnr rmmn, n n12356789, rnrnm1,.2,3,5,6,7,n9v mnn n r v v, wnrrn2,r3m,5,m6,n7,,9n10v mnnn nn23r5678910, wnrnrm. v v, 1r2m3m5n6,79 10n n35678910, vr,n,,,,,,n v mnn n r v wnrrrn n3,r5mm. ,6,m7,n9,10n n35678910,nnm. n v mnn n r v v,r 5,6r,7,r9mn1m0nv, mnn nn r nv56v7,8r910, wrnn6,7r,9nrm10mvn, mnn n n56789,n wmrn.5,nr n r v5v6,7r8n910m. 5,67r9m1m0n, n n , wrnnr,,rmnmnv, mnn nn r nv567v8,9r, wnrmn.5,n6,77,9r,9n nr10m10vmvn m, mnn n nn n n r vn6v7,8r9n10, wmr.n6,nr rmmn rrnvnvnv,n,rnnnm.5,6,n7,9n10. nrr rrmmn rn nvnn,56r.nr rmmmmn rn nvnn,7r.nr rmmnn rrn nvnn,8r. rn nn r nnm,n wvnn,8r. nr rmmn rn nvnrnn,9.. nr rmmn rn nvn,10vnr rmmn rn nvn5. mn rnn1rr nn, nmrn7rr nrmm nn nw. mrmn rnnrn1nvnnrn,n5 2n n6mnnn.r rmmn rn nvnn,8nmrnm rrn nrmr nmnnn,1. :-r. rn nvnn rm rn nvnn r nr rmmn,nr rmmn, m r nn :-.r nn rn nvnn rmn :-.rrnrmnm1n23,5,235,5 5rn nv2nn rm nn10n n,n wrn rm rnrrnrmnm nn,mn . rn nvnn rmnr rmmn, :-. 7 rn nvnnmr mnnr nrmmn : r8910.r nn , :,, rn nvnn rmnnrr rrmmmmn ,-,-, n r- rn,, n n, nvvn,n,n1.12351 2. 3 nn, ,n ,nn rrnr.mnmn, :, rn nvnn rmnn vrrnmrmrmn,mn, ,,n. rrz rnr :. v,r rn rm rm r umn r n r u unumn.n numnr - rnmmn,rnrmn r n v v,r rr-r, m wrr r-,vn mrrrrnr-m.n. vnvr,nrmrmnn, rm rmrrzr nuxrnumn mn n r u unumn.nrnmmn, r v wn - - n - mr nn.xr n m n mnnnr n .nrnmm n nx n n nvnxr n m n vn rn, mr r rn rm rm r munnur u, unumn.nr wr, m mnrr un r rnrwn r nnr rnr m. rnmmmn, rrz rm m n vnnrrnrmnmnnr,r u. m rm nxrn urmnumnn r u, unumn rr unvrnnmm. rmn,n r u,rrz rrw m n rm n r u.nr r r rw rn vn r vn rmnnmrmn,u. rrz rm r unumnrr ,r rn rmnrnmmn, rr u unumn. r mrn:nm mr rnz nv rm rn v,rnrmn r n v,nm nnnrnmmn, vnr rm n r u.n rm n r u,r rz n rnnn v r unumnrr urun rm rm n rm “rnn numn.n nx rnn rm n v” rr nr nn r u r . r nvvnnnn rn n r rn rn rvnn r n mmn,r nrmnrnnrrnrmmmmnn,n ,nn.n rm n r u. nu n n rm r unrmnnmrmrn u unumn. rm,r r,n n rm mr nnm- rm. nnm rm, mrr r nnm- v ,n.nnrm mn nxmr rr nrz xr n n n n, nrr nnvvnnnn rnnn nn. mmnr rn rn rvnn mn ,r nrmnr r u.n rn n w rm n r n nxrmn, r n nrrru mmn,v n r nvnnnn rn n, nwnn r r nrmnrrvnn n rrz r n n rr,rnr,r. nvwnnrmn r rrz r n nn r :n,rnnrv : :, ::, :, :, :,n n rr nrmnrrvnn rn nrrznr rm rmn n nnwn. mr n,n n rm n r u.n r rurnmmn,n n rmnnrn,rmummnn rn,,r rnr nru , mrunum r nrnm,r nn nmn ,rm rm-mxz,n mnrn,rrrrmnm, nnn n, rnmn rmrrr r wmn. nn rm r n nn,nn,n nn,nn, x n,nn,mxn,mn,xn, nn,nr mn.rrn,rrrmrmn,rnn rrrm wr rxmn, r n rxm,xn,rxn, zm, xm, m, rn, zznn, v rnm,r rmnm, mrnm,rnm,rnm mn m,nr rrzrnm. r n mrrrnrmmn, n rr w rm xr ,r rr n,x n, mn n,m n, rn r mn.rr rmmn, n rr w rm rnn mrrn w ,rrrrrmn. x rnm , rn rrrrn n,nn n, rm- vnmrm-nn r, rr rm v n rrmn,zrmn,rrmvn,rr.mn,n rxr,mrn, nrmm , nmn,mn, n,mn,rrmn n, mr,nmn mrn nn ,nnnnmn nn r mrr rmmn, n rr x mr n . r nrm rm w rmn r mr -mxz. nmn rnrmmn, n rr w rm r n mnrn nn r,,r r n rnrmrnm nnn. nr.mrn,r vnrnvr mn r rm r,nn r nmrrn nnr , nmnrnm mrrnmnnrn-rvnnrnnnm.rrnr r ,wvr, mmrn mmr mn n rnrnn, r. nnmmn,,rmrmn,nnn:rmn,nmn,rmn,mn, nmn, mmn nn mn, nmn,n rmn. n r rm-nvr rrmn vr rn n,r rnrmr mnrrrmrmr. nm.n, n rr w rm r n rmrn,v wn rrmrnn rnrwmnnrnn .nxm n rrr n mnm n rm.nm wn mr r r n mrr m m n rmn w r n, r w r rn .mn nm rn nrnv rmn, n vr w.r rmn nrn r wnr nrn v mnnnrn,mrmrn,nm mnnmnrrm,rnrnn w: rmnmn,r rnm nmnrn m m m rnr,,rrrrnrm rn n rrnrnnrnrnmmn r. nm mnn,.nrn mnr n n w n wnm nmmnm.n, mnr n mnr n n w n.nrrnmmn, mnr n n w m.nnrnmmn, mnr n mmn,nr n w rn n. n nr rmmnv,, mnr n n w n r u wrn nn n w rmnr r . r mmn, mnrnmnn wnn rn m,rr rmmn, n rr mnrrr,nmn wrnrn mnrn . rnrmnmn, n rr -mnr n w r n, mvrnn,n ,rmrmrm-rmnxnz,nnn, rn, n rmn mn n ,nr rm rmn. rn nvmn, n rr -mnr n w nn,nnn,n,nnn,nn,rn,rnnn,nrmn,r nn xn, nn, xn. mxn,mn,nrrnrmmn, n rr -mnr n w xn,nvznn,n,rxm,xrnn,,rrxrn rm r nn rn, zn. n, zm, xm, m,nr rmmn, n rr -mnr n w rrn nvnn, rnm,r rnmnm, mrnm,nnm,rnm. rrnrmnvmnnn,, mnnrm,rr r-zrmnnm.r n w vnrrnrmnvmnnn,, nr nr,rr rr-mnn,rxn w m n n, mn n,nr r,xr n. rn mnvmn, n rr -mnr n wnr nn, mr n ,r rrrmn. rnrmnmn, n rr -mnr n wnr rmvnn,rm rm-mxz. rn nvmnn, n rr -mnr n wnr r n,nmn n ,r rrmn. rn mnvmn, n rr -mnr n wnrnmmnnn, rmn rmn. r, u r nrmnrrvnnnn nr nnn r rnnr nn -r nrnr r nrmnrrm :-.nrnmmn nr nnvn-rnnn nr r urn :-nmnrnmnrnr nnn rm n n nn wnn n.nrnmmn, rnrn.rn rnnn,r rm rr nrnn. rm:nr n– rr-z mnrn n vw m rmu m n, n n. rn n