TESIS Solesio Torregrosa - Ruidera - Universidad de Castilla

Transcription

hE/sZ^/^d/>>ʹ>DE,
ĞƉĂƌƚĂŵĞŶƚŽĚĞŝĞŶĐŝĂƐDĠĚŝĐĂƐ
&ĂĐƵůƚĂĚĚĞDĞĚŝĐŝŶĂ
&hE/ME^K/K^E/dZ/^d/>>ʹ>DE,
hŶŝĚĂĚĚĞEĞƵƌŽƉƐŝĐŽĨĂƌŵĂĐŽůŽŐşĂdƌĂƐůĂĐŝŽŶĂů
ŽŵƉůĞũŽ,ŽƐƉŝƚĂůĂƌŝŽhŶŝǀĞƌƐŝƚĂƌŝŽĚĞůďĂĐĞƚĞ
^dh/K^WZ>ZdZ//ME>K^WZK^K^/ED/
D/dKKEZ/>EDK>K^yWZ/DEd>^E&ZD^
EhZK'EZd/s^͘
DĞŵŽƌŝĂĚŝƌŝŐŝĚĂƉŽƌƌĂ͘ŹĂ͘DĂƌşĂ&ƌĂŶĐŝƐĐĂ'ĂůŝŶĚŽŶĂǇĂ͕ĐŽŶůĂƋƵĞŹĂ͘DĂƌşĂ
ĚĞůĂŶĐĂƌŶĂĐŝſŶ^ŽůĞƐŝŽdŽƌƌĞŐƌŽƐĂĂƐƉŝƌĂĂŽďƚĞŶĞƌĞůŐƌĂĚŽĚĞŽĐƚŽƌĂ͘
ůďĂĐĞƚĞ͕ϮϴĚĞ:ƵŶŝŽĚĞϮ͘Ϭϭϯ
ůďĂĐĞƚĞ͕ϮϴĚĞ:ƵŶŝŽĚĞϮ͘Ϭϭϯ
ƌĂ͘ ŹĂ͘ DĂƌşĂ &ƌĂŶĐŝƐĐĂ 'ĂůŝŶĚŽ ŶĂǇĂ͕ /ŶǀĞƐƚŝŐĂĚŽƌĂ &/^ ĚĞů ŽŵƉůĞũŽ
,ŽƐƉŝƚĂůĂƌŝŽƵŶŝǀĞƌƐŝƚĂƌŝŽĚĞůďĂĐĞƚĞ͕
Zd/&/K͗
YƵĞ ůĂƉƌĞƐĞŶƚĞ ƚĞƐŝƐ ĚŽĐƚŽƌĂů͕ƚŝƚƵůĂĚĂ ͞ƐƚƵĚŝŽƐ ƉĂƌĂ ůĂ ĐĂƌĂĐƚĞƌŝǌĂĐŝſŶĚĞ ůĂ
ĚŝŶĄŵŝĐĂ
ŵŝƚŽĐŽŶĚƌŝĂů
ĞŶ
ŵŽĚĞůŽƐ
ĞǆƉĞƌŝŵĞŶƚĂůĞƐ
ĚĞ
ĞŶĨĞƌŵĞĚĂĚĞƐ
ŶĞƵƌŽĚĞŐĞŶĞƌĂƚŝǀĂƐ͟ĐŽŶƐƚŝƚƵǇĞĞůƚƌĂďĂũŽĚĞŝŶǀĞƐƚŝŐĂĐŝſŶƌĞĂůŝǌĂĚŽďĂũŽŵŝĚŝƌĞĐĐŝſŶ
ƉŽƌ ŹĂ͘ DĂƌşĂ ĚĞ ůĂ ŶĐĂƌŶĂĐŝſŶ ^ŽůĞƐŝŽ dŽƌƌĞŐƌŽƐĂ ĞŶ ůĂ hŶŝĚĂĚ ĚĞ
EĞƵƌŽƉƐŝĐŽĨĂƌŵĂĐŽůŽŐşĂ dƌĂƐůĂĐŝŽŶĂů͕ ƉĞƌƚĞŶĞĐŝĞŶƚĞ Ă ůĂ hŶŝĚĂĚ ĚĞ /ŶǀĞƐƚŝŐĂĐŝſŶ ĚĞů
ŽŵƉůĞũŽ,ŽƐƉŝƚĂůĂƌŝŽhŶŝǀĞƌƐŝƚĂƌŝŽĚĞůďĂĐĞƚĞ͕ĚĞƐĚĞƋƵĞƐĞŝŶĐŽƌƉŽƌſĂůŐƌƵƉŽ͕ĞŶ
ŵĂǇŽĚĞϮ͘ϬϬϴ͘
ƐƚĞƚƌĂďĂũŽ͕ƉĞƌƚĞŶĞĐŝĞŶƚĞĂůĄŵďŝƚŽĚĞůĂEĞƵƌŽĨĂƌŵĂĐŽůŽŐşĂ͕ƉƌĞƐĞŶƚĂĐŽŵŽ
ŽďũĞƚŝǀŽƉƌŝŶĐŝƉĂůĞůĞƐƚƵĚŝŽĚĞůŽƐĚŝǀĞƌƐŽƐŵĞĐĂŶŝƐŵŽƐŵŝƚŽĐŽŶĚƌŝĂůĞƐŝŵƉůŝĐĂĚŽƐĞŶ
ůĂĂƉĂƌŝĐŝſŶǇĞǀŽůƵĐŝſŶĚĞůĂƐĚŝĨĞƌĞŶƚĞƐĞŶĨĞƌŵĞĚĂĚĞƐŶĞƵƌŽĚĞŐĞŶĞƌĂƚŝǀĂƐ͕ŚĂĐŝĞŶĚŽ
ĞƐƉĞĐŝĂů ŚŝŶĐĂƉŝĠ ĞŶ ĂƋƵĞůůŽƐ ƌĞůĂĐŝŽŶĂĚŽƐ ĐŽŶ ůĂ ĚŝŶĄŵŝĐĂ ŵŝƚŽĐŽŶĚƌŝĂů͘ WĂƌĂ ƐƵ
ƌĞĂůŝǌĂĐŝſŶ͕ƐĞŚĂĞŵƉůĞĂĚŽƵŶŵŽĚĞůŽĐĞůƵůĂƌĚĞŶĞƵƌŽŶĂƐĚŽƉĂŵŝŶĠƌŐŝĐĂƐ͘
ƐƚĂƚĞƐŝƐƌĞƷŶĞůĂĐĂůŝĚĂĚǇĞůƌŝŐŽƌĐŝĞŶƚşĨŝĐŽŶĞĐĞƐĂƌŝŽƐƉĂƌĂƐĞƌĚĞĨĞŶĚŝĚĂĞŶ
ůĂhŶŝǀĞƌƐŝĚĂĚĚĞĂƐƚŝůůĂʹ>ĂDĂŶĐŚĂ͕ĐŽŵŽƌĞƋƵŝƐŝƚŽŶĞĐĞƐĂƌŝŽƉĂƌĂƋƵĞŹĂ͘DĂƌşĂ
ĚĞůĂŶĐĂƌŶĂĐŝſŶ^ŽůĞƐŝŽdŽƌƌĞŐƌŽƐĂĂƐƉŝƌĞĂůŐƌĂĚŽĚĞŽĐƚŽƌĂ͕ĂƐşĐŽŵŽĂůĂŵĞŶĐŝſŶ
ĚĞ͞ŽĐƚŽƌƵƌŽƉĞƵƐ͘͟
ŶůďĂĐĞƚĞ͕ĂϮϴĚĞ:ƵŶŝŽĚĞϮ͘Ϭϭϯ
&ĚŽ͗͘DĂƌşĂ&ƌĂŶĐŝƐĐĂ'ĂůŝŶĚŽŶĂǇĂ
ŝƌĞĐƚŽƌĂĚĞůĂƚĞƐŝƐ͘
Ϯ
DĂƌşĂ ĚĞ ůĂ ŶĐĂƌŶĂĐŝſŶ ^ŽůĞƐŝŽ dŽƌƌĞŐƌŽƐĂ ĞƐƚĄ ĐŽŶƚƌĂƚĂĚĂ ĚĞƐĚĞ DĂǇŽ ĚĞ
Ϯ͘ϬϬϴĐŽŵŽƚĠĐŶŝĐŽƐƵƉĞƌŝŽƌĚĞĂƉŽǇŽĂůĂŝŶǀĞƐƚŝŐĂĐŝſŶ͕ĂůĂŵƉĂƌŽĚĞůƉƌŽǇĞĐƚŽDZ
ϬϳͬϬϮϯ͕ ĐŽŶĐĞĚŝĚŽ Ă ůĂ ƌĂ͘ DĂƌşĂ &ƌĂŶĐŝƐĐĂ 'ĂůŝŶĚŽ ŶĂǇĂ͘ ĚĞŵĄƐ͕ ĚƵƌĂŶƚĞ ĞƐƚŽƐ
ĂŹŽƐ͕ůĂĚŽĐƚŽƌĂŶĚĂŚĂƉĂƌƚŝĐŝƉĂĚŽĞŶŽƚƌŽƐĚŽƐƉƌŽǇĞĐƚŽƐĚĞŝŶǀĞƐƚŝŐĂĐŝſŶĐŽŶĐĞĚŝĚŽƐ
ĂůĂƌĂ͘'ĂůŝŶĚŽƉŽƌƉĂƌƚĞĚĞůĂ&ƵŶĚĂĐŝſŶƉĂƌĂůĂ/ŶǀĞƐƚŝŐĂĐŝſŶ^ĂŶŝƚĂƌŝĂĚĞů/ŶƐƚŝƚƵƚŽ
ĚĞ^ĂůƵĚĂƌůŽƐ///͕;W/ϬϴͲϬϲϵϯǇW/ϭϭͲϬϬϳϯϲͿ͘
ůŐƵŶŽƐ ĚĞ ůŽƐ ƚƌĂďĂũŽƐ ĂƋƵş ƉƌĞƐĞŶƚĂĚŽƐ ƐŽŶ ĨƌƵƚŽ ĚĞ ůĂ ĐŽůĂďŽƌĂĐŝſŶ ĐŽŶ Ğů
ŐƌƵƉŽ ĚĞů ƌ͘ :ŽĂƋƵşŶ :ŽƌĚĄŶ ƵĞƐŽ͕ ƉƌŽĨĞƐŽƌ ƚŝƚƵůĂƌ ĚĞů ĄƌĞĂ ĚĞ &ĂƌŵĂĐŽůŽŐşĂ ĚĞ ůĂ
&ĂĐƵůƚĂĚĚĞDĞĚŝĐŝŶĂĚĞůďĂĐĞƚĞĚĞůĂhŶŝǀĞƌƐŝĚĂĚĚĞĂƐƚŝůůĂͲ>ĂDĂŶĐŚĂ͘
ƵƌĂŶƚĞ Ğů ĐƵƌƐŽ ĂĐĂĚĠŵŝĐŽ Ϯ͘ϬϬϵͬϮ͘ϬϭϬ͕ ůĂ ĚŽĐƚŽƌĂŶĚĂ ƐƵƉĞƌſ Ğů ƉĞƌŝŽĚŽ ĚĞ
ĚŽĐĞŶĐŝĂĚĞůƉƌŽŐƌĂŵĂĚĞĚŽĐƚŽƌĂĚŽĞŶŝŽŵĞĚŝĐŝŶĂǆƉĞƌŝŵĞŶƚĂů͕ŝŵƉĂƌƚŝĚŽĞŶƉŽƌůĂ
hŶŝǀĞƌƐŝĚĂĚ ĚĞ ĂƐƚŝůůĂͲ>Ă DĂŶĐŚĂ ĞŶ ůĂ &ĂĐƵůƚĂĚ ĚĞ DĞĚŝĐŝŶĂ ĚĞ ůďĂĐĞƚĞ͕ Ğů ĐƵĂů
ĐŽŶƚĂďĂĐŽŶůĂDĞŶĐŝſŶĚĞĂůŝĚĂĚĚĞůDŝŶŝƐƚĞƌŝŽĚĞĚƵĐĂĐŝſŶĚĞƐĚĞĞůĐƵƌƐŽϮϬϬϲͲ
ϮϬϬϳ͕ ;DϮϬϬϲͲϬϬϬϯϳͿ͘ ŝĐŚŽ ƉĞƌŝŽĚŽ ĐŽŶĐůƵǇſ ĐŽŶ ůĂ ŽďƚĞŶĐŝſŶ ĚĞů ŝƉůŽŵĂ ĚĞ
ƐƚƵĚŝŽƐǀĂŶǌĂĚŽƐĞŶDĂǇŽĚĞϮ͘ϬϭϬ͘
Ɛş ŵŝƐŵŽ͕ ůĂ ĚŽĐƚŽƌĂŶĚĂ ƌĞĂůŝǌſ ƵŶĂ ĞƐƚĂŶĐŝĂ ĨŽƌŵĂƚŝǀĂ ĚĞ ĐƵĂƚƌŽ ŵĞƐĞƐ ĚĞ
ĚƵƌĂĐŝſŶ͕ƐƵďǀĞŶĐŝŽŶĂĚĂŐƌĂĐŝĂƐĂƵŶĂŽůƐĂĚĞŵƉůŝĂĐŝſŶĚĞƐƚƵĚŝŽƐĚĞů/ŶƐƚŝƚƵƚŽĚĞ
^ĂůƵĚ ĂƌůŽƐ ///͕ ĞŶ Ğů ůĂďŽƌĂƚŽƌŝŽ ĚĞů ƌ͘ DŝĐŚĂĞů W͘ DƵƌƉŚǇ͕ ĞŶ Ğů DŝƚŽĐŚŽŶĚƌŝĂů
ZĞƐĞĂƌĐŚ ĞŶƚĞƌ ĚĞ ĂŵďƌŝŐĞ͕ ZĞŝŶŽ hŶŝĚŽ͘ ƵƌĂŶƚĞ ĞƐƚĞ ƉĞƌŝŽĚŽ͕ ůĂ ĚŽĐƚŽƌĂŶĚŽ
ƉƌŽĨƵŶĚŝǌſ ƐƵƐ ĐŽŶŽĐŝŵŝĞŶƚŽƐ ƐŽďƌĞ ĞƐƚƌĠƐ ŽǆŝĚĂƚŝǀŽ Ǉ ĂƉƌĞŶĚŝſ Ă ƵƚŝůŝǌĂƌ ŶƵĞǀĂƐ
ƚĠĐŶŝĐĂƐƉĂƌĂůĂĐƵĂŶƚŝĨŝĐĂĐŝſŶĚĞůŵŝƐŵŽ͘&ƌƵƚŽĚĞůĂĐŝƚĂĚĂĞƐƚĂŶĐŝĂ͕ƐĞůůĞǀſĂĐĂďŽ
ƵŶĂƌƚşĐƵůŽĚĞĐŽůĂďŽƌĂĐŝſŶĐŽŶĞůŐƌƵƉŽĚĞůƌ͘DƵƌƉŚǇ͘
ƵƌĂŶƚĞ ĞƐƚŽƐ ĐƵĂƚƌŽ ĂŹŽƐ͕ ůĂ ĚŽĐƚŽƌĂŶĚĂ ŚĂ ƉĂƌƚŝĐŝƉĂĚŽ ĞŶ ůĂƐ ƐŝŐƵŝĞŶƚĞƐ
ƉƵďůŝĐĂĐŝŽŶĞƐ͗
• ^ŽůĞƐŝŽD͕^ĂĞǌͲƚŝĞŶǌĂƌ^͕:ŽƌĚĄŶ:͕'ĂůŝŶĚŽD&͘ŚĂƌĂĐƚĞƌŝǌĂƚŝŽŶŽĨŵŝƚŽƉŚĂŐǇŝŶ
ƚŚĞϲͲK,WĂƌŬŝŶƐŽŶǲƐĚŝƐĞĂƐĞŵŽĚĞů͘dŽǆŝĐŽůŽŐŝĐĂů^ĐŝĞŶĐĞƐ͘WD/͗ϮϮϴϮϭϴϱϬ͘
ϰ
• ^ŽůĞƐŝŽ D͕ WƌŝŵĞ d͕ >ŽŐĂŶ ͕ DƵƌƉŚǇ DW͕ :ŽƌĚĄŶ :͕ 'ĂůŝŶĚŽ D&͘ dŚĞ
ŵŝƚŽĐŚŽŶĚƌŝĂͲƚĂƌŐĞƚĞĚĂŶƚŝͲŽǆŝĚĂŶƚDŝƚŽYƌĞĚƵĐĞƐĂƐƉĞĐƚƐŽĨŵŝƚŽĐŚŽŶĚƌŝĂůĨŝƐƐŝŽŶ
ŝŶƚŚĞϲͲK,ͲŝŶĚƵĐĞĚĐĞůůƵůĂƌŵŽĚĞůŽĨWĂƌŬŝŶƐŽŶǲƐĚŝƐĞĂƐĞ͘DŽůĞĐƵůĂƌĂƐŝƐ
ŽĨŝƐĞĂƐĞ͘WD/͗ϮϮϴϰϲϲϬϳ͘
• ^ŽůĞƐŝŽ D͕ ^ĂĞǌͲƚŝĞŶǌĂƌ ^͕ :ŽƌĚĂŶ :͕ 'ĂůŝŶĚŽ D&͘ ϯͲEŝƚƌŽƉƌŽƉŝŽŶŝĐ ĂĐŝĚ ŝŶĚƵĐĞƐ
ĂƵƚŽƉŚĂŐǇ ďǇ ŵŝƚŽĐŚŽŶĚƌŝĂů ƉĞƌŵĞĂďŝůŝƚǇ ƚƌĂŶƐŝƚŝŽŶ ƉŽƌĞ ĨŽƌŵĂƚŝŽŶ ƌĂƚŚĞƌ ƚŚĂŶ
ĂĐƚŝǀĂƚŝŽŶ ŽĨ ƚŚĞ ŵŝƚŽĐŚŽŶĚƌŝĂů ĨŝƐƐŝŽŶ ƉĂƚŚǁĂǇ͘ ƌ : WŚĂƌŵĂĐŽů͘ Ϯ͘ϬϭϮ͘ WD/͗
ϮϮϱϬϵϴϱϱ͘
• 'ĂůŝŶĚŽ D&͕ ^ŽůĞƐŝŽ D͕ ƚŝĞŶǌĂƌͲƌŽĐĂ ^͕ ĂŵŽƌĂ D:͕ :ŽƌĚĄŶ :͘ DŝƚŽĐŚŽŶĚƌŝĂů
ĚǇŶĂŵŝĐƐ ĂŶĚ ŵŝƚŽƉŚĂŐǇ ŝŶ ƚŚĞ ϲͲŚǇĚƌŽǆǇĚŽƉŵĂŝŶĞ ƉƌĞĐůŝŶŝĐĂů ŵŽĚĞů ŽĨ
WĂƌŬŝŶƐŽŶǲƐĚŝƐĞĂƐĞ͘WĂƌŬŝŶƐŽŶƐŝƐ͘WD/͗ϮϮϵϲϲϰϳϳ͘
• WĞƌĞǌͲůǀĂƌĞǌ ^͕ ^ŽůĞƐŝŽ D͕ ƵĞŶĐĂͲ>ŽƉĞǌ D͕ DĞůĞƌŽͲ&ĞƌŶĂŶĚĞǌ ĚĞ DĞƌĂ ZD͕
sŝůůĂůŽďŽƐ͕<ŵŝƚĂ,͕'ĂůŝŶĚŽD&͕:ŽƌĚĄŶ:͘WŚĂƌŵĂĐŽůŽŐŝĐĂůĐŚĂƌĂĐƚĞƌŝǌĂƚŝŽŶŽĨƚŚĞ
ŵĞĐŚĂŶŝƐŵƐ ŝŶǀŽůǀĞĚ ŝŶ ĚĞůĂǇĞĚ ĐĂůĐŝƵŵ ĚĞƌĞŐƵůĂƚŝŽŶ ŝŶ ^,Ͳ^zϱz ĐĞůůƐ ĐŚĂůůĞŶŐĞĚ
ǁŝƚŚŵĞƚŚĂĚŽŶĞ͘/Ŷƚ:ĞůůŝŽů͘WD/͗ϮϮϳϳϴϳϰϮ͘
• WĞƌĞǌͲůǀĂƌĞǌ ^͕ /ŐůĞƌĂƐͲ'ƵŝŵĂƌĂŝƐ s͕ ^ŽůĞƐŝŽ D͕ DĞůĞƌŽͲ&ĞƌŶĂŶĚĞǌ ĚĞ DĞƌĂ ZD͕
zƵƐƚĞ s:͕ 'ĂůŝŶĚŽ D&͕ :ŽƌĚĄŶ :͘ DĞƚŚĂĚŽŶĞ ŝŶĚƵĐĞƐ ĚĞŐƌĂĚĂƚŝŽŶ ĂŶĚ /&Ͳ
ŵĞĚŝĂƚĞĚ ŶĞĐƌŽƚŝĐͲůŝŬĞ ĐĞůů ĚĞĂƚŚ ŝŶ ŶĞƵƌŽďůĂƐƚŽŵĂ ĐĞůůƐ͘ WŚĂƌŵĂĐŽů ZĞƐ͘ Ϯ͘Ϭϭϭ͘
WD/͗Ϯϭϭϰϱϯϵϴ͘
• dĞƌŶŝĂŶŽǀ ͕ WĠƌĞǌͲKƌƚŝǌ ͕ ^ŽůĞƐŝŽ D͕ 'ĂƌĐşĂͲ'ƵƚŝĠƌƌĞǌ D^͕ KƌƚĞŐĂͲůǀĂƌŽ ͕
EĂǀĂƌƌĞƚĞ&͕>ĞŝǀĂ͕'ĂůŝŶĚŽD&͕DĂŶǌĂŶĂƌĞƐ:͘KǀĞƌĞǆƉƌĞƐƐŝŽŶŽĨϮĐĂŶŶĂďŝŶŽŝĚ
ƌĞĐĞƉƚŽƌƐ ƌĞƐƵůƚƐ ŝŶ ŶĞƵƌŽƉƌŽƚĞĐƚŝŽŶ ĂŐĂŝŶƐƚ ďĞŚĂǀŽƌŝĂů ĂŶĚ ŶĞƵƌŽĐŚĞŵŝĐĂů
ĂůƚĞƌĂƚŽŶƐŝŶĚƵĐĞĚďǇŝŶƚƌĂĐĂƵĚĂƚĞĂĚŵŝŶŝƐƚƌĂƚŝŽŶŽĨϲͲŚǇĚƌŽǆŝĚŽƉĂŵŝŶĞ͘EĞƵƌŽďŝŽů
ŐŝŶŐ͘Ϯ͘ϬϭϮ͘WD/͗ϮϬϵϴϬϬϳϰ͘
ϱ
• WĞƌĞǌͲůǀĂƌĞǌ ^͕ ^ŽůĞƐŝŽ D͕ DĂŶǌĂŶĂƌĞƐ :͕ :ŽƌĚĄŶ :͕ 'ĂůŝŶĚŽ D&͘ >ĂĐƚĂĐǇƐƚŝŶ
ƌĞƋƵŝƌĞƐ ŽǆǇŐĞŶ ƐƉĞĐŝĞƐ ĂŶĚ Ăǆ ƌĞĚŝƐƚƌŝďƵƚŝŽŶ ƚŽ ŝŶĚƵĐĞ ŵŝƚŽĐŚŽŶĚƌŝĂͲŵĞĚŝĂƚĞĚ
ĐĞůůĚĞĂƚŚ͘ƌ:WŚĂƌŵĂĐŽů͘Ϯ͘ϬϬϵ͘WD/͗ϭϵϳϴϱϲϰϵ͘
ϲ
ŐƌĂĚĞĐŝŵŝĞŶƚŽƐ͘
ϭ
ŽŶƚĞŶŝĚŽ
/͘
/EdZKh/ME ͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘ ϯ
/͘ϭ͘ŝŶĄŵŝĐĂŵŝƚŽĐŽŶĚƌŝĂů͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘ ϰ
/͘ϭ͘ϭ͘&ƵƐŝſŶŵŝƚŽĐŽŶĚƌŝĂů͘ ͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘ ϲ
/͘ϭ͘Ϯ͘&ŝƐŝſŶŵŝƚŽĐŽŶĚƌŝĂů ͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘ ϴ
/͘ϭ͘ϯ͘DŽǀŝŵŝĞŶƚŽĚĞůĂƐŵŝƚŽĐŽŶĚƌŝĂƐ͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘ ϭϲ
/͘Ϯ͘DŝƚŽĨĂŐŝĂ͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘ ϭϳ
Ϯ͘ƉŽƉƚŽƐŝƐ ͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘ Ϯϰ
ϯ͘ƐƉĞĐŝĞƐƌĞĂĐƚŝǀĂƐĚĞůŽǆşŐĞŶŽ͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘ ϯϮ
ϰ͘ŶĨĞƌŵĞĚĂĚĞƐEĞƵƌŽĚĞŐĞŶĞƌĂƚŝǀĂƐ͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘ ϯϰ
ϰ͘ϭ͘ŶĨĞƌŵĞĚĂĚĚĞWĂƌŬŝŶƐŽŶ͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘ ϯϲ
ϰ͘Ϯ͘ŶĨĞƌŵĞĚĂĚĚĞ,ƵŶƚŝŶŐƚŽŶ ͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘ ϰϮ
//͘
///͘
,/WMd^/^ ͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘ ϰϳ
K:d/sK^ ͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘ ϰϵ
/s͘Z^h>dK^͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘ ϱϭ
s͘
/^h^/ME ͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘ ϱϯ
s/͘
KE>h^/KE^͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘ ϳϱ
s//͘Zs/dhZ^ ͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘ ϳϳ
s///͘
Ϯ
/>/K'Z&1 ͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘ ϴϯ
Ǥ
V
>Ă ŵŝƚŽĐŽŶĚƌŝĂ ĞƐ ƵŶ ŽƌŐĄŶƵůŽ ĐĞůƵůĂƌ͕ ƉƌĞƐĞŶƚĞ ĞŶ Ğů ĐŝƚŽƉůĂƐŵĂ ĚĞ ůŽƐ
ĞƵĐĂƌŝŽƚĂƐ͕ ;,ĞŶǌĞ Ğƚ Ăů͕͘ ϮϬϬϯͿ͕ ĐƵǇĂ ĨƵŶĐŝſŶ ƉƌŝŶĐŝƉĂů ĞƐ ƐƵŵŝŶŝƐƚƌĂƌ ůĂ ĞŶĞƌŐşĂ
ŶĞĐĞƐĂƌŝĂƉĂƌĂƌĞĂůŝǌĂƌůĂŵĂǇŽƌƉĂƌƚĞĚĞůĂĂĐƚŝǀŝĚĂĚĚĞůĂĐĠůƵůĂ͘ůŽƌŝŐĞŶĞǀŽůƵƚŝǀŽ
ĚĞ ĞƐƚŽƐ ŽƌŐĄŶƵůŽƐ ĨƵĞ ĞǆƉůŝĐĂĚŽ ƉŽƌ DĂƌŐƵůŝƐ͕ ƋƵŝĞŶ͕ ĞŶ ϭ͘ϵϲϳ͕ ƉŽƐƚƵůſ ƐƵ dĞŽƌşĂ
ŶĚŽƐŝŵďŝſƚŝĐĂ͕ ;^ĂŐĂŶ͕ ϭϵϲϳͿ͕ ǀŝŐĞŶƚĞ ĂƷŶ Ă ĚşĂ ĚĞ ŚŽǇ͘ Ŷ ĞůůĂ͕ ƐĞ ƉƌŽƉŽŶĞ ƋƵĞ ůĂ
ŵŝƚŽĐŽŶĚƌŝĂ ĞƐ Ğů ƌĞƐƵůƚĂĚŽ ĚĞ ůĂ ĞǀŽůƵĐŝſŶ ĚĞ ƵŶĂ ƐŝŵďŝŽƐŝƐ ĞŶƚƌĞ ĐŝĞƌƚĂƐ ďĂĐƚĞƌŝĂƐ
ĂĞƌŽďŝĂƐ Ǉ ĂůŐƵŶĂƐ ĐĠůƵůĂƐ ĞƵĐĂƌŝŽƚĂƐ ƉƌŝŵŝƚŝǀĂƐ͕ ƐŝĞŶĚŽ ůĂƐ ƉƌŝŵĞƌĂƐ ŝŶĐůƵŝĚĂƐ ĚĞ
ŵĂŶĞƌĂ ĐĂƐƵĂů ĞŶ ůĂƐ ƐĞŐƵŶĚĂƐ͘ Ğ ĞƐƚĞ ŵŽĚŽ ƐĞ ŽďƚƵǀŽ ƵŶ ŵĞƚĂďŽůŝƐŵŽ ŽǆŝĚĂƚŝǀŽ
ŵĄƐĞĨŝĐŝĞŶƚĞƋƵĞůĂŐůŝĐſůŝƐŝƐĂŶĂĞƌſďŝĐĂ͘
^Ğ ƚƌĂƚĂ ĚĞ ƵŶ ŽƌŐĄŶƵůŽ ƵďŝƋƵŝƚĂƌŝŽ͕ ĐŽŶ ƵŶĂ ĚŝƐƚƌŝďƵĐŝſŶ ŚĞƚĞƌŽŐĠŶĞĂ ƚĂŶƚŽ
ĞŶƚƌĞ ůĂƐ ĚŝƐƚŝŶƚĂƐ ĞƐƉĞĐŝĞƐ͕ ĐŽŵŽ ĞŶƚƌĞ ůŽƐ ĚŝĨĞƌĞŶƚĞƐ ƚŝƉŽƐ ĐĞůƵůĂƌĞƐ ĚĞŶƚƌŽ ĚĞ ƵŶ
ŵŝƐŵŽŽƌŐĂŶŝƐŵŽ͘Ɛş͕ƉŽƌĞũĞŵƉůŽ͕ůĂƐŶĞƵƌŽŶĂƐƉŽƐĞĞŶƵŶĂŐƌĂŶŵĂƐĂŵŝƚŽĐŽŶĚƌŝĂů͕
ĚĞďŝĚŽ Ă ǀĂƌŝŽƐ ĨĂĐƚŽƌĞƐ͕ ĐŽŵŽ ƐŽŶ ƐƵ ƉƌĞĚŽŵŝŶĂŶƚĞ ĨƵŶĐŝſŶ ĞŶĞƌŐĠƚŝĐĂ͕ ƐƵ
ŝŶĐĂƉĂĐŝĚĂĚ ƉĂƌĂ ŝŶŝĐŝĂƌ ůĂ ŐůŝĐſůŝƐŝƐ ĐƵĂŶĚŽ ůĂ ĨŽƐĨŽƌŝůĂĐŝſŶ ŽǆŝĚĂƚŝǀĂ ĞƐ ŝŶǀŝĂďůĞ Ž ůĂ
ƉƌĞƐĞŶĐŝĂĚĞĞůŽŶŐĂĐŝŽŶĞƐĐŽŶƐŝĚĞƌĂďůĞƐ͘
>ĂŵŝƚŽĐŽŶĚƌŝĂĐŽŶƐƚŝƚƵǇĞƚĂŵďŝĠŶƵŶĂĞƐƚƌƵĐƚƵƌĂŶĞĐĞƐĂƌŝĂƉĂƌĂůĂŵƵĞƌƚĞĚĞ
ůĂĐĠůƵůĂ͕ƉŽƌĞũĞŵƉůŽĐƵĂŶĚŽĠƐƚĂƷůƚŝŵĂƐĞƉƌŽĚƵĐĞĂƚƌĂǀĠƐĚĞůĂǀşĂŝŶƚƌşŶƐĞĐĂĚĞůĂ
ĂƉŽƉƚŽƐŝƐ;:ŽƌĚĂŶĞƚĂů͕͘ϮϬϬϯ͖DĐƌŝĚĞĞƚĂů͕͘ϮϬϬϲ͖dŽƌŶĞƌŽĞƚĂů͕͘ϮϬϬϮ͖zĂĨĨĞ͕ϭϵϵϵͿ͘
ĞƵŶŵŽĚŽƐĞĐƵŶĚĂƌŝŽ͕ĞƐƚĞŽƌŐĄŶƵůŽĂĐƚƷĂƚĂŵďŝĠŶĂůŵĂĐĞŶĂŶĚŽƐƵƐƚĂŶĐŝĂƐĐŽŵŽ
ĂŐƵĂ͕ŝŽŶĞƐŽƌĞƐƚŽƐĚĞǀŝƌƵƐǇƉƌŽƚĞşŶĂƐ͕;'ĞŶĂĞƚĂů͕͘ϮϬϬϵ͖,ƵĂŶŐĞƚĂů͕͘ϮϬϭϭ͖^ĞƚŚĞƚ
Ăů͕͘ϮϬϬϱͿ͘
ůĄƐŝĐĂŵĞŶƚĞ͕ĂůĂƐŵŝƚŽĐŽŶĚƌŝĂƐƐĞůĞƐŚĂĂƚƌŝďƵŝĚŽƵŶĂŵŽƌĨŽůŽŐşĂĂůĂƌŐĂĚĂ͕Ɛŝ
ďŝĞŶ ĞƐ ĐŝĞƌƚŽ ƋƵĞ͕ Ă ĚşĂ ĚĞ ŚŽǇ͕ ƐĂďĞŵŽƐ ƋƵĞ ƉƵĞĚĞŶ ǀĂƌŝĂƌ ĚĞ ĨŽƌŵĂ͘ ƐƚĄŶ
ĐŽŶƐƚŝƚƵŝĚĂƐƉŽƌƚƌĞƐĞƐƚƌƵĐƚƵƌĂƐĐůĂƌĂŵĞŶƚĞĚŝĨĞƌĞŶĐŝĂĚĂƐ͕
DĞŵďƌĂŶĂ ĞǆƚĞƌŶĂ͗ ƉĞƌŵĞĂďůĞ Ă ŝŽŶĞƐ͕ Ă ŵĞƚĂďŽůŝƚŽƐ Ǉ Ă ŵƵĐŚŽƐ
•
ƉŽůŝƉĠƉƚŝĚŽƐ͕ĚĞďŝĚŽĂůĂƉƌĞƐĞŶĐŝĂĚĞƉŽƌŽƐ͘
ϯ
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DĞŵďƌĂŶĂŝŶƚĞƌŶĂ͗ĂůĐŽŶƚƌĂƌŝŽƋƵĞĞŶĞůĐĂƐŽĂŶƚĞƌŝŽƌ͕ĞƐƚĂĞƐƵŶĂĞƐƚƌƵĐƚƵƌĂ
ĂůƚĂŵĞŶƚĞ ƐĞůĞĐƚŝǀĂ Ğ ŝŵƉĞƌŵĞĂďůĞ͘ &ŽƌŵĂ ĐƌĞƐƚĂƐ͕ ůĂƐ ĐƵĂůĞƐ ƐŽŶ ŶĞĐĞƐĂƌŝĂƐ
ƉĂƌĂ ĂƵŵĞŶƚĂƌ ƐƵ ƐƵƉĞƌĨŝĐŝĞ Ǉ ƉĞƌŵŝƚŝƌ Ğů ĂŶĐůĂũĞ ĚĞ ƚŽĚŽƐ ůŽƐ ƐŝƐƚĞŵĂƐ
ĞŶǌŝŵĄƚŝĐŽƐ Ǉ ĚĞ ƚƌĂŶƐƉŽƌƚĞ ƚƌĂŶƐŵĞŵďƌĂŶĂ ŶĞĐĞƐĂƌŝŽƐ ƉĂƌĂ Ğů ďƵĞŶ
ĨƵŶĐŝŽŶĂŵŝĞŶƚŽĐĞůƵůĂƌ͘
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DĂƚƌŝǌŵŝƚŽĐŽŶĚƌŝĂů͗ĞƐĞůĞƐƉĂĐŝŽŝŶƚĞƌŝŽƌĚĞůĂŵĞŵďƌĂŶĂŝŶƚĞƌŶĂ͕ĚŽŶĚĞƐĞ
ůůĞǀĂŶĂĐĂďŽŶƵŵĞƌŽƐĂƐƌƵƚĂƐŵĞƚĂďſůŝĐĂƐ͕ĐŽŵŽĞƐĞůĐĂƐŽĚĞůĐŝĐůŽĚĞ<ƌĞďƐ͘
ĞƐĚĞ ƵŶ ƉƵŶƚŽ ĚĞ ǀŝƐƚĂ ďŝŽƋƵşŵŝĐŽ͕ ůĂ ŵŝƚŽĐŽŶĚƌŝĂ ŵƵĞƐƚƌĂ ůĂ ƉĂƌƚŝĐƵůĂƌŝĚĂĚ
ĚĞ ƉŽƐĞĞƌ ƐƵ ƉƌŽƉŝŽ E͕ ŝŶĚĞƉĞŶĚŝĞŶƚĞ ĚĞů ŶƵĐůĞĂƌ Ǉ ĐŽŶ ƵŶĂ ǀĂƌŝĂďŝůŝĚĂĚ ŵƵǇ
ŝŶĨĞƌŝŽƌ͘ƐƚĞŵĂƚĞƌŝĂůŐĞŶĠƚŝĐŽƉƌŽƉŝŽ͕ĚĞůƋƵĞĐĂĚĂŵŝƚŽĐŽŶĚƌŝĂĐŽŶƚŝĞŶĞĞŶƚƌĞĐŝŶĐŽ
ǇĚŝĞǌĐŽƉŝĂƐŝĚĠŶƚŝĐĂƐ͕ƉƌĞƐĞŶƚĂƵŶƉĂƚƌſŶĚĞŚĞƌĞŶĐŝĂĞǆĐůƵƐŝǀĂŵĞŶƚĞŵĂƚĞƌŶĂůǇ͕ĞŶ
ŚƵŵĂŶŽƐ͕ ĐŽĚŝĨŝĐĂ ƉĂƌĂ ƚƌĞĐĞ ƉƌŽƚĞşŶĂƐ͕ ƚŽĚĂƐ ĞůůĂƐ ŝŶǀŽůƵĐƌĂĚĂƐ ĞŶ ůĂ ƉƌŽĚƵĐĐŝſŶ ĚĞ
ĞŶĞƌŐşĂĂƚƌĂǀĠƐĚĞůĂĨŽƐĨŽƌŝůĂĐŝſŶŽǆŝĚĂƚŝǀĂ͕;sŝǀĞƐͲĂƵǌĂĞƚĂů͕͘ϮϬϬϵͿ͘
ů ĞƐƚƵĚŝŽ ŵŝƚŽĐŽŶĚƌŝĂů ƐƵƐĐŝƚĂ ƵŶ ŐƌĂŶ ŝŶƚĞƌĠƐ ĞŶƚƌĞ ůĂ ĐŽŵƵŶŝĚĂĚ ĐŝĞŶƚşĨŝĐĂ
ĚĞďŝĚŽĂǀĂƌŝŽƐĨĂĐƚŽƌĞƐ͕ĐŽŵŽƐŽŶůĂĐŽŵƉůĞũŝĚĂĚĚĞĞƐƚĞŽƌŐĄŶƵůŽ͕ƐƵŝŵƉŽƌƚĂŶĐŝĂĞŶ
ĞůŵĂŶƚĞŶŝŵŝĞŶƚŽĚĞůĂƐĐŽŶĚŝĐŝŽŶĞƐŶĞĐĞƐĂƌŝĂƐƉĂƌĂĞůďƵĞŶĨƵŶĐŝŽŶĂŵŝĞŶƚŽĐĞůƵůĂƌ͕
ůĂ ŐƌĂŶ ĐĂŶƚŝĚĂĚ ĚĞ ƉƌŽĐĞƐŽƐ ďŝŽƋƵşŵŝĐŽƐ ƋƵĞ ƐĞ ƉƌŽĚƵĐĞŶ ĞŶ Ġů Ž ůĂ ƌĞůĂĐŝſŶ ƋƵĞ
ƉƌĞƐĞŶƚĂŶƐƵƐĚŝƐĨƵŶĐŝŽŶĞƐĐŽŶůĂĂƉĂƌŝĐŝſŶĚĞĞŶĨĞƌŵĞĚĂĚĞƐĚĞůŽƐŵĄƐǀĂƌŝŽƉŝŶƚĂƐ͘
Ɛş͕ ƉŽƌ ĞũĞŵƉůŽ͕ ĞƐ ĐŽŶŽĐŝĚĂ ůĂ ƉƌĞƐĞŶĐŝĂ ĚĞ ƚƌĂƐƚŽƌŶŽƐ ŵŝƚŽĐŽŶĚƌŝĂůĞƐ ĞŶ ƉƌŽĐĞƐŽƐ
ŶĞƵƌŽĚĞŐĞŶĞƌĂƚŝǀŽƐ͕ ;ĞĂů͕ ϭϵϵϴͿ͖ ƉĂƚŽůŽŐşĂƐ ĐĂƌĚşĂĐĂƐ͕ ;,ĞƌŶĂŶĚĞǌͲZĞƐĞŶĚŝǌ Ğƚ Ăů͕͘
ϮϬϭϯ͖>ĞŵŝĞƵǆĞƚĂů͕͘ϮϬϬϵ͖>ĞŵŝĞƵǆĞƚĂů͕͘ϮϬϭϭͿ͖ĚĞƐſƌĚĞŶĞƐƉƐŝƋƵŝĄƚƌŝĐŽƐ͕;DĂƌĂǌǌŝƚŝ
ĞƚĂů͕͘ϮϬϭϮͿ͖ĚŝĂďĞƚĞƐŵĞůůŝƚƵƐĚĞƚŝƉŽϮ͕;ŶĚĞƌƐŽŶĞƚĂů͕͘ϮϬϬϵ͖ŽƵƐŚĞůĞƚĂů͕͘ϮϬϬϳ͖
ZŝĞƵƐƐĞƚ͕ϮϬϭϭͿ͖ĞƐĐůĞƌŽƐŝƐůĂƚĞƌĂůĂŵŝŽƚƌſĨŝĐĂ͕;&ĂĞƐĞƚĂů͕͘ϮϬϭϭ͖DĞŶǌŝĞƐĞƚĂů͕͘ϮϬϬϮͿ͖
ƐşŶĚƌŽŵĞĚĞŚşŐĂĚŽŐƌĂƐŽǇŽƚƌĂƐĚŝƐĨƵŶĐŝŽŶĞƐŚĞƉĄƚŝĐĂƐ͕;ĞŐƌŝĐŚĞĞƚĂů͕͘ϮϬϭϯ͖ƌĂƵůƚ
ĞƚĂů͕͘ϮϬϭϯͿ͖ƉƌŽĐĞƐŽƐŽŶĐŽůſŐŝĐŽƐ͕;ŚĞŶ͕ϮϬϭϮ͖<ŝŶŐĞƚĂů͕͘ϮϬϬϲ͖<ƵŵĂƌŝĞƚĂů͕͘ϮϬϭϯ͖
^ŚĂƉŽǀĂůŽǀĞƚĂů͕͘ϮϬϭϭͿ͖ŽĚŝƐĨƵŶĐŝŽŶĞƐƌĞŶĂůĞƐ͕;dĂŶŐĞƚĂů͕͘ϮϬϭϯͿ͘ƉĞƐĂƌĚĞƚŽĚŽƐ
ůŽƐĞƐĨƵĞƌǌŽƐƌĞĂůŝǌĂĚŽƐĞŶĞůĞƐƚƵĚŝŽŵŝƚŽĐŽŶĚƌŝĂů͕ĂƷŶƋƵĞĚĂŶƉŽƌĚĞƐĐƵďƌŝƌŵƵĐŚŽƐ
ŐƌĂŶĚĞƐƐĞĐƌĞƚŽƐĚĞĞƐƚĞƉĞƋƵĞŹŽŽƌŐĄŶƵůŽ͘
I.1. Dinámica mitocondrial
ϰ
ƉĞƐĂƌ ĚĞ ƋƵĞ ŚĂƐƚĂ ŚĂĐĞ ƉŽĐŽƐ ĂŹŽƐ ƐĞ ƉĞŶƐĂďĂ ƋƵĞ ůĂƐ ŵŝƚŽĐŽŶĚƌŝĂƐ ĞƌĂŶ
ŽƌŐĄŶƵůŽƐĞƐƚĄƚŝĐŽƐ͕ŚŽǇĞŶĚşĂƐĂďĞŵŽƐƋƵĞŶĂĚĂŵĄƐůĞũŽƐĚĞůĂƌĞĂůŝĚĂĚ͕ƉƵĞƐĞƐƚĂƐ
ĞƐƚƌƵĐƚƵƌĂƐƐĞĞŶĐƵĞŶƚƌĂŶĞŶĐŽŶƚŝŶƵŽĐĂŵďŝŽǇƌĞĞƐƚƌƵĐƚƵƌĂĐŝſŶ͘ŽŶĐƌĞƚĂŵĞŶƚĞ͕ƐŽŶ
ĐĂƉĂĐĞƐ ĚĞ ƐƵĨƌŝƌ ƉƌŽĐĞƐŽƐ ĚĞ ĨƵƐŝſŶ͕ ĚĞ ĨŝƐŝſŶ Ǉ ĚĞ ŵŽǀĞƌƐĞ Ă ƚƌĂǀĠƐ ĚĞ ůŽƐ
ŵŝĐƌŽƚƷďƵůŽƐ͘ ů ĐŽŶũƵŶƚŽ ĚĞ ĞƐƚŽƐ ƉƌŽĐĞƐŽƐ ƐĞ ůĞƐ ĚĞŶŽŵŝŶĂ ĚŝŶĄŵŝĐĂ ŵŝƚŽĐŽŶĚƌŝĂů͕
;tĞƐƚĞƌŵĂŶŶ͕ ϮϬϭϬͿ͘ ,ĂǇ ĂƵƚŽƌĞƐ ƋƵĞ ƚĂŵďŝĠŶ ŝŶĐůƵǇĞŶ Ă ůĂ ŵŝƚŽĨĂŐŝĂ ĞŶ ůĂ ĐŝƚĂĚĂ
ĚŝŶĄŵŝĐĂ͕ ĂƵŶƋƵĞ͕ ĞŶ ĞƐƚĞ ƚƌĂďĂũŽ͕ ŚĞŵŽƐ ƉƌĞĨĞƌŝĚŽ ĚĞĚŝĐĂƌůĞ ƵŶ ĐĂƉşƚƵůŽ Ă ƉĂƌƚĞ͘
ĞŶƚƌŽĚĞůĂƐĨƵŶĐŝŽŶĞƐĚĞůĂĚŝŶĄŵŝĐĂŵŝƚŽĐŽŶĚƌŝĂů͕ĚĞƐƚĂĐĂŶĂƐƉĞĐƚŽƐŝŶĚŝƐƉĞŶƐĂďůĞƐ
ƉĂƌĂĞůďƵĞŶĨƵŶĐŝŽŶĂŵŝĞŶƚŽĐĞůƵůĂƌ͕ĐŽŵŽƐŽŶ͕
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ů ŵĂŶƚĞŶŝŵŝĞŶƚŽ ĚĞ ůĂ ŝŶƚĞŐƌŝĚĂĚ ĚĞů ŽƌŐĄŶƵůŽ͕ ;ĞƌĞŝƚĞƌͲ,ĂŚŶ Ğƚ Ăů͕͘ ϮϬϭϬͿ͕
ƚĂŶƚŽ Ă ŶŝǀĞů ŵŽƌĨŽůſŐŝĐŽ͕ ;ŚĞŶ Ğƚ Ăů͕͘ ϮϬϬϵͿ͕ ĐŽŵŽ ĨƵŶĐŝŽŶĂů͕ ;>ŝĞƐĂ Ğƚ Ăů͕͘
ϮϬϬϵͿ͘
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>Ă ƌĞƉŽƐŝĐŝſŶ ĚĞ ůĂƐ ŵŝƚŽĐŽŶĚƌŝĂƐ ĚĂŹĂĚĂƐ͕ ǀŝĞũĂƐ Ž ƋƵĞ ƉŽƌ ĐƵĂůƋƵŝĞƌ ĐĂƵƐĂ
ĚĞďĂŶ ƐĞƌ ĞůŝŵŝŶĂĚĂƐ͕ ;^ĞŽ Ğƚ Ăů͕͘ ϮϬϭϬͿ͕ ĂĐƚƵĂŶĚŽ ƉŽƌ ƚĂŶƚŽ ĐŽŵŽ ŵĞĚŝŽ ĚĞ
ĐŽŶƚƌŽůĚĞůĂĐĂůŝĚĂĚĚĞůĂŵŝƚŽĐŽŶĚƌŝĂ͕;ŚĞŶĞƚĂů͕͘ϮϬϬϵͿ͘
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>Ă ƐĞŐƌĞŐĂĐŝſŶ Ǉ ƉƌŽƚĞĐĐŝſŶ ĚĞů E ŵŝƚŽĐŽŶĚƌŝĂů͕ ;,ŽůůĞŶďĞĐŬ Ğƚ Ăů͕͘ ϮϬϬϱ͖
KŬĂŵŽƚŽ Ğƚ Ăů͕͘ ϮϬϬϱ͖ tĞƐƚĞƌŵĂŶŶ͕ ϮϬϬϮͿ͕ ƉĞƌŵŝƚŝĞŶĚŽ Ğů ŝŶƚĞƌĐĂŵďŝŽ ĚĞ
ŵĂƚĞƌŝĂůŐĞŶĠƚŝĐŽĞŶƚƌĞĞƐƚŽƐŽƌŐĄŶƵůŽƐ͕;ŚĞŶĞƚĂů͕͘ϮϬϬϵͿ͘
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ůƌĞĐůƵƚĂŵŝĞŶƚŽĚĞůĂƐŵŝƚŽĐŽŶĚƌŝĂƐŚĂĐŝĂůŽƐĐŽŵƉĂƌƚŝŵĞŶƚŽƐĐĞůƵůĂƌĞƐĚŽŶĚĞ
ƐĞĂŶŵĄƐƉƌĞĐŝƐĂƐĞŶĐĂĚĂŵŽŵĞŶƚŽ͕;ŚĞŶĞƚĂů͕͘ϮϬϬϵͿ͘
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>ĂĨĂĐŝůŝƚĂĐŝſŶĚĞůĂĐŽŵƵŶŝĐĂĐŝſŶĞŶƚƌĞůĂƐŵŝƚŽĐŽŶĚƌŝĂƐǇĞůĐŝƚŽƉůĂƐŵĂ͘ƐƚĞ
ƉƵŶƚŽ ĞƐ ŝŶĚŝƐƉĞŶƐĂďůĞ ƉĂƌĂ ƉŽĚĞƌ ůůĞǀĂƌ Ă ĐĂďŽ ĚĞ ƵŶ ŵŽĚŽ ĞĨŝĐĂǌ Ğů
ƚƌĂŶƐƉŽƌƚĞ ĚĞ ĞƐƚŽƐ ŽƌŐĄŶƵůŽƐ͕ ƐŽďƌĞ ƚŽĚŽ Ă ƚƌĂǀĠƐ ĚĞ ůŽƐ ŵŝĐƌŽƚƷďƵůŽƐ͕ Ă ůŽƐ
ůƵŐĂƌĞƐ ĚŽŶĚĞ ŚĂǇĂ ŵĂǇŽƌĞƐ ƌĞƋƵĞƌŝŵŝĞŶƚŽƐ ĞŶĞƌŐĠƚŝĐŽƐ ĞŶ ĐĂĚĂ ŵŽŵĞŶƚŽ
ĐŽŶĐƌĞƚŽ͕;ŚĞŶĞƚĂů͕͘ϮϬϬϵͿ͘
ƐƚŽƐ ƉƌŽĐĞƐŽƐ ƐĞ ĞŶĐƵĞŶƚƌĂŶ ĞŶ ƵŶ ĚĞůŝĐĂĚŽ ĞƋƵŝůŝďƌŝŽ Ǉ ŶŽ ƉƵĞĚĞŶ ƐĞƌ
ĞŶƚĞŶĚŝĚŽƐ ĐŽŵŽ ĐŽŵƉŽŶĞŶƚĞƐ ĂŝƐůĂĚŽƐ͕ ƐŝŶŽ ƋƵĞ ƉƌĞƐĞŶƚĂŶ ƵŶĂ ŵĂƌĐĂĚĂ
ŝŶƚĞƌĐŽŶĞǆŝſŶǇĚĞƉĞŶĚĞŶĐŝĂůŽƐƵŶŽƐĐŽŶůŽƐŽƚƌŽƐ͘Ɛş͕ůĂƐĚŝƐĨƵŶĐŝŽŶĞƐĞŶĂůŐƵŶŽĚĞ
ĞůůŽƐĂĨĞĐƚĂƌĄŶƚĂŵďŝĠŶĂůƌĞƐƚŽ͘>ĂĐŝƚĂĚĂƌĞůĂĐŝſŶĞƐĞƐƉĞĐŝĂůŵĞŶƚĞĐůĂƌĂĞŶĞůĐĂƐŽĚĞ
ůĂ ĨŝƐŝſŶ Ǉ ůĂ ĨƵƐŝſŶ ŵŝƚŽĐŽŶĚƌŝĂů͕ ǇĂ ƋƵĞ ĞƐ ĐŽŶŽĐŝĚŽ Ğů ŚĞĐŚŽ ĚĞ ƋƵĞ͕ ĐƵĂŶĚŽ ƐĞ
ϱ
ĚĞƐĐŽŵƉĞŶƐĂ ƵŶĂ ĚĞ ĞůůĂƐ͕ ůĂ ŽƚƌĂ ƚĂŵďŝĠŶ ƐĞ ǀĞ ŐƌĂǀĞŵĞŶƚĞ ĂĨĞĐƚĂĚĂ͕ ;ƌĞǀŝƐĂĚŽ ĞŶ
;ŚĞŶĞƚĂů͕͘ϮϬϬϵͿͿ͘
WĞƌŽ ŶŽ ƐſůŽ ĞǆŝƐƚĞ ƵŶĂ ĨƵĞƌƚĞ ŝŶƚĞƌĐŽŶĞǆŝſŶ ĞŶƚƌĞ ůŽƐ ĐŽŵƉŽŶĞŶƚĞƐ ĚĞ ůĂ
ĚŝŶĄŵŝĐĂŵŝƚŽĐŽŶĚƌŝĂů͕ƐŝŶŽƋƵĞƚĂŵďŝĠŶƉĂƌĞĐĞŚĂďĞƌƵŶƐſůŝĚŽǀşŶĐƵůŽĞŶƚƌĞůĂĐŝƚĂĚĂ
ĚŝŶĄŵŝĐĂǇůĂŵƵĞƌƚĞĐĞůƵůĂƌĂƉŽƉƚſƚŝĐĂ͕;KƚĞƌĂĞƚĂů͕͘ϮϬϭϮͿ͘Ɛş͕ĂƵŶƋƵĞůĂŶĂƚƵƌĂůĞǌĂ
ĚĞĞƐƚĂƌĞůĂĐŝſŶŶŽĞƐƚĄĂƷŶĐŽŵƉůĞƚĂŵĞŶƚĞĚŝůƵĐŝĚĂĚĂ͕ůŽƋƵĞƐşƋƵĞƉĂƌĞĐĞĐůĂƌŽĞƐ
ƋƵĞ ĂŵďŽƐ ƉƌŽĐĞƐŽƐ ŶŽ ƐŽŶ ƚŽƚĂůŵĞŶƚĞ ŝŶĚĞƉĞŶĚŝĞŶƚĞƐ͕ ƐŝŶŽ ŵĄƐ ďŝĞŶ ƚŽĚŽ ůŽ
ĐŽŶƚƌĂƌŝŽ͘ŶĞůƉƌĞƐĞŶƚĞƚƌĂďĂũŽ͕ŵĄƐĂĚĞůĂŶƚĞ͕ƚƌĂƚĂƌĞŵŽƐĐŽŶŵĄƐƉƌŽĨƵŶĚŝĚĂĚĞƐƚĞ
ǀşŶĐƵůŽ͘
I.1.1. Fusión mitocondrial.
