Rimonabant (SR141716)

Name: Rimonabant (SR141716)
Brand: Selleck Chemicals
SKU: S3021
Rating: 5 (4 reviews)

For research use only.

Catalog No.S3021

4 publications

Rimonabant (SR141716) Chemical Structure

CAS No. 168273-06-1

Rimonabant (SR141716) is a selective antagonist of CB1 with IC50 of 13.6 nM and EC50 of 17.3 nM in hCB1 transfected HEK 293 membrane. Rimonabant is also a dual inhibitor of acyl CoA:cholesterol acyltransferases(ACAT) 1 and 2 and inhibits mycobacterial MmpL3.

Selleck's Rimonabant (SR141716) has been cited by 4 publications

Nat Commun, 2020, 11(1):5962

PubMed: 33235205 ( click the link to review the publication )

Sci Rep, 2020, 10(1):15556

PubMed: 32968163 ( click the link to review the publication )

Microbiol Immunol, 2020, 10.1111/1348-0421.12777

PubMed: 31981244 ( click the link to review the publication )

Toxicology, 2018, 394:19-26

PubMed: 29191629 ( click the link to review the publication )

Purity & Quality Control

Choose Selective Cannabinoid Receptor Inhibitors

Biological Activity

Description

Features

Efficacious to induce weight reduction and improvements in cardiometabolic risk factors, however was withdrawn in 2009 due to severe depressive disorder and anxiety.

Targets

ACAT1 ^[2] ()	ACAT2 ^[2] ()	MmpL3 ^[7] ()	hCB1 ^[1] (Cell-free assay)	hCB2 ^[1] (Cell-free assay)
			13.6 nM	1.64 μM