mmnnrnrn rmnvn nvnnrv rm m n,rnn, rn rm rm, rm mm mnrnrm,r rm,rrm rmm n,rm mnrnnvnnr rm rn r nn n r rn rrr, nrx mnrnmmn nn. n rm rvnn, rnnvnn rm r,nn n m rvn nr rn v m n n r . rnrmnr rvnvnrrmrnmmnrnnnvnrv,mrn nvnnrrnm rm m nmrnn. rnnvnn,r rm r,n mrmn v rm rrr.nrrmmn, m nmr w rnmmn nvrrnrn, r rrmrn. n, , r,rnrmrr rnrmnrn, n, rm m mnrn,rnn nrmr r.n nn w mn ,n,rnnvnnn m n rm rmnn w mn n,,rn,wrr r,rn rnmmn nvnn r nnrmrrmn. n,nrvn,nr rnr rnrmnrn, rm rrrnrxn mm rn nrm. n, rrnnmwrmn rnv rnnn r r rmrrn. mnrn. xm rrvn rm n, vr:rn nn nnn nn ., nrnrmr nnr:rnnrmr n, , -:-ndn , -: - r vrrnmn:vmnxn ., r rm nst. r -:-nn .:.n r vrnvnn rn m mmn m n n nvnn, rm n, nrmn,nnmn w,r r mnrn r r ,mrn m, rr rm n,..,rvr zr,n nn vnrn r wnr mr zr, r. n n, rnrrvv rnwn n r, rmnr mn rnnvnn w vr nn nnwn r mnrnrm n,m,xrr r rnn m n nrnxn mm, n, mnnn,n w r nrmn r mnrn, rnn rrnrmn rn r.nrnmmn, mn nvnnn n,n ,r m mnrnvn m mnw,rrn,rn m . r rrm m n rnnvnnn nvnn rm rn rznnrnnnnvnnnr n, wnnn,nm,rrrnn nr,, w vn, rrvv, zr,nn . m r nrr ,r r rnn mvnn mrxrn,rnrnrnm, vnmr nznrnrwnn.rn, r v xm..mn . rnr nr rm, , rrnmnuurnrnrmn rn nvnn rn r nv n n r n: :n,nnn mmn,r vn :, :, ::, :,n : r mn ,rmnnrrvnn r r m mnrnrnmmn, m mnnrrn. rm n r u. mnnrrvnn nnnrnrmmmrn,n mnm:n mnrrmnnrrvnn nn rm,r rn n,r r nm mnn nmnr m rmnmn,r rnm rn nn rr rn m n ,r rnm mr, n nr m rr,r r rr. n nnvnnrrvm r mnnrrnnrrrvnn rn n, wrn nn n r rm m n r, m mnrn vnr rnn r nvnnnmnrnnmmn,r , : :, :, : :n:r,nmmn, :,n , :.nrnmmn rn n rm n r u. nn, ,rn rr nn rm r nnnmxz,nmnn,rnn,, mnrrmnn,rmrmrm-n. nr wnmmn,rmrm m nrrmr n rr rvrrn r n. vn vrn r rr rn “mmn”,n r rnv m mnr rmrmmn mnnn wnrn.rn,vnmmnrnvrmmnrrn n m mnn m mn wnn r r n mn n nvnnrrnm wnm: n rn. vm.n16789v vnmn nn,nn n -1 2, wrrmn: o1223355,: oo35, o55,, o -2o nnmnr , o10m: o10,n -n wo nmn , - -1rn -2-3r -5rm 6 rmnn 7 rm rm,nn rmm,n -8r ,n -9m,n . -10rrmmn rnn.m, wrn mn.nn. rn m, wrn vnmn.nn. rn m, wrn xmn n.n. n rn m, wrn 12n vmn.3. 567rn m, nn n nnm8.910, wrn1,2,3,5,6,7,9n1023v 567m 89n 1n. wrn2,3,5,6,7,r9nn10m,vn mnnn nnn012m3.56,. wrn1,2,3,5,6,r7n,9nm10,nvn mnnnnnm.78910, . wrn1,2,3,5,6,r7,nn9mv,n mnn n123567v 89, . wrn2,3,5,6,7r9n10m,nnn nnn2m3.5678910, . ,n v mnn nnm wr12356r7n9m10,nn n35.678910, . n 3, 5, 6, 7, 9,r,nnm,vn mnnn nnn3m5.678910, . wrn 5, 6, 7, 9,nrn10vm m,nnnnnnmn.5678910, . w 5r 6n 7, 9,,nr10nvm m,nnnnnnnm.56789, wrn .5, 6, 7, 9n101vrn mnmn,nnnnm.n5678910, wrn .5,,,n0v mnn nnm. ,6,79 10rn m,nn n56789, wrn .6,n v ,7,9n10vr mn mnmn,nnnnm.n678910, wrn .66,79 10rnnnnnnnrm.nm, wrnnn5, . ,n . ,7,9n10.rn nn r nm, wrn55nn , .. rrnn nnn r nm, wrn6r. . rn nnn rr nnmm, wrn7r. . rn nn r nm,, w wrrnn8r. . rn nn r8r. . r nm, wrn9. . rnn nnnn rr nm, wrn10. . rn nn rnnmm, w, wrnr5. nmrmn rn1n .n7r n r n rrnw. nnmrnmnn rrnnn1m, wrnn5rnn26. nmn . n rn1nn r nm, wrn8.mrmn rrnn . rm nr nnnn r n:-m,r w.rn v. rm r rnnnnn m:-n., wrn.rr nn1102r3n5,2n3n5,5mn5,nn, w wrrnn21rrmm. nn rnn nmn . r nn m,n, wrn. m rrnnnnn m:n-., wr.mr mn rnnnn m,n:,r7n8910. rm r nn :,,, w-r,n-,-,,,.,n. rmrnr nnnn r n:m, wrn. rn m, ,,,n. :. wrn.n rn nrnmnnrnnmm r nrmnrrvnn. r n,r r mn n. r rn m, wrn n n. m n rm rr run. r mu, wrn n n unu numn r r u. mn.rrm rnmrnn m , wrnn n rm m-rm,r r m. , mrr r m- rm. r n:rn nn m , - - ::, - , - :, - : - :,, - ::,n v rrrnzrm rnnrrvnnnn rn n, wrn rm. n r ur,nrmr w,r wrnrrn. nnnn rrm r unumnrr u unu m. r rn m r, wrnmnn, rm r nn nn, rn, rrr mr n ,rm rm-mxz n, rmn rmn ,nmn n ,n. r .rn m r, wrn n rr - nnrmn,rrrnnnn,nn,nn,nn,nn, - n,mrn,xrn,mrn,xxn,n, nzn, xn zm, xm, m, rn,n,znrxm,rxnn,rxn, mnm, mrnm, m,r r z rnm,rnm mn m,r r - r xrnmn,r r r n,x n, mn n,m n, - mr n -rmr n ,r rrrmn, - -nrmnrm-mnxz,,r rrmn,. mn rmn. mnrr rnnnn m , wrn nm mn n w: mnn,r r nmn, n rm, r r nm rm m r rnm nmnrn r rn mn ,r rnm rn n rn nr. rr,rr rrnrrm. mnrnmnn wnn , wrn r rn wrmnnrnn rr rmrn, .rrr,nmn wr v.rm r nrn rnnnm, wrn n rr n ,rm rm-mxz,, rn, r n, mr rmn r nmn n ,n.rm r nrmn n r.n m, wrn n rr - nnnn,,mrxrn,mnnn,,nn,nn,nn,nn, - rn,r r xxn,n, nznn,,rxn zm, xm, m, rn xm,xn,rxn, - - mrnnmm,,r rmnm, mr,nm,rznnm,rnm - r n,rr rrzrrnmn,x n, mn n,m n, -xrrr n - -rrmmrmn-,mxz, - rmmn . m rrnnrrrmvnnn. rn n, wr rrm r nnn rr, m mnrnnn nnn n .nrm m nmrn . vn nr nnn m ,r - :,: - - :, - :, - ::, - :,,n . - m rn m, w:. n r u. rn rn n rm v .rm mr rnnnm, wnrnn, n