From d3fa219633c76518ed018647cf8e2f1800a77cdb Mon Sep 17 00:00:00 2001
From: Sebastian Mueller <sebm@posteo.de>
Date: Mon, 20 May 2019 13:05:29 +0100
Subject: [PATCH 1/7] mention of Cambridge based company and software. added
 figure.

---
 .../barcode_UMI_read1_adapter_fastqc.png        | Bin 0 -> 30820 bytes
 course_files/intro.Rmd                          |   3 ++-
 course_files/umis.Rmd                           |   3 +++
 3 files changed, 5 insertions(+), 1 deletion(-)
 create mode 100644 course_files/figures/barcode_UMI_read1_adapter_fastqc.png

diff --git a/course_files/figures/barcode_UMI_read1_adapter_fastqc.png b/course_files/figures/barcode_UMI_read1_adapter_fastqc.png
new file mode 100644
index 0000000000000000000000000000000000000000..8e60b339422da576d56b1227ba2ff94d9d70f565
GIT binary patch
literal 30820
zcmdpfWmr^e->;4Xl8PcADTsj5O81~!kVb)_OQgG$h7pA=2q@i*3W9WZih$CBG)O2d
zN_U)l3})f;yzlvRzMOqs``V*x-SyAkKkl`kC@V@66HpNxJ9dm%=GH%Vjva#|j~#<)
z;NgP5xkYuC9sCFGcwI&n5B%eSckkb0$LNpA{3EIAqW5jYGSgV|?uAv)Ir|?A-_yNR
zAE>V_e7E0l`POg5LuY~@(s(W%%n&-u9KCrWz~?kQj!?k6ljqLeoM60#_Y%&K{O_>~
z%F6T?5V+1CeDGew-nm?4Zuc3bQ)-iM8&027uPV>5sXApjB3$7%>fG!4!?E3KH@MLG
zhgVjU?Si&*$3b>ghrxNh#}vn5a6A%vgwL@*KWg8?Sjffe@&Ed3@LU@9kc<NM=e<7z
z3}lYiHHX?MGD7C~`3w)KbK>twP)s;*Ho3P#L4QX7S(jeJp7_W%FfT-&BgtgPpXU90
zi#`Soe1ES-qHzb2n|~?3`{-%FG!M!8{$367|Ldj^Y&f{Sl59g+AAeCEQ38jvjZi67
zG5n;LHtD~T(wyJkTgQERFJmk(T%ElTSeTbB9C70pADnI=a=U`;KN0?<c&-}iygZSA
z{i_tJJK;kmgMtyHzXhfDvYkbcF<b0!x^kBw_#S=0xmI8jk-TH{UZuLr)84(TW?0=T
z;l5sZ4%H>KjkXc<lV^X8&Y~d6EcC*2{<S2p3Oz+I`%o9}>Mh?;9o;hP9`2N3eLqHX
z?$8V#4jx_oV(<3fqBY1ihD5IiCq(|-2C5M+eEc6uURB?aO;2af0V#Fg5MH=UpQE$9
zh{OYrVgC7e*SQ4M;)UOo5P-L8%r*+n;rtZf{&ED>wQxhZGS9(p!A|;a-$fHL7%OGw
zHKk+BX?yX1iX!ShAs%v2%u7q@=T@m$p7~u`;kSz*VN{=Hos6(ntbggcGa>j(I?)m^
z8=Scgjrl7-=Qk@v5M51|8|=4GzQ)G;VL|`vZvOYecqcLISI)l&c*A@b30qA=T7T#t
ztVRDKW!i0n!Pe(8H4b0fuf(a2L=p0(8zVPTOU`n**%a-wDrt=-i}&10zx;cOaoEEM
zzthjA&itZm2BAEmEs{(3x9%d6aE1v!O@Hir@ay$Ix`r@d0xB!(p~(D~5^b~7Ys{|9
z%!~Xy!psvN(-*7v(9U5$_huyt^b5yH?Kc+>HG71FB-6==X6@l$O4k3-$H16yCjHW1
zi<C3ir4I&e-hMP`*;Vzv$7mvN*1ll<fv*DBe`xMad#grSBAG7qC4b)eQq3Jl<3Xvz
zL;U_>7FT<{1lBNcxo3>YOF!YoHB0XyyTYiyHbc*?FxH=i=suO{INA_MG0(23d3b=I
zKMdw!rtR?qZq&SJJyeeO-aHQ>%_B{g`qeb2DVZ{flB#m+-hK1QWb5}?7ieg{@^=gu
z*VIU?L=PXIYk6}Hr=v1(p6SPg+lPu$y=BhqsQ>McJ@b=YDRK>>w(nM$1_pUiu1$_F
zv{A9WG7G<y6tXcZ6+m+ZPv<{+_lH7R<QkVXG*=Ca%Cvp8vQm~HLw-qaKy99X-|M7B
z(vTL>hm-v*$0vC+Ccmx^{RjDG9@gd=Fj2frPKbAI&D=A0{Vn@HCE%A-S(9nZAkoG5
z?^OI!3&^8+!28S_YB7JUkKh7Ur|P^(!r#2_WuVv4^iRKbbRxvfu_52O?xMMkXR!>q
z&Cz(s*sFe8l1DgAOR6#1wtekfT$=42+OXp3?Y#GSWh-&T3b|c{XFk#$74Y0gwG@8!
zOznfaSFFvaE3Y+)+qixXqme!`BOEW2lf=|ES@MRnwr~X_o%RS)OhC+bFfVViEMNV{
z$1sP~9^GQcnChs7jL0)35vRhedI$9DWNFoduKnS|uXESN!kHhl<dy3P-sWcnI;)qi
zpctZ`B4VyNyPcWe;*(4joovjWpGYUtVuRdC-x(n&{5R6*FB-_fyJEO|Oq7Pyr8lOo
zNF?-x`d#R`<}f)~tT6W_(@1@`fRZg^M(8iWE>uOwlXZQX;u@^xO_Qk)zu6MkcQf}|
zPWYFjTSQ31y9OBYwC4%vBAMiTpSw1{NmN<*BD^z?M7v5gUOmb{gA=eJ0s-<j0%H8S
z`j6hk8(&jeyqb}yxs$P=^|fDf@2Zh;<g>lM#wftbhScXgx+UHWwDf8dUr#sY;;FcI
zXJ}$wN33A({o0#M#*!RP)4Jxu=Y=6h)sy{-GBJ$V^FpBF318u0g_d|VC7Xj}o9X6k
zy11d5TS?9N4wJ2eCGUm02YKK8C|j_>X@1lHAEF$6qxNZp&@-CrN7=l6k$aXr#=Jms
z`)=5LssU5#U22E~gG0=`@i}IkhkC%)c~>v^Z<B~8N=A}ddj2Ri!S3Y<@Q{&@9I1{@
zMUOz_PEh@JlGriqSAf``Z8twkF|f_L0L!DB1!HoPf!&l5O#N-se~&>~;}PMGa!yS2
z5TR7s%>0l?!4k>_|Lfb3@kK&5=WCIg9E`dhWO~JnSrwuJCEi`d8d632<}qd471cmp
z*3R@w98s6(D~p0O_ABq6Oh{>n(-8%PNRJ-WCnQWfP)cAG-<bLMF|@i}m4DZxoF_B2
zu3l8~*6Zjeab3$Sbb`jxRFUESimVmGdc+#9&y8;BK8$ETop%bj2=orjdH15KS~(4J
zVtFgKGGe^Kaox(q^0vpp*AK6Z6ZI=UZNwbw7^q3B(9_}C_x!M5;J#|>th4LxIoz}s
zTBBD@&F{^^KK*uCUPGLq#s5{#(hl{`P6N01+{fP0==_}F2twrR1b*|zTT~j!l2Xq6
zGDS~$@!t3e8oPwjsTAjwOHk~8EmoM<PFlxDZu1Uq%laVZaqjvo+G|XB@Av5AR-fsu
zA&bo3zgzZ1|B(YlQ_65->4N;4t;&~^Z7YF&o0>OYRL3`a)V!Z+{~Dt*9;3drBJiQ1
z#?+Pap!%!sphMMHZT)jg$CEoGymTthMUCgW*stzYal13M-`yIn_iu=cp=2{<*{w6a
zBR0Fvo15mxywqQ+N5{iKBeRh*`Fc$&M+uR8Cn+TqkHjnwp<*JcgI_>fO%b_yVM}lG
z^qv{3g|X~hmVxL3*A?A^o3>p{$PKRRQ8#YdySf)9uYIoe6d7?Uq-)BF&&z+$r59CS
zhI#NVKb>n$OlyW>pyfChr)@~2QMBP>mX0~TGdU5Zm10`yI};n(6n%1QvH$kT>U^f-
z=<!@~?~@bBj^cWpx2>fy(F$G@-FDj;8@sHdxmu);k94RBjF6Pkv=KJCq#M$tRuX~w
z@N%J<Hp!1`_G-a;YLmA2MF8HJNa#DSpfq`edxh3`PR8tXtj&~C^3XXLH&`!8>`>I-
z*@r3bU$Yai3gpoM%P#fLWw6!EWUWxV_+&M>U6&xzeP3x<eXqfCLNbPSt_A%_L3HJB
zKblaZw>+ZfYRM@Wqh?0c*eYB-tWRvn+#|vvdd0LXxj?sT&2^|d>I<CBlhS<eQl|sz
zbbV$}%lHe!gO=|$OQ+wSc-Q`zlD0ywbtd{<XENpKQNq353Ez_q>h)($v)@e)n+eY;
z>6GSv(!aBNk=OjIHOp`4!mDI(=km3Tl%8Y%oWCZQQN8ytVw*kUAD`L)*bo1egUjsR
z=Oaf6R9FuLhmlJOB-h>{CXuBj&WU}6l(b9Z_asOoofY=tQ#~iIw&2pX$Sdh4>jpFZ
zfkpk*2&#bO`HW)j2ky6vg3SxGkXaRh(}c)!!SwBa(2}q)o3^c!FM@!uZiaNW<-S8O
zd3kQj+C)4#eRjvgMWcUUam^4<b3cze?#qQ7M=9wdn^7!Y=nq9uTD(KQ@@V7nWg^xm
z$CvJMG^*-ZWXh@;EMDGOjpkUgPSL7sM)s@8qW56)rF<;nB43-{E`Kp}<q)l(SQ-B?
ze^vg8{+BF?l}bQ2=?_?65l0eD#xFl8VeW3_Se~P!RH7b|P|T%nVoutT;di-bA#Tx9
zj`m?h@ze18XZs)43fs1oQEZd89E2IV3b0?5cTMSP^2JXo&&R=qfXbOH1ZVgxN8_Vl
zLL_r-zdYI&cHla*=zS(K>g}?mMzN=*;^^)g#0{eE15-RGWTT~kCP%sSO^u#v@urQG
zcppB~8&4FV0JXVkcpxS{1$Sd6F@3e0ko%5%@*sP4PiIs7bMOk+qe-Qp>IasJIPXiK
zW8Q-?*Dmv)nTf3(S-c{Au<}`NX;flGeyPU4U5v(gQGRpVw0=3~(ImxNhkQ%gz6(&>
znyCr!n~6aKX@6wxE9IqwybAYouXnZZ)Wq?}Wjz`$Y(IFroZ~my@n~}3RhAxfS^C_k
zzztCHO_P}A){c6u4_xH*_E^4W|K*+O1@T>_;Trwj<&lbpB=7OZMoHD(W7%d$ToDx)
zy@vTNi8(#00e&}axve`jL~;8quu4h9hCuJ#&Q0e&3gJCf7jQKG|HQ~mo=GHCLKxm~
z+P~h2uWe9YsUZBiPi;O-Vt=gecJ8vR$F}*>kCDnUtE+#)vR{4<B?K3*P@<>N@ngO!
zFLNToLbG7K<95ysJQ9tt+JW2Ww~^6V6E}}|yLqznad~%$RVOyCT3snos|jh7-N-3<
zBg=v?phMMv%q$qWS3Dp(E$oLy3n(`@?x@%D_?faUKYc+j(_7!8%S+UT3WB!hzbl0`