In vitro

Rimonabant dose-dependently reduces ACAT activity in Raw264.7macrophages with IC50 of 2.9 μM and isolated peritoneal macrophages. Rimonabant inhibits ACATactivity in intact CHO-ACAT1 and CHO-ACAT2 cells and in cell-free assays with approximately equal efficiency with IC50 of 1.5 μM and 2.2 μM for CHO-ACAT1 and CHO-ACAT2, respectively. Consistent with ACAT inhibition, Rimonabant treatment blocks ACAT dependent processes in macrophages, oxysterol-induced apoptosis and acetylated-LDL induced foam cell formation. ^[2] Rimonabant antagonizes the inhibitory effects of cannabinoid receptor agonists on both mouse vas deferens contractions and adenylyl cyclase activity in rat brain membranes in a concentration-dependent manner. ^[3] Rimonabant significantly reduces cell growth and induces cell death of human colorectal cancer cells (DLD-1, CaCo-2 and SW620). Rimonabant is able to alter cell cycle distribution in all the cell lines tested. Particularly, Rimonabant produces a G2/M cell cycle arrest in DLD-1 cells without inducing apoptosis or necrosis. ^[4]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Activity Description	PMID
CHO cells	MYHGeY5kfGmxbjDhd5NigQ>?			NYTxcHhQSWKrbHn0fUB1dyCmaYPwcIFk\SCdM1jdMXNTNSBzNEG3NVZCKGKrbnTpcochfG9iaIXtZY4hS0JzIILlZ4VxfG:{IHX4dJJme3OnZDDpckBEUE9iY3XscEBu\W2kcnHu[ZMtKEurPUiuPUBvVQ>?	Mk[0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTB2NkW1OVIoRjFyNE[1OVUzRC:jPh?=
CHO	M4PMUWZ2dmO2aX;uJIF{e2G7			NYHkfVc2SW62YXfvcol{fGmlIHHjeIl3cXS7IITve4Fz\HNiY3HucoFjcW6xaXSgdoVk\XC2b4KgNUBmgHC{ZYPz[YQh[XNiW{PIYWFz[WOqaXTvcolkKGGlaXSgdoVt\WG\|ZTDpckBEUE9iY3XscJMtKEumPUCuNFAzPTF{zszN	MV68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPDd\|NkK0N{c,OTR5M{[yOFM9N2F-
CHO	NEWxS29HfW6ldHnvckBie3OjeR?=			MlTvSIl{eGyjY3Xt[Y51KG:oIFPQMVU2QTRyIHLpcoRqdmdiZoLvcUBz\WOxbXLpcoFvfCCqdX3hckBk[W6wYXLpco9q\CC{ZXPldJRweiBzIHX4dJJme3OnZDDpckBEUE9iY3XscJMtKEurPUCuNFI2\|ryP	MWS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPDd\|NkK0N{c,OTR5M{[yOFM9N2F-
CHO	Mn7kSpVv[3Srb36gZZN{[Xl?			NGqzW\|ZC\m[rbnn0fUB1dyCmaYPwcIFk\SCFUD21OVk1OCCkaX7kbY5oKG[{b32gR4FvdmGkaX7vbYQhemWlZYD0c5IhOiCxZjDoeY1idiCneIDy[ZN{\WRiaX6gR2hQKGOnbHzzMEBMcT1zLkW4{txO	NImxXpk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zNEezOlI1Oyd-MUS3N\|YzPDN:L3G+
CHO	MnnnSpVv[3Srb36gZZN{[Xl?			NV3hUWQ1UW6qaXLpeI9zgSClb37j[Y51emG2aX;uJIFo[Wmwc4SgbJVu[W5icnXjc41jcW6jboSgZ4FvdmGkaX7vbYQhemWlZYD0c5IhfHmyZTCxJIV5eHKnc4Pl[EBqdiCFaHnu[ZNmKEijbYP0[ZIhV3[jcomgLGNJVyliY3XscJMtKEmFNUC9NE4xODcQvF2=	NHzWSoc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zNUexN\|QxOyd-MUW3NVM1ODN:L3G+
CHO	NE\wT3VHfW6ldHnvckBie3OjeR?=			NVi1NWh4UW5idnn0do8h[2GwbnHibY5wcWRicnXj[ZB1d3JiMTDhcpRi\2:waYPtJI9nKFt\|SG3hdoFkcGmmb37pZ{Bi[2mmIILlcIVie2ViYomgR2hQKGOnbHzzMEBM\D1yLkCwNlUyOs7:TR?=	NWrpRmFkRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUW3O\|E1OjhpPkG1O\|cyPDJ6PD;hQi=>
CHO	NFfCe\|RHfW6ldHnvckBie3OjeR?=			MUDJckB3cXS{bzDkbZNxdGGlZX3lcpQhd2ZiQ2CtOVU6PDBiYnnu[Ilv\yC2bzDoeY1idiCFQkGgdoVk\XC2b4Kg[ZhxemW\|c3XkJIlvKEOKTzDj[YxteyxiS3m9NE4xOjYQvF2=	M3O4bFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF3N{exOFI5Lz5zNUe3NVQzQDxxYU6=
CHO	NH\1fXZHfW6ldHnvckBie3OjeR?=			NHy4TZhKdiC4aYTyc{BlcXOybHHj[Y1mdnRib3[gR3AuPTV7NECgZolv\GmwZzD0c{BpfW2jbjDDRlIhemWlZYD0c5Ih\XiycnXzd4VlKGmwIFPIU{Bk\WyuczygT4k:OS53ON88US=>	NE\ITmE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zNUe3NVQzQCd-MUW3O\|E1Ojh:L3G+
CHO	M3rkd2Z2dmO2aX;uJIF{e2G7			MXjJcohq[mm2aX;uJI9nKFt\|SG3TVk0yPDFuN{G2RUBjcW6maX7nJJRwKGi3bXHuJGNDOSC{ZXPldJRweiCneIDy[ZN{\WRiaX6gR2hQKGOnbHzzMEBMcT1yLkCwOVTPxE1?	NWn2bWZyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUW4NFE5PDBpPkG1PFAyQDRyPD;hQi=>
CHO	MlzJSpVv[3Srb36gZZN{[Xl?			MnyyRY51[WexbnnzeIlkKGGldHn2bZR6KGGpYXnud5Qh[2GwbnHibY5wcWRicnXj[ZB1d3JiMTDt[YF{fXKnZDDifUBEWC13NUm0NEBqdmS3Y3XkJIFz[WOqbn;p[EBi[2mmIILlcIVie2ViaX6gR2hQKGOnbHzzMEBM\D1yLkCwNlUyOs7:TR?=	M3PCRVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF4MUSwNFExLz5zNkG0NFAyODxxYU6=
CHO	NGHPSI5HfW6ldHnvckBie3OjeR?=			NXTLTZdZTGm\|cHzhZ4Vu\W62IH;mJJNx\WOrZnnjJGNRNTV3OUSwJIJqdmSrbnegbY4hS0iRIHPlcIx{KHO2YXLsfUB1emGwc3\lZ5Rm\CC5aYToJIh2dWGwIHPhco5i[mmwb3nkJJJm[2WydH;yJFEtKEurPUCuNFI2\|ryP	Ml\vQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTZzNECwNVAoRjF4MUSwNFExRC:jPh?=
CHO	MVvGeY5kfGmxbjDhd5NigQ>?			NILTOHZFcXOybHHj[Y1mdnRib3[gd5Bm[2moaXOgR3AuPTV7NECgZolv\GmwZzDpckBEUE9iY3XscJMhe3SjYnz5JJRz[W6\|ZnXjeIVlKHerdHigbJVu[W5iY3HucoFjcW6xaXSgdoVk\XC2b4KgNkwhU2l;MT61PO69VQ>?	MnnRQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTZzNECwNVAoRjF4MUSwNFExRC:jPh?=
CHOK1	NUO5NpZ3TnWwY4Tpc44h[XO\|YYm=			MljsSpVv[3Srb37hcEBi[3Srdnn0fUBifCCqdX3hckBESjFicnXj[ZB1d3JidILhcpNn\WO2ZXSgbY4hS0iRS{GgZ4VtdHNiYomgX\|M2W0eWUG3nZY1u[VNiYYPzZZktKEurPUCuNFAy\|ryP	NVLKc4pWRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMU[yOlMzQDNpPkG2NlY{Ojh\|PD;hQi=>
HEK293	NGDUd3NHfW6ldHnvckBie3OjeR?=			MV\EbZNxdGGlZX3lcpQhd2ZiW{PIYXNTNTF2MUexOkBnem:vIHj1cYFvKEOEMTDy[YNmeHSxcjD0doFve2[nY4Tl[EBqdiCKRVuyPVMh[2WubIOsJGtqRTBwMECyNe69VQ>?	M3L3eVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF4Mk[zNlg{Lz5zNkK2N\|I5OzxxYU6=
CHO	M1;LZ2Z2dmO2aX;uJIF{e2G7			NIf2UFhFcXOybHHj[Y1mdnRib3[gX\|NJZVOUMUSxO\|E3SSCocn;tJIh2dWGwIFPCNUBz\WOncITvdkBmgHC{ZYPz[YQhcW5iQ1jPJINmdGy\|LDDLbV0xNjByNUVOwG0>	NX;OWG1qRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMU[yO\|k5ODlpPkG2Nlc6QDB7PD;hQi=>
HEK293	NIP6R2xHfW6ldHnvckBie3OjeR?=			M4T2PGRqe3CuYXPlcYVvfCCxZjDbN2heW1JvMUSxO\|E3KG[{b32gbJVu[W5iQ1KxJJJm[2WydH;yJIV5eHKnc4Pl[EBqdiCKRVuyPVMh[2WubIOsJGtlRTBwMECxPO69VQ>?	NFfRXmo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zN{CwOFcyOid-MUewNFQ4OTJ:L3G+
HEK293	NYrxe\|B6TnWwY4Tpc44h[XO\|YYm=			MYfEbZNxdGGlZX3lcpQhd2ZiW{PIYWNRNTV3OUSwJIZzd21iaIXtZY4hS0JzIILlZ4VxfG:{IHX4dJJme3OnZDDpckBJTUt{OUOgZ4VtdHNuIFvpQVAvODB5Md88US=>	MXq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPzByNEexNkc,OTdyMES3NVI9N2F-
HEK293	MkixSpVv[3Srb36gZZN{[Xl?			MlS4SIl{eGyjY3Xt[Y51KG:oIGuzTH1YUU5vNUWyNVIuOiCocn;tJIh2dWGwIFPCNUBz\WOncITvdkBmgHC{ZYPz[YQhcW5iSFXLNlk{KGOnbHzzMEBMcT1yLkCxPO69VQ>?	NIP1foY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zN{CwOFcyOid-MUewNFQ4OTJ:L3G+
CHO	MUnGeY5kfGmxbjDhd5NigQ>?			NYDYOphLUW6qaXLpeIlwdiCxZjDbN2heS1BvNUW5OFAh[mmwZHnu[{B1dyCqdX3hckBz\WOxbXLpcoFvfCCFQkGgdoVk\XC2b4KgbY4hS0iRIHPlcIx{NCCLQ{WwQVAvODB4Md88US=>	NVrPRnBKRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUexPFEyOzhpPkG3NVgyOTN6PD;hQi=>
CHO	MXzGeY5kfGmxbjDhd5NigQ>?			NXjE[2ZHUW6qaXLpeIlwdiCxZjDbN2heS1BvNUW5OFAh[mmwZHnu[{B1dyCqdX3hckBz\WOxbXLpcoFvfCCFQkKgdoVk\XC2b4KgbY4hS0iRIHPlcIx{NCCLQ{WwQVAvPs7:TR?=	MkDGQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTdzOEGxN\|goRjF5MUixNVM5RC:jPh?=
CHO	NGfyfo1HfW6ldHnvckBie3OjeR?=			MlXFSIl{eGyjY3Xt[Y51KG:oIGuzTH1EWC13NUm0NEBnem:vIHj1cYFvKHKnY3;tZolv[W62IFPCNUBz\WOncITvdkBmgHC{ZYPz[YQhcW5iQ1jPJINmdGy\|LDDJR\|UxRTBwMEC2Ne69VQ>?	MUC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPzJ7M{GwPUc,OTd{OUOxNFk9N2F-
CHO	MVzGeY5kfGmxbjDhd5NigQ>?			Ml24SIl{eGyjY3Xt[Y51KG:oIGuzTH1EWC13NUm0NEBnem:vIHj1cYFvKHKnY3;tZolv[W62IFPCNkBz\WOncITvdkBmgHC{ZYPz[YQhcW5iQ1jPJINmdGy\|LDDJR\|UxRTBwNkCzN:69VQ>?	M4Xxc\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF5MkmzNVA6Lz5zN{K5N\|ExQTxxYU6=
HEK293	NUPXR\|hFTnWwY4Tpc44h[XO\|YYm=			M{fXemRqe3CuYXPlcYVvfCCxZjDbN2heS1BvNUW5OFQxKG[{b32gbJVu[W5iQ1KxJJJm[2WydH;yJIV5eHKnc4Pl[EBqdiCKRVuyPVMh[2WubIOsJGtqRTBwMECxNe69VQ>?	M{LtXFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF5M{izNVgxLz5zN{O4N\|E5ODxxYU6=
HEK293	NHi3NpZHfW6ldHnvckBie3OjeR?=			NG\MPYFFcXOybHHj[Y1mdnRib3[gX\|NJZUOSLUW1PVQxKG[{b32gbJVu[W5icnXjc41jcW6jboSgR2IyKHKnY3XweI9zKGW6cILld5Nm\CCrbjDISWszQTNiY3XscJMtKEurPUCuNFE3\|ryP	NFXyeWg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zN{m0NlMxPyd-MUe5OFI{ODd:L3G+
HEK293	MWfGeY5kfGmxbjDhd5NigQ>?			MX;EbZNxdGGlZX3lcpQhd2ZiW{PIYWNRNTV3OUSwJIZzd21iaIXtZY4hemWlb33ibY5idnRiQ1KyJJJm[2WydH;yJIV5eHKnc4Pl[EBqdiCKRVuyPVMh[2WubIOsJGtqRTFwNkVOwG0>	MoXGQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTd7NEKzNFcoRjF5OUSyN\|A4RC:jPh?=
HEK293	NUPFSIlWTnWwY4Tpc44h[XO\|YYm=			Ml\OSIl{eGyjY3Xt[Y51KG:oIGuzTH1EWC13NUm0NEBnem:vIHj1cYFvKHKnY3;tZolv[W62IFPCNUBz\WOncITvdkBmgHC{ZYPz[YQhcW5iSFXLNlk{KGOnbHzzMEBMcT1yLkC0O:69VQ>?	NYC5TJpURGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUe5O\|kzPjFpPkG3PVc6OjZzPD;hQi=>
CHOK1	MUfGeY5kfGmxbjDhd5NigQ>?			MYnEbZNxdGGlZX3lcpQhd2ZiW{PIYXdKVi13NUKxNlIh\nKxbTDoeY1idiC{ZXPvcYJqdmGwdDDDRlIhemWlZYD0c5Ih\XiycnXzd4VlKGmwIFPIU2syKGOnbHzzMEBMcT1zLkm5{txO	NGS1SGo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zN{m3PVI3OSd-MUe5O\|kzPjF:L3G+
HEK293	M2\N[WZ2dmO2aX;uJIF{e2G7			Mo\5SIl{eGyjY3Xt[Y51KG:oIILh[IlwdGmpYX7kJIZzd21iaIXtZY4hS0JzIILlZ4VxfG:{IHX4dJJme3OnZDDpckBJTUt{OUOgZ4VtdHNuIFvpQVAvODBzON88US=>	MVq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDB6M{W2NEc,OThyOEO1OlA9N2F-
HEK293 EBNA	M2DydmZ2dmO2aX;uJIF{e2G7			MVzJcpZmenOnIHHnc45qe3RiYXP0bZZqfHliYYSgbJVu[W5iQ1KxJJJm[2WydH;yJIV5eHKnc4Pl[EBqdiCKRVuyPVMhTUKQQTDj[YxteyCkeTDbN\|VUZUeWUHfhcY1iWyCrbnPvdpBwemG2aX;uJIF{e2G7LDDFR\|UxRTBwMEC0{txO	MXO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDB6M{W2NEc,OThyOEO1OlA9N2F-
HEK293	MXzGeY5kfGmxbjDhd5NigQ>?			NH\kS5VFcXOybHHj[Y1mdnRib3[gdoFlcW:uaXfhcoQh\nKxbTDoeY1idiCFQkKgdoVk\XC2b4Kg[ZhxemW\|c3XkJIlvKEiHS{K5N{Bk\WyuczygT4k:OC53NUVOwG0>	Mn;QQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOThyOEO1OlAoRjF6MEizOVYxRC:jPh?=
CHOK1	MljuSpVv[3Srb36gZZN{[Xl?			Mn;lRY51[WexbnnzeEBi[3Srdnn0fUBifCCqdX3hckBESjFicnXj[ZB1d3JiZYjwdoV{e2WmIHnuJGNJV0tzIHPlcIx{KGK7IHz1Z4ln\XKjc3WgZZN{[XluIFnDOVA:OC5zMt88US=>	M3PEUVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6MkSzO\|EyLz5zOEK0N\|cyOTxxYU6=
CHOK1	M3LIfGZ2dmO2aX;uJIF{e2G7			M{KwXmRqe3CuYXPlcYVvfCCxZjDbN2heX0mQLUW1NlEzNTJiZoLvcUBpfW2jbjDDRlIhemWlZYD0c5Ih\XiycnXzd4VlKGmwIFPIU2syKGOnbHzzMEBKSzVyPUGuO\|bPxE1?	MVu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDJ2M{exNUc,OTh{NEO3NVE9N2F-
HEK	M4DuS2Z2dmO2aX;uJIF{e2G7			NFjBW3dFcXOybHHj[Y1mdnRib3[gX\|NJZUOSLUW1PVQxKG[{b32gbJVu[W5icnXjc41jcW6jboSgR2IyKHKnY3XweI9zKGW6cILld5Nm\CCrbjDISWsh[2WubIOsJGtqRTBwMEGy{txO	MXe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDJ7M{mwPEc,OTh{OUO5NFg9N2F-
HEK	M1\hRWZ2dmO2aX;uJIF{e2G7			NGT3NZpFcXOybHHj[Y1mdnRib3[gX\|NJZUOSLUW1PVQxKG[{b32gbJVu[W5icnXjc41jcW6jboSgR2IzKHKnY3XweI9zKGW6cILld5Nm\CCrbjDISWsh[2WubIOsJGtqRTBwN{pOwG0>	MnP6QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTh{OUO5NFgoRjF6MkmzPVA5RC:jPh?=