rr nn n ,rm rm-mxz,nmnrn, r nn, mr rmn ,n .m m r r nrnmn rrm. n, w wrn rrmm r nm nrr . n nnn . n: n m ,r - - ::, - , - ::, - :, - :, - :,.n .r mnnr m mnnrrnmnnrrvnn rn n. ,rrmnnrrvnn mnnrn m mnrrn m r u. m n . rn, wrn n nn mn r m mn rn m r r nm n mnn rmrmr,rnnr: mnn, rm nmn, r r n nm r rn m n , m nmn rn rn nr r rnm rn n .n mr rr,r r rr. rrvnn mnnn, wrnn mn r nm r nrmn rm n r unn rn n w .rnrvnnnmrnn, nn. r nm r nrmn rm wrnnmn rn n wmnvnn rrnrr u.wnxm n r,rm w rr nmnmnvn. nrwn. xm r mn r nvnn v.rwn ur r :nm rw. mn -nn mnnr, n rw nm rn n , n. wr nr vrn ,-n-mn n nr:,rrn vrnnrw .: nnumn rn:mn n nr r rw rnnrn, nnunr n n. n n r , nmnnn mn nr, nnrn ur n r nrn rnnu,.,r, nr, nnmmnr,n n,nrrnmn.nnu.mnnr.nm. rn rm rnrn. nnrn. mn :, m. :, :, : ,: n,. :, m : numn r m n rw r r : n, . r m. rm-nmxz r nn nm nr .rv rw rn .nmnrrn n m ww n n rnn rmrrnr. r .numn rn w wrrwn . m- . r wrnr nvnrnrx . m r . mmnn vnr.rw w mr m r n mm rn mnrrn n mr-r m nmr-,r n n mn n n r mn r nnnn n nn nrmnn . rrn n xrmnrrrrn . nnrn =. nwumnrwr mm. wnrrnn. r rn wrn , vmrm.. m mnn n m n v rmn n. wr n mrn -r m n mm n nrrnw w mm mrn n n . rrn mvrm. . w nnnxrmn,rrrrn . r nnm mr , nn nrnrmn. rrn nn mrnmn.nnumnnnrxnrm,n.,rn..n w v r wr .n m, **m*n v, < .x rrw-nn mxn rrmn >, mrn. r rnrmn r .nunm r rrnnnnxrmn rrn mn rn. v =. r , *n. n- xn rnm. nwn rnm rnrm.nnrn nwr numn rwnnr r . nr . nn. wnnn r mnnnn w. mm .nrn .wnrr rn r rvn n w r wrm rrrrmnn nv n rwr r nn . n. wn nrn rmnnrw.numnrnn v.rn..nnuznn vv. w rn r mn rn w r w mrmnrw nnnn . nrn mm n.nr rrrnrnr nn, r r v.n wmn *n nr . rwn- xn v= n rnm. n rn r .rnx.rm rm-mxz r nn nm rrrnn wvn . r w r w. mm . xn rnm. r **n v =. rwn- n n n nrnn nrnr r n rnx wr nr rrn r ,rrrr nrmnn .. wrw rv r n . numn rn r .. . rn: ., ., ., ., ., ., ., rn:, , , . m rn: ..unumn numn.rn.:ururn-:.rw w. mnunrznrn:-r m. nn mm nm.nr rnrr n mrn . nnnnxrmn,rrrrn.nw rw rmn rnm rwnmnrrn . . r nm-nrmnx.z m r nn nm rnnr.rw w mrn mnmnrrn nm. rrn n rn m mxrrmnn n v rx rnr-n- n r rm nnn nrmn r rmnr m v ,rrrr. mrw . n rnm rnrm. wnr rn.rnnwnn vnr wn - 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" nrmn w r-m-. ., ***: n"n n nn, *n v v,. v . rw-. v r. r,. r. rv,. r ,. rn r rvnr _ . r zwr nrvx. w rr mnrw rw r rnr rnr wrwrn w mn xr.,n-rn nmnx. nr w n nnr zr r wmrwmmn rn n n rn. n mvv wnrnr n . n -w n n vn r mrrn rv rn w rr,rr vnmr. rrn-rv. w rrn nzn n n . rnx nznn vv. . mm r w n r n n w r n n nrmnxn n . r . r rvrrm nn nnn nn wr wr n n n n n v =.. mnn . **n v =., *n rn n nv rnnr rrn ,rrr.. ww r.rm rnr wn nnn . rw nn-r nnnnm rnnnnn.n6nB-vrm r.rww wn mnrn mrn nnm n mmn w n rv rwrnn nn. mnr . mm.. w. wnmr nnn. nn nrnw nn-r nnm rn :nn6nB- v mvmrnm.r ww wn mnrn mrrrnn nnn.nmmn n . mm.nr w r n6Bn nnnr. wnn-rxmnnnmrn w n. : n n v. :,n. wnxmnrr rrmnn v n rn wxm .. w nn ,..nnr . . nr ,rmn n n. w nrwrmrnrnnmnnn. rwrv nm r nm mnn x vv. nm mnn nnnr m mnrrn rm rmn v wrnn nnrn . mm. rrnn mrmn n r mrmnr m. . w nnmmv mnnmnrrn . rn -n n. * n vv.nnnn r m . n- . rrn v =., **n v = nxrmn nnnnxrmn w. mm n v =. wn mm . rn -n n. * xrmn.rmx - . rrnnnn rn rmn-, r w rv r wrx . =. n- n n. **n v =., *n v xr . rrnnnnxrmn.rm vnmn, r-n w rv r wrx . r n n rnnrm:-n, r m: mm n- . rrnxrmn n. *n v =. nm rn. nr rn. w. wrn w r mm. rn n wr n r wnn . mm n-rmn n nn. w n . .rwrv nnmn rnnm rwnmnrrn rn . mmnmn.rrrn n nn mnrnn n nm mrmn..rw w r,r,nnn. mr rmrnnnmnvnxrmmnn wrrn rnr v rn rr rnr, n r rnrn n. mnw nr. n n nnnrnn nnm xn..-nnrn-n . v n- n- xnn.- n rnrrnnn . v nrnm .num nnnxrmnr mnr n nnnnxrmnr -r nm r v. n wr w.numn r nnrn w r w rn. m wnm rn. nr rn. w. rn n. vrmr mnmn.mn mnn mnr . v n- . - . rn v n- . rrnnrnnnxrmn. nr.numn nnnnxrmnr r r _v mnrnr.num _v-r wnm rn. nr rnn nm. wrn nnrn mmmnrnr rnn r _v. wn n nnnr . m nn nnm mnn xnr..