zQxhWjKbCHMcF!qwS(;!@zjG4x8K1^ut7ZI^S0YEYUbT+LN^`{LHGO|9`m&N6YmMPi
z%E<PkxcaI8e)R2L368~qNbR9{T0&$OCF}gmSjCTOku~Hi8D}~g8u>v!=bioi{ZD&g
z_tUw!>Un;2h0jlxQRs_Wj44&FA(whqrkkiNcN=d7^Ya?-E@$mnWh}K2Qr7%WA;Idb
zTba}B9Xf`BA|mZ(w9%c#=Y(dj+r(pvxw?tsEJy^&Gs8>PRg;QB#WRcjgvlg*YN<e6
zS16@(6RYNFx9Jl;gl0FTcUgD$rY>aU4Ft%-8%;9h-OV_}VDMOsIP9M{XE=l_sLRhj
z(}ibGhffK;7PWnD<mf!WpM(hoJO!=G6U8(6M<nzkf-fQr5<rOQJjWV$$b(upob-}q
zb}bd6J75=SgL6%$wm7VT3B2wN3z8Z2Y^d6Dfd1!0)i|+>tq~-bEWaBhC)RT4xTk5G
z5#e=_>0d+HvgDl!H|K-oF{THJ)^I#4sj<&#u_JA&spJqP>b;a}mX<%WWNC5#M*yvR
zqwEj3Q#7Ip6V3Pg%$@qP2*MWb0Je2D@@qTSQu<{0s5`ElSX87z3Y~NciP_WIy}Ge9
zjtax|7^uV#QM|`FUuK<`GP^$KR&Lw7)RQ>fK2j|&pv8TkO<ABkg#y0KX3!|>-K5un
zl^Bx#N}!u7Qx=zUk*H-#Hh0Uco8w26mjq<FvQNNhNx6+uj83GBKpygHffUQk_(wrl
zAYpi2bFgV9d+;<7<h*$7mjPNNX&r~hvM<t$mhy||uRGzX?b->rCKp2TW~gjDmmfV5
z&p(}pNuoWfn>mT0laTcP3--v^%F2*SdAvh?;Aw#t7LSt9D+8OULkJhXWG699a8AD>
zF{kUr?H)4746z^=V7@$KMvcP3Y5lby$OIa<fnmFd?#AbpL3=bd>xEIJa6k@8GLu{T
z=G2BlAKt1W0Og;F%T682DzEC;wD<lrOYyfp@4Y^j@7jIA7VgEj56ZWD9y#E!DV)c#
zrdJO0F-T#))qn-L8n@9@dhe8th76@N4+?8d8#p)Co$6$5{q>qE0KH}>(&k7HMS%jR
zIX8t!m>K6nnUBffw=naaNc;HIgrQSGk+bRv(|E|aPpaf74nk34WbyE+p2Mw?&~t15
z(xbD#^eAp5_Jj1-<{)YHdbGGd8=aoW)?l7LVjkY?-?v>l*-M;&dpLMinVy)jYmMfE
zXjAw!hl5piw)v!LOLj)0xwYA{I1e&bRCrLzKoYg%TlbOjVFb=NjpCs-L^Hs8v|Y)q
z?+^*5Pj84VYJ9RC_=3aM(kv8$IDsQ-l!EeoDTAf&)VW)>WlvH$s0vl<!*yI8`5O!g
z@k+_ej<frpH7f_Cn`KP)guG6n!K<pdy1Au&&FfxKwnDGS=g<XP5X9{mp>g0Aq?eQO
z^3}DU5M2BNN$3#<DzGxJA$$&p=_u<C9EO(9tg5{#k!4mwaSpl<#DGa4WJ{{W1(Gp9
zU!0B=jMgj92<aS#?%E$J)YN2qLh4pndt9Ms;<bwVPqk6y{4ck=Esxj9=J@MRL$&Im
z4<(y6LY)caj1M%U-L5p7HC*nHMm|92nMZ8yA)7r;aA?GIe7FtQVo=6qOU&yE81K4;
z72O~b5_Bd%kqwSkTgL#LipfsUqAi<}Er^OD2$EnyR{+EIJvb|IO}Ul_=_WW+E{|QR
z76}wsds1Bp<pzGNxv@g@?l`Of*tdd5-&i^?f<px2%BesOG4lwJpR_)W6rPATOfBi+
zlEro;F&1}*B-5%<lLO9w(V($eDq0O1t)fyf8TJ#XQ<(DyE8)y_rp*!jk!oOo703m9
zzBZbJ_%#qeIxjyu>J@h7Oa%k(l&|CAp7X;I#pc=z8m1RYl#735;Bq-p^|$L1^YS?j
zC$Z_fXcaV-);omJ5QEg9UumLET!G~&5l(>RZ<5SB1FWE>lGi;X*i13Nk>Lfmn#YU>
zGecM7FNfpu_pD^>bbXm{(^4;K=<5}!YaTQslQ&oabZv{vc#d@#U9j1w&z;1`<89)K
z#jQuXf}AGUkDty-V7e!PBFD!=YVm5s${rG*ULf#Zq^w(e;g?j}I6v<0<~-YUup1TE
zZ<jhb0l_O8<t(wseu|&z;I8QA-jQr@GwoVqbu(^VGpk!WQzt#D=>^B>w`WsdB-kid
z@IF4=&M}k_jsvRcrKB96e2nVn<XYo)6X9>AKH4aqGjQRH%I(Mj%5C+0#vAF>hbrWW
z(V!S-4^Fe$3VY%`0izV$e{PbPJ@gs!iRC63gy;<pYB)=@;BBadbJ<GEp0SX*>po}2
zTOTnYwcPw`FJO4QH^%HfJ*_g~m1e_g4asF3hw+;>+M?nkdb&y*ZNk;UurkLWWe%88
zU9*9mXf+jc30do)zFfvRfW_XzOfuQ!r{GwL2dOM}J9dpHFJw4x$&^IQo4?O@usnzG
zsqF&1NSTelbx2&FW2h7yayJ)is>*jhH%s#it4Q%bvC?b2iBK^-JT3SUEoblzi7so`
zT0;LpQvoT03CB?BwLhv>@7%6jmR(wGPnd`s-DReMY=ocPZmKngxG$}o8IOh#>A<7h
zHRLmAwu(Ve_gg-SP67ng>e%0Zb!TVCXlQBxU0r#$qq3zqC#ph3M4H%rt86+T$7?NP
zOUf^+kxQvyVX39W!XsmeTHuNHQ~l2kYoQP9tG?>$aJhmY_VAC}PE|VPPFF$<EK_kJ
z-5O<6Z#o4d<S@zaE>yP_WP4g1xt%;ntr3+VmQH)rHH`ro@edhaMtT86!g9k(&ESOr
zQ<d6f&*%lD`%4Fy7zJ?S(-c164{bfj(vYE267wd)e2T9jS(&)i#_S3o*v{R)k5w;_
z1wtgijFJd==M9Sr*82tojnB|?*8ovo(H08DisNyZGyYQ?HfOR-KuCTzdX0h1l0ocl
z<jFSM>b{QXQ!9QhX%{n(EA9z)UbiPSCPWtdWXr<-GXooWF3pepYG?obf1ejKWTy^A
zezO==BF$XgBj`M62f>UmPq^@*(dj&iy7uX^>GSZqmO@RYS)q?th^^A6)i+X_8rBN4
z<K4APvlGk*${d6%LFQ<@uBXTgf0)|2uikQp@4MTfZSK5_a%#L)PFE56OT$^^%N&ec
zd!D5<jW=JvP*T|}C>V7NwMG!mgS_vjU9Rs~HKHPXXxC8R@skbzDNmeV!gx*v5q@Gh
z2WJJgRIT+wx7QIv&pk~to$k>)`(iW{Qcx78Cpi&ftbcVZEm7jiqQ)gv&0-EQVWr%z
zS9QHTHiW|$M7K`5^gWHRIbHbqFqh_}PEX;&{?l*DOezrQl(SXzCYF(zWmOWe<O&_{
z&=`m>ip3J&>K}uT%ErA*WoYApVAc6pwIBJ;g<nO12whW-l`)6}TQb2P_*EXlj6#oN
z-KH*Qi%g5Q$-1njl4kEUV_uKT<mQP6#%DO1&YI-{CsF773Y!qzBY%%`y3G3al|Kd`
zJyGOA;_Vox&&dlb;RAU_K$i24_ay8C+_o*U?uLa9KDFxr3J)Y!#r_vX-ev?SUv+&r
zGrTMtlzepLPhITvKrN3KRkYcrlS5>+^V0F-&9bk?k?4rcczLuCFfqKQ?1hi8Vv5=a
zva`+8>o#bQfiSmEKk%;)-ca4Z5({L2Xn=ioY`iXqmw5?zx4$Y(wRbSqs6YN6v@2|q
z2e}^G$IAhM96ktB;A<0TwP@$#fRcDp+wUFbNC0K=!C>a65BW*bB+*33`v4Q+D%`~4
zLjYOC!3jMSgD-ZPp-zt16)in4O1+Ub;a~poMv6UFy~#;jmXDJW#*cM!;JKVG#uT*D
zv@!VEW(0=~l9xtB;=Lo0A}I)}JDX{BLpK3#LB8k_5i3asts($dqS)pdUk_4vxwU(C
zY|0)BZq>5B(lXd8^ft@0ILWiN6FJpgMqPVL{Vww5RpnNFq=-Mg0M=a_d!(aMA#EB1
ze&xdWpV&dX(S{DdmeZ9p5JWed4U(yn!$*|{^(`6C6*GgQ#u|{x8HD|$B){gHatI%y
zZ=i*{FC{piRZ1$V5oIR6=V09Sk;eZM@a=CBR8eq#F2J0rwjQioKvTkIt*>9Tld<Kp
zkdmtyB<RqXoqIp0o`b35P}w9LGGZnLK^gtkBpvTgv8xP#Aeh=znheNek|y89?%)&W
zv(InCkldEu-#2-6p3L_!i8XBt1Mbd$QsYMv;{)8yubO0m9YCV-54|5t&&i(1>B!?B
zlK0GM&C#KsaaB3`*dtYKb>{(=i^_Dsw^BxXxMYQBf2J>oVos)KehjlR-Rnw26fH5u
z-h<VJ#J%cgxQ&d-#HP=h{R=|BFkY?Pu4l(TLgFmTGts;^j5#8%I4K_IK~6n#IFDi`
zbZL|gla?OBZY-1aSw)ap&$R^oD4?>OGLt0zFF{-txS5VE6mZ{0XAjxWv6|k!v7jMY
zn}uK-6N*5nz?)4ozwxC=4nhlAs6?PeZr3`?2du%W<zm%t5OG2{0ur^+QgbkJmw-iV
zSpQVae@ZVJ36v`<o`5lz7UQ`n%QqZE7|}?G=h_C2e0Ki*{DV|@vq1w7QkXAO_;+C+
zqbLYMz)g<xmlQ5>%Z=GN)dEahkoN6Qj`QamSwP9Ogvg`}L|_0d(mp7{nh1^5T7!hg
zY!&<{m7<7bdKkQz8MrE{ssJn&vr;h7TAY{-jH4#6Yo5yN`NzN-%vbc0^>=X_vj-!b
z^l=#?%|};;DAO_E=2=IDU&J(ja+B(Ybt<6+6JqT1zqR$2x`bGbjb(i1?w{ayVfO0m
zet(>fS?Ex2eBwq1Q`5r;om-)}SDvSea+c)id$`E~F$Q+ah^7z=xe<zJBDuTg?-2jf
ztZdx1ucKMar(`f!Z)s!~+Kzma-Sp!zTN|}1$6OMEGV|M}Dte!|n(ole^J<}mPcR8k
z8~5(_m$}G0n*<K9woxr-i5g8-ZG2|q)T``g$IoH_?vGkx!||s5w$oBm&5B6Fm!T5v
zVNwMwX*=~$Jf`i1B}-b>g|+Vtm=dz`orq&dM?E)2jCc&M`QH<urJ=c3(lJ;HipulP
zzIm+~YZ4^7Mp^4|u_U@qrQO!wnxF{mkno7M9Ww*zq!la2-DQquTRtyWiZ4<B4H5x_
z6eX_96~(FB%=js{D848(Ztc#Er2q{{gE=6f;q$5hY+N3rWTSqEB*VI59C(+uOP7l2
zLI*9Ej*MDyMIte>S4i8qVnj^@Wdoc~xlp#-VHU5G7`6POC{LiwG+ll$X<ZK;8o+Dh
zIgy1Zn~FG{k>$mz{5|ZE!!#(`*KT8SLIrBquuG}IO&&8~ls2l^{JBxLV^$6`NItgm
zXg9DN&+_|j1#<@77jxulbl4$N_?x`wsUR7vj~cnxEODDN_u9U_MxL3;uKm(kbkgw2
z##+L68-cZ_hh7U|i_<)v8y(TrDrdm1VQ#`x6mSeB1DmvpNO<9G!a_NK^`i#VFy}o#
zJ$0cW?wK121O9#MFTQNwLbJhaPRupmnmc*8i{mhB(3Vta|EVwr6t3-7_voN$6Fids