HEK293	NEjYdIpHfW6ldHnvckBie3OjeR?=			NVPWU3FUTGm\|cHzhZ4Vu\W62IH;mJHs{UF2FUD21OVk1OCCocn;tJIh2dWGwIFPCNXIh\XiycnXzd4VlKGmwIFjFT\|I6OyClZXzsd{whU2l;MD6wNFbPxE1?	NInKOmM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOEOzOVk4Pid-MUizN\|U6PzZ:L3G+
CHO	M1XJbWZ2dmO2aX;uJIF{e2G7			MVrEbZNxdGGlZX3lcpQhd2ZiW{PIYXdKVi13NUKxNk0zKG[{b32gbJVu[W5iY3HucoFjcW6xaXSgR2IzKHKnY3XweI9zKGW6cILld5Nm\CCrbjDDTG8h[2WubIOsJGlEPTB;MT63Ou69VQ>?	MnO1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTh\|M{ewPVYoRjF6M{O3NFk3RC:jPh?=
CHO	NWXpdXY3TnWwY4Tpc44h[XO\|YYm=			MnTNSIl{eGyjY3Xt[Y51KG:oIGuzTH1EWC13NUm0NEBnem:vIHj1cYFvKEOEMTDy[YNmeHSxcjDlfJBz\XO\|ZXSgbY4hS0iRIHPlcIx{NCCNaU2wMlAzPc7:TR?=	NI\a[HQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOEO0NlQxOyd-MUizOFI1ODN:L3G+
CHO	NH;meWhHfW6ldHnvckBie3OjeR?=			MUnEbZNxdGGlZX3lcpQhd2ZiW{PIYXdKVi13NUKxNk0zKG[{b32gbJVu[W5iQ1KyJJJm[2WydH;yJIV5eHKnc4Pl[EBqdiCFSF:gZ4VtdHNuIFvpQVEvPTkQvF2=	M{TsS\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6M{SyOFA{Lz5zOEO0NlQxOzxxYU6=
HEK293	MnfNSpVv[3Srb36gZZN{[Xl?			MXfEbZNxdGGlZX3lcpQhd2ZiW{PIYWNRNTV3OUSwJIZzd21iaIXtZY4hS0JzIILlZ4VxfG:{IHX4dJJme3OnZDDpckBJTUt{OUOgZ4VtdHNuIFvpQVAvODB{NN88US=>	M2TLWVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6M{[zN\|UzLz5zOEO2N\|M2OjxxYU6=
CHO	M2i4eWZ2dmO2aX;uJIF{e2G7			NED4T2pFcXOybHHj[Y1mdnRib3[gX\|NJZUOSLUW1PVQxKG[{b32gbJVu[W5iQ1KyJJJm[2WydH;yJIV5eHKnc4Pl[EBqdiCFSF:gZ4VtdHNuIFvpQVAvPTcQvF2=	NHG2VYY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOEO2N\|M2Oid-MUizOlM{PTJ:L3G+
SF9	M3i0fWZ2dmO2aX;uJIF{e2G7			Mnu0RY51[WexbnnzeEBi[3Srdnn0fUBifCC{YYSgR2IyKHKnY3XweI9zKGmwIGPGPUBk\WyuczDhd5Nme3OnZDDhd{BqdmirYnn0bY9vKG:oIFPQMVU2QTRyLYP0bY12dGG2ZXSgS3RR\2GvbXHTJIJqdmSrbnesJGtqRTBwMECwN\|HPxE1?	M2mxU\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6NES4N\|QxLz5zOES0PFM1ODxxYU6=
SF9	MmjtSpVv[3Srb36gZZN{[Xl?			M3;nN2FvfGGpb37pd5Qh[WO2aY\peJkh[XRiaIXtZY4hS0JzIILlZ4VxfG:{IHX4dJJme3OnZDDpckBUTjliY3XscJMh[XO\|ZYPz[YQh[XNiaX7obYJqfGmxbjDv[kBEWC13NUm0NE1{fGmvdXzheIVlKEeWUHfhcY1iWyCkaX7kbY5oNCCNaU2wMlAxODR\|zszN	MoXXQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTh2NEizOFAoRjF6NES4N\|QxRC:jPh?=
SF9	MmTJSpVv[3Srb36gZZN{[Xl?			M4C3W2lvfmW{c3WgZYdwdmm\|dDDheEBpfW2jbjDDRlEhemWlZYD0c5Ih\XiycnXzd4VlKGmwIGPGPUBk\WyuczDhd5Nme3OnZDDhd{Bl\WO{ZXHz[UBqdiCJVGDnZY1u[VNibHX2[YwtKEmFNUC9NE4xODF\|Nd88US=>	NVLrOm9oRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUi0OFg{PDBpPkG4OFQ5OzRyPD;hQi=>
SF9	M3zlWWZ2dmO2aX;uJIF{e2G7			MUDBcpRi\2:waYP0JIFkfGm4aYT5JIF1KGi3bXHuJGNDOiC{ZXPldJRweiCrbjDTSlkh[2WubIOgZZN{\XO\|ZXSgZZMhcW6qaXLpeIlwdiCxZjDDVE02PTl2MD3zeIlufWyjdHXkJGdVWGejbX3hV{BjcW6maX7nMEBMcT1yLkixOe69VQ>?	Ml\mQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTh2NEizOFAoRjF6NES4N\|QxRC:jPh?=
HEK293	NYLkRo5LTnWwY4Tpc44h[XO\|YYm=			MoqySIl{eGyjY3Xt[Y51KG:oIGuzTH1EWC13NUm0NEBnd3KvIHj1cYFvKHKnY3;tZolv[W62IFPCNUBz\WOncITvdkBmgHC{ZYPz[YQhcW5iSFXLNlk{KGOnbHzzJIJ6KGyrcYXp[EB{[2mwdHnscIF1cW:wIHPveY51cW6pLDDLbV0xNjB2zszN	M2H0VlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6NUGxNVU4Lz5zOEWxNVE2PzxxYU6=
CHO-K1	M1XrR2Z2dmO2aX;uJIF{e2G7			Mn3aSIl{eGyjY3Xt[Y51KG:oIGuzTH1UWjF2MUexOkBnem:vIHj1cYFvKEOEMTDy[YNmeHSxcjDlfJBz\XO\|ZXSgbY4hS0iRLVuxJINmdGy\|LDDLbV0xNjByMUG4{txO	MofoQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTh3MUK5NFEoRjF6NUGyPVAyRC:jPh?=
HEK293	NHXrVFZHfW6ldHnvckBie3OjeR?=			MUPBcpRi\2:waYP0JIFkfGm4aYT5JIF1KGi3bXHuJGNDOSC{ZXPldJRweiCneIDy[ZN{\WRiaX6gTGVMOjl\|IHPlcIx{KGG\|c3Xzd4VlKGG\|IHnubIljcXSrb36gc4YhS1BvNUW5OFAue3SrbYXsZZRm\CCdM{XTYWdVWGejbX3hV{BjcW6maX7nMEBM\D1yLkCwNlU4\|ryP	M3j0SVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6NUGyPVAyLz5zOEWxNlkxOTxxYU6=
HEK293	MmLNSpVv[3Srb36gZZN{[Xl?			NHrUO5NFcXOybHHj[Y1mdnRib3[gX\|NJZUOSLUW1PVQxKG[{b32gbJVu[W5iQ1KxJJJm[2WydH;yJIV5eHKnc4Pl[EBqdiCKRVuyPVMh[2WubIOsJGtqRTBwMEC2NVjPxE1?	MlTTQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTh3MUK5NFEoRjF6NUGyPVAyRC:jPh?=
CHO-K1	M4rvSmZ2dmO2aX;uJIF{e2G7			M{m1T2Rqe3CuYXPlcYVvfCCxZjDbN2heS1BvNUW5OFAh\nKxbTDoeY1idiCFQkKgdoVk\XC2b4Kg[ZhxemW\|c3XkJIlvKEOKTz3LNUBk\WyuczygT4k:OC5\|MUROwG0>	NGjGVJc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOEWxNlkxOSd-MUi1NVI6ODF:L3G+
HEK	NIf0fIdHfW6ldHnvckBie3OjeR?=			NYrsV3o{TGm\|cHzhZ4Vu\W62IH;mJHs{UF2FUD21OVk1OCCocn;tJIh2dWGwIILlZ49u[mmwYX70JGNDOSC{ZXPldJRweiCneIDy[ZN{\WRiaX6gTGVMKGOnbHzzMEBMcT1yLkCwPO69VQ>?	NVfOR2tDRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUi1O\|k{QDZpPkG4OVc6Ozh4PD;hQi=>
HEK	NUTuU4pJTnWwY4Tpc44h[XO\|YYm=			MlTNSIl{eGyjY3Xt[Y51KG:oIGuzTH1EWC13NUm0NEBnem:vIHj1cYFvKHKnY3;tZolv[W62IFPCNkBz\WOncITvdkBmgHC{ZYPz[YQhcW5iSFXLJINmdGy\|LDDLbV0xNjd7zszN	Ml\YQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTh3N{mzPFYoRjF6NUe5N\|g3RC:jPh?=
HEK293	Mn3PSpVv[3Srb36gZZN{[Xl?			NHWzSXNFcXOybHHj[Y1mdnRib3[gX\|NJZUOSLUW1PVQxKG[{b32gbJVu[W5iQ1KxJJJm[2WydH;yJIV5eHKnc4Pl[EBqdiCKRVuyPVMh[2WubIOsJGtqRTBwMEGy{txO	MXy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDZ6MEK3Okc,OTh4OECyO\|Y9N2F-
HEK293	NYGyOWJRTnWwY4Tpc44h[XO\|YYm=			MXnEbZNxdGGlZX3lcpQhd2ZiW{PIYWNRNTV3OUSwJIZzd21iaIXtZY4hS0J{IILlZ4VxfG:{IHX4dJJme3OnZDDpckBJTUt{OUOgZ4VtdHNuIFvpQVAvPzoQvF2=	M3\MO\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6NkiwNlc3Lz5zOE[4NFI4PjxxYU6=
HEK293	NYHGR\|hzTnWwY4Tpc44h[XO\|YYm=			NH7QNY9FcXOybHHj[Y1mdnRib3[gX\|NJZUOSLUW1PVQxKG[{b32gbJVu[W5iQ1KxJJJm[2WydH;yJIV5eHKnc4Pl[EBqdiCKRVuyPVMh[2WubIOsJGlEPTB;MD6wNVXPxE1?	Moj6QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTh5MUK4OVYoRjF6N{GyPFU3RC:jPh?=
HEK293	MVnGeY5kfGmxbjDhd5NigQ>?			M{S0c2FvfGGpb37pd5Qh[WO2aY\peJkh[XRiaIXtZY4hS0JzIILlZ4VxfG:{IHX4dJJme3OnZDDpckBJTUt{OUOgZ4VtdHNiYYPz[ZN{\WRiYYOgbY5pcWKrdHnvckBw\iCHdT3HWHAh[mmwZHnu[{whTUN3ME2wMlAyQDMQvF2=	MXO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDdzMki1Okc,OTh5MUK4OVY9N2F-
HEK293	M{DWUGZ2dmO2aX;uJIF{e2G7			NEXhT3dFcXOybHHj[Y1mdnRib3[gX\|NJZUOSLUW1PVQxKG[{b32gbJVu[W5iQ1KyJJJm[2WydH;yJIV5eHKnc4Pl[EBqdiCKRVuyPVMh[2WubIOsJGlEPTB;MT65N\|k5\|ryP	MmrEQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTh5MUK4OVYoRjF6N{GyPFU3RC:jPh?=
HEK293	NELMbJVHfW6ldHnvckBie3OjeR?=			NWq3[nd[UW64ZYLz[UBi\2:waYP0JIFkfGm4aYT5JIF1KGi3bXHuJGNDOSC{ZXPldJRweiCneIDy[ZN{\WRiaX6gTGVMOjl\|IHPlcIx{KGG\|c3Xzd4VlKGG\|IHTlZ5Jm[XOnIHnuJHs{PVOfZ3HtcYFIXFBiYnnu[Ilv\yC{ZXzheIl3\SC2bzDjc451em:u	MVS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDdzMki1Okc,OTh5MUK4OVY9N2F-
CHO	Mlj3SpVv[3Srb36gZZN{[Xl?			NF3KZmpCdnSjZ3;ubZN1KGGldHn2bZR6KGG2IHj1cYFvKEOEMTDy[YNmeHSxcjDpckBEUE9iY3XscJMh[XO\|ZYPz[YQh[XNiR2TQ[4FudWGVIHLpcoRqdmduIFviQVAvODByNkm4{txO	M2HwfFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6OECwO\|cxLz5zOEiwNFc4ODxxYU6=
CHOK1	NEXSeI1HfW6ldHnvckBie3OjeR?=			MnzCSIl{eGyjY3Xt[Y51KG:oIGuzTH1YUU5vNUWyNVIuOiCocn;tJIh2dWGwIFPCNkBz\WOncITvdkBmgHC{ZYPz[YQhcW5iQ1jPT\|Eh[2WubIOgZpkhdGmzdXnkJJNkcW62aXzsZZRqd25ic4DlZ5Rzd22ndIL5MEBKSzVyPUGuO\|bPxE1?	MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDl3NEC0Nkc,OTh7NUSwOFI9N2F-
CHO	M3eyUGZ2dmO2aX;uJIF{e2G7			NX7qfVQyTGm\|cHzhZ4Vu\W62IH;mJHs{UF2ZSV6tOVUzOTJvMjDmdo9uKGi3bXHuJGNDOiC{ZXPldJRweiCneIDy[ZN{\WRiaX6gR2hQKGOnbHzzMEBKSzVyPUGuO\|bPxE1?	M4\PblxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7MEKyOlY3Lz5zOUCyNlY3PjxxYU6=
HEK293	NVThfFI6TnWwY4Tpc44h[XO\|YYm=			M1X1[WRqe3CuYXPlcYVvfCCxZjDbN2heS1BvNUW5OFAh\nKxbTDoeY1idiCFQkKgdoVk\XC2b4Kg[ZhxemW\|c3XkJIlvKEiHS{K5N{Bk\WyuczygTWM2OD1yLkCwNVnPxE1?	M3fpNlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7MEm1OFQ1Lz5zOUC5OVQ1PDxxYU6=
HEK293	NWD6eJVFTnWwY4Tpc44h[XO\|YYm=			MYLEbZNxdGGlZX3lcpQhd2ZiW{PIYWNRNTV3OUSwJIZzd21iaIXtZY4hS0JzIILlZ4VxfG:{IHX4dJJme3OnZDDpckBJTUt{OUOgZ4VtdHNuIFnDOVA:OC5yMUZOwG0>	NVvIRlBwRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUmwPVU1PDRpPkG5NFk2PDR2PD;hQi=>
HEK293	Mm[4SpVv[3Srb36gZZN{[Xl?			MX\BcpRi\2:waYP0JIFkfGm4aYT5JIF1KGi3bXHuJGNDOSC{ZXPldJRweiCneIDy[ZN{\WRiaX6gTGVMOjl\|IHPlcIx{KGG\|c3Xzd4VlKGG\|IHnubIljcXSrb36gc4YhTXVvR2TQJIJqdmSrbnesJGVEPTB;MD6wNVgz\|ryP	MXq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQTB7NUS0OEc,OTlyOUW0OFQ9N2F-
CHO-K1	MVXGeY5kfGmxbjDhd5NigQ>?			MYDBcpRi\2:waYP0JIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iQ1KxJJJm[2WydH;yJIV5eHKnc4Pl[EBqdiCFSF:tT\|Eh[2WubIOgZpkhYzN3U23HWHBo[W2vYTDibY5lcW6pIHHzd4F6NCCNaU2wMlAxODF7zszN	MWC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQTFyMk[5PEc,OTlzMEK2PVg9N2F-
HEK293	MYLGeY5kfGmxbjDhd5NigQ>?			MV3EbZNxdGGlZX3lcpQhd2ZiW{PIYXNTOTRzN{G2RUBnem:vIHj1cYFvKEOEMTDy[YNmeHSxcjDlfJBz\XO\|ZXSgbY4hUEWNMkmzJINmdGy\|LDDLbV0xNjByMEpOwG0>	M3rO[\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7MUCyOlk5Lz5zOUGwNlY6QDxxYU6=
CHOK1	M4Lid2Z2dmO2aX;uJIF{e2G7			MkPnSIl{eGyjY3Xt[Y51KG:oIGuzTH1YUU5vNUWyNVIuOiCocn;tJIh2dWGwIILlZ49u[mmwYX70JINidm6jYnnuc4llKEOEMjDy[YNmeHSxcjDlfJBz\XO\|ZXSgbY4hS0iRS{GgZ4VtdHNiYomgcIlyfWmmIIPjbY51cWyuYYTpc44he3CnY4Tyc41mfHK7LDDJR\|UxRTFwN{dOwG0>	MnLQQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTl{Nkm4NVcoRjF7Mk[5PFE4RC:jPh?=
CHOK1	M1zldGZ2dmO2aX;uJIF{e2G7			NWe0W4Y6SW62YXfvcol{fCCjY4Tpeol1gSCjdDDoeY1idiClYX7uZYJqdm:rZDDDRlEhemWlZYD0c5Ih\XiycnXzd4VlKGmwIFPIU2syKGOnbHzzJIF{e2W\|c3XkJIF{KGODTWCgZYN1cX[rdImsJGVEPTB;MD6yOO69VQ>?	MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQTN{OE[4N{c,OTl\|Mki2PFM9N2F-
CHOK1	M2P6UGZ2dmO2aX;uJIF{e2G7			NFO5XoxCdnSjZ3;ubZN1KGGldHn2bZR6KGG2IHj1cYFvKGOjbn7hZolvd2mmIFPCNkBz\WOncITvdkBmgHC{ZYPz[YQhcW5iQ1jPT\|Eh[2WubIOgZZN{\XO\|ZXSgZZMh[0GPUDDhZ5Rqfmm2eTygSWM2OD1\|MT6yNe69VQ>?	M{j5[lxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7M{K4Olg{Lz5zOUOyPFY5OzxxYU6=
HEK293	NUjob5lRTnWwY4Tpc44h[XO\|YYm=			NFO2fVhFcXOybHHj[Y1mdnRib3[gX\|NJZVOUMUSxO\|E3KG[{b32gbJVu[W5icnXjc41jcW6jboSgR2IyKHKnY3XweI9zKGW6cILld5Nm\CCrbjDISWszQTNiY3XscJMtKEurPUCuNFAyQTl3zszN	M4TxZ\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7M{O4N\|U3Lz5zOUOzPFM2PjxxYU6=
HEK293	M2G5WmZ2dmO2aX;uJIF{e2G7			M1S0V2Rqe3CuYXPlcYVvfCCxZjDbN2heW1JzNEG3NVYh\nKxbTDoeY1idiC{ZXPvcYJqdmGwdDDDRlIhemWlZYD0c5Ih\XiycnXzd4VlKGmwIFjFT\|I6OyClZXzsd{whU2l;MD6zPVgyOc7:TR?=	NEfkeIU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOUOzPFM2Pid-MUmzN\|g{PTZ:L3G+
CHOK1	NXLwVVlvTnWwY4Tpc44h[XO\|YYm=		NX3pe3dVOTBibXnudy=>	NXfRV\|I3SW62YXfvcol{fCCjY4Tpeol1gSCjdDDoeY1idiCFQkGgdoVk\XC2b4Kg[ZhxemW\|c3XkJIlvKEOKT1uxJINmdGy\|IHHzd4V{e2WmIHHzJIlvcGmkaYTpc44hd2ZiQ2CtOVU6PDBvaX7keYNm\CC{ZYPwc45{\SCjZoTldkAyOCCvaX7zJIJ6KEeWUHfhcY1iYzN3U22gZolv\GmwZzDhd5NigSxiS3m9NE4xODF4zszN	NYr5eVN[RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUmzOVEyOTNpPkG5N\|UyOTF\|PD;hQi=>