>Ă ĨƵƐŝſŶ ĚĞů ŽƌŐĄŶƵůŽ ƉĞƌŵŝƚĞ ůĂ ƵŶŝſŶ ĚĞ ĚŽƐ ŵŝƚŽĐŽŶĚƌŝĂƐ͕ ĐŽŶ ůĂ
ĐŽŶƐŝŐƵŝĞŶƚĞŵĞǌĐůĂǇƵŶŝĨŝĐĂĐŝſŶĚĞůĐŽŶƚĞŶŝĚŽĚĞĂŵďĂƐ͕ƉĂƌĂĐŽŵƉůĞŵĞŶƚĂƌĞůE
ŵŝƚŽĐŽŶĚƌŝĂůĚĂŹĂĚŽ͕;ŚĞŶĞƚĂů͕͘ϮϬϬϱĂ͖ŚĞŶĞƚĂů͕͘ϮϬϬϱďͿ͘
ŶůĂƐŶĞƵƌŽŶĂƐ͕ůĂĨƵƐŝſŶŵŝƚŽĐŽŶĚƌŝĂůĞƐĚĞƐƵŵĂŝŵƉŽƌƚĂŶĐŝĂ͕ǇĂƋƵĞƉĞƌŵŝƚĞ
ůĂĨŽƌŵĂĐŝſŶĚĞŐƌĂŶĚĞƐƌĞĚĞƐĚĞĞƐƚŽƐŽƌŐĄŶƵůŽƐ͕ŝŶƚĞƌĐŽŶĞĐƚĂĚĂƐĞŶƚƌĞƐş͕ůĂƐĐƵĂůĞƐ
ƐŽŶƚşƉŝĐĂƐĚĞůĂƐĐĠůƵůĂƐŵĞƚĂďſůŝĐĂŵĞŶƚĞĂĐƚŝǀĂƐ͘>ĂƐĐŝƚĂĚĂƐƌĞĚĞƐĂĐƚƷĂŶĐŽŵŽƵŶ
ƐŝƐƚĞŵĂĞůĠĐƚƌŝĐŽ͕ĞůĐƵĂůĨĂĐŝůŝƚĂůĂƚƌĂŶƐŵŝƐŝſŶĚĞůŽƐƉŽƚĞŶĐŝĂůĞƐĚĞŵĞŵďƌĂŶĂĚĞƐĚĞ
ůĂƐ ĄƌĞĂƐ ƌŝĐĂƐ ĞŶ ŽǆşŐĞŶŽ ŚĂĐŝĂ ůĂƐ ƉŽďƌĞƐ͕ ;^ŬƵůĂĐŚĞǀ͕ ϮϬϬϭͿ͘ ĚĞŵĄƐ͕ ĞƐƚĂ ƌĞůĂĐŝſŶ
ĞŶƚƌĞůĂƐŵŝƚŽĐŽŶĚƌŝĂƐŶŽƐſůŽĞƐŝŵƉŽƌƚĂŶƚĞĚĞŶƚƌŽĚĞůŵĞƚĂďŽůŝƐŵŽĞŶĞƌŐĠƚŝĐŽ͕ƐŝŶŽ
ƋƵĞ ĞƐ ƚĂŵďŝĠŶ ŝŶĚŝƐƉĞŶƐĂďůĞ ƉĂƌĂ ůĂ ĐŽƌƌĞĐƚĂ ƌĞƐƉƵĞƐƚĂ Ă ůĂƐ ƐĞŹĂůĞƐ ĚĞ ĐĂůĐŝŽ͕
;^ǌĂďĂĚŬĂŝĞƚ Ăů͕͘ ϮϬϬϲͿ͕ ĂƐş ĐŽŵŽ ƉĂƌĂ ůĂ ƌĞĂĐĐŝſŶ ĂŶƚĞ ƐŝƚƵĂĐŝŽŶĞƐ ĚĞĞƐƚƌĠƐ ĐĞůƵůĂƌ͕
;dŽŶĚĞƌĂĞƚĂů͕͘ϮϬϬϵͿ͘
ĞƐĚĞƵŶƉƵŶƚŽĚĞǀŝƐƚĂŵĞĐĂŶşƐƚŝĐŽ͕ŶŽƐĞŶĐŽŶƚƌĂŵŽƐĂŶƚĞƵŶƉƌŽĐĞĚŝŵŝĞŶƚŽ
ĐŽŵƉůĞũŽ͕ĨƵĞƌƚĞŵĞŶƚĞůŝŐĂĚŽĂůĂŚŝĚƌſůŝƐŝƐĚĞ'dW͕;>ĞŐƌŽƐĞƚĂů͕͘ϮϬϬϮ͖DĞĞƵƐĞŶĞƚ
Ăů͕͘ ϮϬϬϰͿ͕ ĞŶ Ğů ƋƵĞ ƐĞ ƉƌŽĚƵĐĞ ůĂ ƵŶŝſŶ ĚĞ ĚŽƐ ŵŝƚŽĐŽŶĚƌŝĂƐ ǀĞĐŝŶĂƐ͘ >Ă ĨƵƐŝſŶ ƐĞ
ĚĞƐĂƌƌŽůůĂĞŶĚŽƐĨĂƐĞƐĚŝĨĞƌĞŶĐŝĂĚĂƐĞŝŶĚĞƉĞŶĚŝĞŶƚĞƐĞŶƚƌĞƐş͕ĞŶůĂƐƋƵĞŝŶƚĞƌǀŝĞŶĞŶ
ŵĞĐĂŶŝƐŵŽƐĚŝƐƚŝŶƚŽƐ͕;DĂůŬĂĞƚĂů͕͘ϮϬϬϱ͖DĞĞƵƐĞŶĞƚĂů͕͘ϮϬϬϰͿ͘Ɛş͕ĞŶůĂƉƌŝŵĞƌĂƐĞ
ĨƵƐŝŽŶĂƌĄŶ ůĂƐ ŵĞŵďƌĂŶĂƐ ĞǆƚĞƌŶĂƐ ĚĞ ůĂƐ ŵŝƚŽĐŽŶĚƌŝĂƐ ǀĞĐŝŶĂƐ͕ ŵŝĞŶƚƌĂƐ ƋƵĞ͕ ĞŶ ůĂ
ϲ
ƐĞŐƵŶĚĂ͕ƐƵĐĞĚĞƌĄůŽƉƌŽƉŝŽĐŽŶůĂƐŝŶƚĞƌŶĂƐ͕;,ŽƉƉŝŶƐĞƚĂů͕͘ϮϬϬϳͿ͘
WĂƌĂƋƵĞůĂĨƵƐŝſŶŵŝƚŽĐŽŶĚƌŝĂůƐĞůůĞǀĞĂĐĂďŽ͕ĞƐŶĞĐĞƐĂƌŝŽƋƵĞĞůƉŽƚĞŶĐŝĂůĚĞ
ŵĞŵďƌĂŶĂ ĞƐƚĠ ŝŶƚĂĐƚŽ͕ ;DĞĞƵƐĞŶ Ğƚ Ăů͕͘ ϮϬϬϰͿ͘ WŽƌ ƚĂŶƚŽ͕ ůĂƐ ŵŝƚŽĐŽŶĚƌŝĂƐ
ĚĞƐƉŽůĂƌŝǌĂĚĂƐŶŽƉƵĞĚĞŶ ĞŶƚƌĂƌ ĞŶĨƵƐŝſŶ ǇƋƵĞĚĂŶ ĞǆĐůƵŝĚĂƐ ĚĞů ĐŝĐůŽĨƵƐŝſŶͲĨŝƐŝſŶ͕
;DŽƵůŝĞƚĂů͕͘ϮϬϬϵ͖dǁŝŐĞƚĂů͕͘ϮϬϬϴͿ͕ƐƵĨƌŝĞŶĚŽĞŶƚŽŶĐĞƐŵŝƚŽĨĂŐŝĂ͘ƐƚĂƐĞůĞĐƚŝǀŝĚĂĚ͕
ƋƵĞĐŽŶůůĞǀĂƋƵĞůĂĨƵƐŝſŶƐĞĂĞǆĐůƵƐŝǀĂĚĞĐĠůƵůĂƐĐŽŶƐƵƐŵŝƚŽĐŽŶĚƌŝĂƐƐĂŶĂƐ͕ŶŽƐĞ
ŽďƐĞƌǀĂĞŶĞůĐĂƐŽĚĞůĂĨŝƐŝſŶĚĞůŽƌŐĄŶƵůŽ͘
ƉĂƌƚĞ ĚĞů ƉƌŽĐĞƐŽ ĐůĄƐŝĐŽ ĚĞ ĨƵƐŝſŶ ŵŝƚŽĐŽŶĚƌŝĂů͕ ĞǆŝƐƚĞ ƵŶ ƐĞŐƵŶĚŽ ƚŝƉŽ͕
ĐŽŶŽĐŝĚŽ ĐŽŵŽ ĨƵƐŝſŶ ƚƌĂŶƐŝƚŽƌŝĂ Ž ͞ŬŝƐƐ ĂŶĚ ƌƵŶ͕͟ ĞŶ Ğů ĐƵĂů ƐĞ ƉƌŽĚƵĐĞ ůĂ
ĂƉƌŽǆŝŵĂĐŝſŶ ĚĞ ĚŽƐ ŵŝƚŽĐŽŶĚƌŝĂƐ͕ ůĂ ĨƵƐŝſŶ ĚĞ ƐƵƐ ŵĞŵďƌĂŶĂƐ͕ Ğů ŝŶƚĞƌĐĂŵďŝŽ ĚĞ
ƉƌŽƚĞşŶĂƐ ĚĞů ĞƐƉĂĐŝŽ ŝŶƚĞƌŵĞŵďƌĂŶĂƐ Ǉ ĚĞ ůĂ ŵĂƚƌŝǌ Ǉ ůĂ ƐĞƉĂƌĂĐŝſŶ ĨŝŶĂů ĚĞ ůŽƐ ĚŽƐ
ŽƌŐĄŶƵůŽƐ͘ Ŷ Ğů ͞ŬŝƐƐ ĂŶĚ ƌƵŶ͟ ƉĂƌƚŝĐŝƉĂŶ ƚĂŶƚŽ ůĂ ŵĂƋƵŝŶĂƌŝĂ ƉƌŽĨŝƐŝſŶ ĐŽŵŽ ůĂ
ƉƌŽĨƵƐŝſŶ͕ ;>ŝƵ Ğƚ Ăů͕͘ ϮϬϬϵͿ͖ ƉĞƌŵŝƚŝĞŶĚŽ Ğů ŝŶƚĞƌĐĂŵďŝŽ ĚĞ ĐŽŶƚĞŶŝĚŽƐ ĞŶƚƌĞ ůĂƐ
ŵŝƚŽĐŽŶĚƌŝĂƐ͕ ĂƵŶƋƵĞ ĚĞ ƵŶ ŵŽĚŽ ŵĞŶŽƐ ĞĨĞĐƚŝǀŽ ƋƵĞ ĐƵĂŶĚŽ ůĂ ĨƵƐŝſŶ ƐĞ ƉƌŽĚƵĐĞ
ƉŽƌůĂǀşĂĐůĄƐŝĐĂ͕;>ĞŐƌŽƐĞƚĂů͕͘ϮϬϬϰ͖KŶŽĞƚĂů͕͘ϮϬϬϭͿ͘
DŝƚŽĨƵƐŝŶĂƐϭǇϮ
>ĂƐ ŵŝƚŽĨƵƐŝŶĂƐ͕ ;DĨŶϭ Ǉ DĨŶϮͿ͕ ƐŽŶ ƉƌŽƚĞşŶĂƐ ŝŶƚĞŐƌĂůĞƐ ĚĞ ůĂ ŵĞŵďƌĂŶĂ
ŵŝƚŽĐŽŶĚƌŝĂůĞǆƚĞƌŶĂǇƉŽƐĞĞŶĂĐƚŝǀŝĚĂĚ'dWĂƐĂ͘ŵďĂƐƐĞĞŶĐƵĞŶƚƌĂŶĚŝƐƚƌŝďƵŝĚĂƐƉŽƌ
ƚŽĚŽ Ğů ŽƌŐĂŶŝƐŵŽ͕ ƉƌĞƐĞŶƚĂŶĚŽ ƵŶĂ ŵĂǇŽƌ ĞǆƉƌĞƐŝſŶ ĞŶ ĐŝĞƌƚŽƐ ƚĞũŝĚŽƐ Ǉ ſƌŐĂŶŽƐ͕
;ĂĐŚĞƚĂů͕͘ϮϬϬϱ͖ĂĐŚĞƚĂů͕͘ϮϬϬϯ͖ƵƌĂĞƚĂů͕͘ϮϬϬϯ͖^ĂŶƚĞůĞƚĂů͕͘ϮϬϬϯͿ͘
ƐƚƌƵĐƚƵƌĂůŵĞŶƚĞ͕ ůĂƐ ŵŝƚŽĨƵƐŝŶĂƐ ƉŽƐĞĞŶ ĚŽƐ ƌĞŐŝŽŶĞƐ ƚƌĂŶƐŵĞŵďƌĂŶĂ
ƐĞƉĂƌĂĚĂƐĞŶƚƌĞƐşƐſůŽƉŽƌĚŽƐŽƚƌĞƐĂŵŝŶŽĄĐŝĚŽƐ͘ĚĞŵĄƐ͕ĞŶƐƵĞǆƚƌĞŵŽͲƚĞƌŵŝŶĂů͕
ĐŽŶƚŝĞŶĞŶ ƵŶĂ ĞƐƚƌƵĐƚƵƌĂ ƉƌŽƚĞŝĐĂ ĞŶ ĞƐƉŝƌĂů ƋƵĞ ĂĐƚƷĂ ĐŽŵŽ ĂŶĐůĂũĞ ĂůĂ ŵĞŵďƌĂŶĂ
ĞǆƚĞƌŶĂ ŵŝƚŽĐŽŶĚƌŝĂů͕ ;^ĂŶƚĞů Ğƚ Ăů͕͘ ϮϬϬϭͿ͕ ŐƌĂĐŝĂƐ Ă ůŽ ĐƵĂů ƉƵĞĚĞŶ ĨŽƌŵĂƌ ĚşŵĞƌŽƐ͕
;ŵŽŶſŵĞƌŽƐ Ž ŚĞƚĞƌſŵĞƌŽƐͿ͕ ĞŶƚƌĞ Ɛş ĞŶ ůĂƐ ŵŝƚŽĐŽŶĚƌŝĂƐ ĂĚǇĂĐĞŶƚĞƐ͕ ƐŝĞŵƉƌĞ ĞŶ
ƉŽƐŝĐŝſŶ ƚƌĂŶƐ͘ ƐƚĂƐ ƵŶŝŽŶĞƐ ƐŽŶ ůĂƐ ƋƵĞ ƉĞƌŵŝƚĞŶ ůĂ ĨƵƐŝſŶ ĚĞ ůĂƐ ŵĞŵďƌĂŶĂƐ
ĞǆƚĞƌŶĂƐ͕;ŚĞŶĞƚĂů͕͘ϮϬϬϯ͖/ƐŚŝŚĂƌĂĞƚĂů͕͘ϮϬϬϰ͖<ŽƐŚŝďĂĞƚĂů͕͘ϮϬϬϰͿ͘WŽƌŽƚƌŽůĂĚŽ͕
ϳ
ĞŶ ƐƵ ĞǆƚƌĞŵŽEͲƚĞƌŵŝŶĂů͕ ƉŽƐĞĞŶ ƵŶ ĚŽŵŝŶŝŽ ĞŶ Ğů ƋƵĞ ĞƐƚĄ ĐŽĚŝĨŝĐĂĚĂ ƐƵ ĂĐƚŝǀŝĚĂĚ
'dWĂƐĂ͘
WƌŽƚĞşŶĂĚĞůĂƚƌŽĨŝĂMƉƚŝĐĂƵƚŽƐſŵŝĐĂŽŵŝŶĂŶƚĞ
>Ă ĨƵŶĐŝſŶ ƉƌŝŶĐŝƉĂů ĚĞ KWϭ ĞƐ ĐŽŶƚƌŽůĂƌ ůĂ ĨƵƐŝſŶ ĚĞ ůĂ ŵĞŵďƌĂŶĂ ŝŶƚĞƌŶĂ
ŵŝƚŽĐŽŶĚƌŝĂů͕ ;ŝƉŽůĂƚ Ğƚ Ăů͕͘ ϮϬϬϰͿ͕ ƉĞƌŵŝƚŝĞŶĚŽ ƋƵĞ ƐĞ ƉƌŽĚƵǌĐĂ Ğů ƉƌŽĐĞƐŽ͕ ŐƌĂĐŝĂƐ
ƚĂŵďŝĠŶĂƐƵĚŽŵŝŶŝŽ'dWĂƐĂ͕;DĞĞƵƐĞŶĞƚĂů͕͘ϮϬϬϲͿ͘ŶŵĂŵşĨĞƌŽƐ͕ŶŽĞƐŶĞĐĞƐĂƌŝĂ
ůĂƉƌĞƐĞŶĐŝĂĚĞKWϭĞŶůĂƐĚŽƐŵĞŵďƌĂŶĂƐƋƵĞǀĂŶĂƐƵĨƌŝƌůĂĨƵƐŝſŶƉĂƌĂƋƵĞĠƐƚĂƐĞ
ůůĞǀĞĂĐĂďŽ͘ĞŚĞĐŚŽ͕ĞƐƐƵĨŝĐŝĞŶƚĞĐŽŶƋƵĞůĂƉƌŽƚĞşŶĂĞƐƚĠƉƌĞƐĞŶƚĞƐſůŽĞŶƵŶĂĚĞ
ĞůůĂƐ͕;^ŽŶŐĞƚĂů͕͘ϮϬϬϵͿ͘
KWϭ ĞƐ ƵŶĂ ƉƌŽƚĞşŶĂ ƐƵŵĂŵĞŶƚĞ ĐŽŵƉůĞũĂ͕ ƋƵĞ ƐƵĨƌĞ ƵŶĂ ŝŵƉŽƌƚĂŶƚĞ
ƌĞŐƵůĂĐŝſŶ ƉŽƐƚƌĂŶƐĐƌŝƉĐŝŽŶĂů͘ ^Ğ ĚŝƐƚƌŝďƵǇĞ ĚĞ ƵŶ ŵŽĚŽ ƵďŝĐƵŽ ĞŶ Ğů ŽƌŐĂŶŝƐŵŽ͕
ĞǆƉƌĞƐĄŶĚŽƐĞŵĄƐĞŶĐŝĞƌƚŽƐſƌŐĂŶŽƐǇƚĞũŝĚŽƐ͕;ůĞǆĂŶĚĞƌĞƚĂů͕͘ϮϬϬϬ͖ĞůĞƚƚƌĞĞƚĂů͕͘
ϮϬϬϬͿ͘ ZĞƐƉĞĐƚŽ Ă ƐƵ ůŽĐĂůŝǌĂĐŝſŶ ĐĞůƵůĂƌ͕ ĚĞďŝĚŽ Ă ůĂ ƉƌĞƐĞŶĐŝĂ ĚĞ ƵŶĂ ƐĞĐƵĞŶĐŝĂ
ĐŽŶĐƌĞƚĂ Ǉ ĐŽŶŽĐŝĚĂ͕ ĂƐş ĐŽŵŽ ĚĞ ƵŶĂƐ ŚĠůŝĐĞƐ ƚƌĂŶƐŵĞŵďƌĂŶĂ ĞŶ ƐƵ ĞǆƚƌĞŵŽ EͲ
ƚĞƌŵŝŶĂů͕ ƐĞ ůŽĐĂůŝǌĂ ĂŶĐůĂĚĂ ĞŶ ůĂ ŵĞŵďƌĂŶĂ ŝŶƚĞƌŶĂ ŵŝƚŽĐŽŶĚƌŝĂů ;<ŶŽƚƚ Ğƚ Ăů͕͘
ϮϬϬϴďͿ͘
KWϭƉŽƐĞĞĚŽƐŝƐŽĨŽƌŵĂƐ͕ƐKWϭ͕;ĚĞůŝŶŐůĠƐ͞ƐŚŽƌƚ͟Ϳ͕ĚĞƉĞƋƵĞŹŽƚĂŵĂŹŽǇ
ƐŽůƵďůĞ͕ Ǉ ůKWϭ͕ ;ĚĞů ŝŶŐůĠƐ ͞ůŽŶŐ͟Ϳ͕ ŵĄƐ ŐƌĂŶĚĞ͘ ƐKWϭ ƐĞ ƉƌŽĚƵĐĞ ƉŽƌ ĞƐĐŝƐŝſŶ
ƉƌŽƚĞŽůşƚŝĐĂĚĞůĂƐĞŐƵŶĚĂǇƐĞĞŶĐƵĞŶƚƌĂĞŶĞůĞƐƉĂĐŝŽŝŶƚĞƌŵĞŵďƌĂŶĂ͕ƉŽƐŝďůĞŵĞŶƚĞ
ĂŶĐůĂĚĂĂĂůŐƵŶĂƉƌŽƚĞşŶĂƋƵĞĚĞƐĐŽŶŽĐĞŵŽƐ͕ƐŝĞŶĚŽŶĞĐĞƐĂƌŝĂƉĂƌĂƋƵĞƐĞŵĂŶƚĞŶŐĂ
ůĂ ŵŽƌĨŽůŽŐşĂ ĞŶ ĐƌĞƐƚĂƐ ŵŝƚŽĐŽŶĚƌŝĂůĞƐ͕ ;ŝƉŽůĂƚ Ğƚ Ăů͕͘ ϮϬϬϲͿ͘ ůKWϭ͕ ƉŽƌ ƐƵ ƉĂƌƚĞ͕
ƉŽƐĞĞ ƵŶ ĚŽŵŝŶŝŽ ƚƌĂŶƐŵĞŵďƌĂŶĂ Ăů ƋƵĞ ƐĞ ƉƵĞĚĞŶ ƵŶŝƌ ŵƵĐŚĂƐ ƉƌŽƚĞĂƐĂƐ͘ ^Ğ
ĞŶĐƵĞŶƚƌĂ ĂŶĐůĂĚĂ ƉŽƌ ƵŶŽ ĚĞ ƐƵƐ ĞǆƚƌĞŵŽƐ Ă ůĂ ŵĞŵďƌĂŶĂ ŝŶƚĞƌŶĂ ŵŝƚŽĐŽŶĚƌŝĂů͕
ĂƵŶƋƵĞ͕ƉŽƌƐƵĞǆƚƌĞŵŽůŝďƌĞ͕ƉŽĚƌşĂĞƐƚĂƌůŝŐĂĚĂĂĂůŐƷŶĞůĞŵĞŶƚŽĚĞƐĐŽŶŽĐŝĚŽ͘WĂƌĂ
ƋƵĞƐĞƉƌŽĚƵǌĐĂůĂĨƵƐŝſŶĚĞůĂŵĞŵďƌĂŶĂŝŶƚĞƌŶĂĞƐŶĞĐĞƐĂƌŝĂůĂƉƌĞƐĞŶĐŝĂĚĞůĂƐĚŽƐ
ŝƐŽĨŽƌŵĂƐ͕ ĂƐş ĐŽŵŽ ƋƵĞ ĠƐƚĂƐ ĞƐƚĠŶ ĞŶ ĞƋƵŝůŝďƌŝŽ ĞŶƚƌĞ ĞůůĂƐ͕ ;'ƌŝƉĂƌŝĐ Ğƚ Ăů͕͘ ϮϬϬϳ͖
/ƐŚŝŚĂƌĂĞƚĂů͕͘ϮϬϬϲ͖^ŽŶŐĞƚĂů͕͘ϮϬϬϳͿ͘
I.1.2. Fisión mitocondrial
ϴ
ŽŶƐƚŝƚƵǇĞ Ğů ƷŶŝĐŽ ŵĞĐĂŶŝƐŵŽ ĐĞůƵůĂƌ ƋƵĞ ƉĞƌŵŝƚĞ ƉƌŽĚƵĐŝƌ ŵŝƚŽĐŽŶĚƌŝĂƐ
ŶƵĞǀĂƐ ĚĞƐĚĞ ŽƚƌĂƐ ǇĂ ĞǆŝƐƚĞŶƚĞƐ͕ ĚƵƌĂŶƚĞ ůĂ ĐŝƚŽƋƵŝŶĞƐŝƐ ĐĞůƵůĂƌ͘ Ɛş͕ ƐĞ ŽďƚŝĞŶĞŶ
ŽƌŐĄŶƵůŽƐŵŽƌĨŽůſŐŝĐĂǇĨƵŶĐŝŽŶĂůŵĞŶƚĞĚŝĨĞƌĞŶƚĞƐĞŶƚƌĞƐş͕ůŽŐƌĂŶĚŽƋƵĞĞůĐŽŶƚĞŶŝĚŽ
ŵŝƚŽĐŽŶĚƌŝĂůƉĂƐĞĂůĂƐĐĠůƵůĂƐŚŝũĂƐĐŽƌƌĞĐƚĂŵĞŶƚĞĚƵƌĂŶƚĞůĂĚŝǀŝƐŝſŶĐĞůƵůĂƌ͕;DĞƌǌĞƚ
Ăů͕͘ϮϬϬϳ͖zĂĨĨĞ͕ϭϵϵϵͿ͘
ZĞƐƉĞĐƚŽĂůĂĨƵŶĐŝſŶďŝŽůſŐŝĐĂĚĞĞƐƚĞƉƌŽĐĞƐŽĞŶĞůƐŝƐƚĞŵĂŶĞƌǀŝŽƐŽ͕ůĂĨŝƐŝſŶ
ŵŝƚŽĐŽŶĚƌŝĂů ĞƐƚĄ ŵƵǇ ƌĞůĂĐŝŽŶĂĚĂ ĐŽŶ Ğů ĚĞƐĂƌƌŽůůŽ ĚĞ ůĂƐ ƐŝŶĂƉƐŝƐ͕ ;ŚĂŶŐ Ğƚ Ăů͕͘
ϮϬϬϲĂ͖>ŝĞƚĂů͕͘ϮϬϬϰͿ͕ĂƐşĐŽŵŽĐŽŶůĂůŽĐĂůŝǌĂĐŝſŶĚĞůĂƐŵŝƚŽĐŽŶĚƌŝĂƐĞŶƉŽƐŝĐŝŽŶĞƐ
ĞƐƚƌĂƚĠŐŝĐĂƐ͕ ĐŽŵŽ ƐŽŶ͕ ƉŽƌ ĞũĞŵƉůŽ͕ ůĂƐ ĄƌĞĂƐ ĚĞ ĂůƚŽ ƌĞƋƵĞƌŝŵŝĞŶƚŽ ĞŶĞƌŐĠƚŝĐŽ͘
ĚĞŵĄƐ͕ŚĂǇǀĂƌŝŽƐĞƐƚƵĚŝŽƐƋƵĞĐŽŶĐůƵǇĞŶƋƵĞĞƐƚĞƉƌŽĐĞƐŽƉƵĞĚĞƚĞŶĞƌƚĂŵďŝĠŶƵŶ
ƉĂƉĞůŝŵƉŽƌƚĂŶƚĞĞŶůĂĞůŝŵŝŶĂĐŝſŶĚĞůĂƐŵŝƚŽĐŽŶĚƌŝĂƐĚĂŹĂĚĂƐ͕ǇĂƋƵĞƐĞƌǀŝƌşĂƉĂƌĂ
ŵĂƌĐĂƌůĂƐ ƉĂƌĂ ůĂ ƉŽƐƚĞƌŝŽƌ ŵŝƚŽĨĂŐŝĂ͕ ;ĂƌƐŽƵŵ Ğƚ Ăů͕͘ ϮϬϬϲ͖ dǁŝŐ Ğƚ Ăů͕͘ ϮϬϬϴͿ͘ WŽƌ
ƷůƚŝŵŽ͕ >ĞĞ Ǉ ĐŽůƐ͕͘ ƉƌŽƉŽŶĞŶ ƋƵĞ ůĂ ĨŝƐŝſŶ ĞƐ ŶĞĐĞƐĂƌŝĂ ƉĂƌĂ ůĂ ƉƌĞǀĞŶĐŝſŶ ĚĞ ůĂ
ĞůŽŶŐĂĐŝſŶŵŝƚŽĐŽŶĚƌŝĂůĞǆĐĞƐŝǀĂ͕ůĂĐƵĂůƉƌŽĚƵĐŝƌşĂĨĞŶſŵĞŶŽƐĚĞƐĞŶĞƐĐĞŶĐŝĂĐĞůƵůĂƌ͕
;>ĞĞĞƚĂů͕͘ϮϬϬϳͿ͘
ŶůŽƐƉƌŽĐĞƐŽƐĚĞĨŝƐŝſŶŵŝƚŽĐŽŶĚƌŝĂůůĂƐƉƌŝŶĐŝƉĂůĞƐƉƌŽƚĞşŶĂƐŝŵƉůŝĐĂĚĂƐƐŽŶ
ůĂ WƌŽƚĞşŶĂ ^ŝŵŝůĂƌ Ă ůĂ ŝŶĂŵŝŶĂ ϭ͕ ;ƌƉϭͿ͕ Ǉ &ŝƐϭ͘ ŵďĂƐ ƉĂƌƚŝĐŝƉĂŶ ƚĂŵďŝĠŶ ĞŶ ůĂ
ĨŝƐŝſŶĚĞŽƚƌĂƐŽƌŐĂŶĞůĂƐ͕ĐŽŵŽĞƐĞůĐĂƐŽĚĞůŽƐƉĞƌŽǆŝƐŽŵĂƐ͕;<ŽĐŚĞƚĂů͕͘ϮϬϬϯ͖<ŽĐŚ
Ğƚ Ăů͕͘ ϮϬϬϱͿ͕ Ž ĞŶ ůĂ ĞƐĐŝƐŝſŶ ĚĞ ůŽƐ ĞŶĚŽƐŽŵĂƐ ĚĞƐĚĞ ůĂ ŵĞŵďƌĂŶĂ ƉůĂƐŵĄƚŝĐĂ͕
;ƌĂƐĐŚŝĞƚĂů͕͘ϮϬϭϬͿ͘
WƌŽƚĞşŶĂ^ŝŵŝůĂƌĂůĂŝŶĂŵŝŶĂϭ
>Ă WƌŽƚĞşŶĂ ^ŝŵŝůĂƌ Ă ůĂ ŝŶĂŵŝŶĂ ϭ͕ ;ƌƉϭͿ͕ ĞƐ ĚĞ ŶĂƚƵƌĂůĞǌĂ ƐŽůƵďůĞ͕ ƉŽƐĞĞ
ĂĐƚŝǀŝĚĂĚ 'dWĂƐĂ͕ ƉƌĞƐĞŶƚĂ ŐƌĂŶ ƚĂŵĂŹŽ Ǉ ƐƵ ĚĞĨŝĐŝĞŶĐŝĂ ƉƌŽĚƵĐĞ ůĞƚĂůŝĚĂĚ
ĞŵďƌŝŽŶĂƌŝĂ͕ĐŽŶůĂĂƉĂƌŝĐŝſŶĚĞĞƐƚƌƵĐƚƵƌĂƐĐĂƌĚşĂĐĂƐǇŚĞƉĄƚŝĐĂƐƉŽĐŽĚĞƐĂƌƌŽůůĂĚĂƐ͕
ĂƵŵĞŶƚŽĚĞůĂĂƉŽƉƚŽƐŝƐĞŶůĂĐŽƌƚĞǌĂŶĞƵƌĂůǇĞƐĐĂƐĂĨŽƌŵĂĐŝſŶĚĞƐŝŶĂƉƐŝƐ͕;/ƐŚŝŚĂƌĂ
Ğƚ Ăů͕͘ ϮϬϬϵ͖ hŽ Ğƚ Ăů͕͘ ϮϬϬϵ͖ tĂŬĂďĂǇĂƐŚŝ Ğƚ Ăů͕͘ ϮϬϬϵͿ͘ ^ŝŶ ĞŵďĂƌŐŽ͕ ƐƵ ĂďůĂĐŝſŶ Ă
ĐŽƌƚŽƉůĂǌŽƉĂƌĞĐĞƚĞŶĞƌƵŶĞĨĞĐƚŽƌƉƌŽƚĞĐƚŽƌƐŽďƌĞůĂƐŶĞƵƌŽŶĂƐ͕;KĞƚƚŝŶŐŚĂƵƐĞƚĂů͕͘
ϮϬϭϮͿ͘WĂƌĂĞǆƉůŝĐĂƌĞƐƚĞŚĞĐŚŽ͕ƐĞŚĂƉŽƐƚƵůĂĚŽƋƵĞůĂĐĂƌĞŶĐŝĂĚĞĨŝƐŝſŶŵŝƚŽĐŽŶĚƌŝĂů
ƐĞ ƉŽĚƌşĂ ĐŽŵƉĞŶƐĂƌ ĐŽŶ Ğů ĂƵŵĞŶƚŽ ĚĞ ůĂ ĚĞŐƌĂĚĂĐŝſŶ ĚĞ KWϭ͕ ĂƐş ĐŽŵŽ ĐŽŶ ůĂ
ϵ
ƌĞŐƵůĂĐŝſŶ Ă ůĂ ďĂũĂ ĚĞ ůĂ ĞǆƉƌĞƐŝſŶ ĚĞ ůĂƐ DĨŶƐ͕ ƉƌŽĚƵĐŝĠŶĚŽƐĞ͕ ƉŽƌ ƚĂŶƚŽ͕ ƵŶĂ
ĚŝƐŵŝŶƵĐŝſŶĐŽŵƉĞŶƐĂƚŽƌŝĂĚĞůĂĨƵƐŝſŶŵŝƚŽĐŽŶĚƌŝĂů͕;/ƐŚŝŚĂƌĂĞƚĂů͕͘ϮϬϬϵͿ͘
ƉĂƌƚĞ ĚĞ ůĂ ĨƵŶĐŝſŶ ĐůĄƐŝĐĂ ĐŽŵŽ ŵĞĚŝĂĚŽƌ ĚĞ ůĂ ĨŝƐŝſŶ ŵŝƚŽĐŽŶĚƌŝĂů͕ ƌƉϭ
ũƵĞŐĂƚĂŵďŝĠŶƵŶƉĂƉĞůŝŵƉŽƌƚĂŶƚĞĞŶĞůŵĂŶƚĞŶŝŵŝĞŶƚŽĚĞůĂĞƐƚƌƵĐƚƵƌĂĞŶĐƌĞƐƚĂƐĚĞ
ůĂŵĞŵďƌĂŶĂŝŶƚĞƌŶĂ͕ĂƵŶƋƵĞ͕ĂĚşĂĚĞŚŽǇ͕ĚĞƐĐŽŶŽĐĞŵŽƐĞůŵĞĐĂŶŝƐŵŽĂƚƌĂǀĠƐĚĞů
ĐƵĂůƌĞĂůŝǌĂĞƐƚĂĂĐĐŝſŶ͘Ɛş͕ůŽƋƵĞƐşƋƵĞĐŽŶŽĐĞŵŽƐĞƐĞůŚĞĐŚŽĚĞƋƵĞ͕ĞŶŵŽĚĞůŽƐ
ĞŶ ůŽƐ ƋƵĞ ƐĞ ƉƌŽĚƵĐĞ ůĂ ĂďůĂĐŝſŶ ĚĞ ƌƉϭ͕ ůĂƐ ĨŽƌŵĂƐ ƉƌŽƚĞŽůşƚŝĐĂƐ ĚĞ KWϭ ƐĞ
ĞŶĐƵĞŶƚƌĂŶĂůƚĞƌĂĚĂƐ͕;/ƐŚŝŚĂƌĂĞƚĂů͕͘ϮϬϬϵ͖DŽƉĞƌƚĞƚĂů͕͘ϮϬϬϵͿ͘
ůƉĂƉĞůĚĞƌƉϭĞŶůĂĨŝƐŝſŶŵŝƚŽĐŽŶĚƌŝĂůĐŽŵŝĞŶǌĂĐƵĂŶĚŽ͕ĂŶƚĞƵŶĞƐƚşŵƵůŽ
ĂĐƚŝǀĂĚŽƌ͕ ĞƐƚĂ ƉƌŽƚĞşŶĂ ŵŝŐƌĂ ĚĞƐĚĞ Ğů ĐŝƚŽƉůĂƐŵĂ ŚĂƐƚĂ ůĂ ŵĞŵďƌĂŶĂ ĞǆƚĞƌŶĂ
ŵŝƚŽĐŽŶĚƌŝĂů͕ ;^ŵŝƌŶŽǀĂĞƚ Ăů͕͘ ϭϵϵϴͿ͕ ĂƚƌĂǀĠƐĚĞ ƵŶ ŵĞĐĂŶŝƐŵŽ ĂƵŶĚĞƐĐŽŶŽĐŝĚŽ͘ ^ŝ
ďŝĞŶ͕ ƐĞ ŚĂƉƌŽƉƵĞƐƚŽ ƋƵĞ ĞŶ Ġů ƉŽĚƌşĂŶ ĞƐƚĂƌ ŝŵƉůŝĐĂĚŽƐ ůŽƐŵŝĐƌŽƚƷďƵůŽƐ͕ ĂƐş ĐŽŵŽ
ůŽƐĨŝůĂŵĞŶƚŽƐĚĞĂĐƚŝŶĂ͕;ĞsŽƐĞƚĂů͕͘ϮϬϬϱͿ͘hŶĂǀĞǌĞŶůĂĐŝƚĂĚĂŵĞŵďƌĂŶĂ͕ƌƉϭ
ŶĞĐĞƐŝƚĂĂĚĂƉƚĂĚŽƌĞƐ͕ĐŽŵŽĞƐĞůĐĂƐŽĚĞ&ŝƐϭ͕ƉĂƌĂĂŶĐůĂƌƐĞĂĞůůĂ͕;zŽŽŶĞƚĂů͕͘ϮϬϬϯͿ͘
ĐŽŶƚŝŶƵĂĐŝſŶ͕ƌƉϭĨŽƌŵĂƵŶĂƐĞƐƚƌƵĐƚƵƌĂƐŚĞůŝĐŽŝĚĂůĞƐ͕ƋƵĞĐŽŶƐƚŝƚƵŝƌĄŶůŽƐůƵŐĂƌĞƐ
ƉŽƌ ůŽƐ ƐĞ ǀĂ Ă ƉƌŽĚƵĐŝƌ ůĂ ĞƐĐŝƐŝſŶ ĚĞů ŽƌŐĄŶƵůŽ͕ ;^ŵŝƌŶŽǀĂ Ğƚ Ăů͕͘ ϮϬϬϭͿ͕ Ăů ƐĞƌ ůĂƐ
ƌĞƐƉŽŶƐĂďůĞƐĚĞůĂŽƉƌĞƐŝſŶĚĞůŽƐƚƷďƵůŽƐůŝƉşĚŝĐŽƐƌĞƐƵůƚĂŶƚĞƐĚĞůĂĐŽŶƚƌĂĐĐŝſŶĚĞůĂ
ŵĞŵďƌĂŶĂŵŝƚŽĐŽŶĚƌŝĂů͕Ǉ͕ĞŶƷůƚŝŵŽƚĠƌŵŝŶŽ͕ĚĞůĞƐƚƌĂŶŐƵůĂŵŝĞŶƚŽĚĞůĂŵĞŵďƌĂŶĂ
ĞǆƚĞƌŶĂ͕;ĂŶŝŶŽĞƚĂů͕͘ϮϬϬϰͿ͘
WĂƌĂ ƋƵĞ ĞƐƚĞ ƉƌŽĐĞƐŽ ƐĞ ůůĞǀĞ Ă ĐĂďŽ͕ ƌƉϭ ĚĞďĞ ĚĞ ƐƵĨƌŝƌ ƵŶ ĐĂŵďŝŽ
ĐŽŶĨŽƌŵĂĐŝŽŶĂů͕ƉĂƌĂůŽĐƵĂůĞƐŶĞĐĞƐĂƌŝĂůĂŚŝĚƌſůŝƐŝƐĚĞƵŶĂŵŽůĠĐƵůĂĚĞ'dW͕;<ŶŽƚƚ
Ğƚ Ăů͕͘ ϮϬϬϴĂͿ ;ŚĂŶŐ Ğƚ Ăů͕͘ ϮϬϭϬͿ͘ ĚĞŵĄƐ͕ ŶĞĐĞƐŝƚĂ ƚĂŵďŝĠŶ ĚĞƐĂƌƌŽůůĂƌ ĐŝĞƌƚĂƐ
ŵŽĚŝĨŝĐĂĐŝŽŶĞƐƉŽƐƚĞƌŝŽƌĞƐĂůĂƚƌĂŶƐĐƌŝƉĐŝſŶ͕ĞŶƚƌĞůĂƐƋƵĞĚĞƐƚĂĐĂŶ͕
Ͳ&ŽƐĨŽƌŝůĂĐŝŽŶĞƐ͗ƌƉϭĞƐƐƵƐƚƌĂƚŽĚĞĚŝĨĞƌĞŶƚĞƐĐŝŶĂƐĂƐ͕ĐŽŵŽĞƐĞůĐĂƐŽĚĞůĂ
WƌŽƚĞŝŶͲŝŶĂƐĂ ĚĞƉĞŶĚŝĞŶƚĞ ĚĞ ĐDW͕ ;W<Ϳ͕ ůĂ ĐƵĂů ůĞ ĨŽƐĨŽƌŝůĂ ĞŶ ůĂ ƐĞƌŝŶĂ ϲϯϳ͕
;ƌŝďďƐĞƚĂů͕͘ϮϬϬϳ͖ŚĂŶŐĞƚĂů͕͘ϮϬϬϳͿ͕ƉƌŽĚƵĐŝĞŶĚŽƵŶĂĚŝƐŵŝŶƵĐŝſŶƐŝŐŶŝĨŝĐĂƚŝǀĂĚĞ
ůĂĂĐƚŝǀŝĚĂĚ'dWĂƐĂĚĞƌƉϭ͕;ŚĂŶŐĞƚĂů͕͘ϮϬϬϳͿ͕ĐŽŶůĂĐŽŶƐĞĐƵĞŶƚĞŝŶŚŝďŝĐŝſŶĚĞůĂ
ĨŝƐŝſŶ ŵŝƚŽĐŽŶĚƌŝĂů͕ ;ƌŝďďƐ Ğƚ Ăů͕͘ ϮϬϬϳ͖ ŚĂŶŐ Ğƚ Ăů͕͘ ϮϬϬϳͿ͘ ů &ĂĐƚŽƌ WƌŽŵŽƚŽƌ ĚĞ
DŝƚŽƐŝƐ;DW&Ϳ͕ĞƐƚĂŵďŝĠŶĐĂƉĂǌĚĞĨŽƐĨŽƌŝůĂƌĂƌƉϭ͕ĂƵŶƋƵĞĞƐƚĂǀĞǌĞŶůĂƐĞƌŝŶĂϱϴϱ͘
ϭϬ
ŶĞƐƚĞĐĂƐŽƐĞŚĂĚĞƐĐƌŝƚŽƋƵĞůĂĐŝƚĂĚĂĨŽƐĨŽƌŝůĂĐŝſŶĐŽŶĚƵĐĞĂůĂĞƐƚŝŵƵůĂĐŝſŶĚĞůĂ
ĨŝƐŝſŶ͕ ůŽ ĐƵĂů ƐĞ ŚĂ ƌĞůĂĐŝŽŶĂĚŽ ĐŽŶ ůŽƐ ƉƌŽĐĞƐŽƐ ĚĞ ŵƵĞƌƚĞ ĐĞůƵůĂƌ ĂƉŽƉƚſƚŝĐĂ͕
;dĂŐƵĐŚŝĞƚĂů͕͘ϮϬϬϳͿ͘
KƚƌĂƐƉƌŽƚĞşŶĂƐƋƵĞƚŝĞŶĞŶĂƌƉϭĐŽŵŽƐƵƐƚƌĂƚŽĚĞĨŽƐĨŽƌŝůĂĐŝſŶƐŽŶůĂŝŶĂƐĂ
ĞƉĞŶĚŝĞŶƚĞĚĞŝĐůŝŶĂϱ͕;ĚŬϱͿ͕ĂƵŶƋƵĞĂƋƵşŶŽƐĞĐŽŶŽĐĞĞǆĂĐƚĂŵĞŶƚĞĐſŵŽƐĞĚĂ
ĞůƉƌŽĐĞƐŽ͖ůĂŝŶĂƐĂĞƉĞŶĚŝĞŶƚĞĚĞŝĐůŝŶĂϭĞŶĂƐŽĐŝĂĐŝſŶĐŽŶůĂŝĐůŝŶĂ͕ƋƵĞĂĐƚƷĂ
ƐŽďƌĞůĂ^ĞƌŝŶĂϲϭϲǇƉƌŽĚƵĐĞƵŶĂƵŵĞŶƚŽĚĞůĂĨŝƐŝſŶŵŝƚŽĐŽŶĚƌŝĂůĚƵƌĂŶƚĞůĂŵŝƚŽƐŝƐ
ĐĞůƵůĂƌ͕;dĂŐƵĐŚŝĞƚĂů͕͘ϮϬϬϳͿ͖ǇůĂĐĂůĐŝŶĞƵƌŝŶĂ͕ƋƵĞĂĐƚƷĂĚĞĨŽƐĨŽƌŝůĂŶĚŽĂƌƉϭĞŶĞů
ŵŝƐŵŽ ƐŝƚŝŽ ƋƵĞ ĚŬϭͬŝĐůŝŶĂ ͕ ĐŽŵŽ ĐŽŶƐĞĐƵĞŶĐŝĂ ĚĞ ůŽƐ ĂƵŵĞŶƚŽƐ ĞŶ ůĂ
ĐŽŶĐĞŶƚƌĂĐŝſŶĚĞĐĂůĐŝŽŝŶƚƌĂĐĞůƵůĂƌ͕ĚĄŶĚŽƐĞĞŶƚŽŶĐĞƐƵŶĂƵŵĞŶƚŽĞŶůĂƚĂƐĂĚĞĨŝƐŝſŶ
ŵŝƚŽĐŽŶĚƌŝĂů͕;ĞƌĞŐŚĞƚƚŝĞƚĂů͕͘ϮϬϬϴͿ͘
hďŝƋƵŝŶĂĐŝŽŶĞƐ͗ƐĞƉƌŽĚƵĐĞŶĂƚƌĂǀĠƐĚĞƵŶĂƉƌŽƚĞşŶĂĂƐŽĐŝĂĚĂĂůĂŵĞŵďƌĂŶĂ
ĞǆƚĞƌŶĂ ŵŝƚŽĐŽŶĚƌŝĂů͕ ůůĂŵĂĚĂ DZ, s͕ ƋƵĞ ĞƐ ůĂ ƋƵĞ ĂĐƚƷĂ ƵďŝƋƵŝŶĂŶĚŽ Ă ƌƉϭ͕ Ɛŝ
ďŝĞŶ͕ĂƷŶƐĞĚĞƐĐŽŶŽĐĞŶůĂƐĐŽŶƐĞĐƵĞŶĐŝĂƐĞǆĂĐƚĂƐĚĞĞƐƚĞƉƌŽĐĞƐŽ͕;<ĂƌďŽǁƐŬŝĞƚĂů͕͘
ϮϬϬϳ͖zŽŶĂƐŚŝƌŽĞƚĂů͕͘ϮϬϬϲͿ͘>ĂƐĐĠůƵůĂƐĐĂƌĞŶƚĞƐĚĞDZ,sŵƵĞƐƚƌĂŶŵŝƚŽĐŽŶĚƌŝĂƐ
ŵƵǇĨŝůĂŵĞŶƚŽƐĂƐ͕ĐŽŶĚŝǀĞƌƐŽƐŐƌĂĚŽƐĚĞĞƐƉĞƐŽƌ͕;<ĂƌďŽǁƐŬŝĞƚĂů͕͘ϮϬϬϳͿ͘
^ƵŵŽůŝǌĂĐŝŽŶĞƐ͗ ĞŶ ĞƐƚĞ ĐĂƐŽ ŶŽƐ ĞŶĐŽŶƚƌĂŵŽƐ ĐŽŶ ƋƵĞ ůĂ ƉĞƋƵĞŹĂ ƉƌŽƚĞşŶĂ
^hDKϭ ŝŶƚĞƌĂĐĐŝŽŶĂ ĐŽŶ ƌƉϭ ĞŶ ůĂ ǌŽŶĂ ĐĞŶƚƌĂů ĚĞů ŽƌŐĄŶƵůŽ͘ dƌĂƐ ůĂ ĨŝƐŝſŶ͕ Ğů
ĐŽŵƉůĞũŽĂƉĂƌĞĐĞĞŶůĂƉĂƌƚĞƐƵƉĞƌŝŽƌĚĞƵŶĂĚĞůĂƐŵŝƚŽĐŽŶĚƌŝĂƐŚŝũĂƐ͕;,ĂƌĚĞƌĞƚĂů͕͘
ϮϬϬϰͿ͘ ƵŶƋƵĞ ƐĞ ĚĞƐĐŽŶŽĐĞ Ğů ƐŝŐŶŝĨŝĐĂĚŽ ĞǆĂĐƚŽ ĚĞ ĞƐƚĞ ŚĞĐŚŽ͕ Ɛş ƐĂďĞŵŽƐ ƋƵĞ ůĂ
ƐŽďƌĞĞǆƉƌĞƐŝſŶĚĞ^hDKϭĐŽŶĚƵĐĞĂůĂĨƌĂŐŵĞŶƚĂĐŝſŶŵŝƚŽĐŽŶĚƌŝĂůǇĂůĂĂƉŽƉƚŽƐŝƐ͕
ƚĂů ǀĞǌ ƉŽƌƋƵĞ ^hDKϭ ƉƌŽƚĞŐĞ Ă ƌƉϭ ĚĞ ůĂ ĚĞŐƌĂĚĂĐŝſŶ͕ ĞƐƚĂďŝůŝǌĄŶĚŽůĂ Ǉ
ĂƵŵĞŶƚĂŶĚŽƐƵƵŶŝſŶĂůĂŵŝƚŽĐŽŶĚƌŝĂ͕;,ĂƌĚĞƌĞƚĂů͕͘ϮϬϬϰ͖tĂƐŝĂŬĞƚĂů͕͘ϮϬϬϳͿ͘
dĂŵďŝĠŶ^ĞŶWϱ͕ŽƚƌĂƉƌŽƚĞĂƐĂ͕ĞƐƚĄŝŵƉůŝĐĂĚĂĞŶůĂƐƵŵŽůŝǌĂĐŝſŶĚĞƌƉϭ͘Ɛş͕
ĞƐ ĐŽŶŽĐŝĚŽ Ğů ŚĞĐŚŽ ĚĞ ƋƵĞ͕ ƚĂŶƚŽ ^hDKϭ ĐŽŵŽ ^ĞŶWϱ͕ ŵŝŐƌĂŶ Ă ůĂ ŵŝƚŽĐŽŶĚƌŝĂ
ĚƵƌĂŶƚĞůĂŵŝƚŽƐŝƐĐĞůƵůĂƌ͕ůŽĐƵĂůƉƌŽĚƵĐĞ͕ĂƐƵǀĞǌ͕ůĂĞƐƚŝŵƵůĂĐŝſŶĚĞůĂƚƌĂƐůŽĐĂĐŝſŶ
ĚĞĂǆ͘WŽƌƐƵƉĂƌƚĞ͕ĞƐƚĂƷůƚŝŵĂƉƌŽƚĞşŶĂƉŽĚƌşĂĨŽƌŵĂƌĐŽŵƉůĞũŽƐĞƐƚĂďůĞƐĐŽŶƌƉϭ
ĞŶůĂŵĞŵďƌĂŶĂĞǆƚĞƌŶĂ͕ŝŶĚĞƉĞŶĚŝĞŶƚĞŵĞŶƚĞĚĞ&ŝƐ͕;tĂƐŝĂŬĞƚĂů͕͘ϮϬϬϳͿ͘
ϭϭ
WŽƌƷůƚŝŵŽ͕ŽƚƌĂƉƌŽƚĞşŶĂƋƵĞŝŶƚĞƌǀŝĞŶĞĞŶůĂƐƵŵŽůŝǌĂĐŝſŶĚĞƌƉϭĞƐDh>E͕
ůĂĐƵĂůƐĞĞŶĐƵĞŶƚƌĂĞŶůĂŵĞŵďƌĂŶĂĞǆƚĞƌŶĂŵŝƚŽĐŽŶĚƌŝĂů͘^ĞƚƌĂƚĂĚĞƵŶĂ^hDKϯ
ůŝŐĂƐĂ͕ƋƵĞŝŶƚĞƌĂĐĐŝŽŶĂĐŽŶhďĐϵ͕ƚĂŵďŝĠŶŝŵƉůŝĐĂĚĂĞŶĞůƉƌŽĐĞƐŽ͕ƉĂƌĂƐƵŵŽůŝǌĂƌĂ
ƌƉϭǇĂƵŵĞŶƚĂƌĂƐşůĂĞƐƚĂďŝůŝĚĂĚĚĞĞƐƚĂƷůƚŝŵĂ͕;ƌĂƐĐŚŝĞƚĂů͕͘ϮϬϬϵ͖,ĂƌĚĞƌĞƚĂů͕͘
ϮϬϬϰ͖>ŝĞƚĂů͕͘ϮϬϬϴ͖EĞƵƐƉŝĞůĞƚĂů͕͘ϮϬϬϴͿ͘>ĂƐƵŵŽůŝǌĂĐŝſŶ͕ũƵŶƚŽĐŽŶůĂĨŽƐĨŽƌŝůĂĐŝſŶ͕
ƉƌŽĚƵĐĞůĂŵŝŐƌĂĐŝſŶĚĞƌƉϭĂůĂŵŝƚŽĐŽŶĚƌŝĂ͘
^ʹŶŝƚƌŽƐŝůĂĐŝŽŶĞƐ͗ ŚĂǇ ĞƐƚƵĚŝŽƐ ƋƵĞ ĂĨŝƌŵĂŶ ƋƵĞ ůĂ ^ͲŶŝƚƌŽƐŝůĂĐŝſŶ ĚĞ ƌƉϭ
ƉƌŽĚƵĐŝĚĂ ƉŽƌ Ğů MǆŝĚŽ EşƚƌŝĐŽ ĞƐƚŝŵƵůĂ ůĂ ĨŝƐŝſŶ ŵŝƚŽĐŽŶĚƌŝĂů͕ ;WŝĂŶƚĂĚŽƐŝ͕ ϮϬϭϭͿ͘
ĚĞŵĄƐ͕ƐĂďĞŵŽƐƋƵĞůĂŵƵƚĂĐŝſŶĚĞůƌĞƐŝĚƵŽϲϰϰĚĞĐŝƐƚĞşŶĂĚĞƌƉϭ͕ƐŝƚƵĂĚŽĞŶƵŶ
ůƵŐĂƌ ĐƌşƚŝĐŽ ĚĞ ůĂ ĐŝƚĂĚĂ ƉƌŽƚĞşŶĂ͕ ƉƌĞǀŝĞŶĞ ƐƵ ŶŝƚƌŽƐŝůĂĐŝſŶ Ǉ͕ ĐŽŶ ĞƐƚŽ͕ ƐĞ ĞǀŝƚĂŶ ůŽƐ
ĚĂŹŽƐŶĞƵƌŽƚſǆŝĐŽƐ͘
ĚşĂĚĞŚŽǇ͕ůĂŵŽĚƵůĂĐŝſŶĨĂƌŵĂĐŽůſŐŝĐĂĚĞƌƉϭĞŶĚŝǀĞƌƐŽƐŵŽĚĞůŽƐĞƐƵŶĂ
ƌĞĂůŝĚĂĚ͘ƐƚŽĞƐĚĞďŝĚŽĂƋƵĞŚĂĐĞƉŽĐŽƐĂŹŽƐ͕ĐŽŶĐƌĞƚĂŵĞŶƚĞĞŶϮ͘ϬϬϴ͕ĞůŐƌƵƉŽĚĞ
ĂƐƐŝĚǇͲ^ƚŽŶĞ ƐŝŶƚĞƚŝǌſ ƵŶĂ ŵŽůĠĐƵůĂ ĚĞ ƉĞƋƵĞŹŽ ƚĂŵĂŹŽ ƋƵĞ͕ ƐŝŶ ĞŵďĂƌŐŽ͕ ŚĂ
ƌĞǀŽůƵĐŝŽŶĂĚŽ Ğů ĞƐƚƵĚŝŽ ĚĞ ůĂ ĨŝƐŝſŶ ŵŝƚŽĐŽŶĚƌŝĂů͘ ^Ğ ƚƌĂƚĂ ĚĞ DĚŝǀŝͲϭ͕ Ğů ƉƌŝŵĞƌ
ŝŶŚŝďŝĚŽƌƐĞůĞĐƚŝǀŽĚĞĞƐƚĞƉƌŽĐĞƐŽ͕;ĞůŶŽŵďƌĞƐĞŽďƚŝĞŶĞĚĞůĂĐƌſŶŝŵŽĞŶŝŶŐůĠƐĚĞ
/ŶŚŝďŝĚŽƌ ĚĞ ůĂ ŝǀŝƐŝſŶ DŝƚŽĐŽŶĚƌŝĂů ϭ͕ ;ĂƐƐŝĚǇͲ^ƚŽŶĞ Ğƚ Ăů͕͘ ϮϬϬϴ͖ dĂŶĂŬĂ Ğƚ Ăů͕͘
ϮϬϬϴͿͿ͘ >Ă ƉĂƌƚŝĐƵůĂƌŝĚĂĚ ƋƵĞ ƉƌĞƐĞŶƚĂ ĞƐƚĞ ĨĄƌŵĂĐŽ ƌĞƐƉĞĐƚŽ Ă ƐƵƐ ƉƌĞĚĞĐĞƐŽƌĞƐ͕
ĐŽŵŽĞƐĞůĐĂƐŽĚĞǇŶĂƐŽƌĞ͕ĞƐƋƵĞĂĐƚƷĂĞƐƉĞĐşĨŝĐĂŵĞŶƚĞƐŽďƌĞƌƉͲϭǇŶŽƐŽďƌĞůĂƐ
ĚŝŶĂŵŝŶĂƐĞŶŐĞŶĞƌĂů͘ƐƚĞŚĞĐŚŽĐŽďƌĂĞƐƉĞĐŝĂůƌĞůĞǀĂŶĐŝĂĐƵĂŶĚŽDĚŝǀŝͲϭĞƐƵƐĂĚŽ
ĞŶĞůĞƐƚƵĚŝŽĚĞůĂŝŶĄŵŝĐĂDŝƚŽĐŽŶĚƌŝĂů͕ǇĂƋƵĞĐĂďĞƌĞĐŽƌĚĂƌƋƵĞůŽƐŵĞĚŝĂĚŽƌĞƐĚĞ
ůĂ ĨƵƐŝſŶ ĚĞ ĞƐƚĞ ŽƌŐĄŶƵůŽ͕ ;DĨŶƐ Ǉ KWϭ͕ ƉƌŝŶĐŝƉĂůŵĞŶƚĞͿ͕ ƚĂŵďŝĠŶ ƐŽŶ ƉƌŽƚĞşŶĂƐ
ƉĞƌƚĞŶĞĐŝĞŶƚĞƐĂůĂĨĂŵŝůŝĂĚĞůĂƐĚŝŶĂŵŝŶĂƐ͘
DĚŝǀŝͲϭĞǀŝƚĂĞůĞŶƐĂŵďůĂũĞĚĞƌƉϭĞŶƐƵĨĂƐĞŝŶŝĐŝĂů͕ďůŽƋƵĞĂŶĚŽ͕ƉŽƌƚĂŶƚŽ͕
ĐŽŵƉůĞƚĂŵĞŶƚĞůĂĨŝƐŝſŶĚĞůĂŵŝƚŽĐŽŶĚƌŝĂ͕ƉĞƌŽƐŝŶĂĨĞĐƚĂƌĂůĂĂĐƚŝǀŝĚĂĚ'dWĂƐĂĚĞůĂ
ƉƌŽƚĞşŶĂ͕ǇĂƋƵĞƐƵůƵŐĂƌĚĞĂĐĐŝſŶĞƐƚĄĨƵĞƌĂĚĞĞƐĞĚŽŵŝŶŝŽ͘ĚĞŵĄƐ͕ĞŶĞůĂƌƚşĐƵůŽ
ĞŶĞůƋƵĞůŽƐĂƵƚŽƌĞƐƉƵďůŝĐĂƌŽŶůŽƐƌĞƐƵůƚĂĚŽƐƌĞůĂƚŝǀŽƐĂůĂƐşŶƚĞƐŝƐĚĞDĚŝǀŝͲϭ͕ŚĂĐşĂŶ
ƚĂŵďŝĠŶ ƌĞĨĞƌĞŶĐŝĂ Ăů ŚĞĐŚŽ ĚĞ ƋƵĞ ůĂ ŵŝŐƌĂĐŝſŶ ĚĞ ƌƉϭ Ă ůĂ ŵŝƚŽĐŽŶĚƌŝĂ ĞƌĂ
ĚĞƉĞŶĚŝĞŶƚĞ ĚĞ ůĂ ƉĞƌŵĞĂďŝůŝǌĂĐŝſŶ ĚĞ ůĂ ŵĞŵďƌĂŶĂ ĞǆƚĞƌŶĂ ŵŝƚŽĐŽŶĚƌŝĂů͕ ůŽ ĐƵĂů
ϭϮ
ƌĞůĂĐŝŽŶĂĐůĂƌĂŵĞŶƚĞůĂĨŝƐŝſŶĚĞůŽƌŐĄŶƵůŽǇůĂĂƉŽƉƚŽƐŝƐ͕;ĂƐƐŝĚǇͲ^ƚŽŶĞĞƚĂů͕͘ϮϬϬϴͿ͘
ƐƚĞ ĨĄƌŵĂĐŽ ŶŽ ƐſůŽ ĞƐƚĄ ĐŽŶƚƌŝďƵǇĞŶĚŽ Ăů ŵĞũŽƌ ĐŽŶŽĐŝŵŝĞŶƚŽ ĚĞů
ĨƵŶĐŝŽŶĂŵŝĞŶƚŽ ĚĞ ƌƉͲϭ Ǉ ĚĞů ƉƌŽĐĞƐŽ ĚĞ ůĂ ĨŝƐŝſŶ ŵŝƚŽĐŽŶĚƌŝĂů͕ ƐŝŶŽ ƋƵĞ ŐƌĂĐŝĂƐ Ă
DĚŝǀŝͲϭƐĞĂďƌĞŶŶƵĞǀĂƐǀĞŶƚĂŶĂƐƉĂƌĂ͕ƉŽƌĞũĞŵƉůŽ͕ĞůƵĐŝĚĂƌĨŝŶĂůŵĞŶƚĞĞůƉĂƉĞůƋƵĞ
ůŽƐĂĚĂƉƚĂĚŽƌĞƐĐŽŵŽ&ŝƐϭũƵĞŐĂŶĞŶůĂĨŝƐŝſŶŵŝƚŽĐŽŶĚƌŝĂůĞŝŶĐůƵƐŽĞŶůĂĂƉŽƉƚŽƐŝƐ͕Ž
ƉĂƌĂ ĂĐůĂƌĂƌ ĚĞĨŝŶŝƚŝǀĂŵĞŶƚĞ ůĂ ŶĂƚƵƌĂůĞǌĂ Ǉ Ğů ŵĞĐĂŶŝƐŵŽ ĚĞ ůĂ ƌĞůĂĐŝſŶ ĞŶƚƌĞ ůĂ
ĂƉŽƉƚŽƐŝƐǇůĂĨŝƐŝſŶŵŝƚŽĐŽŶĚƌŝĂů͘
WŽƌ ŽƚƌŽ ůĂĚŽ͕ ĐĂĚĂ ǀĞǌ ƉĂƌĞĐĞ ŚĂďĞƌ ŵĄƐ ĐŽŶƐĞŶƐŽ ĞŶƚƌĞ ůĂ ĐŽŵƵŶŝĚĂĚ
ĐŝĞŶƚşĨŝĐĂ ƐŽďƌĞ Ğů ŚĞĐŚŽ ĚĞ ƋƵĞ ůŽƐ ĚĞƐſƌĚĞŶĞƐ Ă ŶŝǀĞů ŵŝƚŽĐŽŶĚƌŝĂů͕ ĐŽŶĐƌĞƚĂŵĞŶƚĞ
ĂƋƵĞůůŽƐ ƋƵĞ ĂĨĞĐƚĂŶ Ă ůĂ ĚŝŶĄŵŝĐĂ ĚĞ ĞƐƚĞ ŽƌŐĄŶƵůŽ Ǉ ůĂ ĂƉŽƉƚŽƐŝƐ͕ ƉƵĞĚĂŶ ĞƐƚĂƌ
ŝŵƉůŝĐĂĚŽƐĞŶůĂĂƉĂƌŝĐŝſŶĚĞĚŝǀĞƌƐŽƐĞƐƚĂĚŽƐƉĂƚŽůſŐŝĐŽƐ͘'ƌĂĐŝĂƐĂĞƐƚŽ͕DĚŝǀŝͲϭŚĂ
ƐŝĚŽƚĂŵďŝĠŶƵƐĂĚŽĞŶĚŝǀĞƌƐŽƐŵŽĚĞůŽƐĐĞůƵůĂƌĞƐ͕ĂŶŝŵĂůĞƐŽĐŽŶƚĞũŝĚŽƐŚƵŵĂŶŽƐĚĞ
ůĂƐ ŵĄƐ ǀĂƌŝĂĚĂƐ ƉĂƚŽůŽŐşĂƐ͘ Ɛş͕ ĞŶĐŽŶƚƌĂŵŽƐ ĞƐƚƵĚŝŽƐ ƐŽďƌĞ ůĂ ĐŽŶƐƚƌŝĐĐŝſŶ
ĚĞĨĞĐƚƵŽƐĂĚĞůĚƵĐƚƵƐĂƌĞƚƌŝŽƐƵƐƐĞŶƐŝďůĞĂůŽǆşŐĞŶŽ͕;,ŽŶŐĞƚĂů͕͘ϮϬϭϮͿ͖ůĂŝƐƋƵĞŵŝĂͲ
ƌĞƉĞƌĨƵƐŝſŶ ĐĞƌĞďƌĂůĞƐ͕ ;ŚĂŶŐ Ğƚ Ăů͕͘ ϮϬϭϯͿ͖ ĐŝĞƌƚŽƐ ƚŝƉŽƐ ĚĞ ƉƌŽĐĞƐŽƐ ŽŶĐŽůſŐŝĐŽƐ
ŵĂůŝŐŶŽƐ͕ ;ƵŶŶŝĨĨ Ğƚ Ăů͕͘ ϮϬϭϯͿ͕ Ž ŝŶĐůƵƐŽ ƐŽďƌĞ Ğů ĚŽůŽƌ ŶĞƵƌŽƉĄƚŝĐŽ͕ ;&ĞƌƌĂƌŝ Ğƚ Ăů͕͘
ϮϬϭϭͿ͘
ĚĞŵĄƐ͕ĞƐƚĞĨĄƌŵĂĐŽƚĂŵďŝĠŶŚĂƐŝĚŽĞŵƉůĞĂĚŽƉĂƌĂĞůĞƐƚƵĚŝŽĚĞƉƌŽĐĞƐŽƐ
ĨŝƐŝŽůſŐŝĐŽƐ Ž ĚĞ ďŝŽƚĞĐŶŽůŽŐşĂ͕ ĐŽŵŽ ĞƐ Ğů ĐĂƐŽ ĚĞ ůĂ ĞǆŽĐŝƚŽƐŝƐ ĞŶ ůĂƐ ƉůĂƋƵĞƚĂƐ͕
;<ŽƐĞŽŐůƵ Ğƚ Ăů͕͘ ϮϬϭϯͿ͖ ĚĞ ůŽƐ ĞŶƐĂǇŽƐ ĚĞ ƌĞƉƌŽŐƌĂŵĂĐŝſŶ ĐĞůƵůĂƌ ŚĂĐŝĂ ůĂ
ƉůƵƌŝƉŽƚĞŶĐŝĂ͕ĚŽŶĚĞĞƐƚĂƷůƚŝŵĂĞƐŝŶŚŝďŝĚĂƉŽƌDĚŝǀŝͲϭ͕;'ŝǀǀŝŵĂŶŝĞƚĂů͕͘ϮϬϭϮͿ͕ŽĚĞ
ůĂ ĞůĞĐƚƌŽĨŝƐŝŽůŽŐşĂ ĚĞ ůŽƐ ĐĂƌĚŝŽŵŝŽĐŝƚŽƐ͕ ;^Ž Ğƚ Ăů͕͘ ϮϬϭϮͿ͘ DƵĐŚŽƐ ĚĞ ůŽƐ ĞĨĞĐƚŽƐ
ŽďƐĞƌǀĂĚŽƐĞŶůŽƐĚŝƐƚŝŶƚŽƐĂƌƚşĐƵůŽƐƐŽŶĞǆƉůŝĐĂďůĞƐĂƚƌĂǀĠƐĚĞůĂĂĐĐŝſŶŵŽĚƵůĂƚŽƌŝĂ
ƐŽďƌĞůĂĂƉŽƉƚŽƐŝƐƋƵĞ͕ĐŽŵŽĂƉƵŶƚĄďĂŵŽƐĐŽŶĂŶƚĞƌŝŽƌŝĚĂĚ͕ƚŝĞŶĞDĚŝǀŝͲϭ͕ĚĞďŝĚŽĂ
ƋƵĞĞƐĐĂƉĂǌĚĞĚĞƐĂĐŽƉůĂƌůĂĨŝƐŝſŶŵŝƚŽĐŽŶĚƌŝĂůĚĞůĐŝƚĂĚŽƚŝƉŽĚĞŵƵĞƌƚĞĐĞůƵůĂƌ͘
&ŝƐϭ
&ŝƐϭ ĞƐ ůĂ ƷŶŝĐĂ ƉƌŽƚĞşŶĂ ĚĞů ƐŝƐƚĞŵĂ ĨƵƐŝſŶͬĨŝƐŝſŶ ƋƵĞ ŶŽ ƉŽƐĞĞ ĂĐƚŝǀŝĚĂĚ
'dWĂƐĂ͘ ^Ğ ůŽĐĂůŝǌĂ ĞŶ ůĂ ŵĞŵďƌĂŶĂ ŵŝƚŽĐŽŶĚƌŝĂů ĞǆƚĞƌŶĂ͕ Ă ůĂ ƋƵĞ ƐĞ ĞŶĐƵĞŶƚƌĂ
ϭϯ
ĂŶĐůĂĚĂ ƉŽƌ ƐƵƐ ĚŽŵŝŶŝŽƐ ƚƌĂŶƐŵĞŵďƌĂŶĂ͘ WƌĞƐĞŶƚĂ ƵŶ ƉĞƋƵĞŹŽ ƚĂŵĂŹŽ Ǉ ƵŶĂ
ĚŝƐƚƌŝďƵĐŝſŶ ƵďŝĐƵĂ͕ ĨƵŶĐŝŽŶĂŶĚŽ ĐŽŵŽ ƌĞĐĞƉƚŽƌ ĚĞ ŵĞŵďƌĂŶĂ͕ ƉƌŝŶĐŝƉĂůŵĞŶƚĞ ƉĂƌĂ
ƌƉϭ͘
>ĂƵŶŝſŶĚĞƌƉϭĂ&ŝƐϭĞƐĐŽŶƚƌŽǀĞƌƚŝĚĂǇĞŶůĂďŝďůŝŽŐƌĂĨşĂƉŽĚĞŵŽƐĞŶĐŽŶƚƌĂƌ
ƚƌĂďĂũŽƐ ĐŽŶ ĚĂƚŽƐ ĞŶ ĂƉĂƌŝĞŶĐŝĂ ĐŽŶƚƌĂƉƵĞƐƚŽƐ͘ Ɛş͕ ƐĂďĞŵŽƐ ƋƵĞ ůĂ ƐŽďƌĞĞǆƉƌĞƐŝſŶ
ĚĞ&ŝƐϭƉƌŽǀŽĐĂĞůŝŶŝĐŝŽĚĞůĂĨƌĂŐŵĞŶƚĂĐŝſŶŵŝƚŽĐŽŶĚƌŝĂů͕ŵŝĞŶƚƌĂƐƋƵĞůĂĚŝƐŵŝŶƵĐŝſŶ
ĚĞƐƵĞǆƉƌĞƐŝſŶĐŽŶĚƵĐĞĂůďůŽƋƵĞŽĚĞůĂĨŝƐŝſŶ͕ĂƉĞƐĂƌĚĞĐĂƌĞĐĞƌĚĞĞĨĞĐƚŽƐŽďƌĞůĂ
ĨƵƐŝſŶ͕ ;<ĂƌƌĞŶ Ğƚ Ăů͕͘ ϮϬϬϱ͖ DŽǌĚǇ Ğƚ Ăů͕͘ ϮϬϬϬ͖ ^ƚŽũĂŶŽǀƐŬŝ Ğƚ Ăů͕͘ ϮϬϬϰ͖ zŽŽŶ Ğƚ Ăů͕͘
ϮϬϬϯͿ͘ KƚƌŽƐ ĂƵƚŽƌĞƐ͕ ƐŝŶ ĞŵďĂƌŐŽ͕ ƚƌĂƐ ůĂ ĚŝƐŵŝŶƵĐŝſŶ ĚĞ ůĂ ĞǆƉƌĞƐŝſŶ ĚĞ &ŝƐϭ͕ ŶŽ
ŽďƐĞƌǀĂƌŽŶŶŝŶŐƷŶĞĨĞĐƚŽƐŽďƌĞůĂŵŽƌĨŽůŽŐşĂŵŝƚŽĐŽŶĚƌŝĂů͕ůŽĐƵĂůƉĂƌĞĐĞƐƵŐĞƌŝƌƋƵĞ
ůŽƐĚĂƚŽƐŽďƚĞŶŝĚŽƐƉƌĞǀŝĂŵĞŶƚĞĞƌĂŶĚĞďŝĚŽƐĂĞĨĞĐƚŽƐŶŽĞƐƉĞĐşĨŝĐŽƐƉƌŽĚƵĐŝĚŽƐƉŽƌ
Ğů ZEŝ͕ ;ZE ĚĞ ŝŶƚĞƌĨĞƌĞŶĐŝĂͿ͕ ƵƚŝůŝǌĂĚŽ͕ ;KƚĞƌĂ Ğƚ Ăů͕͘ ϮϬϭϬͿ͘ WŽƌ ŽƚƌŽ ůĂĚŽ͕ ĐŽŵŽ
ŝŶĚŝĐĄďĂŵŽƐ ĐŽŶ ĂŶƚĞƌŝŽƌŝĚĂĚ͕ ƐĂďĞŵŽƐ ƋƵĞ ƌƉϭ ƉƵĞĚĞ ƵŶŝƌƐĞ Ă ůĂ ŵŝƚŽĐŽŶĚƌŝĂ Ă
ƚƌĂǀĠƐĚĞŽƚƌŽƐĞůĞŵĞŶƚŽƐƉƌŽƚĞŝĐŽƐĚĞƐĐŽŶŽĐŝĚŽƐ͘ƐƚĞŚĞĐŚŽŚĂƐŝĚŽĐŽŶĨŝƌŵĂĚŽƉŽƌ
ĚŽƐ ŐƌƵƉŽƐ͕ ůŽƐ ĐƵĂůĞƐ ŚĂŶ ĚĞŵŽƐƚƌĂĚŽ ƋƵĞ͕ ĂŶƚĞ Ğů ƐŝůĞŶĐŝĂŵŝĞŶƚŽ ĚĞ &ŝƐϭ͕ ƌƉϭ
ĐŽŶƚŝŶƷĂŵŝŐƌĂŶĚŽĂůĂŵŝƚŽĐŽŶĚƌŝĂ͕;^ƚŽũĂŶŽǀƐŬŝĞƚĂů͕͘ϮϬϬϰͿ͕ǇƵŶŝĠŶĚŽƐĞĂĞůůĂ͕;>ĞĞ
ĞƚĂů͕͘ϮϬϬϰ͖^ƚŽũĂŶŽǀƐŬŝĞƚĂů͕͘ϮϬϬϰͿ͘
ŽŵŽŽĐƵƌƌşĂĞŶĞůĐĂƐŽĚĞƌƉϭ͕ƚĂŵďŝĠŶĠƐƚĂƉƌŽƚĞşŶĂĞƐƚĄƌĞůĂĐŝŽŶĂĚĂĐŽŶůĂ
ĂƉŽƉƚŽƐŝƐ͕ ;>ĞĞ Ğƚ Ăů͕͘ ϮϬϬϰͿ͕ ĐŽŶĨŝƌŵĄŶĚŽƐĞ ĂƐş͕ ĚĞ ŶƵĞǀŽ͕ ůĂ ĞƐƚƌĞĐŚĂ ǀŝŶĐƵůĂĐŝſŶ
ĞŶƚƌĞůĂĨŝƐŝſŶŵŝƚŽĐŽŶĚƌŝĂůǇĞƐƚĞƚŝƉŽĚĞŵƵĞƌƚĞĐĞůƵůĂƌ͘zŶŽƐſůŽĐŽŶůĂĂƉŽƉƚŽƐŝƐ͕
ƐŝŶŽƋƵĞƚĂŵďŝĠŶŚĂƋƵĞĚĂĚŽĐŽŶƐƚĂƚĂĚŽƋƵĞ&ŝƐϭũƵĞŐĂƵŶƉĂƉĞůĞŶůĂŵŝƚŽĨĂŐŝĂǇĞŶ
ůĂƌĞŐƵůĂĐŝſŶĚĞůĂƐĞŶĞƐĐĞŶĐŝĂ͘ĞŚĞĐŚŽ͕>ĞĞǇĐŽůƐĚĞŵŽƐƚƌĂƌŽŶƋƵĞůĂƐŵŝƚŽĐŽŶĚƌŝĂƐ
ĚĞůĂƐĐĠůƵůĂƐƐĞŶĞƐĐĞŶƚĞƐĚĞƐĂƌƌŽůůĂŶƵŶĂůĂƌŐĂŵŝĞŶƚŽĂŶŽƌŵĂů͕ĞůĐƵĂůƐĞĐŽƌƌĞůĂĐŝŽŶſ
ĐŽŶůĂĚŝƐŵŝŶƵĐŝſŶĚĞůŽƐŶŝǀĞůĞƐĚĞ&ŝƐϭ͕ĂƐşĐŽŵŽĐŽŶĞůĂƵŵĞŶƚŽĚĞůŽƐĚĞůĂƐDĨŶƐ͕
;>ĞĞĞƚĂů͕͘ϮϬϬϳͿ͘
&ŝƐϭ ƉŽĚƌşĂ ƚĂŵďŝĠŶ ĞƐƚĂƌ ŝŵƉůŝĐĂĚĂ ĂĚĞŵĄƐ ĞŶ ŽƚƌĂƐ ĨƵŶĐŝŽŶĞƐ ƌĞůĂĐŝŽŶĂĚĂƐ
ĐŽŶůĂŵŝƚŽĐŽŶĚƌŝĂ͕ĂƵŶƋƵĞĞƐƚĂƐŶŽŚĂŶƋƵĞĚĂĚŽĂƷŶƚŽƚĂůŵĞŶƚĞĚŝůƵĐŝĚĂĚĂƐ͘Ɛş͕ŚĂǇ
ĐŝĞƌƚŽƐ ĞƐƚƵĚŝŽƐ ƋƵĞ ĂƚƌŝďƵǇĞŶ Ă ĞƐƚĂ ƉĞƋƵĞŹĂ ƉƌŽƚĞşŶĂ ƵŶ ƉŽƐŝďůĞ ƉĂƉĞů ĞŶ ůĂ
ĂƉĂƌŝĐŝſŶ ĚĞ ůĂ ŶĨĞƌŵĞĚĂĚ ĚĞ WĂƌŬŝŶƐŽŶ͕ ĐŽŶĐƌĞƚĂŵĞŶƚĞ ĞŶ ůŽƐ ĐĂƐŽƐ ĨĂŵŝůŝĂƌĞƐ ĚĞ
ϭϰ
ĞƐƚĂƉĂƚŽůŽŐşĂ͕ĚŽŶĚĞƐĞƌĞůĂĐŝŽŶſůĂƐŵƵƚĂĐŝŽŶĞƐĞŶůĂƐƉƌŽƚĞşŶĂƐŝŶĂƐĂDŝƚŽĐŽŶĚƌŝĂů
WdE/ŶĚƵĐƚŽƌĂĚĞůĂŝŶĂƐĂϭ͕;WŝŶŬϭͿǇhďŝƋƵŝƚŝŶͲůŝŐĂƐĂϯWĂƌŬŝŶ͘&ŝƐϭƉŽĚƌşĂĂĐƚƵĂƌ
ĚĞŝŶƚĞƌŵĞĚŝĂƌŝŽĞŶƚƌĞWŝŶŬϭǇƌƉϭ͕ƉĂƌĂĐŽŶƚƌŽůĂƌůĂĨŝƐŝſŶŵŝƚŽĐŽŶĚƌŝĂů͕;zĂŶŐĞƚĂů͕͘
ϮϬϬϴͿ͘WŽƌŽƚƌŽůĂĚŽ͕ƉĂƌĞĐĞƋƵĞůĂƐŽďƌĞĞǆƉƌĞƐŝſŶĚĞWĂƌŬŝŶĂƵŵĞŶƚĂůĂĚĞŐƌĂĚĂĐŝſŶ
ĚĞ&ŝƐϭ͕;ƵŝĞƚĂů͕͘ϮϬϭϬͿ͘
&ŝŐƵƌĂϭ͘>ĂĨŝƐŝſŶŵŝƚŽĐŽŶĚƌŝĂů͘ƵĂŶĚŽĂƉĂƌĞĐĞŶĞƐƚşŵƵůŽƐĂĐƚŝǀĂĚŽƌĞƐĚĞĞƐƚĞƉƌŽĐĞƐŽ͕ƌƉϭ
ŵŝŐƌĂ ĚĞƐĚĞ Ğů ĐŝƚŽƉůĂƐŵĂ ŚĂƐƚĂ ůĂ ŵĞŵďƌĂŶ ĞǆƚĞƌŶĂ ŵŝƚŽĐŽŶĚƌŝĂů͕ ĚŽŶĚĞ ƐĞ ĂŶĐůĂ Ă &ŝƐϭ͕ Ž Ă ŽƚƌŽƐ