-nnrnn . v n- n- -xn.n- rnrnrnn . v numn nnnnxrmnrnr. . nnnnxrmnr -r mnrnr nnumn nm. wrn wnm rn. nrr rrn n nnrn mmmnr. wwn nn-rr .n w nnwn r n nnnrn. rr n rr rn w n .rn . . rr nwn-nnrn w n xrmn rnrr n w . rrnnnn mnrrnnrr..nnumumnnnnmn.nnx wrrmnr -r nm rn. nr rn n n wnnrn. mwmn vvmnrmnnr rn . mn.r rv nrm : x wrn v rn rnmnr nn. mnmn w- n vr v rwrn.nn v vvvrnmn zr rv w rrm mn rwrnnm.nr rr rn rmn.mn nxrrmnrnn m rrn.n vrvn m rzn n–x nrrmnn . vr rn -xrn m-r, w w m mr w ,, r n m m-r, n -xr rn wn. . : x v z vrn nw umrnn n vr n .numn rn.50mnmm n nrnnn rrw rw n . w n,rnm rrn rrnn,nnr n-r nrn mxzrm rm-r nrn .,nrnrmn-r nmrn, .nwnnr.rr ,. nr r.nr m.rr wrrrm n n nn "n.." n. "" w. mrmm n:rnn n.n wumn.rn r mnxr ""rn nrn r"nn n n .wnumn rnr. nnm.r".mr. mrnmxn n :rn wrn n n r". mm nrn "n".rn w "rn r rr nnnr, n w. wrrrnmmnnnx mr n . wwrr vnrn rnn m n w rr v,. mrnmmr . nn rw .numn nnrn nxr n mm. rn ,rnnr v xm xm: numn r nv r m rrxr r v.numnn m n mm nmnm- xrnnn - .n wrv n.r n n, wn nv r m mrmn ,nn r m wrrnrn: w n n : -mn r:-mn vnr- :,-mn . mn. : xm: ur num r nu n -n-wmn vrnn rw .nmn-nrnr mnrnnr.n..rrm,n n wnr , r rw wnmn n n,,nrn vr n. , w rmrnn rn n w nn rxm, rm n mu rnunz r r ,nr r nnn rwnn n. rnr.n w r w n nr n r nmumnrw. wn n nr n ..n r numn n rw . n rrrnn rw. w nvr n . n r n n ..n wn rn , rr r r r m ,m n r :rvn n .numn :, r rw rm rm-mxnz r n m.nrrrn ..rrwmv rnnr., m wmn rnvrnmn n numn rnnm mnn .,.. .n n , w nrw rmmn r nzrw n rnx.n wrn ,x .un r .numn n .. umn, vr rvn : rn r wrwnm rn w wr n rv v rn n rrrn, w wv wn .m m- mwn w rw nr r n mn nr r n nn, nr ..nnmm n mr rw rn mr, n nm n n r rw nnnn wrnr,. w r , - n v : n vr n .numn rn. .num rn r50mm . n .w . .nnumn .w n . .nuummn .w . .numnn ..w . ..numn .ww .. .nnumn .w . .nuummn .w . .numnn .w r . .num - . n nn . .nnuummn w . . m n . n . . n.. u n.. . . numn .nuruun n.. .numzn - n n.... xm:num nnrwwnnmn r rnu wr u vm- rm m- rm nv m m w z w mnn w m,n wvrmn rmn . nrm mn rw r n w .n., w rmrn w.n m nn.numn n w r rm n rr rnnm- nn,z wn rnn mrm. mnr mn w - nnnr rnn rn w nnrmnn nrmn mnn wn.n r n vw z- , w nnnnm v rnn n nn mrmrnnnmwn.rwr vrnn wmn w n m r r,., n - n n, wn nm rw r r m mnn wn.n v nnm- rmn. rr xmn:zrnmn -nummn mrr ,nnnrnrmn nm nn n n mn,v wnnvwnnwn nnrrxn , r m r n r r nmr r n.rnrrmnn r. r nnm mr ,nnn n m- nmwrxnrnxnm rn wr w n mn zn .n mn n-.rnr r wn m m n rn nz w m nrmn, rnrr wn nr mn wn. nn n . r nm rn, r n rn.. r mnrn n - m rnrmn rn r n..nmmr rmn rrm. . , w - r nnnrn, wrmnn r. n nm mr , xm:r mnmwn wru nnvvnnmn nnrnr m m n rn xr nn v, w mr nr nr.nnrmmn, mrn r w r , nn vn n.. nrnn wrwnr n xr n rrrn. n , wrwn wnnnn n wrr . wn-nr n, wrrrwnr nrmnn . m nn n rr n, w nn nnnrmwnnmr nm rn. nvr r nr nrnr n, mnmn n ,mrnrnr, . rnwr .. m , w m nnrn nwr . ,rn-nnrm n r wn:m rm mnn vnn r n n vn,rn-nmn rnrr nvnnnr.n.vnnnrnn r r n w _ , n rnrrn mnr, mnwnr n rnrn r r,n. nrm nnwnr w _ nnr nn r-m- .. nn,,v,vn rn m m,wnr -. . nnnmn rrnr v xr w -,.wvr wnwnr n rn n nvvnmn: wnr w -,.r w -n. -. n rr wv -. . nnnn wnr . -. - . n , -, wr r v . n n wnr -.n -. r wnwnmr -r.nrmn nn - . mmrz, wn mn nrn m m, rnr, mnn rwnrr. nnnvvn xmn: r numnrrm n mrnn m .numn n. n nn rmnnnm m "n" wn r.rnmn ""nrn n rrn .n umn rn nn rmnn r .. n nnnrn w n rm rn rn-nmrnnnnrrnn.rnrn. w nn r vn n rn rn rn v rm w mrnr . , wn rn :rm n nn.nunmrnnrnn w rrn mrm n. mm nxr . rn n rn __ rrnn-rmnn r r, v rm m rnrr,-nnrn nnnrrn -nn- rnr __ x rwnmrn _ mrn n mrnrn, v __ rnnrrrzrn _ nrrn r r r_ rm,rznrrrn, r-nnrn -rx -m-rrnrn-rn r : rn n rn v n_ n _ nrrnn rzr, mrn _ mrnrn _ rnrn xnrmrn _ rnr rr,-rn, v _ rnrn vr,nrn r rn mrn x xxrn n xr r m nn n rmn r rnm_ n _ rrnnrrrr,,--nnnrn r rnnrmrnrnrn rn n rn v rrnn-nmn rnrr,rm r r v- -mr _ nr n rn _ rrm,mnmnn , v _ rr rn r nnn , vn rnrn , n -- mr n v zxrm :r x w r umnrw rnr-rnv rw rrrn r w r- m n r mn rrrr,nnrw rn, .rvnn wr n v m .., ,- , wn r r w x rrmr.mnrw mmrm n r n rmn x rn rnn n rrm w mmn.wm ., ,- . ,rr n x w n m .n.rm r wn w m mr wn nnn mmnrn nn w w r xn vv, zr rv rnn m. n r vr rm wrx . mmr. mm r n mrn rwmmnn nrnn. xn n wmmn vr..nn n, nn vv zr rv. w n vr rmrmnrw ,r xmn:nznn r num rn umnrwnr nn n n rnx rz .,n mmn w,nr rn nm nm nn . n w n-x .r ., wr nnrmrmr rrnnnn vrrn.nummn mrn. xn w rn r rn r r rmvn nn- n nmr , n nr r r r . r wmn n n,r n nrnrn. w nr w .. nr , mr , wn r nrrn n n vvn rn wr w n n wr.numn rn . r n r. nm wr n n n w n n rnx nnn n rnx r w n rnxn n , n rnx -r r rv =. ..wr rn .. r n n w nnr wr n n nn, nnn =.,.. w r nrn n xm mrr:mnn n m mn wnnnn nm nrnnnn wn- w m nr nr v nnn-r nm. mnr rr n n mnrn.n.mrnr w rv wnm nnnr nn-r. nm.nnrrmrr,n wnrrv. wn xmrv:w n nrrwnnum mnn x vvn vrmnrrn rrmw r rn.n nn. w r nr wr nn-nrmmr n rw n n.n w r m m rnnr m nm .nn n rrrnnnr-n..n.umnrm. nnrx rnn rw w nn-nmmr m n,n n rnnr n mn n w wm rrnnrnrr wr w nrw nm rnnr mnr.x, mrmnm mnn nx vv. n rrnn rrwn n , rnrn .. nrn n rw. m w n rw rn w ,n n xm : n rn rrwnnum mnn n vv rw nm rwnnnm rnn n ., w ., w w r r nmm n mnm mnn nn vv. n nm rn. n nnnn r m mn r ,rv r-wn w n w n rn nrn. n -n rnmnnn nrmn w nn r n rn n, n wmr = rn m mm n =. r mm ..n . rnn n.r-wn -n n nxrmn w nrv n nmr r,nmnr -nrn w n . w rv r .. r , nwr-rn r n, nmr rn w nn r nnrn . mm , r =n., n mm . nn w nn r n rvvr. mm =. n mm =. .. n n mnrnwnn rnnnnrnm rnnnrm nm . -nn rn w. , w v rvn mm -.n.