HEK293	NE\ucYNHfW6ldHnvckBie3OjeR?=			NUXY[\|RoTGm\|cHzhZ4Vu\W62IH;mJHs{UF2{aX3vcoFj[W62IH\yc40hcHWvYX6gR2IyKHKnY3XweI9zKGW6cILld5Nm\CCrbjDISWszQTNiY3XscJMh[nlibHnxeYllKHOlaX70bYxt[XSrb36gZ492dnSrbnesJGtqRTBwMECxPe69VQ>?	NHP2dpo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOUWyNFU4Oid-MUm1NlA2PzJ:L3G+
HEK293	Mne4SpVv[3Srb36gZZN{[Xl?			NF7USpJFcXOybHHj[Y1mdnRib3[gX\|NJZUOSLUW1PVQxKG[{b32gbJVu[W5icnXjc41jcW6jboSgR2IyWiCneIDy[ZN{\WRiaX6gTGVMOjl\|IHPlcIx{NCCLQ{WwQVAvODF\|Mt88US=>	M1PPZlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7NUOwOlk4Lz5zOUWzNFY6PzxxYU6=
HEK293	MXzGeY5kfGmxbjDhd5NigQ>?			NHjLcWVKdn[ncoPlJIFod26rc4SgZYN1cX[rdImgZZQhcHWvYX6gdoVkd22kaX7hcpQhS0JzUjDlfJBz\XO\|ZXSgbY4hUEWNMkmzJINmdGy\|IHHzd4V{e2WmIHHzJIlvcGmkaYTpc44hd2ZiQ2CtOVU6PDBvc4TpcZVt[XSnZDDFeU1IXFBiYnnu[Ilv\yxiRVO1NF0xNjBzNUhOwG0>	M160eFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7NUOwOlk4Lz5zOUWzNFY6PzxxYU6=
HEK293	MV7GeY5kfGmxbjDhd5NigQ>?			NIXsUZVFcXOybHHj[Y1mdnRib3[gX\|NJZUOSLUW1PVQxKG[{b32gbJVu[W5icnXjc41jcW6jboSgR2IzWiCneIDy[ZN{\WRiaX6gTGVMOjl\|IHPlcIx{NCCLQ{WwQVEvPjNzMd88US=>	NIXJ[VU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOUWzNFY6Pyd-MUm1N\|A3QTd:L3G+
HEK293	M1:wcmZ2dmO2aX;uJIF{e2G7	NEDGS4UyOCC3TR?=		NVPufGVuUW62cnnud4lkKGGldHn2bZR6KGG2IHj1cYFvKHKnY3;tZolv[W62IFPCNXIh\XiycnXzd4VlKGmwIFjFT\|I6OyClZXzsd{Bie3Onc4Pl[EBieyCHdT3HWHAh[mmwZHnu[{BifCBzMDD1UUBz\WyjdHn2[UB1dyCkYYPhcEBt\X[nbB?=	MY[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQTV\|ME[5O{c,OTl3M{C2PVc9N2F-
HEK	M3vZXmZ2dmO2aX;uJIF{e2G7			MXHEbZNxdGGlZX3lcpQhd2ZiW{PIYWNRNTV3OUSwJIZzd21iaIXtZY4hemWlb33ibY5idnRiQ1KxJJJm[2WydH;yJIV5eHKnc4Pl[EBqdiCKRVugZ4VtdHNuIFvpQVAvODF{zszN	M1PqbFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7NUm1OVk3Lz5zOUW5OVU6PjxxYU6=
HEK	NWroWooxTnWwY4Tpc44h[XO\|YYm=			NXLEdnFrTGm\|cHzhZ4Vu\W62IH;mJHs{UF2FUD21OVk1OCCocn;tJIh2dWGwIILlZ49u[mmwYX70JGNDOiC{ZXPldJRweiCneIDy[ZN{\WRiaX6gTGVMKGOnbHzzMEBMcT1yLke5{txO	M1vBWlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7NUm1OVk3Lz5zOUW5OVU6PjxxYU6=
CHO-K1	MXTGeY5kfGmxbjDhd5NigQ>?			NVvTWXFJSW62YXfvcol{fCCjY4Tpeol1gSCjdDDoeY1idiCFQkGgdoVk\XC2b4KgeJJidnOoZXP0[YQhcW5iQ1jPMWsy[2WubIOgZpkhT1SSZ3HtcYFcOzWVXTDibY5lcW6pIHHzd4F6NCCNaU2wMlAxOTcQvF2=	NW\QcpBWRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUm2PFM6OThpPkG5Olg{QTF6PD;hQi=>
CHO	MoXESpVv[3Srb36gZZN{[Xl?			NE\G[Y1DcW6maX7nJIFn\mmwaYT5JJRwKGi3bXHuJGNDOiC{ZXPldJRweiCneIDy[ZN{\WRiaX6gR2hQKGOnbHzzJIJ6KGy3Y3nm[ZJie2VicnXwc5J1\XJiZ3Xu[UBie3OjeTygTWM2OD1yLkC5NlXPxE1?	M{n3ZlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7OEWwOFc{Lz5zOUi1NFQ4OzxxYU6=
CHOK1	MXrGeY5kfGmxbjDhd5NigQ>?			NX3xXJRpTGm\|cHzhZ4Vu\W62IH;mJHs{UF2ZSV6tOVUzOTJ{IH\yc40hcHWvYX6gR2IzKHKnY3XweI9zKGW6cILld5Nm\CCrbjDDTG9MOSClZXzsd{whUUN3ME2xMlc3\|ryP	NIi3VlA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOUi1NFQ4Oyd-MUm4OVA1PzN:L3G+
CHO-K1	NFvNdJFHfW6ldHnvckBie3OjeR?=			NU\TeWhJSW62YXfvcol{fCCjY4Tpeol1gSCjdDDoeY1idiC{ZXPvcYJqdmGwdDDDRlEhemWlZYD0c5Ih\XiycnXzd4VlKGmwIFPIU{1MOSClZXzsd{Bie3Onc4Pl[EBieyCrbnjpZol1cW:wIH;mJGNRNTV3OUSwMZN1cW23bHH0[YQhT1SSZ3HtcYFUKGKrbnTpcoctKEmFNUC9NE4xODR3zszN	NF\Ke5M9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOUm1OFk4QCd-MUm5OVQ6Pzh:L3G+
CHO-K1	MWrGeY5kfGmxbjDhd5NigQ>?			M4DIVmlvfmW{c3WgZYdwdmm\|dDDhZ5Rqfmm2eTDheEBpfW2jbjDDRlEhemWlZYD0c5Ih\XiycnXzd4VlKGmwIFPIU{1MOSClZXzsd{BjgSCJVGDnZY1u[VNiYnnu[Ilv\yCjc4PhfUwhUUN3ME2wMlAxOjoQvF2=	MomwQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjByMUW2OFcoRjJyMEG1OlQ4RC:jPh?=
CHO-K1	NW\lUJBETnWwY4Tpc44h[XO\|YYm=			NEe1T49CdnSjZ3;ubZN1KGGldHn2bZR6KGG2IHj1cYFvKEOEMTDy[YNmeHSxcjDlfJBz\XO\|ZXSgbY4hS0iRLVuxJINmdGy\|IHHzd4V{e2WmIHHzJIlvcGmkaYTpc44hd2ZiQ2CtOVU6PDBvaX7keYNm\CCJVGDnZY1u[VNiYnnu[Ilv\yxiSVO1NF0xNjByNEZOwG0>	NYryPI9XRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkCwNVU3PDdpPkKwNFE2PjR5PD;hQi=>
COS7	NH7BO5FHfW6ldHnvckBie3OjeR?=			NIDWZ2xFcXOybHHj[Y1mdnRib3[gX\|NJZUOSLUW1PVQxKG[{b32gbJVu[W5iQ1KxJJJm[2WydH;yJIV5eHKnc4Pl[EBqdiCFT2O3JINmdGy\|LDDJR\|UxRTBwMEC1Ne69VQ>?	Mn7xQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjByMUW2OFcoRjJyMEG1OlQ4RC:jPh?=
CHO	M37L[mZ2dmO2aX;uJIF{e2G7			NYXWW3E2UW64ZYLz[UBi\2:waYP0JIFkfGm4aYT5JIF1KGi3bXHuJJJm[2:vYnnuZY51KEOEMTDy[YNmeHSxcjDlfJBz\XO\|ZXSgbY4hS0iRIHPlcIx{KGK7IHz1Z4ln\XKjc3WgdoVxd3K2ZYKg[4Vv\SCjc4PhfUwhUUN3ME2wMlExQM7:TR?=	MXq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zODB2NUOzO{c,OjByNEWzN\|c9N2F-
CHO	MmDGSpVv[3Srb36gZZN{[Xl?		MXq2NEBucW6\|	NYntOYs6UW64ZYLz[UBi\2:waYP0JIFkfGm4aYT5JIF1KGi3bXHuJINidm6jYnnuc4llKEOEMTDy[YNmeHSxcjDlfJBz\XO\|ZXSgbY4hS0iRIHPlcIx{KGG\|c3Xzd4VlKGG\|IHnubIljcXSrb36gc4Yh\m:{c3vvcIlvNXO2aX31cIF1\WRiY1HNVEBi[2O3bYXsZZRqd25iYX\0[ZIhPjBibXnud{whTUN3ME2wMlAxODFzzszN	NHzsPZc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MEC0O\|c4QSd-MkCwOFc4Pzl:L3G+
CHO	M1jW[WZ2dmO2aX;uJIF{e2G7		M2DxeVMhcHK\|	NXLl[Ix1TGm\|cHzhZ4Vu\W62IH;mJHs{UF2FUD21OVk1OCCocn;tJIh2dWGwIILlZ49u[mmwYX70JINidm6jYnnuc4llKEOEMTDy[YNmeHSxcjDlfJBz\XO\|ZXSgbY4hS0iRIHPlcIx{KGGodHXyJFMhcHK\|IHL5JIxqeXWrZDDzZ4lvfGmubHH0bY9vKGOxdX70bY5oNCCNaU2wMlAxODd2zszN	M37MUlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJyMES3O\|c6Lz5{MEC0O\|c4QTxxYU6=
CHO	NGDGem1HfW6ldHnvckBie3OjeR?=		MX:xNEBucW6\|	NX7EUppWSW62YXfvcol{fCCjY4Tpeol1gSCjdDDoeY1idiClYX7uZYJqdm:rZDDDRlEhemWlZYD0c5Ih\XiycnXzd4VlKGmwIFPIU{Bk\WyuczDjc4V5eHKnc4PpcochT2GucHjhNVUwOTZiYYPz[ZN{\WRiYYOgbY5pcWKrdHnvckBw\iCFUD21OVk1OC2rbnT1Z4VlKEOjMjugdoVt\WG\|ZTDh[pRmeiBzMDDtbY5{KGK7IH3pZ5JwKHCuYYTlJJJm[WSncjygTWM2OD1yLkCwN\|LPxE1?	M4SxZ\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJyMES3O\|c6Lz5{MEC0O\|c4QTxxYU6=
CHO	MXTGeY5kfGmxbjDhd5NigQ>?		NH;YNmM{KGi{cx?=	NUjUVIlyTGm\|cHzhZ4Vu\W62IH;mJHs{UF2FUD21OVk1OCCocn;tJIh2dWGwIILlZ49u[mmwYX70JINidm6jYnnuc4llKEOEMjDy[YNmeHSxcjDlfJBz\XO\|ZXSgbY4hS0iRIHPlcIx{KGGodHXyJFMhcHK\|IHL5JIxqeXWrZDDzZ4lvfGmubHH0bY9vKGOxdX70bY5oNCCNaU2wMlEzPs7:TR?=	NYXPdFZYRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkCwOFc4PzlpPkKwNFQ4Pzd7PD;hQi=>
CHO	NWPEUm9GTnWwY4Tpc44h[XO\|YYm=			MXvBcpRi\2:waYP0JIFkfGm4aYT5JIF1KGi3bXHuJGNDOSC{ZXPldJRweiCneIDy[ZN{\WRiaX6gR2hQKGOnbHzzJIF{e2W\|c3XkJIF{KGmwaHnibZRqd25ib3[gR3AuPTV7NECtbY5lfWOnZDDbN2he[XKjY3jp[I9vcWNiYXPp[EBz\WynYYPlMEBM\D1yLkCwNlUyOs7:TR?=	NVrnSWZNRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkCzOlMyOzJpPkKwN\|Y{OTN{PD;hQi=>
CHO	NITvSnZHfW6ldHnvckBie3OjeR?=			NHzQXIJFcXOybHHj[Y1mdnRib3[gX\|NJZUOSLUW1PVQxKG[{b32gbJVu[W5iQ1KxJJJm[2WydH;yJIV5eHKnc4Pl[EBqdiCFSF:gZ4VtdHNuIFvpQVAvODJ3zszN	NGDBd5U9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MEO2N\|E{Oid-MkCzOlMyOzJ:L3G+
CHO	M3PMXWZ2dmO2aX;uJIF{e2G7			MWDEbZNxdGGlZX3lcpQhd2ZiW{PIYWNRNTV3OUSwJIZzd21iaIXtZY4hS0J{IILlZ4VxfG:{IHX4dJJme3OnZDDpckBEUE9iY3XscJMtKEurPUGuOVjPxE1?	Mn7jQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjB\|NkOxN\|IoRjJyM{[zNVMzRC:jPh?=
CHO-K1	NXXnVZdnTnWwY4Tpc44h[XO\|YYm=		MofGNUBpeg>?	NHvER49FcXOybHHj[Y1mdnRib3[gX\|NJZVeLTj21OVIyOi1{IH\yc40hcHWvYX6gR2IzKHKnY3XweI9zKGW6cILld5Nm\CCrbjDDTG8uUzFiY3XscJMh[W[2ZYKgNUBpeiCkeTDsbZF2cWRic3PpcpRqdGyjdHnvckBkd3WwdHnu[{whUUN3ME2xMlc3\|ryP	NFTJNYI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{ME[3N\|czQSd-MkC2O\|M4Ojl:L3G+
HEK	M3\tXWZ2dmO2aX;uJIF{e2G7			NVfh[\|B{TGm\|cHzhZ4Vu\W62IH;mJHs{UF2FUD21OVk1OCCocn;tJIh2dWGwIFPCNUBz\WOncITvdkBmgHC{ZYPz[YQhcW5iSFXLJINmdGy\|LDDLbV0xNjBzMt88US=>	NXL3UmxoRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkC3NVg1QTJpPkKwO\|E5PDl{PD;hQi=>
HEK	NVvpWpBbTnWwY4Tpc44h[XO\|YYm=			NIn0R2lFcXOybHHj[Y1mdnRib3[gX\|NJZUOSLUW1PVQxKG[{b32gbJVu[W5iQ1KyJJJm[2WydH;yJIV5eHKnc4Pl[EBqdiCKRVugZ4VtdHNuIFvpQVAvPzoQvF2=	MljRQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjB5MUi0PVIoRjJyN{G4OFkzRC:jPh?=
CHO	NFXG[VZHfW6ldHnvckBie3OjeR?=			MYLB[49vcXO2IHHjeIl3cXS7IHH0JIh2dWGwIFPCNUBz\WOncITvdkBmgHC{ZYPz[YQhcW5iQ1jPJINmdGy\|IHPvMYV5eHKnc4PpcochT2GucHjhNVYheHKxdHXpckBie3Onc4Pl[EBieyCvb3LpcIl7[XSrb36gc4YhcW62cnHj[YxtfWyjcjDjZYxkcXWvLDDL[V0xNjByMUJOwG0>	NH\xfY49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MEi0OVk2QSd-MkC4OFU6PTl:L3G+
HEK293	NHP4cGhHfW6ldHnvckBie3OjeR?=			NVy2NmdTTGm\|cHzhZ4Vu\W62IH;mJHs{UF2VUkG0NVcyPiCocn;tJIh2dWGwIFPCNUBz\WOncITvdkBmgHC{ZYPz[YQhcW5iSFXLNlk{KGOnbHzzMEBMcT1yLkCwNVE5\|ryP	NWnEW4R3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkC4OFU6PTlpPkKwPFQ2QTV7PD;hQi=>
HEK293	M1jMPGZ2dmO2aX;uJIF{e2G7			NIf0eZJFcXOybHHj[Y1mdnRib3[gX\|NJZUOSNUW5OFAh\nKxbTDoeY1idiCFQkGgdoVk\XC2b4Kg[ZhxemW\|c3XkJIlvKEiHS{K5N{Bk\WyuczygT4k:OC5yME[xPO69VQ>?	MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zODh2NUm1PUc,OjB6NEW5OVk9N2F-
CHOK1	M3i0VWZ2dmO2aX;uJIF{e2G7			NH\3bHJFcXOybHHj[Y1mdnRib3[gX\|NJZUOSNUW5OFAh\nKxbTDoeY1idiCFQkKgdoVk\XC2b4Kg[ZhxemW\|c3XkJIlvKEOKT1uxJINmdGy\|LDDLbV0xNjNzM988US=>	M{LkdVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJyOES1PVU6Lz5{MEi0OVk2QTxxYU6=
HEK	NXLVZ2ZZTnWwY4Tpc44h[XO\|YYm=			NVGxPWtHTGm\|cHzhZ4Vu\W62IH;mJHs{UF2FUD21OUw6PDBiZoLvcUBz\WOxbXLpcoFvfCCqdX3hckBESjFicnXj[ZB1d3JidILhcpNn\WO2ZXSgbY4hUEWNIHPlcIx{NCCNaU2wMlAyOs7:TR?=	NXr1clQ6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkC5OFMzQTBpPkKwPVQ{OjlyPD;hQi=>
HEK	NHvUTWlHfW6ldHnvckBie3OjeR?=			MljKSIl{eGyjY3Xt[Y51KG:oIGuzTH1EWC13NTy5OFAh\nKxbTDy[YNwdWKrbnHueEBpfW2jbjDDRlIhemWlZYD0c5IhfHKjboPm[YN1\WRiaX6gTGVMKGOnbHzzMEBMcT1yLke5{txO	M{DKNFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJyOUSzNlkxLz5{MEm0N\|I6ODxxYU6=
CHO	MkjuSpVv[3Srb36gZZN{[Xl?			NFLrZmFFcXOybHHj[Y1mdnRib3[gX\|NJZVOUMUSxO\|E3SSCocn;tJIh2dWGwIFPCNUBz\WOncITvdkBmgHC{ZYPz[YQhcW5iQ1jPJINmdGy\|LDDLbV0xNjByMEmzN\|PPxE1?	MX:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTN\|NEi5Nkc,OjF\|M{S4PVI9N2F-
Sf9	M4nvT2Z2dmO2aX;uJIF{e2G7			NGe1cGxFcXOybHHj[Y1mdnRib3[gX\|NJZUOSNUW5OFAh\nKxbTDoeY1idiC{ZXPvcYJqdmGwdDDDRlIhemWlZYD0c5Ih\XiycnXzd4VlKGmwIGPmPUBk\WyuczygT4k:OC56NUGxOO69VQ>?	MVy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTN\|NEi5Nkc,OjF\|M{S4PVI9N2F-
CHO	NGDkR\|ZHfW6ldHnvckBie3OjeR?=			NILkbYdCdnSjZ3;ubZN1KGGldHn2bZR6KGG2IFPCNUBz\WOncITvdkB1emGwc3\lZ5Rm\CCrbjDDTG8h[2WubIOg[ZhxemW\|c3nu[{BieG:jZYH1c5JqdiCjczDhJJJmeG:{dHXyJIZweiCJLYDyc5RmcW5vY3;1dIxm\CC{ZXPldJRwei2vZXTpZZRm\CClYXzjbZVuKHOrZ37hcIlv\yCkeTDibY9tfW2rbnXzZ4Vv[2ViYYPzZZktKEmFNUC9NE4xODUQvF2=	NWHnXHRURGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkGzO\|Y2QDhpPkKxN\|c3PTh6PD;hQi=>
HEK293	NFrnc3lHfW6ldHnvckBie3OjeR?=			NFn4TYNPd26lb33w[ZRqfGm4ZTDpcohq[mm2aX;uJI9nKE2UUEGtcYVlcWG2ZXSgSVIuOTekZYThS{B1emGwc4DvdpQhcW5iaIXtZY4hVVKSMTDlfJBz\XO\|aX7nJGhGUzJ7MzDj[YxteyCkeTDEbZhwdiCybH;0MEBMcT1zLkVOwG0>	MYO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTVzMUm0OUc,OjF3MUG5OFU9N2F-