ĞůĞŵĞŶƚŽƐƉƌŽƚĞŝĐŽƐĚĞƐĐŽŶŽĐŝĚŽƐ͘ŽŶĐƌĞƚĂŵĞŶƚĞ͕ƌƉϭƐĞƵŶĞĞŶůĂƐǌŽŶĂƐĂƚƌĂǀĠƐĚĞůĂƐĐƵĂůĞƐƐĞǀĂ
Ă ƉƌŽĚƵĐŝƌ ůĂ ĞƐĐŝƐŝſŶ ĚĞů ŽƌŐĄŶƵůŽ͘ ĐŽŶƚŝŶƵĂĐŝſŶ͕ ĚĞ ƵŶ ŵŽĚŽ ĚĞƉĞŶĚŝĞŶƚĞ ĚĞ 'dW͕ ůĂƐ ĚŝƐƚŝŶƚĂƐ
ŵŽůĠĐƵůĂƐ ĚĞ ĚŝŶĂŵŝŶĂ ĐŽƐƚƌŝŹĞŶ ůĂƐ ŵĞŵďƌĂŶĂƐ ĚĞů ŽƌŐĄŶƵůŽ͕ ĐŽŶ Ğů ƌĞƐƵůƚĂĚŽ ĨŝŶĂů ĚĞ ƋƵĞ ůĂ
ŵŝƚŽĐŽŶĚƌŝĂŵĂĚƌĞƐĞĚŝǀŝĚĞĞŶĚŽƐŚŝũĂƐ͕ŝŶĚĞƉĞŶĚŝĞŶƚĞƐ͘
ϭϱ
I.1.3. Movimiento de las mitocondrias
>ĂƐ ŵŝƚŽĐŽŶĚƌŝĂƐ ƐĞ ŵƵĞǀĞŶ Ă ƚƌĂǀĠƐ ĚĞ ůŽƐ ŵŝĐƌŽƚƷďƵůŽƐ ĐƵĂŶĚŽ ŶĞĐĞƐŝƚĂŶ
ĚĞƐƉůĂǌĂƌƐĞĂƵŶĂĚŝƐƚĂŶĐŝĂůĂƌŐĂŽĂƵŶĂǀĞůŽĐŝĚĂĚĂůƚĂ͘^ŝŶĞŵďĂƌŐŽ͕ĞŶĞůƌĞƐƚŽĚĞůŽƐ
ĐĂƐŽƐ͕ƉƵĞĚĞŶĚĞƐƉůĂǌĂƌƐĞĂƚƌĂǀĠƐĚĞůŽƐĨŝůĂŵĞŶƚŽƐĚĞĂĐƚŝŶĂ͕ƚĂŵďŝĠŶĚĞƵŶŵŽĚŽ
ďŝĚŝƌĞĐĐŝŽŶĂů͕ĐŽŶůĂĂǇƵĚĂĚĞůŽƐŵŽƚŽƌĞƐĚĞŵŝŽƐŝŶĂ͕;,ŽůůĞŶďĞĐŬĞƚĂů͕͘ϮϬϬϱͿ͘WĂƌĂ
ƚƌĂƐůŽĐĂƌƐĞĂůŽƐŵŝĐƌŽƚƷďƵůŽƐ͕ůĂƐŵŝƚŽĐŽŶĚƌŝĂƐŶĞĐĞƐŝƚĂŶůĂŝŶƚĞƌǀĞŶĐŝſŶĚĞŵŝŽƐŝŶĂƐ
ĚĞůĂĨĂŵŝůŝĂs͕;,ŽůůĞŶďĞĐŬĞƚĂů͕͘ϮϬϬϱͿ͘
ZĞƐƉĞĐƚŽĂůƚƌĂŶƐƉŽƌƚĞĂĐƚŝǀŽĂƚƌĂǀĠƐĚĞůŽƐŵŝĐƌŽƚƷďƵůŽƐ͕ĐĂďĞƌĞĐŽƌĚĂƌƋƵĞ
ĞƐƚĞƉƌŽĐĞƐŽĞƐĞƐƉĞĐŝĂůŵĞŶƚĞŝŵƉŽƌƚĂŶƚĞĞŶĞůĐĂƐŽĐŽŶĐƌĞƚŽĚĞůĂƐŶĞƵƌŽŶĂƐ͕ĚŽŶĚĞ
ůĂůŽĐĂůŝǌĂĐŝſŶĚĞĞƐƚŽƐŽƌŐĄŶƵůŽƐĞŶƉŽƐŝĐŝŽŶĞƐĞƐƚƌĂƚĠŐŝĐĂƐĞƐǀŝƚĂů͕;:ĂŚĂŶŝͲƐůĞƚĂů͕͘
ϮϬϬϵͿ͕ ĂƵŶƋƵĞ ƚĂŵďŝĠŶ ƐĞ ŚĂ ĚĞŵŽƐƚƌĂĚŽ ƋƵĞ ĞƐ ŝŵƉƌĞƐĐŝŶĚŝďůĞ ĞŶ ůĂƐ ĐĠůƵůĂƐ
ƉĞƋƵĞŹĂƐ͕;ĂŵƉĞůůŽĞƚĂů͕͘ϮϬϬϲͿ͘Ɛş͕ůŽƐĚĞĨĞĐƚŽƐĞŶĞůƚƌĂŶƐƉŽƌƚĞĚĞĞƐƚŽƐŽƌŐĄŶƵůŽƐ
ĞƐƚĄŶ ĂƐŽĐŝĂĚŽƐ ĐŽŶ ůĂ ĞƚŝŽƉĂƚŽůŽŐşĂ ĚĞ ĐŝĞƌƚĂƐ ĞŶĨĞƌŵĞĚĂĚĞƐ ŶĞƵƌŽĚĞŐĞŶĞƌĂƚŝǀĂƐ͕
ĐŽŵŽĞƐĞůĐĂƐŽĚĞůĂĚĞWĂƌŬŝŶƐŽŶ͕ůĂĚĞůǌŚĞŝŵĞƌŽůĂĚĞ,ƵŶƚŝŶŐƚŽŶ͕;ĞĂů͕ϮϬϬϳ͖
ZĞǇŶŽůĚƐĞƚĂů͕͘ϮϬϬϰ͖dƌŝŵŵĞƌĞƚĂů͕͘ϮϬϬϱͿ
^Ğ ŚĂ ŽďƐĞƌǀĂĚŽ ƋƵĞ Ğů ŵŽǀŝŵŝĞŶƚŽ ĚĞ ůĂƐ ŵŝƚŽĐŽŶĚƌŝĂƐ ƉƵĞĚĞ ƐĞƌ ƚĂŶƚŽ ĞŶ
ƐĞŶƚŝĚŽ ĂŶƚĞƌſŐƌĂĚŽ ĐŽŵŽ ĞŶ ƌĞƚƌſŐƌĂĚŽ͕ Ɛŝ ďŝĞŶ ůŽƐ ŵĞĐĂŶŝƐŵŽƐ ƋƵĞ ƉĂƌƚŝĐŝƉĂŶ ĞŶ
ĂŵďŽƐƉƌŽĐĞƐŽƐƐŽŶĚŝĨĞƌĞŶƚĞƐ͘Ɛş͕ĞŶĞůƉƌŝŵĞƌĐĂƐŽ͕ĞůĚĞƐƉůĂǌĂŵŝĞŶƚŽƐĞĚĂƌĄŚĂĐŝĂ
ĞůĨŝŶĂůĚĞůŽƐŵŝĐƌŽƚƷďƵůŽƐ͕ĞƐĚĞĐŝƌ͕ĞƐƵŶƚƌĂŶƐƉŽƌƚĞƋƵĞĐŽŵŝĞŶǌĂĞŶĞůƐŽŵĂĐĞůƵůĂƌ
Ǉ ƐĞ ƚƌĂŶƐŵŝƚĞ ŚĂĐŝĂ ůĂƐ ĞƐƚƌƵĐƚƵƌĂƐ ƉĞƌŝĨĠƌŝĐĂƐ͕ ŵŝĞŶƚƌĂƐ ƋƵĞ͕ ĞŶ Ğů ƐĞŐƵŶĚŽ͕ Ğů
ŵŽǀŝŵŝĞŶƚŽ ƐĞƌĄ ũƵƐƚŽ ĞŶ ƐĞŶƚŝĚŽ ĐŽŶƚƌĂƌŝŽ͘ Ŷ Ğů ĚĞƐƉůĂǌĂŵŝĞŶƚŽ ĂŶƚĞƌſŐƌĂĚŽ
ŝŶƚĞƌǀŝĞŶĞŶ ĐŽŵŽ ŵŽƚŽƌĞƐ ĐĞůƵůĂƌĞƐ ůĂƐ ĐŝŶĞƐŝŶĂƐ ϭ Ǉ ϯ͕ ĚĞŶŽŵŝŶĂĚĂƐ </&ϱ Ǉ </&ϭ
ƌĞƐƉĞĐƚŝǀĂŵĞŶƚĞ͕ ;EĂŶŐĂŬƵ Ğƚ Ăů͕͘ ϭϵϵϰ͖ dĂŶĂŬĂ Ğƚ Ăů͕͘ ϭϵϵϴͿ͕ ůĂƐ ĐƵĂůĞƐ ĂĐƚƷĂŶ
ŝŶƚĞƌĂĐĐŝŽŶĂŶĚŽĐŽŶůĂƐŵŝƚŽĐŽŶĚƌŝĂƐĂƚƌĂǀĠƐĚĞůĂƐƉƌŽƚĞşŶĂƐĚĞŵĞŵďƌĂŶĂDŝƌŽϭǇ
DŝƌŽϮ͕ ƋƵĞ ƉŽƐĞĞŶ ĂĐƚŝǀŝĚĂĚ 'dWĂƐĂ͕ ;ZĞŝƐ Ğƚ Ăů͕͘ ϮϬϬϵͿ͘ WŽƌ ƐƵ ƉĂƌƚĞ͕ ĞŶ ĐĂƐŽ ĚĞů
ƌĞƚƌſŐƌĂĚŽ͕ ůĂ ƉƌŽƚĂŐŽŶŝƐƚĂ ĞƐ ůĂ ĚŝŶĞşŶĂ͕ ƵŶĂ ƉƌŽƚĞşŶĂ ŵŽƚŽƌĂ ƋƵĞ ƉƌŽĚƵĐĞ Ğů
ĚĞƐůŝǌĂŵŝĞŶƚŽ ĚĞ ůŽƐ ŵŝĐƌŽƚƷďƵůŽƐ Ă ƚƌĂǀĠƐ ĚĞ ůŽƐ ĂǆŽŶĞƐ͕ ;,ŽůůĞŶďĞĐŬ Ğƚ Ăů͕͘ ϮϬϬϱ͖
sĂƌĂĚŝĞƚĂů͕͘ϮϬϬϰͿ͘>ĂŝŶƚĞƌƌƵƉĐŝſŶĚĞĞƐƚĞƷůƚŝŵŽƉƌŽĐĞƐŽĐŽŶůůĞǀĂůĂŵŽǀŝůŝǌĂĐŝſŶĚĞ
ƌƉϭ ŚĂĐŝĂ ůĂƐ ŵŝƚŽĐŽŶĚƌŝĂƐ͕ ŽďƚĞŶŝĠŶĚŽƐĞ ŵŝƚŽĐŽŶĚƌŝĂƐ ƉĞƌŝŶƵĐůĞĂƌĞƐ Ǉ ĂůĂƌŐĂĚĂƐ͕
ϭϲ
;sĂƌĂĚŝĞƚĂů͕͘ϮϬϬϰͿ͘
ĚşĂ ĚĞ ŚŽǇ͕ ĂƵŶƋƵĞ ĞŵƉĞǌĂŵŽƐ Ă ĐŽŶŽĐĞƌ Ǉ ĞŶƚĞŶĚĞƌ ŵĞũŽƌ ƚĂŶƚŽ Ğů
ŵŽǀŝŵŝĞŶƚŽ Ă ƚƌĂǀĠƐ ĚĞ ůŽƐ ŵŝĐƌŽƚƷďƵůŽƐ ĐŽŵŽ ůĂ ĨƵƐŝſŶ Ǉ ůĂ ĨŝƐŝſŶ ŵŝƚŽĐŽŶĚƌŝĂůĞƐ͕
ĚĞƐĐŽŶŽĐĞŵŽƐ ŵƵĐŚŽƐ ĂƐƉĞĐƚŽƐ ĚĞů ŵĞĐĂŶŝƐŵŽ Ă ƚƌĂǀĠƐ ĚĞů ĐƵĂů ŝŶƚĞƌĂĐƚƷĂŶ ĞƐƚŽƐ
ƚƌĞƐƉƌŽĐĞƐŽƐ͕ƐŝďŝĞŶĞƐĐŝĞƌƚŽƋƵĞƐĞŚĂŽďƐĞƌǀĂĚŽƋƵĞĞůŵŽǀŝŵŝĞŶƚŽĚĞůĂŽƌŐĂŶĞůĂ
ƐĞǀĞĚŝƐŵŝŶƵŝĚŽƚĂŶƚŽƉŽƌůŽƐĚĞĨĞĐƚŽƐĞŶůĂĨŝƐŝſŶĐŽŵŽĞŶůĂĨƵƐŝſŶŵŝƚŽĐŽŶĚƌŝĂůĞƐ͘
Ɛş͕ ĞŶ ůĂ ĨŝƐŝſŶ͕ ůŽƐ ĨĂůůŽƐ ĞŶ Ğů ƚƌĂŶƐƉŽƌƚĞ Ă ƚƌĂǀĠƐ ĚĞ ůŽƐ ĂǆŽŶĞƐ ƐĞ ŚĂŶ
ƌĞůĂĐŝŽŶĂĚŽĐŽŶůĂĨŽƌŵĂĐŝſŶĚĞůĂƌŐĂƐƌĞĚĞƐŵŝƚŽĐŽŶĚƌŝĂůĞƐ͕ĂƚƌĂǀĠƐĚĞůĂƐĐƵĂůĞƐ͕ƉŽƌ
ŵŽƚŝǀŽƐ ĨşƐŝĐŽƐ ĚĞ ĞƐƉĂĐŝŽ͕ ŶŽ ƐĞ ƉƵĞĚĞ ĚĂƌ Ğů ŵŽǀŝŵŝĞŶƚŽ͘ ƐƚĞ ĞĨĞĐƚŽ ĞƐ
ĞƐƉĞĐŝĂůŵĞŶƚĞŶŽƚŽƌŝŽĞŶĞůĐĂƐŽĐŽŶĐƌĞƚŽĚĞůĂƐǀşĂƐŶĞƵƌŽŶĂůĞƐ͕ĚŽŶĚĞĞůĞƐƉĂĐŝŽĞƐ
ǇĂĚĞƉŽƌƐşŵƵǇƌĞĚƵĐŝĚŽ͕;>ŝĞƚĂů͕͘ϮϬϬϰ͖>ŝĞƐĂĞƚĂů͕͘ϮϬϬϵͿ͘WŽƌŽƚƌŽůĂĚŽ͕ĐƵĂŶĚŽůŽƐ
ĚĞĨĞĐƚŽƐ ƐĞ ƉƌŽĚƵĐĞŶ ĞŶ ůĂ ĨƵƐŝſŶ͕ ƐĞ ŚĂ ĚĞƐĐƌŝƚŽ ƋƵĞ ůĂƐ ŵŝƚŽĐŽŶĚƌŝĂƐƉƌĞƐĞŶƚĂŶƵŶ
ŵŽǀŝŵŝĞŶƚŽĐĂſƚŝĐŽ͕ƐŝŶĚŝƌĞĐĐŝſŶĚĞƚĞƌŵŝŶĂĚĂ͕;ŚĞŶĞƚĂů͕͘ϮϬϬϯͿ͘ĚĞŵĄƐ͕ĞŶĞůĐĂƐŽ
ĚĞůĂƐŶĞƵƌŽŶĂƐ͕ůĂƐŐƌĂŶĚĞƐŵŝƚŽĐŽŶĚƌŝĂƐƋƵĞƐĞĨŽƌŵĂŶďůŽƋƵĞĂŶůĂĞŶƚƌĂĚĂĞĨŝĐŝĞŶƚĞ
ĚĞůŽƐŽƌŐĄŶƵůŽƐĞŶůĂƐŶĞƵƌŝƚĂƐ͕ƌĞĚƵĐŝĞŶĚŽĂƐşůĂĐĂŶƚŝĚĂĚĚĞůĂƐŵŝƐŵĂƐƚĂŶƚŽĞŶůŽƐ
ĂǆŽŶĞƐĐŽŵŽĞŶůĂƐĚĞŶĚƌŝƚĂƐ͕;ŚĞŶĞƚĂů͕͘ϮϬϬϳďͿ͘
Ŷ ůŽƐ ƷůƚŝŵŽƐ ĂŹŽƐ͕ ƐĞ ŚĂ ƉƵďůŝĐĂĚŽ ǀĂƌŝŽƐ ƚƌĂďĂũŽƐ ƋƵĞ ƌĞůĂĐŝŽŶĂŶ ĐŽŶ Ğů
ŵŽǀŝŵŝĞŶƚŽ ĚĞ ůĂƐ ŵŝƚŽĐŽŶĚƌŝĂƐ Ă ƚƌĂǀĠƐ ĚĞ ůŽƐ ŵŝĐƌŽƚƷďƵůŽƐ Ă ƵŶĂƐ ƉƌŽƚĞşŶĂƐ
ĐŝƚŽƉůĂƐŵĄƚŝĐĂƐĚĞůĂĨĂŵŝůŝĂĚĞůĂƐ,ŝƐƚŽŶĂƐĞƐĂĐĞƚŝůĂƐĂƐ͕ĐŽŶĐƌĞƚĂŵĞŶƚĞĂůĂĐůĂƐĞ//
ĚĞůƐƵďƚŝƉŽϲ͕;,ϲͿ͕ůĂƐĐƵĂůĞƐŝŶƚĞƌǀŝĞŶĞŶĞŶůĂĚĞƐĂĐĞƚŝůĂĐŝſŶĚĞůŽƐŵŝĐƌŽƚƷďƵůŽƐ
ĚĞ ƚƵďƵůŝŶĂ͕ ǇĂ ƋƵĞ ƐƵ ƐƵƐƚƌĂƚŽ ĞƐ͕ ƉƌĞĐŝƐĂŵĞŶƚĞ͕ ůĂ ƉƌŽƚĞşŶĂ ɲͲƚƵďƵůŝŶĂ͘ WŽƐĞĞŶ
ĂĐƚŝǀŝĚĂĚŝŶƚƌşŶƐĞĐĂƵďŝƋƵŝƚŝŶͲůŝŐĂƐĂǇĞƐƚĄŶŝŵƉůŝĐĂĚĂƐĞŶŵƵĐŚŽƐƉƌŽĐĞƐŽƐĐĞůƵůĂƌĞƐ͕
ĐŽŵŽĞƐĞůĐĂƐŽĚĞůĂĞůŝŵŝŶĂĐŝſŶĂƵƚŽĨĄŐŝĐĂĚĞƉƌŽƚĞşŶĂƐŵĂůƉůĞŐĂĚĂƐ͕ůĂŵŝŐƌĂĐŝſŶ
ĐĞůƵůĂƌŽůĂƐŝŶƚĞƌĂĐĐŝŽŶĞƐĐĠůƵůĂƐͲĐĠůƵůĂ͕;sĂůĞŶǌƵĞůĂͲ&ĞƌŶĂŶĚĞǌĞƚĂů͕͘ϮϬϬϴͿ͘
I.2. Mitofagia
>Ă ŵƵĞƌƚĞ ĐĞůƵůĂ ƉƌŽŐƌĂŵĂĚĂ ƐĞ ƉƌŽĚƵĐĞ ĞŶ ĐŽŶĚŝĐŝŽŶĞƐ ĨŝƐŝŽůſŐŝĐĂƐ ĞŶ ůĂƐ
ĐĠůƵůĂƐĚĞůŽƌŐĂŶŝƐŵŽ͕ƚĞŶŝĞŶĚŽĐŽŵŽƉƌŝŶĐŝƉĂůĨƵŶĐŝſŶĞůĚĞƐĂƌƌŽůůŽŶŽƌŵĂůĚĞƚĞũŝĚŽƐ
Ǉ ſƌŐĂŶŽƐ͕ Ă ƚƌĂǀĠƐ ĚĞ ůĂ ĞůŝŵŝŶĂĐŝſŶ ĚĞ ĐĠůƵůĂƐ ĚĂŹĂĚĂƐ Ǉ ĚĞů ŵĂŶƚĞŶŝŵŝĞŶƚŽ ĚĞ ůĂ
ϭϳ
ŚŽŵĞŽƐƚĂƐŝƐ ƚŝƐƵůĂƌ͘ >Ă ŵƵĞƌƚĞ ĐĞůƵůĂ ƉƌŽŐƌĂŵĂĚĂ ĐŽŵƉƌĞŶĚĞ ƚƌĞƐ ƉƌŽĐĞƐŽƐ
ĚŝĨĞƌĞŶĐŝĂďůĞƐ͗ ůĂ ĂƉŽƉƚŽƐŝƐ͕ ůĂ ŶĞĐƌŽƐŝƐ Ǉ ůĂ ĂƵƚŽĨĂŐŝĂ͘ Ɛş͕ ĞŶ ůĂ ĚĞĐŝƐŝſŶ ĐĞůƵůĂƌ ĚĞ
ƐĞŐƵŝƌ ǀŝǀŝĞŶĚŽ Ž ĚĞ ĞŶƚƌĂƌ ĞŶ ĐƵĂůƋƵŝĞƌĂ ĚĞ ĞƐƚŽƐ ĞƐƚĄ ĨƵĞƌƚĞŵĞŶƚĞ ŝŵƉůŝĐůĂĚĂ ůĂ
ŵŝƚŽĐŽŶĚƌŝĂ͕ ĂƐş ĐŽŵŽ ůĂƐ ŵŽĚŝĨŝĐĂĐŝŽŶĞƐ ƋƵĞ ĞŶ ĞůůĂ ƐĞ ƉƌŽĚƵĐĞŶ ĐƵĂŶĚŽ ĂƉĂƌĞĐĞŶ
ĞƐƚşŵƵůŽƐ ĂĐƚŝǀĂĚŽƌĞƐ ĚĞ ŵƵĞƌƚĞ͕ ;ƌĞǀŝƐĂĚŽ ĞŶ ;ƌĂƐ Ğƚ Ăů͕͘ ϮϬϬϱͿͿ͘ Ŷ ĞƐƚĂ ƚĞƐŝƐ
ĚŽĐƚŽƌĂůƉƌŽĨƵŶĚŝǌĂƌĞŵŽƐĞŶĞůĞƐƚƵĚŝŽĚĞůĂĂƵƚŽĨĂŐŝĂǇƚƌĂƚĂƌĞŵŽƐďƌĞǀĞŵĞŶƚĞĞŶůĂ
ŝŶƚƌŽĚƵĐĐŝſŶůĂĂƉŽƉƚŽƐŝƐ͘
>Ă ĂƵƚŽĨĂŐŝĂ͕ ĨƵĞ ĚĞƐĐƌŝƚĂ ƉŽƌ ƉƌŝŵĞƌĂ ǀĞǌ ƉŽƌ Ğ ƵǀĞ Ǉ ĐŽůĂďŽƌĂĚŽƌĞƐ ĞŶ
ϭ͘ϵϲϯ͕ ;Ğ ƵǀĞ͕ ϭϵϲϯͿ͘ƐƚĞ ƉƌŽĐĞƐŽƉĞƌŵŝƚĞ ĞůƌĞĐŝĐůĂũĞ ĚĞ ůĂƐ ŵĂĐƌŽŵŽůĠĐƵůĂƐ ƋƵĞ
ĐŽŵƉŽŶĞŶ ůĂƐ ĞƐƚƌƵĐƚƵƌĂƐ ƋƵĞ ŚĂŶ ƐŝĚŽ ĚĞŐƌĂĚĂĚĂƐ͕ ƉĂƌĂ ƋƵĞ ƉƵĞĚĂŶ ƐĞƌ ƵƐĂĚĂƐ ĚĞ
ŶƵĞǀŽ ƉŽƌ ůĂƐ ĐĠůƵůĂƐ͘ Ɛ ƵŶĂ ƌƵƚĂ ĐĂƚĂďſůŝĐĂ͕ ĂůƚĂŵĞŶƚĞ ĐŽŶƐĞƌǀĂĚĂ Ǉ ƉƌĞƐĞŶƚĞ ĞŶ
ƚŽĚĂƐůĂƐĐĠůƵůĂƐĞƵĐĂƌŝŽƚĂƐ͘ŶĞůůĂ͕ŐƌĂĐŝĂƐĂůĂĂĐĐŝſŶĚĞůŽƐůŝƐŽƐŽŵĂƐ͕ƐĞƉƌŽĚƵĐĞůĂ
ĞůŝŵŝŶĂĐŝſŶ ĚĞ ŵŽůĠĐƵůĂƐ Ǉ ŽƌŐĄŶƵůŽƐ ƉƌĞƐĞŶƚĞƐ ĞŶ Ğů ĐŝƚŽƉůĂƐŵĂ͘ ^Ğ ĂĐƚŝǀĂ ĞŶ
ƌĞƐƉƵĞƐƚĂĂĚŝǀĞƌƐŽƐĞƐƚşŵƵůŽƐ͕ĐŽŵŽƐŽŶĞůĞƐƚƌĠƐĐĞůƵůĂƌ͕ůĂŝŶĨĞĐĐŝſŶƉŽƌƉĂƚſŐĞŶŽƐ͕
Ğů ĂǇƵŶŽ͕ ůĂ ĂĐƵŵƵůĂĐŝſŶ ĚĞ ŽƌŐĄŶƵůŽƐ ĚĂŹĂĚŽƐ ƉŽƌ ĞǆĐĞƐŽ ĚĞ ZK Ž ůĂƐ
ŵĂůĨŽƌŵĂĐŝŽŶĞƐĐĞůƵůĂƌĞƐŝŶƚĞƌŶĂƐ͘
ůĄƐŝĐĂŵĞŶƚĞ͕ ůĂ ĐŽŵƵŶŝĚĂĚ ĐŝĞŶƚşĨŝĐĂ ĚŝǀŝĚĞ ůĂ ĂƵƚŽĨĂŐŝĂ ĞŶ ƚƌĞƐ ƐƵďƚŝƉŽƐ͗ ůĂ
ŵĂĐƌŽĂƵƚŽĨĂŐŝĂ͕ůĂŵŝĐƌŽĨĂŐŝĂǇůĂĂƵƚŽĨĂŐŝĂŵĞĚŝĂĚĂƉŽƌĐŚĂƉĞƌŽŶĂƐ͘
>ĂŵĂĐƌŽĂƵƚŽĨĂŐŝĂĐŽŶƐƚŝƚƵǇĞůĂƌƵƚĂĚĞĚĞŐƌĂĚĂĐŝſŶĐůĄƐŝĐĂ͘ŶĞůůĂ͕ƐĞĨŽƌŵĂŶ
ůŽƐĂƵƚŽĨĂŐŽƐŽŵĂƐ͕ůŽƐĐƵĂůĞƐ͕ĂůŵĂĚƵƌĂƌ͕ƐĞĨƵŶĚĞŶĐŽŶůŽƐůŝƐŽƐŽŵĂƐƉĂƌĂĚĞŐƌĂĚĂƌ
ĞůĐŽŶƚĞŶŝĚŽŝŶƚĞƌŶŽĚĞůŽƐƉƌŝŵĞƌŽƐ͕ŐƌĂĐŝĂƐĂůĂĂĐĐŝſŶĚĞůĂƐŚŝĚƌŽůĂƐĂƐĄĐŝĚĂƐ͘ƐƚĞ
ƉƌŽĐĞƐŽĞƐƚĄƌĞŐƵůĂĚŽƉŽƌŵĄƐĚĞϯϬƚŐ͕;ƉƌŽƚĞşŶĂƐƌĞůĂĐŝŽŶĂĚĂƐĐŽŶůĂƵƚŽĨĂŐŝĂͿ͕ůĂƐ
ĐƵĂůĞƐĞƐƚĄŶĂůƚĂŵĞŶƚĞĐŽŶƐĞƌǀĂĚĂƐĚĞƐĚĞůĂƐůĞǀĂĚƵƌĂƐŚĂƐƚĂůŽƐŚƵŵĂŶŽƐ͕;ŚĞŶĞƚ
Ăů͕͘ϮϬϭϭ͖,ĞĞƚĂů͕͘ϮϬϬϵͿ͘
ŶůĂŵŝĐƌŽĂƵƚŽĨĂŐŝĂůŽƐůŝƐŽƐŽŵĂƐŝŶǀĂŐŝŶĂŶĂůŽƐĐŽŵƉŽŶĞŶƚĞƐĚĞůĐŝƚŽƉůĂƐŵĂ͕
ƵƐĂŶĚŽƉĂƌĂĞůůŽŝŶǀŽůƵĐŝŽŶĞƐĚĞůĂŵĞŵďƌĂŶĂ͕;DŝũĂůũŝĐĂĞƚĂů͕͘ϮϬϭϭ͖DŽƌƚŝŵŽƌĞĞƚĂů͕͘
ϭϵϴϯ͖DŽƌƚŝŵŽƌĞĞƚĂů͕͘ϭϵϴϴ͖^ĂŚƵĞƚĂů͕͘ϮϬϭϭͿ͘
WŽƌ ƷůƚŝŵŽ͕ ĞǆŝƐƚĞ ůĂ ĂƵƚŽĨĂŐŝĂ ŵĞĚŝĂĚĂ ƉŽƌ ĐŚĂƉĞƌŽŶĂƐ͕ ĞŶ ůĂ ƋƵĞ ĞƐƚĂƐ
ϭϴ
ƉƌŽƚĞşŶĂƐ ũƵĞŐĂŶ ƵŶ ƉĂƉĞů ĨƵŶĚĂŵĞŶƚĂů͕ ;ĞũĂƌĂŶŽ Ğƚ Ăů͕͘ ϮϬϭϬͿ͕ ŝŶĚƵĐŝĞŶĚŽ ůĂ
ƚƌĂƐůŽĐĂĐŝſŶĚĞůĂƐƉƌŽƚĞşŶĂƐĚĞĨĞĐƚƵŽƐĂƐŽŵĂůƉůĞŐĂĚĂƐĂůŝŶƚĞƌŝŽƌĚĞůŽƐůŝƐŽƐŽŵĂƐ͘
ZĞĐŝĞŶƚĞŵĞŶƚĞ ƐĞ ŚĂ ĂĐƵŹĂĚŽ Ğů ƚĠƌŵŝŶŽ ŵŝƚŽĨĂŐŝĂ ƉĂƌĂ ŚĂĐĞƌ ƌĞĨĞƌĞŶĐŝĂ Ăů
ƚŝƉŽ ĚĞ ĂƵƚŽĨĂŐŝĂ ƋƵĞ ĂĨĞĐƚĂ ĞƐƉĞĐşĨŝĐĂŵĞŶƚĞ Ă ůĂ ŵŝƚŽĐŽŶĚƌŝĂ͘ Ɛş͕ ůĂ ŵŝƚŽĨĂŐŝĂ͕
ŝŶĐůƵŝĚĂĚĞŶƚƌŽĚĞůĂĚŝŶĄŵŝĐĂŵŝƚŽĐŽŶĚƌŝĂů͕ĐŽŶƐƚŝƚƵǇĞĞůŵĞĐĂŶŝƐŵŽĂƚƌĂǀĠƐĚĞůĐƵĂů
ůĂƐŵŝƚŽĐŽŶĚƌŝĂƐĚĞĨĞĐƚƵŽƐĂƐŽŝƌƌĞǀĞƌƐŝďůĞŵĞŶƚĞĚĂŹĂĚĂƐƐŽŶĚĞŐƌĂĚĂĚĂƐ͕;ĞƌĞŝƚĞƌͲ
,ĂŚŶĞƚĂů͕͘ϮϬϭϬͿ͘WĂƌĂĞůůŽ͕ĐŽŵŽĞŶĞůĐĂƐŽĚĞůĂĂƵƚŽĨĂŐŝĂ͕ƐĞƵƐĂƵŶƐŝƐƚĞŵĂƋƵĞ
ƉĞƌŵŝƚĞ ƌĞĐŝĐůĂƌ ůĂ ŵĂǇŽƌşĂ ĚĞ ůŽƐ ĐŽŵƉŽŶĞŶƚĞƐ ĚĞ ĞƐƚŽƐ ŽƌŐĄŶƵůŽƐ͕ ĐŽŶǀŝƌƚŝĞŶĚŽ ůŽƐ
ƌĞƐŝĚƵŽƐ ĞŶ ůĂƐ ŵŽůĠĐƵůĂƐ ƋƵĞ Ğů ŽƌŐĂŶŝƐŵŽ ĐŽŶƐŝĚĞƌĞ ŵĄƐ ŶĞĐĞƐĂƌŝĂƐ ĞŶ ĐĂĚĂ
ŵŽŵĞŶƚŽ͕;ŚĞŶĞƚĂů͕͘ϮϬϬϵͿ͘
ŶŝǀĞů ďŝŽƋƵşŵŝĐŽ ƌĞƐƵůƚĂ ĐŽŵƉůĞũŽ͕ ĐƵĂŶĚŽ ŶŽ ŝŵƉŽƐŝďůĞ͕ ĚŝƐƚŝŶŐƵŝƌ ĞŶƚƌĞ ůĂ
ŵĂĐƌŽĂƵƚŽĨĂŐŝĂ Ǉ ůĂ ŵŝƚŽĨĂŐŝĂ͘ ƐƚĞ ŚĞĐŚŽ ƐĞ ǀĞ ĂŐƌĂǀĂĚŽ Ɛŝ ƚĞŶĞŵŽƐ ĞŶ ĐƵĞŶƚĂ ƋƵĞ
ĂŵďŽƐƉƌŽĐĞƐŽƐĞƐƚĄŶĐŽŶƚƌŽůĂĚŽƐƉŽƌůŽƐŵŝƐŵŽƐŐĞŶĞƐ͕ƐŝďŝĞŶĞƐĐŝĞƌƚŽƋƵĞ͕ĞŶĞů
ĐĂƐŽ ĚĞ ůĂ ŵŝƚŽĨĂŐŝĂ͕ ĞƐĞ ĐŽŶƚƌŽů ĐŽĞǆŝƐƚĞ ĐŽŶ ƵŶ ƐŝƐƚĞŵĂ ƉƌŽƉŝŽ ĚĞ ĚĞŐƌĂĚĂĐŝſŶ
ŵŝƚŽĐŽŶĚƌŝĂů͘ >Ă ƌĞůĂĐŝſŶ ĞŶƚƌĞ ĂŵďŽƐ ƚŝƉŽƐ ƐƵƐĐŝƚĂ ŐƌĂŶ ŝŶƚĞƌĠƐ ĞŶƚƌĞ ůĂ ĐŽŵƵŶŝĚĂĚ
ĐŝĞŶƚşĨŝĐĂ͘
>ĂŵŝƚŽĨĂŐŝĂĐŽŶƐƚŝƚƵǇĞƵŶƉƌŽĐĞƐŽĂůƚĂŵĞŶƚĞƌĞŐƵůĂĚŽ͕ĂƵŶƋƵĞĞůŵĞĐĂŶŝƐŵŽ
ĂƚƌĂǀĠƐĚĞůĐƵĂůƐĞƉƌŽĚƵĐĞĞƐƚĂƌĞŐƵůĂĐŝſŶŶŽĞƐĐŽŶŽĐŝĚŽ͘>ŽƋƵĞƐşƋƵĞƉĂƌĞĐĞĞƐƚĂƌ
ĐůĂƌŽ ĞƐ ƋƵĞ ĞƐƚĞ ƚŝƉŽ ĚĞ ĚĞŐƌĂĚĂĐŝſŶ ƐĞ ůůĞǀĂ Ă ĐĂďŽ Ă ƚƌĂǀĠƐ ĚĞ ƵŶ ƐŝƐƚĞŵĂ
ĐŽŶƐƚŝƚƵƚŝǀŽ Ğ ŝŶĚƵĐŝďůĞ Ǉ ƐƵƉŽŶĞ ƵŶ ƉƵŶƚŽ ĐƌşƚŝĐŽ ĞŶ Ğů ĐŽŶƚƌŽů ĚĞ ůĂƐ ŵŝƚŽĐŽŶĚƌŝĂƐ͕
ƚĂŶƚŽ ĚĞƐĚĞ ƵŶ ƉƵŶƚŽ ĚĞ ǀŝƐƚĂ ĐƵĂůŝƚĂƚŝǀŽ ĐŽŵŽ ĐƵĂŶƚŝƚĂƚŝǀŽ͕ ;EĂƌĞŶĚƌĂ Ğƚ Ăů͕͘ ϮϬϬϴ͖
KŬĂŵŽƚŽĞƚĂů͕͘ϮϬϬϱ͖tŝŬƐƚƌŽŵĞƚĂů͕͘ϮϬϬϵͿ͘
WŽĚĞŵŽƐ ĂĨŝƌŵĂƌ ƋƵĞ͕ ĂŶƚĞ ůĂ ƉƌĞƐĞŶĐŝĂ ĚĞ ƵŶĂ ŵŝƚŽĐŽŶĚƌŝĂ ĚĂŹĂĚĂ͕ ƐĞ
ƉƌŽĚƵĐĞĞůĞŶĐĂƉƐƵůĂŵŝĞŶƚŽĚĞůĂŵŝƐŵĂĞŶƵŶĂŵĞŵďƌĂŶĂĚĞĂŝƐůĂŵŝĞŶƚŽ͕ůĂĐƵĂůƐĞ
ĐŽŶǀŝĞƌƚĞ ĞŶ ƵŶ ĂƵƚŽĨĂŐŽƐŽŵĂ ĐƵĂŶĚŽ ĚĞƐĂƌƌŽůůĂ ƵŶĂ ĚŽďůĞ ŵĞŵďƌĂŶĂ͘ ĐŽŶƚŝŶƵĂĐŝſŶ͕ƐĞĚĞƐĞŶĐĂĚĞŶĂůĂĨƵƐŝſŶĚĞůĐŝƚĂĚŽĂƵƚŽĨĂŐŽƐŽŵĂĐŽŶůŽƐůŝƐŽƐŽŵĂƐ͕ĞŶ
ĞůŝŶƚĞƌŝŽƌĚĞůŽƐĐƵĂůĞƐƐĞĞŶĐƵĞŶƚƌĂŶůĂƐĞŶǌŝŵĂƐŚŝĚƌŽůşƚŝĐĂƐ͕ůĂƐĐƵĂůĞƐƉƌŽĚƵĐŝƌĄŶ͕
ĞŶƷůƚŝŵŽƚĠƌŵŝŶŽ͕ůĂĚĞŐƌĂĚĂĐŝſŶĨŝŶĂůĚĞůĂŵŝƚŽĐŽŶĚƌŝĂ͘>ŽƐĂƵƚŽĨĂŐŽƐŽŵĂƐƉŽĚƌşĂŶ
ĨŽƌŵĂƌƐĞ ĚĞƐĚĞ ůĂ ŵĞŵďƌĂŶĂ ĞǆƚĞƌŶĂ ŵŝƚŽĐŽŶĚƌŝĂů͕ ĂƵŶƋƵĞ ĞƐƚĞ ĂƐƉĞĐƚŽ ŶŽ ĞƐ ĚĞů
ϭϵ
ƚŽĚŽ ĐŽŶŽĐŝĚŽ Ă ĚşĂ ĚĞ ŚŽǇ͕ ƉŽƌ ůŽ ƋƵĞ ĂƷŶ ŶŽ ƉŽĚĞŵŽƐ ĂƐĞǀĞƌĂƌ ĐŽŶ ĞǆĂĐƚŝƚƵĚ ƐƵ
ŽƌŝŐĞŶ͕ ;>ĞĞ Ğƚ Ăů͕͘ ϮϬϭϮͿ͘ Ɛş͕ ƉŽƌ ĞũĞŵƉůŽ͕ ĞŶ ƵŶ ĞƐƚƵĚŝŽ ƌĞĂůŝǌĂĚŽ ĞŶ ŚĞƉĂƚŽĐŝƚŽƐ͕
ƋƵĞĚſ ĚĞŵŽƐƚƌĂĚŽ Ğů ŚĞĐŚŽ ĚĞ ƋƵĞ ůĂ ĚĞƐƉŽůĂƌŝǌĂĐŝſŶ ĚĞ ůĂ ŵĞŵďƌĂŶĂ ŵŝƚŽĐŽŶĚƌŝĂů
ƉƌĞĐĞĚĞ Ă ůĂ ŝŶĚƵĐĐŝſŶ ĚĞ ůĂ ŵĂĐƌŽĂƵƚŽĨĂŐŝĂ͘ dƌĂƐ ĞƐƚĞ ƉƌŽĐĞƐŽ͕ ůĂƐ ĐŝƚĂĚĂƐ
ŵŝƚŽĐŽŶĚƌŝĂƐ ĐŽŶ Ğů ƉŽƚĞŶĐŝĂů ĚĞ ŵĞŵďƌĂŶĂ ĂĨĞĐƚĂĚŽ͕ ĐŽůŽĐĂůŝǌĂŶ ĐŽŶ ůŽƐ
ĂƵƚŽĨĂŐŽƐŽŵĂƐ͕;ůŵŽƌĞĞƚĂů͕͘ϮϬϬϭͿ͘
>ĂǀşĂĐůĄƐŝĐĂĚĞĂĐƚŝǀĂĐŝſŶĚĞůĂŵŝƚŽĨĂŐŝĂƐĞƉƌŽĚƵĐĞĂƉĂƌƚŝƌĚĞůĂƉƌŝǀĂĐŝſŶĚĞ
ŶƵƚƌŝĞŶƚĞƐ͕ ůŽ ĐƵĂů ƉƌŽǀŽĐĂ ƋƵĞ ƐĞ ĂĐĞůĞƌĞ Ğů ƌĞĐĂŵďŝŽ ŵŝƚŽĐŽŶĚƌŝĂů͕ ;ĞŶŐũĞů Ğƚ Ăů͕͘
ϮϬϬϴ͖>ĞŵĂƐƚĞƌƐ͕ϮϬϬϱͿ͘Ɛş͕ůĂĐŝƚĂĚĂĚŝƐŵŝŶƵĐŝſŶĚĞůĂƉŽƌƚĞĚĞŶƵƚƌŝĞŶƚĞƐĐŽŶůůĞǀĂƵŶ
ĚĞƐĐĞŶƐŽĚĞůĂĐŽŶĐĞŶƚƌĂĐŝſŶŝŶƚƌĂĐĞůƵůĂƌĚĞdW͘ŶĞƐƚĂƐŝƚƵĂĐŝſŶ͕ůĂWƌŽƚĞŝŶͲŝŶĂƐĂ
ĐƚŝǀĂĚĂ ƉŽƌ ϱǲͲDW ;DW<Ϳ͕ ĞƐ ĂĐƚŝǀĂĚĂ Ǉ ĨŽƐĨŽƌŝůĂ Ă ƐƵ ǀĞǌ Ă ůŽƐ DŝĞŵďƌŽƐ ƐŝŶ
ŽŽƌĚŝŶĂƌĚĞůĂĨĂŵŝůŝĂϱϭ^ŝŵůŝĂƌĂůĂƐŝŶĂƐĂƐƚŝƉŽϭǇϮ;h><ϭǇh><ϮͿ͕ůŽĐƵĂůĂĐƚŝǀĂ͕
ĞŶƷůƚŝŵŽƚĠƌŵŝŶŽ͕ůĂŵŝƚŽĨĂŐŝĂ͕;ŐĂŶĞƚĂů͕͘ϮϬϭϭͿ͘ĂũŽĞƐƚĂƐĐŽŶĚŝĐŝŽŶĞƐ͕ŶŽƐſůŽƐĞ
ŝŶĚƵĐĞůĂŵŝƚŽĨĂŐŝĂ͕ƐŝŶŽƋƵĞ͕ŽďǀŝĂŵĞŶƚĞ͕ƚĂŵďŝĠŶƐĞƉƌŽĚƵĐĞŽƚƌĂƐĞƌŝĞĚĞĐĂŵďŝŽƐĂ
ŶŝǀĞůĐĞůƵůĂƌ͘
>ϯĞƐƵŶŽĚĞůŽƐƉƌŽƚĂŐŽŶŝƐƚĂƐƉƌŝŶĐŝƉĂůĞƐĚĞůĐŝƚĂĚŽƉƌŽĐĞƐŽ͘^ĞƚƌĂƚĂĚĞƵŶĂ
ƉƌŽƚĞşŶĂ ƐŝŵŝůĂƌ Ă ůĂ ƵďŝƋƵŝƚŝŶĂ ƋƵĞ ƐĞ ƐŝŶƚĞƚŝǌĂ ĞŶ ĨŽƌŵĂ ĚĞ ƉŽƌͲ>ϯ Ǉ ƐƵĨƌĞ
ŵŽĚŝĨŝĐĂĐŝŽŶĞƐƉŽƐƚƌĂŶƐĐƌŝƉĐŝŽŶĂůĞƐƉĂƌĂƚƌĂŶƐĨŽƌŵĂƌƐĞĞŶ>ϯͲ/Ǉ͕ƐĞŐƵŝĚĂŵĞŶƚĞ͕ĞŶ
>ϯͲ//͕;<ĂďĞǇĂĞƚĂů͕͘ϮϬϬϬ͖<ĂďĞǇĂĞƚĂů͕͘ϮϬϬϰ͖dĂŶŝĚĂĞƚĂů͕͘ϮϬϬϰͿ͘ŽŶĐƌĞƚĂŵĞŶƚĞ͕
ůĂƐĐŝƚĂĚĂƐŵŽĚŝĨŝĐĂĐŝŽŶĞƐĐŽŶƐŝƐƚĞŶĞŶůĂĞƐĐŝƐŝſŶƉŽƌƉĂƌƚĞĚĞůĂƉƌŽƚĞĂƐĂƚŐϰĚĞůĂ
ƌĞŐŝſŶͲƚĞƌŵŝŶĂůĚĞůĂƌĞĐŝĠŶƐŝŶƚĞƚŝǌĂĚĂƉƌŽͲ>ϯ͕ĐŽŶǀŝƌƚŝĠŶĚŽƐĞĞŶƚŽŶĐĞƐĞƐƚĂƷůƚŝŵĂ
ĞŶ>ϯͲ/͘>ĂƚƌĂŶƐĨŽƌŵĂĐŝſŶĨŝŶĂůĚĞ>ϯͲ/ĞŶ>ϯͲ//ƐĞƉƌŽĚƵĐĞĂƉĂƌƚŝƌĚĞƵŶƌĞƐŝĚƵŽĚĞ
ŐůŝĐŝŶĂ ĞǆƉƵĞƐƚŽ ĞŶ Ğů ĚŽŵŝŶŝŽ ͲƚĞƌŵŝŶĂů ĚĞů ƉƌŝŵĞƌŽ͕ Ğů ĐƵĂů ĞƐ ůŝƉŝĚĂĚŽ ƉŽƌ W͕
;ĨŽƐĨĂƚŝĚŝůĞƚĂŶŽůĂŵŝŶĂͿ͕ ůŽ ƋƵĞ ůĞ ƉĞƌŵŝƚĞ ŝŶƐĞƌƚĂƌƐĞ ĞŶ ůĂ ŵĞŵďƌĂŶĂ ĚĞů
ĂƵƚŽĨĂŐŽƐŽŵĂ͘
WĂƌĂ ƋƵĞ ƐĞ ƉƌŽĚƵǌĐĂ ĞƐƚĞ ƉƌŽĐĞƐŽ͕ ĞƐ ŶĞĐĞƐĂƌŝŽ ƋƵĞ ƐĞ ůůĞǀĞ Ă ĐĂďŽ ƵŶĂ
ƌĞĂĐĐŝſŶ ƐŝŵŝůĂƌ Ă ůĂ ƵďŝƋƵŝŶĂĐŝſŶ͕ ĞŶ ůĂ ƋƵĞ ŝŶƚĞƌǀŝĞŶĞŶ ƚŐϳ͕ ;ĞŶǌŝŵĂ ĂĐƚŝǀĂĚŽƌĂ
ƐŝŵŝůĂƌ Ă ϭͿ͖ ƚŐϯ͕ ;ĞŶǌŝŵĂ ĐŽŶũƵŐĂĚŽƌĂ ƐŝŵŝůĂƌ Ă ϮͿ͕ ĂƐş ĐŽŵŽ Ğů ĐŽŵƉůĞũŽ ƚŐϭϲ>͕
;ĞŶǌŝŵĂ ƐŝŵŝůĂƌ Ă ůĂ ůŝŐĂƐĂ ϯͿ͕ Ă ƚƌĂǀĠƐ ĚĞ ůŽƐ ƌĞƐŝĚƵŽƐ ĚĞ ĐŝƐƚĞşŶĂ ƉƌĞƐĞŶƚĞƐ ĞŶ ƐƵƐ
ϮϬ
ƐŝƚŝŽƐĐĂƚĂůşƚŝĐŽƐ͘ĞƵŶŵŽĚŽƐĞĐƵĞŶĐŝĂů͕ĞůƉƌŝŵĞƌƉĂƐŽƐĞƌşĂůĂĐŽŶũƵŐĂĐŝſŶĚĞƚŐϭϬ
ĂƚŐϭϮ͕ŵĞĚŝĂĚĂƉŽƌƚŐϳ͕ĂƐşĐŽŵŽůĂĚĞƚŐϯĂ>ϯͲ/͘ĐŽŶƚŝŶƵĂĐŝſŶ͕ƚŐϯǇƚŐϭϬ
ĐĂƚĂůŝǌĂŶůĂƐĐŽŶũƵŐĂĐŝŽŶĞƐĚĞƚŐϱĂƚŐϭϮƉŽƌƵŶůĂĚŽ͕ĂƐşĐŽŵŽůĂĚĞ>ϯͲ/ĂWƉĂƌĂ
ƉƌŽĚƵĐŝƌ>ϯͲ//ƉŽƌŽƚƌŽ͕;>ĞĞĞƚĂů͕͘ϮϬϭϮͿ͘ƐƚŽƐĚŽƐƷůƚŝŵŽƐƉƌŽĐĞƐŽƐƚŝĞŶĞŶƵŶĂŐƌĂŶ
ŝŵƉŽƌƚĂŶĐŝĂĞŶůĂĞǆƉĂŶƐŝſŶĚĞůŽƐĂƵƚŽĨĂŐŽƐŽŵĂƐ͕;<ĂďĞǇĂĞƚĂů͕͘ϮϬϬϬ͖<ĂďĞǇĂĞƚĂů͕͘
ϮϬϬϰ͖dĂŶŝĚĂĞƚĂů͕͘ϮϬϬϰͿ͘
KƚƌĂƉƌŽƚĞşŶĂƐŝŐŶŝĨŝĐĂƚŝǀĂĞŶĞůƉƌŽĐĞƐŽĚĞůĂŵŝƚŽĨĂŐŝĂĞƐůĂŵƵůƚŝĚŽŵŝŽƉϲϮ͕
ŝŵƉůŝĐĂĚĂ ĞŶ ůĂ ĂĐƚŝǀĂĐŝſŶ ĚĞů ĨĂĐƚŽƌ ĚĞ ƚƌĂŶƐĐƌŝƉĐŝſŶ E&Ͳʃ͕ ;&ĂĐƚŽƌ EƵĐůĞĂƌ
ƉŽƚĞŶĐŝĂĚŽƌĚĞůĂƐĐĂĚĞŶĂƐůŝŐĞƌĂƐ<ĂƉƉĂĚĞĠůƵůĂƐĂĐƚŝǀĂĚĂƐͿ;DŽƐĐĂƚĞƚĂů͕͘ϮϬϬϵͿ͘
ƐƵŶŝŵƉŽƌƚĂŶƚĞĞũĞĚĞƐĞŹĂůŝǌĂĐŝſŶ͕ǇĂƋƵĞƉŽƐĞĞƵŶĂĂůƚĂĐĂƉĂĐŝĚĂĚƉĂƌĂƌĞĐůƵƚĂƌǇ
ŽůŝŐŽŵĞƌŝǌĂƌŵŽůĠĐƵůĂƐĚĞƐĞŹĂůŝǌĂĐŝſŶĞŶĞůĐŝƚŽƉůĂƐŵĂ͕;ƵƌĂŶĞƚĂů͕͘ϮϬϬϴ͖ƵƌĂŶĞƚ
Ăů͕͘ ϮϬϬϰͿ͘ Ɛ ĐĂƉĂǌ ĚĞ ƵŶŝƌƐĞ ƚĂŶƚŽ Ă >ϯ ĐŽŵŽ Ă ƵďŝƋƵŝƚŝŶĂ͕ ƉŽƌ ůŽ ƋƵĞ ƚŝĞŶĞŶ ƵŶĂ
ĨƵŶĐŝſŶŝŵƉŽƌƚĂŶƚĞĞŶĞůŵĂƌĐĂũĞĚĞƉƌŽƚĞşŶĂƐĚŝƐĨƵŶĐŝŽŶĂůĞƐƉŽůŝƵďŝƋƵŝƚŝŶĂĚĂƐŚĂĐŝĂ
ůŽƐĂƵƚŽĨĂŐŽƐŽŵĂƐ͕ƐŝĞŶĚŽƉŽƌƚĂŶƚŽƵŶĐŽŵƉŽŶĞŶƚĞĐůĂǀĞĞŶĞƐƚŽƐƷůƚŝŵŽƐ͕;WĂŶŬŝǀĞƚ
Ăů͕͘ ϮϬϬϳͿ͘ ĚĞŵĄƐ͕ ĞŶ ůŽƐ ƉĂƐŽƐ ŝŶŝĐŝĂůĞƐ ĚĞ ůĂ ŵŝƚŽĨĂŐŝĂ͕ ƐĞ ƉƌŽĚƵĐĞ ƵŶ
ƌĞĐŽŶŽĐŝŵŝĞŶƚŽĚĞĐĂŶĂůĂŶŝſŶŝĐŽĚĞƉĞŶĚŝĞŶƚĞĚĞǀŽůƚĂũĞ;sͿƉŽƌƉĂƌƚĞĚĞƉϲϮ͕ůŽ
ĐƵĂůĞƐŶĞĐĞƐĂƌŝŽƉĂƌĂƋƵĞƐĞŝŶŝĐŝĞĞůĐŝƚĂĚŽƉƌŽĐĞƐŽ͕;'ĞŝƐůĞƌĞƚĂů͕͘ϮϬϭϬͿ͘
ƉϲϮĐŽŶƐƚŝƚƵǇĞƵŶďƵĞŶŵĂƌĐĂĚŽƌŵŽůĞĐƵůĂƌƉĂƌĂĞƐƚƵĚŝĂƌůĂĂƵƚŽĨĂŐŝĂ͕ĚĞďŝĚŽ
ĂƋƵĞƐƵĚĞŐƌĂĚĂĐŝſŶĞƐƐŝŵƵůƚĄŶĞĂĂůĂĂĐƚŝǀĂĐŝſŶĚĞůĐŝƚĂĚŽƉƌŽĐĞƐŽ͘>ĂŝŵƉůŝĐĂĐŝſŶ
ĚĞ ƉϲϮ ĞŶ ůĂ ŵŝƚŽĨĂŐŝĂ ĞƐƚĄ ĚĞŵŽƐƚƌĂĚĂ ĞŶ ĚŝǀĞƌƐŽƐ ĞƐƚƵĚŝŽƐ͘ Ɛş͕ ƉŽƌ ĞũĞŵƉůŽ͕
ƐĂďĞŵŽƐƋƵĞƐƵƐŝůĞŶĐŝĂŵŝĞŶƚŽƉƌŽĚƵĐĞůĂŝŶŚŝďŝĐŝſŶĚĞůĂƚƵŵŽƌŽŐĠŶĞƐŝƐ͕;DĂƚŚĞǁĞƚ
Ăů͕͘ ϮϬϬϵͿ͕ Ž ƋƵĞ ůŽƐ ŚĞƉĂƚŽĐŝƚŽ ĚĞĨŝĐŝĞŶƚĞƐ ĞŶ DW< Ž ĞŶ h><ϭ ŵƵĞƐƚƌĂŶ ƵŶĂ
ĂĐƵŵƵůĂĐŝſŶĞǆĐĞƐŝǀĂĚĞƉϲϮ͕ĂŐƌĞŐĂĚŽƐĚĞƵďŝƋƵŝƚŝŶĂǇŵŝƚŽĐŽŶĚƌŝĂƐŶŽƌŵĂůĞƐ͕;ŐĂŶ
Ğƚ Ăů͕͘ ϮϬϭϭͿ͘ ĚŝĐŝŽŶĂůŵĞŶƚĞ͕ ĞƐ ĐŽŶŽĐŝĚŽ Ğů ŚĞĐŚŽ ĚĞ ƋƵĞ ƉϲϮ ƐĞ ƵŶĞ Ă >Ͳϯ Ǉ ƐĞ
ĂĐƵŵƵůĂĞŶƌĂƚŽŶĞƐƋƵĞŶŽƉƵĞĚĞŶĚĞƐĂƌƌŽůůĂƌůĂĂƵƚŽĨĂŐŝĂ͕;<ŽŵĂƚƐƵĞƚĂů͕͘ϮϬϬϳͿ͘WŽƌ
ŽƚƌŽ ůĂĚŽ͕ ĞŶ ƌĂƚŽŶĞƐ ĐĂƌĞŶƚĞƐ ĚĞ ƚŐϳ Ǉ͕ ƉŽƌ ƚĂŶƚŽ͕ ĐŽŶ ŵĞĐĂŶŝƐŵŽ ĚĞ ůĂ ĂƵƚŽĨĂŐŝĂ
ĚĂŹĂĚŽ͕ƐĞŚĂŽďƐĞƌǀĂĚŽĂŐƌĞŐĂĚŽƐƉŽůŝƵďŝƋƵŝƚŝŶŝǌĂĚŽƐ͕ƚĂŶƚŽĞŶƐƵĐĞƌĞďƌŽĐŽŵŽĞŶ
ƐƵ ŚşŐĂĚŽ͕ ůŽƐ ĐƵĂůĞƐ ĐŽůŽĐĂůŝǌĂŶ ĐŽŶ ƉϲϮ͘ ^ŝ͕ ĂĚĞŵĄƐ͕ ĞƐƚŽƐ ƌĂƚŽŶĞƐ ŶŽ ĐƵĞŶƚĂŶ ĐŽŶ
ƉϲϮ͕ůŽƐĐŝƚĂĚŽƐĂŐƌĞŐĂĚŽƐŶŽƐŽŶĚĞƚĞĐƚĂďůĞƐ͕ƉŽƌůŽƋƵĞƐĞĞƐƉĞĐƵůĂĐŽŶĞůŚĞĐŚŽĚĞ
ƋƵĞƉϲϮƉŽĚƌşĂƚĞŶĞƌƵŶĂĨƵŶĐŝſŶĞƐƚƌƵĐƚƵƌĂůĞŶƐƵĨŽƌŵĂĐŝſŶ͕;<ŽŵĂƚƐƵĞƚĂů͕͘ϮϬϬϳͿ͘
Ϯϭ
WŽƌƷůƚŝŵŽ͕ŶŽƐƉĂƌĞĐĞŝŵƉŽƌƚĂŶƚĞĚĞƐƚĂĐĂƌĞůŚĞĐŚŽĚĞƋƵĞůĂƐĞůĞĐƚŝǀŝĚĂĚĚĞ
ůĂ ĂƵƚŽĨĂŐŝĂ ŚĂĐŝĂ ůĂƐ ŵŝƚŽĐŽŶĚƌŝĂƐ ĞƐƚĄ ĐŽŶƚƌŽůĂĚĂ ƉŽƌ ŽƚƌĂƐ ƉƌŽƚĞşŶĂƐ͕ ĐŽŵŽ ĞƐ Ğů
ĐĂƐŽ ĚĞ WĂƌŬŝŶͬWŝŶŬϭ Ž E/W͕ ;WƌŽƚĞşŶĂ ĚĞ ϭϴ <Ă ƋƵĞ /ŶƚĞƌĂĐĐŝŽŶĂ ĐŽŶ ĐůͲ
ϮͬĚĞŶŽǀŝƌƵƐͿ͘Ɛş͕ůĂŵŝƚŽĨĂŐŝĂŝŶĚƵĐŝĚĂƉŽƌWĂƌŬŝŶͬWŝŶŬϭƉŽĚƌşĂĞƐƚĂƌŵĞĚŝĂĚĂ͕ĚĞ
ŶƵĞǀŽ͕ƉŽƌsǇĞŶĞůůĂƐĞŚŝƉŽƚŝǌĂƵŶƉĂƉĞůŝŵƉŽƌƚĂŶƚĞƉĂƌĂƉϲϮ͕ĐŽŶĐƌĞƚĂŵĞŶƚĞ
ĞŶůĂĞůŝŵŝŶĂĐŝſŶĚĞůŵŝƚŽĨĂŐŽƐŽŵĂ͕;'ĞŝƐůĞƌĞƚĂů͕͘ϮϬϭϬͿ͘ĞĞƐƚĞƚƌĂďĂũŽ͕ƐĞĚĞĚƵĐĞ
ƚĂŵďŝĠŶƵŶĂĨƵŶĐŝſŶĞŶĞƐƚĂǀşĂƉĂƌĂũͲϭ͕;>ŽĐƵƐũͲϭĚĞůĂŶĨĞƌŵĞĚĂĚĚĞWĂƌŬŝŶƐŽŶͿ͘
WŽƌƐƵƉĂƌƚĞ͕ĞŶƌĞůĂĐŝſŶĂůĂƉƌŽƚĞşŶĂE/W͕ĐŽŶŽĐĞŵŽƐƋƵĞ͕ĞŶŵŽĚĞůŽƐĐĞůƵůĂƌĞƐĞŶ
ůŽƐƋƵĞĂǆǇĂŬĞƐƚĄŶƐŝůĞŶĐŝĂĚŽƐ͕ƉŽƐĞĞƵŶĞĨĞĐƚŽƉƌŽƚĞĐƚŽƌƐŽďƌĞůĂŵƵĞƌƚĞĐĞůƵůĂƌ͕
ƐŝĞŶĚŽŝŶĚĞƉĞŶĚŝĞŶƚĞĚĞůĂƐhWƐ͕;WƌŽƚĞşŶĂƐĚĞƐĂĐŽƉůĂĚŽƌĂƐͿ͕;>ĞĞĞƚĂů͕͘ϮϬϭϮͿ͘
ϮϮ
&ŝŐƵƌĂ Ϯ͘ >Ă ŵŝƚŽĨĂŐŝĂ͘ Ŷ ƉƌĞƐĞŶĐŝĂ ĚĞ ĞƐƚşŵƵůŽƐ ĂĐƚŝǀĂĚŽƌĞƐ ĚĞů ƉƌŽĐĞƐŽ͕ ƐĞ ŝŶŝĐŝĂŶ ůĂƐ
ŵŽĚŝĨŝĐĂĐŝŽŶĞƐĞŶůĂƉƌŽƚĞşŶĂƉƌŽͲ>ϯ͕ƉĂƌĂůůĞŐĂƌĂƐƵĨŽƌŵĂĂĐƚŝǀĂĞŶůĂŵŝƚŽĨĂŐŝĂ͕ĞƐƚŽĞƐ͕>ϯͲ//͘WŽƌ
ŽƚƌŽ ůĂĚŽ͕ ƐĞ ĞŵƉŝĞǌĂ Ă ĨŽƌŵĂƌ Ğů ĨĂŐſĨŽƌŽ ĂůƌĞĚĞĚŽƌ ĚĞ ůĂ ŵŝƚŽĐŽŶĚƌŝĂ͕ Ă ůĂ ƐƵƉĞƌĨŝĐŝĞ ĚĞů ĐƵĂů ƐĞ
ĂĚŚŝĞƌĞŶ͕ĂƉĂƌƚĞĚĞůĂĐŝƚĂĚĂ>ϯͲ//͕ƚŐϭϮͲϱͲϭϲ͘ĐŽŶƚŝŶƵĂĐŝſŶ͕ĞůĨĂŐſĨŽƌŽŝŶǀĂŐŝŶĂƚŽƚĂůŵĞŶƚĞĂůĂ
ŵŝƚŽĐŽŶĚƌŝĂǇƐĞĚĞƐƉƌĞŶĚĞĚĞůĂƐƚŐ͕ĂƉĂƌĞĐŝĞŶĚŽĞŶƚŽŶĐĞƐĞůĂƵƚŽĨĂŐŽƐŽŵĂ͘ƵĂŶĚŽůŽƐůŝƐŽƐŽŵĂƐƐĞ
ƵŶĞŶ Ă ĞƐƚĂ ĞƐƚƌƵĐƚƵƌĂ͕ ƐĞ ƉƌŽĚƵĐĞ ůĂ ůŝďĞƌĂĐŝſŶ ĚĞ ůĂƐ ĞŶǌŝŵĂƐ ĞŶ Ğů ŝŶƚĞƌŝŽƌ ĚĞů ĂƵƚŽĨĂŐŽƐŽŵĂ Ǉ͕ƉŽƌ
ƚĂŶƚŽ͕ůĂĚĞŐƌĂĚĂĐŝſŶĚĞůŽƐĐŽŵƉŽŶĞŶƚĞƐŵŝƚŽĐŽŶĚƌŝĂůĞƐ͕ůŽƐĐƵĂůĞƐƐĞƌĄŶƌĞĐŝĐůĂĚŽƐƉŽƌůĂĐĠůƵůĂ͘
Ϯϯ
2. Apoptosis
ůƚĠƌŵŝŶŽĂƉŽƉƚŽƐŝƐ͕ƉƌŽǀĞŶŝĞŶƚĞĚĞůĂůĞŶŐƵĂŐƌŝĞŐĂ͕ĂůƵĚĞĂůĂĐĂşĚĂĂƌŵſŶŝĐĂ
Ǉ ƉĂƵƐĂĚĂ ƋƵĞ ƐĞ ƉƌŽĚƵĐĞ ĞŶ ŽƚŽŹŽ ĞŶ ůĂƐ ŚŽũĂƐ ĚĞ ůŽƐ ĄƌďŽůĞƐ͘ ů ƉƌŝŵĞƌ ĂƌƚşĐƵůŽ
ĐŝĞŶƚşĨŝĐŽ ĚŽŶĚĞ ƐĞ ŚĂĐĞ ƌĞĨĞƌĞŶĐŝĂ Ă ĞƐƚĞƚŝƉŽĚĞ ŵƵĞƌƚĞ ĐĞůƵůĂƌ ĞƐĞůƉƵďůŝĐĂĚŽ ƉŽƌ
<ĞƌƌĞƚ͘Žů͕ĞŶϭ͘ϵϳϮ͕;<ĞƌƌĞƚĂů͕͘ϭϵϳϮͿ͘
^Ğ ƚƌĂƚĂ ĚĞ ƵŶ ƉƌŽĐĞƐŽ ŽƌĚĞŶĂĚŽ͕ ƚşƉŝĐŽ ĚĞ ŽƌŐĂŶŝƐŵŽƐ ƉůƵƌŝĐĞůƵůĂƌĞƐ͕ ƋƵĞ
ƉƌŽĚƵĐĞĞůŵĞŶŽƌĚĂŹŽƉŽƐŝďůĞĂůĂƐĐĠůƵůĂƐǇĂůŽƐƚĞũŝĚŽƐĐŝƌĐƵŶĚĂŶƚĞƐ͕ĂůĐŽŶƚƌĂƌŝŽĚĞ
ůŽƋƵĞƐƵĐĞĚĞƌşĂƐŝůĂŵƵĞƌƚĞƐĞƉƌŽĚƵũĞƌĂŵĞĚŝĂŶƚĞŶĞĐƌŽƐŝƐ͘>ĂĂƉŽƉƚŽƐŝƐĂĨĞĐƚĂƐſůŽ
ĂůĂƐĐĠůƵůĂƐĚĂŹĂĚĂƐ͕ŶŽŶĞĐĞƐĂƌŝĂŵĞŶƚĞĂƚŽĚĂƐůĂƐĚĞůƚĞũŝĚŽŽůĂǌŽŶĂ͕ƉŽƌůŽƋƵĞĞƐ
ƐƵŵĂŵĞŶƚĞĞƐƉĞĐşĨŝĐĂǇƐĞůĞĐƚŝǀĂ͘ĚĞŵĄƐ͕ĂƋƵşůĂĐĠůƵůĂũƵĞŐĂƵŶƉĂƉĞůĂĐƚŝǀŽĞŶƐƵ
ƉƌŽƉŝĂŵƵĞƌƚĞ͕;,ĞŶƐŽŶĞƚĂů͕͘ϮϬϬϭ͖dŝǁĂƌŝ͕ϮϬϭϮͿ͘
Ŷ ĐŽŶĚŝĐŝŽŶĞƐ ĨŝƐŝŽůſŐŝĐĂƐ͕ ĞŶ ĂĚƵůƚŽƐ͕ ůĂ ĂƉŽƉƚŽƐŝƐ Ǉ ůĂ ŵŝƚŽƐŝƐ ĐĞůƵůĂƌĞƐ ƐĞ
ĞŶĐƵĞŶƚƌĂŶĞŶĞƋƵŝůŝďƌŝŽ͕ƉĞƌŵŝƚŝĞŶĚŽĞƐƚŽƋƵĞĞůŶƷŵĞƌŽĚĞĐĠůƵůĂƐĞŶĞůŽƌŐĂŶŝƐŵŽ
ƐĞĂ ĐŽŶƐƚĂŶƚĞ͘ Ğ ŚĞĐŚŽ͕ ĐƵĂŶĚŽ ĞƐƚĞ ďĂůĂŶĐĞ ƐĞ ƚƌƵŶĐĂ͕ ĂƉĂƌĞĐĞŶ ŝŵƉŽƌƚĂŶƚĞƐ
ĚĞƐſƌĚĞŶĞƐ ĞŶ Ğů ŽƌŐĂŶŝƐŵŽ͕ ĐŽŵŽ ĞƐ Ğů ĐĂƐŽ ĚĞ ůĂƐ ĂĨĞĐĐŝŽŶĞƐ ŶĞŽƉůĄƐŝĐĂƐ Ž ĚĞ ůĂƐ
ĞŶĨĞƌŵĞĚĂĚĞƐĂƵƚŽŝŶŵƵŶĞƐ͕;'ĂůůƵǌǌŝĞƚĂů͕͘ϮϬϭϮͿ͘
ĚşĂ ĚĞ ŚŽǇ ĞǆŝƐƚĞ ƵŶ ĂŵƉůŝŽ ĐŽŶƐĞŶƐŽ ĞŶ ĚĞĨŝŶŝƌ ĚŽƐ ƚŝƉŽƐ ĚĞ ĂƉŽƉƚŽƐŝƐ
ĐůĂƌĂŵĞŶƚĞĚŝĨĞƌĞŶĐŝĂĚĂƐ͕ůĂŝŶƚƌşŶƐĞĐĂǇůĂĞǆƚƌşŶƐĞĐĂ͕ĞŶĨƵŶĐŝſŶĚĞůĂǀşĂĂƚƌĂǀĠƐĚĞ
ůĂ ĐƵĂů ƐĞ ƉƌŽĚƵĐĞ ƐƵ ĂĐƚŝǀĂĐŝſŶ͘ Ŷ ĂŵďŽƐ ĐĂƐŽƐ͕ ůĂƐ ĐĂƐƉĂƐĂƐ͕ ;ĐŝƐƚĞŝŶŝůͲĂƐƉĂƌƚĂƚŽ
ƉƌŽƚĞŝŶĂƐĂͿ͕ ũƵĞŐĂŶ ƵŶ ƉĂƉĞů ŵƵǇ ŝŵƉŽƌƚĂŶƚĞ͘ ĚŝĐŝŽŶĂůŵĞŶƚĞ͕ ĞǆŝƐƚĞ ƵŶ ƚĞƌĐĞƌ
ŵĞĐĂŶŝƐŵŽĚĞŝŶĚƵĐĐŝſŶĚĞůĂĂƉŽƉƚŽƐŝƐ͕ŵƵĐŚŽŵĞŶŽƐĐŽŶŽĐŝĚŽǇĞƐƚƵĚŝĂĚŽ͘^ĞƚƌĂƚĂ
ĚĞ ůĂ ŶĞĐƌŽƉƚŽƐŝƐ͕ ůĂ ĐƵĂů͕ ŚĂƐƚĂ ŚĂĐĞ ƉŽĐŽ ƚŝĞŵƉŽ͕ ƐĞ ƉĞŶƐĂďĂ ƋƵĞ ĞƌĂ ƚŽƚĂůŵĞŶƚĞ
ŝŶĚĞƉĞŶĚŝĞŶƚĞĚĞůĂƐĐĂƐƉĂƐĂƐ͕;<ŝŵĞƚĂů͕͘ϮϬϬϵͿ͘^ŝŶĞŵďĂƌŐŽ͕ĂĐƚƵĂůŵĞŶƚĞƉĂƌĞĐĞƐĞƌ
ƋƵĞůĂƐĐŝƚĂĚĂƐƉƌŽƚĞşŶĂƐƉŽĚƌşĂŶƉĂƌƚŝĐŝƉĂƌĞŶĂůŐƵŶŽƐĐĂƐŽƐĞŶůĂĞũĞĐƵĐŝſŶĚĞůĂƐǀşĂƐ
ůĞƚĂůĞƐĚĞƐĞŹĂůŝǌĂĐŝſŶ͕;<ƌŽĞŵĞƌĞƚĂů͕͘ϮϬϬϵͿ͘ZĞƐƉĞĐƚŽĂůĂŶĞĐƌŽƉƚŽƐŝƐŝŶĚĞƉĞŶĚŝĞŶƚĞ
ĚĞ ĐĂƐƉĂƐĂƐ͕ ƐĞ ŚĂ ŚŝƉŽƚŝǌĂĚŽ ƵŶ ƉĂƉĞů ŝŵƉŽƌƚĂŶƚĞ ƚĂŶƚŽ ƉĂƌĂ /&͕ ;ĞůĂǀĂůůĞĞ Ğƚ Ăů͕͘
ϮϬϭϭͿ͕ĐŽŵŽƉĂƌĂƌƉϭ͕;ƌĂƐĞƚĂů͕͘ϮϬϬϳͿ͘
>ĂǀşĂĞǆƚƌşŶƐĞĐĂƐĞĂĐƚŝǀĂĂƚƌĂǀĠƐĚĞƌĞĐĞƉƚŽƌĞƐĚĞŵƵĞƌƚĞ͘ŶĞůůĂŝŶƚĞƌǀŝĞŶĞŶ
Ϯϰ
ůĂĂƐƉĂƐĂϴĐŽŵŽĂĐƚŝǀĂĚŽƌĂǇůĂϯĐŽŵŽĞĨĞĐƚŽƌĂ͕;,ĞŶŐĂƌƚŶĞƌ͕ϮϬϬϬ͖EŽƵƌĂŝŶŝĞƚĂů͕͘
ϮϬϬϬͿ͘ WŽƌ ƐƵ ƉĂƌƚĞ͕ ĞŶ ůĂ ǀşĂ ŝŶƚƌşŶƐĞĐĂ͕ ůĂ ŵŝƚŽĐŽŶĚƌŝĂ ƚŝĞŶĞ ƵŶ ƉĂƉĞů ĨƵŶĚĂŵĞŶƚĂů͕
;'ŚŽďƌŝĂů Ğƚ Ăů͕͘ ϮϬϬϱͿ͘ Ğ ŚĞĐŚŽ͕ ĞŶ ůĂ ĂĐƚƵĂůŝĚĂĚ͕ ƐĞ ĐŽŶƐŝĚĞƌĂ ƋƵĞ ůĂ ĨƵŶĐŝſŶ ŵĄƐ
ŝŵƉŽƌƚĂŶƚĞĚĞůĂƐŵŝƚŽĐŽŶĚƌŝĂƐ͕ƚƌĂƐůĂĞŶĞƌŐĠƚŝĐĂ͕ĞƐƉƌĞĐŝƐĂŵĞŶƚĞĞƐƚĂ͕ůĂƌĞŐƵůĂĐŝſŶ
ĚĞůĂŵƵĞƌƚĞĐĞůƵůĂƌĂƉŽƉƚſƚŝĐĂ͘
>Ă ĐŝƚĂĚĂ ǀşĂ ĐŽŶƐƚŝƚƵǇĞ ƵŶ ƉƌŽĐĞƐŽ ďŝĞŶ ĐŽŶŽĐŝĚŽ ĞŶ ůĂ ĂĐƚƵĂůŝĚĂĚ͘ ^Ğ ŝŶŝĐŝĂ
ĐƵĂŶĚŽůĂŵŝƚŽĐŽŶĚƌŝĂĚĞƚĞĐƚĂĂůŐƷŶĞƐƚşŵƵůŽŝŶĚƵĐƚŽƌĚĞĂƉŽƉƚŽƐŝƐ͕ĐŽŵŽĞƐĞůĐĂƐŽ
ĚĞůĂƌĂĚŝĂĐŝſŶƵůƚƌĂǀŝŽůĞƚĂ͕ĚĞĂůŐƵŶŽƐƚŝƉŽƐĚĞƋƵŝŵŝŽƚĞƌĂƉŝĂ͕ĚĞůĂƐƐĞŹĂůĞƐĚĞĞƐƚƌĠƐ
ĐĞůƵůĂƌŽĚĞůĚĂŹŽĂůE͕;&ƵůĚĂĞƚĂů͕͘ϮϬϬϲ͖^ŝƚĂŝůŽĞƚĂů͕͘ϮϬϬϮ͖dĂŵƵƌĂĞƚĂů͕͘ϭϵϵϱͿ͘
ƐƚĞŚĞĐŚŽĐŽŶůůĞǀĂůĂĚŝƐŝƉĂĐŝſŶĚĞůƉŽƚĞŶĐŝĂůĚĞ ŵĞŵďƌĂŶĂŵŝƚŽĐŽŶĚƌŝĂů͕ůŽĐƵĂůƐĞ
ƚƌĂĚƵĐĞĞŶůĂĂĨĞĐĐŝſŶĚĞůĂŝŶƚĞŐƌŝĚĂĚĚĞůĂŵĞŵďƌĂŶĂĞǆƚĞƌŶĂŵŝƚŽĐŽŶĚƌŝĂů͕;ƌĞǀŝƐĂĚŽ
ĞŶ;dĂŝƚĞƚĂů͕͘ϮϬϭϬͿͿ͘ĐŽŶƐĞĐƵĞŶĐŝĂĚĞĞƐƚŽƐŚĞĐŚŽƐ͕ƐĞƉƌŽĚƵĐĞůĂĂĐƚŝǀĂĐŝſŶĚĞůĂƐ
ƉƌŽƚĞşŶĂƐƉƌŽĂƉŽƉƚſƚŝĐĂƐĚĞůĂĨĂŵŝůŝĂĚĞĐůͲϮ͕ĐŽŵŽĞƐĞůĐĂƐŽĚĞĂǆ͕;<ŝŵ͕ϮϬϬϱͿ͘
ĐŽŶƚŝŶƵĂĐŝſŶ͕ƐĞůůĞǀĂĂĐĂďŽůĂƉĞƌŵĞĂďŝůŝǌĂĐŝſŶĚĞůĂĐŝƚĂĚĂŵĞŵďƌĂŶĂǇůĂ
ĨŽƌŵĂĐŝſŶĚĞůWWdD͕ĐŽŶůĂĐŽŶƐŝŐƵŝĞŶƚĞůŝďĞƌĂĐŝſŶĚĞůŝƚŽĐƌŽŵŽĚĞƐĚĞĞůĞƐƉĂĐŝŽ
ŝŶƚĞƌŵĞŵďƌĂŶĂ͘ ƐƚĂ ŵŽůĠĐƵůĂ ƉƌŽĐĞĚĞ ĚĞ ůĂƐ ĐƌĞƐƚĂƐ ŵŝƚŽĐŽŶĚƌŝĂůĞƐ ĚŽŶĚĞ͕ ĞŶ
ĐŽŶĚŝĐŝŽŶĞƐĨŝƐŝŽůſŐŝĐĂƐ͕ƐĞĞŶĐƵĞŶƚƌĂĂůŵĂĐĞŶĂĚŽĞŶƐƵĨŽƌŵĂƐŽůƵďůĞƐŽďƌĞĞůϴϱйĚĞ
ƐƵ ĐŽŶĐĞŶƚƌĂĐŝſŶ ƚŽƚĂů͕ ;KĞƚƚŝŶŐŚĂƵƐ Ğƚ Ăů͕͘ ϮϬϭϮͿ͘ >Ă ůŝďĞƌĂĐŝſŶ ĚĞů ŝƚŽĐƌŽŵŽ ƉƌŽĚƵĐĞ͕ Ă ƐƵ ǀĞǌ͕ ůĂ ĂĐƚŝǀĂĐŝſŶ ĚĞ ůĂ ĐĂƐĐĂĚĂ ĚĞ ĐĂƐƉĂƐĂƐ͕ ĨŽƌŵĄŶĚŽƐĞ ĞŶƚŽŶĐĞƐ Ğů
ĂƉŽƉƚŽƐŽŵĂĞŶĞůĐŝƚŽƉůĂƐŵĂ͘
^ŝŵƵůƚĄŶĞĂŵĞŶƚĞĂůĂůŝďĞƌĂĐŝſŶĚĞůŝƚŽĐƌŽŵŽ͕ƚŝĞŶĞůƵŐĂƌƚĂŵďŝĠŶůĂĚĞ/&͕
;&ĂĐƚŽƌ/ŶĚƵĐƚŽƌĚĞůĂƉŽƉƚŽƐŝƐͿ͕ĞůĐƵĂůĞƐĞůĞŶĐĂƌŐĂĚŽĚĞƉƌŽĚƵĐŝƌůĂĐŽŶĚĞŶƐĂĐŝſŶ
ŶƵĐůĞĂƌǇůĂƌŽƚƵƌĂĚĞůĂĐƌŽŵĂƚŝŶĂ͕ĂŵďŽƐƉƌŽĐĞƐŽƐƚşƉŝĐŽƐĚĞůĂĂƉŽƉƚŽƐŝƐ͕;ŝŶŐĞƚĂů͕͘
ϮϬϭϮͿ͘
WŽƌ ŽƚƌŽ ůĂĚŽ͕ ůĂ ŵĞŵďƌĂŶĂ ĐĞůƵůĂƌ ƐĞ ĨƌĂŐŵĞŶƚĂ͕ ĨŽƌŵĂŶĚŽ ĐƵĞƌƉŽƐ ĂŝƐůĂĚŽƐ͕
ĞŶƵŶƉƌŽĐĞƐŽĐŽŶŽĐŝĚŽĐŽŵŽ͞ďĞďďůŝŶŐ͕͟ƋƵĞƉƌĞĐĞĚĞĂůĂĨƌĂŐŵĞŶƚĂĐŝſŶĚĞůEǇ͕