-n, wn r n wnw rrnvnrn.. x wm n rmnrnum mnn n vv mnrvnw wrnr n n r w rv nm mnn wmnmn, w wn n , w rr, mr v nrnmn n, . . n , n _v,mnr,n r_vw n n nn . n . r ,mn , _v, n mrrnnn rnrnnrmn . nnnwrnnrn n- n n . , w rv , n _v, .. n, wn r w nnrn n- n-n r wnn rwr n _v, .. rrr nwn r v , nnnrnnn nnrn- mr r n rn rr w n . n . r n- xm : vnr m rmnrnum mnn n vv r, rnm mn rn nn vmn r -rn-rr nn, w wn w r nr nrn r z.rmrvrrnn, wn w, w -xvrnnr, nwn nr, nwn rn wn v z , nv m n - n _vn r rvvr z.rn rv n rn mr mnr. rv rv r rnnnn nnn rnn nnn v n n nn..nrr-r rxrnr,nrnn _v v, wnrv nnn . n rn. xm nmn: nvun n ,,r ,n rm .numn, w mnr r rrwr nwnnnnnz mn.mr rnmm wnrwrnn , v nm-nnnrmm mnnnrn.rrwnnrrnm nv.wn v n nnrmnmrnwnr w-nn mnnr w r vrn rm rv n nr. n r rnw n rmvrnnn r rn nm . r r n.wrnn nrmnwn wv m w rnm w m r nn m- rm n rr . r nn rm mn,m,r w nrm nrvn n rn w n rn rw mn. n rn, n m m,.nu rw r r nzr n rnx :.rm nnz,n.uruu wr.nnumrnv.n wrrnnnnrmr m nn.numn, . m. rr r v mm n . wrnm nr r - n v rnnvn vr nvn w mvrnmrn m nn mr . w n v r .nnr -m n , mmnn rn r nm n n, r . n r n n r r n nmr w -mn . w, nmnnn r mr rmn mnn wrn -n r vn nrmnr r xr nmmr rn, nrn n r nmn w rn r n r n rvvnrnrr n.r n nrn mnnrnnn nnn w rvv. rm . n mrvwn w nnrnrmr wrnr,nrrn nrnrr rn wr n nrn nmn w n -rnnmnnz. r n wnr, w rnnnnvrnm n. rn , n , w rn n n-n n-rn . mrn,r nrwnznmr rrnnn. nnrnxnr mnnw--nzm- rn n w rn z nn n n wr n r nn. n mn-r nrrnrm wn xr.nr .numnn rm n rnm ,r,r n n rnmn wnr n .rn, n wr rrz wn. r nrvn m ,n n , ,n,nn v mnrrnrr nnr n. nn w nr . mnrm wnm wnw n rn, rrn r rnrnrmnnnnn r nn, w n nnnm .numn.numn.mn nr vn n n n r,n w.rn nn vrn, rn nm r n r n, nnn n r n vn.r mn, w rnvvn r nnvnmnrnrnrmn,rn xr n rmn xn r n rn,rnmnnn,n w.wvvr, wnnwn wrmnnrn, nm ,r, r n,xr n rnmn rnmrnn. mnr m rnrmnvnn m .rmnnn m wmn rnx r n ,mnn rnnr mr n rnn. rmnn, w n n n r rnr n mrrmnr-,n rm wrn rmn. nnrr r mrrnrn r w xvrmn r n n r rnrmn nnr unrm.un r nnvvn r n nnvvnmn m m . m mnrn nmnn r rn xr n,rn wrrn x,rvnvnn.nrrnrrmm ,vnvnn r nzn,rr r n. r wn n n rn rr .numn,wnm r n nzn. nmvvrm . rn n mn nm rn m n rv m nm r r n xr n nn n wnnn rrn nnzn.nr r nn , , w r nn,mn nm .nrnrn w rw . wnr , mn n , n nn.nm r nnrrnnn n rn rn rrr m nn- vrnn, w m rrnmn. n rn r n n n.rrmr, wnr nn,nn n nn mn w r rnrmnmn, rn , -,. n rn nznn r vrnnnr . rn, r v rmv n r , m vn n vv. n vn r r n n rnxn n w nn rn n rn nrvnrrmrxnvrnmnn rn mr . rw . n mn , r mn nr , w mn n n.rrmr, , w rr nnnnnrrnn n rn r rnrmn r-, -. r n.mn rn nn r-nnrnn rnrr w rr wrnn n nvrrn.mn. rn w mn nn r rrmn r n r v wn nr rv. mnnrrrn .unumn rr .nrumnrxn rnwumnn m m mrmnnnn nnmrnx. m- rm nnvn n r nrr r , wnr n n rmn n , r wr - nnn n r n rnrmn. r nm rn nmnnrm nnn. nzn r n rnx, w rn rrw n n r n x. rrr vn nnm w vn mnnmmnr rnn rnnrn,vnn,vnr n mr .n xm : rn rrrrnnnnuurrnnn r , .rn, wrr r rv x,. n rrnmrrv rn wr r - °n r nr n n,.nmnznnrv nnn r..wn.vnrnumn w ° vrn 2 °.nnummnrn.unrun wrrn.r n nrwn wrvnnr. nnumnrnrn.nr2n rmrn n nrm nnw mnn,.,n ,um-n r wrrmnrrnv w rrrrnnvn, vn. rnrnrn,,rn.rnm,:nn rrnrn,r wnn m::n wr :rmn mnm , , mmn r ,.u.,nr n , .w n x,. . r umn . n. m . wr ,rnrnn mvmn,m wr mnn- m. x,. n nr .nnurm . mn wrn r rv x,. rnrn m nr,rm rn wrrr w r. nnr wr -rmn w .rmnrw w rmv vvrmx:rmn.zr rv, r, wrnxn-rn umnr nrnmrnnrur nn-nnmmr rmnnmz nnrnmr mnrrn nrmn wnnrrw . nrn w rrw n mz nnrnmr nrwnmrnr nn-nmmrmnnnrvnx..nmrm-nn., rnnrrn,nnmvmrrnn..nrurmwnn rrn rnn n rnm,rmrnnrnmz m x .numn w nrm rw mnnxrmnn w .