HEK293	NV7ZfW1TTnWwY4Tpc44h[XO\|YYm=			MmnZUo9v[2:vcHX0bZRqfmViaX7obYJqfGmxbjDv[kBOWlB2LX3l[IlifGWmIFWyMVE4[mW2YVegeJJidnOyb4L0JIlvKGi3bXHuJG1TWDRiZYjwdoV{e2mwZzDISWszQTNiY3XscJMh[nliRHn4c44heGyxdDygT4k:PM7:TR?=	M2f0b\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzNUGxPVQ2Lz5{MUWxNVk1PTxxYU6=
HEK293	M32wfWZ2dmO2aX;uJIF{e2G7			NHPIS5dKdmS3Y4Tpc44hd2ZiTWLQNk1u\WSrYYTl[EBGOi1zN3LleIFIKHS{YX7zdI9zfCCrbjDoeY1idiCPUmCyJIV5eHKnc4PpcochUEWNMkmzJINmdGy\|IHnuJJBz\XOnbnPlJI9nKDJidV2gSVIuOTekZYThSy=>	MV28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTVzMUm0OUc,OjF3MUG5OFU9N2F-
HEK293	NVOxNJpCTnWwY4Tpc44h[XO\|YYm=			M3;yVGlvcGmkaYTpc44hd2ZiTWLQN{1u\WSrYYTl[EBGOi1zN3LleIFIKHS{YX7zdI9zfCCrbjDoeY1idiCPUmCzJIV5eHKnc4PpcochUEWNMkmzJINmdGy\|IHnuJJBz\XOnbnPlJI9nKDF3IIXNJGUzNTF5YnX0ZWc>	NED5O3I9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUWxNVk1PSd-MkG1NVE6PDV:L3G+
HEK293	M1r2eGZ2dmO2aX;uJIF{e2G7			M4f6ZWlvcGmkaYTpc44hd2ZiTWLQNU1u\WSrYYTl[EBGOi1zN3LleIFIKHS{YX7zdI9zfCCrbjDoeY1idiCPUmCxJIV5eHKnc4PpcochUEWNMkmzJINmdGy\|IHnuJJBz\XOnbnPlJI9nKDBwNjD0c{A2KHWPIFWyMVE4[mW2YVe=	NW[0ZoM6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkG1NVE6PDVpPkKxOVEyQTR3PD;hQi=>
HEK293	NF\tToxHfW6ldHnvckBie3OjeR?=			MUnJcohq[mm2aX;uJI9nKE2UUEStcYVlcWG2ZXSgSVIuOTekZYThS{B1emGwc4DvdpQhcW5iaIXtZY4hVVKSNDDlfJBz\XO\|aX7nJGhGUzJ7MzDj[YxteyCrbjDwdoV{\W6lZTDv[kAxNjZidH:gOUB2VSCHMj2xO4JmfGGJ	MV28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTVzMUm0OUc,OjF3MUG5OFU9N2F-
HEK	M3fFeGZ2dmO2aX;uJIF{e2G7			NFjHfHZFcXOybHHj[Y1mdnRib3[gX\|NJZUOSLUW1PVQxKG[{b32gbJVu[W5icnXjc41jcW6jboSgR2IyKHKnY3XweI9zKGW6cILld5Nm\CCrbjDISWsh[2WubIOsJGtqRTBwMEGy{txO	M1nIVVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzN{CyOFk5Lz5{MUewNlQ6QDxxYU6=
HEK	MVHGeY5kfGmxbjDhd5NigQ>?			NVe4ZXFYTGm\|cHzhZ4Vu\W62IH;mJHs{UF2FUD21OVk1OCCocn;tJIh2dWGwIILlZ49u[mmwYX70JGNDOiC{ZXPldJRweiCneIDy[ZN{\WRiaX6gTGVMKGOnbHzzMEBMcT1yLke5{txO	M13mO\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzN{CyOFk5Lz5{MUewNlQ6QDxxYU6=
CHO	Mlv1SpVv[3Srb36gZZN{[Xl?		MorUNUBpeg>?	MmDRSIl{eGyjY3Xt[Y51KG:oIGuzTH1EWDV3OUSwJIZzd21iaIXtZY4h[2GwbnHibY5wcWRiQ1KyJJJm[2WydH;yJIV5eHKnc4Pl[EBqdiCFSF:gZ4VtdHNiYYSgdGghPy52IHHmeIVzKDFiaIKgZpkhdGmzdXnkJJNkcW62aXzsZZRqd25iY3;1cpRqdmduIFnDOVA:OS57ON88US=>	NV7kcoFnRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkG3OFE5OzVpPkKxO\|QyQDN3PD;hQi=>
HEK293	NIq2UWRHfW6ldHnvckBie3OjeR?=		NVvPXWVyPSCvaX7z	NIrHN3ZKdmirYnn0bY9vKG:oIHj1cYFvKEWURzDlfJBz\XO\|ZXSgbY4hUEWNMkmzJINmdGy\|IHHzd4V{e2WmIHHzJIlvcGmkaYTpc44hd2ZicH;0ZZN{cXWvIHPoZY5v\WxiY4XydoVvfCCjZoTldkA2KG2rboOgZpkheGG2Y3igZ4xidXBiYYPzZZktKEmFNUC9Nk44Qc7:TR?=	NXTKZW5wRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkG3OFE5OzVpPkKxO\|QyQDN3PD;hQi=>
CHO	MW\GeY5kfGmxbjDhd5NigQ>?		MY[5NEBucW6\|	MlPpSIl{eGyjY3Xt[Y51KG:oIGuzTH1DVVNvN{K1OVE6KG[{b32gbJVu[W5iQ1KxJJJm[2WydH;yJIV5eHKnc4Pl[EBqdiCFSF:gZ4VtdHNiYX\0[ZIhQTBibXnud{BjgSC\|Y3nueIltdGG2aX;uJINwfW62aX7nMEBMcT1yLkCwNFc{\|ryP	Ml3lQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF7NkK1O\|UoRjJzOU[yOVc2RC:jPh?=
CHO-K1	MVHGeY5kfGmxbjDhd5NigQ>?			MoL4RY51[WexbnnzeEBi[3Srdnn0fUBifCCqdX3hckBESjFicnXj[ZB1d3JiZYjwdoV{e2WmIHnuJGNJVy2NMTDj[YxteyClbz3lfJBz\XO\|aX7nJGdidHCqYYGxOkBie3Onc4Pl[EBieyCrbnjpZol1cW:wIH;mJGNRPTV7NECtbY5lfWOnZDDpcpRz[WOnbHz1cIFzKGOjbHPpeY0hdW:kaXzpfoF1cW:wIHL5JIZtfW:{b33leJJ6NCCNZU2wMlAxOTIQvF2=	NVP4N41mRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKzO\|I5OzVpPkKyN\|czQDN3PD;hQi=>
CHO-K1	M4\DdWZ2dmO2aX;uJIF{e2G7			MYDEbZNxdGGlZX3lcpQhd2ZiW{PIYWNRPTV7NECg[pJwdSCqdX3hckBESjFicnXj[ZB1d3JiZYjwdoV{e2WmIHnuJGNJVy2NMTDj[YxteyxiS3m9NE4xODZ{zszN	NGe5OXM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkO3Nlg{PSd-MkKzO\|I5OzV:L3G+
CHO-K1	MY\GeY5kfGmxbjDhd5NigQ>?			MnL3SIl{eGyjY3Xt[Y51KG:oIGuzTH1EWDV3OUSwJIZzd21iQ1KyJJJm[2WydH;yJIV5eHKnc4Pl[EBqdiCFSF:tT\|Eh[2WubIOsJGtqRTBwM{Gz{txO	Mn3nQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ\|N{K4N\|UoRjJ{M{eyPFM2RC:jPh?=
HEK	MUfGeY5kfGmxbjDhd5NigQ>?			MWHEbZNxdGGlZX3lcpQhd2ZiW{PIYWNRNTV3LEm0NEBnem:vIHj1cYFvKHKnY3;tZolv[W62IFPCNUBz\WOncITvdkB1emGwc3\lZ5Rm\CCrbjDISWsh[2WubIOsJGtqRTBwMEGy{txO	NY\nWlJZRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK1OFg1PTdpPkKyOVQ5PDV5PD;hQi=>
HEK	M2nEbmZ2dmO2aX;uJIF{e2G7			NGDvOHZFcXOybHHj[Y1mdnRib3[gX\|NJZUOSLUW1MFk1OCCocn;tJIh2dWGwIILlZ49u[mmwYX70JGNDOiC{ZXPldJRweiC2cnHud4Zm[3SnZDDpckBJTUtiY3XscJMtKEurPUCuO\|nPxE1?	M4HpPVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{NUS4OFU4Lz5{MkW0PFQ2PzxxYU6=
CHO	NGrtOmlHfW6ldHnvckBie3OjeR?=		MWiyJIhzew>?	M3G3U2Rqe3CuYXPlcYVvfCCxZjDbN2heS1B3NTy5OFAh\nKxbTDoeY1idiCFQkGgdoVk\XC2b4Kg[ZhxemW\|c3XkJIlvKEOKTzDj[YxteyCjZoTldkAzKGi{czDifUBtcXG3aXSgd4NqdnSrbHzheIlwdiClb4XueIVzNCCNaU2wMlAyOjcQvF2=	MXS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjlzNkewO{c,OjJ7MU[3NFc9N2F-
CHO	NWHTVZBwTnWwY4Tpc44h[XO\|YYm=		NWrqUGE4OiCqcoO=	NGm4em9FcXOybHHj[Y1mdnRib3[gX\|NJZUOSNUWsPVQxKG[{b32gbJVu[W5iQ1KyJJJm[2WydH;yJIV5eHKnc4Pl[EBqdiCFSF:gZ4VtdHNiYX\0[ZIhOiCqcoOgZpkhdGmzdXnkJJNkcW62aXzsZZRqd25iY3;1cpRmeixiS3m9NE46\|ryP	M2T0R\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{OUG2O\|A4Lz5{MkmxOlcxPzxxYU6=
CHO	M{TqRmZ2dmO2aX;uJIF{e2G7			NVPIS2tPUW64ZYLz[UBi\2:waYP0JIFkfGm4aYT5JIFo[Wmwc4SgR2IyKHKnY3XweI9zKGW6cILld5Nm\CCrbjDoeY1idiCFSF:gZ4VtdHNiYYPz[ZN{\WRiYYOg[YZn\WO2IH;uJIZwenOtb3zpck1{fGmvdXzheIVlKGODTWCgcIV3\WxuIFnDOVA:OC5yNUJOwG0>	MnzGQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ7NUmyOFkoRjJ{OUW5NlQ6RC:jPh?=
CHO	NGDZU3RHfW6ldHnvckBie3OjeR?=		M4jIO\|EhcHJ?	M{TPXGRqe3CuYXPlcYVvfCCxZjDbN2heS1B3NUm0NEBnem:vIHj1cYFvKEOEMTDy[YNmeHSxcjDlfJBz\XO\|ZXSgbY4hS0iRIHPlcIx{KGmwY4XiZZRm\CCob4KgNUBpeixiS3m9NE4xOTB4zszN	NWO1NppuRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkOwO\|I{OzlpPkKzNFczOzN7PD;hQi=>
CHO	MkDaSpVv[3Srb36gZZN{[Xl?	NYOxflJ5RiByLkGgcm0>	NGL1Wo0yKGi{	M1rKXWlvfmW{c3WgZYdwdmm\|dDDhZ5Rqfmm2eTDheEBpfW2jbjDy[YNwdWKrbnHueEBESjFicnXj[ZB1d3JidILhcpNn\WO2ZXSgbY4hS0iRIHPlcIx{KGG\|c3Xzd4VlKGG\|IILl[JVkfGmxbjDv[kBcOzWVXVfUVIdidW2jUzDibY5lcW6pIHH0JF4hOC5zIH7NJIFnfGW{IEGgbJIh[nlibHnxeYllKHOlaX70bYxt[XSrb36gd5Bm[3S{b33leJJ6	MnTiQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN\|NUezNFcoRjJ\|M{W3N\|A4RC:jPh?=
N1E-115	MWXGeY5kfGmxbjDhd5NigQ>?	M4XUSFEhfU1?	M{DxS\|UhdWmwcx?=	MoX6TY53\XK\|ZTDh[49vcXO2IHHjeIl3cXS7IHH0JGNDOSC{ZXPldJRweiCrbjDtc5V{\SCQMVWtNVE2KGOnbHzzJIF{e2W\|c3XkJIF{KGmwaHnibZRqd25ib3[gW2lPKDV3LEKxNk0zNWmwZIXj[YQhTVKNMT:yJJBpd3OyaH;yfYxifGmxbjDheEAyKHWPIITy[YF1\WRiNTDtbY5{KHC{aX;yJJRwKFeLTjC1OUwzOTJvMjDjbIFtdGWwZ3WgZpkhX2W\|dHXyckBjdG:2IHHuZYx6e2m\|	M1vNW\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|M{W3N\|A4Lz5{M{O1O\|MxPzxxYU6=
CHO	MoexSpVv[3Srb36gZZN{[Xl?			MlPKRY51[WexbnnzeEBi[3Srdnn0fUBifCCqdX3hckBIWFJzODD0doFve2[nY4Tl[EBqdiCFSF:gZ4VtdHNiYYPz[ZN{\WRiYYOg[IVtfGF7LWTIR{1qdmS3Y3XkJIJmfGFvYYLy[ZN1cW5icnXjdpVqfG2nboSgbY5kfWKjdHXkJFYxKG2rboOgdJJqd3JidH:g[IVtfGF7LWTIR{Bi\GSrdHnvckBjgSCkZYThMYFzemW\|dHnuJJRz[W6\|bH;jZZRqd25iYYPzZZktKEmFNUC9NVAvOc7:TR?=	NGDpdmc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{[3PVk2PSd-MkO2O\|k6PTV:L3G+
HEK	MXTGeY5kfGmxbjDhd5NigQ>?		NILvOG4yKGi{	NXzOfYVqSW62YXfvcol{fCCjY4Tpeol1gSCjdDDoeY1idiCFQkGgdoVk\XC2b4Kgc5ZmemW6cILld5Nm\CCrbjDISWsh[2WubIOgZZN{\XO\|ZXSgZZMhYzN3U23HWHBo[W2vYTDibY5lcW6pIHHmeIVzKDFiaIKgZpkhdGmzdXnkJJNkcW62aXzsZZRqd25iY3;1cpRqdmdiYX7hcJl{cXNuIFXDOVA:OC5yMEG1{txO	M4HqclxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MUe1OVczLz5{NEG3OVU4OjxxYU6=
CHOK1	NGPHdGNHfW6ldHnvckBie3OjeR?=		M{LzPVEhcHJ?	M332OGRqe3CuYXPlcYVvfCCxZjDbN2heS1B3NUm0NEBnem:vIHj1cYFvKEOEMTDy[YNmeHSxcjDlfJBz\XO\|ZXSgbY4hS0iRS{GgZ4VtdHNiYX\0[ZIhOSCqcjDifUBtcXG3aXSgd4NqdnSrbHzheIlwdiClb4XueIlv\yCjbnHsfZNqeyxiS3m9NE4xODV7zszN	NGm5Zno9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEG3OVU4Oid-MkSxO\|U2PzJ:L3G+
CHO	MXLGeY5kfGmxbjDhd5NigQ>?		NIr3Smg1PSCvaX7z	Mn3SRY51[WexbnnzeEBi[3Srdnn0fUBifCCqdX3hckBESjFicnXj[ZB1d3Jic4ThZox6KGW6cILld5Nm\CCrbjDDTG8h[2WubIOgZ48u\XiycnXzd4lv\yClbz3lfJBz\XO\|aX7nJGdiOTVxMU[gZZN{\XO\|ZXSgZZMh[2GuY3n1cUBkfXK{ZX70JIFnfGW{IES1JI1qdnNiYomg[ox2dy12IFHNJIF{e2G7LDDJR\|UxRTBwMEGz{txO	NFqySoU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NES0OVMyOCd-MkS0OFU{OTB:L3G+
CHO	NHT2VFdHfW6ldHnvckBie3OjeR?=		MnfLOFUhdWmwcx?=	NX\2eowzSW62YXfvcol{fCCjY4Tpeol1gSCjdDDDRlIhemWlZYD0c5IhMHWwa37ve44hd3KrZ3nuLUB{fGGkbImg[ZhxemW\|c3XkJIlvKEOKTzDj[YxteyClbz3lfJBz\XO\|aX7nJINwNWW6cILld5NqdmdiR3GxOU8yPiCjc4Pld5Nm\CCjczDjZYxkcXWvIHP1dpJmdnRiYX\0[ZIhPDVibXnud{BjgSCobIXvMVQhSU1iYYPzZZktKEmFNUC9PU45\|ryP	NVOyd4Z{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS0OFU{OTBpPkK0OFQ2OzFyPD;hQi=>
CHO-K1	M1\0UGZ2dmO2aX;uJIF{e2G7		Mk\sNVAhdWmwcx?=	NGfndlBCdnSjZ3;ubZN1KGGldHn2bZR6KGG2IHj1cYFvKEOEMTDy[YNmeHSxcjDlfJBz\XO\|ZXSgbY4hS0iRLVuxJINmdGy\|IHHzd4V{e2WmIHHzJIlvcGmkaYTpc44hd2ZiQ2CtOVU6PDBvaX7keYNm\CCdM{XTYWdVWGejbX3hV{BjcW6maX7nJIlv[3WkYYTl[EBnd3JiMUCgcYlveyCycnnvdkB1dyCFUD21OVk1OC2laHHscIVv\2VibXXhd5Vz\WRiYX\0[ZIhOSCqcjDifUBj\XSjIHPveY51cW6pLDDLbV0xNjByMUdOwG0>	MVm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDlyMES4OEc,OjR7MEC0PFQ9N2F-
HEK293	NEXyOlJHfW6ldHnvckBie3OjeR?=		NFrqVo03OCCvaX7z	NXT0RoV6TGm\|cHzhZ4Vu\W62IH;mJHs{UF2VUkG0NVcyPkFiZn;ycUBpfW2jbjDDRlEhemWlZYD0c5Ih\XiycnXzd4VlKGmwIFjFT\|I6OyClZXzsd{Bi\nSncjC2NEBucW6\|IHL5JIJmfGFiY3;1cpRqdmduIFvpQVAvODBzON88US=>	Mn3XQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR7MEC0PFQoRjJ2OUCwOFg1RC:jPh?=
CHO-K1	M3XjdGZ2dmO2aX;uJIF{e2G7		MUK2NEBucW6\|	M2DvPGRqe3CuYXPlcYVvfCCxZjDbN2heS1BvNUW5OFAh\nKxbTDoeY1idiCFQkKgdoVk\XC2b4Kg[ZhxemW\|c3XkJIlvKEOKTz3LNUBk\WyuczDh[pRmeiB4MDDtbY5{KGK7IHLleIEh[2:3boTpcoctKEurPUCuOVIz\|ryP	NFLEdZA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEmwNFQ5PCd-MkS5NFA1QDR:L3G+
CHO	M1q0fGZ2dmO2aX;uJIF{e2G7		NUT2N2R1OiCqcoO=	NEfzZVNFcXOybHHj[Y1mdnRib3[gX\|NJZUOSNUWsPVQxKG[{b32gdoVkd22kaX7hcpQhcHWvYX6gR2IyKHKnY3XweI9zKGW6cILld5Nm\CCrbjDDTG8h[2WubIOgZYZ1\XJiMjDodpMh[nlibHnxeYllKHOlaX70bYxt[XSrb36gZ492dnSrbnesJGtqRTBwMEGyOu69VQ>?	MnjpQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR7MEC1OlEoRjJ2OUCwOVYyRC:jPh?=
CHO	NH\yfXRHfW6ldHnvckBie3OjeR?=		NEfFb3ozKGi{cx?=	NH6wUFVFcXOybHHj[Y1mdnRib3[gX\|NJZUOSNUWsPVQxKG[{b32gdoVkd22kaX7hcpQhcHWvYX6gR2IzKHKnY3XweI9zKGW6cILld5Nm\CCrbjDDTG8h[2WubIOgZYZ1\XJiMjDodpMh[nlibHnxeYllKHOlaX70bYxt[XSrb36gZ492dnSrbnesJGtqRTBwOd88US=>	M1LRRVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUCwOVYyLz5{NEmwNFU3OTxxYU6=