ƉŽƌƚĂŶƚŽ͕ĂůĐŽůĂƉƐŽŶƵĐůĞĂƌƚŽƚĂů͕;dŝǁĂƌŝ͕ϮϬϭϮͿ͘ůƉĂƐŽĨŝŶĂůƐĞƌĄůĂĨŽƌŵĂĐŝſŶĚĞůŽƐ
ůůĂŵĂĚŽƐ ĐƵĞƌƉŽƐ ĂƉŽƉƚſƚŝĐŽƐ͕ ƋƵĞ ĐŽŶƚŝĞŶĞŶ ĞůĞŵĞŶƚŽƐ ĚĞƚĞƌŝŽƌĂĚŽƐ͕ ƚĂŶƚŽ
ĐŝƚŽƐſůŝĐŽƐ ĐŽŵŽ ŶƵĐůĞĂƌĞƐ͘ >ŽƐ ĐŝƚĂĚŽƐ ĐƵĞƌƉŽƐ ƐĞƌĄŶ ĞůŝŵŝŶĂĚŽƐ Ă ĐŽŶƚŝŶƵĂĐŝſŶ
Ϯϱ
ŵĞĚŝĂŶƚĞ ĨĂŐŽĐŝƚŽƐŝƐ͕ ŐƌĂĐŝĂƐ Ă ůĂ ƚƌĂƐůŽĐĂĐŝſŶ Ăů ĞǆƚĞƌŝŽƌ ĚĞƐĚĞ ůĂ ĐĂƌĂ ŝŶƚĞƌŶĂ ĚĞ ůĂ
ŵĞŵďƌĂŶĂ ƉůĂƐŵĄƚŝĐĂ ĚĞ ůĂ ĨŽƐĨĂƚŝĚŝůƐĞƌŝŶĂ͕ ůĂ ĐƵĂů ĞƐ ƌĞĐŽŶŽĐŝĚĂ ƉŽƌ ůĂƐ ĐĠůƵůĂƐ
ĨĂŐŽĐşƚŝĐĂƐ͕ ĞǀŝƚĂŶĚŽ ĂƐş ĐƵĂůƋƵŝĞƌ ƉŽƐŝďůĞ ƉƌŽĐĞƐŽ ĚĞ ŝŶĨůĂŵĂĐŝſŶ ĐĞůƵůĂƌ͕ ;,ĞŶƐŽŶ Ğƚ
Ăů͕͘ϮϬϬϭͿ͘
WŽƌ ƚĂŶƚŽ͕ ĚĞ ƵŶ ŵŽĚŽ ĞƐƋƵĞŵĄƚŝĐŽ͕ ƉŽĚƌşĂŵŽƐ ƌĞƐƵŵŝƌ ůĂƐ ƉƌŝŶĐŝƉĂůĞƐ
ĐĂƌĂĐƚĞƌşƐƚŝĐĂƐďŝŽƋƵşŵŝĐĂƐĚĞůĂĂƉŽƉƚŽƐŝƐĂƐş͕;<ƌŽĞŵĞƌĞƚĂů͕͘ϮϬϬϵͿ͕
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ǆƉŽƐŝĐŝſŶĚĞĨŽƐĨĂƚŝĚŝůƐĞƌŝŶĂ͘
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ĐƚŝǀĂĐŝſŶĚĞƉƌŽƚĞşŶĂƐƉƌŽĂƉŽƉƚſƚŝĐĂƐĚĞůĂĨĂŵŝůŝĂĐůͲϮ͘
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ĐƚŝǀĂĐŝſŶĚĞůĂƐĐĂƐƉĂƐĂƐ͘
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&ŽƌŵĂĐŝſŶĚĞůWWdD͘
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ŝƐŝƉĂĐŝſŶĚĞůƉŽƚĞŶĐŝĂůĚĞŵĞŵďƌĂŶĂŵŝƚŽĐŽŶĚƌŝĂů͘
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/ŶĐƌĞŵĞŶƚŽƐĞŶůĂƉƌŽĚƵĐĐŝſŶĚĞZK͘
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ZŽƚƵƌĂĚĞůĂŵĞŵďƌĂŶĂƉůĂƐŵĄƚŝĐĂ͕;͞ďůĞďďŝŶŐ͟Ϳ͘
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&ƌĂŐŵĞŶƚĂĐŝſŶĚĞůE͘
Ϯϲ
&ŝŐƵƌĂ ϯ͘ WWdD͘ >ŽƐ ĐĂŶĂůĞƐ Ed Ǉ s͕ ƐŝƚƵĂĚŽƐ ĞŶ ůĂƐ ŵĞŵďƌĂŶĂƐ ŝŶƚĞƌŶĂ Ǉ ĞǆƚĞƌŶĂ
ŵŝƚŽĐŽŶĚƌŝĂůĞƐ ƌĞƐƉĞĐƚŝǀĂŵĞŶƚĞ͕ ŵĞĚŝĂŶ Ğů ƚƌĂŶƐƉŽƌƚĞ ƐĞůĞĐƚŝǀŽ ĚĞ ĐŝĞƌƚŽƐ ŵĞƚĂďŽůŝƚŽƐ͘ ^ŝŶ ĞŵďĂƌŐŽ͕
ĂŶƚĞĞƐƚşŵƵůŽƐĐŽŶĐƌĞƚŽƐ͕ĂƉĂƌƚŝƌĚĞĞƐƚŽƐĐĂŶĂůĞƐǇĐŽŶůĂƉĂƌƚŝĐŝƉĂĐŝſŶĂĚŝĐŝŽŶĂůĚĞŽƚƌĂƐƉƌŽƚĞşŶĂƐ͕ƐĞ
ĨŽƌŵĂĞůWWdD͘ŽŶƐĞĐƵĞŶƚĞŵĞŶƚĞ͕ƐĞƉƌŽĚƵĐĞĞůŝƚŶĞƌĐĂŵďŝŽŵĂƐŝǀŽĚĞůşƋƵŝĚŽƐǇŵĞƚĂďŽůŝƚŽƐĞŶƚƌĞĞů
ŝŶƚĞƌŝŽƌǇĞůĞǆƚĞƌŝŽƌŵŝƚŽĐŽŶĚƌŝĂůĞƐ͕ůŽĐƵĂůƉƌŽĚƵĐĞůĂůŝďĞƌĂĐŝſŶĚĞůŝƚŽĐƌŽŵŽ͕ĞŶƚƌĞŽƚƌŽƐĨĂĐƚŽƌĞƐǇ͕
ĞŶƷůƚŝŵŽƚĠƌŵŝŶŽ͕ůĂĂƉĂƌŝĐŝſŶĚĞůĞĚĞŵĂŵŝƚŽĐŽŶĚƌŝĂů͘
Ϯϳ
ĞĞŶƚƌĞůĂƐƉƌŽƚĞşŶĂƐŝŵƉůŝĐĂĚĂƐĞŶĞƐƚĞƉƌŽĐĞƐŽ͕ŵƵĐŚĂƐĚĞůĂƐĐƵĂůĞƐǇĂŚĂŶ
ƐŝĚŽ ŶŽŵďƌĂĚĂƐ Ăů ĞǆƉůŝĐĂƌ Ğů ŵĞĐĂŶŝƐŵŽ Ă ƚƌĂǀĠƐ ĚĞů ĐƵĂů ƐĞ ƉƌŽĚƵĐĞ ůĂ ĂƉŽƉƚŽƐŝƐ͕
ĚĞƐƚĂĐĂŶ͕ƐŽďƌĞƚŽĚŽ͕ĚŽƐŐƌĂŶĚĞƐĨĂŵŝůŝĂƐ͗ůĂƐĐĂƐƉĂƐĂƐǇůĂƐĐůͲϮ͘
>ĂƐ ĐĂƐƉĂƐĂƐ ĐŽŶƐƚŝƚƵǇĞŶ ƵŶ ŐƌƵƉŽ ĚĞ ŽŶĐĞ ƉƌŽƚĞşŶĂƐ͕ ĞŶƚƌĞ ůĂƐ ƋƵĞ
ĞŶĐŽŶƚƌĂŵŽƐ ĂůŐƵŶĂƐ ĐŽŶ ĨƵŶĐŝſŶ ŝŶŝĐŝĂĚŽƌĂ Ǉ ŽƚƌĂƐ ĐŽŶ ĞĨĞĐƚŽƌĂ͘ Ɛş͕ ůĂ ƉƌŝŵĞƌĂ ĚĞ
ĞƐƚĂƐƉƌŽƚĞşŶĂƐĞŶƐĞƌĂĐƚŝǀĂĚĂĞŶůĂĂƉŽƉƚŽƐŝƐĞƐůĂƉƌŽͲĂƐƉĂƐĂϵůĂĐƵĂů͕ĞŶƉƌĞƐĞŶĐŝĂ
ĚĞdW͕ƐĞĐŽŶǀŝĞƌƚĞĞŶůĂĂƐƉĂƐĂϵ͕;ŝŶŐĞƚĂů͕͘ϮϬϭϮͿ͘ƐƚĂƷůƚŝŵĂ͕ĂƐƵǀĞǌ͕ƵŶŝĚĂĂ
W&ϭĨŽƌŵĂĞůƉƌŽƚĞŽƐŽŵĂ͕;tĂƐŝůĞǁƐŬŝĞƚĂů͕͘ϮϬϬϵͿ͕ƋƵĞĞƐĞůĞŶĐĂƌŐĂĚŽĨŝŶĂůĚĞůĂ
ĂĐƚŝǀĂĐŝſŶĚĞůƌĞƐƚŽĚĞĐĂƐƉĂƐĂƐĞĨĞĐƚŽƌĂƐ͕ĐŽŵŽĞƐĞůĐĂƐŽĚĞůĂĂƐƉĂƐĂϯ͕;<ƌŽĞŵĞƌ
ĞƚĂů͕͘ϮϬϬϬͿ͘
>ŽƐŽƌŐĂŶŝƐŵŽƐĐƵĞŶƚĂŶĐŽŶŝŶŚŝďŝĚŽƌĞƐĚĞůĂƐĐĂƐƉĂƐĂƐ͕;/WƐ͕ƉŽƌŝŶŚŝďŝĚŽƌĞƐ
ĚĞ ůĂƐ ƉƌŽƚĞşŶĂƐ ĚĞ ůĂ ĂƉŽƉƚŽƐŝƐͿ͕ ƉŽƌ ůŽ ƋƵĞ͕ ĂŶƚĞ ƵŶ ĞƐƚşŵƵůŽ ĂƉŽƉƚſƚŝĐŽ͕ ĞƐƚĂƐ
ƉƌŽƚĞşŶĂƐĚĞďĞƌĄŶĚĞƐĞƌŝŶĂĐƚŝǀĂĚĂƐ͕ƉĂƌĂƋƵĞůĂƐĐĂƐƉĂƐĂƐƉƵĞĚĂŶƌĞĂůŝǌĂƌƐƵƚĂƌĞĂ͘
WĂƌĂ ĞůůŽ͕ ƐŝŵƵůƚĄŶĞĂŵĞŶƚĞ Ă ůĂ ůŝďĞƌĂĐŝſŶ ĚĞ ŝƚŽĐƌŽŵŽ ͕ ƐĞ ƉƌŽĚƵĐĞ ůĂ ĚĞ ŽƚƌĂƐ
ƉƌŽƚĞşŶĂƐ ĐĂƉĂĐĞƐ ĚĞ ŝŶŚŝďŝƌ Ă ůĂƐ /WƐ͘ ^Ğ ƚƌĂƚĂ ĚĞ ^D͕ ;^ĞŐƵŶĚŽ ĐƚŝǀĂĚŽƌ ĚĞ
ĂƐƉĂƐĂƐĞƌŝǀĂĚŽĚĞůĂDŝƚŽĐŽŶĚƌŝĂͿ͕ǇĚĞ/>K͕;WƌŽƚĞşŶĂŝƌĞĐƚĂĚĞhŶŝſŶĂůŽƐ
/ŶŚŝďŝĚŽƌĞƐĚĞůĂƐĂƐƉĂƐĂƐ͕ĚĞďĂũŽWƵŶƚŽ/ƐŽĞůĠĐƚƌŝĐŽͿ͕;DƵŶŽǌͲWŝŶĞĚŽ͕ϮϬϭϮͿ͘
ŽŵŽŝŶĚŝĐĄďĂŵŽƐĂŶƚĞƌŝŽƌŵĞŶƚĞ͕ĂƉĂƌƚĞĚĞůĂƐĐĂƐƉĂƐĂƐŚĂǇŽƚƌĂƐƉƌŽƚĞşŶĂƐ
ƐŝŶ ůĂƐ ĐƵĂůĞƐ ůĂ ĂƉŽƉƚŽƐŝƐ ŶŽ ƐĞ ƉƵĞĚĞ ƉƌŽĚƵĐŝƌ͘ ^Ğ ƚƌĂƚĂ ĚĞ ůŽƐ ĐŽŵƉŽŶĞŶƚĞƐ ĚĞ ůĂ
ĨĂŵŝůŝĂ ĐůͲϮ͕ ůĂ ĐƵĂů ĞŶŐůŽďĂŶ Ă ĚŝĞĐŝŶƵĞǀĞ ŵŝĞŵďƌŽƐ͕ ĐůĂƐŝĨŝĐĂĚŽƐ ĞŶ ůŽƐ ƐŝŐƵŝĞŶƚĞƐ
ŐƌƵƉŽƐ͕
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WƌŽƚĞşŶĂƐĐŽŶĐƵĂƚƌŽĚŽŵŝŶŝŽƐ,͕;ƚĂŵďŝĠŶůůĂŵĂĚĂƐŵƵůƚŝĚŽŵŝŶŝŽͿ͕

WƌŽƉĂŽƉƚſƚŝĐĂƐ͗ Ăǆ͕ ĂŬ Ǉ ŽŬͬDƚĚ͕ ;DĂƌƚŝŶŽƵ Ğƚ Ăů͕͘ ϮϬϭϭͿ͘ ^ŽŶ
ŵĞĚŝĂĚŽƌĂƐ ĚĞ ůĂ ƉĞƌŵĞĂďŝůŝǌĂĐŝſŶ ĚĞ ůĂ ŵĞŵďƌĂŶĂ ĞǆƚĞƌŶĂ
ŵŝƚŽĐŽŶĚƌŝĂů͕ĂƚƌĂǀĠƐĚĞůĂĂƉĞƌƚƵƌĂĚĞůWWdD͕;WŽƌŽĚĞWĞƌŵĞĂďŝůŝĚĂĚ
ǇdƌĂŶƐŝĐŝſŶDŝƚŽĐŽŶĚƌŝĂůͿ͘

ŶƚŝĂƉŽƉƚſƚŝĐĂƐ͗ ĐůͲϮ͕ ĐůͲǆ>͕ ĐůͲǁ͕ DĐůͲϭ Ǉ ϭͬĨůͲϭ͕ ;DĂƌƚŝŶŽƵĞƚ Ăů͕͘
ϮϬϭϭͿ͘ ^ŽŶ ŝŶŚŝďŝĚŽƌĂƐ ĚĞ ůĂ ĨŽƌŵĂĐŝſŶ ĚĞů WWdD͕ ;KĞƚƚŝŶŐŚĂƵƐ Ğƚ Ăů͕͘
ϮϬϭϮͿ͘
Ϯϴ
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WƌŽƚĞşŶĂƐ ĐŽŶ ƚƌĞƐ ĚŽŵŝŶŝŽƐ ,͘ dŽĚŽƐ ƐƵƐ ŵŝĞŵďƌŽƐ ƐŽŶ ƉƌŽĂƉŽƉƚſƚŝĐŽƐ͕
ĂƵŶƋƵĞŶŽƐŽŶĐĂƉĂĐĞƐĚĞŝŶŝĐŝĂƌůĂĂƉŽƉƚŽƐŝƐƉĞƌƐĞ͕ƉŽƌůŽƋƵĞĂĐƚƷĂŶĐŽŵŽ
ĂĐƚŝǀĂĚŽƌĞƐĚĞůŽƐŵƵůƚŝĚŽŵŝŶŝŽ͕;tŝůĨůŝŶŐĞƚĂů͕͘ϮϬϭϮͿ͘
>ĂƉĂƌƚŝĐŝƉĂĐŝſŶĚĞĂǆĞŶůĂĂƉŽƉƚŽƐŝƐĞƐŝŵƉƌĞƐĐŝŶĚŝďůĞ͕ǇĂƋƵĞ͕ĐƵĂŶĚŽĞƐƚĂ
ƉƌŽƚĞşŶĂ Ž ĂŬ ĞƐƚĄŶ ŝŶŚŝďŝĚĂƐ͕ ůĂƐ ĐĠůƵůĂƐ͕ ĞŶ ƉƌĞƐĞŶĐŝĂ ĚĞ ĞƐƚşŵƵůŽƐ ĂƉŽƉƚſƚŝĐŽƐ
ĞƐƉĞĐşĨŝĐŽƐ͕ƐŽŶŝŶĐĂƉĂĐĞƐĚĞůůĞǀĂƌĂĐĂďŽĞůƉƌŽĐĞƐŽ͕;tĞŝĞƚĂů͕͘ϮϬϬϭͿ͘^ĞƚƌĂƚĂĚĞ
ƵŶĂ ƉƌŽƚĞşŶĂ ĐŝƚŽƉůĂƐŵĄƚŝĐĂ ƋƵĞ ŵŝŐƌĂ Ă ůĂ ŵŝƚŽĐŽŶĚƌŝĂ ĐƵĂŶĚŽ ůĂ ĐĠůƵůĂ ĚĞƚĞĐƚĂ ƵŶ
ŝŵƉƵůƐŽĂƉŽƉƚſƚŝĐŽ͘hŶĂǀĞǌĂůůş͕ƐĞŝŶƐĞƌƚĂĞŶůĂŵĞŵďƌĂŶĂĞǆƚĞƌŶĂĚĞĞƐƚĞŽƌŐĄŶƵůŽ͕
ĚŽŶĚĞ ƐƵĨƌĞ ƵŶĂ ŽůŝŐŽŵĞƌŝǌĂĐŝſŶ͘ ^Ƶ ĂĐƚŝǀĂĐŝſŶ ĞƐ ůĂ ĐŽŶƐĞĐƵĞŶĐŝĂ ĚĞ ƵŶ ƉƌŽĐĞƐŽ
ĂůƚĂŵĞŶƚĞƌĞŐƵůĂĚŽǇĐŽŶŵƵĐŚŽƐƉĂƐŽƐ͕;DĂƌƚŝŶŽƵĞƚĂů͕͘ϮϬϬϲͿ͘
ƵĂŶĚŽĞůĞƐƚşŵƵůŽĚĞĂƉŽƉƚŽƐŝƐĐĞƐĂ͕ůĂƉƌŽƚĞşŶĂĂŶƚŝĂƉŽƉƚſƚŝĐĂĐůͲϮďůŽƋƵĞĂ
ůĂƐĂůŝĚĂĚĞůŝƚŽĐƌŽŵŽ͕ĂůƵŶŝƌƐĞĂůĂŵĞŵďƌĂŶĂĞǆƚĞƌŶĂŵŝƚŽĐŽŶĚƌŝĂůĨŽƌŵĂŶĚŽƵŶĂ
ƐĞƌŝĞĚĞŚĞƚĞƌŽĚşŵĞƌŽƐĐŽŶĂǆ͘'ƌĂĐŝĂƐĂĞƐƚŽ͕ůĂĂĐĐŝſŶƉƌŽĂƉŽƉƚſƚŝĐĂĚĞĂǆƋƵĞĚĂ
ŶĞƵƚƌĂůŝǌĂĚĂ͘WŽƌƚĂŶƚŽ͕ĞůďĂůĂŶĐĞĞŶƚƌĞůŽƐŶŝǀĞůĞƐĚĞĂǆǇĐůͲϮĞƐĐƌşƚŝĐŽƉĂƌĂƋƵĞůĂ
ĐĠůƵůĂĚĞĐŝĚĂƐŝĐŽŶƚŝŶƷĂǀŝǀŝĞŶĚŽŽƐŝ͕ƉŽƌĞůĐŽŶƚƌĂƌŝŽ͕ĞŶƚƌĂĞŶĂƉŽƉƚŽƐŝƐ͕;>ŝĞƚĂů͕͘
ϮϬϭϮͿ͘
Ϯϵ
&ŝŐƵƌĂ ϰ͘ >Ă ĂƉŽƉƚŽƐŝƐ͘ ŶƚĞ ƵŶ ĞƐƚşŵƵůŽ ĂƉŽƉƚſƚŝƚĐŽ͕ ůĂ ĨŽƐĨĂƚŝĚŝůƐĞƌŝŶĂ ƐĞ ƚƌĂƐůŽĐĂ Ă ůĂ ĐĂƌĂ
ĞǆƚĞƌŝŽƌ ĚĞ ůĂ ŵĞŵďƌĂŶĂŵŝƚŽĐŽŶĚƌŝĂů ĞǆƚĞƌŶĂ͘ ^ŝŵƵůƚĄŶĞĂŵĞŶƚĞ͕ ĂǆŵŝŐƌĂ Ă ůĂĐŝƚĂĚĂ ŵĞŵďƌĂŶĂ͘
ĐŽŶƚŝŶƵĂĐŝſŶ͕ ƐĞ ƉƌŽĚƵĐĞ ůĂ ĂĐƚŝǀĂĐŝſŶ ĚĞ ůĂƐ ĐĂƐƉĂƐĂƐ ŝŶŝĐŝĂĚŽƌĂƐ͕ ĐŽŶ ůĂ ĐŽŶƐŝŐƵŝĞŶƚĞ ĨŽƌŵĂĐŝſŶ ĚĞů
WWdDǇůĂůŝďĞƌĂĐŝſŶĂůĞƐƉĂĐŝŽĞǆƚƌĂŵŝƚŽĐŽŶĚƌŝĂůĚĞĚŝǀĞƌƐŽƐĨĂĐƚŽƌĞƐƉƌŽĂƉŽƉƚſƚŝĐŽƐ͕ĐŽŵŽĞƐĞůĐĂƐŽ
ĚĞů ĐŝƚŽĐƌŽŵŽ ͕ ůŽƐ ĐƵĂůĞƐ͕ Ă ƐƵ ǀĞǌ͕ ŝŶĚƵĐĞŶ ůĂ ĂĐƚŝǀĂĐŝſŶ ĚĞ ůĂƐ ĐĂƐƉĂƐĂƐ ĞĨĞĐƚŽƌĂƐ͘ dŽĚŽƐ ĞƐƚŽƐ
ƉƌŽĐĞƐŽƐ ƚŝĞŶĞŶ ĐŽŵŽ ĐŽŶƐĞĐƵĞŶĐŝĂ ůĂ ĨŽƌŵĂĐŝſŶ ĚĞů ĂƉŽƉƚŽƐŽŵĂ͘ ƉĂƌƚŝƌ ĚĞ ĞƐƚĞ ƉƵŶƚŽ͕ Ğů ŶƷĐůĞŽ
ĐĞůƵůĂƌ ƐĞ ĐŽŶĚĞŶƐĂ͕ ĂƉĂƌĞĐĞ Ğů ĐŽŶŽĐŝĚŽ ͞ďůĞďďŝŶŐ͟ Ǉ͕ ĨŝŶĂůŵĞŶƚĞ͕ ƐĞ ƉƌŽĚƵĐĞ ůĂ ĚĞŐƌĂĚĂĐŝſŶ ĚĞů
ŵĂƚĞƌŝĂůĐĞůƵůĂƌŐƌĂĐŝĂƐĂůŽƐůůĂŵĂĚŽƐĐƵĞƌƉŽƐĂƉŽƉƚſƚŝĐŽƐ͕ĐŽŶĂƵƐĞŶĐŝĂĚĞŝŶĨůĂŵĂĐŝſŶ͘
>ĂĞǆŝƐƚĞŶĐŝĂĚĞƵŶŶĞǆŽĞŶƚƌĞůĂĂƉŽƉƚŽƐŝƐǇůŽƐĚŝĨĞƌĞŶƚĞƐĐŽŵƉŽŶĞŶƚĞƐĚĞůĂ
ĚŝŶĄŵŝĐĂ ŵŝƚŽĐŽŶĚƌŝĂů ƐĞ ĞŶĐƵĞŶƚƌĂ ĂŵƉůŝĂŵĞŶƚĞ ĚĞŵŽƐƚƌĂĚĂ ĞŶ ůĂ ďŝďůŝŽŐƌĂĨşĂ͘ WŽƌ
ĞũĞŵƉůŽ͕ ƐĂďĞŵŽƐ ƋƵĞ͕ ĚƵƌĂŶƚĞ Ğů ƉƌŽĐĞƐŽ ĚĞ ĂƉŽƉƚŽƐŝƐ͕ ůĂƐ ŵŝƚŽĐŽŶĚƌŝĂƐ
ĨƌĂŐŵĞŶƚĂĚĂƐƐŽŶƐĞŶƐŝďůĞƐĂůĂŝŶƐĞƌĐŝſŶĚĞĂǆĞŶůĂŵĞŵďƌĂŶĂĞǆƚĞƌŶĂ͘ƐƚĞŚĞĐŚŽ
ƉƵĞĚĞƐĞƌƐƵƉƌŝŵŝĚŽƉŽƌůĂĨƵƐŝſŶŵŝƚŽĐŽŶĚƌŝĂů͕;WĂůŵĞƌĞƚĂů͕͘ϮϬϭϭͿ͘
^ŝŶ ĞŵďĂƌŐŽ͕ ůĂ ĞŶǀĞƌŐĂĚƵƌĂ ĚĞ ůĂ ƌĞůĂĐŝſŶ ĞŶƚƌĞ ůĂ ĂƉŽƉƚŽƐŝƐ Ǉ ůĂ ĨŝƐŝſŶ
ŵŝƚŽĐŽŶĚƌŝĂů ĞƐ ƵŶ ĂƐƵŶƚŽ ƋƵĞ ƉƌŽĚƵĐĞ ďĂƐƚĂŶƚĞ ƉŽůĠŵŝĐĂ ĞŶƚƌĞ ůĂ ĐŽŵƵŶŝĚĂĚ
ĐŝĞŶƚşĨŝĐĂ͘ WŽĚĞŵŽƐ ĞũĞŵƉůŝĨŝĐĂƌ ůĂ ĐŝƚĂĚĂ ĐŽŶƚƌŽǀĞƌƐŝĂ ĞǆƉŽŶŝĞŶĚŽ ĚŽƐ ĞƐƚƵĚŝŽƐ
ƌĞĂůŝǌĂĚŽƐĞŶƌĂƚŽŶĞƐĞŶůŽƐƋƵĞƌƉϭƐĞĞŶĐŽŶƚƌĂďĂƐŝůĞŶĐŝĂĚŽ͘ŶƵŶŽĚĞĞůůŽƐ͕ĞŶĞů
ƋƵĞƚƌĂďĂũĂƌŽŶĐŽŶĨŝďƌŽďůĂƐƚŽƐĞŵďƌŝŽŶĂƌŝŽƐŶŽŝŶŵŽƌƚĂůŝǌĂĚŽƐ͕ŶŽŽďƐĞƌǀĂƌŽŶŶŝŶŐƷŶ
ƌĞƚƌĂƐŽĞŶůĂĂƉŽƉƚŽƐŝƐ͕;tĂŬĂďĂǇĂƐŚŝĞƚĂů͕͘ϮϬϬϵͿ͘^ŝŶĞŵďĂƌŐŽ͕ĞŶĞůŽƚƌŽ͕ĞŶĞůƋƵĞ
ƵƐĂƌŽŶ Ğů ŵŝƐŵŽ ŵŽĚĞůŽ ĂƵŶƋƵĞ ĞŶ ĞƐƚĞ ĐĂƐŽ ůŽƐ ĨŝďƌŽďůĂƐƚŽƐ Ɛş ƋƵĞ ĞƐƚĂďĂŶ
ŝŶŵŽƌƚĂůŝǌĂĚŽƐ͕ƐşƋƵĞĐŽŶƐƚĂƚĂƌŽŶůĂĂƵƐĞŶĐŝĂĚĞĂƉŽƉƚŽƐŝƐ͕ŽďƐĞƌǀĂŶĚŽƚĂŵďŝĠŶƋƵĞ
ůĂĂďůĂĐŝſŶĐŽŵƉůĞƚĂĚĞůĂĐŝƚĂĚĂƉƌŽƚĞşŶĂŶŽďůŽƋƵĞſůĂĨƌĂŐŵĞŶƚĂĐŝſŶŵŝƚŽĐŽŶĚƌŝĂů͕
ĂƵŶƋƵĞƐşƋƵĞůĂƌĞƚƌĂƐſĐŽŶƐŝĚĞƌĂďůĞŵĞŶƚĞ͕ƚĂůǀĞǌĂƚƌĂǀĠƐĚĞƵŶƉŽƐŝďůĞŵĞĐĂŶŝƐŵŽ
ĐŽŵƉĞŶƐĂƚŽƌŝŽ͕;/ƐŚŝŚĂƌĂĞƚĂů͕͘ϮϬϬϵͿ͘ĚĞŵĄƐ͕ĂƉŽǇĂŶĚŽĞůƐĞŐƵŶĚŽĚĞůŽƐƚƌĂďĂũŽƐ͕
ĞƐ ĐŽŶŽĐŝĚŽ Ğů ŚĞĐŚŽ ĚĞ ƋƵĞ ůĂ ƚƌĂƐůŽĐĂĐŝſŶ ĚĞ Ăǆ Ă ůĂ ŵŝƚŽĐŽŶĚƌŝĂ ĚƵƌĂŶƚĞ ůĂ
ĂƉŽƉƚŽƐŝƐĞƐĚĞƉĞŶĚŝĞŶƚĞĚĞƌƉϭǇĨĂĐŝůŝƚĂĚĂƉŽƌůĂĐĂƌĚŝŽůŝƉŝŶĂ͕;KĞƚƚŝŶŐŚĂƵƐĞƚĂů͕͘
ϮϬϭϮͿ͘
WŽƌ ŽƚƌŽ ůĂĚŽ͕ ƵƐĂŶĚŽ Ğů ŵƵƚĂŶƚĞ ĚŽŵŝŶĂŶƚĞ ŶĞŐĂƚŝǀŽ ĚĞ ƌƉϭ͕ <ϯϴ͕ ŚĂ
ƋƵĞĚĂĚŽĚĞŵŽƐƚƌĂĚŽƋƵĞůĂĨƌĂŐŵĞŶƚĂĐŝſŶƋƵĞƐĞƉƌŽĚƵĐĞĞŶůŽƐƉĂƐŽƐŝŶŝĐŝĂůĞƐĚĞůĂ
ĂƉŽƉƚŽƐŝƐ ƉƵĞĚĞ ƐĞƌ ŝŶŚŝďŝĚĂ ŵĞĚŝĂŶƚĞ ůĂ ƐŽďƌĞĞǆƉƌĞƐŝſŶ ĚĞ <ϯϴ͕ ůŽ ĐƵĂů ĐŽŶůůĞǀĂ
ƚĂŵďŝĠŶƵŶĚĞƐĐĞŶƐŽĞŶůĂůŝďĞƌĂĐŝſŶĚĞŝƚŽĐƌŽŵŽ͕;&ƌĂŶŬĞƚĂů͕͘ϮϬϬϭͿ͘ĚĞŵĄƐ͕ůĂ
ϯϬ
ĞǆƉƌĞƐŝſŶĚĞ<ϯϴƉƵĞĚĞĐŽŶƚƌĂƌƌĞƐƚĂƌůĂƌĞŵŽĚĞůĂĐŝſŶĚĞůĂƐĐƌĞƐƚĂƐŵŝƚŽĐŽŶĚƌŝĂůĞƐ
ŝŶĚƵĐŝĚĂ ƉŽƌ Ăů ƐŽďƌĞĞǆƉƌĞƐŝſŶ ĚĞ ůĂ ƉƌŽƚĞşŶĂ ƉƌŽĂƉŽƉƚſƚŝĐĂ ŝŬ͕ ƉĞƌƚĞŶĞĐŝĞŶƚĞ Ă ůĂ
ĨĂŵŝůŝĂĚĞĐůϮ͕;'ĞƌŵĂŝŶĞƚĂů͕͘ϮϬϬϱͿ͘
ŽŶƚŝŶƵĂŶĚŽ ĐŽŶ ŵŽĚĞůŽƐ ĞŶ ůŽƐ ƋƵĞ ƌƉϭ ĞƐƚĄ ĂĨĞĐƚĂĚŽ͕ ŚĂǇ ĞƐƚƵĚŝŽƐ ƋƵĞ
ĚĞŵƵĞƐƚƌĂŶƋƵĞůĂƐŶĞƵƌŽŶĂƐƋƵĞĐĂƌĞĐĞŶĚĞƌƉϭĨƵŶĐŝŽŶĂůĚĞƵŶŵŽĚŽƚƌĂŶƐŝƚŽƌŝŽ͕
ĚĞƐĂƌƌŽůůĂŶ ƵŶ ĨĞŶŽƚŝƉŽ ŵŝƚŽĐŽŶĚƌŝĂů ĞůŽŶŐĂĚŽ Ǉ ŵƵĞƐƚƌĂŶ ƌĞƐŝƐƚĞŶĐŝĂ Ă ǀĂƌŝŽƐ
ĞƐƚşŵƵůŽƐ ƉƌŽĂƉŽƉƚſƚŝĐŽƐ͕ ĐŽŵŽ ĞƐ Ğů ĐĂƐŽ ĚĞ ůĂ ĞƐƚĂƵƌŽƐƉŽƌŝŶĂ͕ ;ŽƐƚĂ Ğƚ Ăů͕͘ ϮϬϭϬ͖
DĞƵĞƌĞƚĂů͕͘ϮϬϬϳ͖zŽƵŶŐĞƚĂů͕͘ϮϬϭϬͿ͖ůĂƌŽƚĞŶŽŶĂ͕;YŝĞƚĂů͕͘ϮϬϭϮͿ͖ĞůDWWн͕;DĞƵĞƌ
Ğƚ Ăů͕͘ ϮϬϬϳͿ͖ Ğů ƉĠƉƚŝĚŽ ɴ ĂŵŝůŽŝĚĞ ;ɴͿ͕ ;DĂŶĐǌĂŬ Ğƚ Ăů͕͘ ϮϬϭϭͿ͖ Ğů ſǆŝĚŽ ŶşƚƌŝĐŽ͕
;ĂƌƐŽƵŵ Ğƚ Ăů͕͘ ϮϬϬϲ͖ zƵĂŶ Ğƚ Ăů͕͘ ϮϬϬϳͿ͖ Ğů ƉĞƌſǆŝĚŽ ĚĞ ŚŝĚƌſŐĞŶŽ͕ ;ŚĞƵŶŐ Ğƚ Ăů͕͘
ϮϬϬϳ͖:ĂŚĂŶŝͲƐůĞƚĂů͕͘ϮϬϬϳͿ͖ǇůĂŵĞƚĂŶĨĞƚĂŶŝŵĂ͕;dŝĂŶĞƚĂů͕͘ϮϬϬϵͿ͘
dĂŵďŝĠŶůĂƐŵŽĚŝĨŝĐĂĐŝŽŶĞƐƉŽƐƚƌĂŶƐĐƌŝƉĐŝŽŶĂůĞƐƋƵĞƐƵĨƌĞƌƉϭƉĂƌĞĐĞŶũƵŐĂƌ
ƵŶƉĂƉĞůĞŶůĂƌĞůĂĐŝſŶĞŶƚƌĞůĂĨŝƐŝſŶŵŝƚŽĐŽŶĚƌŝĂůǇůĂĂƉŽƉƚŽƐŝƐ͘Ɛş͕ůĂŝŶŚŝďŝĐŝſŶĚĞůĂ
ĐĂůĐŝŶĞƵƌŝŶĂ͕ ůĂ ĐƵĂů ĨŽƐĨŽƌŝůĂ Ă ƌƉϭ ĞŶ ^Ğƌϲϯϳ͕ ƉƌĞǀŝĞŶĞ ůĂ ŵŝŐƌĂĐŝſŶ ĚĞ ƌƉϭ Ă ůĂ
ŵŝƚŽĐŽŶĚƌŝĂ͕ ƉƌŽĚƵĐŝĞŶĚŽ ĞƐƚĞ ŚĞĐŚŽ͕ Ă ƐƵ ǀĞǌ͕ ůĂ ŝŶŚŝďŝĐŝſŶ ĚĞ ůĂ ůŝďĞƌĂĐŝſŶ ĚĞ
ŝƚŽĐƌŽŵŽ ͕ ;ĞƌĞŐŚĞƚƚŝ Ğƚ Ăů͕͘ ϮϬϬϴͿ͘ W<͕ ŽƚƌĂ ƉƌŽƚĞşŶĂ ƋƵĞ ƚĂŵďŝĠŶ ĂĐƚƷĂ
ĨŽƐĨŽƌŝůĂŶĚŽĂƌƉϭĞŶĞůŵŝƐŵŽƐƵďƐƚƌĂƚŽ͕ƉƌŽĚƵĐĞƚĂŵďŝĠŶůĂŝŶŚŝďŝĐŝſŶĚĞůĂĨŝƐŝſŶ
ĚĞ ƵŶ ŵŽĚŽ ƐŝŵŝůĂƌ͕ ĂƐş ĐŽŵŽ ƵŶ ĂƵŵĞŶƚŽ ĚĞ ůĂ ƌĞƐŝƐƚĞŶĐŝĂ Ă ůŽƐ ĞƐƚşŵƵůŽƐ
ƉƌŽĂƉŽƉƚſƚŝĐŽƐ͕;ƌŝďďƐĞƚĂů͕͘ϮϬϬϳͿ͘
WŽƌ ƷůƚŝŵŽ ĚĞŶƚƌŽ ĚĞů ĞƐƚƵĚŝŽ ĚĞ ůĂ ƌĞůĂĐŝſŶ ĞŶƚƌĞ ƌƉϭ Ǉ ůĂ ĂƉŽƉƚŽƐŝƐ͕ ĞƐ
ĐŽŶŽĐŝĚŽĞůŚĞĐŚŽĚĞƋƵĞ͕ĞŶůĂĨŽƌŵĂĐŝſŶĚĞůŽƐůůĂŵĂĚŽƐƐŝƚŝŽƐĚĞŚĞŵŝĨƵƐŝſŶ͕ĞƐƚĄŶ
ĞŶǀƵĞůƚŽƐ ƚĂŶƚŽ ƌƉϭ ĐŽŵŽ Ăǆ͘ ^Ğ ƚƌĂƚĂ ĚĞ ůƵŐĂƌĞƐ ĚŽŶĚĞ ƐĞ ƉŽŶĞŶ ĞŶ ĐŽŶƚĂĐƚŽ
ĚŝƌĞĐƚŽ ůĂƐ ŵĞŵďƌĂŶĂƐ ŝŶƚĞƌŶĂ Ǉ ĞǆƚĞƌŶĂ ĚĞ ůĂƐ ŵŝƚŽĐŽŶĚƌŝĂƐ͕ ƉƌŽĚƵĐŝĠŶĚŽƐĞ ĂƐş Ğů
ŝŶƚĞƌĐĂŵďŝŽĚĞůşƉŝĚŽƐĚĞůĂƐĐŝƚĂĚĂƐŵĞŵďƌĂŶĂƐ͘ƐƚĞŚĞĐŚŽƉƌŽƉŝĐŝĂƋƵĞƐĞƉƌŽĚƵǌĐĂ
ůĂŝŶƐĞƌĐŝſŶǇŽůŝŐŽŵĞƌŝǌĂĐŝſŶĚĞůĂƉƌŽƚĞşŶĂĂǆĞŶůĂŵĞŵďƌĂŶĂŵŝƚŽĐŽŶĚƌŝĂůĞǆƚĞƌŶĂ͕
;DŽŶƚĞƐƐƵŝƚĞƚĂů͕͘ϮϬϭϬͿ͘ŶŽƚƌŽƚƌĂďĂũŽƌĞĂůŝǌĂĚŽĞŶŶĞƵƌŽŶĂƐ͕ƐĞŚĂŽďƐĞƌǀĂĚŽƋƵĞ͕
ĐƵĂŶĚŽĞƐƚĞƉƌŽĐĞƐŽĞƐŝŶĚƵĐŝĚŽƉŽƌĞůĚŽŶĂŶƚĞĚĞſǆŝĚŽŶşƚƌŝĐŽ͕ůĂŽůŝŐŽŵĞƌŝǌĂĐŝſŶĚĞ
Ăǆ ĞŶ ůĂ ŵĞŵďƌĂŶĂ ŵŝƚŽĐŽŶĚƌŝĂů ĐŽŶƚŝŶƷĂ ƐŝĞŶĚŽ ĚĞƉĞŶĚŝĞŶƚĞ ĚĞ ƌƉϭ͕ ƉĞƌŽ
ŝŶĚĞƉĞŶĚŝĞŶƚĞĚĞůĂƐĐĂƐƉĂƐĂƐ͕ǇĂƋƵĞŶŽƐĞƉƌŽĚƵĐĞůĂĂĐƚŝǀĂĐŝſŶĚĞůĂƐŵŝƐŵĂƐ͕;zƵĂŶ
ĞƚĂů͕͘ϮϬϬϳͿ͘
ϯϭ
ů ĞƐƚƵĚŝŽ ĚĞ &ŝƐϭ ƉƵĞĚĞ ƚĂŵďŝĠŶ ĂƌƌŽũĂƌ ůƵǌ ƐŽďƌĞ ĞƐƚĞ ĂƐƵŶƚŽ͘ Ɛş͕ ƉŽƌ
ĞũĞŵƉůŽ͕ ƐĂďĞŵŽƐ ƋƵĞ ůĂ ƐŽďƌĞĞǆƉƌĞƐŝſŶ ĚĞ ĞƐƚĂ ƉƌŽƚĞşŶĂ ŝŶĚƵĐĞ ĨƌĂŐŵĞŶƚĂĐŝſŶ
ŵŝƚŽĐŽŶĚƌŝĂů Ǉ ĂƉŽƉƚŽƐŝƐ͕ ;WĂůŵĞƌ Ğƚ Ăů͕͘ ϮϬϭϭͿ͕ ŵŝĞŶƚƌĂƐ ƋƵĞ͕ ƐƵ ƐŝůĞŶĐŝĂŵŝĞŶƚŽ͕ Ăů
ŝŐƵĂů ƋƵĞ Ğů ĚĞ KWϭ͕ ƉƌŽƚĞŐĞ Ă ůĂƐ ĐĠůƵůĂƐ ĚĞ ĞƐƚĞ ƚŝƉŽ ĚĞ ŵƵĞƌƚĞ ĐĞůƵůĂƌ͕
ŝŶĚĞƉĞŶĚŝĞŶƚĞŵĞŶƚĞĚĞůĂĨƌĂŐŵĞŶƚĂĐŝſŶŵŝƚŽĐŽŶĚƌŝĂů͕;^ƚŽũĂŶŽǀƐŬŝĞƚĂů͕͘ϮϬϬϰͿ͘
dŽĚŽƐĞƐƚŽƐĚĂƚŽƐ͕ĂĚşĂĚĞŚŽǇ͕ƉĂƌĞĐĞŶŝŶĚŝĐĂƌƋƵĞůĂĂƉŽƉƚŽƐŝƐĞƐĨĂĐŝůŝƚĂĚĂ
ƉŽƌƌƉϭ͕ǇĂƋƵĞĞƐƚĂƉƌŽƚĞşŶĂƉĂƌƚŝĐŝƉĂĞŶƐƵĐĞƐŽƐƚĂŶŝŵƉŽƌƚĂŶƚĞƐƉĂƌĂƋƵĞƐĞƉƵĞĚĂ
ƉƌŽĚƵĐŝƌ ĞƐƚĂ ŵƵĞƌƚĞ ĐĞůƵůĂƌ ĐŽŵŽ ƐŽŶ ůĂ ƉĞƌŵĞĂďŝůŝǌĂĐŝſŶ ĚĞ ůĂ ŵĞŵďƌĂŶĂ ĞǆƚĞƌŶĂ
ŵŝƚŽĐŽŶĚƌŝĂů Ž ůĂ ƌĞŵŽĚĞůĂĐŝſŶ ĚĞ ůĂƐ ĐƌĞƐƚĂƐ ŵŝƚŽĐŽŶĚƌŝĂůĞƐ͕ ;KĞƚƚŝŶŐŚĂƵƐ Ğƚ Ăů͕͘
ϮϬϭϮͿ͘ ^ŝŶ ĞŵďĂƌŐŽ͕ ŶŽ ŚĂǇ ƵŶĂŶŝŵŝĚĂĚ ƐŽďƌĞ Ğů ŚĞĐŚŽ ĚĞ ƋƵĞ ůĂ ĨƌĂŐŵĞŶƚĂĐŝſŶ
ŵŝƚŽĐŽŶĚƌŝĂůŽďƐĞƌǀĂĚĂĞŶůĂĨŝƐŝſŶĚĞůŽƌŐĄŶƵůŽƐĞĂƵŶƉĂƐŽĞƐƚƌŝĐƚĂŵĞŶƚĞŶĞĐĞƐĂƌŝŽ
ƉĂƌĂƋƵĞƐĞƉƌŽĚƵǌĐĂůĂĂƉŽƉƚŽƐŝƐ͘
3. Especies reactivas del oxígeno
>ĂƐZKĐŽŶƐƚŝƚƵǇĞŶƵŶŚĞƚĞƌŽŐĠŶĞŽŐƌƵƉŽĚĞŵŽůĠĐƵůĂƐĞŶĞůƋƵĞƐĞŝŶĐůƵǇĞŶ
ŝŽŶĞƐ ĚĞů ŽǆşŐĞŶŽ͕ ƌĂĚŝĐĂůĞƐ ůŝďƌĞƐ Ǉ ƉĞƌſǆŝĚŽƐ͕ ĚĞ ŶĂƚƵƌĂůĞǌĂ ƚĂŶƚŽ ŽƌŐĄŶŝĐĂ ĐŽŵŽ
ŝŶŽƌŐĄŶŝĐĂ͘^ƵĞůĞŶƐĞƌĚĞƚĂŵĂŹŽƉĞƋƵĞŹŽǇƚĞŶĞƌƵŶĂǀŝĚĂŵĞĚŝĂĐŽƌƚĂ͘ĚĞŵĄƐ͕ƐŽŶ
ƐƵŵĂŵĞŶƚĞ ŝŶĞƐƚĂďůĞƐ͕ ƉŽƌ ůŽ ƋƵĞ ƚŝĞŶĞŶ ƵŶĂ ĂůƚĂ ƚĞŶĚĞŶĐŝĂ Ă ƌĞĂĐĐŝŽŶĂƌ ĐŽŶ ŽƚƌŽƐ
ĐŽŵƉƵĞƐƚŽƐ͘ƐƚĞĞĨĞĐƚŽƐĞǀĞŝŶĐƌĞŵĞŶƚĂĚŽ͕ĞŶĞůĐĂƐŽĚĞůŽƐƌĂĚŝĐĂůĞƐůŝďƌĞƐ͕ƉŽƌůĂ
ƉƌĞƐĞŶĐŝĂĚĞĞůĞĐƚƌŽŶĞƐĚĞƐĂƉĂƌĞĂĚŽƐĞŶƐƵĐĂƉĂĚĞǀĂůĞŶĐŝĂ͘ůŽƌŝŐĞŶĚĞůĂƐZKůŽ
ĞŶĐŽŶƚƌĂŵŽƐ͕ƉƌŝŶĐŝƉĂůŵĞŶƚĞ͕ĞŶůĂĐĂĚĞŶĂĚĞƚƌĂŶƐƉŽƌƚĞĚĞĞůĞĐƚƌŽŶĞƐŵŝƚŽĐŽŶĚƌŝĂů͕
ĚŽŶĚĞĞŶƚƌĞĞůϮǇĞůϯйĚĞůŽǆşŐĞŶŽƚŽƚĂůĨŽƌŵĂZKĐŽŶƚŝŶƵĂŵĞŶƚĞ͕ŵŝĞŶƚƌĂƐƋƵĞ͕Ğů
ƌĞƐƚŽ ĚĞů ŽǆşŐĞŶŽ͕ ĞƐ ƵƚŝůŝǌĂĚŽ ƉĂƌĂ ůĂ ŐĞŶĞƌĂĐŝſŶ ĚĞ ĂŐƵĂ͕ ;ŵĞƐ Ğƚ Ăů͕͘ ϭϵϵϯͿ͘
ŽŶĐƌĞƚĂŵĞŶƚĞ͕ ĚƵƌĂŶƚĞ ĞƐƚĞ ƉƌŽĐĞƐŽ͕ ƐĞ ůůĞǀĂ Ă ĐĂďŽ ƵŶĂ Ž ĚŽƐ ƌĞĚƵĐĐŝŽŶĞƐ ĚĞ
ŽǆşŐĞŶŽŵŽůĞĐƵůĂƌ͕ŐĞŶĞƌĄŶĚŽƐĞĞŶƚŽŶĐĞƐŝſŶƐƵƉĞƌſǆŝĚŽĐŽŵŽƌĂĚŝĐĂůǇŽƚƌĂƐZKŶŽ
ƌĂĚŝĐĂůĞƐ͕ĐŽŵŽĞƐĞůĐĂƐŽĚĞů,ϮKϮ͕;yƵ͕ϮϬϬϰͿ͘
ƐƵ ǀĞǌ͕ ĞƐƚŽƐ ŵĞƚĂďŽůŝƚŽƐ ƉƵĞĚĞŶ ƐĞƌ ĐŽŶǀĞƌƚŝĚŽƐ ĞŶ ŽƚƌŽƐ ZK͕ ĐŽŵŽ Ğů
ƌĂĚŝĐĂůĐĂƌďŽŶĂƚŽ͕ĂƵŶƋƵĞĞŶĞƐƚĞĐĂƐŽĞƐŶĞĐĞƐĂƌŝĂůĂƉƌĞƐĞŶĐŝĂĚĞƉĞƌŽǆŝŶŝƚƌŝƚŽƐ͘ƐƚĂ
ƌĞĂĐĐŝſŶ ƐĞ ƌĞƚƌŽĂůŝŵĞŶƚĂ Ă Ɛş ŵŝƐŵĂ͕ ǇĂ ƋƵĞ ůŽƐ ƉĞƌŽǆŝŶŝƚƌŝƚŽƐ ŵŝƚŽĐŽŶĚƌŝĂůĞƐ ƐŽŶ
ƉƌŽĚƵĐƚŽƐĚĞ ůĂ ƌĞĂĐĐŝſŶ ĚĞů ĂŶŝſŶ ƐƵƉĞƌſǆŝĚŽǇ Ğů ſǆŝĚŽ ŶşƚƌŝĐŽ͕ Ğů ĐƵĂů ĞƐ ŐĞŶĞƌĂĚŽ
ϯϮ
ƉŽƌůĂƐſǆŝĚŽŶşƚƌŝĐŽƐŝŶƚĞƚĂƐĂƐ͕;ĂĚĞŶĂƐĞƚĂů͕͘ϮϬϬϬͿ͘
Ŷ ŵĞŶŽƌ ŵĞĚŝĚĂ͕ ůĂƐ ZK ƉƵĞĚĞŶ ƚĂŵďŝĠŶ ƐĞƌ ƐŝŶƚĞƚŝǌĂĚĂƐ ƉŽƌ ĚŝǀĞƌƐŽƐ
ƐŝƐƚĞŵĂƐ ĞŶǌŝŵĄƚŝĐŽƐ ĚĞ ƐƵƐƚĂŶĐŝĂƐ ƚŝƉŽ ƌĞĚŽǆ͕ ;EW, Ž E,Ϳ͕ Ž ƉŽƌ ůĂƐ ĐĠůƵůĂƐ
ĨĂŐŽĐşƚŝĐĂƐ͕ ůŽƐ ŶĞƵƚƌſĨŝůŽƐ Ǉ ůŽƐ ŵĂĐƌſĨĂŐŽƐ͕ ;ƌĞǀŝƐĂĚŽ ĞŶ ;,ŽŝĚĂů͕ ϮϬϬϭͿͿ͘ WŽƌ ƷůƚŝŵŽ͕
ĐŝĞƌƚŽƐĨĂĐƚŽƌĞƐĞǆſŐĞŶŽƐ͕ĐŽŵŽƐŽŶůĂĞǆƉŽƐŝĐŝſŶĂƌĂĚŝĂĐŝſŶŝŽŶŝǌĂŶƚĞ͕ĞůƚĂďĂĐŽŽĞů
ĐŽŶƚĂĐƚŽĐŽŶĐŝĞƌƚŽƐŚĞƌďŝĐŝĚĂƐǇƉĞƐƚŝĐŝĚĂƐ͕ƚĂŵďŝĠŶƉƵĞĚĞŶŝŶĚƵĐŝƌůĂĨŽƌŵĂĐŝſŶZK͕
;ŽŶŶĞƌĞƚĂů͕͘ϮϬϬϮ͖ZĂĚĂĞƚĂů͕͘ϮϬϬϴͿ͘
>ĂƐ ZK ũƵĞŐĂŶ ƵŶ ƉĂƉĞů ĨƵŶĚĂŵĞŶƚĂů ĞŶ Ğů ŵĂŶƚĞŶŝŵŝĞŶƚŽ ĚĞů ďƵĞŶ
ĨƵŶĐŝŽŶĂŵŝĞŶƚŽ ĐĞůƵůĂƌ͕ ĂĐƚƵĂŶĚŽ ĐŽŵŽ ƐĞŐƵŶĚŽƐ ŵĞŶƐĂũĞƌŽƐ ĞŶ ĚŝǀĞƌƐŽƐ ƉƌŽĐĞƐŽƐ͘
^ŽŶ ŝŵƉƌĞƐĐŝŶĚŝďůĞƐ ĞŶ ůĂ ƐşŶƚĞƐŝƐ ĚĞ ĂůŐƵŶĂƐ ŚŽƌŵŽŶĂƐ͕ ĐŽŵŽ ůĂ ƚŝƌŽǆŝŶĂ͕ Ǉ ĞŶ ůĂ
ĞůŝŵŝŶĂĐŝſŶ ĚĞ ĐŝĞƌƚŽƐ ƚŝƉŽƐ ĚĞ ďĂĐƚĞƌŝĂƐ Ǉ ƉĂƚſŐĞŶŽƐ͕ ĞŶĐĂƉƐƵůĂĚŽƐ ƉƌĞǀŝĂŵĞŶƚĞ͕
;ƌŶŽůĚĞƚĂů͕͘ϭϵϵϴ͖>ĂŶŶŝĞƚĂů͕͘ϮϬϬϭ͖zƵŬĞƚĂů͕͘ϮϬϭϮͿ͘ĚĞŵĄƐ͕ǀĂƌŝĂƐƉƌŽƚĞşŶĂƐĚĞ
ƐĞŹĂůŝǌĂĐŝſŶ͕ ĐŽŵŽ E&Ͳʃ͕ W/ϯͲ<͕ DW< Ǉ Ɖϱϯ ĚĞƐĂƌƌŽůůĂŶ ƐƵƐ ƌĞƐƉĞĐƚŝǀŽƐ ƌŽůĞƐ
ĐĞůƵůĂƌĞƐĞŶƌĞƐƉƵĞƐƚĂĂůĂŐĞŶĞƌĂĐŝſŶĚĞZK͕;ƵƌĚŽŶĞƚĂů͕͘ϭϵϴϵ͖&ŝŶŬĞů͕ϭϵϵϴ͖>ĞĞ
Ğƚ Ăů͕͘ ϮϬϭϭ͖ DĂƌƚŝŶĚĂůĞ Ğƚ Ăů͕͘ ϮϬϬϮͿ͘ ĚŝĐŝŽŶĂůŵĞŶƚĞ͕ ƉĂƌĂ Ğů ŵĂŶƚĞŶŝŵŝĞŶƚŽ ĚĞů
ďĂůĂŶĐĞ ƌĞĚŽǆ ĐĞůƵůĂƌ ĞƐ ŶĞĐĞƐĂƌŝĂ ůĂ ƉƌĞƐĞŶĐŝĂ ĚĞ ZK͕ ĐŽŶĐƌĞƚĂŵĞŶƚĞ ĚĞů ,ϮKϮ
ůŝďĞƌĂĚŽĚĞƐĚĞůĂŵŝƚŽĐŽŶĚƌŝĂĂůĐŝƚŽƐŽů͕;<ŽǁĂůƚŽǁƐŬŝĞƚĂů͕͘ϮϬϬϵͿ͘
ĚĞŵĄƐ͕ůĂƐZKƚŝĞŶĞŶƚĂŵďŝĠŶƵŶĂĨƵŶĐŝſŶŝŵƉƌĞƐĐŝŶĚŝďůĞĞŶĞůĐŝĐůŽĐĞůƵůĂƌ͘
ĞŚĞĐŚŽ͕ĞůƉĂƉĞůĚĞů,ϮKϮĞŶůĂƉƌŽůŝĨĞƌĂĐŝſŶĐĞůƵůĂƌĞŶŵĂŵşĨĞƌŽƐŚĂƐŝĚŽĞƐƚƵĚŝĂĚŽ
ĞŶĚŝǀĞƌƐŽƐŵŽĚĞůŽƐĐĞůƵůĂƌĞƐ͕;ĂƉŽƌŽƐƐŝĞƚĂů͕͘ϮϬϬϯ͖ŚƵŶŐĞƚĂů͕͘ϮϬϬϵ͖^ŝŐĂƵĚĞƚĂů͕͘
ϮϬϬϱ͖ ^ƚŽŶĞ Ğƚ Ăů͕͘ ϮϬϬϮ͖ ^ƚŽŶĞ Ğƚ Ăů͕͘ ϮϬϬϲͿ͘ Ɛş͕ ƐĂďĞŵŽƐ ƋƵĞ ůĂ ƌĞĚƵĐĐŝſŶ ĚĞ ůĂ
ƉƌŽĚƵĐĐŝſŶ ĚĞ ZK^ ĞŶĚſŐĞŶĂƐ ƉŽƌ ƉĂƌƚĞ ĚĞ ŝŶĐƌĞŵĞŶƚŽƐ ĞŶ Ğů ƐŝƐƚĞŵĂ ĂŶƚŝŽǆŝĚĂŶƚĞ͕
ŝŶŚŝďĞ ůĂ ƉƌŽůŝĨĞƌĂĐŝſŶ ĚĞ ůĂƐ ĐĠůƵůĂƐ ƚƵŵŽƌĂůĞƐ Ǉ ĚĞ ůĂƐ ĚĞů ŵƷƐĐƵůŽ ůŝƐŽ ĞƐƋƵĞůĠƚŝĐŽ͕
;ĂƉŽƌŽƐƐŝĞƚĂů͕͘ϮϬϬϯ͖^ŝŐĂƵĚĞƚĂů͕͘ϮϬϬϱ͖^ƚŽŶĞĞƚĂů͕͘ϮϬϬϮͿ͘dĂŵďŝĠŶƐĞƉƌŽĚƵĐĞůĂ
ƉĂƌĂĚĂ ĚĞů ĐŝĐůŽ ĐĞůƵůĂƌ ĞŶ ůĂ ĨĂƐĞ 'ϭ͕ ůŽ ĐƵĂů ĚĞŵƵĞƐƚƌĂ ƋƵĞ ůĂ ƉƌĞƐĞŶĐŝĂ ĚĞ ĞƐƚĂƐ
ƐƵƐƚĂŶĐŝĂƐĞŶĞƐƚĂĚŽĞƐƚĂĐŝŽŶĂƌŝŽĞŶůĂĐĠůƵůĂĞƐŶĞĐĞƐĂƌŝĂƉĂƌĂƋƵĞĐŽŵŝĞŶĐĞůĂĨĂƐĞ^
ĚĞůĐŝƚĂĚŽĐŝĐůŽ͕;>ĞĞĞƚĂů͕͘ϮϬϭϭ͖^ĞŬŚĂƌĂŵĞƚĂů͕͘ϭϵϵϴͿ͘
^ŝŶĞŵďĂƌŐŽĞƐƚĂŵďŝĠŶĚĞƐŽďƌĂĐŽŶŽĐŝĚŽĞůƉĂƉĞůĚĞůĞƚĠƌĞŽĞŶĞůŽƌŐĂŶŝƐŵŽ
ƋƵĞ ũƵĞŐĂŶ ůĂƐ ZK͕ Ăů ĞƐƚĂƌ ĞƐƚĂƐ ƐƵƐƚĂŶĐŝĂƐ ŝŵƉůŝĐĂĚĂƐ ĞŶ ůĂ ŵƵĞƌƚĞ ĐĞůƵůĂƌ͕ ĞŶ ůĂ
ϯϯ
ƐĞŶĞƐĐĞŶĐŝĂ Ǉ ĞŶ ůĂ ĂƉĂƌŝĐŝſŶ Ǉ ƉƌŽŐƌĞƐŝſŶ ĚĞ ƉĂƚŽůŽŐşĂƐ ĚĞ ĚŝǀĞƌƐŽ şŶĚŽůĞ͕ ;ƌŽŐĞ͕
ϮϬϬϮ͖ DĂƌƚŝŶĚĂůĞ Ğƚ Ăů͕͘ ϮϬϬϮͿ͘ Ɛş͕ ĐƵĂŶĚŽ ƐƵ ĐŽŶĐĞŶƚƌĂĐŝſŶ ƐĞ ŝŶĐƌĞŵĞŶƚĂ
ĐŽŶƐŝĚĞƌĂďůĞŵĞŶƚĞ ĐŽŵŽ ƌĞƐƉƵĞƐƚĂ Ă ĐŝĞƌƚŽƐ ĞƐƚşŵƵůŽƐ͕ Ž ĐƵĂŶĚŽ Ğů ƐŝƐƚĞŵĂ
ĂŶƚŝŽǆŝĚĂŶƚĞ ĚĞů ŽƌŐĂŶŝƐŵŽ ĚŝƐŵŝŶƵǇĞ ƐƵ ĂĐĐŝſŶ͕ ůĂƐ ZK ƐĞ ƚŽƌŶĂŶ ƉĞůŝŐƌŽƐŽƐ
ĞŶĞŵŝŐŽƐĚĞůďƵĞŶĨƵŶĐŝŽŶĂŵŝĞŶƚŽĐĞůƵůĂƌ͕ĂůĚĂŹĂƌĚŝǀĞƌƐĂƐĞƐƚƌƵĐƚƵƌĂƐ͕ƉƌŽĚƵĐŝĞŶĚŽ
ĞƐƚƌĠƐĐĞůƵůĂƌ͕;ĞǀĂƐĂŐĂǇĂŵĞƚĂů͕͘ϮϬϬϰ͖sŝŶĐĞŶƚĞƚĂů͕͘ϮϬϬϳͿ͘ĨĞĐƚĂŶƐŽďƌĞƚŽĚŽĂůĂ
ŵŝƚŽĐŽŶĚƌŝĂ͕ĚĞďŝĚŽĂůĂĐĞƌĐĂŶşĂĨşƐŝĐĂĐŽŶĞƐƚĞŽƌŐĄŶƵůŽ͕;ŽǀĞƌŝƐ͕ϭϵϵϴ͖<ŽǁĂůƚŽǁƐŬŝ
ĞƚĂů͕͘ϮϬϬϵͿ͘
4. Enfermedades Neurodegenerativas
ƐƚĂ ĚĞŶŽŵŝŶĂĐŝſŶ ĞŶŐůŽďĂ ĚŝǀĞƌƐĂƐ ƉĂƚŽůŽŐşĂƐ͕ ĐĂƌĂĐƚĞƌŝǌĂĚĂƐ ƚŽĚĂƐ ĞůůĂƐ ƉŽƌ
ƉƌŽĚƵĐŝƌ ƚƌĂƐƚŽƌŶŽƐ ĐŽŐŶŝƚŝǀŽƐ Ǉ ĐĂŵďŝŽƐ ĞŶ ůĂ ĐŽŶĚƵĐƚĂ ĚĞ ůŽƐ ƉĂĐŝĞŶƚĞƐ ƋƵĞ ůĂƐ
ƐƵĨƌĞŶ͕ĚĞďŝĚŽĂƵŶŝŶĐƌĞŵĞŶƚŽĚĞůĂŵƵĞƌƚĞŶĞƵƌŽŶĂů͕;ƌĞǀŝƐĂĚŽĞŶ;DĂƚƚƐŽŶ͕ϮϬϬϬͿͿ͘
ŽŶĐƌĞƚĂŵĞŶƚĞ͕ĞŶĞƐƚĞƚƌĂďĂũŽ͕ŶŽƐǀĂŵŽƐĂĐĞŶƚƌĂƌĞŶĚŽƐĚĞůĂƐƉĂƚŽůŽŐşĂƐƋƵĞƐĞ
ĞŶŐůŽďĂŶĚĞŶƚƌŽĚĞĞƐƚĞŐƌƵƉŽ͗>ĂĞŶĨĞƌŵĞĚĂĚĚĞWĂƌŬŝŶƐŽŶǇůĂĚĞ,ƵŶƚŝŶŐƚŽŶ͘
W
,
ƚŝŽůŽŐşĂ͘
ƐƉŽƌĄĚŝĐĂ͘ ^ſůŽ ƚŝĞŶĞŶ 'ĞŶĠƚŝĐĂ͘
ďĂƐĞŐĞŶĠƚŝĐĂĞůϭϬͲϮϬйĚĞ
ůŽƐĐĂƐŽƐ͘
ĚĂĚĚĞĂƉĂƌŝĐŝſŶ͘
ƉĂƌƚŝƌĚĞů ƋƵŝŶƚŽ Ž ƐĞǆƚŽ ƵĂůƋƵŝĞƌĂ͘ ů ϳϱй ĚĞ ůŽƐ
ĚĞĐĞŶŝŽ
ĞŶ
ůĂ
W ĂĨĞĐƚĂĚŽƐ ĚĞƐĂƌƌŽůůĂŶ ůĂ
ĞƐƉŽƌĄĚŝĐĂ͘^ŽďƌĞůĂĐƵĂƌƚĂ ĞŶĨĞƌŵĞĚĂĚ ĂŶƚĞƐ ĚĞ ůŽƐ
/ŶĐŝĚĞŶĐŝĂ͕;ƉŽƌĐĂĚĂ
ĚĠĐĂĚĂĞŶůĂĨĂŵŝůŝĂƌ͘
ϱϱĂŹŽƐ͘
ϭϱͲϮϬĐĂƐŽƐ͘
ϰͲϴĐĂƐŽƐ͘
ϭϬϬ͘ϬϬϬŚĂďŝƚĂŶƚĞƐͿ͘
WƌĞǀĂůĞŶĐŝĂ͕
;ƉŽƌ
ĐĂĚĂ ϭϲϬͲϭϳϬĐĂƐŽƐ͘
ϱͲϭϬĐĂƐŽƐ͘
ϭϬϬ͘ϬϬϬŚĂďŝƚĂŶƚĞƐͿ͘
ŽŶĂĐĞƌĞďƌĂůĂĨĞĐƚĂĚĂ͘
EĞƵƌŽŶĂƐ ĚŽƉĂŵŝŶĠƌŐŝĐĂƐ EĞƵƌŽŶĂƐ ĞƉƐŽŶŽƐĂƐ ĚĞ
ĚĞůĂƐƵďƐƚĂŶƚŝĂŶŝŐƌĂ͘
ƚĂŵĂŹŽ
ŵĞĚŝĂŶŽ
ĞƐƚƌŝĂĚŽĐĞƌĞďƌĂů͘
ĐƵŵƵůĂĐŝŽŶĞƐƉƌŽƚĞŝĐĂƐ͘
ϯϰ
^ş͘ƵĞƌƉŽƐĚĞ>ĞǁŝƐ͘
EŽ͘
ĚĞů
DĂŶŝĨĞƐƚĂĐŝŽŶĞƐ
^ş͘
^ş͘
ůƚĞƌĂĐŝŽŶĞƐĐŽŶŐŶŝƚŝǀĂƐ͘
^ş͘
^ş͘
WƌŝŶĐŝƉĂůĞƐ
dĞŵďůŽƌĞŶƌĞƉŽƐŽ͘ZŝŐŝĚĞǌ DŽǀŝŵŝĞŶƚŽƐ
ŵĂŶŝĨĞƐƚĂĐŝŽŶĞƐĐůşŶŝĐĂƐ͘
ŵƵƐĐƵůĂƌ͘
ƉƐŝƋƵŝĄƚƌŝĐĂƐ͘
WĠƌĚŝĚĂ
ƉŽƐƚƵƌĂůĞƐ͘
ĐŽƌĠŝĐŽƐ͘
ƌĂĚŝĐŝŶĞƐŝĂ͘ WĠƌĚŝĚĂĚĞĞǆƉƌĞƐŝſŶĨĄĐŝĂů
ĚĞ
ƌĞĨůĞũŽƐ Ǉ
ŵƵĞĐĂƐ
ƌĞƉĞŶƚŝŶĂƐ͘
ĞƚĞƌŝŽƌŽŶĞƵƌŽůſŐŝĐŽ͘
dĂďůĂϭ͘ŽŵƉĂƌĂĐŝſŶĚĞůŽƐƉƌŝŶĐŝƉĂůĞƐƌĂƐŐŽƐĚĞůĂWǇůĂ,͘
ĞƐĚĞ ƵŶ ƉƵŶƚŽ ĚĞ ǀŝƐƚĂ ƐŝŶƚŽŵĂƚŽůſŐŝĐŽ͕ ƚŽĚĂƐ ůĂƐ ĞŶĨĞƌŵĞĚĂĚĞƐ
ŶĞƵƌŽĚĞŐĞŶĞƌĂƚŝǀĂƐ ƐƵĞůĞŶ ƉƌĞƐĞŶƚĂƌ ƵŶ ŝŶŝĐŝŽ ŝŶƐŝĚŝŽƐŽ Ǉ ƵŶ ĚĞƐĂƌƌŽůůŽ ƉƌŽŐƌĞƐŝǀŽ Ğ
ŝƌƌĞǀĞƌƐŝďůĞ͕ĞŶĞůƋƵĞƐĞƉƌŽĚƵĐĞůĂƉĠƌĚŝĚĂƉĂƵůĂƚŝŶĂĚĞůĂƐĐĂƉĂĐŝĚĂĚĞƐŵĞŶƚĂůĞƐǇ
ĨşƐŝĐĂƐ ĚĞ ůĂƐ ƉĞƌƐŽŶĂƐ ƋƵĞ ůĂƐ ƉĂĚĞĐĞŶ͘ DƵĐŚĂƐ ǀĞĐĞƐ͕ ĞŶ ĞƐƚĞ ƉƌŽĐĞƐŽ ĂƉĂƌĞĐĞŶ
ƚƌĂƐƚŽƌŶŽƐƉƐŝƋƵŝĄƚƌŝĐŽƐĐŽŶĐŽŵŝƚĂŶƚĞƐ͕ĐŽŵŽĞƐĞůĐĂƐŽĚĞůĂĚĞƉƌĞƐŝſŶ͕;^ŝŶŐĞƌ͕ϮϬϭϮ͖
^ƚĂƌŬƐƚĞŝŶĞƚĂů͕͘ϮϬϭϮͿ͘
hŶĂĚĞůĂƐĐĂƌĂĐƚĞƌşƐƚŝĐĂƐĐŽŵƵŶĞƐĚĞůĂŵĂǇŽƌşĂĚĞĞƐƚĂƐĞŶĨĞƌŵĞĚĂĚĞƐĞƐĞů
ŚĞĐŚŽ ĚĞ ƉŽƐĞĞƌ ƵŶĂ ĞƚŝŽůŽŐşĂ ŵƵůƚŝĨĂĐƚŽƌŝĂů͕ ůŽ ĐƵĂů ĐŽŵƉůŝĐĂ ĞŶŽƌŵĞŵĞŶƚĞ ƐƵ
ƚƌĂƚĂŵŝĞŶƚŽ͕;/ƋďĂůĞƚĂů͕͘ϮϬϭϬ͖ZŝĞƐƐĞƚĂů͕͘ϭϵϵϵͿ͘ƐƉƌĞĐŝƐĂŵĞŶƚĞƉŽƌĞƐƚŽƋƵĞ͕ĂĚşĂ
ĚĞ ŚŽǇ͕ ĐĂƌĞĐĞŵŽƐ ĚĞ ĂƌŵĂƐ ƚĞƌĂƉĠƵƚŝĐĂƐ ĞĨŝĐĂĐĞƐ͕ ĐŽŶƚĂŶĚŽ ůŽƐ ĞŶĨĞƌŵŽƐ
ĞǆĐůƵƐŝǀĂŵĞŶƚĞ ĐŽŶ ĨĄƌŵĂĐŽƐ ĚĞ ƚŝƉŽ ƉĂůŝĂƚŝǀŽ Ǉ͕ ƐſůŽ ĞŶ ĂůŐƵŶĂƐ ƉŽĐĂƐ ĞǆĐĞƉĐŝŽŶĞƐ͕
ƐŝŶƚŽŵĄƚŝĐŽ͘
>Ă ŝŵƉŽƐŝďŝůŝĚĂĚ ĂĐƚƵĂů ĚĞ ĐƵƌĂƌ ĞƐƚĂƐ ĞŶĨĞƌŵĞĚĂĚĞƐ͕ ƐƵŵĂĚĂ Ă ůĂƐ ĂůƚĂƐ
ŝŶĐŝĚĞŶĐŝĂ Ǉ ƉƌĞǀĂůĞŶĐŝĂ ĚĞ ĞƐƚĞ ƚŝƉŽ ĚĞ ƉĂƚŽůŽŐşĂƐ ĞŶ ůŽƐ ůůĂŵĂĚŽƐ ƉĂşƐĞƐ
ĚĞƐĂƌƌŽůůĂĚŽƐ͕ƉƌŽĚƵĐĞŶƋƵĞ͕ĂƉĂƌƚĞĚĞůůſŐŝĐŽƐƵĨƌŝŵŝĞŶƚŽĚĞƉĂĐŝĞŶƚĞƐ͕ĨĂŵŝůŝĂƌĞƐǇ
ĐƵŝĚĂĚŽƌĞƐ͕ ƐĞ ƉƌŽĚƵǌĐĂ ƵŶ ĂůƚŽ ŐĂƐƚŽ ĞĐŽŶſŵŝĐŽ ƉĂƌĂ ůŽƐ ƐŝƐƚĞŵĂƐ ĚĞ ƐĂůƵĚ͕
;DƵĂŶŐƉĂŝƐĂŶ Ğƚ Ăů͕͘ ϮϬϭϭ͖ WƌŝŶŐƐŚĞŝŵ Ğƚ Ăů͕͘ ϮϬϭϮͿ͘ WŽƌ ƚĂŶƚŽ͕ ƌĞƐƵůƚĂ ŝŶĚŝƐƉĞŶƐĂďůĞ
ůůĞǀĂƌ Ă ĐĂďŽ ĞƐƚƵĚŝŽƐ Ă ƚƌĂǀĠƐ ĚĞ ůŽƐ ĐƵĂůĞƐ ƉŽĚĂŵŽƐ ĐŽŶŽĐĞƌ ŵĄƐ Ǉ ŵĞũŽƌ ůĂƐ
ĞŶĨĞƌŵĞĚĂĚĞƐŶĞƵƌŽĚĞŐĞŶĞƌĂƚŝǀĂƐ͕ĂƐşĐŽŵŽůŽƐŵĞĐĂŶŝƐŵŽƐŵŽůĞĐƵůĂƌĞƐǇĐĞůƵůĂƌĞƐ
ƋƵĞůĂƐƉƌŽĚƵĐĞŶ͕ƉĂƌĂĂƐşƉŽĚĞƌŚĂůůĂƌĂƌŵĂƐƚĞƌĂƉĠƵƚŝĐĂƐĞĨŝĐĂĐĞƐƋƵĞŶŽƐƉĞƌŵŝƚĂŶ
ƚƌĂƚĂƌŽƉƌĞǀĞŶŝƌĞƐƚĂƐƉĂƚŽůŽŐşĂƐ͘
ϯϱ
>ĂƐĚŝƐĨƵŶĐŝŽŶĞƐĞŶůŽƐĚŝǀĞƌƐŽƐĐŽŵƉŽŶĞŶƚĞƐĚĞůĂĚŝŶĄŵŝĐĂŵŝƚŽĐŽŶĚƌŝĂů͕ĞŶ
ůĂ ŵŝƚŽĨĂŐŝĂ Ǉ ĞŶ ůĂ ĂƉŽƉƚŽƐŝƐ ĞƐƚĄŶ şŶƚŝŵĂŵĞŶƚĞ ƌĞůĂĐŝŽŶĂĚĂƐ ĐŽŶ ůĂ ĂƉĂƌŝĐŝſŶ ĚĞ
ĚŝǀĞƌƐĂƐ ƉĂƚŽůŽŐşĂƐ͕ ĐŽŵŽ ĞƐ Ğů ĐĂƐŽ ĚĞ ůĂƐ ĞŶĨĞƌŵĞĚĂĚĞƐ ŶĞƵƌŽĚĞŐĞŶĞƌĂƚŝǀĂƐ͕
;ƌĞǀŝƐĂĚŽĞŶ;ŽƌƌĞŝĂĞƚĂů͕͘ϮϬϭϮ͖>ŝŶĞƚĂů͕͘ϮϬϬϲͿͿ͘ĞŚĞĐŚŽ͕ĞƐƚƵĚŝŽƐƌĞĐŝĞŶƚĞƐŚĂŶ
ƌĞǀĞůĂĚŽ ƵŶ ĨƵŶĐŝŽŶĂŵŝĞŶƚŽ ĂŶŽƌŵĂů ƚĂŶƚŽ ĚĞ ůŽƐ ŐĞŶĞƐ ƋƵĞ ĐŽĚŝĨŝĐĂŶ ƉĂƌĂ ůŽƐ
ĐŽŵƉŽŶĞŶƚĞƐĚĞůĂĨƵƐŝſŶĐŽŵŽĚĞĂƋƵĞůůŽƐƋƵĞůŽŚĂĐĞŶƉĂƌĂůĂĨŝƐŝſŶ͕ĞŶƉĂĐŝĞŶƚĞƐ
ĐŽŶĞƐƚĞƚŝƉŽĚĞƉĂƚŽůŽŐşĂƐ͕;ZĞĚĚǇ͕ϮϬϬϴͿ͘
4.1. Enfermedad de Parkinson
ů ŝŐƵĂů ƋƵĞ ƐƵĐĞĚşĂ ĞŶ ůĂ ,͕ ƚĂŵďŝĠŶ ĞŶ Ğů ĐĂƐŽ ĚĞ ůĂ W ůĂƐ ĚŝƐĨƵŶĐŝŽŶĞƐ
ŵŝƚŽĐŽŶĚƌŝĂůĞƐ ũƵĞŐĂŶ ƵŶ ŝŵƉŽƌƚĂŶƚĞ ƉĂƉĞů ĞŶ ůĂ ĂƉĂƌŝĐŝſŶ Ǉ ĞǀŽůƵĐŝſŶ ĚĞ ĞƐƚĂ
ĞŶĨĞƌŵĞĚĂĚ͕ ;^ŽďƌŝĚŽ͕ ϮϬϬϵ͖ sĂŶ >ĂĂƌ Ğƚ Ăů͕͘ ϮϬϬϵͿ͕ ŽďƐĞƌǀĄŶĚŽƐĞ͕ ĞŶ ŵŽĚĞůŽƐ
ĐĞůƵůĂƌĞƐ ĚĞ ůĂ ĞŶĨĞƌŵĞĚĂĚ͕ ŝŶĐƌĞŵĞŶƚŽƐ ĐŽŶƐŝĚĞƌĂďůĞƐ ĞŶ ůĂ ĨƌĂŐŵĞŶƚĂĐŝſŶ