-n. r rrw rwrr wrn r rv x,. n n w wr rrnn nnn r .rrwn , r nnmn r wr r,. r , ww . mr rw n n wrrwn m rw- xnmvrnnrnrr r , r w =r.n m--rn. mmvrn r r w -rn mr n600nm vrn n r nn m . rn600nmw =.,nrn ,600nmr =. mn, v nnm m.nnrn n wnr m rx wn m. m rm w. x nrmn m r w r w nnr wrrw r nn. °nvr mnr, w nn nr n wr r n wr rmn rrv rmv nn . . rnn n °n uwrnvnr mr rwnn n =r.nr.n,,. mnumnrnrrnr,nn m wr r n60n0nmn mmr r mnnn nm, r wr w n m r n .r mn w r nn n. nnmrm.rn w, mr .r w rrm n xm n-rmn mr w mmrn v n- rx.r rn x nn nmmn wvn r nn , nm xm mnm nm r rnr mxnrm r. wnnn nr-rm rm n, n rm -rm : m-r,r,m. : , r rr m-r, .rm m m-r, , n-rmn nr .r x w mnr r n wn n n rm nm nmnmrrm,n r mnr . r ,rrr m wr n.nrznrrnrnrw r. n nr rmnn vm . . w rr nn r n n rzn n -xrn n m- n w mx w wr. mxr w n m r, r n mmn wr vw n xmrr r n vr rm.mmrn vnr m r n mrxm w mr. n mrr n wmrn rmrn nv.r wr n mrn ,r-rn -x w x vn n mm rr r.r r n r n n. nr wmn rnrnr mrmrn, >,., rr mmrn nrm, v rx nnnn r . r n nn= wr w x w -. r , wrnnnn rnz rnrrm -wnr: wn .nn.u mmnrm rrnwr wrwnn,n., , =..r600nm =.,n r mn w r nn m 600nm nr n, w nm - vm :. m wn wr .nn wn mn °.r, wrrnrrn mm n rmm rmrmn r nwrwrmn r mn °,n rwr nrn. ,n r mn °.r nn wr mn n w rn r rmn. nmr n w n rvrn n w mrnrmn r . n nn n r nxxrnnrn wn nn- n n rm-n.vrrmrn, nn rm r r rm rn w nzr mn rm n, nnvn n rmn nn nnzr n, -, r v.rr, v r wxn, r mwnnx r n rrm x, rr wrnr n -nrrrr . n xn, rn r w . r n rr n xnr rmr w rm wrrvn, nnn . rmnnzr w rmn n, -, r v n rr wr n mn r rr.nnrmn- . mn, nxn x nnn rnr wmn. rnrn nm, v nnvrn, n wrmn vrn..n wrm xn nn nmn nvrnwr v.. nvr w6n00vrn rnr ,.numn rn w =nm=.... r wvrnnwr m wr-nrnr mwnnr n m600nm. r mnn n ° . mm n r r rn nn,rnrn w w n r wn v nrrn rm mnnrr'n mn.n nnznrrnnnnrr wr w r nr mmn, r xnrn,nnrnnnrrrmnnvrmn nn wrn wrrr xx.. rnnnnn, r rrm n nr:, r rnrnn rn n xrn wm_ xr,rmmn w n w , .numn ,m n , nmn rrn nm n w . rn wnm_ n rn nxr n nwr n " xr n rmxnn rrvn r n n nwr wr nmn "n .., w wn n . r r -. rn-r r w. nvnrn, rvrrnrn n rr vr rn mnnn mnn n n rnvrn, mn rr rr'r .mn -m w n rn m 'nrnxrnn n vn mrx mn : w nn . rwrnrmr vrnrmr rr rnr nrrr m TTAT EAATAAAA IDATAA N:AAT AA 7 IDTT NTA :AAEATA TIDTTNAT:AEAATTA AATTA AATTA IDTANTT:T E 4E IDN: IADTTN:A7AETTATATAAA T AAT IADAANT:TT E TTETTAA IDTT NTTAAA : AIDTTTNTT:A7E1AATTAAATE IADNA:T TATAAAT TT IDTNA:T ETAITDTNA:AE7A2ATAATAATA A NT:A1A E ID T NTA :TATTT 7 E ID IADATNT:TE7 v A IAA DTT NAAA :AATT 2 ETT AT IAA DTT NT:TAAAEA AIADATANTA: 7E4AAr rrmn wr n rnnn rn mr- .n rm rm w , .rnnnrn w rmn w wr .rnn wr r mm w rnn rrnn r mn °,w n w nv- m vm . nn nn nr mn °n r. m w rnx vmm.n rnnr nnrnwr n mr . w m2. rnr wr r :r,w r ° wn nnr rm mrr w: nnrrn . nvrn nmn nnn rm. n w w rmrn w n. rn. rm nr n w nr nn- rmr n nxm rmrrr wnn- vr ,rrnn m r m r v x .. vm nrmmrrr °,n w n r-mn ,m, , mmr x mmnn, w w r mn w. rr n wr nr :.rm r wr n m n m r n, , m -m r mn.m, rm , xwm r n mnrn nr n wr. n r n nrmnrnmn w rn-nn n m wn n, mz, w nnw n. m2rn w m w m,n rmm m, rn.n. m. m n , rrrn,n r wv.rmnn wrr n w r wn n . r wrmnnrrnn nn xnvrn... n nr .numn r w r rr r rnrn n wnvrn rn wr. =..600nm=..r w vnrnr , w mr. wnum-nrrnn m wrrwnnn600nmr rn. mm nm. w m wnn n °, r wrnr , r mn °. mn. rnnn w m rmvnrnnrr nnrznnnr nrnrn. ,rmrr v wrrrmnr-,r.n rm,n . rmrnvr rn umnrw nmn m wr-wrn.rn mnm,rnw w.mr r mmrnnr ,- .x5wr rrrv m .., nn rn m nr.xrmn wrnn n m r n. n r w n w n x n uur rxn , wn nn w rmn mrn r rrr m. nzm r n ,n v zn ., . mmn mm vnr wr w n,n mrnn2n n nvnr, r n x n . mmn. mmn x nr nrm n n,- v xn w rm wr n .r x . m rm r w r r r r x rm n m x n rnnn. x wn- mr rmn rm rn mn rr'nrn. v x zx nr n nr w z mrr nnrrrvv nnw,n nmnvr rn, rzn n nrr.r wr wn r r rxrmnn n v mnn . °n r n r n mr m rn rzn . rz wr . * mmnx nnn. ,. ,.2, w r n2 2n.nrz w. mnm mrmnmr. wnr rwn., m wr n nmn mn . mmvnn.r mrm.xn. w, nrvvmnr vmn wr n rvrnrr w - r x n, w wr rnnrn,r w .r n w . m w r m m w vn nvnr rvrvn r . ° w r v.r w rn nn nnm,mrw mrnrr, mnr,, m.nr, w, rnnv w v vnzr wrr xrmn, wr.mnr wn.vn wr.rv wr rn n u ww rrn n,ur r mm r w n r mm rwn . r r .numn rn wrr r r r m n.n = n n, vrn r w -rn mn 600nm.,nnr , r mnn r n n nrn w, r r nn6nn mr nn rmv mr mnrnn n x m. wr w w . mmn n wn. wr r nn rn m nnr.x, wrn r °rnn m wr w r nr w w n wrrmrm m.r wr w2 n rTMxr nzmx,n r r mn °r 2 w r nnr r mn rnnn n nm., mrnnz nmn wrn mnn w nr rn n °,2. rmn nmr nx r nzn rr r m.numn rn . r wrr r r m wn.600nnm =.,nnnrn, , vrrn mnnr w w-rnn. m n,r r nn nn m. nrnn mx7n.wrmrr vrrm mn,nmrv nr wn wr rrnn w rmm. wnr . mm, r wrn nrn w rn m wr w wr rrn n mn nr,nrnn. r r r wr r n m,nm,nn. r rn n, n n rnxxr .r rm n w n w . nn. n w mnr nnnn,. nr. mm n w n n rnxxrnn r rn n,r,n mnzn . mmm v. xr n rnx w nnn n nmnrzr wm , n,,n n rnr v nrn n . n w n n rn rmn r r mn nn nmn w xmrmm wrr n m mxz rmn m 2. nx rn n °, v .rwn num nu numnrrnu rrumn rn. r w r -°nr rrnm .vn m n rv nn ..r rvrn nr , n wm -rn mm nx n n m- ,rrnn m m =m..nn nm =n..nx,, m wrnvrrn ,r wrr m-n,rn w r nn. m . n n rm rnn rw .n n m -w mrrr w mrr n m rwrnr - w m. rn-n mnrnrn r. v wr w nrnn, w rn m wrnnnnn.n wrnrmm.n rnmnn w. mm n w rmv mnr w. wrnm w w mr rn w mnr n rrv w m nnrn mn °vr rwrv wr n. rmn. rw nnurmw nrmnnrrumnnnrrrmnu mr n m rwrnr -m m-wnn m n w rm rn rwr rr mrr w .rn r . v nnn.rnn w m. rn-n nnr r w. mm w . rmn wnr w nrnnnr w rmv mr. wnrm w m wr rnnn °vnr.r mwnrrv wnr r n mrm nr.v w m n r .rn mn rvmnn m nrmn.nr w r -°nr rrnm r wr -r rv nn ..rvrn rnr , nm =. n mmvrn n m- ,rrnn mmn.nn n n, vrn r wr -rn m wmnm =..rnr n, r mnn wn r v- x .m rnn,mr wn rnnn. n rn n.r mn r - . nrrm xrmnn nrn r r n w rm n-r,mr w mnm r vrrmn. wr n vn nrr-nrm , mnn nnmrr °,nvnnrr r r v w mnr n.nnmm-rz n,n rrnrm. wn rrn wn.rr m, -m r wrn w n rn nn. m n w rm n n wrr r nm mn rmn rnvrnn n °n . m,.. n,r , wr r nvr nr r n,r-wn w nr r ,n w n n r.nm wrr w rrm n ,rn w .n mmmn wrmrnr,n r,n v.nnxrrmxrmn . mm n mn,n ,n rxr n w n mn n .n n,r rx mn w mm mnr r mm n. rmnn, n w w nr-wn w n, nrr . n.mrm nrmn w wrrnnv vr nrnm.. wn vrn... r- r , x . mrnnmr w n nrm nnn. rnm w n.nn v . w nr r rrm wnrmrrrmrwn rn w m rvnnnnn r n. w n r nrn n mz -mrm mr . rn w rv -nnrmnnn wmz w mn r w, rrr rnnvr . r vr mnrrn m rxrmnnnm, wn w nw mnnn rn. nnnm r w, rrr rnnvrrmnmz mnrn vnrrmnxrrmrnnn.. nrn rvn m w n n nm r ,wz wrnr,r rrn r . rn v nm rnxrmnnmm nn wn wr rnrrn,nn nmnrrxrm.nnnm v xxm mrmnnn wrn rmnrrmn nn rr rrnr nrn,r nn r nnnrmn n r v vnnrmn .. rn v w w rmnn rnxm :rmnn vum nrw .numn rn - rv nrmnr nrrnmrrrv ->nn mvrn--,°,n 2 -nrmx m,nvnrn rnrnrnnr - - , w , -> r . ° : : - - - , ,- =.. -: , - - - - --> ° ° - - =. rrnrn * . - . v . -nn nr =.r r -->rr mnnrn rrnnr m n --> - w x r r m vm -rr n : m w- - . mm .r mnm rwnn wrn -:mv rmrn rw,rnr nx rwm, mx w w ->:.n mmwn -> - . m - nmx rwnrrnwn::. mm:. mm:. mm - r nrrmnrnnrm w x w - rrwvr mnnvr n, mxr n rrvr r nr :rrnm r rn rer o m n mm ocmoun na oonusanceron suaeoncesocoroncenraonemarsuosmnramon. m . m resrearoraee noona e rna nraraee mm . m . m resreare ooasssur amae easc. . m anresssoreare oassum . m resrven roenanssoveearne aosnesauem suae. m m . m ssovencea ser -e °ere, suanaean mese m m m . m sereere, -anneonorae m m . m auo -c ° -rnne m . m °ave, m auocave, -sarc ac . m m . m sere °ere, -enaanne m m . m war ° . mossove auocave, v -rone m m . m auocave, -erne m m . m auoc °ave, m m-oonnuoosaomrcum ac sa . m m . m sere ° °ere, -uamnaee m m . m sere °ere, cne mm . m auoc°ave,-reonne mm . m auocave,-roan a m. m . m roecrom sere °ere, -rosne . m ° a m . m roecrom sereere, -ane m m . m auoc ° °ave, m m-onsonreocore. mm . mauoc °ave, -osnooeucrnaee m m . m warmossove auocave, -eucne m m . m warmossove auoc °ave, m-sne . m m . m auocave, -oneoonronceore m m . m auoc ° °ave, on m m . m . m warmossove sereere, coname m m . m . m ser -e °ere, -anoenc ac m m . m - ° emcacumnzo s . m sereere, -amnoeac ac m m . m . m ser -e °ere, roxa m m . m . m roecrom ser -e °ere, rroocxnoere m m . m . - ° roc m roecrom sereere, roxaomrnee m m . m . m - ° roco roecrom sereere, amnere m m . m . m roec - ° rocore rom ser -e °ere, v amn12m m . m . m roecrom ser -e °ere, a m+. m --oavn acc +a ac comsse,e mc warmossove, sereere, momv ween,o . m. m roecrom - ° m+. --oavn acac +a ac comsse,e mc m warmossove, sereere, momv ween,o . m. m roecrom - ° uarnne . m m . m sereere, saenocneoremesuae. m m . m sereere, rac . m m . m warmossove auocave, acum core . m m m . m ser oum aceae . . m m-e °ere, ssoven-oumroen . m ssoven m oosae moosum roen. m ssoven monoae ne craoere . m ssoven m caorounmaeroen . m ssoven m e masure,, aerusse °roz.ao,n acnomsoermaeenaoeoown-eorsee unsee: . mm . m sereere,-r rco aocnoarme uceeoe mm.