CHO	MXXGeY5kfGmxbjDhd5NigQ>?		MWq5NEBucW6\|	NIjlfHNC\2:waYP0JIFkfGm4aYT5JIF1KEeSUkW1JEh2dmuwb4fuJI9zcWerbjmg[ZhxemW\|c3XkJIlvKEOKTzDj[YxteyCjc4Pld5Nm\CCjczDpcohq[mm2aX;uJI9nKEySST3pcoR2[2WmIHLleIEu[XK{ZYP0bY4hfHKjboPsc4NifGmxbjDh[pRmeiB7MDDtbY5{KGK7IHz1cYlv\XOlZX7j[UBie3OjeTygSWM2OD1{LkCx{txO	NYKyNmttRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5NFA2PjFpPkK0PVAxPTZzPD;hQi=>
RD-HGA16	NV3zVYNqTnWwY4Tpc44h[XO\|YYm=			M2X1bmFvfGGpb37pd5Qh[WO2aY\peJkh[XRiQ1KxMW9ZOSCqZYTldo9lcW2ncjCoeY5sdm:5bjDvdolocW5rIHX4dJJme3OnZDDpckBTTC2KR1GxOkBk\WyuczDhd5Nme3OnZDDhd{BqdmirYnn0bY9vKG:oIH;y[ZhqdiCDLXnu[JVk\WRiY3HsZ4l2dSCvb3LpcIl7[XSrb36gZpkh\my3b4LvcYV1emmlIHntZYdqdmdicHzheIUhemWjZHXyJIFv[Wy7c3nzMEBM\T1yLkCwNe69VQ>?	NFjqdY49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEm0OFc{PCd-MkS5OFQ4OzR:L3G+
RD-HGA16	MlzXSpVv[3Srb36gZZN{[Xl?			NUnvfGU{SW62YXfvcol{fCCjY4Tpeol1gSCjdDDDRlEhemWlZYD0c5IhMHWwa37ve44hd3KrZ3nuLUBmgHC{ZYPz[YQhcW5iUlStTGdCOTZiY3XscJMh[XO\|ZYPz[YQh[XNiaX7obYJqfGmxbjDv[kBEWDV3OUSwMYlv\HWlZXSgZ4Ft[2m3bTDtc4JqdGm8YYTpc44h[nliZnz1c5JwdWW2cnnjJIlu[WerbnegdIxifGVicnXh[IVzKGGwYXz5d4l{NCCNZU2wMlAxOTIQvF2=	M1HjOlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUS0O\|M1Lz5{NEm0OFc{PDxxYU6=
Sf9	MkH5SpVv[3Srb36gZZN{[Xl?		M4[1XFIxKG2rboO=	M1nyRWlvfmW{c3WgZYdwdmm\|dDDhZ5Rqfmm2eTDheEBpfW2jbjDDRlEhemWlZYD0c5Ih\XiycnXzd4VlKGmwIGPmPUBk\WyuczDjc4V5eHKnc4PpcochT2KndHGx[4FudWF{IHHu[EBTW0d2IHHzd4V{e2WmIHHzJIRm\3KjZHH0bY9vKG:oIGvnZY1u[S1\|M2DdS3RRKGGodHXyJFIxKG2rboOgZpkhe3SnYXT5MZN1[XSnIFfUVIF{\SCjc4PhfUwhTUN3ME2wMlA2\|ryP	NFTrNVQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUC5OlI6Pyd-MkWwPVYzQTd:L3G+
Sf9	NXrlZXNMTnWwY4Tpc44h[XO\|YYm=		M1nk[FIxKG2rboO=	M1\VXWlvfmW{c3WgZYdwdmm\|dDDhZ5Rqfmm2eTDheEBpfW2jbjDDRlEhemWlZYD0c5Ih\XiycnXzd4VlKGmwIGPmPUBk\WyuczDjc4V5eHKnc4PpcochT2KndHGx[4FudWF{IHHu[EBTW0d2IHHzd4V{e2WmIHHzJIRm\3KjZHH0bY9vKG:oIGvnZY1u[S1\|M2DdS3RRKGGodHXyJFIxKG2rboOgZpkhe3SnYXT5MZN1[XSnIFfUVIF{\SCjc4PhfUwhTUN3ME2wMlA2ODF{zszN	NGnhS2o9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUC5OlI6Pyd-MkWwPVYzQTd:L3G+
CHO	M3LDOGZ2dmO2aX;uJIF{e2G7			NYO5bo9ESW62YXfvcol{fCCjY4Tpeol1gSCjZ3HpcpN1KEOEMWKgLJVvc26xd36gc5Jq\2mwKTDDTG8h[2WubIOgd5Ri[my7IHX4dJJme3OrbnegS4FteGijMU[gZZN{\XO\|ZXSgZZMhcW6qaXLpeIlwdiCxZjDDVFU2QTRyLXnu[JVk\WRiaX7jdoVie2ViaX6gbY51emGlZXzseYxieiClYXzjbZVuKGyndnXsJJBz\S22cnXheIVlKDFyIH3pcpMh[mWob4LlJGNRPTV7NECgd5RqdXWuYYTpc44h[nlibXnjdo9xdGG2ZTDy[YFl\XJiYnHz[YQh[XO\|YYmsJGlEPTB;MD6wNVM2\|ryP	NHLMNoM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkG1NVI{OSd-Mk[xOVEzOzF:L3G+
CHO	NWjnOodNTnWwY4Tpc44h[XO\|YYm=			M4f5XmFvfGGpb37pd5Qh[WO2aY\peJkh[WejaX7zeEBESjKUIDj1cotvd3ewIH;ybYdqdiliQ1jPJINmdGy\|IIP0ZYJtgSCneIDy[ZN{cW6pIFfhcJBp[TF4IHHzd4V{e2WmIHHzJIlvcGmkaYTpc44hd2ZiQ2C1OVk1OC2rbnT1Z4VlKGmwY4LlZZNmKGmwIHnueJJi[2WubIXsZZIh[2GuY3n1cUBt\X[nbDDwdoUufHKnYYTl[EAyOCCvaX7zJIJm\m:{ZTDDVFU2QTRyIIP0bY12dGG2aX;uJIJ6KG2rY4LvdIxifGVicnXh[IVzKGKjc3XkJIF{e2G7LDDJR\|UxRTlwMd88US=>	M2TDTlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MUWxNlMyLz5{NkG1NVI{OTxxYU6=
HEK293	MojISpVv[3Srb36gZZN{[Xl?			MVHJcY1m\GmjdHWgZY51[WexbnnzeE9Kdn[ncoPlJIFod26rc4SgZYN1cX[rdImgZZQhcGWvYXfncJV1cW6rbj30ZYdo\WRiaIXtZY4hS0JzIILlZ4VxfG:{IHX4dJJme3OnZDDpckBJTUt{OUOgZ4VtdHNiYYPz[ZN{\WRiYYOgdoV3\XK\|YXygc4YhOSC3TTDDVFU2NDl2MD3pcoR2[2WmIHnubIljcXSrb36gc4YhPSC3TTDmc5J{c2:uaX6tbY5lfWOnZDDjRW1RKGGlY4XteYxifGmxbjDifUBscW6ndHnjJINCVVBiYYPzZZk>	MmjoQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ{MEO2OVgoRjJ4MkCzOlU5RC:jPh?=
HEK293	MomxSpVv[3Srb36gZZN{[Xl?		MorDPVAhdWmwcx?=	NEX6cI1FcXOybHHj[Y1mdnRib3[gX\|NJZS2FUD21OVk1OCCocn;tJIh2dWGwIILlZ49u[mmwYX70JGNDOSC{ZXPldJRweiCneIDy[ZN{\WRiaX6gTGVMOjl\|IHPlcIx{KGGodHXyJFkxKG2rboOgZpkhS2:vcHX0bZRqd25iYnnu[Ilv\yCjc4PhfUwhU2mncU2wMlAyOs7:TR?=	MX:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjd3NkC5O{c,OjZ5NU[wPVc9N2F-
HEK293	MoPpSpVv[3Srb36gZZN{[Xl?		NHKweo46OCCvaX7z	NIfqRWxFcXOybHHj[Y1mdnRib3[gX\|NJZS2FUD21OVk1OCCocn;tJIh2dWGwIILlZ49u[mmwYX70JGNDOiC{ZXPldJRweiCneIDy[ZN{\WRiaX6gTGVMOjl\|IHPlcIx{KGGodHXyJFkxKG2rboOgZpkhS2:vcHX0bZRqd25iYnnu[Ilv\yCjc4PhfUwhU2mncU2wMlc6\|ryP	NHjrb\|Q9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{Nke1OlA6Pyd-Mk[3OVYxQTd:L3G+
CHO-K1	NYnPOXZXTnWwY4Tpc44h[XO\|YYm=			MlPxRY51[WexbnnzeEBi[3Srdnn0fUBifCCqdX3hckBESjFicnXj[ZB1d3JiZYjwdoV{e2WmIHnuJGNJVy2NMTDj[YxteyCjc4Pld5Nm\CCjczDpcohq[mm2aX;uJI9nKEOSNUW5OFAucW6mdXPl[EBqdnS{YXPlcIx2dGG{IHPhcINqfW1ibX;ibYxqgmG2aX;uJIJ6KEOjbHPlbY4uPCCDTT3zeIFqdmmwZzDiZZNm\CCITFnQVkBie3OjeTygT4U:OC5yMEGx{txO	MkfSQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ6MkexN\|coRjJ4OEK3NVM4RC:jPh?=
CHO	Mle3SpVv[3Srb36gZZN{[Xl?		M4\aPFkxKHOnY4O=	NWPPW4djUW64ZYLz[UBi\2:waYP0JIFkfGm4aYT5JIF1KGi3bXHuJGNDOSC{ZXPldJRweiCneIDy[ZN{\WRiaX6gR2hQKGOnbHzzJIF{e2W\|c3XkJIF{KGmwY4LlZZNmKGmwIHnueJJi[2WubIXsZZIh[2GuY3n1cUBud2KrbHn6ZZRqd25iYX\0[ZIhQTBic3Xjd{BjgSCFYXzj[YlvNTRiQV2td5RicW6rbnegZoF{\WRiRlzJVHIh[XO\|YYmsJGVEPTB;MD6wNFXPxE1?	MYK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjh{N{GzO{c,OjZ6MkexN\|c9N2F-
SJ-GBM2	M4e1dJFJXFNiYYPzZZk>			NXO0c5VReUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGPKMWdDVTJiY3XscJM>	MWq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
A673	MnXudWhVWyCjc4PhfS=>			NFjpfXJyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiQU[3N{Bk\Wyucx?=	Mkn1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
SK-N-MC	MmewdWhVWyCjc4PhfS=>			M4mxNZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCVSz3OMW1EKGOnbHzz	Ml7KQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
BT-37	MUDxTHRUKGG\|c3H5			MWjxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhSlRvM{egZ4VtdHN?	Mk\1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
SK-N-SH	MkfxdWhVWyCjc4PhfS=>			M{mxSJFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCVSz3OMXNJKGOnbHzz	MkjCQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
NB1643	MmLhdWhVWyCjc4PhfS=>			NV6zZotUeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IF7CNVY1OyClZXzsdy=>	NVfQWoQ5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
LAN-5	MnvkdWhVWyCjc4PhfS=>			NV\SelA6eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IFzBUk02KGOnbHzz	NWfjcllqRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
BT-12	NGDZdnhyUFSVIHHzd4F6			MYjxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhSlRvMUKgZ4VtdHN?	MXS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
OHS-50	NVPmWmR4eUiWUzDhd5NigQ>?			M2\NXpFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCRSGOtOVAh[2WubIO=	MkezQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
RD	NWL4TYJWeUiWUzDhd5NigQ>?			MUHxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhWkRiY3XscJM>	NIfMblI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
A673	M{i3TZFJXFNiYYPzZZk>			MkTIdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgRVY4OyClZXzsd{k>	NYLS[pk1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
SK-N-MC	MXTxTHRUKGG\|c3H5			NFrPcZByUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBUUy2QLV3DJINmdGy\|	NXP2T2JjRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
DAOY	Ml7MdWhVWyCjc4PhfS=>			MXrxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDERW9[KGOnbHzz	NIDhU\|k9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
TC32	M{PybZFJXFNiYYPzZZk>			NGjneIlyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBVSzN{IHPlcIx{	NWnRRYFlRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
U-2 OS	NEflPYVyUFSVIHHzd4F6			MY\xTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDVMVIhV1NiY3XscJM>	MlzOQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
Rh41	NHzPUJByUFSVIHHzd4F6			NIrpOJhyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBTcDRzIHPlcIx{	NW[2[2FqRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
Saos-2	NGTzO4VyUFSVIHHzd4F6			NGjDSZhyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBU[W:\|LUKgZ4VtdHN?	NXXkSYVpRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
CHOK1	M2\OXGZ2dmO2aX;uJIF{e2G7		MYK5NEBucW6\|	MnHXTY53\XK\|ZTDh[49vcXO2IHHjeIl3cXS7IHH0JGMufGW{bXnuZYxtgSCycn;sbY5sNXSjZ3fl[EBud3W\|ZTDDRlIhemWlZYD0c5Ih\XiycnXzd4VlKGmwIFPIU2syKGOnbHzzJIhiemKxcnnu[{Bj\XSjLXfhcIFkfG:\|aXThd4Uh\W68eX3lJIZ2e2WmIHLleIEu[XK{ZYP0bY4h[XO\|ZYPz[YQh[XNiaX7jdoVie2ViaX6gZoV1[S2jcoLld5RqdiC{ZXPyeYl1dWWwdDDh[pRmeiB7MDDtbY5{KGK7IHPo[Y1qdHWvaX7ld4NmdnRiYYPzZZktKEWFNUC9NE4xOTYQvF2=	M2nlfFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7OUO5O\|Q1Lz5{OUmzPVc1PDxxYU6=
HEK293	NVHjNFI2TnWwY4Tpc44h[XO\|YYm=			Ml7sRY51[WexbnnzeEBi[3Srdnn0fUBifCCqdX3hckBESjFicnXj[ZB1d3JiZYjwdoV{e2WmIHnuJGhGUzJ7MzDj[YxteyCkeTDHWHBo[W2vYWOgZolv\GmwZzDhd5NigSxiS3W9NE4xODB{zszN	MV:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODB5N{[wPUc,OzByN{e2NFk9N2F-
HEK293	NVjwd21mTnWwY4Tpc44h[XO\|YYm=		MX65NEB{\WO\|	MWXJcpZmenOnIHHnc45qe3RiYXP0bZZqfHliYYSgbJVu[W5iQ1KxJJJm[2WydH;yJIV5eHKnc4Pl[EBqdiCKRVuyPVMh[2WubIOgZ48u\XiycnXzd4lv\yCJYXzwbIFyOTZiYYPz[ZN{\WRiYYOgbY5pcWKrdHnvckBw\iClYXzjbZVuKG2xYnnsbZpifGmxbjDh[pRmeiB7MDDz[YN{KGK7IHPhcINmcW5vNDDBRW0h\HmnLXLhd4VlKE[OSWDSJIF{e2G7LDDFR\|UxRTBwNUi2{txO	M3z1clxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNyMEe3OlA6Lz5\|MEC3O\|YxQTxxYU6=
HEK293	NYftVJhvTnWwY4Tpc44h[XO\|YYm=		M1PqNFMxKG2rboO=	M1TabWlvfmW{c3WgZYdwdmm\|dDDhZ5Rqfmm2eTDheEBpfW2jbjDDRlEhemWlZYD0c5Ih\XiycnXzd4VlKGmwIFjFT\|I6OyClZXzsd{Bie3Onc4Pl[EBieyCrbnjpZol1cW:wIH;mJIZwenOtb3zpck1qdmS3Y3XkJINCVVBiYXPjeY12dGG2aX;uJIFnfGW{IEOwJI1qdnNiYomgTHRTTiCjc4PhfUwhTUN3ME2wMlAxPDIQvF2=	NIP5eVM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9\|MEOzPVM5Pyd-M{CzN\|k{QDd:L3G+
CHO	NEHEV\|BHfW6ldHnvckBie3OjeR?=			NFzsVGJFcXOybHHj[Y1mdnRib3[gX\|NJZS2FUEW1PVQxKG[{b32gbJVu[W5icnXjc41jcW6jboSgZ4FvdmGkaX7vbYQhS0JzIILlZ4VxfG:{IHX4dJJme3OnZDDpckBEUE9iY3XscJMh[nlicnHkbY9tcWejbnSgZolv\GmwZzDhd5NigSxiS3m9NE4yPDQQvF2=	NHPNblg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9\|MU[wPVYxQCd-M{G2NFk3ODh:L3G+
CHO	MXnGeY5kfGmxbjDhd5NigQ>?			Ml;FRYdwdmm\|dDDhZ5Rqfmm2eTDheEBpfW2jbjDHVHI2PSCneIDy[ZN{\WRiaX6gR2hQKGOnbHzzJIF{e2W\|c3XkJIF{KGmwZIXjeIlwdiCxZjDMVGkucW6mdXPl[EBj\XSjLXHydoV{fGmwIILlZ5J2cXSvZX70JIJ6KGKndHGt[4Ft[WO2b4Pp[IF{\SCnbor5cYUh\nKjZ33lcpQh[2:vcHzlcYVvfGG2aX;uJI1mfGixZDygSWM2OD1{LkCx{txO	NHLMVpI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOTFxJ{7DbGVOSkx:L3G+
CHO	MlHjSpVv[3Srb36gZZN{[Xl?			NUPtPFlTSWexbnnzeEBi[3Srdnn0fUBifCCqdX3hckBIWFJzODDlfJBz\XO\|ZXSgbY4hS0iRIHPlcIx{KGG\|c3Xzd4VlKGG\|IHnu[JVkfGmxbjDv[kBj\XSjLXHydoV{fGmwIILlZ5J2cXSvZX70JIJ6KGKndHGt[4Ft[WO2b4Pp[IF{\SCnbor5cYUh\nKjZ33lcpQh[2:vcHzlcYVvfGG2aX;uJI1mfGixZDygSWM2OD1zMD6x{txO	NU\UU45{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTFzLze+R4hGVUKOPD;hQi=>

... Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID
Western blot	p-LRP6 / LRP6 / Lgr5 ; PubMed: 29354056 Front Pharmacol Representative Western blot analysis of Lgr5, LRP6 and phosphorylated (Ser1490) LRP6. GAPDH was used as loading control. β-catenin; PubMed: 29354056 Front Pharmacol Representative Western blot analysis (left) of β-Catenin in total protein lysates from GTG7 cells. Right, densitometric analysis of β-Catenin normalized vs. GAPDH, used as loading control. Results are expressed as means ± SD of 3 independent experiments performed at least in duplicate (∗∗p < 0.01). CD44 / Lgr5 / CD133 / EpCAM ; PubMed: 29354056 Front Pharmacol Representative Western blot analysis of CD44, Lgr5, CD133 and EpCAM in total protein lysates from HCT116 cells. GAPDH was used as loading control.	29354056
Immunofluorescence	Lgr5 ; PubMed: 29354056 Front Pharmacol Confocal microscopy analysis of Lgr5 (red fluorescence) in GTG7 cells treated with Rimonabant at indicated doses for 18 h. Nuclei were stained with Hoechst (blue fluorescence); GFP (green); Scale bar = 5 μm. β-catenin; PubMed: 29354056 Front Pharmacol Confocal microscopy analysis of β-Catenin (red) in GTG7 cells treated with Rimonabant at indicated doses for 18 h. Nuclei were stained with Hoechst (blue fluorescence); GFP (green); Scale bar = 5 μm.	29354056