ŵŝƚŽĐŽŶĚƌŝĂůǇĞŶůĂŵƵĞƌƚĞĐĞůƵůĂƌ͕;ĂƌƐŽƵŵĞƚĂů͕͘ϮϬϬϲͿ͘EŽƐĞŶĐŽŶƚƌĂŵŽƐĂŶƚĞůĂ
ƐĞŐƵŶĚĂƉĂƚŽůŽŐşĂŶĞƵƌŽĚĞŐĞŶĞƌĂƚŝǀĂ͕ĞŶƚĠƌŵŝŶŽƐĚĞŝŶĐŝĚĞŶĐŝĂ͕ƐſůŽĚĞƚƌĄƐĚĞůĂ͕
;ĂƵĞƌĞƚĂů͕͘ϮϬϬϯͿ͘>ĂĞĚĂĚŵĞĚŝĂĚĞĂƉĂƌŝĐŝſŶƐŽŶϱϱĂŹŽƐǇƐƵŝŶĐŝĚĞŶĐŝĂĂƵŵĞŶƚĂ
ĐŽŶƐŝĚĞƌĂďůĞŵĞŶƚĞ ĐŽŶ ůĂ ĞĚĂĚ͕ ;ĚĞ >ĂƵ Ğƚ Ăů͕͘ ϮϬϬϲͿ͘ >ŽƐ ƉƌŝŶĐŝƉĂůĞƐ ƐşŶƚŽŵĂƐ ƋƵĞ
ƉƌĞƐĞŶƚĂŶ ůŽƐ ƉĂĐŝĞŶƚĞƐ ĚĞ W͕ ůŽƐ ĐƵĂůĞƐ ƐĞ ǀĂŶ ĂŐƵĚŝǌĂŶĚŽ ĐŽŶ Ğů ƉĂƐŽ ĚĞů ƚŝĞŵƉŽ͕
ƐŽŶ ůĂ ďƌĂĚŝƋƵŝŶĞƐŝĂ Ǉ ůĂ ĂƉĂƌŝĐŝſŶ ĚĞů ĚĞŶŽŵŝŶĂĚŽ ƚĞŵďůŽƌ ĚĞ ƌĞƉŽƐŽ ĚĞ ƌŝŐŝĚĞǌ
ŵƵƐĐƵůĂƌ͕;tŽŽĚͲ<ĂĐǌŵĂƌĞƚĂů͕͘ϮϬϬϴͿ͘
ƵĂŶĚŽ ůŽƐ ƐşŶƚŽŵĂƐ ĚĞ ůĂ ĞŶĨĞƌŵĞĚĂĚ ƐĞ ŵĂŶŝĨŝĞƐƚĂŶ͕ ǇĂ ƐĞ ŚĂ ƉƌŽĚƵĐŝĚŽ ůĂ
ƉĠƌĚŝĚĂĚĞĂƉƌŽǆŝŵĂĚĂŵĞŶƚĞƵŶϲϬйĚĞůĂƐŶĞƵƌŽŶĂƐĚŽƉĂŵŝŶĠƌŐŝĐĂƐ͕ĂƐşĐŽŵŽĚĞƵŶ
ϴϬй ĚĞ ůĂ ĚŽƉĂŵŝŶĂ ĚĞů ĞƐƚƌŝĂĚŽ͕ ;ĂƵĞƌ Ğƚ Ăů͕͘ ϮϬϬϯͿ͘ ^ŝŶ ĞŵďĂƌŐŽ͕ ŶŽ ƐſůŽ ƐĞ ǀĞŶ
ĂĨĞĐƚĂĚĂƐĞƐƚĂƐǌŽŶĂƐĐĞƌĞďƌĂůĞƐ͕ƐŝŶŽƋƵĞƐĞŚĂŽďƐĞƌǀĂĚŽĐĂŵďŝŽƐŚŝƐƚŽƉĂƚŽůſŐŝĐŽƐ
ĞŶ ŵƵĐŚĂƐ ŽƚƌĂƐ͕ ŝŶĐůƵƐŽ ĞŶ ĂůŐƵŶĂƐ ŶŽ ĚŽƉĂŵŝŶĠƌŐŝĐĂƐ͕ ;ƌĂĂŬ Ğƚ Ăů͕͘ ϭϵϵϱͿ͘ >Ă
ĂŵƉůŝƚƵĚ ĚĞů ĐŝƚĂĚŽ ĚĂŹŽ ƉƌĞƐĞŶƚĞ ĞŶ Ğů ŵŽŵĞŶƚŽ ĚĞů ĚŝĂŐŶſƐƚŝĐŽ ĞƐ ƵŶ ŚĞĐŚŽ
ůŝŵŝƚĂŶƚĞƉĂƌĂĞůƵƐŽĚĞƚĞƌĂƉŝĂƐĐŝƚŽƉƌŽƚĞĐƚŽƌĂƐ͕ĐŽŶĂŶƚŝŽǆŝĚĂŶƚĞƐ͕ĞŶĞůƚƌĂƚĂŵŝĞŶƚŽ
ĞŶ ĞƐƚĂ ƉĂƚŽůŽŐşĂ͕ ĚĞďŝĚŽ Ă ƋƵĞ ŶŽ ƐĞ ƉƵĞĚĞ ƉƌŽƚĞŐĞƌ ĚĞů ĚĂŹŽ ŽǆŝĚĂƚŝǀŽ Ă ůĂƐ
ŶĞƵƌŽŶĂƐƋƵĞǇĂĞƐƚĄŶŵƵĞƌƚĂƐ͘
ƚŝŽůſŐŝĐĂŵĞŶƚĞ͕ ůĂ ĐĂƌĂĐƚĞƌşƐƚŝĐĂ ƉƌŝŶĐŝƉĂů ĚĞ ůĂ W ĞƐ ůĂ ƉĠƌĚŝĚĂ ĚĞ ůĂƐ
ϯϲ
ŶĞƵƌŽŶĂƐĚŽƉĂŵŝŶĠƌŐŝĐĂƐ͕ƉƌŽĚƵĐŝĚĂƉŽƌůĂĚĞŐĞŶĞƌĂĐŝſŶĚĞůůĂǀşĂĚŽƉĂŵŝŶĠƌŐŝĐĂĚĞů
ƐŝƐƚĞŵĂ ŶŝŐƌŽĞƐƚƌŝĂĚŽ ĐĞƌĞďƌĂů͕ ;sŝǀĞƐͲĂƵǌĂ Ğƚ Ăů͕͘ ϮϬϬϵͿ͘ ĚĞŵĄƐ͕ ůĂƐ ŶĞƵƌŽŶĂƐ ƋƵĞ
ůŽŐƌĂŶ ƐŽďƌĞǀŝǀŝƌ ƉƌĞƐĞŶƚĂŶ ůŽƐ ĚĞŶŽŵŝŶĂĚŽƐ ƵĞƌƉŽƐ ĚĞ >ĞǁŝƐ͕ ƋƵĞ ƐŽŶ ŝŶĐůƵƐŝŽŶĞƐ
ĞƐĨĠƌŝĐĂƐ ĞŽƐŝŶſĨŝůĂƐ ŝŶƚƌĂĐŝƚŽƉůĂƐŵĄƚŝĐĂƐ͕ ĐŽŵƉƵĞƐƚĂƐ ƉƌŝŶĐŝƉĂůŵĞŶƚĞ ƉŽƌ ůĂ
ĂŐƌĞŐĂĐŝſŶĚĞǀĂƌŝĂƐƉƌŽƚĞşŶĂƐ͕ĐŽŵŽĞƐĞůĐĂƐŽĚĞɲͲƐŝŶƵĐůĞşŶĂ͕WĂƌŬŝŶǇƵďŝƋƵŝƚŝŶĂ͕Ǉ
ĚĞ ŶĞƵƌŽĨŝůĂŵĞŶƚŽƐ͕ ;^ŚƵůƚƐ͕ ϮϬϬϲͿ͘ WƌĞĐŝƐĂŵĞŶƚĞ͕ ůĂ ŝĚĞŶƚŝĨŝĐĂĐŝſŶ ĚĞ ĞƐƚĂƐ
ĞƐƚƌƵĐƚƵƌĂƐ͕ ƉŽƐƚ ŵŽƌƚĞŵ͕ ĞŶ ůĂƐ ǌŽŶĂƐ ĐĞƌĞďƌĂůĞƐ ĚĂŹĂĚĂƐ ĐŽŶƐƚŝƚƵǇĞ Ğů ƉƌŝŶĐŝƉĂů
ĐƌŝƚĞƌŝŽĚŝĂŐŶſƐƚŝĐŽĚĞůĂĞŶĨĞƌŵĞĚĂĚĞŶůĂĂĐƚƵĂůŝĚĂĚ͕;^ŚƵůƚƐ͕ϮϬϬϲͿ͘
>Ă ĐĂƵƐĂ ƉƌŝŶĐŝƉĂů ĚĞ ůĂ ĂƉĂƌŝĐŝſŶ ĚĞ ĞƐƚĂ ĞŶĨĞƌŵĞĚĂĚ ŶŽ ŚĂ ƐŝĚŽ
ĐŽŵƉůĞƚĂŵĞŶƚĞĚŝůƵĐŝĚĂĚĂĂĚşĂĚĞŚŽǇ͘^ĂďĞŵŽƐƋƵĞƐſůŽƵŶƉĞƋƵĞŹŽƉŽƌĐĞŶƚĂũĞĚĞ
ůŽƐĐĂƐŽƐƚŝĞŶĞŶƐƵďĂƐĞĞŶŵƵƚĂĐŝŽŶĞƐƉƌŽĚƵĐŝĚĂƐĞŶĐŝĞƌƚŽƐŐĞŶĞƐ͕;tŽŽĚͲ<ĂĐǌŵĂƌ
Ğƚ Ăů͕͘ ϮϬϬϴͿ͕ ĐŽŶĐƌĞƚĂŵĞŶƚĞ ĞŶ ůŽƐ ƋƵĞ ĐŽĚŝĨŝĐĂŶ ƉĂƌĂ ůĂ ƉƌŽƚĞşŶĂ ƐŝŶĄƉƚŝĐĂ ɲͲ
ƐŝŶƵĐůĞşŶĂ͕ ;WŽůǇŵĞƌŽƉŽƵůŽƐ Ğƚ Ăů͕͘ ϭϵϵϳͿ͖ WĂƌŬŝŶ͕ ;<ŝƚĂĚĂ Ğƚ Ăů͕͘ ϭϵϵϴͿ͖ ůĂ ĐŚĂƉĞƌŽŶĂ
ƉƵƚĂƚŝǀĂĂŶƚŝŽǆŝĚĂŶƚĞũͲϭ͕;ŽŶŝĨĂƚŝĞƚĂů͕͘ϮϬϬϯͿ͖WŝŶŬϭ͕;sĂůĞŶƚĞĞƚĂů͕͘ϮϬϬϰͿ͖ůĂƐĞƌŝŶĂ
ƉƌŽƚĞĂƐĂ ŵŝƚŽĐŽŶĚƌŝĂů KD/ͬ,dZϮ͕ ;^ƚƌĂƵƐƐ Ğƚ Ăů͕͘ ϮϬϬϱͿ͖ Ǉ >Z<<Ϯ͕ ;ŝŶĂƐĂ Ϯ ZŝĐĂ ĞŶ
ZĞƉĞƚŝĐŝŽŶĞƐĚĞ>ĞƵĐŝŶĂͿ͕;ŝŵƉƌŝĐŚĞƚĂů͕͘ϮϬϬϰͿ͘ƐƚŽƐƚŝƉŽƐĚĞƉĂƌŬŝŶƐŽŶŝƐŵŽƐƐƵĞůĞŶ
ƉƌĞƐĞŶƚĂƌƵŶ ĚĞƐĂƌƌŽůůŽŵĄƐ ůĞŶƚŽ͕ ĂƐş ĐŽŵŽ ƵŶĂ ĂƉĂƌŝĐŝſŶ Ă ĞĚĂĚĞƐ ŵĄƐ ƚĞŵƉƌĂŶĂƐ͕
;,ĂƚĂŶŽĞƚĂů͕͘ϮϬϬϰͿ͘ĚĞŵĄƐ͕ĞŶĞƐƚŽƐƉĂĐŝĞŶƚĞƐƉƵĞĚĞŶŶŽĞŶĐŽŶƚƌĂƌƐĞƵĞƌƉŽƐĚĞ
>ĞǁŝƐ͕ůŽĐƵĂůŚĂĐĞƚĂŵďĂůĞĂƌƐĞĞůƵƐŽĚĞůĂŝĚĞŶƚŝĨŝĐĂĐŝſŶĚĞĞƐƚĂƐĞƐƚƌƵĐƚƵƌĂƐĐŽŵŽ
ĐƌŝƚĞƌŝŽƉƌŝŶĐŝƉĂůƉĂƌĂĞůĚŝĂŐŶſƐƚŝĐŽĚĞůĂĞŶĨĞƌŵĞĚĂĚ͕;sŝǀĞƐͲĂƵǌĂĞƚĂů͕͘ϮϬϭϭͿ͘
^ŝŶ ĞŵďĂƌŐŽ͕ ĞŶ ůĂ ŵĂǇŽƌ ƉĂƌƚĞ ĚĞ ůŽƐ ĞŶĨĞƌŵŽƐ ŶŽ ŚĂůůĂŵŽƐ ŵƵƚĂĐŝŽŶĞƐ ĞŶ
ŶŝŶŐƵŶŽĚĞĞƐƚŽƐŐĞŶĞƐ͕ůŽĐƵĂůƉĂƌĞĐĞŝŶĚŝĐĂƌƵŶŝŶŝĐŝŽĞƐƉŽƌĄĚŝĐŽǇŵƵůƚŝĨĂĐƚŽƌŝĂůĚĞ
ůĂ ĞŶĨĞƌŵĞĚĂĚ͕ ;sŝǀĞƐͲĂƵǌĂ Ğƚ Ăů͕͘ ϮϬϬϵͿ͘ Ŷ ĞƐƚŽƐ ĐĂƐŽƐ͕ ĞŶĐŽŶƚƌĂŵŽƐ ƋƵĞ ůĂƐ
ƉƌŝŵĞƌĂƐŵĂŶŝĨĞƐƚĂĐŝŽŶĞƐĚĞůĂƉĂƚŽůŽŐşĂŽĐƵƌƌĞŶĂĞĚĂĚĞƐƐƵƉĞƌŝŽƌĞƐ͕ƌĞƐƉĞĐƚŽĂůĂW
ĚĞ ƚŝƉŽ ŚĞƌĞĚŝƚĂƌŝŽ Ž ĨĂŵŝůŝĂƌ͘ ĚĞŵĄƐ͕ ůĂ ƉƌŽŐƌĞƐŝſŶ ƐƵĞůĞ ƐĞƌ ŵĄƐ ůĞŶƚĂ Ǉ ůŽƐ
ĞŶĨĞƌŵŽƐƐƵĞůĞŶǀŝǀŝƌĚƵƌĂŶƚĞƵŶƉĞƌŝŽĚŽƐƵƉĞƌŝŽƌĚĞĂŹŽƐ͘
>ĂƌĞůĂĐŝſŶĚĞůĂŵŝƚŽĐŽŶĚƌŝĂĐŽŶůĂĂƉĂƌŝĐŝſŶĚĞƐşŶĚƌŽŵĞƐĚĞƉĂƌŬŝŶƐŽŶŝƐŵŽ
ƐĞĞŵƉĞǌſĂĞƐƚƵĚŝĂƌĞŶůĂĚĠĐĂĚĂĚĞůŽƐϴϬ͕ĐƵĂŶĚŽǀĂƌŝŽƐĐŝĞŶƚşĨŝĐŽƐĐŽŶƐƚĂƚĂƌŽŶƋƵĞ
ůŽƐ ƚŽǆŝĐſŵĂŶŽƐ ƋƵĞ ĐŽŶƐƵŵşĂŶ DdWW͕ ;ϭͲŵĞƚŝůͲϰͲĨĞŶŝůͲϰͲƉƌŽƉŝŽŶƉŝƌŝĚŝŶĂͿ͕ ĐŽŵŽ
ƐƵƐƚĂŶĐŝĂ ĚĞ ĂďƵƐŽ͕ ĚĞƐĂƌƌŽůůĂďĂŶ ƐşŶĚƌŽŵĞƐ ŵƵǇ ƐŝŵŝůĂƌĞƐ Ă ůŽƐ ĚĞ ůĂ W͕ ĐŽŶ
ϯϳ
ĂĨĞĐĐŝŽŶĞƐĚĞƚŝƉŽŵŽƚŽƌ͘ĚĞŵĄƐ͕ůŽƐƐşŶƚŽŵĂƐƐĞĂƚĞŶƵĂďĂŶƚƌĂƐĞůƚƌĂƚĂŵŝĞŶƚŽĐŽŶ
>ͲKW͕ ;>ĂŶŐƐƚŽŶ Ğƚ Ăů͕͘ ϭϵϴϯͿ͘ ĐŽŶƚŝŶƵĂĐŝſŶ͕ ƐĞ ĐŽŶƐƚĂƚſ ƋƵĞ ĞƐƚŽƐ
ĚƌŽŐŽĚĞƉĞŶĚŝĞŶƚĞƐƐĞŝŶǇĞĐƚĂďĂŶ͕ĐŽŶũƵŶƚĂŵĞŶƚĞĐŽŶĞůDdWW͕ƵŶĂƉĞƋƵĞŹĂƉŽƌĐŝſŶ
ĚĞ DdWd͕ ƋƵĞ ĞƌĂ ƵŶ ƉƌŽĚƵĐƚŽ ƐĞĐƵŶĚĂƌŝŽ ĚĞ ůĂ ƐşŶƚĞƐŝƐ ĚĞů ƉƌŝŵĞƌŽ͕ ĂĚĞŵĄƐ ĚĞ ƵŶ
ĂŐĞŶƚĞŝŶĚƵĐƚŽƌĚĞůĂW͘
DĄƐĂĚĞůĂŶƚĞ͕ůĂƌĞůĂĐŝſŶĞŶƚƌĞĞůĐŝƚĂĚŽŽƌŐĄŶƵůŽǇůĂWƉĂƌĞĐŝſĚĞĨŝŶŝƌƐĞĂƷŶ
ŵĞũŽƌ͕ ĐƵĂŶĚŽ ƐĞ ĐŽŶƐƚĂƚſ ƋƵĞ͕ ĞŶ ĐĞƌĞďƌŽƐ ƉŽƐƚ ŵŽƌƚĞŵ ĚĞ ƉĂĐŝĞŶƚĞƐ ĚĞ W͕ ƐĞ
ĞŶĐŽŶƚƌĂďĂŶ ĚĞĨŝĐŝĞŶĐŝĂƐ ĚĞ ŚĂƐƚĂ ƵŶ ϯϱй ĞŶ ůĂ ĂĐƚŝǀŝĚĂĚ ĚĞů ŽŵƉůĞũŽ / ĚĞ ůĂ d
ŵŝƚŽĐŽŶĚƌŝĂů ĚĞ ůĂƐ ŶĞƵƌŽŶĂƐ ĚĞ ůĂ ƐƵďƐƚĂƚŝĂ ŶŝŐƌĂ͕ ĂƐş ĐŽŵŽ ƵŶ ŝŶĐƌĞŵĞŶƚŽ ĚĞ ůŽƐ
ŵĂƌĐĂĚŽƌĞƐĚĞĞƐƚƌĠƐŽǆŝĚĂƚŝǀŽ͕ ;^ĐŚĂƉŝƌĂ Ğƚ Ăů͕͘ ϭϵϵϬͿ͘ ƉĂƌƚŝƌĚĞ ĂƋƵş͕ ƐĞ ĞŶĐŽŶƚƌſ
ĞƐƚĂ ĚƐŝĨƵŶĐŝſŶ ƚĂŵďŝĠŶ ĞŶ ŵƵĐŚŽƐ ƚĞũŝĚŽƐ ĚĞ ƉĂĐŝĞŶƚĞƐ ĚĞ W͕ ĞŶƚƌĞ ĞůůŽƐ͕ ƉŽƌ
ĞũĞŵƉůŽ͕ĞŶŵƷƐĐƵůŽĞƐƋƵĞůĠƚŝĐŽǇƉůĂƋƵĞƚĂƐ͕;ŝŶĚŽĨĨĞƚĂů͕͘ϭϵϴϵ͖,ĂĂƐĞƚĂů͕͘ϭϵϵϱ͖
WĂƌŬĞƌĞƚĂů͕͘ϭϵϴϵͿ͘
>ĂĐĂƵƐĂĂƉĂƌƚŝƌĚĞůĂĐƵĂůůŽƐĚĂŹŽƐĞŶĞůŽŵƉůĞũŽ/ĞƐƚĄŶĞŶůĂďĂƐĞĚĞůĂW
ŶŽĞƐƚĄƚŽƚĂůŵĞŶƚĞĚŝůƵĐŝĚĂĚĂ͘WŽĚƌşĂƐĞƌƋƵĞĞůďůŽƋƵĞŽĚĞůĐŝƚĂĚŽĐŽŵƉůĞũŽƉƌŽĚƵǌĐĂ
ůĂ ŵƵĞƌƚĞ ĐĞůƵůĂƌ Ă ƚƌĂǀĠƐ ĚĞ ůĂ ĂĐƚŝǀĂĐŝſŶ ĚĞ ůĂ ǀşĂ ŝŶƚƌşŶƐĞĐĂ ĚĞ ůĂ ĂƉŽƉƚŽƐŝƐ͕
;DŽĐŚŝǌƵŬŝĞƚĂů͕͘ϮϬϬϭ͖sŝůĂĞƚĂů͕͘ϮϬϬϭͿ͕ĂƵŶƋƵĞĞŶŵŝƚŽĐŽŶĚƌŝĂƐĂŝƐůĂĚĂƐĚĞĐĞƌĞďƌŽ͕
ůĂĚŝƐĨƵŶĐŝſŶĚĞůŽŵƉůĞũŽ/ĐĂƵƐĂĚĂƚĂŶƚŽĚĞŵŽĚŽĨĂƌŵĂĐŽůſŐŝĐŽĐŽŵŽŐĞŶĠƚŝĐŽ͕ĞƐ
ŝŶĐĂƉĂǌĚĞ ĂĐƚŝǀĂƌ ůĂ ĐŝƚĂĚĂ ŵƵĞƌƚĞ ĐĞůƵůĂƌ͘ ^ŝŶĞŵďĂƌŐŽ͕ ƐşƋƵĞ ƐĞ ƌĞĚƵĐĞ Ğů ůşŵŝƚĞĂ
ƉĂƌƚŝƌĚĞůĐƵĂůƐĞĂĐƚŝǀĂůĂĂƉŽƉƚŽƐŝƐŵĞĚŝĂĚĂƉŽƌĂǆ͕ůŽĐƵĂůŚĂĐĞĂůĂƐŶĞƵƌŽŶĂƐŵĄƐ
ƐĞŶƐŝďůĞƐĂůĂĚĞŐƌĂĚĂĐŝſŶƉŽƌĞƐƚĂǀşĂ͕;WĞƌŝĞƌĞƚĂů͕͘ϮϬϬϳ͖WĞƌŝĞƌĞƚĂů͕͘ϮϬϬϱͿ͘
ů ĚĂŹŽ ƉƌŽĚƵĐŝĚŽ ĞŶ Ğů ŽŵƉůĞũŽ / ĚĞ ůĂ d ĞŶ ƉĂĐŝĞŶƚĞƐ ĚĞ W ƉŽĚƌşĂ ƐĞƌ
ĚĞďŝĚŽĂůŝŶĐƌĞŵĞŶƚŽĞŶůĂƉƌŽĚƵĐĐŝſŶĚĞůĂƐZK͕ůĂƐĐƵĂůĞƐĚĂŹĂƌşĂŶĞůŵƚE͕ĞŶĞů
ƋƵĞĞƐƚĄŶĐŽĚŝĨŝĐĂĚŽƐƐŝĞƚĞĚĞůŽƐĂƉƌŽǆŝŵĂĚĂŵĞŶƚĞĐƵĂƌĞŶƚĂǇƐĞŝƐĐŽŵƉŽŶĞŶƚĞƐĚĞů
ŽŵƉůĞũŽ /͕ ;sŝǀĞƐͲĂƵǌĂ Ğƚ Ăů͕͘ ϮϬϬϵͿ͘ ƐƚŽƐ ĚĂƚŽƐ ƐĞ ǀĞŶ ĐŽƌƌŽďŽƌĂĚŽƐ ƉŽƌ ŽƚƌŽ
ƚƌĂďĂũŽ ĞŶ Ğů ƋƵĞ ŚĂŶ ĐŽŶƐƚĂƚĂĚŽ Ğů ŝŶĐƌĞŵĞŶƚŽ ƐŝŐŶŝĨŝĐĂƚŝǀŽ ĞŶ ůĂ ĐĂŶƚŝĚĂĚ ĚĞ
ĚĞůĞĐŝŽŶĞƐ ĞŶ Ğů ŵƚE ĚĞ ŶĞƵƌŽŶĂƐ ĚĞ ƉĂĐŝĞŶƚĞƐ ĚĞ W͕ ;<ƌĂǇƚƐďĞƌŐ Ğƚ Ăů͕͘ ϮϬϬϲͿ͘
WĂƌĞĐĞƐĞƌƋƵĞůŽƐĚŝƐƚŝŶƚŽƐŚĂƉůŽŝĚĞƐĚĞůŵƚEƋƵĞƐĞĨŽƌŵĂŶĞŶĞůĐĞƌĞďƌŽĚĞĞƐƚĂƐ
ƉĂĐŝĞŶƚĞƐ ƉŽĚƌşĂŶ ĞƐƚĂƌ ŝŶĨůƵǇĞŶĚŽ ŶĞŐĂƚŝǀĂŵĞŶƚĞ ƐŽďƌĞ Ğů Ɖ, ĚĞů ĐŝƚŽƉůĂƐŵĂ͕ ĂƐş
ϯϴ
ĐŽŵŽƐŽďƌĞůĂƌĞŐƵůĂĐŝſŶĚĞůĐĂůĐŝŽ͕ůŽĐƵĂůƚŝĞŶĞŶƵŶĂĐůĂƌĂƌĞůĂĐŝſŶĐŽŶůĂŝŶƚĞŐƌŝĚĂĚ
ŶĞƵƌŽŶĂů͕;<ĂǌƵŶŽĞƚĂů͕͘ϮϬϬϲͿ͘
>ĂƐ ZK ƚĂŵďŝĠŶ ũƵĞŐĂŶ ƵŶ ƉĂƉĞů ŝŵƉŽƌƚĂŶƚĞ ĞŶ ĞƐƚĂ ƉĂƚŽůŽŐşĂ͘ Ɛş͕ ƐĞ ŚĂ
ĚĞŵŽƐƚƌĂĚŽůĂƉƌĞƐĞŶĐŝĂĚĞĂůƚĞƌĂĐŝŽŶĞƐƚĂŶƚŽĞŶůŽƐŶŝǀĞůĞƐĚĞĂŶƚŝŽǆŝĚĂŶƚĞƐĐŽŵŽĞŶ
ůĂƐ ĚŝĂŶĂƐ ĚĞ ŽǆŝĚĂĐŝſŶ͕ ;:ĞŶŶĞƌ͕ ϮϬϬϯͿ͘ Ğ ŚĞĐŚŽ͕ ůĂ ĐĂƵƐĂ ĚĞ ĞƐƚŽƐ ŝŶĐƌĞŵĞŶƚŽƐ ůĂ
ƉŽĚĞŵŽƐďƵƐĐĂƌĞŶůĂĐŝƚĂĚĂŝŶŚŝďŝĐŝſŶĚĞůŽŵƉůĞũŽ/ĚĞůĂd͕ůĂĐƵĂůƉƵĞĚĞƉƌŽĚƵĐŝƌ
ƵŶ ŝŶĐƌĞŵĞŶƚŽ ĞŶ ůĂ ƉƌŽĚƵĐĐŝſŶ ĚĞ ƌĂĚŝĐĂůĞƐ ůŝďƌĞƐ͕ ;&ŝƐŬƵŵ Ğƚ Ăů͕͘ ϮϬϬϯ͖ KƌƚŚ Ğƚ Ăů͕͘
ϮϬϬϮ͖ dƵƌƌĞŶƐ͕ ϮϬϬϯͿ͘ Ɛş͕ ŚĂǇ ƵŶĂ ŝŶƚĞƌĞƐĂŶƚĞ ƌĞǀŝƐŝſŶ ƐŽďƌĞ ůŽƐ ĞĨĞĐƚŽƐ ƉƌŽĚƵĐŝĚŽƐ
ƉŽƌĞůWĂƌĂƋƵĂƚ͕ƵŶŚĞƌďŝĐŝĚĂƋƵĞĂĐƚƷĂŝŶŚŝďŝĞŶĚŽĞůĐŽŵƉůĞũŽ/ĚĞůĂd͕ĞŶůĂƋƵĞƐĞ
ĐŽŶƐƚĂƚĂƵŶŝŵƉŽƌƚĂŶƚĞƉĂƉĞůƉĂƌĂĞůĂŶŝſŶƐƵƉĞƌſǆŝĚŽ͕ĞůĐƵĂůĞƐĐĂƉĂǌĚĞƌĞĂĐĐŝŽŶĂƌ
Ǉ ĚĂŹĂƌ ŵƵĐŚĂƐ ŵĂĐƌŽŵŽůĠĐƵůĂƐ͕ ĂƐş ĐŽŵŽ ĚĞ ŐĞŶĞƌĂƌ ŶƵĞǀĂƐ ZK͘ ĚŝĐŝŽŶĂůŵĞŶƚĞ͕
ĞƐƚĞŚĞƌďŝĐŝĚĂƚŝĞŶĞůĂŚĂďŝůŝĚĂĚĚĞŽǆŝĚĂƌĂůŐƵŶŽƐĞƋƵŝǀĂůĞŶƚĞƐĚĞƌĞĚƵĐĐŝſŶ͕ĐŽŵŽĞƐ
Ğů ĐĂƐŽ ĚĞů EW, Ž ĚĞů ŐůƵƚĂƚŝſŶ ƌĞĚƵĐŝĚŽ͘ Ɛş ŵŝƐŵŽ͕ ƐĞ ƉƌŽƉŽŶĞ ƵŶ ƉĂƉĞů
ŝŵƉŽƌƚĂŶƚĞĞŶĞƐƚĂǀşĂƉĂƌĂĞůſǆŝĚŽŶşƚƌŝĐŽ͕ŽƚƌĂŝŵƉŽƌƚĂŶƚĞZK͕;ƌĞǀŝƐĂĚŽĞŶ;DŽƌĂŶ
ĞƚĂů͕͘ϮϬϭϬͿͿ͘
ĞďŝĚŽĂůĂĂĨĞĐƚĂĐŝſŶƋƵĞ͕ĐŽŵŽĐŽŵĞŶƚĄďĂŵŽƐĐŽŶĂŶƚĞƌŝŽƌŝĚĂĚ͕ƉƌĞƐĞŶƚĂĞů
ŽŵƉůĞũŽ / ĚĞ ůĂ d ĞŶ ůŽƐ ĞŶĨĞƌŵŽƐ ĚĞ W͕ ƵŶ ŵŽĚĞůŽ ŵƵǇ ĞǆƚĞŶĚŝĚŽ ĚĞ W ĞŶ
ĐƵůƚŝǀŽƐĞƐ͕ƉƌĞĐŝƐĂŵĞŶƚĞ͕ĞůŽďƚĞŶŝĚŽŵĞĚŝĂŶƚĞůĂŝŶŚŝďŝĐŝſŶĚĞůĐŝƚĂĚŽĐŽŵƉůĞũŽĐŽŶ
ĨĄƌŵĂĐŽƐĞƐƉĞĐşĨŝĐŽƐ͘ĚĞŵĄƐ͕ĂĚşĂĚĞŚŽǇƐĂďĞŵŽƐƋƵĞĂůŐƵŶĂƐĚĞĞƐƚĂƐƐƵƐƚĂŶĐŝĂƐ͕
ĐŽŵŽ ĞƐ Ğů ĐĂƐŽ ĚĞ ZŽƚĞŶŽŶĂ Ž ĚĞ DWdW͕ ;ϭͲŵĞƚŝůͲϰͲĨĞŶŝůͲϭ͕Ϯ͕ϯ͕ϲͲƚĞƚƌĂŚŝĚƌŽƉŝƌŝĚŝŶĂͿ͕
ŝŶĚƵĐĞŶƚĂŵďŝĠŶŝŶĐƌĞŵĞŶƚŽƐĞŶůĂƚĂƐĂĚĞĨŝƐŝſŶŵŝƚŽĐŽŶĚƌŝĂů͕;^ĐŚĂƉŝƌĂĞƚĂů͕͘ϭϵϵϬͿ͕
ĚĞďŝĚŽƉƌŽďĂďůĞŵĞŶƚĞĂůĂƵŵĞŶƚŽĚĞůĂƐZKƋƵĞƉƌŽĚƵĐĞŶ͕;ŽŐĂĞƌƚƐĞƚĂů͕͘ϮϬϬϴͿ͘
ϲͲŚŝĚƌŽǆŝĚŽƉĂŵŝŶĂ͕ ;ϲͲK,Ϳ͕ ƉŽƌ ƐƵ ƉĂƌƚĞ͕ ĐŽŶƐƚŝƚƵǇĞ ƵŶ ŵŽĚĞůŽ ĐůĄƐŝĐŽ ĚĞ
ĞƐƚĂ ĞŶĨĞƌŵĞĚĂĚ͕ ƚĂŶƚŽ ĞŶ ĂŶŝŵĂůĞƐ ĐŽŵŽ ĞŶ ĐĠůƵůĂƐ͕ ;^ĐŚǁĂƌƚŝŶŐ Ğƚ Ăů͕͘ ϭϵϵϲĂ͖
^ĐŚǁĂƌƚŝŶŐĞƚĂů͕͘ϭϵϵϲďͿ͘^ĞƚƌĂƚĂĚĞƵŶĂŶĞƵƌŽƚŽǆŝŶĂƉƌŽĚƵĐŝĚĂĞŶĞůŵĞƚĂďŽůŝƐŵŽĚĞ
ůĂĚŽƉĂŵŝŶĂ͕;'ƌĂŚĂŵ͕ϭϵϳϴͿ͕ƉƌĞƐĞŶƚĞĚĞƵŶŵŽĚŽĞŶĚſŐĞŶŽĞŶĞůĐĞƌĞďƌŽ͕;ƵƌƚŝƵƐ
Ğƚ Ăů͕͘ ϭϵϳϰͿ͕ Ǉ ĞŶ ůĂ ŽƌŝŶĂ͕ ;ŶĚƌĞǁ Ğƚ Ăů͕͘ ϭϵϵϯͿ͘ 'ƌĂŶ ƉĂƌƚĞ ĚĞů ĐŽŶŽĐŝŵŝĞŶƚŽ ƋƵĞ
ƚĞŶĞŵŽƐĂĚşĂĚĞŚŽǇƐŽďƌĞůŽƐĞĨĞĐƚŽƐĚĞůĂĚŽƉĂŵŝŶĂĞŶĞůƐŝƐƚĞŵĂŶĞƌǀŝŽƐŽĐĞŶƚƌĂů
ŚĂ ƐŝĚŽ ŽďƚĞŶŝĚŽ ŐƌĂĐŝĂƐ Ă ĞƐƚĂ ƐƵƐƚĂŶĐŝĂ ĞŶ ĚŝǀĞƌƐŽƐ ŽƌŐĂŶŝƐŵŽƐ͘ Ŷ Ğů ĐĂƐŽ ĚĞ ůŽƐ
ĂŶŝŵĂůĞƐ͕ ƉƌĞƐĞŶƚĂ Ğů ƉƌŽďůĞŵĂ ĚĞ ŶŽ ƐĞƌ ĐĂƉĂǌ ĚĞ ĂƚƌĂǀĞƐĂƌ ůĂ ďĂƌƌĞƌĂ
ϯϵ
ŚĞŵĂƚŽĞŶĐĞĨĄůŝĐĂ͘^ŝŶĞŵďĂƌŐŽ͕ǇĂĞŶůŽƐĂŹŽƐƐĞƐĞŶƚĂ͕ƐĞĞŶĐŽŶƚƌſĞůŵŽĚŽĚĞŚĂĐĞƌ
ůůĞŐĂƌ ůĂ ϲͲK, Ăů ĐĞƌĞďƌŽ͗ Ă ƚƌĂǀĠƐ ĚĞ ŝŶǇĞĐĐŝŽŶĞƐ ĞƐƚĞƌŽƚĄǆŝĐĂƐ ŝŶƚƌĂ ĐƌĂŶĞĂůĞƐ͕
ĐŽŶĐƌĞƚĂŵĞŶƚĞĞŶůĂƐƵďƐƚĂŶƚŝĂŶŝŐƌĂƉĂƌƐĐŽŵƉĂĐƚĂ͕;hŶŐĞƌƐƚĞĚƚ͕ϭϵϲϴͿ͘
ƐƚĂ ŵŽůĠĐƵůĂ ŚĂ ƐŝĚŽ ƵƚŝůŝǌĂĚĂ ĂŵƉůŝĂŵĞŶƚĞ ĞŶ ŵŽĚĞůŽƐ ƉƌĞĐůşŶŝĐŽƐ ƉĂƌĂ
ĞƐƚƵĚŝĂƌ ůŽƐ ĞĨĞĐƚŽƐ ĚĞ ĨĄƌŵĂĐŽƐ ĂŶƚŝƉĂƌŬŝŶƐŽŶŝĂŶŽƐ Ž ĚĞ ƚĞƌĂƉŝĂƐ ŶĞƵƌŽƉƌŽƚĞĐƚŽƌĂƐ͕
;ŚĂŶ Ğƚ Ăů͕͘ ϮϬϭϬ͖ /ůŝũŝĐ Ğƚ Ăů͕͘ ϮϬϭϭ͖ :ŝĂŶŐ Ğƚ Ăů͕͘ ϭϵϵϯͿ͕ Ǉ ĞŶ ĞŶƐĂǇŽƐ ĚĞ ĚŝǀĞƌƐŽƐ
ƉƌŽĐĞĚŝŵŝĞŶƚŽƐ ĐůşŶŝĐŽƐ ĞŶĐĂŵŝŶĂĚŽƐ Ăů ƚƌĂŶƐƉůĂŶƚĞ ĐĞůƵůĂƌ͕ ;ũŽƌŬůƵŶĚ Ğƚ Ăů͕͘ ϮϬϬϮ͖
<ŝƌŝŬ Ğƚ Ăů͕͘ ϮϬϬϮ͖ ZŽǇ Ğƚ Ăů͕͘ ϮϬϬϲͿ͘ ^ŝŶ ĞŵďĂƌŐŽ͕ ĞƐƚĞ ŵŽĚĞůŽ͕ ĐŽŵŽ ƐƵĞůĞ ƐƵĐĞĚĞƌ
ŚĂďŝƚƵĂůŵĞŶƚĞĞŶůĂĐŝĞŶĐŝĂ͕ŶŽĞƐƉĞƌĨĞĐƚŽ͘Ɛş͕ƵŶĂĚĞůĂƐƉƌŝŶĐŝƉĂůĞƐĐƌşƚŝĐĂƐƋƵĞƐĞ
ƌĞĂůŝǌĂĞƐůĂĚĞƋƵĞϲͲK,ŶŽĞƐĐĂƉĂǌĚĞŝŶĚƵĐŝƌůĂĨŽƌŵĂĐŝſŶĚĞůŽƐĐƵĞƌƉŽƐĚĞ>ĞǁǇ
ŶŝĚĞŶŝŶŐƷŶƚŝƉŽĚĞĂŐƌĞŐĂĚŽƐĚĞŶĂƚƵƌĂůĞǌĂƉƌŽƚĠŝĐĂ͕ĂŵďŽƐƌĂƐŐŽƐĐĂƌĂĐƚĞƌşƐƚŝĐŽƐĚĞ
ůŽƐĐĞƌĞďƌŽƐĚĞůŽƐƉĂĐŝĞŶƚĞƐĚĞW͕ĂƉĞƐĂƌĚĞƋƵĞƐşƋƵĞĞƐĐĂƉĂǌĚĞŝŶƚĞƌĂĐƚƵĂƌĐŽŶ
ůĂ ƉƌŽƚĞşŶĂ ɲͲƐŝŶƵĐůĞşŶĂ͕ ;ůǀĞƐ ĚĂ ŽƐƚĂ Ğƚ Ăů͕͘ ϮϬϬϲͿ͘ dĂŵďŝĠŶ ĞƐ ĐŝĞƌƚŽ ƋƵĞ ĞƐƚĂ
ŶĞƵƌŽƚŽǆŝŶĂ͕ Ăů ŝŐƵĂů ƋƵĞ ŵƵĐŚŽƐ ŽƚƌŽƐ ĨĄƌŵĂĐŽƐ ƵƐĂĚŽƐ ƉĂƌĂ ĐƌĞĂƌ ŵŽĚĞůŽƐ ĚĞ
ĞŶĨĞƌŵĞĚĂĚĞƐŶĞƵƌŽĚĞŐĞŶĞƌĂƚŝǀĂƐ͕ƉƌŽĚƵĐĞƐşŶĚƌŽŵĞƐĂŐƵĚŽƐ͕ƉŽƌůŽƋƵĞŶŽƌĞŵĞĚĂ
ůĂƉƌŽŐƌĞƐŝǀŝĚĂĚ͕ĂƐşĐŽŵŽĞůĞĨĞĐƚŽĚĞůĂĞĚĂĚ͕ƋƵĞƉƌĞƐĞŶƚĂůĂW͕;dŝĞƵ͕ϮϬϭϭͿ͘
ŶŵŽĚĞůŽƐĐĞůƵůĂƌĞƐ͕ƉŽƌƐƵƉĂƌƚĞ͕ŚĂƋƵĞĚĂĚŽƐŽďƌĂĚĂŵĞŶƚĞĚĞŵŽƐƚƌĂĚĂůĂ
ĐĂƉĂĐŝĚĂĚ ĚĞ ĞƐƚĂ ŶĞƵƌŽƚŽǆŝŶĂ ƉĂƌĂ ŝŶĚƵĐŝƌ ůĂ ŵƵĞƌƚĞ ĐĞůƵůĂƌ ĂƉŽƉƚſƚŝĐĂ ĚĞ ůĂƐ
ŶĞƵƌŽŶĂƐĚŽƉĂŵŝŶĠƌŐŝĐĂƐ͕ĐƌĞĂŶĚŽƵŶĞƐĐĞŶĂƌŝŽƐŝŵŝůĂƌĂůŽďƐĞƌǀĂĚŽĞŶůŽƐƉĂĐŝĞŶƚĞƐ
ĚĞ W͘ Ɛş͕ ĞŶĐŽŶƚƌĂŵŽƐ ĚĂƚŽƐ ĐŽŶĨŝƌŵĂŶĚŽ ĞƐƚĞ ŚĞĐŚŽ ĞŶ ƚƌĂďĂũŽƐ ƌĞĂůŝǌĂĚŽƐ ĞŶ
ĐĠůƵůĂƐ ^<ͲEͲ^,͕ ƉƌŽǀĞŶŝĞŶƚĞƐ ĚĞ ŶĞƵƌŽďůĂƐƚŽŵĂ ŚƵŵĂŶŽ͕ ;^ŚŝŵŝǌƵ Ğƚ Ăů͕͘ ϮϬϬϮͿ͖ ĞŶ
WϭϮ͕ ;ĐĠůƵůĂƐ ƉƌŽǀĞŶŝĞŶƚĞƐ ĚĞ ĨĞŽĐƌŽŵŽĐŝƚŽŵĂ͕ ;EŝĞ Ğƚ Ăů͕͘ ϮϬϬϮͿ͖ ĞŶ ĐĠůƵůĂƐ
ĐƌŽŵĂĨŝŶĞƐ͕;'ĂůŝŶĚŽĞƚĂů͕͘ϮϬϬϯͿ͖ŽĞŶůĂůşŶĞĂĐĞůƵůĂƌƋƵĞŚĞŵŽƐƵƚŝůŝǌĂĚŽĞŶŶƵĞƐƚƌŽ
ƚƌĂďĂũŽ͕ĞƐƚŽ͕^,Ͳ^zϱz͕ĐƵǇŽŽƌŝŐĞŶĞƐƚĂŵďŝĠŶƵŶŶĞƵƌŽďůĂƐƚŽŵĂŚƵŵĂŶŽ͕;ǀŽŶŽĞůůŶ
Ğƚ Ăů͕͘ ϮϬϬϭͿ͘ >Ă ĐŝƚĂĚĂ ůşŶĞĂ ^,Ͳ^zϱz͕ ƉƌŽǀŝĞŶĞ ĚĞ ŶĞƵƌŽďůĂƐƚŽŵĂ ŚƵŵĂŶŽ Ǉ ĞƐ ĚĞ
ŶĂƚƵůĂƌĞǌĂ ĚŽƉĂŵŝŶĠƌŐŝĐĂ͕ ƐŝĞŶĚŽ͕ ƉŽƌ ƚĂŶƚŽ͕ ƐĞŶƐŝďůĞ Ăů ĞĨĞĐƚŽ ĚĞ ůĂ ϲͲK,͕
;^ŝŵĂŶƚŽǀĞƚĂů͕͘ϭϵϵϲ͖^ƚŽƌĐŚĞƚĂů͕͘ϮϬϬϬ͖dŝĨĨĂŶǇͲĂƐƚŝŐůŝŽŶŝĞƚĂů͕͘ϭϵϴϮͿ͘
ůŵĞĐĂŶŝƐŵŽĚĞĂĐĐŝſŶĚĞϲͲK,ŶŽŚĂƐŝĚŽƚŽƚĂůŵĞŶƚĞĞůƵĐŝĚĂĚŽĂĚşĂĚĞ
ŚŽǇ͕ĂƵŶƋƵĞƐşƋƵĞƐĂďĞŵŽƐƋƵĞ͕ĞƐƚĂŶĞƵƌŽƚŽǆŝŶĂ͕ĞŶƚƌĂĞŶůĂƐŶĞƵƌŽŶĂƐĂƚƌĂǀĠƐĚĞ
ϰϬ
ůŽƐƚƌĂƐƉŽƌƚĂĚŽƌĞƐĚĞĚŽƉĂŵŝŶĂ͕ůŽƐĐƵĂůĞƐŵƵĞƐƚƌĂŶƵŶĂĂůƚĂĂĨŝŶŝĚĂĚƉŽƌĞůůĂ͕;'ůŝŶŬĂ
Ğƚ Ăů͕͘ ϭϵϵϳ͖ :ŽŶƐƐŽŶ Ğƚ Ăů͕͘ ϭϵϳϭ͖ >ƵƚŚŵĂŶ Ğƚ Ăů͕͘ ϭϵϴϵͿ͘ ĞƐƉƵĠƐ͕ ƐƵĨƌĞ ĚŝǀĞƌƐĂƐ
ƌĞĂĐĐŝŽŶĞƐ͕ ůĂƐ ĐƵĂůĞƐ ƉƌŽĚƵĐĞŶ ƐƵ ŽǆŝĚĂĐŝſŶ Ǉ ůĂ ĐŽŶƐĞĐƵĞŶƚĞ ƉƌŽĚƵĐĐŝſŶ ĚĞ ƉĂƌĂͲ
ƋƵŝŶŽŶĂƐǇĚĞ,ϮKϮ͕;'ƌĂŚĂŵĞƚĂů͕͘ϭϵϳϴ͖^ĂŶĞƌĞƚĂů͕͘ϭϵϳϭͿ͘>ůĞŐĂĚŽƐĂĞƐƚĞƉƵŶƚŽ͕
ĐůĄƐŝĐĂŵĞŶƚĞ ƐĞ ƉŽƐƚƵůĂďĂ ƋƵĞ ϲͲK, ƉŽĚşĂ ƐĞŐƵŝƌ ĚŽƐ ŵĞĐĂŶŝƐŵŽƐ ĚĞ ĂĐĐŝſŶ
ŝŶĚĞƉĞŶĚŝĞŶƚĞƐ͕ ĂƵŶƋƵĞ ƐŝŶĠƌŐŝĐŽƐ͗ ůĂ ĨŽƌŵĂĐŝſŶ ĚŝƌĞĐƚĂ ĚĞ ƌĂĚŝĐĂůĞƐ ůŝďƌĞƐ Ǉ ůĂ
ŝŶŚŝďŝĐŝſŶĚĞůĂĂĐƚŝǀŝĚĂĚĚĞůĂĐĂĚĞŶĂĚĞƚƌĂŶƐƉŽƌƚĞĚĞĞůĞĐƚƌŽŶĞƐ͕;'ůŝŶŬĂĞƚĂů͕͘ϭϵϵϳ͖
<ŽƐƚƌǌĞǁĂĞƚĂů͕͘ϭϵϳϰͿ͘
ZĞƐƉĞĐƚŽĂůĂĂĐƚŝǀĂĐŝſŶĚĞůƉƌŝŵĞƌŽĚĞůŽƐĐŝƚĂĚŽƐŵĞĐĂŶŝƐŵŽƐ͕ƉĂƌĞĐĞŚĂďĞƌ
ƵŶĂŶŝŵŝĚĂĚ ĞŶƚƌĞ ůĂ ĐŽŵƵŶŝĚĂĚ ĐŝĞŶƚşĨŝĐĂ͘ Ɛş͕ ĞŶĐŽŶƚƌĂŵŽƐ ŵƵĐŚŽƐ ƚƌĂďĂũŽƐ ĞŶ ůĂ
ďŝďůŝŽŐƌĂĨşĂ ƋƵĞ ŵƵĞƐƚƌĂŶ ƋƵĞ͕ ĚĞƐĚĞ ŚĂĐĞ ďĂƐƚĂŶƚĞƐ ĂŹŽƐ͕ Ğů ĞƐƚƵĚŝŽ ĚĞ ůĂƐ ZK
ƉƌŽĚƵĐŝĚĂƐƉŽƌϲK,ǇĚĞůĞĨĞĐƚŽĚĞůŽƐĂŶƚŝŽǆŝĚĂŶƚĞƐĞŶĞƐƚĞŵŽĚĞůŽ͕ŚĂƐŝĚŽƵŶĂ
ĞƐƚƌĂƚĞŐŝĂďĂƐƚĂŶƚĞƐĞŐƵŝĚĂ͕ƚĂŶƚŽĞŶƐŝƐƚĞŵĂƐĐĞůƵůĂƌĞƐ͕;ďĂĚĞƚĂů͕͘ϭϵϵϱ͖'ĂƐƐĞŶĞƚ
Ăů͕͘ϭϵϵϴ͖dŝĨĨĂŶǇͲĂƐƚŝŐůŝŽŶŝĞƚĂů͕͘ϭϵϴϮͿ͕ĐŽŵŽĂŶŝŵĂůĞƐ͕;ĂĚĞƚĞƚĂů͕͘ϭϵϴϵ͖<ƵŵĂƌĞƚ
Ăů͕͘ϭϵϵϱ͖WĞƌƵŵĂůĞƚĂů͕͘ϭϵϵϮͿ͘ϲͲK,͕ĐŽŵŽŝŶĚŝĐĄďĂŵŽƐĐŽŶĂŶƚĞƌŝŽƌŝĚĂĚ͕ĞƐĐĂƉĂǌ
ĚĞ ƉƌŽĚƵĐŝƌ ƵŶ ŝŶĐƌĞŵĞŶƚŽ ĐŽŶƐŝĚĞƌĂďůĞ ĚĞ ůĂ ĐŽŶĐĞŶƚƌĂĐŝſŶ ĚĞ ZK͕ ŐƌĂĐŝĂƐ Ă ůŽƐ
ĐŝĐůŽƐ ĚĞ ĂƵƚŽ ŽǆŝĚĂĐŝſŶ ƋƵĞ ƐƵĨƌĞ͕ ;ďĂĚ Ğƚ Ăů͕͘ ϭϵϵϱ͖ DŝĐŚĞů Ğƚ Ăů͕͘ ϭϵϵϬ͖ dŝĨĨĂŶǇͲ
ĂƐƚŝŐůŝŽŶŝĞƚĂů͕͘ϭϵϴϮͿ͘DĄƐƌĞĐŝĞŶƚĞŵĞŶƚĞŚĂƋƵĞĚĂĚŽĐŽŶƐƚĂƚĂĚŽƋƵĞĞƐƚĂƐZKƐŽŶ
ůĂƐĐĂƵƐĂŶƚĞƐ͕ĂƐƵǀĞǌ͕ĚĞůŽƐŝŶĐƌĞŵĞŶƚŽƐĞŶůĂĨŝƐŝſŶŵŝƚŽĐŽŶĚƌŝĂůǇĞŶůĂĂƉŽƉƚŽƐŝƐ
ƋƵĞƐĞŽďƐĞƌǀĂŶ͕;ŝƐǁĂƐĞƚĂů͕͘ϮϬϬϱ͖'ŽŵĞǌͲ>ĂǌĂƌŽĞƚĂů͕͘ϮϬϬϴď͖:ĞŶŶĞƌ͕ϮϬϬϯ͖<ƵůŝĐŚ
ĞƚĂů͕͘ϮϬϬϳͿ͘ĚĞŵĄƐ͕ĚĞďŝĚŽĂůŝŶĐƌĞŵĞŶƚŽĞŶůĂƉƌŽĚƵĐĐŝſŶĚĞZK͕ĞůŵĞƚĂďŽůŝƐŵŽ
ĚĞů ĐĂůĐŝŽ ƐĞ ǀĞ ƚĂŵďŝĠŶ ĂĨĞĐƚĂĚŽ͕ ůŽ ĐƵĂů ƉƌŽĚƵĐĞ͕ Ă ƐƵ ǀĞǌ͕ ŵƵĞƌƚĞ ĞǆĐŝƚŽƚſǆŝĐĂ Ž
ĚƐŝĨƵŶĐŝŽŶĞƐŵŝƚŽĐŽŶĚƌŝĂůĞƐ͕ĂĐƚŝǀĄŶĚŽƐĞ͕ĞŶĂŵďŽƐĐĂƐŽƐ͕ůĂƐĐĂƐƉĂƐĂƐǇ͕ƉŽƌƚĂŶƚŽ͕ůĂ
ĂƉŽƉƚŽƐŝƐ͕;ĂŶŶŽŶĞƚĂů͕͘ϮϬϭϬ͖,ĞŶĐŚĐůŝĨĨĞĞƚĂů͕͘ϮϬϬϴ͖<ĂŶƚŚĂƐĂŵǇĞƚĂů͕͘ϮϬϭϬͿ͘
ƉĞƐĂƌ ĚĞ ůĂ ƵŶĂŶŝŵŝĚĂĚ ĞǆŝƐƚĞŶƚĞ ƐŽďƌĞ Ğů ŚĞĐŚŽ ĚĞ ƋƵĞ ϲͲK, ŝŶĚƵĐĞ
ŝŶĐƌĞŵĞŶƚŽƐĐŽŶƐŝĚĞƌĂďůĞƐĞŶůĂƉƌŽĚƵĐĐŝſŶĚĞZK͕ŚĂǇĚĂƚŽƐĞŶĂƉĂƌŝĞŶĐŝĂŽƉƵĞƐƚŽƐ
ƌĞƐƉĞĐƚŽ Ă ůĂ ĐĂƉĂĐŝĚĂĚ ĐŝƚŽƉƌŽƚĞĐƚŽƌĂ ĚĞ ůĂƐ ďĂƌƌĞƌĂƐ ĂŶƚŝ ŽǆŝĚĂŶƚĞƐ ĐŽŶƚƌĂ Ğů ĚĂŹŽ
ĐŝƚŽƚſǆŝĐŽƉƌŽĚƵĐŝĚŽƉŽƌƉĂƌƚĞĚĞĞƐƚĂŶĞƵƌŽƚŽǆŝŶĂ͘Ɛş͕ƉŽƌĞũĞŵƉůŽ͕ŚĂǇƚƌĂďĂũŽƐƋƵĞ
ŵƵĞƐƚƌĂŶ ƋƵĞ Ɛş ƋƵĞ ĞǆŝƐƚĞ ĞƐƚĂ ƉƌŽƚĞĐĐŝſŶ͕ ƉŽƌ ƉĂƌƚĞ ĚĞ ůĂƐ ĞŶǌŝŵĂƐ ĐĂƚĂůĂƐĂ Ǉ
ƐƵƉĞƌſǆŝĚŽĚŝƐŵƵƚĂƐĂ͕;ƐĂŶƵŵĂĞƚĂů͕͘ϭϵϵϴ͖ĂƌŬĂƚƐĞƚĂů͕͘ϮϬϬϮ͖<ĂďƵƚŽĞƚĂů͕͘ϭϵϵϵ͖
ϰϭ
<ƵůŝĐŚĞƚĂů͕͘ϮϬϬϳͿ͕ŵŝĞŶƚƌĂƐƋƵĞ͕ĞŶŽƚƌŽƐ͕ƐĞĂĨŝƌŵĂũƵƐƚŽůŽĐŽŶƚƌĂƌŝŽ͕;ůƵŵĞƚĂů͕͘
ϮϬϬϬ͖ŚŽŝĞƚĂů͕͘ϭϵϵϵ͖,ĂŶƌŽƚƚĞƚĂů͕͘ϮϬϬϲ͖/ǌƵŵŝĞƚĂů͕͘ϮϬϬϱ͖^ĂŝƚŽĞƚĂů͕͘ϮϬϬϳͿ͘
^ŝŶ ĞŵďĂƌŐŽ͕ ĞŶ ƌĞůĂĐŝſŶ ĐŽŶ Ğů ĞĨĞĐƚŽ ĚĞ ϲͲK, ƐŽďƌĞ Ğů ŵĞƚĂďŽůŝƐŵŽ
ĞŶĞƌŐĠƚŝĐŽŚĂǇďĂƐƚĂŶƚĞĐŽŶƚƌŽǀĞƌƐŝĂ͘Ɛş͕ĞŶƵŶƚƌĂďĂũŽƌĞĂůŝǌĂĚŽĞŶ^,Ͳ^zϱz͕ƋƵĞĚſ
ĚĞŵŽƐƚƌĂĚŽ ƋƵĞ ϲͲK, ŝŶĚƵĐşĂ ĂƉŽƉƚŽƐŝƐ͕ ƉĞƌŽ ŶŽ ĞƌĂ ĐĂƉĂǌ ĚĞ ƌĞĚƵĐŝƌ ůĂ
ĐŽŶĐĞŶƚƌĂĐŝſŶ ŝŶƚƌĂĐĞůƵůĂƌ ĚĞ dW͕ Ğů ƌĂƚŝŽ ŝŶƚƌĂĐĞůƵůĂƌ dWͬW Ž Ğů ĐŽŶƚĞŶŝĚŽ ĞŶ
E͘ĚŝĐŝŽŶĂůŵĞŶƚĞ͕ůĂƉƌĞǀĞŶĐŝſŶŽůĂŝŶĚƵĐĐŝſŶĚĞůĂŐůŝĐſůŝƐŝƐŶŽĂůƚĞƌſĞůşŶĚŝĐĞĚĞ
ŵƵĞƌƚĞ ĐĞůƵůĂƌ ƉƌŽĚƵĐŝĚŽ ƉŽƌ ĞƐƚĂ ŶĞƵƌŽƚŽǆŝŶĂ͘ ĐŽŶƚŝŶƵĂĐŝſŶ͕ ĞƐƚƵĚŝĂƌŽŶ Ğů ĞĨĞĐƚŽ
ĚĞů ĂŶƚŝŽǆŝĚĂŶƚĞ ƚŽĐŽĨĞƌŽů͕ Ğů ĐƵĂů Ɛş ƋƵĞ ĨƵĞ ĐĂƉĂǌ ĚĞ ĂƚĞŶƵĂƌ ůĂ ŵƵĞƌƚĞ ĐĞůƵůĂƌ
ŝŶĚƵĐŝĚĂ ƉŽƌ ϲͲK,͕ ;^ƚŽƌĐŚ Ğƚ Ăů͕͘ ϮϬϬϬͿ͘ Ɛş͕ ĞƐƚĞ ƚƌĂďĂũŽ ƉĂƌĞĐĞ ŶĞŐĂƌ ůĂ ĂĐĐŝſŶ
ŝŶŚŝďŝƚŽƌŝĂĚĞĞƐƚĂŶĞƵƌŽƚŽǆŝŶĂƐŽďƌĞĞůĐŽŵƉůĞũŽ/ĚĞůĂd͕ĂůŝŐƵĂůƋƵĞůŽŚĂĐĞŽƚƌŽ
ĂƵƚŽƌ͕ ;DĂǌǌŝŽĞƚ Ăů͕͘ ϮϬϬϰͿ͘ ^ŝŶ ĞŵďĂƌŐŽ͕ƚĂŵďŝĠŶ ŚĂǇ ĂƌƚşĐƵůŽƐ ĞŶ ůŽƐƋƵĞ ƐşƋƵĞ ƐĞ
ŽďƐĞƌǀĂĞƐƚĞĞĨĞĐƚŽ͕;'ůŝŶŬĂĞƚĂů͕͘ϭϵϵϴ͖'ůŝŶŬĂĞƚĂů͕͘ϭϵϵϲͿ͘
ƵŶƋƵĞ ŚĂǇ ďĂƐƚĂŶƚĞ ƵŶĂŶŝŵŝĚĂĚ ƐŽďƌĞ ƋƵĞ Ğů ƚŝƉŽ ĚĞ ŵƵĞƌƚĞ ŶĞƵƌŽŶĂů ƋƵĞ
ŝŶĚƵĐĞϲͲK,ĞƐĂƉŽƉƚſƚŝĐĂ͕ŚĂǇƵŶƚƌĂďĂũŽŝŶƚĞƌĞƐĂŶƚĞƐŽďƌĞĞƐƚĞĂƐƉĞĐƚŽ͘Ɛş͕ƵŶ
ŐƌƵƉŽ ĚĞŵŽƐƚƌſ͕ ƚƌĂďĂũĂŶĚŽ ĐŽŶ ĐĠůƵůĂƐ WϭϮ͕ ƋƵĞ͕ ĐŽŵŽ ŝŶĚŝĐĄďĂŵŽƐ͕ ůĂ ĂƉŽƉƚŽƐŝƐ
ĐŽŶƐƚŝƚƵşĂĞůƉƌŝŶĐŝƉĂůŵŽĚŽĚĞŵƵĞƌƚĞĐĞůƵůĂƌ͕ƚƌĂƐůĂĂĚŝĐŝſŶĚĞϲͲK,ĂĚŽƐŝƐďĂũĂƐ͕
ŵŝĞŶƚƌĂƐƋƵĞ͕ĐƵĂŶĚŽƐĞĂŹĂĚşĂĂĚŽƐŝƐŵĄƐĞůĞǀĂĚĂƐ͕ĞůƚŝƉŽĚĞŵƵĞƌƚĞŽďƐĞƌǀĂĚŽĞƌĂ
ŶĞĐƌſƚŝĐŽ͕;KĐŚƵĞƚĂů͕͘ϭϵϵϴ͖tĂůŬŝŶƐŚĂǁĞƚĂů͕͘ϭϵϵϰͿ͘
4.2. Enfermedad de Huntington
^Ğ ƚƌĂƚĂ ĚĞ ƵŶĂ ƉĂƚŽůŽŐşĂ ĂƵƚŽƐſŵŝĐĂ ĚŽŵŝŶĂŶƚĞ͕ ƉŽƌ ůŽ ƋƵĞ ƐƵ ŽƌŝŐĞŶ ĞƐ
ĐůĂƌĂŵĞŶƚĞ ŐĞŶĠƚŝĐŽ͕ ůŽ ĐƵĂů ŶŽ ĞƐ ŵƵǇ ĐŽŵƷŶ ĞŶ Ğů ĐĂƐŽ ĚĞ ůĂƐ ĞŶĨĞƌŵĞĚĂĚĞƐ
ŶĞƵƌŽĚĞŐĞŶĞƌĂƚŝǀĂƐ͘ ŽŶĐƌĞƚĂŵĞŶƚĞ͕ ĞŶ ĞƐƚĞ ĐĂƐŽ ƐĞ ƉƌŽĚƵĐĞ ůĂ ƌĞƉĞƚŝĐŝſŶ
ĚĞƐŵĞƐƵƌĂĚĂĚĞůƚƌŝŶƵĐůĞſƚŝĚŽ'ĞŶĞůŐĞŶƋƵĞĐŽĚŝĨŝĐĂƉĂƌĂůĂƉƌŽƚĞşŶĂŚƵŶƚŝŶŐƚŝŶĂ
;,ƚƚͿ͕ ;DĂƌƚŝŶ͕ ϭϵϴϮͿ͘ ƐƚĂ ƌĞŐŝſŶ ƐĞ ƌĞƉŝƚĞ ĞŶƚƌĞ ŽŶĐĞ Ǉ ƚƌĞŝŶƚĂ Ǉ ĐŝŶĐŽ ǀĞĐĞƐ ĞŶ
ŝŶĚŝǀŝĚƵŽƐ ƐĂŶŽƐ͕ ŵŝĞŶƚƌĂƐ ƋƵĞ͕ ƵŶ ǀĂůŽƌ ƐƵƉĞƌŝŽƌ͕ ŝŶĚŝĐĂ ƵŶ ƌŝĞƐŐŽ ŝŵƉŽƌƚĂŶƚĞ ĚĞ
ĚĞƐĂƌƌŽůůĂƌůĂ,͕;ZƵďŝŶƐǌƚĞŝŶĞƚĂů͕͘ϭϵϵϲͿ͘ĚĞŵĄƐ͕ƐĞŚĂĚĞƐĐƌŝƚŽƋƵĞ͕ĐƵĂŶƚŽŵĂǇŽƌ
ƐĞĂ Ğů ŶƷŵĞƌŽ ĚĞ ƌĞƉĞƚŝĐŝŽŶĞƐ ĚĞů ƚƌŝŶƵĐůĞſƚŝĚŽ͕ ĐŽŶ ŵĂǇŽƌ ƐĞǀĞƌŝĚĂĚ ƐĞ ǀĂŶ Ă
ŵĂŶŝĨŝĞƐƚĂƌůŽƐƐşŶƚŽŵĂƐĚĞůĂ,͕;ƌĂŶĚƚĞƚĂů͕͘ϭϵϵϲ͖/ůůĂƌŝŽƐŚŬŝŶĞƚĂů͕͘ϭϵϵϰͿ͘
ϰϮ
>ŽƐ ƉƌŝŶĐŝƉĂůĞƐ ƐşŶƚŽŵĂƐ ĚĞ ĞƐƚĂ ƉĂƚŽůŽŐşĂ ƐŽŶ ůĂƐ ĚŝƐĨƵŶĐŝŽŶĞƐ ƉƐŝƋƵŝĄƚƌŝĐĂƐ͕
;ƉĞƌƐŽŶĂůŝĚĂĚ ĂŶƚŝƐŽĐŝĂů͕ ĚĞƐſƌĚĞŶĞƐ ƉƐŝĐŽƐŽŵĄƚŝĐŽƐ Ž ĂĨĞĐƚŝǀŽƐ͕ ĞƐƋƵŝǌŽĨƌĞŶŝĂ͘͘͘Ϳ͖ Ğů
ĚĞĐůŝǀĞĐŽŐŶŝƚŝǀŽǇůŽƐŵŽǀŝŵŝĞŶƚŽƐĐŽƌĞŝĨŽƌŵĞƐ͕;ŚĞŶ͕ϮϬϭϭ͖EĂŶĐĞ͕ϭϵϵϳ͖sŽŶƐĂƚƚĞů
ĞƚĂů͕͘ϭϵϵϴͿ͘>ŽƐĐŝƚĂĚŽƐƐşŶƚŽŵĂƐƉƵĞĚĞŶƉƌĞƐĞŶƚĂƌĐŝĞƌƚĂƐǀĂƌŝĂĐŝŽŶĞƐĞŶĨƵŶĐŝſŶĚĞ
ƐŝůĂĞŶĨĞƌŵĞĚĂĚƐĞƉƌĞƐĞŶƚĂĞŶŝŶĚŝǀŝĚƵŽƐĚĞĞĚĂĚŝŐƵĂůŽŝŶĨĞƌŝŽƌĂǀĞŝŶƚĞĂŹŽƐ͕;,
ƚĞŵƉƌĂŶĂŽũƵǀĞŶŝůͿ͕ŽƐŝƐĞƚƌĂƚĂĚĞƉĂĐŝĞŶƚĞƐƋƵĞƐƵƉĞƌĂŶĞƐƚĂĞĚĂĚ͕;,ĂĚƵůƚĂͿ͘Ɛş͕
ŵŝĞŶƚƌĂƐ ƋƵĞ ĞŶ Ğů ƉƌŝŵĞƌ ĐĂƐŽ ĞŶĐŽŶƚƌĂŵŽƐ ĨƌĞĐƵĞŶƚĞƐ ĞƉŝƐŽĚŝŽƐ ĚĞ ƉƌŽďůĞŵĂƐ
ŵĞŶƚĂůĞƐ Ǉ ƌŝŐŝĚĞǌ͕ ůŽƐ ŵŽǀŝŵŝĞŶƚŽƐ ĐŽƌĠŝĐŽƐ ƐŽŶ ŵĄƐ ƚşƉŝĐŽƐ ĞŶ ůŽƐ ƉĂĐŝĞŶƚĞƐ ĚĞů
ƐĞŐƵŶĚŽŐƌƵƉŽ͘ƵƌŝŽƐĂŵĞŶƚĞ͕ƉĂƌĞĐĞĞǆŝƐƚŝƌƵŶĂƌĞůĂĐŝſŶŝŶǀĞƌƐĂŵĞŶƚĞƉƌŽƉŽƌĐŝŽŶĂů
ĞŶƚƌĞĞůŵŽŵĞŶƚŽĚĞĂƉĂƌŝĐŝſŶĚĞůŽƐƉƌŝŵĞƌŽƐƐşŶƚŽŵĂƐĚĞůĂĞŶĨĞƌŵĞĚĂĚǇůĂĐĂƌŐĂ
ĚĞƌĞƉĞƚŝĐŝŽŶĞƐĚĞůƚƌŝŶƵĐůĞſƚŝĚŽ'͕ůŽĐƵĂůƐĞŚĂĐĞĂƷŶŵĄƐƉĂƚĞŶƚĞĞŶƚƌĞůŽƐĐĂƐŽƐ
ĚĞ,ĚĞƚŝƉŽũƵǀĞŶŝů͕;ƌŝŶŬŵĂŶĞƚĂů͕͘ϭϵϵϳ͖dƌŽƚƚŝĞƌĞƚĂů͕͘ϭϵϵϰͿ͘ůŝŐƵĂůƋƵĞƐƵĐĞĚĞ
ĞŶĞůĐĂƐŽĚĞŽƚƌĂƐĞŶĨĞƌŵĞĚĂĚĞƐŶĞƵƌŽĚĞŐĞŶĞƌĂƚŝǀĂƐ͕ƚĂŵƉŽĐŽĂƋƵşůŽƐŵĞĐĂŶŝƐŵŽƐ
ƉĂƚŽůſŐŝĐŽƐ Ă ƚƌĂǀĠƐ ĚĞ ůŽƐ ĐƵĂůĞƐ ƐĞ ƉƌŽĚƵĐĞŶ ĞƐƚŽƐ ƐşŶƚŽŵĂƐ ĞƐƚĄŶ ĚŝůƵĐŝĚĂĚŽƐ͕
ƉŽƐƚƵůĄŶĚŽƐĞƵŶƉĂƉĞůŝŵƉŽƌƚĂŶƚĞƉĂƌĂůŽƐĚĞĨĞĐƚŽƐ ĞŶůĂŵŝƚŽĨĂŐŝĂ͕ůĂƐĚŝƐĨƵŶĐŝŽŶĞƐ
ŵŝƚŽĐŽŶĚƌŝĂůĞƐ͕ĞůĞƐƚƌĠƐŽǆŝĚĂƚŝǀŽŽůĂĂƉŽƉƚŽƐŝƐ͘
>Ă ŵƵƚĂĐŝſŶ ĞŶ ůĂ ƉƌŽƚĞşŶĂ ,ƚƚ ĐŽŶĚƵĐĞ Ă ůĂ ĂĐƵŵƵůĂĐŝſŶ ĚĞ ƉŽůŝŐůƵƚĂŵŝŶĂƐ͕
;ƚĂŵďŝĠŶ ůůĂŵĂĚĂ WŽůǇYͿ͕ ůĂƐ ĐƵĂůĞƐ ĞůŽŶŐĂŶ ,ƚƚ ĞŶ ƐƵ ĞǆƚƌĞŵŽ EͲƚĞƌŵŝŶĂů͕ ;,Z'͕
ϭϵϵϯͿ͘ ƐƚĞ ŚĞĐŚŽ ĐŽŶůůĞǀĂ͕ Ă ƐƵ ǀĞǌ͕ ƵŶ ĐĂŵďŝŽ ĐŽŶĨŽƌŵĂĐŝŽŶĂů ĞŶ ůĂ ,ƚƚ ŵƵƚĂĚĂ͕
ĨŽƌŵĄŶĚŽƐĞĞŶƚŽŶĐĞƐĂŐƌĞŐĂĚŽƐŝŶƚƌĂĐŝƚŽƉůĂƐŵĄƚŝĐŽƐĞŝŶƚƌĂŶƵĐůĞĂƌĞƐ͘ŶĐŽŶĚŝĐŝŽŶĞƐ
ĨŝƐŝŽůſŐŝĐĂƐ͕ůĂĚĞŐƌĂĚĂĐŝſŶĚĞůŽƐĂŐƌĞŐĂĚŽƐĚĞ,ƚƚƐĞůůĞǀĂĂĐĂďŽĂƚƌĂǀĠƐĚĞůƐŝƐƚĞŵĂ
ƵďŝƋƵŝƚŝŶĂͲƉƌŽƚĞŽƐŽŵĂ͘ ^ŝŶ ĞŵďĂƌŐŽ͕ ĞŶ ƉĂĐŝĞŶƚĞ ĚĞ ,͕ ĚĞďŝĚŽ Ăů ĞǆĐĞƐŽ ĚĞ ĞƐƚŽƐ
ĂŐƌĞŐĂĚŽƐ͕ ĞƐƚĞ ƐŝƐƚĞŵĂ ƐĞ ĞŶĐƵĞŶƚƌĂ ƐĂƚƵƌĂĚŽ͕ ƉŽƌ ůŽ ƋƵĞ ĚĞũĂ ĚĞ ƐĞƌ ĞĨŝĐĂǌ͕
ƉƌŽĚƵĐŝĠŶĚŽƐĞĞŶƚŽŶĐĞƐůĂĂĐƵŵƵůĂĐŝſŶĚĞůŽƐŵŝƐŵŽƐ͘WƌĞĐŝƐĂŵĞŶƚĞůĂƉƌĞƐĞŶĐŝĂĚĞ
ůŽƐ ĐŝƚĂĚŽƐ ĂŐƌĞŐĂĚŽƐ ĐŽŶƐƚŝƚƵǇĞ ƵŶŽ ĚĞ ůŽƐ ĐƌŝƚĞƌŝŽƐ ĚŝĂŐŶſƐƚŝĐŽƐ ĐůĂƌŽƐ ĚĞ ĞƐƚĂ
ƉĂƚŽůŽŐşĂ͕;ĂǀŝĞƐĞƚĂů͕͘ϭϵϵϳ͖ŝ&ŝŐůŝĂĞƚĂů͕͘ϭϵϵϳͿ͘ĐŽŶƐĞĐƵĞŶĐŝĂĚĞůĂƐŵƵƚĂĐŝŽŶĞƐ
ĞŶůĂĐŝƚĂĚĂƉƌŽƚĞşŶĂ͕ƐĞĚĞƐĞŶĐĂĚĞŶĂůĂŵƵĞƌƚĞŶĞƵƌŽŶĂů͕ƐŽďƌĞƚŽĚŽĞŶůĂǌŽŶĂĚĞů
ĞƐƚƌŝĂĚŽ Ǉ ĚĞ ůĂ ĐŽƌƚĞǌĂ ĐĞƌĞďƌĂůĞƐ͕ ;ŝ&ŝŐůŝĂ Ğƚ Ăů͕͘ ϭϵϵϳͿ͘ ŽŵŽ ĐŽŶƐĞĐƵĞŶĐŝĂ͕ ƐĞ
ĚĞƐĞŶĐĂĚĞŶĂƌĄ ůĂ ŶĞƵƌŽĚĞŐĞŶĞƌĂĐŝſŶ ĞŶ Ğů ŝŶĚŝǀŝĚŝŽ͕ ƉĂƌĞĐŝĞŶĚŽ ůŽƐ ƐşŶƚŽŵĂƐ ƚşƉŝĐŽƐ
ĚĞĞƐƚĂƉĂƚŽůŽŐşĂ͕ƋƵĞĚĞƐĐƌŝďşĂŵŽƐĐŽŶĂŶƚĞƌŝŽƌŝĚĂĚ͘
ϰϯ
>Ă ĞǆƉƌĞƐŝſŶ ĚĞ ůĂ ƉƌŽƚĞşŶĂ ,ƚƚ ŵƵƚĂĚĂ Ǉ ůĂ ĐŽŶƐĞĐƵĞŶƚĞ ĂĐƵŵƵůĂĐŝſŶ ĚĞ
ƉŽůŝŐůƵƚĂŵŝŶĂ͕ ƋƵĞ ƐĞ ŽďƐĞƌǀĂ ĞŶ ůŽƐ ƉĂĐŝĞŶƚĞƐ ĚĞ ,͕ ƉŽĚƌşĂ ĞƐƚĂƌ ƌĞůĂĐŝŽŶĂĚĂ ĐŽŶ
ĚŝƐĨƵŶĐŝŽŶĞƐ ŵŝƚŽĐŽŶĚƌŝĂůĞƐ͕ ;ŽƐƐǇͲtĞƚǌĞů Ğƚ Ăů͕͘ ϮϬϬϴ͖ ŚĞŶ͕ ϮϬϭϭͿ͕ ĐŽŵŽ
ŝŶĚŝĐĄďĂŵŽƐĂůƉƌŝŶĐŝƉŝŽĚĞĞƐƚĞĐĂƉşƚƵůŽ͘Ɛş͕ƐĂďĞŵŽƐƋƵĞůĂĨŽƌŵĂŵƵƚĂĚĂĚĞůĂ,ƚƚ͕
ƐĞ ƵŶĞ ĚŝƌĞĐƚĂŵĞŶƚĞ Ă ůĂ ŵĞŵďƌĂŶĂ ĞǆƚĞƌŶĂ ŵŝƚŽĐŽŶĚƌŝĂů ĞŶ ƌĂƚŽŶĞƐ ƚƌĂŶƐŐĠŶŝĐŽƐ͕
;WĂŶŽǀ Ğƚ Ăů͕͘ ϮϬϬϮͿ͕ Ǉ ĨŽƌŵĂ ĞƐƚƌƵĐƚƵƌĂƐ ůĂƌŐĂƐ͕ ƐŝŵŝůĂƌĞƐ Ă ůĂƐ ĐƌĞĂĚĂƐ ƉŽƌ ƌƉϭ͕
;>ĂďƌŽƵƐƐĞ Ğƚ Ăů͕͘ ϭϵϵϵ͖ ^ŵŝƌŶŽǀĂ Ğƚ Ăů͕͘ ϮϬϬϭͿ͘ Ğ ŚĞĐŚŽ͕ ĞŶ ĞƐƚĂ ĞŶĨĞƌŵĞĚĂĚ͕ ƐĞ
ƉƌŽĚƵĐĞŶ ĚĞĨĞĐƚŽƐ ŝŵƉŽƌƚĂŶƚĞƐ ĞŶ ůĂ ĂĐƚŝǀŝĚĂĚ ĚĞ ůŽƐ ĐŽŵƉůĞũŽƐ // Ǉ /// ĚĞ ůĂ d͕
ĐŽŶĐƌĞƚĂŵĞŶƚĞ ĞŶ ůĂƐ ŶĞƵƌŽŶĂƐ ĚĞ ůĂ ǌŽŶĂ ĐĂƵĚĂĚŽ Ǉ ĚĞů ƉƵƚĄŵĞŶ͕ ĂƵŶƋƵĞ ŶŽ ƐĞ
ŽďƐĞƌǀſŶŝŶŐƷŶĞĨĞĐƚŽĞŶůĂƐĐŽƌƚŝĐĂůĞƐŽůĂƐĚĞůĐĞƌĞďĞůŽ͕ŶŝĞŶĨŝďƌŽďůĂƐƚŽƐ͕;ƌĞŶŶĂŶ
ĞƚĂů͕͘ϭϵϴϱ͖ƌŽǁŶĞĞƚĂů͕͘ϭϵϵϳ͖'ƵĞƚĂů͕͘ϭϵϵϲ͖dĂďƌŝǌŝĞƚĂů͕͘ϭϵϵϵͿ͘
Ɛş͕ ĐŽƌƌŽďŽƌĂŶĚŽ ůĂ ĂĨĞĐĐŝſŶ ŵŝƚŽĐŽŶĚƌŝĂů ƉƌĞƐĞŶƚĞ ĞŶ ĞŶĨĞƌŵŽƐ ĚĞ , ƋƵĞ
ĂƉƵŶƚĄďĂŵŽƐ ĐŽŶ ĂŶƚĞƌŝŽƌŝĚĂĚ͕ ĞŶ ŵŽĚĞůŽƐ ĞǆƉĞƌŝŵĞŶƚĂůĞƐ ĨĂƌŵĂĐŽůſŐŝĐŽƐ ĐŽŶ
ŶĞƵƌŽŶĂƐ ĐŽƌƚŝĐĂůĞƐ ĚĞ ƌĂƚĂ ƚƌĂƚĂĚĂƐ ĐŽŶ Ğů ŝŶŚŝďŝĚŽƌ ĚĞů ŽŵƉůĞũŽ // ĚĞ Ă d͕ ϯEW͕
;ĐŝĚŽϯͲEŝƚƌŽƉƌŽƉŝſŶŝĐŽͿ͕ƐĞŽďƐĞƌǀſůĂĐŽŶĚĞŶƐĂĐŝſŶǇĨƌĂŐŵĞŶƚĂĐŝſŶŵŝƚŽĐŽŶĚƌŝĂůĞƐ͕
ůĂƐĐƵĂůĞƐĨƵĞƌŽŶĞǀŝƚĂĚĂƐŵĞĚŝĂŶƚĞĞůƵƐŽĚĞƚƌĂƚĂŵŝĞŶƚŽƐĂŶƚŝŽǆŝĚĂŶƚĞƐ͕;>ŝŽƚĞƚĂů͕͘