zQlPtEzOr6Y&H--h@7OUA=s)>K2X+)LASRXI<=B6)*c_y=fVri#pj}7@#wLR?Lm#UI
zc!i+-qRa1gmlR9|yrp9I4eB~;V}a$c#6^mtoC$}i)yBq)<|C2fhg(Jw6YkFC*py!H
z;b640hzX0o;e&7lsKLBl!wet$Ru;bMjcEPtlq|kiA!LNeZNa(i;VVCF%_)%{u7tx_
z5cpa})cJIfdvNk>ze`gb4-PCOV0y;vDL8NtB>^$^O*<X>2W(2hahJrHM=r><;xJ7X
z4_E6@Hkw#t3=F>(4r%|>+VM0h0KA@-Kr&S9>?FRy*S@9UUYXnoTj$bwPFf6F2Yxxo
z%fLYfMF(KduUvv~UcY6-{2_BMPi!fg_t}RCwFg5H0>ES&b26ViW0nobS!VRg7(z}b
zeL&8=tG)HXK+1&0Ys;~An4TcH0GY-s1zw1L(MbYp0U>Inqa!(%P(gUfC5y=s?Sn}o
z;#Hn$T2i9ox=Jm%dKo@SIO&*3il58QRyD=H&*rmU5O&e2vuU`rWy<%u_6rwf3Xok3
zi8Z0kS<bq-`AEITq#88{AtPf`K^<>n3rGdo;3`U!p{a1Mdp#vf<7@w_&O94FNcAv@
zvyk>z1N>PmfvW|HKN(^6CV|I{89xQ8-fe8Ys1?lAiTH`vGVZr&n2*hvoy8u53f`>!
z_z^3gL9hNJgA^|nrnCKNKBk#g;o1;NO;Mz=;l0U--_rj69tRFGzQ-bO;Pc)FZcc%Q
z%o@uC1eyyN`|78KUiXoJasw}Vu0mXs7Cp!&*3p|^M45xP%!Stv5jpTX236qi*0xy_
zY6mf5%z`|AxJU4V87K;KSHC2h7B*RL`C#ayP8PJS1d$5VA%RLUVfGaUHPSeHVm&hg
zeFe<?`st(lpgVAE-@wjk>bqU(J$z`dBKipo7)gt}1%+462;O{j3^aX3=XHHw>UP6!
z-x)8Np|!7Oe@!?*t&s*yiRm&xfB1!Bhi_S9u^IxnysN4*zTv~gMSSRK973d<*YO#z
z9grw9KR7>kcrb(jPM7ATyr{Bc$%8vi-osIZGR@Xyo@H+3SB9VJxi-r3G)l7Jv2%d@
zmIzRk!WX1iH=C(K@5f|paEDmC`3K8_zG+;zZW0i1aXF?l{iU_Oi(`YE?+3dXRF~>2
z?Y+pb9z6PrasnzeE(ml;Wzy4y;a)4tpU7J(b%+@dJo)M3Sd|9HQvwD6E|#}gD~8_a
zWnl#uk5?Woypv+6FmL7f8>0LAOlPbbhOa@=Je!$h%xxgO^)qk)S&EJNEW}dL{1z+W
zkPzz7B-b+kbTPsh7nAf^T$O`S?DO_Ejt6V!c2Ez7d?uNhLC8An;ufT7xEFqD&GFd+
zWb<CxLRey5Xr#HPGeE&}ezNqrd_S}B+LkB?7$J#f=4Km<{s{-$Zw4!L6jjFpbwRE;
z@}sf{0CZLJI&5bIMmr4=KX4H-aCu87A|~$|MVK!hFX+AMYPJ8!3XubX@Dc)iwK>(S
z9QHa{&q&#ex%OZWjUUvoP};x-RsQf<d2>v~_$i%RKurkkg`yD!@I+j;HjBt!XvBgR
zfDKTx`F@lxm3nNrd^Nkrvuv;GdG~D?G0Ei%dh=f*skzU`Vs+aG!G+WKFyeeX#_)=<
zM(lJyONn|YtY8ob+mL2R1E|y&ZGqh^+>OHy<Z#RxWL0H1nn1FrYkppOx`ZA0d~Ld8
z(4=>#J1UQo?e@LFEQIsF0NA)UU|QrZ%Tj_V7Nu=#bkA{BDi4=?Rc%h$9^B92a7x5-
zvlyp6UZ`M!InA38B&%edk+Qqu2`P7^sWI3l&$Ogf<$GOSov42hZ2^Eb#ny?$b1iI3
ztrb>Z+_u`L6Gbdqr}aFGHs{o9Vr@0@dp0Lyim!TYMaqv_>@JHpa{W&&b)MyV%^^42
z<@yKJP<g=Uit96Z+F7fgSq(&JWAZ+|&%15@kOEar;8C$`c-50{Mym#Z#%yP0Z#*YZ
zneCeV*dy@gEnsN|=|K`r=7Ln5cr<^>Xl5ioQ33ybHB7V_8glc8h4)(E;km&N1=91N
z7-cn<2^#HCa^1oyV({&YKwsTGXLG%<T4xqhTd3_lQO)&8A~dq;-H$J9VyVN4Llh-y
z8`Cc7lPOJ#8I}Xv4%Rcv#d+GO38L`1(EDD!`>QVVAgiY|W~aIeaQgfWBm_Az;iRKv
zsLaA|Mvlu;rN3Kq(k`MbSf6eVnO5};*V!>y&<}mtof?G0mhe5R{me`>u<1@#2xtF4
zyGJ|1dJs$$*{y@ct^4Nxn!5%Ta)~|A67w94sv=8MI<_r~ZUaV+KP0jE5DJr|>C;y&
zuq32}`Z3OCA=XOLc9;l|<r0l<{e~be@jt2FhmD%p8J^*?<o!EWyxjXLe`a_|PIYKr
z1#o44yl<-*02F6{@Q1`h2M-e`ooc9I9yyaW=U$<Lb@i4cK1QYy32U(tfs6~D1GbH_
z`chgFB3FRlXYp4{JzNJQYd`xH+@gOj!Xl87tYu>3Eu#^s4icyetZaRe!9)sKBP5xh
zn%{84;>a%hM$je^6l%H@VLeZ@iUD%wIh)C#(9)*nPWQD`S_y0Y?ChJ@Ul!8p>ONpo
zR+mQBxG{ibx%@O)um%_e`@r7*%-@*c(*&Pdd>Wy7XB|r_;L*e|9<7u$qE-r%oWU!Q
zJ=`=NuarS=mdL!#O!2(_gM-K``nmZ}V;%8${{aH|4Alt<QQ>YN8#uerIqyONe4Ot2
zo1PF{aLA$!Juq-b?${shV(_FkIjAzY9#d5^&_p$jzXQ-%;$3PK$2(W7Sp^%)4Fv${
zCy+=)0E}-cIIPF`2~q_)hDrqB=%)j7#~H@`^f|BF0irJDj9_=|8gnuo@Ke%zBlDUy
z&XBeYpde>~FEHmVd|V5|WUPHAm9c}hNzM~h>%L?1oGeahYSqel^;FZjUjn!>V{sPg
zGiCr$rr6(jDGAx`s`8lX>7C3LxG(^Mv+ua);D0~@q6x>Zo{OeU>xn)~Ro4K^Bxnpx
zZ;BjMZ%I@|W>&Csfu>HOutBRGQ&3$|KY@w_fI>^yE>__Xd802rBNS>rc8S=yd0}aF
zZo}BVyEz?r$gAcvVQfQa1#&yK&U@7Ec)VJmK<!MYH#B3|^}FpGGlz76T9+n+TBJqp
zb3dBE<u+C}4hdcTLh&Yw$CPZ@Fc=3J$RDSiNF6vlPSv@~^$|MHuCh7Fn7))h5s&Om
zUWpVky`$+l%&9T^C2ii31%&W`Bj5h<c7g=6`Zx}Ta^|<II7}0@onA*oth7a3G5a8+
z@OcV}{=mOZVpfPj;B<6BSVY3jtlX|8^8mESl_$~xoe~q!O}cM0Tr#s%&^%x7#e>}D
zZr<*f0R^HQkW&k*&rmtsrP!Iv^^q3n+wH<KreVn?q!H8MO-gK*XHBWrljp<Q3-)+G
z17ijXWZD6`nXNVFKjerlyt($(;J9l^gX3%3xFLbr`22m>ju<B$TU?vE;BqoENp62q
zvjD*5D~vB_4;O^vtzyhF=vd!C0?E@7^PoC35g>OU4dCae=crFX`v8$|3rx8k$|^`|
z%0+SV)jZeI$N-Zf6(67JkFTw|twyI;A>_yhQF-RYwH$BH!S6;pr%s)k5-)Ze1HBw~
zrk$&*Q<N=)KV%{JBw77xU*j}WvWe7>zs^8j_;aYA`t=kjA}0>uD9H86om4D<7=@W|
zu(C@18y?TIr4r|9oF9PPvp8`@HP#i-cX9($S&#dVBVH>TaKkIILcvh2ohJp|)E&qV
z@LpDM(V=LWH6HrZ5gdBzt^)~b3jBx_VAg_0jt5|0d(@6%-$B(sh4I82Z0QP)SBU92
zm>cij6bCfj7Tw;)2E9HYO$BFDpu}IG&qX7)76(UgIvfR$ocI$9$QpLsk%9BGVhWaJ
zYS6x0RHlysQ_EdO)D+0K69rS1iO}%Z<Y{5i5U4i=19cM?&Moip#ALjH!+<<Rtl%iB
z#R;C@!>KH{j^5=H1!3aoE~g~}$_6hS#Dw!w4_2|_52%rK4z$C(qiZD%4{u6lkYmH)
zjr~vY1MelA#q_M7PgeDf+N`omQR(w-FTC|TZ+!FB>o*XQb5bxMdHXz7sk-&?r5<`F
zV&p|Bn<4h(KnkvQ;dfpz_-i~-QTvyhDf+t&6Q8~`HRS9M<|qhtabk@bm`npXmhj+n
zjO!fepb;x4(n>GcPc9+gAkAcVRJ0nZtCJjjSJu0+u`w;oDR#^A&HFHCklj(x<0`pM
zs)yGS^DJ<`t|wy)SD_!k9_~1rnts^YWK-Q*%>R(u`BVHFSX~RXZ7?ZTtRlNie4D@f
zQW0ojkVAXeWrb)ZG8s!iIoZp`&8MMh+k<JZ(gf{QPaZ}X<0N3iUcf3hcrXszEDy44
z4O}f~`P`+V)E#jhT?4H5>Vt1<5NQNe51O6QNnXJx3T-2&!f`p<=0bZ(W~wnsH0PQO
zD2tDwqzFMJ@UEPrq-@d2f^~uN5-MplBbf7NQ3osGs9sF^b>3h3<Tj?E0~kRb$o3UL
z&V|=rweU$T5kTBT^hfR@<T8N2^FyoMKr5nB>tquivmQZeaB|=de^yL~Kqc>2*8|oc
zll+UhA$A-^PCyepSSdnNoVyl#XjlOHMtuh<n{u8=w=PB?z;3+#<=9%a58@SwSbrMa
zXW&-TS6!>aOgV7Xz>L7z;>gu6pg^Q;V4UNZe-4@pJ`QUE3K?1A$c)Oul=J!A$e<Wv
zEE-&M!;wTk22g_hR4g;(Stq!1_Y(@0b7BHSak8}e8(H2Enda32D!+KVOB9BwX?-}_
zERSjf%ktZ1OTpL(X@X_@`HYN><#3>Zi2)g)C#H&?%Y-S3ovpNh*g5)VfF3$$;aY%8
z=HqB{EHDLX2e{<qpy8Z84>p}0lDm(!y!4&qVAI-CvLg7ZaM8-%Nl0LG3}pi5jJ<kF
zOVWS=5Se_!fg8emcrQpbYf@)D#Lra1=rAT$d=_zpM?%1iInoO~LUd!&T7&<Zora9}
z1TFll&R^FmdSL#qdVds^Q$XFyG1NMs$Do9tTjvc7gO7HCAQ&+WrXdfy$gPXWy*ARM
z2i1EkS<nV`#e9t<4fI3ZVSN1(B3AUdm<v!iqN!*5Bf$^t<+&rW0RqPWwuguoIGz8x
zIG)_@xY$U3u_d-=4(z`i9D8=~-#MjeoaO;mk$S`FopfIamr1a_K4*`Y951^BT^(DC
zYXu!J!WOpKuV^721L)m6U{<Dz`T)F_9$0oNWipvVKm?@z&qdAJVnEuVP<1W{LE(*n
zC|{V1F?hou<zxLTNPP`&RUXJ*!STM4KV*e48u0*3HbN;UHv0sa3Kth^C0rc=h-_i!
zYXq2rQXmh~ws9Ob1OTO#oL&{U7Yg8f!noasv++=GgsG&1lyRu)DNthq3dLa7b4037
z0jZ|Bb&8?$5<ojf0PV=UdI{}XTU7%)?|a_&qZi}{x&~i#+d+6Oj4?`M=(#&3;OrxG