° aennenm . msere°ere,eonaeerra suae m m. m . m sereereananeseem m m . m se- ° suae monoraer-e°ere vouon:rrn rnn r, r r . n m onnaoassum roenosae cenraon mo-uoounmroenosae rae . n m moruensenosaeuerouoonn: =: m r- mr wr, =rnn r, = rmmrr u .n: vrn :50mnmmnnrnnn rwnumn rn nr n mm > n n n .. . *>.. *>>.. *>>.. v *>>. .. .. . .. >.. >. **>>. .. . .. .... .. . . *>. **>. *>.. .. * n -.nn n vrrn **n nnrnnn vn vn: nrnnwrn rnn wnn rn nn wnr nr., n SE I n rv. VNAD NO:1 SETDIEDDRNWON:A VNATDE 2 SE IERWNA VNTTDDEDNROW:N3 SE IDNOA VNATDD :4 SE DRWNA VN IDNO:5 SEATDIEDDLNWONA VNATD :6 SE IEDRWN AT D NO:7 SDEDRWNA NEATDIEDDRNWO:8 SAETDDIDDRNNO:9 SAETDEIDWNNO:10 SEDIRWN TD D NO:11 SEEDRIWN TD D NO:12 SEDDRWN T ID NO:13 SE TEEDRIWDNNO:14 SD TEEER DEDIW LDN W NO:15 STEDEDIRDNNO:16 SDEEDRIW WD NO:17 SEEEDRIN WD NO:18 SDEDDRIN WDNNO:19 SDEEERIWDNNO:20 SDEEDLIWDNNO:21 SAEEDRIWDNNO:22 SDEADRIWDNNO:23 SDEEARIWDNNO:24 SDEEDAIWDNNO:25 SDEEDRIADNNO:26 SDEE IDNO:2 ED 7 SRWIADNO:28 v DSE EEDRWIDNO:29 SD EERWN E IDNO:30 SDERWN DRID NO:31 SAEWN NATIDDNO:32 SVE IEDDRNWON:A33 SEATDIEDDRNWONA NATD :34 SEEDRWNA VNATIDDEDNROW:35 STEDEEIRDWNO:36 STEDEIDNO:37 SDLW DEEEIDNO:38 SERW E ID NO:39 SE DEDRW E IDNO:40 SDEDLW RWNIDNO:41 SDEDRIDNO:42 SEEW E IDNO:43 SEERWIDNO:44 SDRW EEDAIDNO:45 SEEW D IDNO:46 SEERA ARWIDNO:47 SAEDRIDNO:48 SEEW D IDNO:49 SAELW KTIIDNO:50 SEKIITTR AKD NO:51 SETIKITT F ID NO:52 SN EEEM MPIP IDIV VDNDOR:53 SEEMPIIDR VDNO:54 SE IDRNOA NEMP :55 SE IIDVDR AIorS NO:56 FwEaKrARKPHrNmereuence STECCTIADTNO:57 SE IDAANAOT:AC5A8CATCTAAGACCAGCGA v GSGETAGCCACAGCTGTATCTATTC SGAGITD CT C CANTOA:CA5A9GGGTGAAATCGTT TETGGIDNO:60 SEAIATGGGAGGCATGCA G D NO:61 SAECGATACATAGCCGACCTGAGA CRAeAvCI eTD rGsGN eAOC: PGrA6T2 mTeTrGTGeACuTeAnAGcGeA SCE SAEACITD IGDANGO NA:GG6C3ATAGGCTGTAC GCCGCAGCO:64 SE IDACCTTCAC ACGATAGNCO:65 SE IDNATCAAAGTCTTTCCCTTTC TSCEATAAAGOT:CC6G6CTTCCGTCA STEAGIGD TG G IADGNTOC:TG6G7GCCGTGTCT GTCATGGNAO:68 ReorterGG1AAAeCGuAeAnGcTeGTTC SCECTGIADCGNGOA:AA6T9 SE IDNO:7CCTT CATCCGCAATT0 SE IDNO:CCTCC CCTGCTACGAA71 SE IDNO:AGTTT TCGCAGCAAA72 SE IDNO:TATTG CCAGTGTGGCC73 SE IDNO:G7ATC CAGTCACGCAA4 SE IDNO:ACAAT SDVNATDEDRW75 SE SIESDIVD NA I INDANTO ND:ED7R6WNA DV O:77 SENATIDEDRWNA VNATDDENO:78 SE IDDRNWONAV VNATDEDRW:79 SVE IDNON:AV8L0 SNEATDIEDDRWNAVLK VN NO:81 SEATDIEDDRNWNAVLKL DVN O:82 SEATDEDRWNAV VNTSIDDNO:83 SE IEDDRNWONA VNATDEDRW:S84 SE IDNA VN O:85 SEASDIEDDRWNA VNATDEDNO:86 SE IDRNYON:A87 v VSNATDEDRWNV TEEEDIRDWNO:88 STEDDDIRDNO:89 STEDEEIWDNO:90 STER EEID NO:91 SEEDR DLID NO:92 SVEWN NAID NO:93 SETEIEDDRNWONA TDE :94 SEEDR MRLISDKFNFOR:D95 r FILRKK rrnrn: n r nn n mn n rn nrnrr rn, rn.nnnw mrrn rnmrn rn.rmn,,n :.:. .r. r, r,m.. ,n ,rmn , r, w . n m, :. mr.n.rmnnm n .rnr. :. x, . . : : . rw rmnn nr r nmn nn m, ,mnm.n.-n r, . r. ,- rn rmr mmnrw m , n, . n. rn r mrn r rz, v., r.nr ,-n . n nzn.nm n rm nm rn ,. nvrmnn, m- r. m rnrr r nmnn .- nn . .r n , rmnn,nmrn, r,mr. nw rvn n rn .n ,- rm rn w rrrn n,wzrn, - r,mn, , . rmnrwn zvnm, vnnrrrn, .w .nrm, r. v nr,vnr .,rn.r, r r r nn ,. r mr , . r xr n r nmn rnn n v r-,nr. w mn m. , .x m rnrnn rm mnr n rr,r.rm.n nr, . x mmn. r xn zr. , .rwr ,rn r :. ,,-.

Claims

vm.n167892v vnmn nn,nn n -1, wrn: oo12233rm 5,5,: oo35,5, o -2o n5nmn , oo1rm: 100,n n w o nmn , - -1rn rmn -23rmn -5rrmmn -6rm,,n - -7r n -8m,n 9 rm,n -10rrmn nr wnrrnm mnrwmn rvn5,6,7,9n10r . r nrn rmn, wnr n. rm n r n n n .5679r1run. nn r n m, wrnn .n ,,,n . r0.rn nn r .56r n m, wrn .7rr.8v .91rn..

0. rrmrnr nnnn r n:-mr, wrn. r rn nn m . rm r n , wrn. rrmrnn r nnnn m:-,.,:n, wrn. r rn nn -. . mr mrn rnn m m, :, wrr7n8910. : wrn .n n r . rrmn nn rr num, wrn 1r 6789u 2u numn r .n vnumnv.nmn nn,nn n -1, wrrn: o123m5,: oo23355, o5,, oo5n -2nmnrm, o10: o10, o nmn n w n , - -1rn -2rmn 3 rrmmn - -5r n -6m,n 7 rrm,n -8rmm,,nn-9v -.n w10r rn mrm wmnn5,6,7,9n10r. . rrnn nmn, wrrnnnnm5,6,7,,9n10. .56r wrn ..7r .8rr ..910.n. rrnmnrn r n m , wrn. r nn :-r. rm r nnnnn m:- , wrn. rn nn m . r ,,n, wrn. mrnrnnnn m ,: w-. .mr mn rn : rr7n8910. :n. m, wrn.r rn nn m , - n: - ::,, - - :, - :, - ::, - :,n.r nrmnrrvrnnn mrn n n. r n nn rr. , wrn rm rrzv. r rn m r, wrn n n rmm n r u,r r wrn n n unum r u numn r r u. n,r rn m , wrn n rr mr rmn ,rrmnrmn-mxnzn,, rn, r n, r nmn n ,n rmn rmn, - rn wrn n rr rm r nn nnn,,mrxrn,mnn,nn,nn,nn,nn, - zm,rn,xrm,rn,x mxn,n, nznn,,rxxmn,xn,rxn, - rnm,r rm, rn, zn - mn m,r nm, mrnm,rnm,rnm - r rzrnm xrnn,r r r n,x n, mn n,m n, - -rrrmn - rm rm-mxz - rmn . mn r mnrnmnrmn n wrnn. n rmr , wrn r rn wrn n rr mn,rrr,nmn wr. mnrrn . rm r n rn m, wrn n rr mr n ,rm rmn-mxnzn,,nmnrn,nr n, rmn rm ,n. , wrn r n.rnrnnrnmnr n m n rn n w r rrvnn mnn. , wrn r rnm rnnn r nrmnrrnu. rvnm n rn n w rm n r un.nmn

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