ϮϬϬϵͿ͘ Ğ ŚĞĐŚŽ͕ ƉĂƌĞĐĞ ĐůĂƌĂ ĞŶƚƌĞ ůĂ ĐŽŵƵŶŝĚĂĚ ĐŝĞŶƚşĨŝĐĂ ůĂ ŝŵƉůŝĐĂĐŝſŶ ĚĞů ĞƐƚƌĠƐ
ŽǆŝĚĂƚŝǀŽĞŶůĂ,͘Ɛş͕ƉŽƌĞũĞŵƉůŽ͕ĞŶĞůĐĂƵĚĂĚŽĐĞƌĞďƌĂůĚĞƉĂĐŝĞŶƚĞƐĚĞ,ŚĂƐŝĚŽ
ĞŶĐŽŶƚƌĂĚŽƵŶŝŶĐƌĞŵĞŶƚŽƐŝŐŶŝĨŝĐĂƚŝǀŽĚĞϴͲŚŝĚƌŽǆŝĚĞŽǆŝŐƵĂŶŽƐŝŶĂ͕ůŽĐƵĂůĐŽŶƐƚŝƚƵǇĞ
ƵŶ ĐŽŶŽĐŝĚŽ ŵĂƌĐĂĚŽƌ ĚĞ ĚĂŹŽ ŽǆŝĚĂƚŝǀŽ Ăů E͕ ;ƌŽǁŶĞ Ğƚ Ăů͕͘ ϭϵϵϳͿ͘ ƐƚĞ ŵŝƐŵŽ
ƉĂƌĄŵĞƚƌŽ͕ ĞŶƐĂǇĂĚŽ ĞŶ Ğů ŵƚE͕ ŵŽƐƚƌſ ƋƵĞ ƚĂŵďŝĠŶ Ğů ŵĂƚĞƌŝĂů ŐĞŶĠƚŝĐŽ ĚĞ ůĂƐ
ŵŝƚŽĐŽŶĚƌŝĂƐ ĚĞ ůĂ ĐŽƌƚĞǌĂ ƉĂƌŝĞƚĂů ĞƐƚĂďĂ ĚĂŹĂĚŽ͕ ĞŶ ůŽƐ ĞƐƚĂĚşŽƐ ĂǀĂŶǌĂĚŽƐ ĚĞ ůĂ
ĞŶĨĞƌŵĞĚĂĚ͘ dĂŵďŝĠŶ ĞŶ ůŽƐ ůĞƵĐŽĐŝƚŽƐ ƉĞƌŝĨĠƌŝĐŽƐ ĚĞ ĞƐƚŽƐ ƉĂĐŝĞŶƚĞƐ ƐĞ ĞŶĐŽŶƚƌſ Ğů
ĐŝƚĂĚŽĚĂŹŽ͕;ŚĞŶĞƚĂů͕͘ϮϬϬϳĂͿ͘^ŝŶĞŵďĂƌŐŽ͕ŶŽƐĞŽďƐĞƌǀſŶŝŶŐƵŶĂǀĂƌŝĂĐŝſŶĞŶůĂ
ĐŽƌƚĞǌĂĨƌŽŶƚĂůŶŝĞŶĞůĐĞƌĞďĞůŽ͕;WŽůŝĚŽƌŝĞƚĂů͕͘ϭϵϵϵͿ͘
WŽƌ ŽƚƌŽ ůĂĚŽ͕ ƚĂŵďŝĠŶ ůĂ ƉƌĞƐĞŶĐŝĂ ĚĞ ƉĞƌŽǆŝĚĂĐŝſŶ ůŝƉşĚŝĐĂ͕ ƵŶĂ ĚĞ ůĂƐ
ĐŽŶƐĞĐƵĞŶĐŝĂƐ ĚĞů ĞƐƚƌĠƐ ŽǆŝĚĂƚŝǀŽ ƉƌŽĚƵĐŝĚŽ ƉŽƌ ůĂƐ ZK͕ ŚĂ ƋƵĞĚĂĚŽ ĚĞŵŽƐƚƌĂĚĂ͕
ŐƌĂĐŝĂƐĂůĞƐƚƵĚŝŽĚĞůĂĐŽŶĐĞŶƚƌĂĐŝſŶĚĞŵĂůŽŶĚŝĂůĚĞŚşĚŽ͕ůĂĐƵĂůŵŽƐƚƌſŝŶĐƌĞŵĞŶƚŽƐ
ĐŽŶƐŝĚĞƌĂďůĞƐĞŶĞůĐĞƌĞďƌŽĚĞƉĂĐŝĞŶƚĞƐĚĞ,͕ůŽƋƵĞƐĞĐŽƌƌĞůĂĐŝŽŶĂƉƌĞĐŝƐĂŵĞŶƚĞ
ĐŽŶ ƵŶ ĂƵŵĞŶƚŽĚĞ ůĂ ĐŝƚĂĚĂƉĞƌŽǆŝĚĂĐŝſŶ ůŝƉşĚŝĐĂ͕ ;ƌŽǁŶĞ Ğƚ Ăů͕͘ ϭϵϵϵͿ͘ ĚĞŵĄƐ͕ Ăů
ϰϰ
ƌĞĂůŝǌĂƌ ĞƐƚĞ ĞŶƐĂǇŽ ĞŶ ƐĂŶŐƌĞ ƉĞƌŝĨĠƌŝĐĂ͕ ƐĞ ĚĞƚĞƌŵŝŶſ ŶŽ ƐſůŽ ƵŶ ŝŶĐƌĞŵĞŶƚŽ ĚĞ ůĂ
ĐŽŶĐĞŶƚƌĂĐŝſŶ ĚĞ ŵĂůŽŶĚŝĂůĚĞŚşĚŽ͕ ƐŝŶŽ ƋƵĞ͕ ĂĚĞŵĄƐ͕ ĞƐƚĞ ĂƵŵĞŶƚŽ ƐĞ ƉŽĚşĂ
ĐŽƌƌĞůĂĐŝŽŶĂƌ ĐůĂƌĂŵĞŶƚĞ ĐŽŶ Ğů ŐƌĂĚŽ ĚĞ ƐĞǀĞƌŝĚĂĚ ĚĞ ůĂ ĞŶĨĞƌŵĞĚĂĚ͕ ;ŚĞŶ Ğƚ Ăů͕͘
ϮϬϬϳĂͿ͘ WŽƌ ƷůƚŝŵŽ͕ Ă ƚƌĂǀĠƐ ĚĞů ĞƐƚƵĚŝŽ ĚĞ ůĂ ĂĐƚŝǀŝĚĂĚ ĚĞů ĞŶǌŝŵĂ ĂĐŽŶŝƚĂƐĂ͕ ƐĞ
ŵŽƐƚƌĂƌŽŶ ŝŶĐƌĞŵĞŶƚŽƐ ĞŶ ůŽƐ ŶŝǀĞůĞƐ ĚĞ ĞƐƚƌĠƐ ŽǆŝĚĂƚŝǀŽ ĞŶ ĐŝĞƌƚĂƐ ƌĞŐŝŽŶĞƐ
ĐĞƌĞďƌĂůĞƐĐŽŶĐƌĞƚĂƐĚĞƉĂĐŝĞŶƚĞƐĚĞ,͕;dĂďƌŝǌŝĞƚĂů͕͘ϭϵϵϵͿ͘ŽŶƚŽĚŽĞƐƚŽ͕ƐĂďĞŵŽƐ
ƋƵĞĞůĐŝƚĂĚŽĞƐƚƌĠƐŽǆŝĚĂƚŝǀŽƉŽĚƌşĂƉƌŽŵŽǀĞƌůĂĂŐƌĞŐĂĐŝſŶĚĞůŵƵƚĂŶƚĞĚĞ,ƚƚ͕ĂƐş
ĐŽŵŽ ůĂ ŵƵĞƌƚĞ ŶĞƵƌŽŶĂů ƉƌŽĚƵĐŝĚĂ ƉŽƌ Ğů ĚĂŹŽ ĞŶ ůĂ ĨƵŶĐŝſŶ ĚĞů ƉƌŽƚĞŽƐŽŵĂ͕
;'ŽƐǁĂŵŝĞƚĂů͕͘ϮϬϬϲͿ͘
ĚŝĐŝŽŶĂůŵĞŶƚĞ͕ ŚĂ ƋƵĞĚĂĚŽ ĚĞŵŽƐƚƌĂĚŽ ƋƵĞ͕ ĞŶ ĞƐƚĂ ĞŶĨĞƌŵĞĚĂĚ͕ Ğů
ŵŽǀŝŵŝĞŶƚŽ ĚĞ ůĂƐ ŵŝƚŽĐŽŶĚƌŝĂƐ ĞƐƚĄ ŐƌĂǀĞŵĞŶƚĞ ĂĨĞĐƚĂĚŽ͕ ůŽ ĐƵĂů ŶŽ ŚĂĐĞ ƐŝŶŽ
ŝŶĐƌĞŵĞŶƚĂƌ Ğů ĚĂŹŽ ŶĞƵƌŽŶĂů͕ ;ŚĂŶŐ Ğƚ Ăů͕͘ ϮϬϬϲď͖ Kƌƌ Ğƚ Ăů͕͘ ϮϬϬϴͿ͘ WŽƌ ƐƵ ƉĂƌƚĞ͕
ƉĂƌĞĐĞƐĞƌƋƵĞůĂƉƌŽƚĞşŶĂŵƵƚĂŶƚĞ,ƚƚƚŝĞŶĞƚĂŵďŝĠŶĞĨĞĐƚŽƐŽďƌĞůĂĨƵƐŝſŶǇůĂĨŝƐŝſŶ
ŵŝƚŽĐŽŶĚƌŝĂůĞƐ͘Ɛş͕ĞŶƵŶŵŽĚĞůŽĐĞůƵůĂƌĐŽŶ,Ğ>Ă͕ƋƵĞĚſĚĞŵŽƐƚƌĂĚŽƋƵĞůĂĐŝƚĂĚĂ
ƉƌŽƚĞşŶĂ ƉƌŽĚƵĐşĂ ƵŶ ŝŶĐƌĞŵĞŶƚŽ ĐŽŶƐŝĚĞƌĂďůĞ ĚĞ ůĂ ĨƌĂŐŵĞŶƚĂĐŝſŶ ŵŝƚŽĐŽŶĚƌŝĂů
ŵĞĚŝĂĚĂƉŽƌƌƉϭ͘ĚĞŵĄƐ͕ƉĂƌĂĐŽŶĨŝƌŵĂƌĞƐƚŽƐĚĂƚŽƐ͕ůŽƐĂƵƚŽƌĞƐƵƐĂƌŽŶƵŶŵŽĚĞůŽ
ƚƌĂŶƐŐĠŶŝĐŽ ĚĞ , ĐƌĞĂĚŽ ĞŶ ĂĞŶŽƌŚĂďĚŝƚŝƐ ĞůĞŐĂŶƐ͘ Ŷ Ġů͕ ŽďƐĞƌǀĂƌŽŶ ƋƵĞ ůĂ
ƐƵƉƌĞƐŝſŶĚĞƌƉϭŵĞĚŝĂŶƚĞĞůƵƐŽĚĞZEŝƌĞǀŝƌƚŝſůĂƐĚĞĨŝĐŝĞŶĐŝĂƐĞŶůĂŵŽǀŝůŝĚĂĚƋƵĞ
ƉƌĞƐĞŶƚĂďĂŶĞƐƚŽƐŐƵƐĂŶŽƐ͕;tĂŶŐĞƚĂů͕͘ϮϬϬϴďͿ͘
ůƵƐŽĚĞŵŽĚĞůŽƐĨĂƌŵĂĐŽůſŐŝĐŽƐƋƵĞŵŝŵĞƚŝĐĞŶůŽƐƐşŶƚŽŵĂƐŶĞƵƌŽďŝŽůſŐŝĐŽƐ
Ǉ ĐůşŶŝĐŽƐ ĚĞ ĚŝǀĞƌƐĂƐ ƉĂƚŽůſŐŝĐĂƐ ĞƐƚĄ ĂŵƉůŝĂŵĞŶƚĞ ĚŝĨƵŶĚŝĚŽ ĞŶƚƌĞ ůĂ ĐŽŵƵŶŝĚĂĚ
ĐŝĞŶƚşĨŝĐĂ͘ Ɛş͕ ĐŽŵŽ ĐŽŵĞŶƚĄďĂŵŽƐ ĐŽŶ ĂŶƚĞƌŝŽƌŝĚĂĚ͕ ĞŶ Ğů ĐĂƐŽ ĚĞ ůĂ , ĞƐ ŵƵǇ
ĐŽŵƷŶƵƚŝůŝǌĂƌŝŶŚŝďŝĚŽƌĞƐĚĞůŽŵƉůĞũŽ//ĚĞůĂd͕ĐŽŵŽƉŽƌĞũĞŵƉůŽůĂŶĞƵƌŽƚŽǆŝŶĂ
ϯEW͕ ůĂ ĐƵĂů ĞƐ ĐĂƉĂǌ ĚĞ ƉƌŽĚƵĐŝƌ ƵŶĂ ĚŝƐĐŝŶĞƐŝĂ ƐŝŵŝůĂƌ ĞŶ ŵƵĐŚŽƐ ĂƐƉĞĐƚŽƐ Ă ůĂ
ŽďƐĞƌǀĂĚĂ ĞŶ ƉĂĐŝĞŶƚĞƐ ĚĞ ,͕ ;ƌŽƵŝůůĞƚ Ğƚ Ăů͕͘ ϮϬϬϱͿ͘ ^Ğ ƚƌĂƚĂ ĚĞ ƵŶ ŝŶŚŝďŝĚŽƌ
ŝƌƌĞǀĞƌƐŝďůĞĚĞůĂĞŶǌŝŵĂƐƵĐĐŝŶĂƚŽĚĞƐŚŝĚƌŽŐĞŶĂƐĂ͕;ƌŽƵŝůůĞƚĞƚĂů͕͘ϭϵϵϴͿ͕ƉƌŽĚƵĐŝĚŽ
ƉŽƌĚŝǀĞƌƐĂƐĞƐƉĞĐŝĞƐĨƷŶŐŝĐĂƐ͕ƉƌĞƐĞŶƚĞƚĂŵďŝĠŶĞŶĂůŐƵŶŽƐŵŝĞŵďƌŽƐĚĞůĂĨĂŵŝůŝĂĚĞ
ůĂƐůĞŐƵŵŝŶŽƐĂƐ͘
>ĂĂĚŵŝŶŝƐƚƌĂĐŝſŶƐŝƐƚĠŵŝĐĂĚĞϯEWĞŶŵŽĚĞůŽƐĂŶŝŵĂůĞƐƉƌŽĚƵũŽƵŶĚĞƚĞƌŝŽƌŽ
ƉƌŽŐƌĞƐŝǀŽ ĞŶ ůĂ ůŽĐŽŵŽĐŝſŶ Ǉ ĞŶ Ğů ĐŽŵƉŽƌƚĂŵŝĞŶƚŽ͕ ůŽ ĐƵĂů ƌĞŵĞĚĂ ůŽƐ ƐşŶƚŽŵĂƐ
ϰϱ
ŽďƐĞƌǀĂĚŽƐĞŶƉĂĐŝĞŶƚĞƐĚĞ,͘ĚĞŵĄƐ͕ƐĞŽďƐĞƌǀſƋƵĞ͕ĞŶĨƵŶĐŝſŶĚĞůŽƐƚŝĞŵƉŽƐĚĞ
ƚƌĂƚĂŵŝĞŶƚŽĐŽŶϯEW͕ƐĞƉƌŽĚƵĐşĂŚŝƉĞƌĂĐƚŝǀŝĚĂĚ͕;ĐĂƌĂĐƚĞƌşƐƚŝĐĂƚşƉŝĐĂĚĞůŽƐĞƐƚĂĚşŽƐ
ŝŶŝĐŝĂůĞƐĚĞůĂ,Ϳ͕ŽŚŝƉŽĂĐƚŝǀŝĚĂĚ͕;ŵĄƐĐŽŵƷŶĞŶůĂƐĨĂƐĞƐƚĂƌĚşĂƐĚĞůĂ,Ϳ͕ĞŶůŽƐ
ĐŝƚĂĚŽƐŵŽĚĞůŽƐĂŶŝŵĂůĞƐ͘ƐƚĞŚĞĐŚŽĞƐŝŵƉŽƌƚĂŶƚĞ͕ǇĂƋƵĞƉĞƌŵŝƚĞƚĞƐƚĂƌĨĄƌŵĂĐŽƐƵ
ŽƉĐŝŽŶĞƐƚĞƌĂƉĞƷƚŝĐĂƐ͕ƉĂůŝĂƚŝǀĂƐŽĚŝĂŐŶſƐƚŝĐĂƐƉĂƌĂĂƉůŝĐĂƌĞŶůĂƐĚŝĨĞƌĞŶƚĞƐĨĂƐĞƐĚĞ
ůĂ,͕;ŽƌůŽŶŐĂŶĞƚĂů͕͘ϭϵϵϳͿ͘
ĚĞŵĄƐ͕ ŚĂǇ ƵŶ ƚƌĂďĂũŽ ŵƵǇ ŝŶƚĞƌĞƐĂŶƚĞ ĞŶ Ğů ƋƵĞ ƋƵĞĚĂ ĚĞŵŽƐƚƌĂĚŽ ƋƵĞ ůĂ
ĂĚŵŝŶŝƐƚƌĂĐŝſŶ ƐŝƐƚĠŵŝĐĂ ĚĞ ϯEW ƉƌŽĚƵĐĞ ƵŶĂ ĚĞŐĞŶĞƌĂĐŝſŶ ƐƵŵĂŵĞŶƚĞ ĞƐƉĞĐşĨŝĐĂ Ǉ
ďŝůĂƚĞƌĂůĚĞůĞƐƚƌŝĂĚŽĐĞƌĞďƌĂůĞŶƌĂƚĂƐ͕ůĂĐƵĂůƉƵĞĚĞƐĞƌĐůĂƐŝĨŝĐĂĚĂĞŶĨƵŶĐŝſŶĚĞƐƵ
ŐƌĂǀĞĚĂĚ ĞŶƚƌĞ ŵĞĚŝĂ Ǉ ƐĞǀĞƌĂ͘ ^ŝŶ ĞŵďĂƌŐŽ͕ ĞŶ Ğů ŵŝƐŵŽ ƚƌĂďĂũŽ͕ ůŽƐ ĂƵƚŽƌĞƐ
ƌĞĐŽŶŽĐĞŶƋƵĞůŽƐĞĨĞĐƚŽƐĚĞůƚƌĂƚĂŵŝĞŶƚŽĐŽŶϯEWĞŶƐƵŵŽĚĞůŽƐŽŶŝŵƉƌĞĚĞĐŝďůĞƐ͕
ǇĂ ƋƵĞ Ğů ĨĄƌŵĂĐŽ ƉƌŽĚƵĐĞ ůĞƐŝŽŶĞƐ ĚĞ ƐĞǀĞƌŝĚĂĚ ǀĂƌŝĂďůĞ Ǉ ĂůƚĞƌĞĂĐŝŽŶĞƐ ĚĞů
ĐŽŵƉŽƌƚĂŵŝĞŶƚŽ͕ ĂƵŶƋƵĞ ĞƐƚĂƐ ƷůƚŝŵĂƐŶŽ ĨƵĞƌŽŶ ĚĞ ŐƌĂŶ ĞŵďĞƌŐĂĚƵƌĂ͘ Ŷ ůĂƐ ƌĂƚĂƐ
ĞŶ ůĂƐ ƋƵĞ ůŽƐ ĚĂŹŽƐ ĨƵĞƌŽŶ ŵĄƐ ĐŽŶƐŝĚĞƌĂďůĞƐ͕ ƐĞ ĐŽŶƐƚĂƚſ ƚĂŵďŝĠŶ ƵŶĂ ƉĠƌĚŝĚĂ
ŶĞƵƌŽŶĂů ŐĞŶĞƌĂůŝǌĂĚĂ Ǉ ƵŶ ŝŶĐƌĞŵĞŶƚŽ ĞŶ ůĂ ĞǆƉƌĞƐŝſŶ ĚĞ ůĂ WƌŽƚĞşŶĂ 'ůŝĂů &ŝďƌŝůĂƌ
ĐşĚŝĐĂ͕;'&WͿ͕ĞŶůŽƐĂƐƚƌŽĐŝƚŽƐĐŝƌĐƵŶĚĂŶƚĞƐĂůĄƌĞĂĚĞůĂůĞƐŝſŶ͕ŵŝĞŶƚƌĂƐƋƵĞĞŶĞů
ůƵŐĂƌ ĚĞ ŝŶǇĞĐĐŝſŶ ĚĞ ϯEW͕ ŶŽ ƐĞ ĚĞƚĞĐƚſ ŝŶŵƵŶŽƌĞĂĐƚŝǀŝĚĂĚ ĚĞ ůĂ ƉƌŽƚĞşŶĂ '&W͘
ĚĐŝŽŶĂůŵĞŶƚĞ͕ ĞŶ ƵŶ ĐŝĞƌƚŽ ƉŽƌĐĞŶƚĂũĞ ĚĞ ĂŶŝŵĂůĞƐ͕ ŶŽ ƐĞ ŽďƐĞƌǀſ ŶŝŶŐƷŶ ƚŝƉŽ ĚĞ
ůĞƐŝſŶ͕ Ă ƉĞƐĂƌ ĚĞ ƋƵĞ ĠƐƚŽƐ ŵŽƐƚƌĂďĂŶ ĂůƚĞƌĂĐŝŽŶĞƐ ĞŶ Ğů ĐŽŵƉŽƌƚĂŵŝĞŶƚŽ͕
ĐŽŵƉĂƌĂĚŽƐĐŽŶůŽƐĂŶŝŵĂůĞƐƉĞƌƚĞŶĞĐŝĞŶƚĞƐĂůŐƌƵƉŽĐŽŶƚƌŽů͕;sŝƐĞƚĂů͕͘ϭϵϵϵͿ͘
WŽƌƷůƚŝŵŽ͕ĂƉŽǇĂŶĚŽůŽƐĚĂƚŽƐŽďƚĞŶŝĚŽƐĞŶĂĞŶŽƌŚĂďĚŝƚŝƐĞůĞŐĂŶƐ͕ƚĂŵďŝĠŶ
ĞŶƵŶŵŽĚĞůŽĚĞϯEWƐĞŚĂŽďƐĞƌǀĂĚŽƋƵĞĞůŝŶĐƌĞŵĞŶƚŽĚĞůĂĨƵƐŝſŶŽůĂƌĞĚƵĐĐŝſŶĚĞ
ůĂ ĨŝƐŝſŶ ƋƵĞ ƉƌŽĚƵĐĞ ĞƐƚĂ ƚŽǆŝŶĂ ƉƵĞĚĞŶ ĐŽŵƉĞŶƐĂƌ ůŽƐ ĞĨĞĐƚŽƐ ĚĞ ůĂ ĞǆƉƌĞƐŝſŶ ĚĞů
ŵƵƚĂŶƚĞĚĞ,ƚƚ͘WŽƌƚĂŶƚŽ͕ĞůĐŝƚĂĚŽŵƵƚĂŶƚĞ͕ƉŽĚƌşĂĂĨĞĐƚĂƌĂůĞƋƵŝůŝďƌŝŽĨƵƐŝſŶͲĨŝƐŝſŶ͕
ƐŝďŝĞŶƐĞĚĞƐĐŽŶŽĐĞĐſŵŽƐĞƉƌŽĚƵĐŝƌşĂĞǆĂĐƚĂŵĞŶƚĞĞƐƚĞƉƌŽĐĞƐŽ͘
ϰϲ
//͘,ŝƉſƚĞƐŝƐ
Ǥ
V
ĐƚƵĂůŵĞŶƚĞ͕ ƉŽƐĞĞŵŽƐ ŚĞƌƌĂŵŝĞŶƚĂƐ ĨĂƌŵĂĐŽůſŐŝĐĂƐ ďŝĞŶ ĐŽŶŽĐŝĚĂƐ ƋƵĞ ŶŽƐ
ƉĞƌŵŝƚĞŶ ĐƌĞĂƌ ŵŽĚĞůŽƐ ĚĞ ĞŶĨĞƌŵĞĚĂĚĞƐ ŶĞƵƌŽĚĞŐĞŶĞƌĂƚŝǀĂƐ͕ ƚĂŶƚŽ ĞŶ ƐŝƐƚĞŵĂƐ
ĐĞůƵůĂƌĞƐĐŽŵŽĂŶŝŵĂůĞƐ͘ŶŶƵĞƐƚƌŽĐĂƐŽĐŽŶĐƌĞƚŽ͕ƚƌĂďĂũĂŵŽƐĐŽŶĐƵůƚŝǀŽƐĐĞůƵůĂƌĞƐ
ĚŽƉĂŵŝŶĠƌŐŝĐŽƐ ĚĞ ^,Ͳ^zϱz͕ Ă ůŽƐ ƋƵĞ ĂŹĂĚŝŵŽƐ ĂŐĞŶƚĞƐ ŝŶĚƵĐƚŽƌĞƐ ĚĞ ůĂƐ ĐŝƚĂĚĂƐ
ƉĂƚŽůŽŐşĂƐ͘Ɛş͕ĞŶĞƐƚĂƚĞƐŝƐƵƚŝůŝǌĂŵŽƐϲͲK,ĞŶĞůĐĂƐŽĚĞůĂWǇϯEWĞŶĞůĚĞůĂ
,͘
EƵĞƐƚƌĂ ŚŝƉſƚĞƐŝƐ ĚĞ ƚƌĂďĂũŽ ĞƐ ƋƵĞ ůĂƐ ǀĂƌŝĂĐŝŽŶĞƐ ƋƵĞ ƐĞ ŽďƐĞƌǀĂŶ ĞŶ ůĂ
ŵŽƌĨŽůŽŐşĂŵŝƚŽĐŽŶĚƌŝĂů͕ƚƌĂƐĞůƚƌĂƚĂŵŝĞŶƚŽĚĞůŽƐĐƵůƚŝǀŽƐĐĞůƵůĂƌĞƐĐŽŶϲͲK,ŽĐŽŶ
ϯEW͕ƐŽŶĐŽŶƐĞĐƵĞŶĐŝĂĚĞŝŵƉŽƌƚĂŶƚĞƐĂůƚĞƌĂĐŝŽŶĞƐĞŶůĂŵŝƚŽĐŽŶĚƌŝĂ͕ƋƵĞĐŽŶĚƵĐĞŶ͕
ĞŶ ƷůƚŝŵŽ ƚĠƌŵŝŶŽ͕ Ă ůĂ ŵŝƚŽĨĂŐŝĂ͘ ^ŝŶ ĞŵďĂƌŐŽ͕ ůĂƐ ĚŝĨĞƌĞŶĐŝĂƐ ĞŶ ůĂ ĨŽƌŵĂ ĚĞ ůĂƐ
ŵŝƚŽĐŽŶĚƌŝĂƐ ƋƵĞ ƐĞ ŽďƐĞƌǀĂ ƚƌĂƐ Ğů ƚƌĂƚĂŵŝĞŶƚŽ ĐŽŶ ϲͲK, Ǉ ĐŽŶ ϯEW ŶŽƐ ŚĂĐĞŶ
ŚŝƉŽƚŝǌĂƌƋƵĞůŽƐŵĞĐĂŶŝƐŵŽƐĞŶůĂďĂƐĞĚĞĞƐƚŽƐƉƌŽĐĞƐŽƐ͕ĂƷŶĐŽŶĚƵĐŝĞŶĚŽĂůŵŝƐŵŽ
ĨŝŶĂů͕ĚĞďĞŶƐĞƌĚŝĨĞƌĞŶƚĞƐ͘ƐşŵŝƐŵŽ͕ŶƵĞƐƚƌĂŚŝƉſƚĞƐŝƐĞƐƋƵĞ͕ĞŶĂŵďŽƐŵŽĚĞůŽƐĚĞ
ĞŶĨĞƌŵĞĚĂĚĞƐ ŶĞƵƌŽĚĞŐĞŶĞƚŝǀĂƐ͕ ůĂ ƉƌŽĚƵĐĐŝſŶ ĚĞ ZK ƐĞ ŝŶĐƌĞŵĞŶƚĂƌĄ͕ ƉƵĚŝĞŶĚŽ
ŵĞĚŝĂƌ ĞƐƚĂƐ ŵŽůĠĐƵůĂƐ ĂůŐƵŶŽƐ ĚĞ ůŽƐ ĐĂŵďŝŽƐ ƉƌŽĚƵĐŝĚŽƐ ĞŶ ŶƵĞƐƚƌŽƐ ĐƵůƚŝǀŽƐ
ĐĞůƵůĂƌĞƐ͘
ϰϳ
///͘KďũĞƚŝǀŽƐ
Ǥ
ůŽďũĞƚŝǀŽƉƌŝŶĐŝƉĂůĚĞĞƐƚĂƚĞƐŝƐĚŽĐƚŽƌĂůĞƐƌĞĂůŝǌĂƌƵŶĞƐƚƵĚŝŽŵŝŶƵĐŝŽƐŽǇĞŶ
ƉƌŽĨƵŶĚŝĚĂĚ ĚĞů ĞƐƚĂĚŽ ĚĞ ůĂ ŵŽƌĨŽůŽŐşĂ ŵŝƚŽĐŽŶĚƌŝĂů Ǉ ůĂ ŵŝƚŽĨĂŐŝĂ͕ ĞŶ ŵŽĚĞůŽƐ
ĨĂƌŵĂĐŽůſŐŝĐŽƐĚĞ,ǇW͘
>ŽƐŽďũĞƚŝǀŽƐĞƐƉĞĐşĨŝĐŽƐƋƵĞŶŽƐƉůĂŶƚĞĂŵŽƐƐŽŶůŽƐƐŝŐƵŝĞŶƚĞƐ͗
•
KďƐĞƌǀĂƌ ůŽƐ ŚŝƉŽƚĠƚŝĐŽƐ ĐĂŵďŝŽƐ ŵŽƌĨŽůſŐŝĐŽƐ ƉƌŽĚƵĐŝĚŽƐ ĞŶ ůĂ
ŵŝƚŽĐŽŶĚƌŝĂ͕ ĂƐş ĐŽŵŽ ůĂ ƉŽƐŝďůĞ ŝŵƉůŝĐĂĐŝſŶ ĚĞ ůĂ ĨŝƐŝſŶ ŵŝƚŽĐŽŶĚƌŝĂů
ŵĞĚŝĂĚĂƉŽƌƌƉϭĞŶůŽƐŵŝƐŵŽƐǇĞůĞĨĞĐƚŽĚĞDĚŝǀŝͲϭ͘
•
ŶĂůŝǌĂƌůĂƌĞůĂĐŝſŶĞŶƚƌĞůĂŵŝŐƌĂĐŝſŶŵŝƚŽĐŽŶĚƌŝĂůĚĞůĂƉƌŽƚĞşŶĂĂǆǇ
ůĂĨŝƐŝſŶŵŝƚŽĐŽŶĚƌŝĂů͘
•
ƐƚƵĚŝĂƌ Ğů ƉĂƉĞů ĚĞ ůĂƐ ZK ĞŶ ůĂƐ ƉŽƐŝďůĞƐ ĂůƚĞƌĂĐŝŽŶĞƐ ŽďƐĞƌǀĂĚĂƐ͕
ĐƵĂŶƚŝĨŝĐĂƌ Ğů ĚĂŹŽ ƉƌŽĚƵĐŝĚŽ ƉŽƌ ůĂƐ ŵŝƐŵĂƐ Ǉ ĚĞƚĞƌŵŝŶĂƌ ƐƵ ƌĞůĂĐŝſŶ
ĐŽŶůĂŝŶĚƵĐĐŝſŶĚĞůĂĨŝƐŝſŶŵŝƚŽĐŽŶĚƌŝĂůǇůĂŵŝƚŽĨĂŐŝĂ͘
•
ƐĐůĂƌĞĐĞƌ Ğů ĞĨĞĐƚŽ ĚĞ DŝƚŽY ƐŽďƌĞ ůĂƐ ǀşĂƐ ŵŝƚŽĐŽŶĚƌŝĂůĞƐ ĞŶ ůĂƐ ƋƵĞ
ŚĞŵŽƐĐĞŶƚƌĂĚŽĞƐƚĞƚƌĂďĂũŽ͘
•
ŽŵƉƌŽďĂƌ Ɛŝ͕ ĞŶ ŶƵĞƐƚƌĂƐ ĐŽŶĚŝĐŝŽŶĞƐ ĚĞ ƚƌĂďĂũŽ͕ ƐĞ ƉƌŽĚƵĐĞ ůĂ
ĂĐƚŝǀĂĐŝſŶĚĞůĂǀşĂŵŝƚŽĐŽŶĚƌŝĂůĚĞůĂĂƵƚŽĨĂŐŝĂĞŝŶƚĞŶƚĂƌĚŝůƵĐŝĚĂƌƐƵ
ƌĞůĂĐŝſŶĐŽŶůĂĨŝƐŝſŶĚĞůŽƌŐĄŶƵůŽ͘
ϰϵ
/s͘ZĞƐƵůƚĂĚŽƐ
Ǥ >ŽƐƉĂƉĞƌƐƋƵĞǀĂŶĂƋƵşŽĐƵƉĂŶϰϬƉĄŐŝŶĂƐ͘
ϱϭ
s͘ŝƐĐƵƐŝſŶ
Ǥ
V
>ŽƐĂƌƚşĐƵůŽƐŝŶĐůƵŝĚŽƐĞŶĞƐƚĂƚĞƐŝƐĚŽĐƚŽƌĂůŚĂŶƐŝĚŽƌĞĂůŝǌĂĚŽƐĞŶĚŽƐŵŽĚĞůŽƐ
ĚĞ ĞŶĨĞƌŵĞĚĂĚĞƐ ŶĞƵƌŽĚĞŐĞŶĞƌĂƚŝǀĂƐ ĚŝƐƚŝŶƚĂƐ͘ WŽƌ ƵŶ ůĂĚŽ͕ ůĂ ĂĚŝĐŝſŶ ĚĞ ϲͲK, Ă
ůĂƐ^,Ͳ^zϱzƉƌŽĚƵũŽƵŶŝŶĐƌĞŵĞŶƚŽĐŽŶƐŝĚĞƌĂďůĞĚĞůĂƉƌŽĚƵĐĐŝſŶŝŶƚƌĂĐĞůƵůĂƌĚĞZK͕
ĂƐşĐŽŵŽůĂŝŶŚŝďŝĐŝſŶĚĞůĐŽŵƉůĞũŽ/ĚĞůĂd͘ŵďŽƐƉĂƌĄŵĞƚƌŽƐĂĐƚƷĂŶĐůĂƌĂŵĞŶƚĞ
ĐŽŵŽ ĂŐĞŶƚĞƐ ƉĂƌŬŝŶƐŽŶşƐƚŝĐŽƐ͕ ĐŽŵŽ ŚĂ ƐŝĚŽ ĂƉƵŶƚĂĚŽ ĞŶ ĚŝǀĞƌƐŽƐ ƚƌĂďĂũŽƐ ƉƌĞǀŝŽƐ͕
;ĞƚĂƌďĞƚĞƚĂů͕͘ϮϬϬϮ͖ůĂŶĚŝŶŝĞƚĂů͕͘ϮϬϬϴ͖ŽǀĞĞƚĂů͕͘ϮϬϭϮ͖^ĐŚŽďĞƌ͕ϮϬϬϰͿ͘WŽƌƐƵ
ƉĂƌƚĞ͕ĞŶĞůĐĂƐŽĚĞůĂ,͕ĞůŵŽĚĞůŽƵƐĂĚŽĨƵĞĞůĚĞůĂŝŶŚŝďŝĐŝſŶĚĞůĐŽŵƉůĞũŽ//ĚĞůĂ
d͕ ƚĂŵďŝĠŶ ĂŵƉůŝĂŵĞŶƚĞ ĞƐƚƵĚŝĂĚŽ Ǉ ƵƚŝůŝǌĂĚŽ ƉŽƌ ŽƚƌŽƐ ŐƌƵƉŽƐ͕ ;ŽƌůŽŶŐĂŶ Ğƚ Ăů͕͘
ϭϵϵϳ͖ƌŽƵŝůůĞƚĞƚĂů͕͘ϮϬϬϱ͖>ŝŽƚĞƚĂů͕͘ϮϬϬϵ͖EĂƉŽůŝƚĂŶŽĞƚĂů͕͘ϮϬϬϰ͖sŝƐĞƚĂů͕͘ϭϵϵϵͿ͘
WĂƌĂŽďƚĞŶĞƌĞƐƚĞĞĨĞĐƚŽ͕ĞŶĞƐƚĞĐĂƐŽĂŹĂĚŝŵŽƐϯEWĂŶƵĞƐƚƌŽƐĐƵůƚŝǀŽƐĐĞůƵůĂƌĞƐ͘
ůĞƐƚƵĚŝŽĚĞůĂŵŽƌĨŽůŽŐşĂŵŝƚŽĐŽŶĚƌŝĂůŶŽƐŽĨƌĞĐĞŝŶĨŽƌŵĂĐŝſŶƐŽďƌĞĞůĞƐƚĂĚŽ
ĚĞĞƐƚŽƐŽƌŐĄŶƵůŽƐǇƐŽďƌĞƐƵƐƉŽƐŝďůĞƐĚŝƐĨƵŶĐŝŽŶĞƐ͕ĞƐƉĞĐŝĂůŵĞŶƚĞĞŶĞůĐĂƐŽĚĞůĂƐ
ĞŶĨĞƌŵĞĚĂĚĞƐ ŶĞƵƌŽĚĞŐĞŶĞƌĂƚŝǀĂƐ͕ ;ƌĞǀŝƐĂĚŽ ĞŶ ;:ŽŚƌŝ Ğƚ Ăů͕͘ ϮϬϭϮͿͿ͘ Ŷ ŶƵĞƐƚƌŽƐ
ƚƌĂďĂũŽƐ͕ůĂŽďƐĞƌǀĂĐŝſŶĚĞůŽƐĐĂŵďŝŽƐĞŶůĂĨŽƌŵĂĚĞůĂƐŵŝƚŽĐŽŶĚƌŝĂƐƐŝĞŵƉƌĞĞƐƚĄ
ƉƌĞƐĞŶƚĞ͕ƐŝĞŶĚŽĞůƉĂƐŽŝŶŝĐŝĂů͘
>ĂŵŽƌĨŽůŽŐşĂŵŝƚŽĐŽŶĚƌŝĂůĨƵĞǀŝƐƵĂůŝǌĂĚĂŐƌĂĐŝĂƐĂůƵƐŽĚĞůƉůĄƐŵŝĚŽƉƐZĞĚϮͲ
ŵŝƚŽ͕ Ğů ĐƵĂů ƉĞƌŵŝƚĞ ůĂ ŐĞŶĞƌĂĐŝſŶ ĚĞ ƵŶĂ ƉƌŽƚĞşŶĂ ƋƵŝŵĠƌŝĐĂ ĞǆĐůƵƐŝǀĂŵĞŶƚĞ
ŵŝƚŽĐŽŶĚƌŝĂůǀŝƐŝďůĞĂϱϴϯŶŵ͕ƐŝƐĞĞǆĐŝƚĂŶƉƌĞǀŝĂŵĞŶƚĞůĂƐŵƵĞƐƚƌĂƐĂϱϱϴŶŵ͕;DĂƚǌ
Ğƚ Ăů͕͘ ϭϵϵϵ͖ ZŝǌǌƵƚŽ Ğƚ Ăů͕͘ ϭϵϵϱͿ͘ Ɛ ŝŵƉŽƌƚĂŶƚĞ ƌĞĐŽƌĚĂƌ Ğů ŚĞĐŚŽ ĚĞ ƋƵĞ ůĂƐ
ŵŝƚŽĐŽŶĚƌŝĂƐƐĞĞŶĐƵĞŶƚƌĂŶƉŽƌĚĞďĂũŽĞůůşŵŝƚĞĚĞƌĞƐŽůƵĐŝſŶĚĞůĂŵŝĐƌŽƐĐŽƉşĂſƉƚŝĐĂ
ĐŽŶůĂƋƵĞĐŽŶƚĂŵŽƐĂĐƚƵĂůŵĞŶƚĞ͕;<ĞŶŶĂĚǇĞƚĂů͕͘ϮϬϬϰͿ͕ƉŽƌůŽƋƵĞ͕ůĂƐŝŵĄŐĞŶĞƐƋƵĞ
ŽďƚĞŶĞŵŽƐŵĞĚŝĂŶƚĞĞƐƚĂƚĠĐŶŝĐĂ͕ŶŽƐĞĐŽƌƌĞƐƉŽŶĚĞŶĐŽŶŵŝƚŽĐŽŶĚƌŝĂƐĂŝƐůĂĚĂƐ͕ƐŝŶŽ
ĐŽŶĞůĐŽŶũƵŶƚŽĚĞůĂƐŵŝƐŵĂƐƉƌĞƐĞŶƚĞĞŶĐĂĚĂƵŶĂĚĞůĂƐĐĠůƵůĂƐ͘
Ŷ ĐŽŶĚŝĐŝŽŶĞƐ ĐŽŶƚƌŽů͕ ŶƵĞƐƚƌŽƐ ĐƵůƚŝǀŽƐ ĐĞůƵůĂƌĞƐ ƉƌĞƐĞŶƚĂďĂŶ ŝŶƚƌŝŶĐĂĚĂƐ
ƌĞĚĞƐŵŝƚŽĐŽŶĚƌŝĂůĞƐĚĞĨŽƌŵĂĂůĂƌŐĂĚĂ͘^ŝŶĞŵďĂƌŐŽ͕ƚƌĂƐƚƌĞƐŚŽƌĂƐĚĞƚƌĂƚĂŵŝĞŶƚŽ͕
ϲͲK,ĨƵĞ ĐĂƉĂǌ ĚĞŵŽĚŝĨŝĐĂƌůĂ ŵŽƌĨŽůŽŐşĂ ĚĞ ůŽƐ ŽƌŐĄŶƵůŽƐ͘ Ɛş͕ ƐĞ ƌŽŵƉŝĞƌŽŶ ůĂƐ
ϱϯ
ĐŝƚĂĚĂƐ ƌĞĚĞƐ Ǉ͕ ĞŶ ƐƵ ůƵŐĂƌ͕ ĂƉĂƌĞĐŝĞƌŽŶ ĞƐƚƌƵĐƚƵƌĂƐ ƌĞĚŽŶĚĞĂĚĂƐ Ǉ ĚĞ ůŽĐĂůŝǌĂĐŝſŶ
ƉĞƌŝŶƵĐůĞĂƌ͘ ŽŶĐƌĞƚĂŵĞŶƚĞ͕ ůĂƐ ŝŵĄŐĞŶĞƐ ŵŽƐƚƌĂďĂŶ ƵŶ ŐƌĂŶ ŶƷŵĞƌŽ ĚĞ ƉĞƋƵĞŹŽƐ
ƉƵŶƚŽƐ͕ ĨŽƌŵĂŶĚŽ ĐŽŵƉŽƐŝĐŝŽŶĞƐ ĐŽŶ ĨŽƌŵĂ ĚĞ ƌĂĐŝŵŽ͘ ƐƚĂƐ ŽďƐĞƌǀĂĐŝŽŶĞƐ
ĐŽŶĐƵĞƌĚĂŶĐŽŶůĂƐŽďƚĞŶŝĚĂƐƉƌĞǀŝĂŵĞŶƚĞƉŽƌŽƚƌŽƐŐƌƵƉŽƐ͕;'ƵŽĞƚĂů͕͘ϮϬϭϯ͖>ŝĞƐĂĞƚ
Ăů͕͘ϮϬϬϵ͖tĂŶŐĞƚĂů͕͘ϮϬϬϴĂͿ͕ĂƐşĐŽŵŽĐŽŶůŽƐĚĂƚŽƐƉƵďůŝĐĂĚŽƐƉƌĞǀŝĂŵĞŶƚĞĞŶŽƚƌŽ
ƚƌĂďĂũŽƌĞĂůŝǌĂĚŽĞŶůĂŵŝƐŵĂůşŶĞĂĐĞůƵůĂƌ͕;'ŽŵĞǌͲ>ĂǌĂƌŽĞƚĂů͕͘ϮϬϬϴĂͿ͘
Ŷ Ğů ŵŽĚĞůŽ ĚĞ , ƉŽƌ ĂĚŝĐŝſŶ ĚĞ ϯEW͕ ƐĞ ŽďƐĞƌǀſ ƚĂŵďŝĠŶ ƵŶ ĐĂŵďŝŽ
ŝŵƉŽƌƚĂŶƚĞ ĞŶ ůĂ ĨŽƌŵĂ ĚĞ ůĂƐ ŵŝƚŽĐŽŶĚƌŝĂƐ͕ ůĂƐ ĐƵĂůĞƐ ĐŽŶƐƚŝƚƵǇĞƌŽŶ ŐƌĂŶĚĞƐ
ĐŽŶŐůŽŵĞƌĂĚŽƐƉƵŶƚĞĂĚŽƐĚĞĚŝƐƚƌŝďƵĐŝſŶƉĞƌŝŶƵĐůĞĂƌ͘ƐƚĂƐǀĂƌŝĂĐŝŽŶĞƐƐĞŽďƐĞƌǀĂƌŽŶ
Ă ƚŝĞŵƉŽƐ ŵƵǇ ƚĞŵƉƌĂŶŽƐ Ğ ŝŶĨĞƌŝŽƌĞƐ Ă ƚƌĞƐ ŚŽƌĂƐ͕ ĐŽŶĐƌĞƚĂŵĞŶƚĞ ĚƵƌĂŶƚĞ ůŽƐ
ƉƌŝŵĞƌŽƐ ƐĞƐĞŶƚĂ ŵŝŶƵƚŽƐ ƚƌĂƐ Ğů ƚƌĂƚĂŵŝĞŶƚŽ͘ ƋƵş͕ ĞŶ ƌĞůĂĐŝſŶ ĐŽŶ ůŽƐ ĚĂƚŽƐ
ŽďƚĞŶŝĚŽƐĞŶĞůĐĂƐŽĚĞůĂϲͲK,͕ůĂƐŝŵĄŐĞŶĞƐŵŽƐƚƌĂďĂŶĞŶĞƐƚĞĐĂƐŽƵŶŶƷŵĞƌŽ
ŵƵǇŝŶĨĞƌŝŽƌĚĞĞƐƚƌƵĐƚƵƌĂƐƉƵŶƚĞĂĚĂƐ͕ƉĞƌŽĚĞƵŶƚĂŵĂŹŽŶĞƚĂŵĞŶƚĞƐƵƉĞƌŝŽƌ͘
ĚĞŵĄƐ͕ ůŽƐ ĞĨĞĐƚŽƐ ƉƌŽĚƵĐŝĚŽƐ ƉŽƌ ϯEW ƐŽďƌĞ ůĂ ŵŽƌĨŽůŽŐşĂ ŵŝƚŽĐŽŶĚƌŝĂů ŶŽ
ĨƵĞƌŽŶƌĞǀĞƌƐŝďůĞƐ͘ƐƚĞŚĞĐŚŽĨƵĞĐŽƌƌŽďŽƌĂĚŽƌĞĂůŝǌĂŶĚŽƵŶƐĞŶĐŝůůŽĞǆƉĞƌŝŵĞŶƚŽ͗ĞŶ
ƉƌŝŵĞƌ ůƵŐĂƌ͕ ƚƌĂƚĂŵŽƐŶƵĞƐƚƌŽƐ ĐƵůƚŝǀŽƐ ĐŽŶ ϯEW͕ ĚƵƌĂŶƚĞ ƵŶĂ ŚŽƌĂ͘ ĐŽŶƚŝŶƵĂĐŝſŶ͕
ƐƵƐƚŝƚƵŝŵŽƐ Ğů ŵĞĚŝŽ ĐŽŶ Ğů ĨĄƌŵĂĐŽ ƉŽƌ ŵĞĚŝŽ ƐŝŶ ŶŝŶŐƷŶ ƚƌĂƚĂŵŝĞŶƚŽ Ǉ ĞƐƉĞƌĂŵŽƐ
ŽƚƌĂƐƚƌĞƐŚŽƌĂƐ͘dƌĂƐĞƐƚĞƉƌŽĐĞƐŽ͕ǀŝƐƵĂůŝǌĂŵŽƐĚĞŶƵĞǀŽůĂŵŽƌĨŽůŽŐşĂŵŝƚŽĐŽŶĚƌŝĂů
ŵĞĚŝĂŶƚĞ ŵŝĐƌŽƐĐŽƉşĂ ĐŽŶĨŽĐĂů͕ ŽďƐĞƌǀĂŶĚŽ ƋƵĞ͕ ůŽƐ ƌĞƐƵůƚĂĚŽƐ ŽďƚĞŶŝĚŽƐ͕ ĞƌĂŶ
ƐŝŵŝůĂƌĞƐĂůŽƐƉƌŽĚƵĐŝĚŽƐƚƌĂƐƚƌĞƐŚŽƌĂƐĚĞƚƌĂƚĂŵŝĞŶƚŽĐŽŶϯEW͘
WŽƌƚĂŶƚŽ͕ƚŽĚŽƐĞƐƚŽƐĚĂƚŽƐƉĂƌĞĐşĂŶŝŶĚŝĐĂƌƋƵĞ͕ĞŶĞůĐĂƐŽĚĞůĂWǇĞŶĞůĚĞ
ůĂ,͕ůŽƐĐĂŵďŝŽƐĞŶůĂĨŽƌŵĂĚĞůĂƐŵŝƚŽĐŽŶĚƌŝĂƐƐĞĞƐƚĂďĂŶƉƌŽĚƵĐŝĞŶĚŽĂƚƌĂǀĠƐĚĞ
ŵĞĐĂŶŝƐŵŽƐ ŵŽůĞĐƵůĂƌĞƐ ĚŝĨĞƌĞŶƚĞƐ͘ Ɛş͕ Ă ĐŽŶƚŝŶƵĂĐŝſŶ͕ ƉƌŽĐĞĚŝŵŽƐ Ă ĂŶĂůŝǌĂƌ ůĂƐ
ƌƵƚĂƐŵĞƚĂďſůŝĐĂƐĂĐƚŝǀĂĚĂƐĞŶůŽƐĚŽƐŵŽĚĞůŽƐĚĞĞŶĨĞƌŵĞĚĂĚĞƐŶĞƵƌŽĚĞŐĞŶĞƌĂƚŝǀĂƐ͘
ŽŶĐƌĞƚĂŵĞŶƚĞ͕ŶŽƐĐĞŶƚƌĂŵŽƐĞŶĂƋƵĞůůĂƐƋƵĞƉĂƌƚŝĐŝƉĂŶĞŶůĂŵĂƋƵŝŶĂƌŝĂĚĞůĂĨŝƐŝſŶ
ŵŝƚŽĐŽŶĚƌŝĂůǇĞŶůŽƐĐĂŵďŝŽƐŵŽƌĨŽůſŐŝĐŽƐŽďƐĞƌǀĂĚŽƐ͘
Ɛş͕ ŶƵĞƐƚƌŽ ƉƌŝŵĞƌ ŽďũĞƚŝǀŽ ĨƵĞ ĐŽŶŽĐĞƌ ůĂ ƌĞůĞǀĂŶĐŝĂ Ğ ŝŵƉůŝĐĂĐŝſŶ ĚĞ ůĂ
ƉƌŽƚĞşŶĂƌƉϭĞŶŶƵĞƐƚƌŽƐƌĞƐƵůƚĂĚŽƐ͕ůĂĐƵĂů͕ĐŽŵŽŝŶĚŝĐĄďĂŵŽƐĞŶůĂŝŶƚƌŽĚƵĐĐŝſŶĂ
ĞƐƚĞƚƌĂďĂũŽ͕ĞƐůĂƉƌŝŶĐŝƉĂůĞŶĐĂƌŐĂĚĂĚĞůĂĨŝƐŝſŶĚĞůŽƌŐĄŶƵůŽ͕;ĞƌǀĞŶǇĞƚĂů͕͘ϮϬϬϭ͖
ϱϰ
s/͘ŝƐĐƵƐŝſŶ
<ĂƌďŽǁƐŬŝĞƚĂů͕͘ϮϬϬϰ͖DŽǌĚǇĞƚĂů͕͘ϮϬϬϬ͖KƚƐƵŐĂĞƚĂů͕͘ϭϵϵϴͿ͘ƌƉϭ͕ĞŶĐŽŶĚŝĐŝŽŶĞƐ
ĨŝƐŝŽůſŐŝĐĂƐ͕ ƐĞ ĞŶĐƵĞŶƚƌĂ ĞŶ Ğů ĐŝƚŽƐŽů ĐĞůƵůĂƌ͕ ĚŽŶĚĞ ĨŽƌŵĂ ŽůŝŐſŵĞƌŽƐ͕ ĂƵŶƋƵĞ
ƚĂŵďŝĠŶƉƌĞƐĞŶƚĂƵŶĂƉĞƋƵĞŹĂĨƌĂĐĐŝſŶŵŝƚŽĐŽŶĚƌŝĂů͘ƵĂŶĚŽĂƉĂƌĞĐĞƵŶĞƐƚşŵƵůŽĚĞ
ĨŝƐŝſŶĚĞůŽƌŐĄŶƵůŽ͕ƌƉϭŵŝŐƌĂĂůĂŵĞŵďƌĂŶĂŵŝƚŽĐŽŶĚƌŝĂůĞǆƚĞƌŶĂ͕ĂůĂƋƵĞƐĞƵŶĞĂ
ƚƌĂǀĠƐ ĚĞ ƌĞĐĞƉƚŽƌĞƐ ƉƌŽƚĞŝĐŽƐ ĞƐƉĞĐşĨŝĐŽƐ͘ ůůş͕ ĨŽƌŵĂ ĞƐƚƌƵĐƚƵƌĂƐ ĂŶƵůĂƌĞƐ ĂůƌĞĚĞĚŽƌ
ĚĞůĂŵŝƚŽĐŽŶĚƌŝĂ͕ĞŶůŽƐůƵŐĂƌĞƐĐŽŶĐƌĞƚŽƐĞŶůŽƐƋƵĞƐĞǀĂĂƉƌŽĚƵĐŝƌůĂĐŽŶƐƚƌŝĐĐŝſŶ
ĚĞ ůĂƐ ŵĞŵďƌĂŶĂƐ Ǉ͕ ĞŶ ƷůƚŝŵŽ ƚĠƌŵŝŶŽ͕ ůĂ ĞƐĐŝƐŝſŶ ĚĞů ŽƌŐĄŶƵůŽ͕ ;>ĂďƌŽƵƐƐĞ Ğƚ Ăů͕͘
ϭϵϵϵ͖ >ĞŐĞƐƐĞͲDŝůůĞƌ Ğƚ Ăů͕͘ ϮϬϬϯͿ͕ ƐŝĞŶĚŽ ĞƐƚĂ ƷůƚŝŵĂ ĚĞƉĞŶĚŝĞŶƚĞ ĚĞ ůĂ ŚŝĚƌſůŝƐŝƐ ĚĞ
'dW͕;&ƵŬƵƐŚŝŵĂĞƚĂů͕͘ϮϬϬϭ͖/ŶŐĞƌŵĂŶĞƚĂů͕͘ϮϬϬϱ͖ŚƵĞƚĂů͕͘ϮϬϬϰͿ͘
WĂƌĂĞůĞƐƚƵĚŝŽĚĞůĂŚŝƉŽƚĠƚŝĐĂƚƌĂƐůŽĐĂĐŝſŶĚĞƌƉϭ͕ƚƌĂŶƐĨĞĐƚĂŵŽƐůŽƐĐƵůƚŝǀŽƐ
ĐĞůƵůĂƌĞƐ ĐŽŶ Ğů ƉůĄƐŵŝĚŽ '&WͲƌƉϭ Ǉ ŽďƐĞƌǀĂŵŽƐ ůĂ ůŽĐĂůŝǌĂĐŝſŶ ŝŶƚƌĂĐĞůƵůĂƌ ĚĞ ůĂ
ĐŝƚĂĚĂ ƉƌŽƚĞşŶĂ͘ Ŷ ĐŽŶĚŝĐŝŽŶĞƐ ĐŽŶƚƌŽů͕ ůĂ ĨůƵŽƌĞƐĐĞŶĐŝĂ ƉƌŽĚƵĐŝĚĂ ƉŽƌ '&WͲƌƉϭ ƐĞ
ƉƌĞƐĞŶƚſĚŝƐƉĞƌƐĂƉŽƌƚŽĚŽĞůŝŶƚĞƌŝŽƌĐĞůƵůĂƌ͕ĞǆĐĞƉƚŽƉŽƌĞůŶƷĐůĞŽ͘^ŝŶĞŵďĂƌŐŽ͕ƚƌĂƐ
ůĂĂĚŝĐŝſŶĚĞϲͲK,ĂŶƵĞƐƚƌŽƐĐƵůƚŝǀŽƐĐĞůƵůĂƌĞƐ͕'&WͲƌƉϭŵŝŐƌĂďĂĂůĂŵŝƚŽĐŽŶĚƌŝĂ͕
ƉŽƌ ůŽ ƋƵĞ Ğů ƉĂƚƌſŶ ĚĞ ůĂ ĐŝƚĂĚĂ ĨůƵŽƌĞƐĐĞŶĐŝĂ ĐĂŵďŝĂďĂ ďƌƵƐĐĂŵĞŶƚĞ͕ ĂƉĂƌĞĐŝĞŶĚŽ
ĞŶƚŽŶĐĞƐƉĞƋƵĞŹĂƐĞƐƚƌƵĐƚƵƌĂƐƉƵŶƚĞĂĚĂƐ͕ĞŶůŽƐůƵŐĂƌĞƐĞŶůŽƐƋƵĞƐĞĞŶĐƵĞŶƚƌĂŶůĂƐ
ŵŝƚŽĐŽŶĚƌŝĂƐ͘
WĂƌĂŝŶĐŝĚŝƌŵĄƐƐŽďƌĞĞƐƚĞĂƐƉĞĐƚŽ͕ĞƐƚƵĚŝĂŵŽƐ͕ŵĞĚŝĂŶƚĞtĞƐƚĞƌŶůŽƚƚŝŶŐ͕ůĂ
ĚŝƐƚƌŝďƵĐŝſŶ ŝŶƚƌĂĐĞůƵůĂƌ ĚĞ ƌƉϭ͘ Ŷ ƵŶ ƉƌŝŵĞƌ ĞǆƉĞƌŝŵĞŶƚŽ͕ ĐŽŵƉƌŽďĂŵŽƐ ƋƵĞ ůŽƐ
ŶŝǀĞůĞƐ ƚŽƚĂůĞƐ ĚĞ ƌƉϭ ĞŶĐŽŶƚƌĂĚŽƐ ĞŶ ůŽƐ ĞǆƚƌĂĐƚŽƐ ĐĞůƵůĂƌĞƐ ĞƌĂŶ ĐŽŶƐƚĂŶƚĞƐ Ă ůŽ
ůĂƌŐŽĚĞůƚŝĞŵƉŽ͘ĐŽŶƚŝŶƵĂĐŝſŶ͕ƚƌĂƐƌĞĂůŝǌĂƌĞůĨƌĂĐĐŝŽŶĂŵŝĞŶƚŽĐĞůƵůĂƌĚĞůŽƐĐŝƚĂĚŽƐ
ůŝƐĂĚŽƐ͕ŽďƐĞƌǀĂŵŽƐƋƵĞůĂĐĂŶƚŝĚĂĚĚĞƌƉϭƉƌĞƐĞŶƚĞĞŶůĂƐŵƵĞƐƚƌĂƐƚƌĂƚĂĚĂƐĐŽŶϲͲ
K,ĂƵŵĞŶƚĂďĂĐŽŶƐŝĚĞƌĂďůĞŵĞŶƚĞĞŶůĂĨƌĂĐĐŝſŶŵŝƚŽĐŽŶĚƌŝĂů͕ĞŶƌĞůĂĐŝſŶĐŽŶůŽƐ
ĚĂƚŽƐ ŽďƚĞŶŝĚŽƐ ĞŶ ĐŽŶĚŝĐŝŽŶĞƐ ĐŽŶƚƌŽů͕ ƐŽďƌĞ ƚŽĚŽ ƚƌĂƐ ƚƌĞƐ Ǉ ƐĞŝƐ ŚŽƌĂƐ ĚĞ
ƚƌĂƚĂŵŝĞŶƚŽĐŽŶϲͲK,͘ƐƚŽƐĚĂƚŽƐ͕ĐŽƌƌŽďŽƌĂŶ͕ƉŽƌƚĂŶƚŽ͕ůŽƐŽďƚĞŶŝĚŽƐŵĞĚŝĂŶƚĞ
ƚĠĐŶŝĐĂƐĚĞŵŝĐƌŽƐĐŽƉŝĂĐŽŶĨŽĐĂů͘
ŶĞůĐĂƐŽĚĞŶƵĞƐƚƌŽŵŽĚĞůŽĨĂƌŵĂĐŽůſŐŝĐŽĐĞůƵůĂƌĚĞ,͕ĐƌĞĂĚŽĐŽŶϯEW͕Ğů
ƌĞƐƵůƚĂĚŽ ĨƵĞ ũƵƐƚĂŵĞŶƚĞ Ğů ĐŽŶƚƌĂƌŝŽ͕ ĞƐƚŽ ĞƐ͕ ĐƵĂŶĚŽ ƵƚŝůŝǌĂŵŽƐ ƚĠĐŶŝĐĂƐ ĚĞ
ŵŝĐƌŽƐĐŽƉşĂĐŽŶĨŽĐĂůŶŽƐĞŽďƐĞƌǀſŶŝŶŐƵŶĂǀĂƌŝĂĐŝſŶĞŶĞůƉĂƚƌſŶĚĞĨůƵŽƌĞƐĐĞŶĐŝĂĚĞ
'&WͲƌƉϭ͘WŽƌƚĂŶƚŽ͕ƉŽĚĞŵŽƐĂĨŝƌŵĂƌƋƵĞ͕ĞŶĞƐƚĞĐĂƐŽ͕ŶŽƐĞĂĐƚŝǀſůĂŵŝŐƌĂĐŝſŶĚĞ
ϱϱ
ƌƉϭ Ă ůĂ ŵŝƚŽĐŽŶĚƌŝĂ͘ Ɛş͕ ĚĞ ĞƐƚŽƐ ĚĂƚŽƐ ƐĞ ĚĞƐƉƌĞŶĚĞ ƋƵĞ ƌƉϭ ŶŽ ƉĂƌƚŝĐŝƉĂ
ĂĐƚŝǀĂŵĞŶƚĞ ĞŶ ůŽƐ ĐĂŵďŝŽƐ ŵŽƌĨŽůſŐŝĐŽƐ ŝŶĚƵĐŝĚŽƐ ƉŽƌ ϯEW ĞŶ Ğů ŽƌŐĄŶƵůŽ͘
ĚŝĐŝŽŶĂůŵĞŶƚĞ͕ĂůŝŐƵĂůƋƵĞĞŶĞůŵŽĚĞůŽĚĞW͕ƚĂŵďŝĠŶĂƋƵşƋƵŝƐŝŵŽƐĐŽƌƌŽďŽƌĂƌůŽƐ
ƌĞƐƵůƚĂĚŽƐŽďƚĞŶŝĚŽƐ͕ŵĞĚŝĂŶƚĞůĂƚĠĐŶŝĐĂĚĞtĞƐƚĞƌŶůŽƚƚŝŶŐ͘dƌĂƐĞůƚƌĂƚĂŵŝĞŶƚŽĐŽŶ
ϯEW͕ůĂƐŵĞŵďƌĂŶĂƐŵŽƐƚƌĂƌŽŶƋƵĞ͕ĞĨĞĐƚŝǀĂŵĞŶƚĞ͕ůĂĐĂŶƚŝĚĂĚĚĞƌƉϭƉƌĞƐĞŶƚĞĞŶůĂ
ŵŝƚŽĐŽŶĚƌŝĂŶŽĂƵŵĞŶƚſĐŽŶƐŝĚĞƌĂďůĞŵĞŶƚĞ͕ƌĞƐƉĞĐƚŽĂůĂƐĐŽŶĚŝĐŝŽŶĞƐĐŽŶƚƌŽů͘
WŽƌ ƚĂŶƚŽ͕ ůůĞŐĂĚŽƐ Ă ĞƐƚĞ ƉƵŶƚŽ͕ ůĂ ĐĂƵƐĂ ĚĞ ůŽƐ ƌĄƉŝĚŽƐ Ǉ ĚƌĄƐƚŝĐŽƐ ĐĂŵďŝŽƐ
ŵŽƌĨŽůſŐŝĐŽƐŝŶĚƵĐŝĚŽƐƉŽƌϯEWĞŶůĂƐŵŝƚŽĐŽŶĚƌŝĂƐ ĂƷŶŶŽŚĂďşĂƐŝĚŽĚŝůƵĐŝĚĂĚĂ͕ǇĂ
ƋƵĞ ĠƐƚŽƐ ŶŽ ƉŽĚşĂŶ ƐĞƌ ĂƚƌŝďƵŝĚŽƐ Ă ůĂ ĂĐƚŝǀĂĐŝſŶ ĚĞ ůĂ ĨŝƐŝſŶ ŵŝƚŽĐŽŶĚƌŝĂů͘ ^ŝŶ
ĞŵďĂƌŐŽ͕ ƉŽĚƌşĂ ƐĞƌ ůĂ ĨŽƌŵĂĐŝſŶ ĚĞů WWdD͕ Ǉ Ğů ĐŽŶƐŝŐƵŝĞŶƚĞ ĞĚĞŵĂ ŵŝƚŽĐŽŶĚƌŝĂů͕
ĞƐƚƵǀŝĞƌĂŶ ĞŶ ůĂ ďĂƐĞ ĚĞ ůĂƐ ǀĂƌŝĂĐŝŽŶĞƐ ĞŶ ůĂ ĨŽƌŵĂ ĚĞ ůŽƐ ŽƌŐĄŶƵůŽƐ͘ Ɛş͕ ĞŶ ůĂ
ďŝďůŝŽŐƌĂĨşĂ͕ĞŶĐŽŶƚƌĂŵŽƐƋƵĞŽƚƌŽŝŶŚŝďŝĚŽƌĚĞůĐŽŵƉůĞũŽ//ĚĞůĂd͕ĞŶĞƐƚĞĐĂƐŽĞů
ŵĂůŽŶĂƚŽ͕ĞƐ ƉƌĞĐŝƐĂŵĞŶƚĞ ĚĞ ƉƌŽĚƵĐŝƌ Ğů ĐŝƚĂĚŽ ĞĚĞŵĂ͕ĞŶ ĐƵůƚŝǀŽƐ ĐĞůƵůĂƌĞƐĚĞ ^,Ͳ
^zϱz͕ ;&ĞƌŶĂŶĚĞǌͲ'ŽŵĞǌ Ğƚ Ăů͕͘ ϮϬϬϱͿ͘ WĂƌĂ ĐŽƌƌŽďƌŽĂƌ ĞƐƚĂ ŚŝƉſƚĞƐŝƐ͕ ƌĞĂůŝǌĂŵŽƐ Ğů
ĂŶĄůŝƐŝƐĚĞůĂĨŽƌŵĂĐŝſŶĚĞůWWdD͕ƚĂŶƚŽŝŶǀŝǀŽĐŽŵŽĞŶŵŝƚŽĐŽŶĚƌŝĂĂŝƐůĂĚĂ͘
WĂƌĂ Ğů ĞƐƚƵĚŝŽ ŝŶ ǀŝǀŽ ĚĞ ĞƐƚĞ ƉƌŽĐĞƐŽ͕ ƌĞĂůŝǌĂŵŽƐ ůĂ ŵĞĚŝĐŝſŶ ĚĞ ůĂ
ĨůƵŽƌĞƐĐĞŶĐŝĂ ĚĞ ůĂ ĐĂůĐĞşŶĂ ĞŶ ŶƵĞƐƚƌŽƐ ĐƵůƚŝǀŽƐ ĐĞůƵůĂƌĞƐ͘ ^Ğ ƚƌĂƚĂ ĚĞ ƵŶĂ ŵŽůĠĐƵůĂ
ĨůƵŽƌĞƐĐĞŶƚĞĐĂƉĂǌĚĞĂƚƌĂǀĞƐĂƌƚŽĚĂƐůĂƐŵĞŵďƌĂŶĂƐďŝŽůſŐŝĐĂƐĐĞůƵůĂƌĞƐǇ͕ƉŽƌƚĂŶƚŽ͕
ĚĞ ĞŶƚƌĂƌ Ăů ŝŶƚĞƌŝŽƌ ŵŝƚŽĐŽŶĚƌŝĂů͘ ƵĂŶĚŽ ĞƐƚĂ ƐƵƐƚĂŶĐŝĂ ĞƐ ƋƵĞůĂĚĂ ƉŽƌ ĂůŐƷŶ
ĞůĞŵĞŶƚŽ͕ ĐŽŵŽ ĞƐ Ğů ĐĂƐŽ ĚĞů ĐŽďĂůƚŽ͕ ƐĞ ĂƉĂŐĂ͘ sĂůŝĠŶĚŽŶŽƐ ĚĞ ůĂ ĐĂƉĂĐŝĚĂĚ ĚĞů
ĐŽďĂůƚŽ ƉĂƌĂ ĂƚƌĂǀĞƐĂƌ ůĂ ŵĞŵďƌĂŶĂ ĐĞůƵůĂƌ͕ ƉĞƌŽ ŶŽ ůĂ ĚĞů ĐŝƚĂĚŽ ŽƌŐĄŶƵůŽ͕
ĞƐƚƵĚŝĂŵŽƐ ůĂ ŝŶƚĞŶƐŝĚĂĚ Ǉ ůĂ ůŽĐĂůŝǌĂĐŝſŶ ĚĞ ůĂ ĨůƵŽƌĞƐĐĞŶĐŝĂ ƉƌĞƐĞŶƚĞ ĞŶ ŶƵĞƐƚƌŽƐ
ĐƵůƚŝǀŽƐ͘ Ɛş͕ ƐſůŽ ĞŶ Ğů ĐĂƐŽ ĚĞ ƋƵĞ ƐĞ ƉƌŽĚƵǌĐĂ ůĂ ĨŽƌŵĂĐŝſŶ ĚĞů WWdD͕ Ğů ĐŽďĂůƚŽ
ĞŶƚƌĂƌĄĞŶĐŽŶƚĂĐƚŽĐŽŶůĂĐĂůĐĞşŶĂŝŶƚƌĂŵŝƚŽĐŽŶĚƌŝĂů͕ĂƉĂŐĂŶĚŽůĂĨůƵŽƌĞƐĐĞŶĐŝĂ͘WŽƌ
ƚĂŶƚŽ͕ Ɛŝ ůĂƐ ĐĠůƵůĂƐ ƉƌĞƐĞŶƚĂŶ ƵŶĂ ĨůƵŽƌĞƐĐĞŶĐŝĂ ŝŶƚĞŶƐĂ Ǉ ůŽĐĂůŝǌĂĚĂ ĞŶ ǌŽŶĂƐ
ĐŽŶĐƌĞƚĂƐ͕;ĞŶůĂƐŵŝƚŽĐŽŶĚƌŝĂƐͿ͕ƉŽĚƌĞŵŽƐĂĨŝƌŵĂƌƋƵĞŶŽŚĂǇĞĚĞŵĂ͕ŵŝĞŶƚƌĂƐƋƵĞ͕
Ɛŝ ůĂ ĐŝƚĂĚĂ ĨůƵŽƌĞƐĐĞŶĐŝĂ ĂƉĂƌĞĐĞ ĚŝƐƉĞƌƐĂ Ǉ ĐŽŶ ƵŶĂ ŝŶƚĞŶƐŝĚĂĚ ŵĞŶŽƌ͕ Ğů WWdD ƐĞ
ŚĂďƌĄĨŽƌŵĂĚŽǇĞůĐŽďĂůƚŽǇůĂĐĂůĐĞşŶĂŚĂďƌĄŶĞŶƚƌĂĚŽĞŶĐŽŶƚĂĐƚŽ͘
Ɛş͕ƚƌĂƐƚƌĞŝŶƚĂŵŝŶƵƚŽƐĚĞƚƌĂƚĂŵŝĞŶƚŽĐŽŶϯEW͕ĂƉĂƌĞĐşĂƵŶĂĐůĂƌĂĚŝƐƉĞƌƐŝſŶ
ϱϲ
ĚĞůĂĐŝƚĂĚĂĨůƵŽƌĞƐĐĞŶĐŝĂ͕ůŽĐƵĂůƐĞĐŽƌƌĞůĂĐŝŽŶĂĐůĂƌĂŵĞŶƚĞ͕ĐŽŵŽŝŶĚŝĐĄďĂŵŽƐ͕ĐŽŶ
ůĂĨŽƌŵĂĐŝſŶǇĂƉĞƌƚƵƌĂĚĞůWWdD͘ĚŝĐŝŽŶĂůŵĞŶƚĞ͕ƌĞĂůŝǌĂŵŽƐƚĂŵďŝĠŶĞůĞƐƚƵĚŝŽĚĞůĂ
ĂƉĞƌƚƵƌĂ ĚĞů ƉŽƌŽ Ǉ ĚĞ ůĂ ĨŽƌŵĂĐŝſŶ ĚĞů ĐŽŶƐŝŐƵŝĞŶƚĞ ĞĚĞŵĂ ĚĞů ŽƌŐĄŶƵůŽ ĞŶ
ŵŝƚŽĐŽŶĚƌŝĂĂŝƐůĂĚĂ͘Ɛş͕ĐŽŶƐƚĂƚĂŵŽƐƋƵĞϯEWĞƐ͕ĞĨĞĐƚŝǀĂŵĞŶƚĞ͕ƵŶĂŐĞŶƚĞŝŶĚƵĐƚŽƌ
ĚĞ ĂŵďŽƐ ƉƌŽĐĞƐŽƐ͕ Ă ƚƌĂǀĠƐ ĚĞ ƵŶĂ ƌƵƚĂ ĐůĄƐŝĐĂ ĚĞƉĞŶĚŝĞŶƚĞ ĚĞ ĐŝĐůŽƐƉŽƌŝŶĂ ͕ ;ƵŶ
ŝŶŚŝďŝĚŽƌĚĞůĂĨŽƌŵĂĐŝſŶĚĞůWWdDͿ͘ƐƚŽƐĚĂƚŽƐĐŽŶĐƵĞƌĚĂŶĐŽŶůŽƐƉƵďůŝĐĂĚŽƐƉŽƌƵŶ
ŐƌƵƉŽ ũĂƉŽŶĠƐ͕ ;EŝƐŚŝŵƵƌĂ Ğƚ Ăů͕͘ ϮϬϬϴͿ͘ ĚĞŵĄƐ͕ ĂƉŽǇĂŶĚŽ ĂƷŶ ŵĄƐ ŶƵĞƐƚƌŽƐ
ƌĞƐƵůƚĂĚŽƐ͕ ŽƚƌŽ ĞƋƵŝƉŽ͕ ;>ĞǀĞŶƚŚĂů Ğƚ Ăů͕͘ ϮϬϬϬͿ͕ ĚĞŵŽƐƚƌſ͕ ĞŶ ƵŶ ŵŽĚĞůŽ ĚĞ ƌĂƚĂƐ
ůĞƐŝŽŶĂĚĂƐĐŽŶϯEW͕ƋƵĞůĂƐƉƌŽƉŝĞĚĂĚĞƐŶĞƵƌŽƉƌŽƚĞĐƚŽƌĂƐĚĞĐŝĐůŽƐƉŽƌŝŶĂĞƐƚĂďĂŶ
ŵĞĚŝĂĚĂƐ ƉŽƌ ƐƵ ĐĂƉĂĐŝĚĂĚ ƉĂƌĂ ƉƌĞǀĞŶŝƌ ůĂ ĂƉĞƌƚƵƌĂ ĚĞů WWdD͕ ĚƵƌĂŶƚĞ ůĂƐ
ĞǆƉŽƐŝĐŝŽŶĞƐĂĂůƚŽƐŶŝǀĞůĞƐĚĞĐĂůĐŝŽŽĂĞƐƚƌĠƐŽǆŝĚĂƚŝǀŽ͘
WĂƌĂ ĞƐƚƵĚŝĂƌ ŵĄƐ ĞŶ ƉƌŽĨƵŶĚŝĚĂĚ ůĂ ŵŝŐƌĂĐŝſŶ ŵŝƚŽĐŽŶĚƌŝĂů ĚĞ ƌƉϭ Ǉ ƐƵ
ŚŝƉŽƚĠƚŝĐĂ ƌĞůĂĐŝſŶ ĐŽŶ ůŽƐ ĐĂŵďŝŽƐ ŵŽƌĨŽůſŐŝĐŽƐ ŽďƐĞƌǀĂĚŽƐ ĞŶ ŶƵĞƐƚƌŽƐ ƚƌĂďĂũŽƐ͕
ƵƚŝůŝǌĂŵŽƐ DĚŝǀŝͲϭ͘ ƐƚĞ ĨĄƌŵĂĐŽ͕ ĐƵǇĂƐ ĐĂƌĂĐƚĞƌşƐƚŝĐĂƐ ŚĂŶ ƐŝĚŽ ƚƌĂƚĂĚĂƐ ĞŶ
ƉƌŽĨƵŶĚŝĚĂĚĞŶůĂŝŶƚƌŽĚƵĐĐŝſŶĚĞĞƐƚĞƚƌĂďĂũŽ͕ĂĐƚƷĂƵŶŝĠŶĚŽƐĞĂƵŶƐŝƚŝŽĂůŽƐƚĠƌŝĐŽ
ĚĞƌƉϭ͕ƉƌŽĚƵĐŝĞŶĚŽĂƐşůĂŝŶŚŝďŝĐŝſŶĞƐƉĞĐşĨŝĐĂĚĞůĂĂĐƚŝǀŝĚĂĚĚĞůĂƉƌŽƚĞşŶĂ͕;ŶŽƐſůŽ
ĚĞƐƵĐĂƉĂĐŝĚĂĚ'dWĂƐĂͿ͕Ǉ͕ƉŽƌĐŽŶƐŝŐƵŝĞŶƚĞ͕ĚĞůĂĨŝƐŝſŶŵŝƚŽĐŽŶĚƌŝĂů͕;ĂƐƐŝĚǇͲ^ƚŽŶĞ
ĞƚĂů͕͘ϮϬϬϴͿ͘
ŶĞůĐĂƐŽĚĞůŵŽĚĞůŽĚĞW͕DĚŝǀŝͲϭĨƵĞĐĂƉĂǌĚĞĞǀŝƚĂƌůĂŵŝŐƌĂĐŝſŶŚĂĐŝĂůĂ
ŵŝƚŽĐŽŶĚƌŝĂ ĚĞ ƌƉϭ͕ ĂƐş ĐŽŵŽ ĚĞ ĚŝƐŵŝŶƵŝƌ ƐŝŐŶŝĨŝĐĂƚŝǀĂŵĞŶƚĞ ůĂ ŵĂŐŶŝƚƵĚ ĚĞ ůĂ
ĚŝƐĨƵŶĐŝſŶ ĞŶ ůĂ ŵŽƌĨŽůŽŐşĂ ĚĞů ŽƌŐĄŶƵůŽ͕ ŝŶĚƵĐŝĚĂ ƉŽƌ ϲͲK,͘ ƐƚŽƐ ĚĂƚŽƐ
ĐŽŶĐƵĞƌĚĂŶĐŽŶůŽƐŽďƚĞŶŝĚŽƐƉŽƌŽƚƌŽƐŐƌƵƉŽƐ͕ĚŽŶĚĞŵƵĞƐƚƌĂŶƋƵĞDĚŝǀŝͲϭ͕ƚƌĂƐůĂ
ĂĚŝĐŝſŶĚĞĚŝǀĞƌƐŽƐĨĄƌŵĂĐŽƐŝŶĚƵĐƚŽƌĞƐĚĞůĂĨŝƐŝſŶŵŝƚŽĐŽŶĚƌŝĂů͕ĞƐĐĂƉĂǌĚĞƉƌĞǀĞŶŝƌ
ůĂ ĨŽƌŵĂĐŝſŶ ĚĞ ůĂƐ ĞƐƚƌƵĐƚƵƌĂƐ ƉƵŶƚĞĂĚĂƐ Ă ƚƌĂǀĠƐ ĚĞ ůĂƐ ĐƵĂůĞƐ ƌƉϭ ƐĞ ƵŶĞ Ă ůĂ
ŵŝƚŽĐŽŶĚƌŝĂ͕ ůŽ ĐƵĂů ƐĞƚƌĂĚƵĐĞ ĞŶ ƵŶĂ ƌĞĚƵĐĐŝſŶ ĐŽŶƐŝĚĞƌĂďůĞĚĞ ůĂ ĨŝƐŝſŶ ĚĞů ĐŝƚĂĚŽ
ŽƌŐĄŶƵůŽ͕ ;ĂƐƐŝĚǇͲ^ƚŽŶĞ Ğƚ Ăů͕͘ ϮϬϬϴ͖ ĞƌĞŐŚĞƚƚŝ Ğƚ Ăů͕͘ ϮϬϬϴͿ͘ WŽƌ ƚĂŶƚŽ͕ ƉŽĚĞŵŽƐ
ĐŽŶĐůƵŝƌƋƵĞ͕ĞŶĞůĐĂƐŽĚĞůĂW͕ůĂĨŝƐŝſŶŵŝƚŽĐŽŶĚƌŝĂůĞƐůĂĐĂƵƐĂŶƚĞĚĞůĂƐĚŝĨĞƌĞŶĐŝĂƐ
ƋƵĞƐĞĂƉƌĞĐŝĂŶĞŶůĂĨŽƌŵĂĚĞůĂƐŵŝƚŽĐŽŶĚƌŝĂƐ͕ĂƐşĐŽŵŽƋƵĞůĂĐŝƚĂĚĂĨŝƐŝſŶƉƵĞĚĞ
ƐĞƌŵŽĚƵůĂĚĂĨĂƌŵĂĐŽůſŐŝĐĂŵĞŶƚĞĂƚƌĂǀĠƐĚĞůƵƐŽĚĞDĚŝǀŝͲϭ͘
ϱϳ