z`c+tng+S{9alaoF)qD0bfCn(hC_G+iFlT&T=ULbv{|%)h|3y2CI~=}sV`hEaTetcg
z++Fp`z3;e!uuD1Q7lFhQWwF^*U{Y9Na%~z<3<D6xWcR1fYUurpPCFg9&L%*)2TTjW
zJ>LjHHYSSr<e@KDXNe+>sV78X@F`LNWidrk2va~trqKpRwm!_6cj9+hqcr$sgbaEG
zHoCtY6*$o*5SS6gMKN0Gkg~GZBMChoXr9IRJ<T=xR$)qHNIEW?`FqfYy5cZo(o^0l
zl-KI(>#KRwbmPa5AEuzZkyc$v0@^)ZXGcj;q#xMUFALZVU*2!1c(4)_g9-la`T4wz
z7v@?*eCK)or_lfR<+}XYd8W~THY>6FY@PY2CX?87&@}oI(<5;5h>8Rw){$t7l}8+H
zl<XV~zZ)|lZ}3WwY2=2A=kgP)HT(BOHl^&ub#rhqbm{_Y^`Hsa0nsV5q}u+c5w7JV
zC&;)!{R@OY1Hlzq5b>pdMjB0(narbc_js9g*+Y;Q1c9KEZ^YWU98hk7%%p)B>#w(@
z5bSsXx?W{Kha^W`MkLl19*0qa)o~k`F&$qtd^Q`KEGYtIAC6ppM73jZl}Mp*uNnqd
z3FmJgmSq4`rUpW4O~YsXy$Iuy*R&*|jdt{%z=!_IFt&04)gM+p1<j})W?@0|8*p1q
zJjl7nYDc=uBf+&lcGT24ppm5)Sn2$XS=hZ?O85wlS~yeK=eRN|yuw>!v(^X>i-Ok>
zB#c0}0F~hk$*y)*to5}N5l9w>7$-yv*gnSvMB9%jP#mZbKa-~aB^%n6&#Ml!YB=xX
zHJA|q5>KD^L&W(QNblhxi<@&CK$jdSwyZetLRGGp1Nf4X+-3YvK%w89QMnD}OByJ$
z+&S^`BHp24heX`i1_L}mK1M%DMhHjg7gfR4ue<b}7cm7B>)UaB5m0{W0tDjZ>a>>S
zhygw}x19eyd`hRGEB&Vz;20_r_#!QFpV(0@V51&vZ1-4KLEQ$z2v8=7mWr5>n-g%Z
z^a<2{k@UX?jwWt<jyV?%eqdrO==L!=9ljH6iJ&X#VT3SW1Vmnrp?bi)8Pu$(+D2fZ
zsb3+_KxsAw3~y`0S9(|*VEobgDmX?8z$rxt^i7y?ZvN0qeoI#9&~nU`;^mn+?P=hc
zXNRB7kwBhuU~YnY9OJ9e2afss_qB{6Y)=v3D5?=Kl1hY^O3FY7=!iY3Hk9DG3c#H6
zuk|PxNP-^^4NhUpt-wwm7Q`@Z2hJ8p0bvFpGEzVlh6(}#!Y`F|5vrW6O!OKtfgdE{
zu^`c4-Y97H>%#bNO3GsH?4b~W7(iEY)4KPFUjIodmb3%+(^baM!vL9B3$$ODZymGn
zssZVek&$`zlC>i$9|TYe?|n1gr?sUZh{t$WDD&a~&#dP%;%Xm)A2@Z8-eEu|K5(91
zqD&W<GawkIw;4iXI1&&!(<TiLqXyxn)l;pTP=Sw@1E2<z?Y7b%vp0L|oBQs<VE2%1
zFgbK_9|T}~DG^@bKj`?Z{Grfw3ufp7+n}~HTYq`phy@OkL{AJq;X_U>jKMIVPhar?
z&M9f#p?Mn$NO=|rPZp_QM6nC^d72?!no}WJ9fL`crl8Hx4M@wIrrTGbdreaTmip|C
zFr8<iHf(($`Q7e!CGZ&P3nr^`m<+<GRV)i8@y&~niHpPKT5=heO~02=>jva{-d^p9
za3ar~e`NP{vr1gXyoVb^eiJXstP7}|mL?iB{ri=C5EmESxvErmQ<C-uCRil)OE)vT
z4}Ppb{V|62l`HKcJeKcq*?KfD_Y8x()L)C+(w$=*@5Y=wd9om&{rl+XXopQw(QQvx
z1`zc*>vPr6rSGX2Zf)i6+8Sy;@HFS@i3$+a+*o<`e+l<6t&cx19@fNU8J*4v>S-rX
z;qT@JL7y^6NIaXzR#^ZU+DI4eTiU2eIW9iKWIso~=}|*n6#^8zK{8zP^h<>c$ck?q
zVnZ`&!uW-{K+%dr(9mpV=S`GR2`r^f=9}I3f#L#KH0SkMQj|4_9jJ0k7W~qZFf>2Z
z%tV5xVn$39$*NT*3#M{DfbQV-KuE?N=-RmfASIpoa#{yQ4KSz`iMAScJm@_Ig_mnA
z;q`b{+5lZIoKZd!#vVdXa7{MldHqYM{a(d{Ju8HWjUnKh%{w&Ae|?MLmmckb($uPH
z=33$8PeZlrWri(~g9DUb0)pCQHYb+~kmu~`;v5a+R2)Dz3!TPzE4+cB;{36eGmp(Z
z9Whj67~RdrgU|zy7hLn~s=WH~B1{vwjmQQm=tC<2Ie%87qCq|ST1^Dw5i(r?hV6B7
z&kci{;75Ru;t>l+1q9j>p>_%73}UC=7wPiQc{4E)6Q=#0pBY4m71SBGkElIJ5`g98
z-h07_L7!9#!-*G^P!9aQC#Q80w9ZfK$qi;4x!^zJ3n+j3Rc1&62^jmc*Zq+DcupAf
zkLgtW4op$GNU<9Ppd;LYEnc7%;rI~)W-vXGT>)9N@H!Y6U<exdZ;q>=bZ{V#NX!z!
z`>sYWZ^9el-~Bo2bH6=mIK6N_gc$l#f2_}jnf5F7tEerUR%Fa*^YbH5F}JG22Inq<
z>($d4e}7cw@Sa{8XwO!CuSfg%itiDrwg9&Clhhk}*gUw>W9(Th3n?;VK>5Q6wbghz
zgB#!nv1A71!rE~dAs_@f+))tR;0CbdMYbZ8PptqKwDLQ^QCYx*7mLHGjsTfI*)<bP
z#*dFq3)0MW3<W-SGoeM_3HymRB(?dll~}NIPvEgv%?sCxiU8gyyg$PWP2T)zdFUes
z7(-ya{3C4@#MOX4Odweal(Mw5`9PR;>2y7zq0XPm&<3VIBJM@+ZOC!7fYg}}_?X*B
z07mc8Jg9<D3B3hqGZpfj{J+FVhn3bQurlXS?SVW4E;ou0qLpwwUJ!qGrHyx<hq(d}
zyv$h)g_s6IU`6W?pKbhB1`q+8*ajQX9yUJzq;nj`BerWPz$3{4SIvc4jttKN!!b!%
z1g4ndMiT)Yiz>&!ia^$o+CORt-50pD7ZG{&JW;SU)hYj`Ueg7omI6he+Bq;!4{^j1
z7CYn7#N`2}c0M^=E|Z)1&P4ItzB8{ZP&gXkw@WW#H4C)Y%A-JuRak^cm&-RQpUvKz
z)5Y9Gy(j?a6$Xt|>2^ZPGk8vSFp14C8{3ygGX1WY=bk;?W*x`meCXY7j&bb|caV*W
zxfgFL9ef^T19!^fh@t1evqJm|?^-??FcB+st!cQ~3}tFX39&@F+Szeu%zWG5+uQrL
zu1Vb!MKKZcKy!L+ndN!}xD73V*Afzvu5apDMwiZ&dgq)M-T&>YC?Kqp)6S0am=`E;
zo=AmpP<vUu9<X5O<N_I}**=$f4#>t9&H!(FJz|{*9l4JAVo`{FuN*`S2U$QPnLMFd
zmw%6<NU`TREqQbqApKNuP$V=TWs6ej`QC)SRNb62S-rYdJiG5jIwyu&!+<H<OkBu>
zc<hXr%J7MB9n=a<m`Ddd_%s!%3yq>XNu*%aw^fImf=Ba>y_dlC!OqyZ+w7PRMT8fq
z-H#F-#Ws6m>{2eKTY1|mLLN;HQa3$s(@3D}W!?mCfgJhxY#OEl{7KLAChL=<_6X?r
zC-|H5u=%q<a&_~Yp+Ul-pc(uTVdz*kU`&t`j@SPCK|#e)6WQ(x=Lha^fTR%Gqf4I)
z?lu|Y^QMyY|1qWzQLeoUNZe3KqhJ64Swv7+#xv-mj)16BuN~-73wYpa)A#%7>TD2x
z!tvyRbC$2m3q+7&@^^19o1K6@UIsH(24=yj7=c6jpl76&%mB6Re{M5UfsjbH{^YF{
zh|<gy0oT!2pR-~OFl?b=cp=10g2n()5D{M99-#uB+0sw;2E_Z$yZ{6JeY0B@0I3Tt
zD+?iD9pwdRxXt(3ZRk1}NO)2q3_36f3>3JL^~(Au>?*#GIFhUG{8KJ3#}t+Y8gD~C
zdo%+AxRkgr>FTs+1!>ldb8dKc9ceCf0&>v>u6%~HV=`2K^;ijGaCj~K-1YyKp&9`s
zydRR(y8*sX(&a1JdlMpVT7c>13!UaJ`oR4D{B#1Aujn8!kUuz<e*<G`Gsb&0p#%Te
z`-7k1khgB15#%WzFQziR$<S3>jcKXcU_%^0$Yhoej{4!%D{J_}+VNY4A-GV6<MAqj
zp`{ET>0wO(j)5C#5C?@-W<kK3QW6Na={t1*LmZo=TJUH9i*)dyVuEc042FBKJ|jGe
zmNC)S1FOQP2z!b1MD_Wk<Pw>Gc_O7+_oAtwC*)^bSPhB;0*?*{ew^3cqcD3K2CmX#
zASm>xmEfpLH<D4FAe-atmD7O-Ex{c_;R5BL5*3V<s(t#`r|M!svci0Q(@eJmxEryW
zV@?pPjcUXUllX_K-xQoVNm_ptx+Dgp5x+_fs>0;H@6R|x{eL6?BA5#-14>|^M3Zg~
zbYKV=C<e;aVwfE32;I7F6yzy=CoV9WQm1fzQ#0zvxrg@Wt}gk=G#M)uKR<?gj6wSU
zwm@39FwL;Fptb1gr5KjWF&m{p8&Z$q!pwGpa~*n3+bPg%(IhhgzrN$eiusOLQoF${
z!Ba2H4LizTH-fPe=~H_T6OSl}XMPs@QMI9G4;-2sp&AwH6v3_prddg1ue+hAB`Pqm
zW^ai0+Y3&J%|`&)`2pg!)<)vDnPGYUZ<2Xbn(sIaIsUKdO5yCN8me^6w;I4FC@wJd
zWWTER=t#6u)7NY2xN&$1?XNp&kUyHYfGXXdNinArTc=5EGRRZP9xs8FkslFUE5M6_
zCh2)MkS3Vj!a?sqM3+|&b0f`DV<Ep}l~?cP34GpvFnM3<F1j{|UVucv7g!UWp7!3O
zq~)DfMh%a%&och4^#g4A4@;i>`>S7*?T+$p!Oj?eCP<S|Trxb{4owYX!drH*>)4@}
zE-?66fU!W~2eNImVjwL8UtT$j0kE>V3+wcR=>MN@P#7cu;q|2R^n`>jXkv_6c^b;U
zj%gMhdeLVO8K?z5C}aKsVQ%u@U?c{Ntv`*3Tvx`Bz`g&0E(BzP#3wLe*5{e5zhwc*
zsiJkGg)Yhj#zqo_o2;vVOPC8)UibB(qEFxH0(kJn|JI2e%pIKn2O0%vWY_5&gLRB3
zB(PFid^%J^Ea19o0l2Q}eM@QM&6jORiSgLs9oa!HltXc|O-*?gG#5%@76F)`R-cmR
zdDf0vIY~-eAEL2ln0|;X#?+An3gA)fa#qBSCh!X}nN-l&vmA`E(M!jVT!sA8YV!{T
z;GiyznkPgy(3XIh*+FUhPMAO-=EbKo5Dp4svVMzWb6OQ(-~ydQ7L*GYz(B931$xEG
zVBlNH?t74dZlK#>cI4T-oi>J#lvfrYiD`5P7$_c6T`i#XQ~F0_A#E-o=UoHV+N1NX
zvdsmoC#IuOfP^hRwYNaHbceoE8H79)>r{i{ZIH77&3Oqt2>~9jDoB6$oqB3=#AaZ=