In vivo

Rimonabant is administered intraperitoneally or orally potently and dose-dependently antagonize classical pharmacological and behavioural effectos of cannabinoid receptor agonists. ^[3] In the mouse model of azoxymethane-induced colon carcinogenesis, Rimonabant significantly decreased aberrant crypt foci (ACF) formation, which precedes colorectal cancer. ^[4] Rimonabant (10 mg/kg by gavage) is fed for 2 weeks to 3-month-old male obese Zucker rats as an impaired glucose tolerance model and for 10 weeks to 6-month-old male obese Zucker rats as a model of the metabolic syndrome. RANTES (Regulated upon Activation, Normal T cell Expressed, and Secreted) and MCP-1 (monocyte chemotactic protein-1) serum levels are increased in obese vs lean Zucker rats and significantly reduced by long-term treatment with Rimonabant, which slowes weight gain in rats with the metabolic syndrome. Neutrophils and monocytes are significantly increased in young and old obese vs lean Zucker rats and lowered by Rimonabant. Platelet-bound fibrinogen is significantly enhanced in obese vs lean Zucker rats of both age, and is reduced by Rimonabant. Platelets from obese rats are more sensitive to thrombin-induced aggregation and adhesion to fibrinogen, which are both attenuated by Rimonabant therapy. ^[5]

Protocol

Kinase Assay: ^[1]	- Collapse Radioligand Binding Assay: Human CB1 and CB2 stably transfect HEK 293 cells and cell membrane is purified. 0.2-8 μg of the purified membrane is incubated with 0.75 nM [³H] CP55,940 and Rimonabant in the incubation buffer (50 mM Tris-HCl, 5 mM MgCl₂, 1 mM EDTA, 0.3%BSA, pH 7.4). The non-specific binding is defined in the presence of 1 μM of CP55,940. The reactions are incubated for one and a half hours at 30 °C in Multiscreen. The reactions are terminated by manifold filtration and washed four times with ice-cold wash buffer (50mM Tris, pH 7.4, 0.25% BSA).The radioactivity bound to the filters is measured by Topcount. The IC50 is determined as the concentration of Rimonabant required to inhibit 50% of the binding of [³H] CP55,940 and calculated by non-linear regression.
Cell Research: ^[2]	- Collapse Cell lines: Raw 264.7 cells Concentrations: 0,1,4 μM Incubation Time: 17 hours Method: Raw 264.7 cells (2 × 10⁶ /well) in 12-well plates are rinsed with PBS and refed culture media supplemented with varying amounts of Rimonabant 1 hour prior to supplementation with 7-ketocholesterol (7KC). All wells are adjusted to receive equal amounts of vehicle. Following 16-hour incubation, caspase-3 and caspase 3-like activity are determined using a fluorogenic substrate (Ac-DEVD-AFC) and a spectrofluorometer equipped with a microplate reader. (Only for Reference)
Animal Research: ^[3]	- Collapse Animal Models: Male mice and male rats Dosages: 20 ml/kg (mice) and 5 ml/kg (rats) Administration: Rimonabant is administered i.p. (30 minutes) or p.o. (1hour) before the i.v. injection of WIN55212-2. (Only for Reference)

References

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Solubility (25°C)

In vitro	DMSO	25 mg/mL (53.9 mM)
	Water	Insoluble
	Ethanol	'''''2 mg/mL
In vivo	Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 5% DMSO+40% PEG 300+5% Tween 80+dd H2O For best results, use promptly after mixing.	5 mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information Download Rimonabant (SR141716) SDF

Molecular Weight	463.79
Formula	C₂₂H₂₁Cl₃N₄O
CAS No.	168273-06-1
Storage	3 years-20°C powder 2 years-80°C in solvent
Synonyms	N/A
Smiles	CC1=C(N(N=C1C(=O)NN2CCCCC2)C3=C(C=C(C=C3)Cl)Cl)C4=CC=C(C=C4)Cl

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Method for preparing DMSO master liquid: ： mg drug pre-dissolved in μL DMSO (Master liquid concentration mg/mL， Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation：Take μL DMSO master liquid, next addμL PEG300， mix and clarify, next addμL Tween 80，mix and clarify, next add μL ddH₂O，mix and clarify.

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Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

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Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
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Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2021-09-06)

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT00750347	Completed	Drug: Rimonabant and Paracetamol and placebo	Pain	University Hospital Clermont-Ferrand	September 2008	Phase 1
NCT00656487	Completed	Drug: rimonabant\|Drug: placebo	Cannabis Dependence\|Cannabis Withdrawal	The Scripps Research Institute\|National Institute on Drug Abuse (NIDA)	April 30 2008	Phase 2
NCT00546325	Completed	Drug: Rimonabant\|Drug: Placebo	Diabetes Mellitus Type 2	Sanofi	October 2007	Phase 3
NCT00525681	Completed	Drug: cyclosporine A\|Drug: tacrolimus	Renal Transplantation	University of Oslo School of Pharmacy	September 2007	Phase 4
NCT00584389	Terminated	Drug: rimonabant\|Behavioral: Dietary intervention	Obesity	University of Surrey\|European Foundation for the Study of Diabetes\|Royal Surrey County Hospital NHS Foundation Trust	July 2007	Phase 4
NCT01041170	Completed	Drug: THC\|Drug: Rimonobant\|Drug: Rimonabant	Cannabis\|Dependence	National Institute on Drug Abuse (NIDA)\|National Institutes of Health Clinical Center (CC)	April 16 2006	Phase 1

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Rimonabant (SR141716)