WŽƌ Ğů ĐŽŶƚƌĂƌŝŽ͕ ĞŶ Ğů ŵŽĚĞůŽ ĚĞ ,͕ ůĂ ĂĚŝĐŝſŶ ĚĞ DĚŝǀŝͲϭ Ă ůŽƐ ĐƵůƚŝǀŽƐ
ĐĞůƵůĂƌĞƐ ƚƌĂƚĂĚŽƐ ĐŽŶ ϯEW͕ ŶŽ ĨƵĞ ĐĂƉĂǌ ĚĞ ƉƌŽĚƵĐŝƌ ŶŝŶŐƵŶĂ ĚŝĨĞƌĞŶĐŝĂ ĞŶ ůĂ
ŵŽƌĨŽůŽŐşĂŵŝƚŽĐŽŶĚƌŝĂů͕ƌĞƐƉĞĐƚŽĂůĂŽďƐĞƌǀĂĚĂĐƵĂŶĚŽƐĞĂŹĂĚşĂƐŽůĂŵĞŶƚĞϯEW͘>Ă
ĐŽŶĐĞŶƚƌĂĐŝſŶ ĚĞ DĚŝǀŝͲϭ ƵƐĂĚĂ ĞŶ ŶƵĞƐƚƌŽƐ ĞǆƉĞƌŝŵĞŶƚŽƐ͕ ;ϭϬ ђDͿ͕ ĨƵĞ ƐƵĨŝĐŝĞŶƚĞ
ƉĂƌĂ ŝŶŚŝďŝƌ ůĂ ĨŝƐŝſŶ ŵŝƚŽĐŽŶĚƌŝĂů͕ ǇĂ ƋƵĞ ƉƌŽĚƵũŽ ƵŶ ĂƵŵĞŶƚŽ ĚĞ ůĂ ĞůŽŶŐĂĐŝſŶ
ŵŝƚŽĐŽŶĚƌŝĂůƚƌĂƐƐƵĂĚŝĐŝſŶĂŶƵĞƐƚƌŽƐĐƵůƚŝǀŽƐĐĞůƵůĂƌĞƐ͘ƐƚĞŚĞĐŚŽĐŽŶĐƵĞƌĚĂĐŽŶůĂ
ĂƵƐĞŶĐŝĂ ĚĞ ŵŝŐƌĂĐŝſŶ ĚĞ ƌƉϭ͕ ŽďƐĞƌǀĂĚĂ ƉƌĞǀŝĂŵĞŶƚĞ͕ ĂƐş ĐŽŵŽ ĐŽŶ ůŽƐ ĚĂƚŽƐ
ƌĞůĂƚŝǀŽƐ Ă ůĂ ĂƉĞƌƚƵƌĂ ĚĞů WWdD͘ WŽƌ ƚĂŶƚŽ͕ ĞŶ ĞƐƚĞ ĐĂƐŽ͕ ƉŽĚĞŵŽƐ ĂĨŝƌŵĂƌ ƋƵĞ ůĂ
ĐĂƵƐĂ ĚĞ ůŽƐ ĐĂŵďŝŽƐ ĞŶ ůĂ ŵŽƌĨŽůŽŐşĂ ĚĞů ŽƌŐĄŶƵůŽ ĞƐ ůĂ ĨŽƌŵĂĐŝſŶ ĚĞů WWdD Ǉ Ğů
ĐŽŶƐŝŐƵŝĞŶƚĞĞĚĞŵĂŵŝƚŽĐŽŶĚƌŝĂů͕ƉŽƌůŽƋƵĞůĂĨŝƐŝſŶĚĞůŽƌŐĄŶƵůŽŶŽĞƐƚĄĂĐƚŝǀĂĚĂǇ
DĚŝǀŝͲϭŶŽƉƌŽĚƵĐĞŶŝŶŐƵŶĂŵŽĚƵůĂĐŝſŶƐŽďƌĞůŽƐĐĂŵďŝŽƐŵŽƌĨŽůſŐŝĐŽƐŝŶĚƵĐŝĚŽƐƉŽƌ
ϯEW͘
Ăǆ͕ ĞƐ ƵŶĂ ƉƌŽƚĞşŶĂ ƉĞƌƚĞŶĞĐŝĞŶƚĞ Ă ůĂ ĨĂŵŝůŝĂ ĚĞ ůĂƐ ĐůͲϮ͘ Ğ ŶĂƚƵƌĂůĞǌĂ
ĐŝƚŽƐſůŝĐĂ͕ŵŝŐƌĂĂůĂŵŝƚŽĐŽŶĚƌŝĂĐƵĂŶĚŽĂƉĂƌĞĐĞƵŶĞƐƚşŵƵůŽĂĐƚŝǀĂĚŽƌ͕;ƐŚŬƚŽƌĂďĞƚ
Ăů͕͘ ϮϬϬϰ͖ DĞůŝŶŽ Ğƚ Ăů͕͘ ϮϬϬϰ͖ ^ĂƌŬĂƌ Ğƚ Ăů͕͘ ϮϬϬϯ͖ ^ŵĂŝůŝ Ğƚ Ăů͕͘ ϮϬϬϭͿ͘ ĚĞŵĄƐ͕ ĞƐƚĄ
ĨƵĞƌƚĞŵĞŶƚĞ ƌĞůĂĐŝŽŶĂĚĂ ĐŽŶ ůŽƐ ƉƌŽĐĞƐŽƐ ŶĞƵƌŽĚĞŐĞŶĞƌĂƚŝǀŽƐ͕ ;'ŽŵĞǌͲ>ĂǌĂƌŽ Ğƚ Ăů͕͘
ϮϬϬϴď͖ WĞƌĞǌͲůǀĂƌĞǌ Ğƚ Ăů͕͘ ϮϬϬϵͿ͕ ĂƐŝŐŶĄŶĚŽƐĞůĞ ƚĂŵďŝĠŶ ƵŶ ƉŽƐŝďůĞ ƉĂƉĞů ĞŶ ůĂ
ĚŝŶĄŵŝĐĂŵŝƚŽĐŽŶĚƌŝĂů͕ĐŽŶĐƌĞƚĂŵĞŶƚĞĞŶůĂĨŝƐŝſŶĚĞůŽƌŐĄŶƵůŽ͕;ĂƐƐŝĚǇͲ^ƚŽŶĞĞƚĂů͕͘
ϮϬϬϴ͖tƵĞƚĂů͕͘ϮϬϭϭ͖zƵĂŶĞƚĂů͕͘ϮϬϬϳͿ͘ƉŽǇĂŶĚŽĞƐƚĂŚŝƉſƚĞƐŝƐ͕ĞŶĐŽŶƚƌĂŵŽƐ͕ƉŽƌ
ĞũĞŵƉůŽ͕ĞůŚĞĐŚŽĚĞƋƵĞĂǆĐŽůŽĐĂůŝǌĂĐŽŶƌƉϭǇĐŽŶDĨŶϮĞŶůĂƐŵŝƚŽĐŽŶĚƌŝĂƐĚĞ
ĐĠůƵůĂƐĂƉŽƉƚſƚŝĐĂƐ͕ĐŽŶĐƌĞƚĂŵĞŶƚĞĞŶůŽƐůƵŐĂƌĞƐĞŶůŽƐƋƵĞƐĞƉƌŽĚƵĐĞůĂĨŝƐŝſŶĚĞů
ŽƌŐĄŶƵůŽ͕ ;<ĂƌďŽǁƐŬŝ Ğƚ Ăů͕͘ ϮϬϬϮͿ͘ ĚĞŵĄƐ͕ ĞŶ ůĂ ůşŶĞĂ ĚĞ ĞƐĂƐ ŽďƐĞƌǀĂĐŝŽŶĞƐ͕ ůĂ
ƌĞĚƵĐĐŝſŶĚĞůĂĂĐƵŵƵůĂĐŝſŶĚĞĂǆĞŶůĂŵŝƚŽĐŽŶĚƌŝĂ͕ƐĞĐŽƌƌĞůĂĐŝŽŶſĐŽŶůĂƐƵƉƌĞƐŝſŶ
ŐĞŶĠƚŝĐĂ ƉĂƌĐŝĂů ƚĂŶƚŽ ĚĞ ƌƉϭ ĐŽŵŽ ĚĞ &ŝƐϭ͕ ;>ĞĞ Ğƚ Ăů͕͘ ϮϬϬϰͿ͘ ^ŝŶ ĞŵďĂƌŐŽ͕ ĐŽŵŽ
ŚĞŵŽƐŝŶĚŝĐĂĚŽĞŶůĂŝŶƚƌŽĚƵĐĐŝſŶĚĞĞƐƚĞƚƌĂďĂũŽ͕ůĂƉĂƌƚŝĐŝƉĂĐŝſŶĚĞĂǆĞŶůĂĨŝƐŝſŶ
ŵŝƚŽĐŽŶĚƌŝĂůĞƐĐŽŶƚƌŽǀĞƌƚŝĚĂ͕;ŶƚŝŐŶĂŶŝĞƚĂů͕͘ϮϬϬϲͿ͘Ɛş͕ƉŽƌĞũĞŵƉůŽ͕ĞŶƵŶŵŽĚĞůŽ
ĚĞ ŶĞƵƌŽĚĞŐĞŶĞƌĂĐŝſŶ ĐƌĞĂĚŽ ĞŶ ĐĠůƵůĂƐ D& ŵƵƌŝŶĂƐ ĐĂƌĞŶƚĞƐ ĚĞ Ăǆ͕ ůĂ ĐŝƚĂĚĂ
ƉƌŽƚĞşŶĂ ŶŽ ĨƵĞ ŶĞĐĞƐĂƌŝĂ ƉĂƌĂ ƋƵĞ ƐĞ ƉƌŽĚƵũĞƐĞ ůĂ ĨƌĂŐŵĞŶƚĂĐŝſŶ ŵŝƚŽĐŽŶĚƌŝĂů͕
ƐĞĐƵŶĚĂƌŝĂĂůĂĂĚŝĐŝſŶĚĞϲͲK,͕;'ŽŵĞǌͲ>ĂǌĂƌŽĞƚĂů͕͘ϮϬϬϴĂͿ͘
WŽƌƚĂŶƚŽ͕ĂĐŽŶƚŝŶƵĂĐŝſŶ͕ƉƌŽĐĞĚŝŵŽƐĂĞƐƚƵĚŝĂƌƐŝůĂƚƌĂƐůŽĐĂĐŝſŶĚĞĂǆĂůĂ
ϱϴ
ŵŝƚŽĐŽŶĚƌŝĂƉŽĚşĂƚĞŶĞƌĂůŐƵŶĂƌĞůĂĐŝſŶĐŽŶůŽƐĐĂŵďŝŽƐŵŽƌĨŽůſŐŝĐŽƐŽďƐĞƌǀĂĚŽƐ͕ĂƐş
ĐŽŵŽĐŽŶůĂŵŝŐƌĂĐŝſŶŵŝƚŽĐŽŶĚƌŝĂůĚĞƌƉϭ͕ƋƵĞĐŽŶƐƚĂƚĂŵŽƐĞŶĞůŵŽĚĞůŽĚĞW͘
Ŷ ĐŽŶĚŝĐŝŽŶĞƐ ĐŽŶƚƌŽů͕ Ğů ƉůĄƐŵŝĚŽ '&WͲĂǆ ƉƌĞƐĞŶƚĂ ƵŶĂ ĚŝƐƚƌŝďƵĐŝſŶ
ŚŽŵŽŐĠŶĞĂ ƉŽƌ ƚŽĚĂ ůĂ ĐĠůƵůĂ͕ ŵŽƐƚƌĂŶĚŽ͕ ƉŽƌ ƚĂŶƚŽ͕ ƵŶ ƉĂƚƌſŶ ĚĞ ĨůƵŽƌĞƐĐĞŶĐŝĂ
ŝŶƚƌĂĐĞůƵůĂƌĐŽŶƐƚĂŶƚĞ͕ĂƵŶƋƵĞ͕ĞŶĞƐƚĞĐĂƐŽ͕ůĂĐŝƚĂĚĂĨůƵŽƌĞƐĐĞŶĐŝĂƚĂŵďŝĠŶĂƉĂƌĞĐĞ
ĞŶ Ğů ŶƷĐůĞŽ͘ ^ŝŶ ĞŵďĂƌŐŽ͕ ƚƌĂƐ ĚŽĐĞ ŚŽƌĂƐ ĚĞ ƚƌĂƚĂŵŝĞŶƚŽ ĐŽŶ ϲͲK,͕ ĞŶ ůĂƐ
ŝŵĄŐĞŶĞƐĚĞĐŽŶĨŽĐĂů͕ƐĞŽďƐĞƌǀĂďĂƵŶĂĐůĂƌĂůŽĐĂůŝǌĂĐŝſŶĚĞůĂĨůƵŽƌĞƐĐĞŶĐŝĂĞŵŝƚŝĚĂ
ƉŽƌĞůƉůĄƐŵŝĚŽ'&WͲĂǆĞŶƉĞƋƵĞŹĂƐƌĞŐŝŽŶĞƐƉƵŶƚĞĂĚĂƐ͕ĐŽŶƵŶĂĂůƚĂŝŶƚĞŶƐŝĚĂĚ͕ůŽ
ĐƵĂůŝŶĚŝĐĂďĂŝŶĞƋƵşǀŽĐĂŵĞŶƚĞƋƵĞĂǆŚĂďşĂŵŝŐƌĂĚŽĂůĂŵŝƚŽĐŽŶĚƌŝĂ͘WĂƌĂĐŽŶƐƚĂƚĂƌ
ĞƐƚŽƐĚĂƚŽƐ͕ƉƌŽĐĞĚŝŵŽƐĂĂŶĂůŝǌĂƌŶƵĞƐƚƌŽƐĐƵůƚŝǀŽƐĐĞůƵůĂƌĞƐŵĞĚŝĂŶƚĞůĂƚĠĐŶŝĐĂĚĞ
tĞƐƚĞƌŶ ůŽƚƚŝŶŐ͘ Ɛş͕ Ɛŝ ďŝĞŶ ůĂ ĐŽŶĐĞŶƚƌĂĐŝſŶ ƚŽƚĂů ĚĞ Ăǆ Ă ůŽ ůĂƌŐŽ ĚĞů ƚŝĞŵƉŽ
ƉĞƌŵĂŶĞĐşĂ ďĂƐƚĂŶƚĞ ĐŽŶƐƚĂŶƚĞ͕ ůĂ ĐĂŶƚŝĚĂĚ ĚĞ ĞƐƚĂ ƉƌŽƚĞşŶĂ ƉƌĞƐĞŶƚĞ ĞŶ ůĂ
ŵŝƚŽĐŽŶĚƌŝĂ ƚƌĂƐ ĚŽĐĞ ŚŽƌĂƐ ĚĞ ƚƌĂƚĂŵŝĞŶƚŽ ĐŽŶ ϲͲK, ƐƵĨƌşĂ ƵŶ ĂƵŵĞŶƚŽ
ĞƐƉĞĐƚĂĐƵůĂƌ͘ WŽƌ ƚĂŶƚŽ͕ ĞŶ ĞƐƚĞ ŵŽĚĞůŽ ĚĞ ĞŶĨĞƌŵĞĚĂĚ ŶĞƵƌŽĚĞŐĞŶĞƌĂƚŝǀĂ͕ ůĂ
ŵŝŐƌĂĐŝſŶĂůĂŵŝƚŽĐŽŶĚƌŝĂĚĞĂǆƋƵĞƐĞŽďƐĞƌǀĂĞƐŝŶĚĞƉĞŶĚŝĞŶƚĞĚĞůĂƚƌĂƐůŽĐĂĐŝſŶ
ĂůŽƌŐĄŶƵůŽĚĞƌƉϭ͘
ŽƌƌŽďŽƌĂŶĚŽ ĞƐƚŽƐ ƌĞƐƵůƚĂĚŽƐ͕ ŚĂǇ ƵŶ ƚƌĂďĂũŽ ƌĞĂůŝǌĂĚŽ ĞŶ ŶƵĞƐƚƌŽ ŵŝƐŵŽ
ŵŽĚĞůŽĐĞůƵůĂƌ͕ĞŶĞůƋƵĞƵƚŝůŝǌĂƌŽŶƚĂŵďŝĠŶϲͲK,͕ĞŶĞůĐƵĂůƋƵĞĚĂĚĞŵŽƐƚƌĂĚĂůĂ
ƚƌĂƐůŽĐĂĐŝſŶŵŝƚŽĐŽŶĚƌŝĂůĚĞĂǆƚƌĂƐůĂĂĚŝĐŝſŶĚĞůĂĐŝƚĂĚĂŶĞƵƌŽƚŽǆŝŶĂĂůŽƐĐƵůƚŝǀŽƐ
ĐĞůƵůĂƌĞƐ͕ƚĂŵďŝĠŶĂƚŝĞŵƉŽƐĞůĞǀĂĚŽƐ͕ĂƉĞƐĂƌĚĞƋƵĞ͕ĞŶĞƐĞĐĂƐŽ͕ůĂĚŽƐŝƐƵƚŝůŝǌĂĚĂ
ĚĞůĂŶĞƵƌŽƚŽǆŝŶĂĞƐƐƵƉĞƌŝŽƌĂůĂĞŵƉůĞĂĚĂĞŶŶƵĞƐƚƌŽŵŽĚĞůŽĚĞW͕;'ŽŵĞǌͲ>ĂǌĂƌŽ
ĞƚĂů͕͘ϮϬϬϴĂͿ͘
WŽƌ ƐƵ ƉĂƌƚĞ͕ ĞŶ ŶƵĞƐƚƌŽ ŵŽĚĞůŽ ĨĂƌŵĂĐŽůſŐŝĐŽ ĚĞ , ƉŽƌ ĂĚŝĐŝſŶ ĚĞ ϯEW͕
ƚĂŵďŝĠŶ ĐŽŶƐƚĂƚĂŵŽƐ ůĂ ŵŝŐƌĂĐŝſŶ ŵŝƚŽĐŽŶĚƌŝĂů ĚĞ Ăǆ͘ Ŷ ƉƌŝŵĞƌ ůƵŐĂƌ͕ Ğů ĂŶĄůŝƐŝƐ
ŵĞĚŝĂŶƚĞ ŵŝĐƌŽƐĐŽƉşĂ ĐŽŶĨŽĐĂů ŵŽƐƚƌſ ƵŶ ŝŶĐƌĞŵĞŶƚŽ ĐŽŶƐŝĚĞƌĂďůĞ ĞŶ ůĂ ƉƌŽƉŽƌĐŝſŶ
ĚĞ ĐĠůƵůĂƐ ƋƵĞ ƉƌĞƐĞŶƚĂďĂŶ ĂŐƌĞŐĂĐŝſŶ ŵŝƚŽĐŽŶĚƌŝĂů ĚĞ ĞƐƚĂ ƉƌŽƚĞşŶĂ͕ ƌĞƐƉĞĐƚŽ Ă ůĂƐ
ĐŽŶĚŝĐŝŽŶĞƐ ĐŽŶƚƌŽů͘ ĚĞŵĄƐ͕ ŐƌĂĐŝĂƐ Ă ůŽƐ ĞǆƉĞƌŝŵĞŶƚŽƐ ĚĞ tĞƐƚĞƌŶ ůŽƚƚŝŶŐ͕
ĐŽƌƌŽďŽƌĂŵŽƐ ĞƐƚŽƐ ĚĂƚŽƐ͕ ĚĞŵŽƐƚƌĂŶĚŽ ƋƵĞ͕ ĞĨĞĐƚŝǀĂŵĞŶƚĞ͕ ůĂ ĐĂŶƚŝĚĂĚ ĚĞ Ăǆ
ƉƌĞƐĞŶƚĞĞŶůĂŵŝƚŽĐŽŶĚƌŝĂůƐĞŝŶĐƌĞŵĞŶƚĂďĂĐŽŶƐŝĚĞƌĂďůĞŵĞŶƚĞƚƌĂƐůĂĂĚŝĐŝſŶĚĞϯEW
ĂŶƵĞƐƚƌŽƐĐƵůƚŝǀŽƐĐĞůƵůĂƌĞƐ͘
ϱϵ
ŶĞƐƚĞĐĂƐŽ͕ĞůŵĞĐĂŶŝƐŵŽƋƵĞƉƌŽĚƵũŽůĂŵŝŐƌĂĐŝſŶĚĞĂǆ͕ŝŶĚĞƉĞŶĚŝĞŶƚĞĚĞ
ůĂƚƌĂƐůŽĐĂĐŝſŶŵŝƚŽĐŽŶĚƌŝĂůĚĞƌƉϭ͕ƉĂƌĞĐĞĞƐƚĂƌƌĞůĂĐŝŽŶĂĚŽĐŽŶůĂƉĞƌŵĞĂďŝůŝǌĂĐŝſŶ
ĚĞůĂŵĞŵďƌĂŶĂŵŝƚŽĐŽŶĚƌŝĂůĞǆƚĞƌŶĂ͕ůŽĐƵĂů͕ĂƐƵǀĞǌ͕ƉŽĚƌşĂĐŽŶĚƵĐŝƌĂůĂĂƉŽƉƚŽƐŝƐ
ĐĞůƵůĂƌ ĚĞƉĞŶĚŝĞŶƚĞ ĚĞ Ăǆ͘ Ŷ ůĂ ůşŶĞĂ ĚĞ ĞƐƚĂ ŽďƐĞƌǀĂĐŝſŶ ĞŶĐŽŶƚƌĂŵŽƐ ǀĂƌŝŽƐ
ƚƌĂďĂũŽƐƉƌĞǀŝŽƐ͕ƌĞĂůŝǌĂĚŽƐƚŽĚŽƐĞůůŽƐĞŶŵŽĚĞůŽƐĐĞůƵůĂƌĞƐĚŝĨĞƌĞŶƚĞƐĂůŽƐŶƵĞƐƚƌŽƐ͕
;'ŽŵĞǌͲ>ĂǌĂƌŽĞƚĂů͕͘ϮϬϬϴď͖WĞƌĞǌͲůǀĂƌĞǌĞƚĂů͕͘ϮϬϬϵ͖^ŵĂŝůŝĞƚĂů͕͘ϮϬϬϭͿ͘ƐşŵŝƐŵŽ͕
ĐŽƌƌŽďŽƌĂŶĚŽ ŶƵĞƐƚƌŽƐ ĚĂƚŽƐ͕ ĞŶ ƵŶ ĞƐƚƵĚŝŽ ƌĞĂůŝǌĂĚŽ ĞŶ ŶĞƵƌŽŶĂƐ ĚĞ ůĂ ƌĞŐŝſŶ ĚĞů
ĞƐƚƌŝĂĚŽ ĐĞƌĞďƌĂů ƚƌĂƚĂĚĂƐ ĐŽŶ ϯEW͕ ƐĞ ŽďƐĞƌǀſ ůĂ ĂĐƚŝǀĂĐŝſŶ ĚĞ ǀĂƌŝĂƐ ƉƌŽƚĞşŶĂƐ
ƉƌŽĂƉŽƉƚſƚŝĐĂƐ͕ĞŶƚƌĞĞůůĂƐĂǆǇĂŬ͕;'ĂůĂƐĞƚĂů͕͘ϮϬϬϰͿ͘
ĐŽŶƚŝŶƵĂĐŝſŶ͕ ƚĂŵďŝĠŶ ĞŶ Ğů ĐĂƐŽ ĚĞ ůĂ ŵŝŐƌĂĐŝſŶ ŵŝƚŽĐŽŶĚƌŝĂů ĚĞ Ăǆ͕
ƋƵŝƐŝŵŽƐ ĞƐƚƵĚŝĂƌ Ğů ĞĨĞĐƚŽ ƋƵĞ DĚŝǀŝͲϭ ĞũĞƌĐşĂ ƐŽďƌĞ ŶƵĞƐƚƌŽƐ ĐƵůƚŝǀŽƐ ĐĞůƵůĂƌĞƐ
ƚƌĂƚĂĚŽƐĐŽŶϲͲK,ŽĐŽŶϯEW͘
Ɛş͕ ĐƵĂŶĚŽ Ă ůŽƐ ĐƵůƚŝǀŽƐ ƐĞ ůĞƐ ĂŹĂĚŝſ ϲͲK,͕ ůĂ ƚƌĂƐůŽĐĂĐŝſŶ ĚĞ Ăǆ Ăů
ŽƌŐĄŶƵůŽŶŽƉƵĚŽƐĞƌĞǀŝƚĂĚĂŵĞĚŝĂŶƚĞůĂŝŶŚŝďŝĐŝſŶĚĞůĂĂĐƚŝǀŝĚĂĚĚĞƌƉϭ͕ƉƌŽĚƵĐŝĚĂ
ƉŽƌDĚŝǀŝͲϭ͘hŶĂƉŽƐŝďůĞũƵƐƚŝĨŝĐĂĐŝſŶƉĂƌĂĞƐƚĞƌĞƐƵůƚĂĚŽƉŽĚƌşĂƐĞƌƋƵĞ͕ƚƌĂƐůĂĂĚŝĐŝſŶ
ĚĞϲͲK,ĂůĂƐ^,Ͳ^zϱz͕ůĂŵŝŐƌĂĐŝſŶĚĞĂǆĨƵĞƌĂƵŶƉĂƐŽƉŽƐƚĞƌŝŽƌĞŶĞůƚŝĞŵƉŽĂůĂ
ĨƌĂŐŵĞŶƚĂĐŝſŶ ŵŝƚŽĐŽŶĚƌŝĂů͕ ƉƌŽĚƵĐŝĠŶĚŽƐĞ ĞƐƚĂ ƷůƚŝŵĂ Ă ƚƌĂǀĠƐ ĚĞ ƵŶ ŵĞĐĂŶŝƐŵŽ
ĚŝĨĞƌĞŶƚĞ͘ƐƚĂŚŝƉſƚĞƐŝƐƐĞǀĞƌĞĨŽƌǌĂĚĂƉŽƌůĂĂƵƐĞŶĐŝĂĚĞĂŐƌĞŐĂĐŝſŶŵŝƚŽĐŽŶĚƌŝĂůĚĞ
Ăǆ Ă ůŽƐ ƚŝĞŵƉŽƐ Ă ůŽƐ ƋƵĞ Ɛş ƋƵĞ ŽďƐĞƌǀĂŵŽƐ ůĂ ĚĞ ƌƉϭ͕ ;ĚŽĐĞ ŚŽƌĂƐ ĨƌĞŶƚĞ Ă ƚƌĞƐ
ŚŽƌĂƐ͕ƌĞƐƉĞĐƚŝǀĂŵĞŶƚĞͿ͘
WŽƌ ƚĂŶƚŽ͕ ůŽƐ ƌĞƐƵůƚĂĚŽƐ ŽďƚĞŶŝĚŽƐ ĞŶ ŶƵĞƐƚƌŽ ŵŽĚĞůŽ ĚĞ W ƉĂƌĞĐĞŶ
ĐŽŶƚƌĂĚĞĐŝƌ ůĂ ĨƵŶĐŝſŶ ĐůĄƐŝĐĂ ƋƵĞ ƐĞ ůĞ ĂƐŝŐŶĂďĂ Ă ůĂ ĨŝƐŝſŶ ŵŝƚŽĐŽŶĚƌŝĂů͕ ĞƐƚŽ ĞƐ͕ ƵŶ
ƉĂƐŽ ƉƌĞǀŝŽ Ă ůĂ ŵƵĞƌƚĞ ĐĞůƵůĂƌ ĂƉŽƉƚſƚŝĐĂ͘ WƌŽďĂďůĞŵĞŶƚĞ͕ ĞŶ ůĂ ďĂƐĞ ĚĞ ĞƐƚĂ
ĐŽŶƚƌŽǀĞƌƐŝĂ͕ƐĞĞŶĐƵĞŶƚƌĂĞůŚĞĐŚŽĚĞƋƵĞ͕ĞŶĞůŵŽĚĞůŽĚĞW͕ůĂŝŶŚŝďŝĐŝſŶĚĞƌƉϭ͕
ĂƉĂƌƚĞĚĞĐŽŵƉƌŽŵĞƚĞƌƐĞƌŝĂŵĞŶƚĞůĂĨŝƐŝſŶŵŝƚŽĐŽŶĚƌŝĂů͕ƉŽĚƌşĂƉƌŽĚƵĐŝƌŽƚƌĂƐĞƌŝĞ
ĚĞĞĨĞĐƚŽƐĐŽůĂƚĞƌĂůĞƐ͘dĂŵďŝĠŶĞƐĐŝĞƌƚŽƋƵĞ͕ĞůŵŽĚĞůŽĐĞůƵůĂƌĐŽŶĐƌĞƚŽĞŶĞůƋƵĞƐĞ
ƌĞĂůŝǌĂŶ ůŽƐ ĚŝĨĞƌĞŶƚĞƐ ƚƌĂďĂũŽƐ͕ ƉƵĞĚĞ ƚĞŶĞƌ ƵŶĂ ŝŵƉŽƌƚĂŶƚĞ ŝŶĨůƵĞŶĐŝĂ ĞŶ ůŽƐ
ƌĞƐƵůƚĂĚŽƐƌĞůĂƚŝǀŽƐĂůĂƌĞůĂĐŝſŶĞŶƚƌĞůĂĨŝƐŝſŶŵŝƚŽĐŽŶĚƌŝĂůǇůĂĂƉŽƉƚŽƐŝƐ͕ĚĞďŝĚŽĂůĂƐ
ĚŝĨĞƌĞŶĐŝĂƐƋƵĞůĂĨƵŶĐŝſŶǇŵŽƌĨŽůŽŐşĂŵŝƚŽĐŽŶĚƌŝĂůĞƐƉƌĞƐĞŶƚĂŶĞŶĐĂĚĂƚŝƉŽĐĞůƵůĂƌ͘
ϲϬ
ŶĞůĐĂƐŽĚĞůŵŽĚĞůŽĚĞ,͕ƚĂŵƉŽĐŽĞŶĐŽŶƚƌĂŵŽƐĚŝĨĞƌĞŶĐŝĂĂůŐƵŶĂĞŶƚƌĞůŽƐ
ǀĂůŽƌĞƐŽďƚĞŶŝĚŽƐƚƌĂƐƚƌĂƚĂƌĞǆĐůƵƐŝǀĂŵĞŶƚĞŶƵĞƐƚƌŽƐĐƵůƚŝǀŽƐĐŽŶϯEWǇĐƵĂŶĚŽ͕ũƵŶƚŽ
ĐŽŶ Ğů ŝŶŚŝďŝĚŽƌ ĚĞů ĐŽŵƉůĞũŽ // ĚĞ ůĂ d͕ ĂŹĂĚşĂŵŽƐ DĚŝǀŝͲϭ͘ >Ă ĞǆƉůŝĐĂĐŝſŶ Ă ĞƐƚĂ
ŽďƐĞƌǀĂĐŝſŶůĂƉŽĚĞŵŽƐŚĂůůĂƌĞŶůĂĨŽƌŵĂĐŝſŶĚĞůWWdD͕ůĂĐƵĂůƐĞƉƌŽĚƵĐĞĂƚŝĞŵƉŽƐ
ĐŽƌƚŽƐ ƚƌĂƐ Ğů ƚƌĂƚĂŵŝĞŶƚŽ ĐŽŶ ϯEW͘ ĚĞŵĄƐ͕ ůĂ ĂƵƐĞŶĐŝĂ ĚĞ ĂĐƚŝǀĂĐŝſŶ ĚĞ ůĂ ĨŝƐŝſŶ
ŵŝƚŽĐŽŶĚƌŝĂů ĞŶ ĞƐƚĞ ŵŽĚĞůŽ ŚĂĐşĂ ƉƌĞƐĂŐŝĂƌ ĚĞ ĂŶƚĞŵĂŶŽ Ğů ŶƵůŽ ĞĨĞĐƚŽ ĚĞ DĚŝǀŝͲϭ
ƐŽďƌĞůĂŵŝŐƌĂĐŝſŶŵŝƚŽĐŽŶĚƌŝĂůĚĞĂǆ͘
ƉĂƌƚŝƌĚĞůŽƐĚĂƚŽƐŽďƚĞŶŝĚŽƐ͕ĂƐşĐŽŵŽĚĞůĂďŝďůŝŽŐƌĂĨşĂĚŝƐƉŽŶŝďůĞ͕ƉŽĚĞŵŽƐ
ĂĨŝƌŵĂƌ ƋƵĞ ůĂ ĨƌĂŐŵĞŶƚĂĐŝſŶ ŵŝƚŽĐŽŶĚƌŝĂů ƉŽƌ Ɛş ŵŝƐŵĂ ŶŽ ĞƐ ĐĂƉĂǌ ĚĞ ŝŶĚƵĐŝƌ ůĂ
ŵƵĞƌƚĞ ĐĞůƵůĂƌ͘ ^ŝŶ ĞŵďĂƌŐŽ͕ ĂƷŶ ŚĂǇ ŵƵĐŚĂƐ ĚƵĚĂƐ ƐŽďƌĞ Ğů ŚĞĐŚŽ ĚĞ ƋƵĞ ůŽƐ
ĐĂŵďŝŽƐĞŶůĂŵŽƌĨŽůŽŐşĂĚĞĞƐƚĞŽƌŐĄŶƵůŽƐĞĂŶŝŵƉƌĞƐĐŝŶĚŝďůĞƐƉĂƌĂƋƵĞƐĞƉƌŽĚƵǌĐĂ
ůĂĐŝƚĂĚĂŵƵĞƌƚĞ͕;>ĂŶĚĞƐĞƚĂů͕͘ϮϬϭϭͿ͘
>ĂƐ ZK ĐŽŶƐƚŝƚƵǇĞŶ ƵŶ ŐƌƵƉŽ ĚĞ ŵŽůĠĐƵůĂƐ ŶĞĐĞƐĂƌŝĂƐ ƉĂƌĂ Ğů ĐŽƌƌĞĐƚŽ
ĨƵŶĐŝŽŶĂŵŝĞŶƚŽĚĞůĂƐĐĠůƵůĂƐ͕ĐƵǇĂŝŵƉŽƌƚĂŶĐŝĂƌĂĚŝĐĂ͕ƉŽƌĞũĞŵƉůŽ͕ĞŶƐƵĐĂƉĂĐŝĚĂĚ
ƉĂƌĂŽǆŝĚĂƌƵŶĂƐĞƌŝĞĚĞĨĂĐƚŽƌĞƐŝŵƉůŝĐĂĚŽƐĞŶůĂƐĞŹĂůŝǌĂĐŝſŶĐĞůƵůĂƌ͕;DĂĚĂŵĂŶĐŚŝĞƚ
Ăů͕͘ϮϬϭϯͿ͘ƐƚĞŚĞĐŚŽůĂƐĐŽŶǀŝĞƌƚĞĞŶŵĞĚŝĂĚŽƌĂƐĚĞůŽƐĐŝƚĂĚŽƐƉƌŽĐĞƐŽƐ͕ƐŝĞŶĚŽƉŽƌ
ƚĂŶƚŽŝŵƉƌĞƐĐŝŶĚŝďůĞƐƉĂƌĂĞůĐƌĞĐŝŵŝĞŶƚŽǇůĂǀŝĚĂĚĞůĂƐĐĠůƵůĂƐ͘
^ŝŶ ĞŵďĂƌŐŽ͕ ĐƵĂŶĚŽ ƐĞ ƉƌŽĚƵĐĞŶ ŝŶĐƌĞŵĞŶƚŽƐ ĐŽŶƐŝĚĞƌĂďůĞƐ ĞŶ ƐƵ
ĐŽŶĐĞŶƚƌĂĐŝſŶ Ž ĐƵĂŶĚŽ ĚŝƐŵŝŶƵǇĞŶ ůĂƐ ĚĞĨĞŶƐĂƐ ĂŶƚŝŽǆŝĚĂŶƚĞƐ͕ ĂƉĂƌĞĐĞ Ğů ĐŽŶŽĐŝĚŽ
ĞƐƚƌĠƐ ŽǆŝĚĂƚŝǀŽ͘ ĂũŽ ĞƐƚĂƐ ĐŽŶĚŝĐŝŽŶĞƐ͕ ůĂƐ ZK ƐĞ ĐŽŶǀŝĞƌƚĞŶ ĞŶ ĚĞůĞƚĠƌĞĂƐ ƉĂƌĂ Ğů
ŽƌŐĂŶŝƐŵŽ͕ ĂƵŵĞŶƚĂŶĚŽ ĞŶƚŽŶĐĞƐ ůĂ ƚĂƐĂ ĚĞ ĂƉŽƉƚŽƐŝƐ ĐĞůƵůĂƌ͕ ;:ĂďƐ͕ ϭϵϵϵ͖ DĂĐŝƉ Ğƚ
Ăů͕͘ϮϬϬϯͿ͕ǇĂĨĞĐƚĂŶĚŽ͕ĚĞƵŶŵŽĚŽŵƵǇĞƐƉĞĐŝĂů͕ĂůĂƐŵŝƚŽĐŽŶĚƌŝĂƐ͕ƉŽƌůĂƐƌĂǌŽŶĞƐ
ƋƵĞ ĂƉŽƌƚĄďĂŵŽƐ ĞŶ ůĂ ŝŶƚƌŽĚƵĐĐŝſŶ Ă ĞƐƚĞ ƚƌĂďĂũŽ͘ Ɛş͕ ƉŽƌ ĐŝƚĂƌ ƵŶ ĞũĞŵƉůŽ͕ ĐŽŶ Ğů
ƉĂƐŽ ĚĞ ůŽƐ ĂŹŽƐ͕ ůĂ ƉůĂƐƚŝĐŝĚĂĚ ĚĞ ĞƐƚŽƐ ŽƌŐĄŶƵůŽƐ Ǉ ƐƵ ĐĂƉĂĐŝĚĂĚ ĚĞ ďŝŽŐĠŶĞƐŝƐ
ĚĞĐƌĞĐĞŶ ĐŽŶƐŝĚĞƌĂďůĞŵĞŶƚĞ͕ ĚĞďŝĚŽ Ăů ĚĞƐĐĞŶƐŽ ĚĞ ůĂ ĂĐƚŝǀŝĚĂĚ ĚĞ W'Ͳϭɲ͘ ƐƚĞ
ŚĞĐŚŽ ĞƐƚĄ ĐĂƵƐĂĚŽ ƉŽƌ ƵŶ ĂƵŵĞŶƚŽ ĞŶ ůĂ ƉƌŽĚƵĐĐŝſŶ ĚĞ ůĂƐ ZK͕ ƉƌŽƉŽƌĐŝŽŶĂů Ăů
ŝŶĐƌĞŵĞŶƚŽĚĞůĂĞĚĂĚ͕;YŝĂŶŐĞƚĂů͕͘ϮϬϬϳ͖ZĞǌŶŝĐŬĞƚĂů͕͘ϮϬϬϳͿ͘
WŽƌƚĂŶƚŽ͕ƐŝŐƵŝĞŶĚŽĐŽŶŶƵĞƐƚƌŽƚƌĂďĂũŽ͕ĂĐŽŶƚŝŶƵĂĐŝſŶ͕ĚĞĐŝĚŝŵŽƐĞƐƚƵĚŝĂƌƐŝ
ůŽƐĚĞƐĞƋƵŝůŝďƌŝŽƐĞŶůĂĐŽŶĐĞŶƚƌĂĐŝſŶŝŶƚƌĂĐĞůƵůĂƌĚĞZKƉŽĚşĂŶũƵŐĂƌĂůŐƷŶƉĂƉĞůĞŶ
ϲϭ
ůĂƐ ĂůƚĞƌĂĐŝŽŶĞƐ ŵŝƚŽĐŽŶĚƌŝĂůĞƐ ŽďƐĞƌǀĂĚĂƐ͕ ƚĂŶƚŽ ĞŶ ŶƵĞƐƚƌŽ ŵŽĚĞůŽ ĐĞůƵůĂƌ ĚĞ W͕
ĐŽŵŽĞŶĞůĚĞ,͘
ŶĞůĐĂƐŽĚĞůĚĞůĂW͕ĞůĞƐƚƌĠƐŽǆŝĚĂƚŝǀŽĞƐƵŶĐŽŶŽĐŝĚŽĂŐĞŶƚĞĞƚŝŽůſŐŝĐŽĚĞ
ĞƐƚĂ ĞŶĨĞƌŵĞĚĂĚ͕ ƚĂŶƚŽ Ă ŶŝǀĞů ŐĞŶĠƚŝĐŽ͕ ĐŽŵŽ ƉĂƚŽůſŐŝĐŽ Ǉ ƚŽǆŝĐŽůſŐŝĐŽ͕ ;ďŽƵͲ
^ůĞŝŵĂŶ Ğƚ Ăů͕͘ ϮϬϬϲ͖ 'ƌĞĞŶĂŵǇƌĞ Ğƚ Ăů͕͘ ϮϬϬϰͿ͘ ĚĞŵĄƐ͕ ĐŽŵŽ ĐŽŶƐĞĐƵĞŶĐŝĂ ĚĞ ůĂ
ĂƵƚŽŽǆŝĚĂĐŝſŶ ĚĞ ϲͲK,͕ ĂƉĂƌĞĐĞŶ ĐŝĞƌƚŽƐ ƚŝƉŽƐ ĚĞ ZK͕ ĐŽŵŽ ĞƐ Ğů ĐĂƐŽ ĚĞ ,ϮKϮ͕
ƌĂĚŝĐĂůĞƐĚĞƚŝƉŽŚŝĚƌŽǆŝůŽǇƋƵŝŶŽŶĂƐ͕;'ĞĞĞƚĂů͕͘ϭϵϴϵͿ͘ůĞǆĐĞƐŽĞŶůĂŐĞŶĞƌĂĐŝſŶĚĞ
,ϮKϮĐŽŶĚƵĐĞĂůĂĨŽƌŵĂĐŝſŶĚĞƌĂĚŝĐĂůĞƐƉĞƌŽǆŝůŽĂůƚĂŵĞŶƚĞƌĞĂĐƚŝǀŽƐ͕ůŽĐƵĂůƐƵĐĞĚĞ
ĚĞƵŶŵŽĚŽƉĂƌƚŝĐƵůĂƌŵĞŶƚĞŵĂƌĐĂĚŽĞŶƉƌĞƐĞŶĐŝĂĚĞ&ĞнϮ͕ĂƚƌĂǀĠƐĚĞůĂZĞĂĐĐŝſŶĚĞ
&ĞŶƚŽŶ͘ >ŽƐ ĐŝƚĂĚŽƐ ƌĂĚŝĐĂůĞƐ ƉĞƌŽǆŝůŽ ƉƵĞĚĞŶ ĚĂŹĂƌ ƐĞƌŝĂŵĞŶƚĞ Ă ůĂ ŵŝƚŽĐŽŶĚƌŝĂ͕
;&ĂƌŝƐƐĞƚĂů͕͘ϮϬϬϱͿ͘
ŶƉƌŝŵĞƌůƵŐĂƌ͕ĐƵĂŶƚŝĨŝĐĂŵŽƐůĂƉƌŽĚƵĐĐŝſŶĚĞZKƚƌĂƐůĂĂĚŝĐŝſŶĚĞϲͲK,͘
WĂƌĂ ĞůůŽ͕ ƌĞĂůŝǌĂŵŽƐ ůĂ ŵĞĚŝĐŝſŶ ĚĞů ƌĂƚŝŽ DŝƚŽ WͬDŝƚŽ ƉŽƌ ŵĞĚŝŽ ĚĞ ƚĠĐŶŝĐĂƐ ĚĞ
ĞƐƉĞĐƚƌŽŵĞƚƌşĂ ĚĞ ŵĂƐĂ͕ ůŽ ĐƵĂů ƉƌŽƉŽƌĐŝŽŶĂ ƵŶĂ ŵĞĚŝĚĂ ŵƵǇ ĞƐƉĞĐşĨŝĐĂ ĚĞ ůĂ
ĐŽŶĐĞŶƚƌĂĐŝſŶĚĞ,ϮKϮŝŶƚƌĂŵŝƚŽĐŽŶĚƌŝĂů͘Ɛş͕ĂƚƌĂǀĠƐĚĞĞƐƚĞĞŶƐĂǇŽ͕ĐŽŵƉƌŽďĂŵŽƐ
ƋƵĞ͕ƚƌĂƐƚƌĞƐŚŽƌĂƐĚĞƚƌĂƚĂŵŝĞŶƚŽĐŽŶϲͲK,͕ĐŽŵŽĐĂďşĂĞƐƉĞƌĂƌ͕ƐĞƉƌŽĚƵĐşĂƵŶ
ŝŶĐƌĞŵĞŶƚŽ ĚĞ ůĂ ƉƌŽĚƵĐĐŝſŶ ĚĞ ZK ĞŶ Ğů ĐŽŵƉĂƌƚŝŵŝĞŶƚŽ ŵŝƚŽĐŽŶĚƌŝĂů͕ ůŽ ĐƵĂů
ĐŽŶĐƵĞƌĚĂ ĐŽŶ ůŽƐ ĚĂƚŽƐ ŽďƚĞŶŝĚŽƐ ĞŶ ƵŶ ĞƐƚƵĚŝŽ ĂŶƚĞƌŝŽƌ͕ ƌĞĂůŝǌĂĚŽ ƚĂŵďŝĠŶ ĞŶ ^,Ͳ
^zϱzƚƌĂƚĂĚĂƐĐŽŶϲͲK,͕;:ŽƌĚĂŶĞƚĂů͕͘ϮϬϬϰͿ͘
hŶĂ ǀĞǌ ĐŽŶƐƚĂƚĂĚŽ Ğů ŝŶĐƌĞŵĞŶƚŽ ĞŶ ůĂ ĐŽŶĐĞŶƚƌĂĐŝſŶ ĚĞ ZK ŝŶĚƵĐŝĚŽ ĞŶ
ŶƵĞƐƚƌŽ ŵŽĚĞůŽ ĚĞ W͕ ŶŽƐ ĐĞŶƚƌĂŵŽƐ ĞŶ Ğů ĞƐƚƵĚŝŽ ĚĞ ůŽƐ ƉŽƐŝďůĞƐ ĚĂŹŽƐ ƋƵĞ ĞƐƚĂƐ
ŵŽůĠĐƵůĂƐ ƉŽĚşĂŶ ŚĂďĞƌ ĐĂƵƐĂĚŽ ĞŶ ŶƵĞƐƚƌĂƐ ĐĠůƵůĂƐ͘ WĂƌĂ ĞůůŽ͕ƌĞĂůŝǌĂŵŽƐ Ğů ĂŶĄůŝƐŝƐ
ĚĞůĞƐƚĂĚŽĚĞůEŵŝƚŽĐŽŶĚƌŝĂů͕;ŵĞĚŝĂŶƚĞƚĠĐŶŝĐĂƐĚĞWZƐĞŵŝĐƵĂŶƚŝƚĂƚŝǀĂͿ͕ǇĚĞůĂ
ŚŝƉŽƚĠƚŝĐĂ ĨŽƌŵĂĐŝſŶĚĞ ĐĂƌďŽŶŝůŽƐ ĞŶ ůŽƐ ĞǆƚƌĞŵŽƐ ĚĞ ůĂƐ ƉƌŽƚĞşŶĂƐ͕ ;Ă ƚƌĂǀĠƐ ĚĞ ƵŶ
ĞŶƐĂǇŽ ĚĞ >/^Ϳ͘ ŵďŽƐ ƉĂƌĄŵĞƚƌŽƐ ƌĞƉƌĞƐĞŶƚĂŶ ĐŽŶŽĐŝĚŽƐ ŵĂƌĐĂĚŽƌĞƐ ĚĞ ĞƐƚƌĠƐ
ŽǆŝĚĂƚŝǀŽ ĐĞůƵůĂƌ͘ Ɛş͕ ĐŽŶƐƚĂƚĂŵŽƐ ƋƵĞ͕ ĞŶ ŶƵĞƐƚƌŽ ŵŽĚĞůŽ͕ ŶŽ ŚĂůůĂŵŽƐ ŶŝŶŐƵŶĂ
ǀĂƌŝĂĐŝſŶ ƐŝŐŶŝĨŝĐĂƚŝǀĂ͕ ĐŽŶ ƌĞƐƉĞĐƚŽ Ă ůĂƐ ĐŽŶĚŝĐŝŽŶĞƐ ĐŽŶƚƌŽů͕ Ŷŝ ĞŶ ůĂ ŝŶƚĞŐƌŝĚĂĚ ĚĞů
EŵŝƚŽĐŽŶĚƌŝĂůŶŝĞŶůĂƚĂƐĂĚĞĨŽƌŵĂĐŝſŶĚĞĐĂƌďŽŶŝůŽƐƉƌŽƚĞŝĐŽƐ͘
Ŷ ĐŽŶĚŝĐŝŽŶĞƐ ďĂƐĂůĞƐ͕ ůĂƐ ZK ŝŶĚƵĐĞŶ ƵŶ ŶŝǀĞů ďĂũŽ ĚĞ ůĞƐŝŽŶĞƐ ĞŶ Ğů E
ϲϮ
ŵŝƚŽĐŽŶĚƌŝĂů͕ ĞŶ ƌĞůĂĐŝſŶ Ăů ƉƌŽĚƵĐŝĚŽ ĞŶ Ğů E ŶƵĐůĞĂƌ͘ ^ŝŶ ĞŵďĂƌŐŽ͕ ĞƐƚĞ ƷůƚŝŵŽ
ƉƵĞĚĞ ƐĞƌ ƌĞƉĂƌĂĚŽ ƌĄƉŝĚĂŵĞŶƚĞ͕ ;ZŝĐŚƚĞƌ Ğƚ Ăů͕͘ ϭϵϴϴͿ͘ WŽƌ ĐŽŶƚƌĂ͕ ĐƵĂŶĚŽ ůĂ
ĞǆƉŽƐŝĐŝſŶĂůĂƐZKĞƐĚĞƚŝƉŽĐƌſŶŝĐŽ͕ĐŽŵŽĞŶĞůĚĂŹŽƉŽƌŝƐƋƵĞŵŝĂͲƌĞƉĞƌĐƵƐŝſŶŽ
ĞŶ Ğů ĐĂƐŽ ĚĞ ůĂƐ ĞŶĨĞƌŵĞĚĂĚĞƐ ŶĞƵƌŽĚĞŐĞŶĞƌĂƚŝǀĂƐ͕ ůĂƐ ŵĂĐƌŽŵŽůĠĐƵůĂƐ
ŵŝƚŽĐŽŶĚƌŝĂůĞƐ͕ĐŽŵŽĞƐĞůĐĂƐŽĚĞůEŽĚĞůĂƐƉƌŽƚĞşŶĂƐƋƵĞĐŽŵƉŽŶĞŶůĂd͕Ɛş
ƋƵĞ ƐƵĨƌĞŶ ŝŵƉŽƌƚĂŶƚĞƐ ůĞƐŝŽŶĞƐ͕ ƐŝĞŶĚŽ ĞƐƚĂƐ͕ ĂĚĞŵĄƐ͕ ŵĄƐ ĞǆƚĞŶƐŝǀĂƐ ƋƵĞ ůĂƐ
ŝŶĚƵĐŝĚĂƐ ĞŶ Ğů ŵĂƚĞƌŝĂů ŐĞŶĠƚŝĐŽ Ž ĞŶ ůĂƐ ƉƌŽƚĞşŶĂƐ ĐĞůƵůĂƌĞƐ͕ ƉŽƌ ůĂƐ ƌĂǌŽŶĞƐ ƋƵĞ
ŝŶĚŝĐĄďĂŵŽƐĞŶůĂŝŶƚƌŽĚƵĐĐŝſŶ͕;zĂŬĞƐĞƚĂů͕͘ϭϵϵϳͿ͘ĚĞŵĄƐ͕ĞůĚĂŹŽƉƌŽĚƵĐŝĚŽƐƵĞůĞ
ƐĞƌ ŵĄƐ ƉĞƌƐŝƐƚĞŶƚĞ ĞŶ Ğů E ŵŝƚŽĐŽŶĚƌŝĂů͕ ĚĞďŝĚŽ Ă ůĂ ĂĨĞĐƚĂĐŝſŶ ĚĞ ůĂ d Ǉ Ă ůĂ
ƉƌŽĚƵĐĐŝſŶĐŽŶƚŝŶƵĂĚĞZKƉŽƌƉĂƌƚĞĚĞůĂƉĞƌŽǆŝĚĂĐŝſŶůŝƉşĚŝĐĂ͘ĞŚĞĐŚŽ͕ĞŶĞƐƚŽƐ
ĐĂƐŽƐ͕ĂƉĂƌĞĐĞĂƵƚŽŵĄƚŝĐĂŵĞŶƚĞůĂƉĂƌĂĚĂĚĞůĐŝĐůŽĐĞůƵůĂƌǇůĂĂƉŽƉƚŽƐŝƐ͕;zĂŬĞƐĞƚĂů͕͘
ϭϵϵϳͿ͘
WŽƌ ƚĂŶƚŽ͕ ůĂ ũƵƐƚŝĨŝĐĂĐŝſŶ ĚĞ ůŽƐ ƌĞƐƵůƚĂĚŽƐ ŽďƚĞŶŝĚŽƐ ůĂ ĞŶĐŽŶƚƌĂŵŽƐ͕
ƉƌŝŶĐŝƉĂůŵĞŶƚĞ͕ ĞŶ ĚŽƐ ĨĂĐƚŽƌĞƐ͗ Ğů ƚŝĞŵƉŽ ĚĞ ĞǆƉŽƐŝĐŝſŶ ĚĞ ŶƵĞƐƚƌŽƐ ĐƵůƚŝǀŽƐ Ă ϲͲ
K,͕;ϯŚŽƌĂƐͿ͕ǇůĂĐŽŶĐĞŶƚƌĂĐŝſŶĚĞůĂŵŝƐŵĂ͕;ϱϬђDͿ͘ŵďŽƐƉĂƌĄŵĞƚƌŽƐ͕ĐŽŵŽ
ĐŽŶƐƚĂƚĂŵŽƐ ŵĞĚŝĂŶƚĞ ůĂ ŵĞĚŝĐŝſŶ ĚĞ ůĂ ǀŝĂďŝůŝĚĂĚ ĐĞůƵůĂƌ Ăů ĐŽŵŝĞŶǌŽ ĚĞ ŶƵĞƐƚƌŽƐ
ĞǆƉĞƌŝŵĞŶƚŽƐ͕ĐŽŶƐƚŝƚƵǇĞŶƵŶĞƐĐĞŶĂƌŝŽĚĞĐŽŶĚŝĐŝŽŶĞƐƐƵďƚſǆŝĐĂƐ͕ƉŽƌůŽƋƵĞŶŽĐĂďĞ
ĞƐƉĞƌĂƌ ŐƌĂŶĚĞƐ ĚĂŹŽƐ ĞŶ ůĂƐ ŵĂĐƌŽŵŽůĠĐƵůĂƐ ŵŝƚŽĐŽŶĚƌŝĂůĞƐ͕ ĐŽŵŽ ĞƐ Ğů ĐĂƐŽ ĚĞů
E͘
WŽƌƐƵƉĂƌƚĞ͕ĞŶŶƵĞƐƚƌŽŵŽĚĞůŽĚĞ,͕ŽďƐĞƌǀĂŵŽƐƋƵĞϯEWƚĂŵďŝĠŶŝŶĚƵĐĞ
ƵŶĂƵŵĞŶƚŽĚĞůĂƉƌŽĚƵĐĐŝſŶĚĞZKŝŶƚƌĂĐĞůƵůĂƌ͘^ŝŶĞŵďĂƌŐŽ͕ĐŽŵŽŝŶĚŝĐĄďĂŵŽƐĐŽŶ
ĂŶƚĞƌŝŽƌŝĚĂĚ͕ƉĂƌĞĐĞŶŽĞǆŝƐƚŝƌƵŶĂƌĞůĂĐŝſŶƐŝŐŶŝĨŝĐĂƚŝǀĂĞŶƚƌĞĞůƚƌĂƚĂŵŝĞŶƚŽĐŽŶϯEWǇ
ůĂ ĂĐƚŝǀĂĐŝſŶ ĚĞ ůĂĨŝƐŝſŶ ŵŝƚŽĐŽŶĚƌŝĂů͘ Ğ ŚĞĐŚŽ͕ ĞŶĞƐƚĞ ĐĂƐŽ͕ ůĂƉƌŽĚƵĐĐŝſŶ ĚĞ ZK
ĨƵĞ ďůŽƋƵĞĂĚĂ ĐƵĂŶĚŽ ƐĞ ƵƐſ ĐŝĐůŽƐƉŽƌŝŶĂ ͕ ůŽ ĐƵĂů ĐŽƌƌŽďŽƌĂ ůŽƐ ĚĂƚŽƐ ŽďƚĞŶŝĚŽƐ
ƉƌĞǀŝĂŵĞŶƚĞ͕ƋƵĞƐƵŐĞƌşĂŶƵŶĂĐůĂƌĂŝŵƉůŝĐĂĐŝſŶĚĞůWWdDǇĚĞůĐŽŶƐŝŐƵŝĞŶƚĞĞĚĞŵĂ
ŵŝƚŽĐŽŶĚƌŝĂů͕ĞŶůĂĞƚŝŽůŽŐşĂĚĞůŽƐĐĂŵďŝŽƐŵŝƚŽĐŽŶĚƌŝĂůĞƐŽďƐĞƌǀĂĚŽƐƚƌĂƐůĂĂĚŝĐŝſŶ
ĚĞϯEWĂŶƵĞƐƚƌŽƐĐƵůƚŝǀŽƐĐĞůƵůĂƌĞƐ͘
ĚĞŵĄƐ͕ƚĂŵďŝĠŶĞŶĞƐƚĞƉĂƌĄŵĞƚƌŽŶŽƐƉĂƌĞĐŝſŽƉŽƌƚƵŶŽĞƐƚƵĚŝĂƌĞůĞĨĞĐƚŽĚĞ
DĚŝǀŝͲϭƐŽďƌĞůĂŵŽĚƵůĂĐŝſŶĚĞůĂƉƌŽĚƵĐĐŝſŶĚĞZK͘ŶĞůĐĂƐŽĚĞŶƵĞƐƚƌŽŵŽĚĞůŽ
ĐĞůƵůĂƌĚĞϲͲK,͕ĞůĐŝƚĂĚŽĨĄƌŵĂĐŽŶŽĨƵĞĐĂƉĂǌĚĞĚĞĐƌĞĐĞƌĞůƌĂƚŝŽDŝƚŽWͬDŝƚŽ͕
ϲϯ
ŽďƚĞŶŝĠŶĚŽƐĞ ǀĂůŽƌĞƐ ŵƵǇ ƐŝŵŝůĂƌĞƐ ĐƵĂŶĚŽ ůŽƐ ĐƵůƚŝǀŽƐ ĐĞůƵůĂƌĞƐ ĞƌĂŶ ƚƌĂƚĂĚŽƐ
ĞǆĐůƵƐŝǀĂŵĞŶƚĞ ĐŽŶ ϲͲK, Ž ĐƵĂŶĚŽ͕ Ă ĞƐƚĂ ŶĞƵƌŽƚŽǆŝŶĂ͕ ƐĞ ůĞ ĂŹĂĚşĂ DĚŝǀŝͲϭ͘ WŽƌ
ƚĂŶƚŽ͕ĞŶĞƐƚĞĞƐĐĞŶĂƌŝŽ͕ƉŽĚĞŵŽƐĐŽŶĐůƵŝƌƋƵĞůĂƉƌŽĚƵĐĐŝſŶĚĞZK͕ĞƐƉĞĐŝĂůŵĞŶƚĞ
ĚĞ ,ϮKϮ͕ ŝŶĚƵĐŝĚĂ ƉŽƌ ƉĂƌƚĞ ĚĞ ϲͲK,͕ ĞƐ ƵŶ ƉĂƐŽ ĂŶƚĞƌŝŽƌ ĞŶ Ğů ƚŝĞŵƉŽ Ă ůĂ ĨŝƐŝſŶ
ŵŝƚŽĐŽŶĚƌŝĂ͕ǇĂƋƵĞůĂŝŶŚŝďŝĐŝſŶĚĞĞƐƚĞƷůƚŝŵŽƉƌŽĐĞƐŽ͕ƉŽƌƉĂƌƚĞĚĞDĚŝǀŝͲϭ͕ŶŽĞƐ
ĐĂƉĂǌĚĞďůŽƋƵĞĂƌůĂƉƌŽĚƵĐĐŝſŶĚĞůĐŝƚĂĚŽZK͘
WŽƌ ƐƵ ƉĂƌƚĞ͕ Ğů ĞĨĞĐƚŽ ŽďƐĞƌǀĂĚŽ ĞŶ Ğů ĐĂƐŽ ĚĞ ŶƵĞƐƚƌŽ ŵŽĚĞůŽ ĚĞ , ĨƵĞ
ƐŝŵŝůĂƌ͘ Ŷ ĞƐƚĞ ĐĂƐŽ͕ ŽďƐĞƌǀĂŵŽƐ ƋƵĞ DĚŝǀŝͲϭ ŶŽ ĞƌĂ ĐĂƉĂǌ ĚĞ ĞǀŝƚĂƌ Ž ƌĞǀĞƌƚŝƌ ůŽƐ
ŝŶĐƌĞŵĞŶƚŽƐĞŶůĂƉƌŽĚƵĐĐŝſŶĚĞƉĞƌſǆŝĚŽƐ͕ŝŶĚƵĐŝĚŽƐƉŽƌϯEW͘>ĂĞǆƉůŝĐĂĐŝſŶĂĞƐƚĞ
ĨĞŶſŵĞŶŽůĂƉŽĚĞŵŽƐĞŶĐŽŶƚƌĂƌĞŶƵŶƚƌĂďĂũŽ͕ĞŶĞůƋƵĞ͕ƵƐĂŶĚŽƵŶŵŽĚĞůŽĚĞϯEW͕
ƐĞƐŝƚƷĂĞůĞĚĞŵĂŵŝƚŽĐŽŶĚƌŝĂůĐŽŵŽƵŶƉĂƐŽƉƌĞǀŝŽĂůĂƉƌŽĚƵĐĐŝſŶĚĞZK͘ĞŚĞĐŚŽ͕
ůŽƐĂƵƚŽƌĞƐĐŽŶƐƚĂƚĂŶƋƵĞ͕ĞŶĞůĐŝƚĂĚŽŵŽĚĞůŽ͕ĞƐƚĞƷůƚŝŵŽƉƌŽĐĞƐŽĞƐŝŶĚĞƉĞŶĚŝĞŶƚĞ
ĚĞůĂĨƌĂŐŵĞŶƚĂĐŝſŶŵŝƚŽĐŽŶĚƌŝĂůǇĚĞůĂŵƵĞƌƚĞĐĞůƵůĂƌĂƉŽƉƚſƚŝĐĂ͕;>ŝŽƚĞƚĂů͕͘ϮϬϬϵͿ͘
ĐŽŶƚŝŶƵĂĐŝſŶ͕ ƉĂƌĂ ĞƐƚƵĚŝĂƌ ŵĄƐ ĞŶ ƉƌŽĨƵŶĚŝĚĂĚ Ğů ƉĂƉĞů ĚĞ ůĂƐ ZK ĞŶ
ŶƵĞƐƚƌĂƐ ĐŽŶĚŝĐŝŽŶĞƐ͕ ƵƚŝůŝǌĂŵŽƐ ǀĂƌŝŽƐ ĂŶƚŝŽǆŝĚĂŶƚĞƐ͘ ů ĞƐƚƵĚŝŽ ƉŽƌ ƉĂƌƚĞ ĚĞ ůĂ
ĐŽŵƵŶŝĚĂĚ ĐŝĞŶƚşĨŝĐĂ ĚĞ ƉĞƋƵĞŹĂƐ ŵŽůĠĐƵůĂƐ ĂŶƚŝŽǆŝĚĂŶƚĞƐ͕ Ž ŵŝŵĠƚŝĐĂƐ ĚĞ ůŽƐ
ĂŶƚŝŽǆŝĚĂŶƚĞƐ͕ĐŽŵŽĞůĞŵĞŶƚŽƐƉƌŽƚĞĐƚŽƌĞƐĐŽŶƚƌĂůŽƐĚĂŹŽƐƉƌŽĚƵĐŝĚŽƐĞŶĞů^ŝƐƚĞŵĂ
EĞƌǀŝŽƐŽ ĞŶƚƌĂů͕ ĐŽŵŽĞƐ Ğů ĐĂƐŽ ĚĞ ůĂ ŶĞƵƌŽĚĞŐĞŶĞƌĂĐŝſŶ ĚŽƉĂŵŝŶĠƌŐŝĐĂ͕ ǀŝĞŶĞ ĚĞ
ůĞũŽƐ͕ŵŽƐƚƌĂŶĚŽƌĞƐƵůƚĂĚŽƐƉŽƐŝƚŝǀŽƐĞŶĂůŐƵŶŽƐĐĂƐŽƐ͕;ĚůĂŵĞƚĂů͕͘ϮϬϬϱ͖ĞƌǀĞŶǇĞƚ
Ăů͕͘ϮϬϬϭ͖ŚĂŶĚƌĂŶĞƚĂů͕͘ϮϬϬϵ͖^ŵŝƚŚĞƚĂů͕͘ϮϬϬϯͿ͘
ůĄƐŝĐĂŵĞŶƚĞ͕ ĞƐƚĂƐ ŵŽůĠĐƵůĂƐ ĂĐƚƵĂďĂŶ Ă ŶŝǀĞů ƐŝƐƚĠŵŝĐŽ͕ ƉĞŶĞƚƌĂŶĚŽ ƉŽĐŽ Ž
ŶĂĚĂ ĞŶ ůĂ ŵŝƚŽĐŽŶĚƌŝĂ͘ ĞŶƚƌŽ ĚĞ ĞƐƚĞ ŐƌƵƉŽ͕ ĞŶĐŽŶƚƌĂŵŽƐ͕ ƉŽƌ ĞũĞŵƉůŽ͕ ůĂ ĞŶǌŝŵĂ
ĐĂƚĂůĂƐĂ͕ Ğů dDWK> Ǉ Ğů DŶdW͕ ƚŽĚŽƐ ĞůůŽƐ ƵƚŝůŝǌĂĚŽƐ ĞŶ ŶƵĞƐƚƌŽ ƚƌĂďĂũŽ͘ ^ŝŶ
ĞŵďĂƌŐŽ͕ Ă ƉĞƐĂƌ ĚĞ ůĂ ƉŽĐĂ ĐĂƉĂĐŝĚĂĚ ĚĞ ĞƐƚĂƐ ƐƵƐƚĂŶĐŝĂƐ ƉĂƌĂ ĞŶƚƌĂƌ Ăů ŝŶƚĞƌŝŽƌ
ŵŝƚŽĐŽŶĚƌŝĂů͕ ĞƐ ĐŝĞƌƚŽ ƋƵĞ ŚĂǇ ƚƌĂďĂũŽƐ ĞŶ ůŽƐ ƋƵĞ ŚĂ ƋƵĞĚĂĚŽ ĚĞŵŽƐƚƌĂĚŽ ƋƵĞ͕
ĂůŐƵŶŽƐĚĞ ĞƐƚŽƐ ĂŶƚŝŽǆŝĚĂŶƚĞƐ ƐŝƐƚĠŵŝĐŽƐ͕ ĐŽŵŽ ůĂ ǀŝƚĂŵŝŶĂ͕ ůĂ EͲĂĐĞƚŝů ĐŝƐƚĞşŶĂ͕ Ğů
ĄĐŝĚŽ ĂƐĐſƌďŝĐŽ͕ Ğů ƉŝƌƵǀĂƚŽ Ž ůĂ ƉƌŽƉŝĂ ĞŶǌŝŵĂ ĐĂƚĂůĂƐĂ͕ ƐŽŶ ĐĂƉĂĐĞƐ ĚĞ ĞũĞƌĐĞƌ ƵŶĂ
ĐůĂƌĂ ĂĐĐŝſŶ ĐŝƚŽƉƌŽƚĞĐƚŽƌĂ͕ ĞŶ ĚŝƐƚŝŶƚŽƐ ŵŽĚĞůŽƐ ĂŶŝŵĂůĞƐ Ǉ ĐĞůƵůĂƌĞƐ ĞŶ ůŽƐ ƋƵĞ Ğů
ĂŐĞŶƚĞƚſǆŝĐŽĞƌĂϲͲK,͕;&ĞƌŶĂŶĚĞǌͲ'ŽŵĞǌĞƚĂů͕͘ϮϬϬϲ͖'ĂůŝŶĚŽĞƚĂů͕͘ϮϬϬϯ͖:ŽƌĚĂŶ
ϲϰ
ĞƚĂů͕͘ϮϬϬϰ͖>ĂŝĞƚĂů͕͘ϭϵϵϳͿ
ĚĞŵĄƐ͕ ƌĞĐŝĞŶƚĞŵĞŶƚĞ ƐĞ ŚĂ ůŽŐƌĂĚŽ ƐŝŶƚĞƚŝǌĂƌ ĂŶƚŝŽǆŝĚĂŶƚĞƐ ĚŝƌŝŐŝĚŽƐ
ĞǆĐůƵƐŝǀĂŵĞŶƚĞ Ă ůĂ ŵŝƚŽĐŽŶĚƌŝĂ͕ ĚŽŶĚĞ ƐĞ ĂĐƵŵƵůĂŶ ĞŶ ĂůƚĂƐ ĐŽŶĐĞŶƚƌĂĐŝŽŶĞƐ͕
;ĂǇƌĂƐǇ Ğƚ Ăů͕͘ ϮϬϭϯ͖ ŚĂŶĂƐĞŬĂƌĂŶ Ğƚ Ăů͕͘ ϮϬϬϱ͖ ^ŵŝƚŚ Ğƚ Ăů͕͘ ϮϬϭϭĂ͖ ^ŵŝƚŚ Ğƚ Ăů͕͘
ϮϬϭϭďͿ͘ƐƚĞŚĞĐŚŽƐƵƉŽŶĞƵŶĂǀĞŶƚĂũĂƉĂƌĂƋƵĞůĂƐĐŝƚĂĚĂƐŵŽůĠĐƵůĂƐƉƵĞĚĂŶĞũĞƌĐĞƌ
ƐƵ ĂĐĐŝſŶ͕ ĂĚŵŝŶŝƐƚƌĂŶĚŽ ĐŽŶĐĞŶƚƌĂĐŝŽŶĞƐ ŵĞŶŽƌĞƐ ĚĞ ůĂƐ ŵŝƐŵĂƐ͕ ǇĂ ƋƵĞ͕ ĐŽŵŽ
ŝŶĚŝĐĄďĂŵŽƐ ĞŶ ůĂ ŝŶƚƌŽĚƵĐĐŝſŶ͕ ůĂ ƉƌŝŶĐŝƉĂů ĨƵĞŶƚĞ ĚĞ ƉƌŽĚƵĐĐŝſŶ ĚĞ ĞƐƚĂƐ ZK ƐĞ
ĞŶĐƵĞŶƚƌĂ ĞŶ ůĂ d ŵŝƚŽĐŽŶĚƌŝĂů͕ ƉŽƌ ůŽ ƋƵĞ͕ ĂĐƚƵĂŶĚŽ ƉƌĞĐŝƐĂŵĞŶƚĞ Ă ĞƐƚĞ ŶŝǀĞů͕
ƐĞƌĄŶ ŵĄƐ ĞĨĞĐƚŝǀĂƐ ĞƐƚĂƐ ĞƐƚƌĂƚĞŐŝĂƐ͘ Ŷ ĞƐƚĞ ƚƌĂďĂũŽ͕ ĚĞ ĞŶƚƌĞ ĞƐƚĞ ƚŝƉŽ ĚĞ
ĂŶƚŝŽǆŝĚĂŶƚĞƐ͕ŚĞŵŽƐĐŽŶƚĂĚŽĐŽŶDŝƚŽY͕;ĐŚƚĂǇĞƚĂů͕͘ϮϬϬϮ͖^ŵŝƚŚĞƚĂů͕͘ϮϬϭϬͿ͘
ůƉƌŝŵĞƌŽĚĞůŽƐĂŶƚŝŽǆŝĚĂŶƚĞƐƋƵĞĚĞĐŝĚŝŵŽƐƵƚŝůŝǌĂƌĨƵĞůĂĐĂƚĂůĂƐĂ͕ǇĂƋƵĞ͕ĞŶ
ŶƵĞƐƚƌŽŵŽĚĞůŽĚĞW͕ĞƐƚĂĞŶǌŝŵĂŶŽƐĨƵĞŵƵǇƷƚŝůƉĂƌĂĐŽŵƉƌĞŶĚĞƌĞůŽƌŝŐĞŶĐĞůƵůĂƌ
ĚĞ ůĂƐ ZK ƋƵĞ ŽďƐĞƌǀĄďĂŵŽƐ͘ Ɛş͕ ĐŽŵŽ ŝŶĚŝĐĄďĂŵŽƐ ĂŶƚĞƌŝŽƌŵĞŶƚĞ͕ Ğů ƉƌŝŶĐŝƉĂů
ŵĞƚĂďŽůŝƚŽƉƌŽĚƵĐŝĚŽƉŽƌϲͲK,ĞƐ,ϮKϮ͘ƐƚĂŵŽůĠĐƵůĂƉƌĞƐĞŶƚĂƵŶĂůĂůƚŽŐƌĂĚŽĚĞ
ĚŝĨƵƐŝſŶĂƚƌĂǀĠƐĚĞůĂƐŵĞŵďƌĂŶĂƐ͕ƉŽƌůŽƋƵĞůŽƐŶŝǀĞůĞƐĚĞĞƐƚĂZKĚĞŶƚƌŽǇĨƵĞƌĂ
ĚĞůĂĐĠůƵůĂƐĞĞŶĐƵĞŶƚƌĂŶĞŶĞƋƵŝůŝďƌŝŽĚŝŶĄŵŝĐŽ͕;ŶƚƵŶĞƐĞƚĂů͕͘ϮϬϬϬͿ͘WŽƌƚĂŶƚŽ͕ĞŶ
ŶƵĞƐƚƌŽŵŽĚĞůŽĐĞůƵůĂƌ͕ŶŽƉŽĚşĂŵŽƐĚĞƚĞƌŵŝŶĂƌĐŽŶĞǆĂĐƚŝƚƵĚƐŝĞůŝŶĐƌĞŵĞŶƚŽĞŶůĂ
ĐŽŶĐĞŶƚƌĂĐŝſŶ ĚĞ ,ϮKϮ ŵŝƚŽĐŽŶĚƌŝĂů ŽĐƵƌƌşĂ ĐŽŵŽ ĐŽŶƐĞĐƵĞŶĐŝĂ ĚĞ ůĂ ĂƵƚŽ ŽǆŝĚĂĐŝſŶ
ĚĞϲͲK,ĞŶĞůĐŝƚŽƐŽů͕ĞŶĞůŽƌŐĄŶƵůŽŽŝŶĐůƵƐŽĨƵĞƌĂĚĞůĂĐĠůƵůĂ͘
WĂƌĂ ŝŶƚĞŶƚĂƌ ĂĐůĂƌĂƌ ĞƐƚĞ ĂƐƉĞĐƚŽ͕ ĐŽŵŽ ŝŶĚŝĐĄďĂŵŽƐ͕ ĂŹĂĚŝŵŽƐ Ă ŶƵĞƐƚƌŽƐ
ĐƵůƚŝǀŽƐĐĞůƵůĂƌĞƐůĂĐŝƚĂĚĂĞŶǌŝŵĂ͕ůĂĐƵĂůĐĂƚĂůŝǌĂůĂĚĞƐĐŽŵƉŽƐŝĐŝſŶĚĞ,ϮKϮĞŶKϮǇ
ĞŶ ,ϮK͕ ;ǀĂŶƐ͕ ϭϵϬϳͿ͘ >Ă ŝŶĐĂƉĂĐŝĚĂĚ ĚĞ ůĂ ĐĂƚĂůĂƐĂ ƉĂƌĂ ƚƌĂƐƉĂƐĂƌ ůĂ ŵĞŵďƌĂŶĂ
ŵŝƚŽĐŽŶĚƌŝĂů ŚĂĐĞ ƋƵĞ ƐſůŽ ƉƵĞĚĂ ĞũĞƌĐĞƌ ƐƵ ĂĐĐŝſŶ ĐƵĂŶĚŽ Ğů ,ϮKϮ ƉƌĞƐĞŶƚĞ ƵŶĂ
ůŽĐĂůŝǌĂĐŝſŶĞǆƚƌĂĐĞůƵůĂƌ͘
dƌĂƐůĂĂĚŝĐŝſŶĚĞůĂĐĂƚĂůĂƐĂ͕ƐĞƉƌŽĚƵũŽƵŶĂĚŝƐŵŝŶƵĐŝſŶƐŝŐŶŝĨŝĐĂƚŝǀĂĚĞůƌĂƚŝŽ
DŝƚŽWͬDŝƚŽ͕ ůŽ ĐƵĂů ƐŝŐŶŝĨŝĐĂ ƋƵĞ ƵŶĂ ƉĂƌƚĞ ŝŵƉŽƌƚĂŶƚĞ ĚĞů ,ϮKϮ ŐĞŶĞƌĂĚŽ ƉŽƌ ϲͲ
K, ƉƌŽǀŝĞŶĞ ĚĞ ůŽƐ ĐŝĐůŽƐ ĚĞ ĂƵƚŽ ŽǆŝĚĂĐŝſŶ ƋƵĞ Ğů ĐŝƚĂĚŽ ĨĄƌŵĂĐŽ ƐƵĨƌĞ ĞŶ Ğů
ĞƐƉĂĐŝŽĞǆƚƌĂĐĞůƵůĂƌ͘ŶůĂůşŶĞĂĚĞŶƵĞƐƚƌŽƐĚĂƚŽƐǇĂƉŽǇĂŶĚŽŶƵĞƐƚƌĂŚŝƉſƚĞƐŝƐ͕ŽƚƌŽ
ŐƌƵƉŽ ŚĂ ĚĞŵŽƐƚƌĂĚŽ ƋƵĞ ůĂ ĂĚŝĐŝſŶ ĚĞ ƐƵƐƚĂŶĐŝĂƐ ĐŽŶ ĂĐĐŝſŶ ĂŶƚŝŽǆŝĚĂŶƚĞ ĚĞ
ϲϱ
ůŽĐĂůŝǌĂĐŝſŶĞǆƚƌĂĐĞůƵůĂƌ͕ĐŽŵŽĞƐĞůĐĂƐŽĚĞůĂĐŝƚĂĚĂĐĂƚĂůĂƐĂŽĚĞůĂŵĞƚĂůŽƉŽƌĨŝƌŝŶĂ͕
ĐŽŶĨŝĞƌĞ Ă ůŽƐ ĐƵůƚŝǀŽƐ ƉƌŽƚĞĐĐŝſŶ ĐŽŶƚƌĂ ůĂ ĐŝƚŽƚŽǆŝĐŝĚĂĚ ŝŶĚƵĐŝĚĂ ƉŽƌ ϲͲK,͕ ĞŶƵŶ
ŵŽĚĞůŽĐƌĞĂĚŽĞŶĐĠůƵůĂƐĚĞůĂůşŶĞĂĐĞůƵůĂƌϲϱ͕;<ƵůŝĐŚĞƚĂů͕͘ϮϬϬϯͿ͘
WŽƌƐƵƉĂƌƚĞ͕ĞŶĞůĐĂƐŽĚĞdDWK>͕DŶdWǇDŝƚŽY͕ƵƐĂŵŽƐĞƐƚŽƐĨĄƌŵĂĐŽƐ
ƉĂƌĂ ŽďƐĞƌǀĂƌ Ğů ĞĨĞĐƚŽƋƵĞ ůĂ ŝŶŚŝďŝĐŝſŶ ĚĞ ůĂ ƉƌŽĚƵĐĐŝſŶ ĞǆĐĞƐŝǀĂ ĚĞ ZK͕ ŝŶĚƵĐŝĚĂ
ƉŽƌ ϲͲK, Ǉ ƉŽƌ ϯEW͕ ƉƌŽĚƵĐşĂ ƐŽďƌĞ ůŽƐ ĚŝǀĞƌƐŽƐ ƉĂƌĄŵĞƚƌŽƐ ŵŝƚŽĐŽŶĚƌŝĂůĞƐ
ŽďƐĞƌǀĂĚŽƐŚĂƐƚĂĞůŵŽŵĞŶƚŽ͘
Ɛş͕ dDWK>͕ ĞŶ ŶƵĞƐƚƌŽ ŵŽĚĞůŽ ĐĞůƵůĂƌ ĚĞ W͕ ĨƵĞ ĐĂƉĂǌ ĚĞ ƌĞǀĞƌƚŝƌ Ğů
ŝŶĐƌĞŵĞŶƚŽ ĞŶ ůĂƚĂƐĂ ĚĞ ŵŝŐƌĂĐŝſŶ ŵŝƚŽĐŽŶĚƌŝĂů ĚĞ ƌƉϭ͕ ŝŶĚƵĐŝĚŽƉŽƌϲͲK,͘ WŽƌ
ƚĂŶƚŽ͕ Ă ůĂ ǀŝƐƚĂ ĚĞ ĞƐƚŽƐ ĚĂƚŽƐ͕ ƉŽĚĞŵŽƐ ĂĨŝƌŵĂƌ ƋƵĞ Ğů ĞƐƚƌĠƐ ŽǆŝĚĂƚŝǀŽ ƉĂƌƚŝĐŝƉĂ
ĂĐƚŝǀĂŵĞŶƚĞ ĞŶ ůŽƐ ŝŶĐƌĞŵĞŶƚŽƐ ĞŶ ůĂ ĨŝƐŝſŶ ŵŝƚŽĐŽŶĚƌŝĂů͕ ĐƵĂŶĚŽ ĞƐƚŽƐ ƐŽŶ
ƐĞĐƵŶĚĂƌŝŽƐĂůĂĂĚŝĐŝſŶĚĞϲͲK,͘
dDWK> ĞƐ ƵŶĂ ŶŝƚƌſǆŝĚŽ ĚĞ ƉŝƉĞƌŝĚŝŶĂ ĞƐƚĂďůĞ Ǉ ƐŽůƵďůĞ ĞŶ ĂŐƵĂ͕ ;^ĂŵƵŶŝ Ğƚ