zZzM!wmIf&K;>0UWr~>?sl&M%3>(X>XsQ;c8qvp7Hym!V-%zC_qECxoc?-B9^VEGSx
z-pkr6L?Don8?!NMuP`j5id28Q{6iqa6&mb;uX@r^uqX}_wFKSe-W2o*0{=CgzCfO;
zxM#C8^Km*ja;Yz7NkLkhGbFOZKgTwR)^Yt?LY{RGvA@5B_HfNXhrHNp4iTK66#e$N
z*0-}o|5VEXW#p#P-~r$EU|{?Fr9=0NLK3`-+mJZbBK>Nz{$ro*qnuHKmb-QJAHqht
zCh}c6mqwKP9=vtnWbe3Sy_MEKT63nDxc=Jg8g<zH)_$)m6$h=!q9#tO+`Kn)LsJTX
zUogg*kZ3y4((vM7pRQl7@nedj;L@&!fV4tzafgRpF|qRO!{8reAs1>ii2U893q+d-
z=<KJYZx0i+6xQA?8+&m%l318IX!%K}KbYsvOp~1S-jmVOxEsOStBZ#5dCOD%A51$E
zX@}PD)lV)mVZMI##ebyQb7#}<-opM~QbKu+f(U4W?=~|B_k{Pa&y0-Xw-6d`CB0o{
z5gyS_I24!uL?23Wp&d;gc86)v0dfh_sfOH2nn*$IOPotPE@9sB4a@6h`1-6lGIjM~
z^r_$jT=JbuDatK<Z|_*QlueA$7n?41<OsRnKX9p^)~RruHfU!Y@{Tr0*)vKzNlUWX
z^5V2N54-)_&+dj>vM0Bb|J-##?c+xq-u@9SVB~j`NLVppTW@Ksj-r0K=c9axp!?+T
z#|;Y3-G64*Cr}Ofb@lm@(zn?uo!+_Mr+eg24wyX9x4GA3Slph)tvx+pn#BHLOu~Hy
zxm4$$<Tq)vG~Tok7$WYa;o&iFZ~vtiU25;H>@k_-ro8($X~(T9sx?xUG}8)SuLv%S
zI-vJhx!^bHq_JO-yDP(cDDY1JUCQL%5(UP~-e#v39j<guDc!HnXehc+t?yyCC$;qP
zWD>c6xH!AlMu~UkX8VTz6+QR0FB7{N8`o1N3sm<v(~h$!?Yk8-sONkqKl!6Z`CC$r
zX65~HyKm9bA#{%gr&Ki*$ysoh=EEkp*P;S0R36+}n#w47TlS@-n+Vr8FMq=Cf}V(q
zj_bkJMB7S9Kwn3Qgy8-2Cqi52{rfunwiCI;H|7%TY)U!IJ_Yw@*L~brD&zQ)^P}3k
ze6zi%prNcFB+&G}_!aST&-_hp_6s9IWRYPFK}ve3##Q3W!o2r}8f+gMFxBK(YXfDW
zzPhjwUOP%K`&}PjEMRLL=mFRL^ap?L)bZ-q5(T<7nHBJ`+kCF1h576>octldDefUr
zIdZUgZ)r(7HNbYydpZz&PVd5%&;2!e@e&&{OPe1*<UT5<^(3~9JUOo97PHY`;OpaJ
z`C)T@a4m^F+jH?QlZ&8N>xVFwCM5#xY&}mN_~{={ANt1`%IS!^lV0%k9|muln)IsU
zk}Ew#k?0U9k@sCUu%FxxY#=lhCr*0gm{aO%n!35UuD7(5P{r+gkv-`ft(bfA<%zCG
zeHn86ce|%2<6Q4@v+IdE=D5s$8+nz(l_&)ML><X<y1vg}8q^b)&t^IqUs?knt39aa
z={V;-`FQi6h?kqxhFekEeJ6;2``kH-G?AI;{VNO<oWleKTOH&VJXh~(=v@}yT}*kE
zGrHLr6=>@@PZ7}Jy)V1et1a=~iAOxwao2fkS&1x)>tOcEbWjp$iB9!yPws9^v+I|T
z#S7y5?B`u}H}72qHOh^e1Ba!(3p$rSd+fO_ZCfrKf7zs8Zx}y&ZGU^bha&I-O}vD#
z?ZNfk<nS*!b@blaO{a6j^>v<1SFL;5k4Gpa;gZ#NCZ5-MSHa|fY7mt~fbU#*t!d%W
zW!I>PUicjT{hR1zn^D)-rOrF@c<^>|fwvAT?JEp;?>qF~N0<&dp;#nqUrkIFgakN_
zw;h!6EbaI=jO?%kn;2Gl?t5uWoj$>-FQKbbUCpyr+0;-!@nQKgu+8-(```Q~t(K&s
zXY&u{HlIe2vM}o;^(7KcSCN<`472OiEPeoA=a6VW5Y_QK`1aA&wsQOS(%e=^$lz5`
zi@vaRB1MxsrOMlNJqZ&Qc<ElN3#S9Pyth>Czekw9-Rhvosald<Y7D8=BU1Di;$lgn
zwv?t20LfPHxwua*sG5oj?Okmyzf?Q_$VP3{ep_RS#t94{Ky$#BxGJ~ad^5bZk@x0X
zlRNJgS93vX{<Kx37o$+qr>&GZ5wiWeo)_gSB(_S=(|CI3gY6AWob1!%_)O$I;JsJ0
z*|+>9=ZVU6P8G@LXn%p#oxZo!D@!ZPiaj;kZ$DD6bX3`AZ4Sp>AouMLmUYKv0bdK_
z)Zc$XBFawZ<grnq&tAQf;GHe_;Je9EE6+wSEc~>@Q-<a+`pL$iS=&}F-GI}zI=e-)
zE9AC@0_}olvZE;4hY5IKHjfu4k@o9lN`ccIUQ~3C?O7jjcaTxM&0+)p($2E&S2j`7
z`nnJ{&mhAk<3HMSz!eRVO>yI~UV9!>L0gZsWwP~7m!KaBOeGPPBvqcViEwq$ZZS1(
z(v}TS*4~a~ak<s;WPT-H-H)vP{3#+SR726ognM5So7ZwyNMO$HYSqLrAxl71M*?TN
zKVob*!!*Ej-EVx_zA}O3v;>DD9UXbd+aHVeGWw(veAC@ZffL;%n_>qZ(QwBXc(eVc
zEwkMXbtf;tBbT<jmb=&X_9p3=-R-#NDcK}Kk<NwH)!X?!MGmhFQX=YKf3zmwY+F1%
zm*hR0a?xbOdkK7GgNw`C(JGFzw|9NhZ=!kf2bsj?e$Qg#ME%5ek+$?klh?d<NPw-r
zm+PEZc9|64_n^9WZwhH$zr6A${ZV({b87VbR~-{2V|_0RSH?L)TcT5MsiSAT>ukDI
z*W+WYTL{>xHRRK6BLt?(u7&JB-191B`nnrLBKX)}n>pu0$^CDSwMFy@3J}aEkDF`S
zS5d4f#GSFTAW7_|5Z~W0+<ZUm4~zy&%j}}a)NI9rz$O;`D}ILe>z{10hkUG-j7F07
zt>kRlT5nB>Z1_o(a73PiJ$jYm!Bil8*Ts&taxD{=aA~LW^@QZsV)xRJEwh(J`*_vF
zr#<ZkU+xpTlAF5Q_LoIC>q(HJr)uPMTzEV}+s~pJzKy-;YG^JojUp0`G&icoDYp4t
zEb=ymPi+y7f9Md?uH5LA&=wV3vR?`l*v}Od-IQ8l`+SRYRcd*A$9<flIO?tbz3;)V
z--&Av6L>!_BYXW;Jm&1q2Q%4kTXxpq4h+C)duRW(4cGS&-^JN!h-;AJ0@~{`et*-g
zqV!-<)qZ7trGYwU+EgPxdXf3-Ot1e1J-h<8Y;s#aO7gs2!J${e-4|Irww9?4{lMrU
zTYY@F@5s<$&85g^d<hgbQ7)q85nn%8Q!6F%*-xGvM~2pix|JR~MzMkUe*~~CAww+(
zv}Ncd+Lcf>R3@1^_&ms9(fY!j)rg&p2coZ6Js3aBF3+V(mlV*5ZQONY`%wR+Bs7ym
zRNmdli&yPH-fZBm_wmtH{ag|KQOg{KgHI6&c9yD@d#`ryMedBRKO5chPRdNB7!{pY
z@eQ^+qqrF!^+B@95Ks7fADz>1j8OgE>)->X?)>9sanmF&B-vH|40!*itt*d9Dtr6Y
zIBAm;m8Ds3W$U<5TH~%QlT?;wny4sbj=PCUDhSH7sb%OmrIrg+)>tBvnYkjFTds@?
z;)>#iii#+kg77lGsdqlV_wD|5@45G!=lk5}dG7h%d(U|eF&@XL%iTIQKR>T+G-I%k
zEsQ;=<V$M|A$<p|y`a3YnByJTrh0ckc3M24`((rbdL*7KW>?u__Hajd)av0a*v_^6
z7w=ObLw43zhgK&%u%{gCCk6yN<DEqs&BdJT02%8pPLjMdzSNt1Xnk!bY46^{NO@hj
z!)JQup2;?ncFFC;`|!3ymvZeY5A0V`hkF?@k>hvrAg(QgE-l<9<9BbLtLoJ7UyT53
zgr(RWVZ8E)_tnx!X>19S*8l;rnx>#UpIk-G#;(pYy5peKMy~Q5yC3Gux5aOhd-0~7
z#hi$xEc2)u@o@MA`QGGwXQZ_LK77tG-c))@3J#H*_xQ<g4-544w4FHmw-%S79b1}d
zdYfno&24&{?Dn^AOIXK>ILw_1#dWsfPUSq`o>3WaGgN;%iTnLn$*HmIRq=_Uk*XN7
zxoX)|&K6VGu|I0YYK9E(8kuMB{I=_0{VR^30a8D9<KZjBj7%B3sBF=ZKN!Z;0%Ydn
zj}ELXwE{Q0P2GyTSn~bUQy<>Mczuc}Zvp+b%H%tr0oMV*0^T5A9#G>tw02s&tHjFA
zP{vPpU^P!T#n0qU^p~6MQ<K$=H126OZxDm96L-dv?RMgi%eowST?RCDHp~i~gI&Y$
zOkpce7c<MG*;PSyY4H&qoSSR7Te8Wfwb4;!){ngQJhO&7wN0!Ludurw*Qwi><+3pG
ztDkF}b+B(Ip58C}8M<X>!{o9LDx|RMJhsykwIpG&S0oNSqT$ORsq205%ud?f1M!Aa
z|H<nse%2y2y!$rq6j>bpN&Ne=*g3rz7;%3@5iXk67{5ZwqdSQPJ85Tcr?fs#DaRZ!
z<e~P^Kjau}*|LyuV@3H$%88<PKK-d@D2RYw(+vmdmB>AZ(tnkxE1kZ^)3YXz`5;}S
zdWL|yJ#4W+NP;xvF0MgUb_h*qHRZbg&J$3;r)<82b!pX6<$z-o#Ptsb3$RpDxNxs>
z;T}TtiMtyevGF`+SD;k;P36mb_XKEGU-?`EqFXts@tPh}U9B~lTIZU9KK6@BE3}U)
z@<OTvMq$lmj+g|He{^H9p56j*(Ci1T1xGO@3{rbW)o|=Pk8aIv5pe^Yu=3#}qSeJZ
zF<dsmcz5a~gOhEj&YiG~+F^K=no-;O@>y_~9OP#c(Rcw2^_4$(2^h%Ye=I6mcl?cR
zsj_xy``f;vD|!BU7oT3RQgsR9=4>g;%Mp9=BE*2X@kK%%?yXc$sw^hlldEtOxKwo+
zLJqf$t?1h$b8vE|6t}`)e<!59`_qbg--T=18;)JZ5ngT^83K>YVf72K28Ju6ths)v
z>wrh?8Rz<$wF(A*)CY@oTU^{zahly1eFWWBZ#^~B+1i^)G7cS@YkKau+ORayY{1g!
z;nHpEuJ@1n^gkOfVIRA=6xJcM%ztOL1nis4X18Rop$V8PLz}7CP-~>S$+Y>-_{1NM
zokR`=BBk~!E@KR2Oivs2Nt4;ADf4cs_x)qxNv16+wk?NHlOL{bsqpa39BlchZ*<6m
zAmOf_UorDNd3^8wEH^*M?cajpl5ROj*NVKxVlk<^M|v{hOWn(d+LN+(YF%0tRZ7e9
zS_KWZ3kl&S3EG|J#>LdmHJlmq+<mquOek8Z_yOK`O7WL16sGy7VuC^4K#g$frp@$|
zpX;voy3`}Y#J0DAU8;9Cvsf;Vn8Nz9-Mlm?Z=Uu7E4S8_@#JLN)x&pxx*;|Q3cGtl
zUomo`@=l7m{wNw$c3L%&<#XF717tC%-yuExVDYz_H>L-a0Cb|^MgXDReTJ=?j8k5(
zjZ{3l(`~BvB6rBBIC$ImNYyywDZDK+r-hkeR%B+TZEXmF33PAGUVL~ofroRbp3zSL
z=8tFBywzH3u%64_p>?V9z^}az)5RN2MX{E?2c(nnp&QSa3&WZ;_df;eGM_Z{A86eO
zpxv`OZL4c*aR?8~*cJe)mdhlX?fuzOmI=Hk|Cv7UZ4K$p))&@snHqN<-%Pj=HdxU9
z)O89bPp7&`nQ*+fVlWKX&P8j;8ZwutTtX2B$6LA={Y7N$eWGke003$+?sGYsJIb~Y
zjKXwm)iM^3wk-;TET~vu=0BB<YM@=RD^a|B_?TfXdb&gVa3k0&LsU~$T0-9uC_r=(
z=Kc)JxZMh<15K~>wK9?kv7EZgQ^R8`xmBRargwzRQ4N;ej0L(V*#%7A34m2y)~XQ(
zSE9#a2RqPPb+$*x$WM#KrQy0PJ!uo>{awPXO}?^E=>`o@<Zr#h3>Yx%(zzSs{XBJo
z8mp;5x;j@&*Qc@Wfgd~q(y(y=Ta{xSrAKkRPpu7$=^BSB^R06J9-+hTipfMYjDA{X
zwY!No0ciMLs$)&01gzXdzR~^-2yAPlqkH%Agg_(t5xh-)xwN8VGvF_+1m(ajt>o0Y
zSTVm~%rhy(Y;8GSmOjR-KsXJk4IWdSe*ilpi6nQMjQ|}L>1~kGrF&zwo0sMC(drz3
z<Q?-R41YGH;SQp9`Pa9py2~j3i5xX5O}aaBDOie~3>IToOUIlsqmwygCP70EPbrMp
zG(xamrCLg@!q;NOD^=<;T>0f3OFQ`)nr^~!!jG0fnZ21RU;y{%>ezO!c?!%4!;e3f
zWLL({5Lc`P*0CF+6H;GN$|RAz=~GWgk-KgecP>pIm1Ufep*hQCVLNDXOFq121W=<4
zPm|X0`ysi$c1Hr>!-gH0RiB7MIWdyZ>PchN)ib#*#sXaGsR`E8l_tw_#nKoIhZX%O
z4ng{6j37(J9$1@!td8e4{V*_^KvFW$07BcMd01%-)?L~@vg*<wH`up}>8}xxJlK%T
zg3gs!U%s2qNvu$1MSwsMrmD!C>O8@vwv~#MS<?orLc-yAsyLFDiqC*#tYO3s{)OHD
z{a;ow>vuF2%g;=f$eXE5v2o4cBew?2)35nmA<9-^;*bWed}{fTA`>~Z!`j2Y@j^}~
zZyZR4VR$6KC&QGZdHRMRSY2p}sZTU0%)Y6E4tUV*v+>iNql2vYC-;tWTT!StH!7@$
z>|oZG*abP9I~O_Lf;()uetD~2#5(0g%cYzXzk)m*GuWG!*ojJ?mGDy^m4Z`}3&&`b
zxGIU-HTV5Q#b=+-1`e(cvdOBeT;bJ&9WiGfEQ@sEz;QVS{eAPiRW;1cVq_a{P#<8N
zqk-7CAkd04BDaZ=XaS=Pe1Ax``5v5`$vqk;_x@8?wz4AhX40tDCgb_H!2Z9p?H0o~
zm1C;c(EO@Fwptl@Pjx2ju#Ze=f?b}3!|gCDy!m_pfhm*hm7~tJOGe;!l(nkreWPwf
z>H9`GbuIWoBljIfvPi}b)s)CZgE2z+qHt2AYvZt>g)&x0uDXwI(6Fs}V!Ak|YZpS4
zuXO8<$fOMFaYwoDCD`os$>P6Q>KnHHwoXZJ-FlUi>%Q#X0v{TcZxs+-o@4(l{P+Ct
zdW*#5^rhsGdAU;0>Vc9?-lzYo`j;y|cB_TUt0uv6cm^S!5w!Iia*UK}s@yx}VJL_6
zll9PvhrJAkXQ8rC=#5uX0kc7*7irDip8eKjW@uP%es9}^pD^y1m@=k{+(2v?Ut$~V
z_1?+G#=8|?{LqQcoHXrvgI<`ABU0NcTBn0(Cj#mbA+W1f#0rR$#p_f9u`7TSSH^ai
zyk#HmO710Ph-%uwx&<VTek{cjpVD!5r8Cye30;J8=03H?%>)G(vd{R&#-4y7+@fMQ
z{c%_3-LNN$N}0363U>X6+Kk^#hljzSN(!<{ea1b*Lsx&*gV5XbIv_Q|A&=b@`#C35
zH4$p#Z6JWuL=o&8(`bQlW|^;<SIZyQ&>cds!CoQWrJfO#*ve?~@(T(dW385%7O*hg
z$2E3KF`k}boSD<U2(0NyM@rT`F780BKp&d1Cp$Vyb$ZS@#m)4!ih}+6Vh5Nxy@dmL
zl3fiU^CrC(96wj`gpgk#3>$t3eWTrgl3Wwnj=fs3bo&{PkLh&<H5EX5DHWk|Xi;wK
zY@4`e!16;DGmGtl=wVE|b25rMaDlNE%%LRz`-0=u6@_8VMsQP!9ij+bvyT!;c}2q9
zv>u>N4f0f*W~=fc*Iz`<Q#H87g#o9c=FD4`gJ*{x;G1fft!7QT+NXEoI@d&fNCY&M
znUhIGK!Ny-Tw;L!EYOpjl?HVK#epghKvC1km+(|S!84}Gc<4xf`D=f-d=2)oq}h}r
z(X0k3a7{;0^zke$T9Y%RlATl%j20Aqes%OR7Zk~x&8_u&nV;vYyPC<E^`9yK9=M0m
z0<(B&bP3KRnvM^5^JYnH9<a%^D+s|QG@bWa7Ay;-q>DB21B4VJVGi{dMw=$on0Zaz
zK4RsR#`Lgt$i-(W?uN4k@>q1yPI6S#P*?kG=@MkwXxI&Ne5AXCV$VKYkjJ4^?nc-5
z5#bWL;58Np#FqrTV!&SRArXZsNIJjK6XY@7*Zmfe27Nr@2_AOyie`4Br`WH<X9W4y
zFBIO_x^PFsY|JI@;cQTK<X-}M@obrS$WW*^J&2x7x3hARSX9aS1^jWc0;ac@E37F%
zG*XZ$h}w~vK?Y}0>kZs=Hi_qa3{gTOwAdk~UAq~*zX)lQ_;GIKMg_!zVbl)FrhZyR
z)z|3oil@>r1Blm#_L3z0qd<!2;+!qEN>Cs=XXXjsn8(YaiDgRmguKtZ7Q~JqyOvc`
zJB=!u!~6WyNc`v+cfZ%@n3{RC@QtyXz3z(=+4?2hBedAkh{?53sLjv%yoP+gE601#
z9P<L2+fa-29FSu9p(zw=L)jT-G^}kM!z<9a>eQbeg$ojZr((EuVK##?aU-0H4nGM^
zti|f{og>Y6b?{kqc)Rzc#gY(t&*P;AsSKHp;uxT19X-U-eT2@+*p5cp0^}f2ZCt<=
zTw(JK0}E4Z00y+Qd~onjZ~+Sk#<WczsT!-Gr_R#&`Maa5A!J2pR_X}IJQ99it{YRI
zM$X9xEm$qZUo{ROIFn*d7&pM;T;QELw8FC4p!x0jbN;j57VIEnH~*ho!jK2;)E@PR
za@A7Y@B;Hc7+sup^co6L;2cL+=BN<xsh(tUXCl~UfHz$udf(#N3L%-!B9v*LA2D2L
z`T6;~^CY%a03$+4>_B1)x-$Bb#I7~KA0F%kEnMYae|%n3q)3RLR#X<owvSstrUVl{
zd|-DAiMHwY@Q*s9_Ka9z3y8in_5=KEs(6lW(;YxouA0hSPYbYz^DQ16hcJV4oe3p0
z=f=c&Z^;!x8h#2y^S}}2$x}qyRhxO=diH0;&BwG1IUNO;lm1+&3$|&e;SaT2#j0kC
z5#exvTZcn^bx)NDRjj+YaOAVZFw@P(4+}S*Whe1myb6C&_B&*bo_?_Kv=k&U@6L{U
zZ69aPBiW`DYNB>~5O@}kTx?2_^yOg6V4qt%o~e@PU2H_C;>XOit>&<DSIT?31Q>t5
zzd32TL(Gr#$AmbNQ}cog66w4WNocMp3G$fX3Fn12fNWm~Jccz1q@2&b@8i?ifv@a<
zjO=9hUwgrdB(iYFxHh~gz5iHE3#z}f)e#4t>arq$!e{7%75SiG?b^w6)YL!M{-RcY
z_=vZdh<*Jo+fBCZ9rglLsCy8i51|GQ_Ju+}5WFL1L;RgQq0u3wvtB{*_X1KGZ7cIL
zC|gsl6HbU~#0a`$pADUsqFARVz{#qMGb!vfkqiui=qY@ENzzR^=y(dhCm`ciW&q`v
zD0+;-Ly1sr5Ss=8B1mSynw?fAx-<41&yeHLWpHD^>Ek!gCHUqF(8JZChHDCY#fmWY
z7JkF6CA9l7%vhT9%S_%xgCfJKlT&`j*;vYuey_E>5+H2b0ieVsS=$S&ZPTV~dW{~n
z_}+8qsY@^C+p25Vz5;W9^6E)kV22qy+jujISJ4SP$&Zl|Q_>?#{>gw)6slqAV%R}Y
z1YgGl*xTX92};#R^}BOIUP0;2y>!pY7-nT7zZzX!@RV0zL9EP+)l6-8l+Qtt+Ad(6
ztn%`Y*-)6!Am-~ZAe0e%u@ICxlV%%YLwb&XQM^E8$Pa%fc$rnHg9;T?z97bNWH_W2
zk42};^eKVff?4yH<ld`g8sw0?fX}^Ml*>1~b$K2lo36|4hn;MCrO@0z)JO`S*U=|L
zDZ23b0J5%t*cMxnmUt1SFDL|Ovr$^~`I$FviY8q%2B?{N1JJg>k+cMMceV>0I<mW)
z=zTpeO7NWL{I|G(M$a=9zi>Pe=?;J58xMm8$4z^8YZ~wN<>=I&<-B2|!;j$YF@=%M
zJ$rbj2)CjP#Qo%S;;CA|f76_Qc*^IkNU`qsEyvHRe(S9H?R6Rkpvz~~zQJBH^*%PV
zIE0#BI{lS6{mYTUmDVfz@n;VXexp&~so#>*GyD9r?*1R%rKmotvcaoR>(tIm-ymMl
zzp(&|+mCPhSI$@3_Hmn1xx2;fpR)cRnOm<?{Wliq_3WVS-%vtdCA>IN>FV*lUs^)$
z-k_KrI1Fv6#N8jOx?Xmco;>D}_yy=_jY3KV5L<BOAC0dl&1wt^xvtmu9j@HrPB}d7
zVSc3w93vWFkYQ!#7kUQ#f7ts~ku0V7z@oSRi}#hvw8qfnmD6m0RnYFv)r;*}h?l|#
zz{sySemj|=(AMKh{i%OM89SbYtv%0Fj~*_fZ_cWO%8QQ0-s&did4B(N_3bW_Ftmux
z=>2QeMt;DFfgUUh4K55m45z!M`VDpUdNqE%D?^!zMn#iOQU9R&sJ?+Yd3)`X7xf$?
z;#k_sb=v}$o34;1O2P@ZrYs^S%?<}vtbNtnmNMV)7;NTA>)pHMD@T@WAB`y-%Cw_@
zK^(MUG8rLhLZ_eE*?q!jJ1L}Ed(g|NDVsA>`rgz6O2XR#p&b6wi4P}Ij=vCO7%zXt
z<dwRP>|VjdD@^~NqS5W2y?!XaU)KBw1cr0I?)KjEM3D(x!nZ!lfo?&3t)-aZrSKwk
z&8aWqo$NnC|3unlEg8-Wjd9gA6@jRX+<d?nJ>ygs^G=Fbj#s}NM{f|`J_+1>v-(Ok
zIN)pyxJX#w3u%JvnQ?+`axK-zwZ(F82WlAH{L1Uy4}COn>(zYm#eC&fw^qMbth+QE
z?^C3)jshGYCTOV9E6kEU6PivvO)rjNnG9sl2FJfI;ywIo(DH+~M1zNR!N@^Bg8x^E
z(N(2b4QIS$`-p@e;z}ddYJH6t_O{WT2JGTLw|^~gI`=H*yh-;$7)28>@%2^Z_d_4K
z?#(6pzTw&HRiqCT#@15#>VSIT`_@C#BKL(}_~KHIf5-2p-;b>SMmQn1i#2bx-EH{}
T`uf#6#diLz<1a<0uigG1tpjU>

literal 0
HcmV?d00001

diff --git a/course_files/intro.Rmd b/course_files/intro.Rmd
index 751f1e67b..5536006bb 100644
--- a/course_files/intro.Rmd
+++ b/course_files/intro.Rmd
@@ -26,7 +26,7 @@ opts_chunk$set(fig.align = "center", echo=FALSE)
 * Allows to study new biological questions in which __cell-specific changes in transcriptome are important__, e.g. cell type identification, heterogeneity of cell responses, stochasticity of gene expression, inference of gene regulatory networks across the cells.
 * Datasets range __from $10^2$ to $10^6$ cells__ and increase in size every year
 * Currently there are several different protocols in use, e.g. SMART-seq2 [@Picelli2013-sb], CELL-seq [@Hashimshony2012-kd] and Drop-seq [@Macosko2015-ix]
-* There are also commercial platforms available, including the [Fluidigm C1](https://www.fluidigm.com/products/c1-system), [Wafergen ICELL8](https://www.wafergen.com/products/icell8-single-cell-system) and the [10X Genomics Chromium](https://www.10xgenomics.com/single-cell/)
+* There are also commercial platforms available, including the [Fluidigm C1](https://www.fluidigm.com/products/c1-system), [Wafergen ICELL8](https://www.wafergen.com/products/icell8-single-cell-system), the [10X Genomics Chromium](https://www.10xgenomics.com/single-cell/) and even a platform developed in Cambridgeshire: [Nadia from Dolomite Bio](https://www.dolomite-bio.com/product/nadia-instrument).
 * Several computational analysis methods from bulk RNA-seq __can__ be used
 * __In most cases__ computational analysis requires adaptation of the existing methods or development of new ones
 
@@ -56,6 +56,7 @@ Today, there are also several different platforms available for carrying out one
 * [Seurat](http://satijalab.org/seurat/) is an R package designed for QC, analysis, and exploration of single cell RNA-seq data.
 * [ASAP](https://asap.epfl.ch/) (Automated Single-cell Analysis Pipeline) is an interactive web-based platform for single-cell analysis.
 * [Bioconductor](https://master.bioconductor.org/packages/release/workflows/html/simpleSingleCell.html) is a open-source, open-development software project for the analysis of high-throughput genomics data, including packages for the analysis of single-cell data.
+* [dropSeqPipe](https://github.com/Hoohm/dropSeqPipe) is dropSeq pre-processing pipeline based on the popular [snakmake](https://snakemake.readthedocs.io/en/stable/) framework combining some of the above software (co-developed by Sebastian Mueller, one of the instructors).
 
 
 ## Challenges
diff --git a/course_files/umis.Rmd b/course_files/umis.Rmd
index 537068bab..82ca0f96b 100644
--- a/course_files/umis.Rmd
+++ b/course_files/umis.Rmd
@@ -38,6 +38,9 @@ After processing the reads from a UMI experiment, the following conventions are
 knitr::include_graphics("figures/UMI-Seq-reads.png")
 ```
 
+```{r intro-umi-fastqc-adapter, out.width = '90%', fig.cap="FastQC adapter content plot of too long Read 1 for a DropSeq sample. Barcode (12bp) and UMI (8bp) make up first 20 bp, the remaining sequence is ininformative poly-T."}
+knitr::include_graphics("figures/barcode_UMI_read1_adapter_fastqc.png")
+```
 ### Counting Barcodes
 
 In theory, every unique UMI-transcript pair should represent all reads originating from a single RNA molecule. However, in practice this is frequently not the case and the most common reasons are:

From c1d4028c6a4fa9d9593a75e56102a6ccbde74c52 Mon Sep 17 00:00:00 2001
From: Sebastian Mueller <sebm@posteo.de>
Date: Tue, 17 Dec 2019 10:50:17 +0000
Subject: [PATCH 2/7] Minor fix clustering: code and reference

---
 course_files/clustering.Rmd | 4 ++--
 1 file changed, 2 insertions(+), 2 deletions(-)

diff --git a/course_files/clustering.Rmd b/course_files/clustering.Rmd
index 8f6d05339..ad1f73dca 100644
--- a/course_files/clustering.Rmd
+++ b/course_files/clustering.Rmd
@@ -60,7 +60,7 @@ Now we are ready to run `SC3` (we also ask it to calculate biological properties
 deng <- sc3(deng, ks = 10, biology = TRUE, n_cores = 1)
 ```
 
-`SC3` result consists of several different outputs (please look in [@Kiselev2016-bq] and [SC3 vignette](http://bioconductor.org/packages/release/bioc/vignettes/SC3/inst/doc/my-vignette.html) for more details). Here we show some of them:
+`SC3` result consists of several different outputs (please look in [@Kiselev2016-bq] and [SC3 vignette](https://bioconductor.org/packages/release/bioc/vignettes/SC3/inst/doc/SC3.html) for more details). Here we show some of them:
 
 Consensus matrix:
 ```{r, fig.height=6}
@@ -123,7 +123,7 @@ Now we are going to apply _k_-means clustering algorithm to the cloud of points
 
 We will start with $k=8$:
 ```{r clust-tsne-kmeans2, fig.cap = "tSNE map of the patient data with 8 colored clusters, identified by the k-means clustering algorithm"}
-colData(deng)$tSNE_kmeans <- as.character(kmeans(deng@reducedDims$TSNE, centers = 8)$clust)
+colData(deng)$tSNE_kmeans <- as.character(kmeans(reducedDim(deng)$TSNE, centers = 8)$clust)
 plotTSNE(deng, colour_by = "tSNE_kmeans")
 ```
 

From c6d20099177e7e62a94a6c567f376c6ff3fa782e Mon Sep 17 00:00:00 2001
From: Sebastian Mueller <sebm@posteo.de>
Date: Tue, 17 Dec 2019 11:24:21 +0000
Subject: [PATCH 3/7] Fixing some bugs in exprs-qc*.Rmd

---
 course_files/exprs-qc-reads.Rmd | 13 +++++++++----
 course_files/exprs-qc.Rmd       | 13 +++++++++----
 2 files changed, 18 insertions(+), 8 deletions(-)

diff --git a/course_files/exprs-qc-reads.Rmd b/course_files/exprs-qc-reads.Rmd
index 774657249..ba9e93207 100644
--- a/course_files/exprs-qc-reads.Rmd
+++ b/course_files/exprs-qc-reads.Rmd
@@ -38,13 +38,18 @@ reads <- reads[keep_feature, ]
 ```
 
 ```{r}
-isSpike(reads, "ERCC") <- grepl("^ERCC-", rownames(reads))
-isSpike(reads, "MT") <- rownames(reads) %in% 
-    c("ENSG00000198899", "ENSG00000198727", "ENSG00000198888",
+is.spike=grepl("^ERCC-", rownames(reads))
+reads  <- splitAltExps(reads, ifelse(is.spike, "ERCC", "gene"))
+altExpNames(reads)
+
+is.mt <- rownames(reads) %in%        
+  c("ENSG00000198899", "ENSG00000198727", "ENSG00000198888",
     "ENSG00000198886", "ENSG00000212907", "ENSG00000198786",
     "ENSG00000198695", "ENSG00000198712", "ENSG00000198804",
     "ENSG00000198763", "ENSG00000228253", "ENSG00000198938",
     "ENSG00000198840")
+reads <-  splitAltExps(reads, ifelse(is.mt, "MT", "gene"))
+altExpNames(reads)
 ```
 
 ```{r}
@@ -148,7 +153,7 @@ table(reads$outlier)
 ```{r}
 plotReducedDim(
     reads,
-    use_dimred = "PCA_coldata",
+    use_dimred = "PCA",
     size_by = "total_features_by_counts", 
     shape_by = "use", 
     colour_by = "outlier"
diff --git a/course_files/exprs-qc.Rmd b/course_files/exprs-qc.Rmd
index 8dfcc09e4..a38b0a3c5 100644
--- a/course_files/exprs-qc.Rmd
+++ b/course_files/exprs-qc.Rmd
@@ -64,13 +64,18 @@ umi <- umi[keep_feature, ]
 
 Define control features (genes) - ERCC spike-ins and mitochondrial genes ([provided](http://jdblischak.github.io/singleCellSeq/analysis/qc-filter-ipsc.html) by the authors):
 ```{r}
-isSpike(umi, "ERCC") <- grepl("^ERCC-", rownames(umi))
-isSpike(umi, "MT") <- rownames(umi) %in% 
-    c("ENSG00000198899", "ENSG00000198727", "ENSG00000198888",
+is.spike <- grepl("^ERCC-", rownames(umi))
+umi  <- splitAltExps(umi, ifelse(is.spike, "ERCC", "gene"))
+altExpNames(umi)
+
+is.mt <- rownames(umi) %in%        
+  c("ENSG00000198899", "ENSG00000198727", "ENSG00000198888",
     "ENSG00000198886", "ENSG00000212907", "ENSG00000198786",
     "ENSG00000198695", "ENSG00000198712", "ENSG00000198804",
     "ENSG00000198763", "ENSG00000228253", "ENSG00000198938",
     "ENSG00000198840")
+umi <-  splitAltExps(umi, ifelse(is.mt, "MT", "gene"))
+altExpNames(umi)
 ```
 
 Calculate the quality metrics:
@@ -253,7 +258,7 @@ Then, we can use a PCA plot to see a 2D representation of the cells ordered by t
 ```{r}
 plotReducedDim(
     umi,
-    use_dimred = "PCA_coldata",
+    use_dimred = "PCA",
     size_by = "total_features_by_counts", 
     shape_by = "use", 
     colour_by = "outlier"

From 1ddc26694490ed88c9f8204a0b60ed0625cf0610 Mon Sep 17 00:00:00 2001
From: Sebastian Mueller <sebm@posteo.de>
Date: Tue, 17 Dec 2019 11:33:46 +0000
Subject: [PATCH 4/7] minor fix in exprs-norm*.Rmd

---
 course_files/exprs-norm-reads.Rmd | 4 ++--
 course_files/exprs-norm.Rmd       | 4 ++--
 2 files changed, 4 insertions(+), 4 deletions(-)

diff --git a/course_files/exprs-norm-reads.Rmd b/course_files/exprs-norm-reads.Rmd
index 085566999..c1b021826 100644
--- a/course_files/exprs-norm-reads.Rmd
+++ b/course_files/exprs-norm-reads.Rmd
@@ -31,7 +31,7 @@ plotPCA(
 ```
 
 ```{r norm-pca-cpm-reads, fig.cap = "PCA plot of the tung data after CPM normalisation"}
-logcounts(reads.qc) <- log2(calculateCPM(reads.qc, use_size_factors = FALSE) + 1)
+logcounts(reads.qc) <- log2(calculateCPM(reads.qc, use_size_factors = NULL) + 1)
 plotPCA(
     reads.qc[endog_genes, ],
     colour_by = "batch",
@@ -55,7 +55,7 @@ plotRLE(
 ```{r norm-pca-lsf-umi, fig.cap = "PCA plot of the tung data after LSF normalisation"}
 qclust <- quickCluster(reads.qc, min.size = 30)
 reads.qc <- computeSumFactors(reads.qc, sizes = 15, clusters = qclust)
-reads.qc <- normalize(reads.qc)
+reads.qc <- logNormCounts(reads.qc)
 plotPCA(
     reads.qc[endog_genes, ],
     colour_by = "batch",
diff --git a/course_files/exprs-norm.Rmd b/course_files/exprs-norm.Rmd
index db2dde91c..02852bb04 100644
--- a/course_files/exprs-norm.Rmd
+++ b/course_files/exprs-norm.Rmd
@@ -131,7 +131,7 @@ plotPCA(
 
 ### CPM
 ```{r norm-pca-cpm, fig.cap = "PCA plot of the tung data after CPM normalisation"}
-logcounts(umi.qc) <- log2(calculateCPM(umi.qc, use_size_factors = FALSE) + 1)
+logcounts(umi.qc) <- log2(calculateCPM(umi.qc, use_size_factors = NULL) + 1)
 plotPCA(
     umi.qc[endog_genes, ],
     colour_by = "batch",
@@ -156,7 +156,7 @@ plotRLE(
 ```{r norm-pca-lsf, fig.cap = "PCA plot of the tung data after LSF normalisation"}
 qclust <- quickCluster(umi.qc, min.size = 30)
 umi.qc <- computeSumFactors(umi.qc, sizes = 15, clusters = qclust)
-umi.qc <- normalize(umi.qc)
+umi.qc <- logNormCounts(umi.qc)
 plotPCA(
     umi.qc[endog_genes, ],
     colour_by = "batch",

From 3de13a8485738f9cb7854bd55b13668f803c55bb Mon Sep 17 00:00:00 2001
From: Sebastian Mueller <sebm@posteo.de>
Date: Tue, 17 Dec 2019 11:47:37 +0000
Subject: [PATCH 5/7] minor fix in clustering.Rmd

---
 course_files/clustering.Rmd | 2 +-
 1 file changed, 1 insertion(+), 1 deletion(-)

diff --git a/course_files/clustering.Rmd b/course_files/clustering.Rmd
index ad1f73dca..d0c0cff2d 100644
--- a/course_files/clustering.Rmd
+++ b/course_files/clustering.Rmd
@@ -123,7 +123,7 @@ Now we are going to apply _k_-means clustering algorithm to the cloud of points
 
 We will start with $k=8$:
 ```{r clust-tsne-kmeans2, fig.cap = "tSNE map of the patient data with 8 colored clusters, identified by the k-means clustering algorithm"}
-colData(deng)$tSNE_kmeans <- as.character(kmeans(reducedDim(deng)$TSNE, centers = 8)$clust)
+colData(deng)$tSNE_kmeans <- as.character(kmeans(reducedDim(deng), centers = 8)$clust)
 plotTSNE(deng, colour_by = "tSNE_kmeans")
 ```
 

From be2dad230b6d93b93225bd5f0e0df5559ada10ef Mon Sep 17 00:00:00 2001
From: Sebastian Mueller <sebm@posteo.de>
Date: Tue, 17 Dec 2019 11:49:41 +0000
Subject: [PATCH 6/7] minor fix in dropouts.Rmd

---
 course_files/dropouts.Rmd | 4 ++--
 1 file changed, 2 insertions(+), 2 deletions(-)

diff --git a/course_files/dropouts.Rmd b/course_files/dropouts.Rmd
index 98ed7ddf3..376323636 100644
--- a/course_files/dropouts.Rmd
+++ b/course_files/dropouts.Rmd
@@ -61,7 +61,7 @@ expression matrix. This can be extracted from our SingleCellExperiment object us
 command below. 
 
 ```{r}
-expr_matrix <- M3Drop::M3DropConvertData(deng)
+expr_matrix <- M3Drop::M3DropConvertData(counts(deng))
 ```
 
 This function is compatible with most single-cell RNA-seq analysis packages including:
@@ -272,7 +272,7 @@ far too many genes will be called as significant. Thus we will take the top 1500
 by effect size.
 
 ```{r, fig.width=8, fig.height=5}
-deng_int <- NBumiConvertData(deng)
+deng_int <- NBumiConvertData(counts(deng))
 DANB_fit <- NBumiFitModel(deng_int) # DANB is fit to the raw count matrix
 # Perform DANB feature selection
 DropFS <- NBumiFeatureSelectionCombinedDrop(DANB_fit, method="fdr", qval.thresh=0.01, suppress.plot=FALSE)

From a67c6671869eb3b0030082443ec44f04df243ac7 Mon Sep 17 00:00:00 2001
From: Sebastian Mueller <sebm@posteo.de>
Date: Tue, 17 Dec 2019 11:52:11 +0000
Subject: [PATCH 7/7] minor fix in imputation.Rmd

---
 course_files/imputation.Rmd | 2 +-
 1 file changed, 1 insertion(+), 1 deletion(-)

diff --git a/course_files/imputation.Rmd b/course_files/imputation.Rmd
index 50a3ee650..3415b27a0 100644
--- a/course_files/imputation.Rmd
+++ b/course_files/imputation.Rmd
@@ -142,7 +142,7 @@ enhances trajectory-like structure in a dataset, in contrast to scImpute and
 DrImpute which assume a cluster-like structure to the underlying data.
 
 ```{r, eval=FALSE}
-res <- magic(t(deng@assays[["logcounts"]]), genes="all_genes", k=10, t="auto")
+res <- magic(t(deng@assays@data$logcounts), genes="all_genes", k=10, t="auto")
 ```
 
 ```{r, eval=FALSE}