Ăů͕͘ϭϵϵϬͿ͕ĐĂƉĂǌĚĞĂƚƌĂǀĞƐĂƌůĂƐŵĞŵďƌĂŶĂƐďŝŽůſŐŝĐĂƐ͕;>ĂŝŐŚƚĞƚĂů͕͘ϭϵϵϳͿ͘^ƵĂĐĐŝſŶ
ĂŶƚŝŽǆŝĚĂŶƚĞĞƐĞũĞƌĐŝĚĂĂƚƌĂǀĠƐĚĞƐƵĐĂƉĂĐŝĚĂĚƉĂƌĂŶĞƵƚƌĂůŝǌĂƌƌĂĚŝĐĂůĞƐƐƵƉĞƌſǆŝĚŽ͕
;>ĂŝŐŚƚĞƚĂů͕͘ϭϵϵϳͿ͕ƉƵĚŝĞŶĚŽĂĐƚƵĂƌĐŽŵŽƵŶĂƵƚĠŶƚŝĐŽŵŝŵĠƚŝĐŽĚĞůĂ^K͕;>ĂŝŐŚƚĞƚ
Ăů͕͘ ϭϵϵϳͿ͘ ĚŝĐŝŽŶĂůŵĞŶƚĞ͕ dDWK> ĞƐ ĐĂƉĂǌ ĚĞ ĂŵŝŶŽƌĂƌ ůĂ ĨŽƌŵĂĐŝſŶ ĚĞ ƌĂĚŝĐĂůĞƐ
ŚŝĚƌŽǆŝůŽ͕ Ă ƚƌĂǀĠƐ ĚĞ ůĂ ŶĞƵƚƌĂůŝǌĂĐŝſŶ ĚĞů ƐƵƉĞƌſǆŝĚŽ Ž ĚĞ ůĂ ĚŝƐŵŝŶƵĐŝſŶ ĚĞ ůĂƐ
ĐŽŶĐĞŶƚƌĂĐŝŽŶĞƐŝŶƚƌĂĐĞůƵůĂƌĞƐĚĞ&ĞнϮ͕Ǉ͕ƉŽƌƚĂŶƚŽ͕ĚĞůĂƌĞĚƵĐĐŝſŶĚĞůĂĞŶǀĞƌŐĂĚƵƌĂ
ĚĞ ůĂƐ ƌĞĂĐĐŝŽŶĞƐ ĚĞ &ĞŶƚŽŶ Ǉ ĚĞ ,ĂďĞƌͲtĞŝƐƐ͕ ;DŝƚĐŚĞůů Ğƚ Ăů͕͘ ϭϵϵϬ͖ DŽŶƚŝ Ğƚ Ăů͕͘
ϭϵϵϲ͖^ĂƐĂŬŝĞƚĂů͕͘ϭϵϵϴͿ͘
WŽƌƐƵƉĂƌƚĞ͕ƐŝŐƵŝĞŶĚŽĞŶŶƵĞƐƚƌŽŵŽĚĞůŽĚĞW͕DŶdWŵŽƐƚƌſƵŶĂĂĐĐŝſŶ
ŵƵǇ ƐŝŵŝůĂƌ Ă ůĂ ĞũĞƌĐŝĚĂ ƉŽƌ dDWK>͘ Ɛş͕ ĞƐƚĞ ĂŶƚŝŽǆŝĚĂŶƚĞ͕ Ăů ĐŽŶƚƌĂƌƌĞƐƚĂƌ ůĂ
ƉƌŽĚƵĐĐŝſŶĚĞZK͕ĨƵĞƚĂŵďŝĠŶĐĂƉĂǌĚĞĞǀŝƚĂƌůĂĨŝƐŝſŶŵŝƚŽĐŽŶĚƌŝĂůĞǆĐĞƐŝǀĂ͘
DŶdWĞƐƵŶĂƉƌŽĨŝƌŝŶĂĞƐƚĂďůĞǇĐĂƉĂǌĚĞƉĞŶĞƚƌĂƌůĂƐŵĞŵďƌĂŶĂƐďŝŽůſŐŝĐĂƐ͘
ůĄƐŝĐĂŵĞŶƚĞ͕ ĞƐƚĂ ŵŽůĠĐƵůĂ ŚĂ ƐŝĚŽ ĐŽŶƐŝĚĞƌĂĚĂ ĐŽŵŽ ƵŶ ŵŝŵĠƚŝĐŽ ĚĞ ůĂ ^K͕
;ĂƌůĞǇͲhƐŵĂƌ Ğƚ Ăů͕͘ ϭϵϵϲ͖ ĂǇ Ğƚ Ăů͕͘ ϭϵϵϲ͖ ĂǇ Ğƚ Ăů͕͘ ϭϵϵϱ͖ ŝŶŐĂƌĞůůŝ Ğƚ Ăů͕͘ ϭϵϵϲͿ͕
ĂƵŶƋƵĞ͕ Ă ĚşĂ ĚĞ ŚŽǇ͕ ŚĂǇ ƚƌĂďĂũŽƐ ƋƵĞ ŶŝĞŐĂŶ ĞƐƚĞ ĞǆƚƌĞŵŽ͕ ;ĂƚŝŶŝĐͲ,ĂďĞƌůĞ Ğƚ Ăů͕͘
ϲϲ
ϮϬϬϵ͖ ZĞďŽƵĐĂƐ Ğƚ Ăů͕͘ ϮϬϬϴĂ͖ ZĞďŽƵĐĂƐ Ğƚ Ăů͕͘ ϮϬϬϴďͿ͘ ^ŝŶ ĞŵďĂƌŐŽ͕ ůŽ ƋƵĞ Ɛş ƋƵĞ
ƉĂƌĞĐĞ ĐŽŶƐƚĂƚĂĚŽ ĞƐ ůĂ ĐĂƉĂĐŝĚĂĚ ĚĞ ĞƐƚĞ ĂŶƚŝŽǆŝĚĂŶƚĞ ƉĂƌĂ ŝŶĂĐƚŝǀĂƌ ůŽƐ ƌĂĚŝĐĂůĞƐ
ƐƵƉĞƌſǆŝĚŽ͘ĚŝĐŝŽŶĂůŵĞŶƚĞ͕DŶdWƉŽƐĞĞƚĂŵďŝĠŶĞĨĞĐƚŽĐŽŶƚƌĂůŽƐƉĞƌŽǆŝŶŝƚƌŝƚŽƐ͕
ĂƵŶƋƵĞŶŽĞƐĐĂƉĂǌĚĞĂĐƚƵĂƌĐŽŶƚƌĂĞůſǆŝĚŽŶşƚƌŝĐŽ͕;^ǌĂďŽĞƚĂů͕͘ϭϵϵϲͿ͘
ĐŽŶƚŝŶƵĂĐŝſŶ͕ ƉĂƌĂ ĐŽƌƌŽďŽƌĂƌ ĞƐƚŽƐ ƌĞƐƵůƚĂĚŽƐ͕ ƌĞĂůŝǌĂŵŽƐ ůŽƐ ŵŝƐŵŽƐ
ĞƐƚƵĚŝŽƐƉĞƌŽƵƐĂŶĚŽ͕ĞƐƚĂǀĞǌ͕DŝƚŽY͘^ĞƚƌĂƚĂĚĞƵŶĂŵŽůĠĐƵůĂƋƵĞĞũĞƌĐĞƵŶĂĂĐĐŝſŶ
ƉƌŽƚĞĐƚŽƌĂƐŽďƌĞůĂŵŝƚŽĐŽŶĚƌŝĂ͕ĚŝƐŵŝŶƵǇĞŶĚŽůŽƐŶŝǀĞůĞƐĚĞZKĞŶǀĂƌŝŽƐŵŽĚĞůŽƐ
ĂŶŝŵĂůĞƐ͕ ;:ĂŵĞƐ Ğƚ Ăů͕͘ ϮϬϬϱͿ͘ ŽŶĐƌĞƚĂŵĞŶƚĞ͕ ĞũĞƌĐĞ ƐƵ ĂĐĐŝſŶ Ă ƚƌĂǀĠƐ ĚĞ ůĂ
ĚŝƐŵŝŶƵĐŝſŶĚĞůĚĂŹŽŽǆŝĚĂƚŝǀŽĂůĂƐƉƌŽƚĞşŶĂƐ͕ůŽƐůşƉŝĚŽƐǇĞůEĚĞĠƐƚĂ͕;<ĞůƐŽĞƚ
Ăů͕͘ϮϬϬϭ͖^ƵďƌĂŵĂŶŝĂŶĞƚĂů͕͘ϮϬϭϬͿ͘
DŝƚŽY ĐŽŶũƵŐĂ ůĂ ĂĐĐŝſŶ ĂŶƚŝŽǆŝĚĂŶƚĞ ĚĞ ůĂ ŽĞŶǌŝŵĂ YϭϬ ĐŽŶƵŶĂ ĐĂĚĞŶĂ ĚĞů
ĐĂƚŝſŶ ůŝƉſĨŝůŽ ƚƌŝĨĞŶŝůĨŽƐĨŽŶŝŽ͕ ;dWWͿ͕ ƵŶŝĚŽƐ͕ ĂŵďŽƐ ĞůĞŵĞŶƚŽƐ͕ Ă ƚƌĂǀĠƐ ĚĞ ƵŶĂ ƐĞƌŝĞ
ĚĞ ĚŝĞǌ ĐĂƌďŽŶŽƐ ĂůŝĨĄƚŝĐŽƐ͕ ĨŽƌŵĂŶĚŽ ĞŶƚŽŶĐĞƐ ĚdWW͘ 'ƌĂĐŝĂƐ ƉƌĞĐŝƐĂŵĞŶƚĞ Ă ĞƐƚĂ
ĐĂĚĞŶĂ Ǉ Ă dWW͕ ĞƐƚĂ ŵŽůĠĐƵůĂ ĞƐ ĐĂƉƚĂĚĂ ƉŽƌ ůĂ ŵŝƚŽĐŽŶĚƌŝĂ ƌĄƉŝĚĂŵĞŶƚĞ Ǉ ĚĞ ƵŶ
ŵŽĚŽ ĞǆƚĞŶƐŽ͘ Ɛş͕ DŝƚŽY ĐŽŶƐŝŐƵĞ ĂůĐĂŶǌĂƌ ŝŶ ǀŝǀŽ ĐŽŶĐĞŶƚƌĂĐŝŽŶĞƐ ƵŶĂƐ ĐŝĞŶ ǀĞĐĞƐ
ƐƵƉĞƌŝŽƌĞƐĞŶĞůŝŶƚĞƌŝŽƌĚĞůĂŵŝƚŽĐŽŶĚƌŝĂ͕ƌĞƐƉĞĐƚŽĂůĂƐŽďƚĞŶŝĚĂƐĞŶĞůĐŝƚŽƉůĂƐŵĂ͕
ƉƌĞƐĞŶƚĄŶĚŽƐĞ͕ĂƐƵǀĞǌ͕ĞŶĞƐƚĞƷůƚŝŵŽĐŽŵƉĂƌƚŝŵŝĞŶƚŽĞŶƚƌĞĐŝŶĐŽǇĚŝĞǌǀĞĐĞƐŵĄƐ
ĐŽŶĐĞŶƚƌĂĚŽ ƋƵĞ ĞŶ Ğů ĞƐƉĂĐŝŽ ĞǆƚƌĂĐĞůƵůĂƌ͕ ;'ƌŝŶŝƵƐ Ğƚ Ăů͕͘ ϭϵϳϬ͖ <ĞůƐŽ Ğƚ Ăů͕͘ ϮϬϬϭ͖
DƵƌƉŚǇĞƚĂů͕͘ϮϬϬϬ͖^ŵŝƚŚĞƚĂů͕͘ϮϬϬϯͿ͘hŶĂǀĞǌĚĞŶƚƌŽĚĞůŽƌŐĄŶƵůŽ͕ƐĞƌĞĚƵĐĞĂƐƵ
ĨŽƌŵĂĂĐƚŝǀĂ͕ĞƐƚŽĞƐ͕ĞůƵďŝƋƵŝŶŽů͕;DƵƌƉŚǇ͕ϮϬϬϴͿ͘
ĚĞŵĄƐ͕ ƐĂďĞŵŽƐ ƋƵĞ DŝƚŽY ĞƐ ĐĂƉĂǌ ĚĞ ƌĂůĞŶƚŝǌĂƌ ůĂ ƉƌŽŐƌĞƐŝſŶ ĚĞ ůĂ W͕
ĐŽŵŽƐĞĚĞŵƵĞƐƚƌĂĞŶƵŶƚƌĂďĂũŽĞŶĞůƋƵĞƐĞŵŝĚŝĞƌŽŶǀĂƌŝŽƐŵĂƌĐĂĚŽƌĞƐĐůşŶŝĐŽƐĚĞ
ůĂ ĐŝƚĂĚĂ ĞŶĨĞƌŵĞĚĂĚ͕ ĐŽŶĐƌĞƚĂŵĞŶƚĞ ĂƋƵĞůůŽƐ ĞŶŐůŽďĂĚŽƐ ĞŶ ůĂ ƐĐĂůĂ hŶŝĨŝĐĂĚĂ ĚĞ
ƵĂŶƚŝĨŝĐĂĐŝſŶĚĞůĂŶĨĞƌŵĞĚĂĚĚĞWĂƌŬŝŶƐŽŶ;hŶŝĨŝĞĚWĂƌŬŝŶƐŽŶŝƐĞĂƐĞZĂƚŝŶŐ^ĐĂůĞͿ͕
ŽďƐĞƌǀĄŶĚŽƐĞŵĞũŽƌşĂƐƐŝŐŶŝĨŝĐĂƚŝǀĂƐĞŶǀĂƌŝŽƐĚĞĞůůŽƐ͕;^ŶŽǁĞƚĂů͕͘ϮϬϭϬͿ͘
Ŷ ƉƌŝŵĞƌ ůƵŐĂƌ͕ ĞƐ ŝŵƉŽƌƚĂŶƚĞ ƌĞĐĂůĐĂƌ ƋƵĞ ůĂ ĐĂĚĞŶĂ ĂůŝĨĄƚŝĐĂ ƵŶŝĚĂ Ă dWW͕
ĂŹĂĚŝĚĂĂůĂŵŝƐŵĂĐŽŶĐĞŶƚƌĂĐŝſŶƋƵĞDŝƚŽY͕ŶŽĨƵĞĐĂƉĂǌĚĞŝŶĚƵĐŝƌŶŝŶŐƷŶĞĨĞĐƚŽ
ƐŽďƌĞŶŝŶŐƵŶŽĚĞůŽƐƉĂƌĄŵĞƚƌŽƐƋƵĞĐƵĂŶƚŝĨŝĐĂŵŽƐĞŶŶƵĞƐƚƌŽƐĐƵůƚŝǀŽƐĐĞůƵůĂƌĞƐĚĞ
^,Ͳ^zϱz͕ŶŝĐƵĂŶĚŽƐĞĂŹĂĚŝſƐŽůŽŶŝĐƵĂŶĚŽĚdWWĨƵĞĂĚŝĐŝŽŶĂĚŽĐŽŶũƵŶƚĂŵĞŶƚĞĐŽŶ
ϲϳ
ϲͲK,͕ ĐŽŵŽ ĐĂďşĂ ĞƐƉĞƌĂƌ͘ ŽŶ ĞƐƚŽƐ ĚĂƚŽƐ͕ ĞǆĐůƵŝŵŽƐ ůĂ ƉŽƐŝďŝůŝĚĂĚ ĚĞ ƵŶ ĞĨĞĐƚŽ
ŝŶĞƐƉĞĐşĨŝĐŽ͕ƉƌŽĚƵĐŝĚŽƉŽƌĞůǀĞŚşĐƵůŽ͕ĞŶǀĞǌĚĞƉŽƌĞůĂŶƚŝŽǆŝĚĂŶƚĞ͘
Ŷ ŶƵĞƐƚƌŽ ŵŽĚĞůŽ ĚĞ W͕ DŝƚŽY ĨƵĞ ĐĂƉĂǌ ĚĞ ĞǀŝƚĂƌ ůĂ ĨƌĂŐŵĞŶƚĂĐŝſŶ
ŵŝƚŽĐŽŶĚƌŝĂů͘ Ğ ŚĞĐŚŽ͕ ĐƵĂŶĚŽ ϲͲK, ĨƵĞ ĂŹĂĚŝĚĂ ĐŽŶũƵŶƚĂŵĞŶƚĞ ĐŽŶ DŝƚŽY͕ ůĂƐ
ŝŵĄŐĞŶĞƐ ĚĞ ĐŽŶĨŽĐĂů ŵŽƐƚƌĂƌŽŶ Ă ůĂƐ ĐĠůƵůĂƐ ĐŽŶ ƐƵƐ ŵŝƚŽĐŽŶĚƌŝĂƐ ƌĞƚŝĐƵůĂƌĞƐ͘ WŽƌ
ƚĂŶƚŽ͕ Ă ƉĂƌƚŝƌ ĚĞ ĞƐƚĂƐ ŽďƐĞƌǀĂĐŝŽŶĞƐ͕ ƉŽĚĞŵŽƐ ĐŽŶĐůƵŝƌ ƋƵĞ ůŽƐ ĐĂŵďŝŽƐ ƌĞĚŽǆ
ƉƌŽĚƵĐŝĚŽƐƉŽƌ ϲͲK,ĞŶ ůĂƐ ŵŝƚŽĐŽŶĚƌŝĂƐ ƐŽŶĞǀĞŶƚŽƐ ƚĞŵƉƌĂŶŽƐ͕ ĂŶƚĞƌŝŽƌĞƐ Ă ůĂƐ
ŵŽĚŝĨŝĐĂĐŝŽŶĞƐŵŽƌĨŽůſŐŝĐĂƐĚĞĞƐƚŽƐŽƌŐĄŶƵůŽƐ͘ĐŽŶƚŝŶƵĂĐŝſŶ͕ĞƐƚƵĚŝĂŵŽƐĞůĞĨĞĐƚŽ
ĚĞDŝƚŽYƐŽďƌĞůĂƚƌĂƐůŽĐĂĐŝſŶĂůĂŵŝƚŽĐŽŶĚƌŝĂĚĞƌƉϭǇĚĞĂǆ͕ƚƌĂƐůĂĂĚŝĐŝſŶĚĞϲͲ
K,͘ Ɛş͕ ŽďƐĞƌǀĂŵŽƐ ƋƵĞ DŝƚŽY ĞƌĂ ƚĂŵďŝĠŶ ĐĂƉĂǌ ĚĞ ĞǀŝƚĂƌ ĂŵďŽƐ ĞǀĞŶƚŽƐ͕
ĐƵĂŶĚŽĞƐƚŽƐĞƌĂŶŝŶĚƵĐŝĚŽƐƉŽƌϲͲK,͘
ůĂǀŝƐƚĂĚĞĞƐƚŽƐƌĞƐƵůƚĂĚŽƐ͕ĐŽŶĐůƵŝŵŽƐƋƵĞůĂƐZKŐĞŶĞƌĂĚĂƐƉŽƌϲͲK,
ĞƐƚĄŶĨƵĞƌƚĞŵĞŶƚĞŝŵƉůŝĐĂĚĂƐĞŶůĂŝŶĚƵĐĐŝſŶĚĞůĂĨŝƐŝſŶŵŝƚŽĐŽŶĚƌŝĂů͕ĞŶĞƐƚĞŵŽĚĞůŽ
ĚĞ W͘ Ɛş͕ ĞƐƚĂƐ ŵŽůĠĐƵůĂƐ ƉŽĚƌşĂŶ ƉƌŽĚƵĐŝƌ ĐŝĞƌƚŽƐ ĐĂŵďŝŽƐ ĞŶ Ğů ĞƐƚĂĚŽ ĚĞ
ƌĞĚƵĐĐŝſŶͲŽǆŝĚĂĐŝſŶ ĚĞ ƌƉϭ͕ ƉŽƐƚĞƌŝŽƌĞƐ Ă ůĂ ƚƌĂĚƵĐĐŝſŶ ƉƌŽƚĞŝĐĂ͘ Ğ ŚĞĐŚŽ͕ ůĂƐ
ŵŽĚŝĨŝĐĂĐŝŽŶĞƐŝŶĚƵĐŝĚĂƐĞŶƌƉϭƉŽƌůŽƐĐĂŵďŝŽƐĞŶĞůĞƐƚĂƚƵƐƌĞĚŽǆ͕ƉŽĚƌşĂŶĞƐƚĂƌĞŶ
ůĂ ďĂƐĞ ĚĞ ůŽƐ ĂƵŵĞŶƚŽƐ ĚĞů ĚĂŹŽ ŶĞƵƌŽŶĂů ŽďƐĞƌǀĂĚŽ ĞŶ ůŽƐ ƉƌŽĐĞƐŽƐ
ŶĞƵƌŽĚĞŐĞŶĞƌĂƚŝǀŽƐ͕ ;ĂƌƐŽƵŵ Ğƚ Ăů͕͘ ϮϬϬϲ͖ ZĞĚĚǇ Ğƚ Ăů͕͘ ϮϬϭϭͿ͘ ŽƌƌŽďŽƌĂŶĚŽ
ŶƵĞƐƚƌŽƐ ĚĂƚŽƐ͕ ĞǆŝƐƚĞ ƵŶĂ ƉƵďůŝĐĂĐŝſŶ ĞŶ ůĂ ƋƵĞ DŝƚŽY ƉƌŽĚƵũŽ ƚĂŵďŝĠŶ ƉƌŽƚĞĐĐŝſŶ
ƐŽďƌĞ ůĂƐ ĞƐƚƌƵĐƚƵƌĂƐ ŵŝƚŽĐŽŶĚƌŝĂůĞƐ͕ ƉƌĞǀŝŶŝĞŶĚŽ ůĂ ĞǆƉƌĞƐŝſŶ ĂŶŽƌŵĂů ĚĞ ůŽƐ ŐĞŶĞƐ
ŵŝƚŽĐŽŶĚƌŝĂůĞƐ͘ ů ĐŝƚĂĚŽ ƚƌĂďĂũŽ ĞƐƚĄ ƌĞĂůŝǌĂĚŽ ĞŶ ƵŶ ŵŽĚĞůŽ ĚĞ ĞŶĨĞƌŵĞĚĂĚ
ŶĞƵƌŽĚĞŐĞŶĞƌĂƚŝǀĂĞŶĞůƋƵĞƐĞĞƐƚƵĚŝĂďĂůĂƚŽǆŝĐŝĚĂĚĚĞůɴͲĂŵŝůŽŝĚĞĞŶĐĠůƵůĂƐEϮĂ͕
;DĂŶĐǌĂŬĞƚĂů͕͘ϮϬϭϬͿ͘
Ŷ ŶƵĞƐƚƌŽ ŵŽĚĞůŽ ĚĞ ,͕ ĐŽŵŽ ĐĂďşĂ ĞƐƉĞƌĂƌ͕ Ŷŝ dDWK> Ŷŝ DŶdW
ƉƌŽĚƵũĞƌŽŶ ŶŝŶŐƷŶ ĞĨĞĐƚŽ ƐŽďƌĞ ůĂ ŵŽƌĨŽůŽŐşĂ ŵŝƚŽĐŽŶĚƌŝĂů͘ ĚĞŵĄƐ͕ ĚĞďŝĚŽ Ă ůĂ
ĂƵƐĞŶĐŝĂĚĞŵŝŐƌĂĐŝſŶĚĞƌƉϭĂůĂŵŝƚŽĐŽŶĚƌŝĂ͕ĂůĂĐŽŶƐƚĂƚĂĐŝſŶĚĞůĂĨŽƌŵĂĐŝſŶĚĞů
WWdDǇĂůĂŝƌƌĞǀĞƌƐŝďŝůŝĚĂĚĚĞůĚĂŹŽĞŶůĂŵŽƌĨŽůŽŐşĂŵŝƚŽĐŽŶĚƌŝĂůƋƵĞƐĞŽďƐĞƌǀĂďĂ͕
ŶŽĐƌĞşŵŽƐŶĞĐĞƐĂƌŝŽƌĞĂůŝǌĂƌĞůĞƐƚƵĚŝŽĐŽŶDŝƚŽYŶŝĐŽŶĞŶǌŝŵĂĐĂƚĂůĂƐĂ͘
ĐŽŶƚŝŶƵĂĐŝſŶĚĞĐŝĚŝŵŽƐŝŶĐŝĚŝƌƐŽďƌĞůĂŚŝƉŽƚĠƚŝĐĂĂĐƚŝǀĂĐŝſŶĚĞůĂĂƵƚŽĨĂŐŝĂ
ϲϴ
ĞŶ ŶƵĞƐƚƌŽƐ ŵŽĚĞůŽƐ ĐĞůƵůĂƌĞƐ ĚĞ ĞŶĨĞƌŵĞĚĂĚĞƐ ŶĞƵƌŽĚĞŐĞŶĞƌĂƚŝǀĂƐ͘ WĂƌĂ ĞůůŽ͕ ĞŶ
ĞƐƚĞĐĂƐŽŶŽƐĐĞŶƚƌĂŵŽƐĞŶůĂǀŝƐƵĂůŝǌĂĐŝſŶǇĞŶĞůƌĞĐƵĞŶƚŽĚĞůŽƐĂƵƚŽĨĂŐŽƐŽŵĂƐ͘Ğ
ŚĞĐŚŽ͕ ĐŽŵŽ ŝŶĚŝĐĄďĂŵŽƐ ĞŶ ůĂ ŝŶƚƌŽĚƵĐĐŝſŶ Ă ĞƐƚĞ ƚƌĂďĂũŽ͕ ůĂ ĨŽƌŵĂĐŝſŶ ĚĞ ĞƐƚĂƐ
ĞƐƚƌƵĐƚƵƌĂƐĞƐƵŶƉĂƐŽŶĞĐĞƐĂƌŝŽĞŶĐƵĂůƋƵŝĞƌƉƌŽĐĞƐŽĚĞŵĂĐƌŽĂƵƚŽĨĂŐŝĂƉŽƌůŽƋƵĞ͕
Ğů ŝŶĐƌĞŵĞŶƚŽ ĚĞ ƐƵ ƉƌĞƐĞŶĐŝĂ ĞŶ ůĂƐ ĐĠůƵůĂƐ͕ ĞƐƵŶ ƐŝŐŶŽ ŝŶĞƋƵşǀŽĐŽĚĞ ůĂ ĂĐƚŝǀĂĐŝſŶ
ĚĞů ĐŝƚĂĚŽ ƉƌŽĐĞƐŽ͘ WĂƌĂ ƉŽĚĞƌ ŽďƐĞƌǀĂƌ Ǉ ĐŽŶƚĂƌ ůŽƐ ĂƵƚŽĨĂŐŽƐŽŵĂƐ͕ ƵƐĂŵŽƐ Ğů
ƉůĄƐŵŝĚŽ '&WͲ>ϯ͘ Ɛş͕ >ϯ͕ ĐŽŵŽ ĂƉƵŶƚĄďĂŵŽƐ ĞŶ Ğů ĂƉĂƌƚĂĚŽ ĚĞĚŝĐĂĚŽ Ă ůĂ
ŵŝƚŽĨĂŐŝĂ͕ĞƐƵŶĂƉƌŽƚĞşŶĂƋƵĞ͕ĐƵĂŶĚŽƐĞŝŶĚƵĐĞĞƐƚĞƚŝƉŽĚĞĚĞŐƌĂĚĂĐŝſŶ͕ƐĞĐŽŶũƵŐĂ
ĐŽŶůĂĨŽƐĨĂƚŝĚŝůƐĞƌŝŶĂǇƐĞƵŶĞĂůĂƐŵĞŵďƌĂŶĂƐĚĞůŽƐĂƵƚŽĨĂŐŽƐŽŵĂƐ͕;<ĂďĞǇĂĞƚĂů͕͘
ϮϬϬϬ͖ <ĂďĞǇĂ Ğƚ Ăů͕͘ ϮϬϬϰ͖ <ŝŵ Ğƚ Ăů͕͘ ϮϬϭϬͿ͕ ĂĐƚƵĂŶĚŽ ĐŽŵŽ ƵŶŽ ĚĞ ůŽƐ ƉƌŝŶĐŝƉĂůĞƐ
ĂĐƚŽƌĞƐ ĚĞ ĞƐƚĞ ƉƌŽĐĞƐŽ͘ WŽƌ ƚĂŶƚŽ͕ ĂŶƚĞ ůĂ ĂĐƚŝǀĂĐŝſŶ ĚĞů ƉƌŽĐĞƐŽ͕ ƐĞ ƉƌŽĚƵĐŝƌĄ ƵŶĂ
ĂŐƌĞŐĂĐŝſŶ ĚĞů ƉůĄƐŵŝĚŽ ĞŶ ůŽƐ ĂƵƚŽĨĂŐŽƐŽŵĂƐ ĚĞ ůĂƐ ŵŝƚŽĐŽŶĚƌŝĂƐ ƋƵĞ ǀĂŶ Ă ƐĞƌ
ĞůŝŵŝŶĂĚĂƐ͘
Ŷ ƉƌŝŵĞƌ ůƵŐĂƌ ĚĞŶƚƌŽ ĚĞ ĞƐƚĞ ĂƉĂƌƚĂĚŽ͕ ƚƌĂďĂũĂŵŽƐ ƐŽďƌĞ ůĂ ŚŝƉſƚĞƐŝƐ͕
ĂƉŽǇĂĚĂƉŽƌŽƚƌŽƐŐƌƵƉŽƐ͕ĚĞƋƵĞůŽƐŝŶĐƌĞŵĞŶƚŽƐĞŶůĂŐĞŶĞƌĂĐŝſŶĚĞZKũƵĞŐĂŶƵŶ
ƉĂƉĞůŝŵƉŽƌƚĂŶƚĞĞŶůĂĂĐƚŝǀĂĐŝſŶĚĞůĂĂƵƚŽĨĂŐŝĂ͕;<ŽŶŐĂƌĂĞƚĂů͕͘ϮϬϭϮ͖^ĐŚĞƌǌͲ^ŚŽƵǀĂů
Ğƚ Ăů͕͘ ϮϬϬϳͿ͘ Ɛş͕ ŝŶŝĐŝĂůŵĞŶƚĞ͕ ƚƌĂďĂũĂŵŽƐ ĐŽŶ ,ϮKϮ͕ ƵŶĂ ƉŽƚĞŶƚĞ ZK͘ ^Ğ ƚƌĂƚĂ ĚĞ͕
ĐŽŵŽŝŶĚŝĐĄďĂŵŽƐĐŽŶĂŶƚĞƌŝŽƌŝĚĂĚ͕ĞůƉƌŝŶĐŝƉĂůŵĞƚĂďŽůŝƚŽƉƌŽĚƵĐŝĚŽĞŶůĂŽǆŝĚĂĐŝſŶ
ĚĞůĂϲͲK,͘
ŶĐŽŶĚŝĐŝŽŶĞƐďĂƐĂůĞƐ͕ůĂƐĐĠůƵůĂƐƉƌĞƐĞŶƚĂďĂŶƵŶŶƷŵĞƌŽĚĞĂƵƚŽĨĂŐŽƐŽŵĂƐ
ŝŐƵĂůŽŝŶĨĞƌŝŽƌĂĐŝŶĐŽ͘^ŝŶĞŵďĂƌŐŽ͕ƚƌĂƐůĂĂĚŝĐŝſŶĚĞ,ϮKϮ͕ƐĞĐŽŶƐƚĂƚſƵŶĂƵŵĞŶƚŽ
ƐŝŐŶŝĨŝĐĂƚŝǀŽ ĞŶ ůĂ ĐĂŶƚŝĚĂĚ ĚĞ ĂƵƚŽĨĂŐŽƐŽŵĂƐ ƉƌĞƐĞŶƚĞƐ ĞŶ ŶƵĞƐƚƌĂƐ ĐĠůƵůĂƐ
ƚƌĂŶƐĨĞĐƚĂĚĂƐ͘ ƐƚŽƐĚĂƚŽƐ ĐŽƌƌŽďŽƌĂŶ ůŽƐ ŽďƚĞŶŝĚŽƐ ƉŽƌ ŽƚƌŽƐ ŐƌƵƉŽƐ ĂŶƚĞƌŝŽƌŵĞŶƚĞ͕
ĞŶ ƚƌĂďĂũŽƐ ƌĞĂůŝǌĂĚŽƐ ĞŶ ĚŝĨĞƌĞŶƚĞƐ ŵŽĚĞůŽƐ ĐĞůƵůĂƌĞƐ͕ ;,Ă Ğƚ Ăů͕͘ ϮϬϭϮ͖ >ĞĞ Ğƚ Ăů͕͘
ϮϬϬϵ͖>ƵŽĞƚĂů͕͘ϮϬϭϭͿ͘ĚĞŵĄƐ͕ĞŶůĂůşŶĞĂĚĞŶƵĞƐƚƌŽƐƌĞƐƵůƚĂĚŽƐ͕ĞŶŽƚƌŽĂƌƚşĐƵůŽ͕ƐĞ
ĐŽŶĐůƵǇĞ ƋƵĞ ůĂ ĂĐĐŝſŶ ĚĞ ,ϮKϮ ĞƐ ĞƐĞŶĐŝĂů ĞŶ Ğů ƉƌŽĐĞƐŽ ĚĞ ĨŽƌŵĂĐŝſŶ ĚĞ ůŽƐ
ĂƵƚŽĨĂŐŽƐŽŵĂƐ Ǉ͕ ƉŽƌ ĞŶĚĞ͕ ĞŶ ůĂ ĚĞŐƌĂĚĂĐŝſŶ ĐĞůƵůĂƌ ŵĞĚŝĂŶƚĞ ĂƵƚŽĨĂŐŝĂ͕ ;^ĐŚĞƌǌͲ
^ŚŽƵǀĂůĞƚĂů͕͘ϮϬϬϳͿ͘
ĚŝĐŝŽŶĂůŵĞŶƚĞ͕ ƌĞƉĞƚŝŵŽƐ Ğů ŵŝƐŵŽ ĞǆƉĞƌŝŵĞŶƚŽ ƵƐĂŶĚŽ͕ ĞŶ ĞƐƚĞ ĐĂƐŽ͕ ϲͲ
K, ĐŽŵŽ ƉŽƐŝďůĞ ĂŐĞŶƚĞ ŝŶĚƵĐƚŽƌ ĚĞ ůĂ ĂƵƚŽĨĂŐŝĂ͘ Ğ ŶƵĞǀŽ ŽďƐĞƌǀĂŵŽƐ͕ ĐŽŵŽ
ϲϵ
ĐĂďşĂ ĞƐƉĞƌĂƌ͕ ƋƵĞ Ğů ŶƷŵĞƌŽ ĚĞ ĂƵƚŽĨĂŐŽƐŽŵĂƐ ƉƌĞƐĞŶƚĞƐ ĞŶ ŶƵĞƐƚƌĂƐ ĐĠůƵůĂƐ
ƚƌĂŶƐĨĞĐƚĂĚĂƐ ĂƵŵĞŶƚĂďĂ ĚĞ ƵŶ ŵŽĚŽ ĐŽŶƐŝĚĞƌĂďůĞ͕ ĚĞ ƵŶ ŵŽĚŽ ĚĞƉĞŶĚŝĞŶƚĞ ĚĞů
ƚŝĞŵƉŽĚĞƚƌĂƚĂŵŝĞŶƚŽǇĚĞůĂĚŽƐŝƐĚĞůĂŶĞƵƌŽƚŽǆŝŶĂƵƚŝůŝǌĂĚĂ͘Ɛş͕ĐƵĂŶĚŽĂŹĂĚşĂŵŽƐ
ůĂ ŶĞƵƌŽƚŽǆŝŶĂ Ă ƵŶĂ ĐŽŶĐĞŶƚƌĂĐŝſŶ ĚĞ ϱϬ ђD͕ ůĂ ŵŝƐŵĂ ƵƐĂĚĂ ĞŶ Ğů ƌĞƐƚŽ ĚĞ
ĞǆƉĞƌŝŵĞŶƚŽƐ ĚŝƐĐƵƚŝĚŽƐ ĞŶ ĞƐƚĞ ƚƌĂďĂũŽ͕ Ğů ĞĨĞĐƚŽ ĐŽŵĞŶǌĂďĂ Ă ƐĞƌ ĞǀŝĚĞŶƚĞ ƚƌĂƐ
ŶƵĞǀĞ ŚŽƌĂƐ ĚĞ ƚƌĂƚĂŵŝĞŶƚŽ͕ ƐŝĞŶĚŽ ŵƵǇ ƐŝŐŶŝĨŝĐĂƚŝǀŽ ĐƵĂŶĚŽ Ğů ƚŝĞŵƉŽ ƐĞ
ŝŶĐƌĞŵĞŶƚĂďĂŚĂƐƚĂĚŽĐĞŚŽƌĂƐ͘
WŽƌ ƐƵ ƉĂƌƚĞ͕ ůŽƐ ĚĂƚŽƐ ĚĞ tĞƐƚĞƌŶ ůŽƚƚŝŶŐ ĐŽƌƌŽďŽƌĂƌŽŶ ůĂƐ ŽďƐĞƌǀĂĐŝŽŶĞƐ
ĂŶƚĞƌŝŽƌĞƐ͘ŶĞƐƚĞĐĂƐŽ͕ĚĞĐŝĚŝŵŽƐĞƐƚƵĚŝĂƌůĂƉƌĞƐĞŶĐŝĂƌĞůĂƚŝǀĂĚĞůĂƐĚŽƐĨŽƌŵĂƐĚĞ
ůĂ ƉƌŽƚĞşŶĂ >ϯ͘ Ɛş͕ ĞŶ ĐŽŶĚŝĐŝŽŶĞƐ ďĂƐĂůĞƐ͕ ůĂ ŵĂǇŽƌşĂ ĚĞ >ϯ ĂƉĂƌĞĐşĂ ĐŽŵŽ >ϯͲ/͕
ŵŝĞŶƚƌĂƐƋƵĞ͕ƚƌĂƐĚŽĐĞŚŽƌĂƐĚĞƚƌĂƚĂŵŝĞŶƚŽĐŽŶϲͲK,͕ůĂĨŽƌŵĂĐŝſŶĚĞ>ϯͲ//ĞƌĂ
ĞǀŝĚĞŶƚĞĞŶŶƵĞƐƚƌŽƐĐƵůƚŝǀŽƐĐĞůƵůĂƌĞƐĚĞ^,Ͳ^zϱz͕ƐŝĞŶĚŽƐƵƉƌĞƐĞŶĐŝĂƐƵƉĞƌŝŽƌĂůĂ
ĚĞůĂĨŽƌŵĂƐŝŶĐŽŶũƵŐĂƌĚĞůĂƉƌŽƚĞşŶĂ͕ĞƐƚŽĞƐ͕>ϯͲ/͘Ɛş͕ůĂĂĐƚŝǀĂĐŝſŶĚĞůĂŵŝƚŽĨĂŐŝĂ
ƋƵĞŽďƐĞƌǀĂŵŽƐĞŶŶƵĞƐƚƌŽƐĐƵůƚŝǀŽƐĐĞůƵůĂƌĞƐ͕ƐĞĐƵŶĚĂƌŝĂĂůĂĂĚŝĐŝſŶĚĞϲͲK,͕ŚĂ
ƐŝĚŽ ŽďƐĞƌǀĂĚĂ ƉŽƌ ŽƚƌŽ ŐƌƵƉŽ ĐŽŶ ĂŶƚĞƌŝŽƌŝĚĂĚ͕ ĞŶ ƵŶ ƚƌĂďĂũŽ ĞŶ Ğů ƋƵĞ ŝŶƚĞŶƚĂŶ
ĚŝůƵĐŝĚĂƌĞůŵĞĐĂŶŝƐŵŽŵŽůĞĐƵůĂƌƋƵĞƉƌŽĚƵĐĞĞƐƚĞƉƌŽĐĞƐŽ͕;ĂŐĚĂĞƚĂů͕͘ϮϬϬϴͿ͘Ğ
ŚĞĐŚŽ͕ŚĂǇƵŶŝŶƚĞƌĞƐĂŶƚĞĞĚŝƚŽƌŝĂůĞŶĞůƋƵĞƐĞĐŽŵĞŶƚĂůĂĂĐƚŝǀĂĐŝſŶĚĞůĂĂƵƚŽĨĂŐŝĂ
ĞŶ ĚŝǀĞƌƐŽƐ ŵŽĚĞůŽƐ ĚĞ W͕ ƚĂŶƚŽ ŐĞŶĠƚŝĐŽƐ ĐŽŵŽ ĨĂƌŵĂĐŽůſŐŝĐŽƐ͕ ;'ŽŶǌĂůĞǌͲWŽůŽ Ğƚ
Ăů͕͘ϮϬϭϯͿ͘
ŶůĂďŝďůŝŽŐƌĂĨşĂ͕ĞŶĐŽŶƚƌĂŵŽƐƵŶƚƌĂďĂũŽĞŶĞůƋƵĞƋƵĞĚſĚĞŵŽƐƚƌĂĚŽƋƵĞůĂ
ĚŝƐƚĂŶĐŝĂ ĞŶƚƌĞ ůŽƐ ĂƵƚŽĨĂŐŽƐŽŵĂƐ Ǉ ůĂ ŵŝƚŽĐŽŶĚƌŝĂ ĚŝƐŵŝŶƵşĂ ĐŽŶƐŝĚĞƌĂďůĞŵĞŶƚĞ
ĐƵĂŶĚŽ ƐĞ ĂĐƚŝǀĂďĂ ůĂ ŵŝƚŽĨĂŐŝĂ͕ ůůĞŐĂŶĚŽ ŝŶĐůƵƐŽ Ă ĐŽůŽĐĂůŝǌĂƌ ĂŵďŽƐ ĞůĞŵĞŶƚŽƐ͕
;,ĂŵĂƐĂŬŝĞƚĂů͕͘ϮϬϭϯͿ͘WŽƌƚĂŶƚŽ͕ĂĐŽŶƚŝŶƵĂĐŝſŶ͕ĚĞĐŝĚŝŵŽƐĞƐƚƵĚŝĂƌĞƐƚĞƉĂƌĄŵĞƚƌŽ
ĞŶŶƵĞƐƚƌŽƐĐƵůƚŝǀŽƐĐĞůƵůĂƌĞƐƚƌĂƚĂĚŽƐĐŽŶϲͲK,͕ĐŽŵƉƌŽďĂŶĚŽƋƵĞ͕ĞĨĞĐƚŝǀĂŵĞŶƚĞ͕
ůĂ ĐŝƚĂĚĂ ĚŝƐƚĂŶĐŝĂ ĚĞĐƌĞĐşĂ ŶŽƚŽƌŝĂŵĞŶƚĞ͕ ĞŶ ůŽƐ ĐƵůƚŝǀŽƐ ĐĞůƵůĂƌĞƐ ĚĞ ^,Ͳ^zϱz͕ ĞŶ
ĐŽŵƉĂƌĂĐŝſŶĐŽŶůŽƋƵĞƐƵĐĞĚşĂĞŶĐŽŶĚŝĐŝŽŶĞƐĐŽŶƚƌŽů͘Ɛş͕ĚĞĞƐƚŽƐĚĂƚŽƐƐĞĞǆƚƌĂĞůĂ
ĐŽŶĐůƵƐŝſŶĚĞƋƵĞůĂĨŽƌŵĂĐŝſŶĚĞůŽƐĂƵƚŽĨĂŐŽƐŽŵĂƐŽĐƵƌƌĞůĞũŽƐĚĞůĐŝƚĂĚŽŽƌŐĄŶƵůŽ͘
WŽƐƚĞƌŝŽƌŵĞŶƚĞ͕ ĞƐƚĂƐ ĞƐƚƌƵĐƚƵƌĂƐ ŵŝŐƌĂŶ ŚĂĐŝĂ ůĂ ŵŝƚŽĐŽŶĚƌŝĂ͕ ĚŽŶĚĞ ĐŽůŽĐĂůŝǌĂŶ
ĂŵďŽƐ ĞůĞŵĞŶƚŽƐ͕ Ă ƚŝĞŵƉŽƐ ƚĂƌĚşŽƐ ƚƌĂƐ Ğů ƚƌĂƚĂŵŝĞŶƚŽ͕ ĐŽŵŽ ĞƐ Ğů ĐĂƐŽ ĚĞ ĚŽĐĞ
ŚŽƌĂƐ͘
ϳϬ
ƉŽǇĂŶĚŽ ĞƐƚĂƐ ŽďƐĞƌǀĂĐŝŽŶĞƐ͕ ŚĂǇ ŽƚƌŽ ƚƌĂďĂũŽ ĞŶ Ğů ƋƵĞ ƐĞ ƌĞƉŽƌƚſ ƋƵĞ ůŽƐ
ĐŽŵƉŽŶĞŶƚĞƐĐŝƚŽƉůĂƐŵĄƚŝĐŽƐƐĞĚĞŐƌĂĚĂďĂŶĚƵƌĂŶƚĞĞůƉĞƌŝŽĚŽŝŶŝĐŝĂůĚĞƉƌŝǀĂĐŝſŶĚĞ
ŶƵƚƌŝĞŶƚĞƐ͕ ĞƐƚŽ ĞƐ͕ ĞŶ ůĂƐ ƉƌŝŵĞƌĂƐ ƐĞŝƐ ŚŽƌĂƐ͕ ŵŝĞŶƚƌĂƐ ƋƵĞ͕ ůĂƐ ŵŝƚŽĐŽŶĚƌŝĂƐ͕
ŶĞĐĞƐŝƚĂďĂŶ ŵĄƐ ƚŝĞŵƉŽ ƉĂƌĂ ƐƵĨƌŝƌ ĞƐƚĞ ƉƌŽĐĞƐŽ͕ ;<ƌŝƐƚĞŶƐĞŶ Ğƚ Ăů͕͘ ϮϬϬϴͿ͘ ĚĞŵĄƐ͕
ĐƵĂŶĚŽ ĞŶ ŶƵĞƐƚƌŽƐ ĞǆƉĞƌŝŵĞŶƚŽƐ ĐŽƚĞũĄďĂŵŽƐ ůĂ ĚŝƐƚĂŶĐŝĂ ĞǆŝƐƚĞŶƚĞ ĞŶƚƌĞ ůŽƐ
ĂƵƚŽĨĂŐŽƐŽŵĂƐ Ǉ ůĂƐ ŵŝƚŽĐŽŶĚƌŝĂƐ ĐŽŶ ůĂƐ ĚŝĨĞƌĞŶƚĞƐ ŵŽƌĨŽůŽŐşĂƐ ĚĞů ŽƌŐĄŶƵůŽ͕
ĐŽŵƉƌŽďĄďĂŵŽƐ ƋƵĞ͕ ĐƵĂŶĚŽ ĞƐƚĂ ƷůƚŝŵĂ ĞƌĂ ĚĞ ƚŝƉŽ ƉƵŶƚĞĂĚŽ͕ ůŽƐ ĂƵƚŽĨĂŐŽƐŽŵĂƐ
ĞƐƚĂďĂŶƐŝŐŶŝĨŝĐĂƚŝǀĂŵĞŶƚĞŵĄƐĐĞƌĐĂĚĞůŽƐŽƌŐĄŶƵůŽƐƋƵĞĐƵĂŶĚŽĞƌĂĂůĂƌŐĂĚĂ͘ƐƚŽƐ
ĚĂƚŽƐ ŝŶĐŝĚĞŶ ĞŶ ůĂ ŚŝƉſƚĞƐŝƐ ĚĞů ĐŽŶƚƌŽů ĚĞ ĐĂůŝĚĂĚ ŵŝƚŽĐŽŶĚƌŝĂů͕ ĂƉƵŶƚĂĚĂ ƉŽƌ ŽƚƌŽƐ
ŐƌƵƉŽƐ͕ ůĂ ĐƵĂů ƉŽƐƚƵůĂ ƋƵĞ ůĂƐ ŵŝƚŽĐŽŶĚƌŝĂƐ ƋƵĞ ƉƌĞƐĞŶƚĂŶ ĚŝƐĨƵŶĐŝŽŶĞƐ ĨƵŶĐŝŽŶĂůĞƐ
ƐŽŶ ƐƵƐĐĞƉƚŝďůĞƐ ĚĞ ƐĞƌ ĚĞŐƌĂĚĂĚĂƐ͘ Ŷ ĞƐĞ ĞƐĐĞŶĂƌŝŽ͕ ůĂ ĞůŽŶŐĂĐŝſŶ ŵŝƚŽĐŽŶĚƌŝĂů
ĂĐƚƵĂƌşĂ ĐŽŵŽ ƵŶ ŵĞĐĂŶŝƐŵŽ ƉƌŽƚĞĐƚŽƌ ĐŽŶƚƌĂ ůĂ ŵŝƚŽĨĂŐŝĂ͕ ;'ŽŵĞƐ Ğƚ Ăů͕͘ ϮϬϭϭ͖
ZĂŵďŽůĚĞƚĂů͕͘ϮϬϭϭͿ͘
ĂŵďŝĂŶĚŽĚĞŵŽĚĞůŽĐĞůƵůĂƌ͕ĞŶĞůĐĂƐŽĚĞůĚĞ,͕ƚĂŵďŝĠŶĂƋƵşĐŽŶƐƚĂƚĂŵŽƐ
ƵŶŝŶĐƌĞŵĞŶƚŽĐŽŶƐŝĚĞƌĂďůĞĞŶůĂƚĂƐĂĚĞĂƵƚŽĨĂŐŝĂ͕ŽďƐĞƌǀĂĚĂĂƚƌĂǀĠƐĚĞůĂƵŵĞŶƚŽ
ĞŶĞůŶƷŵĞƌŽĚĞĂƵƚŽĨĂŐŽƐŽŵĂƐ͕ƚƌĂƐĞůƚƌĂƚĂŵŝĞŶƚŽĐŽŶϯEW͘ĚŝĐŝŽŶĂůŵĞŶƚĞ͕ĐƵĂŶĚŽ
ĞƐƚƵĚŝĂŵŽƐ Ğů ƉƌŽĐĞƐŽ ŵĞĚŝĂŶƚĞ ƚĠĐŶŝĐĂƐ ĚĞ tĞƐƚĞƌŶ ůŽƚƚŝŶŐ͕ ůŽƐ ƌĞƐƵůƚĂĚŽƐ ŶŽƐ
ŝŶĚŝĐĂƌŽŶ͕ ĚĞ ŶƵĞǀŽ͕ ƋƵĞ ůĂ ĨŽƌŵĂ ĐŽŶũƵŐĂĚĂ ĚĞ >ϯ͕ ĞƐƚŽ ĞƐ͕ >ϯͲ//͕ ĂƉĂƌĞĐşĂ ĞŶ
ŶƵĞƐƚƌĂƐŵĞŵďƌĂŶĂƐƚƌĂƐĞůƚƌĂƚĂŵŝĞŶƚŽĚĞůŽƐĐƵůƚŝǀŽƐĐĞůƵůĂƌĞƐĐŽŶϯEW͘
ĚĞŵĄƐ͕ ƉĂƌĂ ŝŶĐŝĚŝƌ ŵĄƐ ĞŶ Ğů ĞƐƚƵĚŝŽ ĚĞ ůĂ ĂĐƚŝǀĂĐŝſŶ ĚĞ ůĂ ĂƵƚŽĨĂŐŝĂ ĞŶ
ŶƵĞƐƚƌŽŵŽĚĞůŽĚĞ,͕ĚĞĐŝĚŝŵŽƐĞŶĞƐƚĞĐĂƐŽĐƵĂŶƚŝĨŝĐĂƌůĂĐĂŶƚŝĚĂĚĚĞƉƌŽƚĞşŶĂƉϲϮ
ƉƌĞƐĞŶƚĞĞŶŶƵĞƐƚƌŽƐĐƵůƚŝǀŽƐ͕ƚƌĂƐůĂĂĚŝĐŝſŶĚĞůŝŶŚŝďŝĚŽƌĚĞůĐŽŵƉůĞũŽ//ĚĞůĂd͘>Ă
ĐŝƚĂĚĂ ƉƌŽƚĞşŶĂ͕ ĐŽŵŽ ŝŶĚŝĐĄďĂŵŽƐ ĞŶ ůĂ ŝŶƚƌŽĚƵĐĐŝſŶ ĚĞ ĞƐƚĞ ƚƌĂďĂũŽ͕ ĞƐ ĚĞŐƌĂĚĂĚĂ
ĐƵĂŶĚŽ ůĂ ĂƵƚŽĨĂŐŝĂ ƐĞ ĂĐƚŝǀĂ͘ Ɛş͕ ĞŶ ƐŝŶƚŽŶşĂ ĐŽŶ ůŽƐ ĚĂƚŽƐ ŽďƚĞŶŝĚŽƐ Ă ƉĂƌƚŝƌ ĚĞů
ĞƐƚƵĚŝŽ ĚĞ >ϯ͕ ĞŶ ůŽƐ ůŝƐĂĚŽƐ ĐĞůƵůĂƌĞƐ ƋƵĞ ĐŽŶƚĞŶşĂŶ ϯEW ŽďƐĞƌǀĄďĂŵŽƐ ƵŶĂ
ĚŝƐŵŝŶƵĐŝſŶĐŽŶƐŝĚĞƌĂďůĞĚĞůĂĐĂŶƚŝĚĂĚĚĞƉϲϮ͘
WŽƌƚĂŶƚŽ͕ĞŶĞƐƚĞƐĞŐƵŶĚŽŵŽĚĞůŽĐĞůƵůĂƌ͕ůĂŵŝƚŽĨĂŐŝĂƚĂŵďŝĠŶĞƐƚĄĂĐƚŝǀĂĚĂ͘
ƐƚŽƐĚĂƚŽƐ͕ƐŝŐƵĞŶůĂůşŶĞĂĚĞůŽƐƉƵďůŝĐĂĚŽƐƉŽƌŽƚƌŽŐƌƵƉŽ͕ĞŶůŽƐƋƵĞĚĞŵŽƐƚƌĂďĂŶ͕
Ă ƚƌĂǀĠƐ ĚĞů ƵƐŽ ĚĞ ƚĠĐŶŝĐĂƐ ĚĞ ĞƐƚĞƌŽƚĂǆŝĂ͕ ƋƵĞ͕ ĞŶ ůĂ ǌŽŶĂ ĚĞů ĞƐƚƌŝĂĚŽ ĐĞƌĞďƌĂů ĚĞ
ƌĂƚĂƐƚƌĂƚĂĚĂƐĐŽŶϯEW͕ƐĞŝŶĚƵĐşĂĞůĐŝƚĂĚŽƉƌŽĐĞƐŽ͕;ŚĂŶŐĞƚĂů͕͘ϮϬϬϵͿ͘
ϳϭ
>ŽƐ ƌĞƐƵůƚĂĚŽƐ ĂƋƵş ĞǆƉƵĞƐƚŽƐ ƌĞůĂƚŝǀŽƐ Ă ůŽƐ ĞĨĞĐƚŽƐ ĚĞů ĐŝƚĂĚŽ ŝŶŚŝďŝĚŽƌ ĚĞů
ĐŽŵƉůĞũŽ//ĚĞůĂdƐŽďƌĞůĂĂƵƚŽĨĂŐŝĂŚĂŶƐŝĚŽŽďũĞƚŽĚĞƵŶŝŶƚĞƌĞƐĂŶƚĞĐŽŵĞŶƚĂƌŝŽ
ĂŶƵĞƐƚƌŽĂƌƚşĐƵůŽ͕ƉƵďůŝĐĂĚŽĞŶůĂŵŝƐŵĂƌĞǀŝƐƚĂƋƵĞĞůƚƌĂďĂũŽ͘ŶĠů͕ƐĞŝŶĐŝĚĞĞŶůĂ
ŝŵƉůŝĐĂĐŝſŶĚĞůĂŵŝƚŽĐŽŶĚƌŝĂĞŶůŽƐĐĂŵďŝŽƐĞŶůĂŵŝƚŽĐŽŶĚƌŝĂƉƌŽĚƵĐŝĚŽƐƉŽƌϯEWǇ
ƐĞ ƉƌŽƉŽŶĞŶ ŶƵĞǀĂƐ ƉƌĞŐƵŶƚĂƐ͕ ƋƵĞ ĂďƌĞŶ ůĂ ƉƵĞƌƚĂ Ă ŶƵĞǀŽƐ ƚƌĂďĂũŽƐ ĞŶ Ğů ŵŝƐŵŽ
ŵŽĚĞůŽ͘ Ɛş͕ ƉŽƌ ĞũĞŵƉůŽ͕ ůŽƐ ĂƵƚŽƌĞƐ ĚĞů ĐŝƚĂĚŽ ĐŽŵĞŶƚĂƌŝŽ ĐŽŶƐŝĚĞƌĂŶ ŽƉŽƌƚƵŶŽ
ŝŶĐŝĚŝƌ ĞŶ Ğů ŵĞĐĂŶŝƐŵŽ ĞǆĂĐƚŽ Ă ƚƌĂǀĠƐ ĚĞů ĐƵĂů ϯEW ŝŶĚƵĐĞ ĂƵƚŽĨĂŐŝĂ͕ Ž ĞŶ ůĂ
ƉŽƐŝďŝůŝĚĂĚĚĞůĂĞǆŝƐƚĞŶĐŝĂĚĞŚŝƉŽƚĠƚŝĐŽƐŵĞĐĂŶŝƐŵŽƐƌĞŐƵůĂĚŽƌĞƐĞŶůĂĂƵƚŽĨĂŐŝĂǇĞŶ
ůĂĂƉŽƉƚŽƐŝƐ͕;'ŽŶǌĂůĞǌͲWŽůŽĞƚĂů͕͘ϮϬϭϮͿ͘
dĂŵďŝĠŶ ĞŶ ĞƐƚĞ ĐĂƐŽ ƋƵŝƐŝŵŽƐ ĐŽŵƉƌŽďĂƌ Ğů ĞĨĞĐƚŽ ƋƵĞ DĚŝǀŝͲϭ ƉƌŽĚƵĐşĂ
ƐŽďƌĞůŽƐŝŶĐƌĞŵĞŶƚŽƐŽďƐĞƌǀĂĚŽƐĞŶůĂƚĂƐĂĚĞŵŝƚŽĨĂŐŝĂ͘^ŝŶĞŵďĂƌŐŽ͕ĚĞďŝĚŽĂůŽƐ
ƌĞƐƵůƚĂĚŽƐŽďƚĞŶŝĚŽƐŚĂƐƚĂĞůŵŽŵĞŶƚŽ͕ůŽƐĐƵĂůĞƐŝŶĚŝĐĂďĂŶĐůĂƌĂŵĞŶƚĞƋƵĞƌƉϭŶŽ
ĞƐƚĂďĂŝŵƉůŝĐĂĚŽĞŶůĂƐĚŝƐĨƵŶĐŝŽŶĞƐŵŝƚŽĐŽŶĚƌŝĂůĞƐƉƌĞƐĞŶƚĞƐĞŶŶƵĞƐƚƌŽŵŽĚĞůŽĚĞ
,͕ ŶŽ ĐƌĞşŵŽƐ ŶĞĐĞƐĂƌŝŽ ŚĂĐĞƌ ĞƐƚĞ ĞƐƚƵĚŝŽ ĞŶ ůŽƐ ĐƵůƚŝǀŽƐ ƚƌĂƚĂĚŽƐ ĐŽŶ ϯEW͕
ůŝŵŝƚĄŶĚŽŶŽƐĞǆĐůƵƐŝǀĂŵĞŶƚĞĂĂƋƵĞůůŽƐĞŶůŽƐƋƵĞŚĂďşĂŵŽƐĂŹĂĚŝĚŽϲͲK,͘
Ɛş͕ ĞŶ Ğů ĐĂƐŽ ĚĞů ŵŽĚĞůŽ ĚĞ W͕ ĐŽƌƌŽďŽƌĂŵŽƐ ƋƵĞ͕ ĞĨĞĐƚŝǀĂŵĞŶƚĞ͕ ĐƵĂŶĚŽ
ĞƐƚĂŵŽůĠĐƵůĂĞƌĂĂŹĂĚŝĚĂĂŶƵĞƐƚƌŽƐĐƵůƚŝǀŽƐĐĞůƵůĂƌĞƐĐŽŶũƵŶƚĂŵĞŶƚĞĐŽŶϲͲK,͕ůĂ
ĨŽƌŵĂĐŝſŶ ĚĞ >ϯͲ// ĚĞĐƌĞĐşĂ ĐŽŶƐŝĚĞƌĂďůĞŵĞŶƚĞ͕ ƌĞƐƉĞĐƚŽ Ă ůŽƐ ǀĂůŽƌĞƐ ŽďƚĞŶŝĚŽƐ
ĐƵĂŶĚŽĞůƚƌĂƚĂŵŝĞŶƚŽƐĞƌĞĂůŝǌĂďĂĞǆĐůƵƐŝǀĂŵĞŶƚĞĐŽŶůĂŶĞƵƌŽƚŽǆŝŶĂ͘
ůĂ ǀŝƐƚĂ ĚĞ ĞƐƚŽƐ ĚĂƚŽƐ͕ ƉŽĚĞŵŽƐ ĂĨŝƌŵĂƌ ƋƵĞ ůĂ ŝŶĚƵĐĐŝſŶ ĚĞ ůĂ ĂƵƚŽĨĂŐŝĂ
ƐĞĐƵŶĚĂƌŝĂ Ă ůĂ ĂĚŝĐŝſŶ ĚĞ ϲͲK, ƉĂƌĞĐĞ ƐĞƌ ĐŽŶƐĞĐƵĞŶĐŝĂ ĚĞ ůĂ ĨƌĂŐŵĞŶƚĂĐŝſŶ
ŵŝƚŽĐŽŶĚƌŝĂů͕ ĚĞƉĞŶĚŝĞŶƚĞ͕ ĞŶ Ğů ĐĂƐŽ ĚĞ ĞƐƚĂ ŶĞƵƌŽƚŽǆŝŶĂ͕ ĚĞ ůĂ ƚƌĂƐůŽĐĂĐŝſŶ Ăů
ŽƌŐĄŶƵůŽĚĞƌƉϭ͘ƐƚŽƐƌĞƐƵůƚĂĚŽƐĐŽŶĐƵĞƌĚĂŶĐŽŶůŽƐŽďƚĞŶŝĚŽƐƉŽƌŽƚƌŽŐƌƵƉŽ͕ĞŶ
ůŽƐƋƵĞƐĞĂĨŝƌŵĂƋƵĞůŽƐĐŝƚĂĚŽƐĐĂŵďŝŽƐĞŶůĂĨŽƌŵĂĚĞůŽƌŐĄŶƵůŽ͕ƐĞĐƵŶĚĂƌŝŽƐĂůĂ
ŵŝŐƌĂĐŝſŶĂůŽƌŐĄŶƵůŽĚĞƌƉϭ͕ĐŽŶƐƚŝƚƵǇĞŶƵŶƌĞƋƵŝƐŝƚŽƉƌĞǀŝŽŶĞĐĞƐĂƌŝŽƉĂƌĂƋƵĞƐĞ
ƉƌŽĚƵǌĐĂ ĞƐƚĞ ƉƌŽĐĞƐŽ͕ ;dǁŝŐ Ğƚ Ăů͕͘ ϮϬϬϴͿ͘ >Ă ũƵƐƚŝĨŝĐĂĐŝſŶ ƉĂƌĂ ĞƐƚĂ ƌĞĂůŝĚĂĚ ƐĞ
ĞŶĐƵĞŶƚƌĂ͕ ĞŶ ƉĂƌƚĞ͕ ĞŶ Ğů ŚĞĐŚŽ ĨşƐŝĐŽ ĚĞ ƋƵĞ͕ ĐƵĂŶƚŽ ŵĞŶŽƌ ƐĞĂ Ğů ƚĂŵĂŹŽ ĚĞ ůĂ
ŵŝƚŽĐŽŶĚƌŝĂ ƋƵĞ ǀĂ Ă ƐĞƌ ĞůŝŵŝŶĂĚĂ͕ ŵĞŶŽƌ ĐĂŶƚŝĚĂĚ ĚĞ ĞŶĞƌŐşĂ ŶĞĐĞƐŝƚĂƌĄ ůĂ ĐĠůƵůĂ
ƉĂƌĂƌĞĂůŝǌĂƌůĂŵŝƚŽĨĂŐŝĂ͘
ϳϮ
ĚĞŵĄƐ͕ŚĂǇŵĄƐĚĂƚŽƐƋƵĞŝŶĐŝĚĞŶĞŶůĂƌĞůĂĐŝſŶĞǆŝƐƚĞŶƚĞĞŶƚƌĞůĂŵŝƚŽĨĂŐŝĂǇ
ůĂ ĨƌĂŐŵĞŶƚĂĐŝſŶ ŵŝƚŽĐŽŶĚƌŝĂů ĚĞƉĞŶĚŝĞŶƚĞ ĚĞ ƌƉϭ͘ Ɛş͕ ƉŽƌ ĞũĞŵƉůŽ͕ ƐĂďĞŵŽƐ ƋƵĞ͕
ĂŶƚĞƵŶĚĂŹŽŝŶĚƵĐŝĚŽƉŽƌƐƵƐƚĂŶĐŝĂƐŽǆŝĚĂŶƚĞƐ͕ĐŽŵŽĞƐĞůĐĂƐŽĚĞůĂƐZK͕ůĂƐĐĠůƵůĂƐ
ƉƌŽĚƵĐĞŶ͕ĂƚƌĂǀĠƐĚĞƉƌŽĐĞƐŽƐĚĞĨŝƐŝſŶ͕ŵŝƚŽĐŽŶĚƌŝĂƐŚŝũĂƐĐŽŶĚŝĨĞƌĞŶƚĞƐƉŽƚĞŶĐŝĂůĞƐ
ĚĞ ŵĞŵďƌĂŶĂ͘ ƐƚĞ ŚĞĐŚŽ ĐŽŶůůĞǀĂ ƋƵĞ͕ ĂƋƵĞůůĂƐ ĐŽŶ Ğů ƉŽƚĞŶĐŝĂů ŵĄƐ ďĂũŽ͕ ƐĞĂŶ
ŵĂƌĐĂĚĂƐ ƉĂƌĂ ůĂ ĚĞŐƌĂĚĂĐŝſŶ ŵŝƚŽĨĄŐŝĐĂ͕ ŵŝĞŶƚƌĂƐ ƋƵĞ͕ ůĂƐ ŵŝƚŽĐŽŶĚƌŝĂƐ ŵĂĚƌĞ͕
ƉĞƌŵĂŶĞǌĐĂŶŝŶƚĂĐƚĂƐ͕;'ŽŵĞƐĞƚĂů͕͘ϮϬϬϴ͖dǁŝŐĞƚĂů͕͘ϮϬϬϴͿ͘^ŝŶĞŵďĂƌŐŽ͕ĂƉĞƐĂƌĚĞ
ůĂĨƵĞƌƚĞĚĞƉĞŶĚĞŶĐŝĂƋƵĞůĂŵŝƚŽĨĂŐŝĂƉĂƌĞĐĞƚĞŶĞƌĐŽŶůĂĨŝƐŝſŶŵŝƚŽĐŽŶĚƌŝĂů͕ŚĂǇƵŶ
ŝŶƚĞƌĞƐĂŶƚĞ ƚƌĂďĂũŽ ĞŶ Ğů ƋƵĞ ƐĞ ĚĞŵƵĞƐƚƌĂ ƋƵĞ ĞƐƚĞ ƉƌŽĐĞƐŽ ĞƐ ĂƵƚſŶŽŵŽ ĐŽŶ
ƌĞƐƉĞĐƚŽĂůĂŵŝŐƌĂĐŝſŶŵŝƚŽĐŽŶĚƌŝĂůĚĞĂǆ͕;'ŽŵĞƐĞƚĂů͕͘ϮϬϭϭͿ͘
WŽƌ ƷůƚŝŵŽ͕ ĞŶ Ğů ĐĂƐŽ ĚĞ ŶƵĞƐƚƌŽ ŵŽĚĞůŽ ĚĞ ,͕ ŶŽƐ ƉĂƌĞĐŝſ ŝŶƚĞƌĞƐĂŶƚĞ
ƚĞƌŵŝŶĂƌ ĚĞ ƉĞƌĨŝůĂƌ Ğů ƉĂƉĞů ĚĞ ůĂƐ ZK ĞŶ ůĂƐ ĚŝƐĨƵŶĐŝŽŶĞƐ ŽďƐĞƌǀĂĚĂƐ͘ WĂƌĂ ĞůůŽ͕
ĞƐƚƵĚŝĂŵŽƐ ŵĄƐ ĞŶ ƉƌŽĨƵŶĚŝĚĂĚ Ğů ƉĂƉĞů ĚĞ ĞƐƚĂƐ ĞƐƉĞĐŝĞƐ ƐŽďƌĞ ůŽƐ ŝŶĐƌĞŵĞŶƚŽƐ
ŽďƐĞƌǀĂĚŽƐĞŶůĂƚĂƐĂĚĞĂƵƚŽĨĂŐŝĂ͘Ɛş͕ĂŹĂĚŝŵŽƐƚĂŵďŝĠŶĂƋƵşĂůŐƵŶŽƐĂŶƚŝŽǆŝĚĂŶƚĞƐ
Ă ůŽƐ ĐƵůƚŝǀŽƐ ĐĞůƵůĂƌĞƐ ƚƌĂŶƐĨĞĐƚĂĚŽƐ ĐŽŶ '&WͲ>ϯ͘ ŽŶĐƌĞƚĂŵĞŶƚĞ͕ ůŽƐ ĨĄƌŵĂĐŽƐ
ĞŵƉůĞĂĚŽƐ ĨƵĞƌŽŶ dDWK> Ǉ DŶdW͕ ĂŵďŽƐ ĚĞ ƚŝƉŽ ƐŝƐƚĠŵŝĐŽ͕ ĐŽŵŽ ŝŶĚŝĐĄďĂŵŽƐ
ĐŽŶ ĂŶƚĞƌŝŽƌŝĚĂĚ͘ ƐƚĂƐ ƐƵƐƚĂŶĐŝĂƐ ĨƵĞƌŽŶ ĐĂƉĂĐĞƐ ĚĞ ƉƌŽĚƵĐŝƌ ƵŶĂ ůŝŐĞƌĂ͕ ĂƵŶƋƵĞ ŶŽ
ĞƐƚĂĚşƐƚŝĐĂŵĞŶƚĞƐŝŐŶŝĨŝĐĂƚŝǀĂ͕ĚŝƐŵŝŶƵĐŝſŶĚĞůĂƚĂƐĂĚĞĂƵƚŽĨĂŐŝĂĞŶŶƵĞƐƚƌŽŵŽĚĞůŽ
ĚĞ ,͘ Ɛş͕ ůĂƐ ĐĠůƵůĂƐ ƉƌĞƐĞŶƚĂƌŽŶ ƵŶ ŶƷŵĞƌŽ ĚĞ ĂƵƚŽĨĂŐŽƐŽŵĂƐ ƐĞŶƐŝďůĞŵĞŶƚĞ
ŝŶĨĞƌŝŽƌ ĐƵĂŶĚŽ ϯEW ƐĞ ĂŹĂĚşĂ ĐŽŶũƵŶƚĂŵĞŶƚĞ ĐŽŶ ůŽƐ ĐŝƚĂĚŽƐ ĂŶƚŝŽǆŝĚĂŶƚĞƐ͕ ĞŶ
ƌĞůĂĐŝſŶĂůŽƐĞĨĞĐƚŽƐŽďƐĞƌǀĂĚŽƐĐƵĂŶĚŽƐĞĂŹĂĚşĂĠůƐŽůŽ͘
WŽƌƚĂŶƚŽ͕ĞŶĞƐƚĞŵŽĚĞůŽĐĞůƵůĂƌ͕ůĂŵŝƚŽĨĂŐŝĂĞƐƐĞĐƵŶĚĂƌŝĂĂůĂĨŽƌŵĂĐŝſŶǇĂ
ůĂ ĂƉĞƌƚƵƌĂ ĚĞů WWdD͘ Ɛ ƉŽƌ ĞůůŽ ƋƵĞ ĞƐƚĞ ƉƌŽĐĞƐŽ ĞƐ ŝŶĚĞƉĞŶĚŝĞŶƚĞ ĚĞ ůŽƐ
ŵĞĐĂŶŝƐŵŽƐĚĞĨŝƐŝſŶŵŝƚŽĐŽŶĚƌŝĂů͕ĐŽŵŽƐĞĐŽŶƐƚĂƚĂƉŽƌůĂĂƵƐĞŶĐŝĂĚĞŵŝŐƌĂĐŝſŶĚĞ
ƌƉϭƋƵĞŝŶĚŝĐĄďĂŵŽƐĐŽŶĂŶƚĞƌŝŽƌŝĚĂĚ͘ĚŝĐŝŽŶĂůŵĞŶƚĞ͕ƚĂŵďŝĠŶĞŶĞƐƚĞŵŽĚĞůŽ͕ůĂƐ
ZK͕ũƵŶƚŽĐŽŶĞůĐŝƚĂĚŽWWdD͕ƉŽĚƌşĂŶŵĞĚŝĂƌ͕ĂůŵĞŶŽƐƉĂƌĐŝĂůŵĞŶƚĞ͕ůĂĂĐƚŝǀĂĐŝſŶ
ĚĞ ůĂ ĂƵƚŽĨĂŐŝĂ͕ ǇĂ ƋƵĞ ĞƐƚĂ ƷůƚŝŵĂ ƉƌĞĐĞĚĞ ƚĞŵƉŽƌĂůŵĞŶƚĞ Ă ůĂ ĂƉŽƉƚŽƐŝƐ͘
ŽƌƌŽďŽƌĂŶĚŽ ĞƐƚĂƐ ŽďƐĞƌǀĂĐŝŽŶĞƐ͕ ƐĞ ĞŶĐƵĞŶƚƌĂŶ ůŽƐ ĚĂƚŽƐ ŽďƚĞŶŝĚŽƐ ĞŶ ŶƵĞƐƚƌŽ
ƚƌĂďĂũŽ Ǉ ĞǆƉƵĞƐƚŽƐ ĐŽŶ ĂŶƚĞƌŝŽƌŝĚĂĚ͕ ĞŶ ƌĞůĂĐŝſŶ Ăů ƵƐŽ ĚĞ ĂŶƚŝŽǆŝĚĂŶƚĞƐ ĞŶ ůŽƐ
ĐƵůƚŝǀŽƐĐĞůƵůĂƌĞƐƚƌĂƚĂĚŽƐĐŽŶϯEW͘
ϳϯ
ϳϰ
s/͘ŽŶĐůƵƐŝŽŶĞƐ
Ǥ
•
•
•
•
•
•
ϲͲK,͕ ƵŶ ĐŽŶŽĐŝĚŽ ĂŐĞŶƚĞ ŝŶĚƵĐƚŽƌ ĚĞ ůĂ W͕ ĂĐƚŝǀĂ ůĂ ĨŝƐŝſŶ ŵŝƚŽĐŽŶĚƌŝĂů͕
ĚĞƉĞŶĚŝĞŶƚĞ ĚĞ ƌƉϭ Ǉ ĞŶ ůĂ ƋƵĞ ĂǆũƵĞŐĂ ƵŶ ŝŵƉŽƌƚĂŶƚĞ ƉĂƉĞů͘ ĐŽŶƐĞĐƵĞŶĐŝĂ ĚĞ
ĞƐƚĞƉƌŽĐĞƐŽ͕ůĂƐŵŝƚŽĐŽŶĚƌŝĂƐĐĂŵďŝĂŶĚƌĄƐƚŝĐĂŵĞŶƚĞƐƵŵŽƌĨŽůŽŐşĂǇůĂŵŝƚŽĨĂŐŝĂƐĞ
ĂĐƚŝǀĂ͘
>Ă ĐĂƵƐĂ ĚĞ ĞƐƚŽƐ ĞĨĞĐƚŽƐ ŽďƐĞƌǀĂĚŽƐ ůĂ ĞŶĐŽŶƚƌĂŵŽƐ ĞŶ Ğů ŝŶĐƌĞŵĞŶƚŽ ĞŶ ůĂ
ĐŽŶĐĞŶƚƌĂĐŝſŶĚĞZKŝŶƚƌĂĐĞůƵůĂƌĞƐƉƌŽĚƵĐŝĚĂƐƉŽƌϲͲK,͘
ů ĚĂŹŽ ŝŶĚƵĐŝĚŽ ƉŽƌ ĞƐƚĂƐ ZK ŶŽ ĞƐ ĐĂƉĂǌ ĚĞ ĂĨĞĐƚĂƌ ŐƌĂǀĞŵĞŶƚĞ Ă ůĂƐ ĞƐƚƌƵĐƚƵƌĂƐ
ŵŝƚŽĐŽŶĚƌŝĂůĞƐ͕ ĐŽŵŽ Ğů ŵƚE͕ ĚĞďŝĚŽ Ă ůĂƐ ĐŽŶĚŝĐŝŽŶĞƐ ƐƵďƚſǆŝĐĂƐ ĞŶ ůĂƐ ƋƵĞ ƐĞ
ĚĞƐĂƌƌŽůůĂƌŽŶůŽƐĞǆƉĞƌŝŵĞŶƚŽƐ͘
ů ƵƐŽ ĚĞ ĂŶƚŝŽǆŝĚĂŶƚĞƐ ĐŽŶƚƌĂƌƌĞƐƚĂ ůŽƐ ĞĨĞĐƚŽƐ ƐŽďƌĞ ůĂ ŵŽƌĨŽůŽŐşĂŵŝƚŽĐŽŶĚƌŝĂů͕ ĂƐş
ĐŽŵŽƐŽďƌĞůĂŵŝŐƌĂĐŝſŶĂůŽƌŐĄŶƵůŽĚĞĂǆǇĚĞƌƉϭ͕ĐƵĂŶĚŽĞƐƚŽƐƐŽŶŝŶĚƵĐŝĚŽƐƉŽƌ
ϲͲK,͘
ϯEW͕ĞůĐƵĂůĞƐĐĂƉĂǌĚĞƌĞŵĞĚĂƌůĂ,͕ƉƌŽĚƵĐĞ͕ĞŶŶƵĞƐƚƌŽƐĐƵůƚŝǀŽƐĐĞůƵůĂƌĞƐ͕ĞĚĞŵĂ
ŵŝƚŽĐŽŶĚƌŝĂů͕ƐĞĐƵŶĚĂƌŝŽĂůĂĨŽƌŵĂĐŝſŶĚĞůWWdD͘ƐƚĞƉŽƌŽ͕ĂƐƵǀĞǌ͕ĞƐĞůĚĞƚŽŶĂŶƚĞ
ĚĞůĂƐĚŝƐĨƵŶĐŝŽŶĞƐŽďƐĞƌǀĂĚĂƐĞŶůĂŵŽƌĨŽůŽŐşĂĚĞůŽƌŐĄŶƵůŽ͘
Ɛş ŵŝƐŵŽ͕ ůĂ ĨŽƌŵĂĐŝſŶ ĚĞů ĐŝƚĂĚŽ WWdD͕ ĂƐş ĐŽŵŽ ůŽƐ ŝŶĐƌĞŵĞŶƚŽƐ ĞŶ ůĂ
ĐŽŶĐĞŶƚƌĂĐŝſŶĚĞZKƋƵĞŝŶĚƵĐĞϯEW͕ƐŽŶůŽƐĐĂƵƐĂŶƚĞƐĚĞůĂŵŝƚŽĨĂŐŝĂŽďƐĞƌǀĂĚĂĞŶ
ĞƐƚĞŵŽĚĞůŽ͘
ϳϱ
s//͘ďƌĞǀŝĂƚƵƌĂƐ
Ǥ ϯEW͗ĐŝĚŽϯͲŶŝƚƌŽƉƚŽƉŝſŶŝĐŽ͘
ϲͲK,͗ϲͲ,ŝĚƌŽǆŝĚŽƉĂŵŝŶĂ͘
ɴ͗WĠƉƚŝĚŽĞƚĂŵŝůŽŝĚĞ͘
E͗ĐŝĚŽĞƐŽǆŝƌƌŝďŽŶƵĐůĞŝĐŽ͘
/&͗&ĂĐƚŽƌ/ŶĚƵĐƚŽƌĚĞůĂƉŽƉƚŽƐŝƐ͘
DW͗DŽŶŽĨŽƐĨĂƚŽĚĞĚĞŶŝŶĂ͘
DW<͗ϱǲͲDWWƌŽƚĞŝŶͲŝŶĂƐĂĐƚŝǀĂĚĂ͘
Ed͗ĚĞŶŝŶĂEƵĐůĞſƚŝĚŽdƌĂŶƐůŽĐĂƐĂ͘
W&ϭ͗&ĂĐƚŽƌϭĚĞůĂWƌŽƚĞĂƐĂĐƚŝǀĂĚŽƌĂĚĞůĂƉŽƉƚŽƐŝƐ͘
WW͗'ĞŶWƌĞĐƵƌƐŽƌĚĞůĂWƌŽƚĞşŶĂŵŝůŽŝĚĞ͘
ZE͗ĐŝĚŽZŝďŽŶƵĐůĞŝĐŽ͘
ZEŝ͗ĐŝĚŽZŝďŽŶƵĐůĞŝĐŽĚĞ/ŶƚĞƌĨĞƌĞŶĐŝĂ͘
ƚŐ͗WƌŽƚĞşŶĂZĞůĂĐŝŽŶĂĚĂĐŽŶůĂƵƚŽĨĂŐŝĂ͘
dW͗ĚĞŶŽƐşŶdƌŝĨŽƐĨĂƚŽ͘
ĂŬ͗ůŝŵŝŶĂĚŽƌĚĞůŽƐŶƚĂŐŽŶŝƐƚĂƐĚĞůŽƐ,ŽŵſůŽŐŽƐĚĞĐůͲϮ͘
Ăǆ͗WƌŽƚĞşŶĂyƐŽĐŝĂĚĂĂĐůͲϮ͘
͗ĐŝĚŽďŝĐŝŶĐŽŶşŶŝĐŽ͘
ĐůͲϮ͗WƌŽƚĞşŶĂĚĞĠůƵůĂƐĚĞ>ŝŶĨŽŵĂ͕ĚĞƚŝƉŽϮ͘
ĐůͲy>͗WƌŽƚĞşŶĂǆƚƌĂ'ƌĂŶĚĞĚĞĠůƵůĂƐĚĞ>ŝŶĨŽŵĂ͘
E&͗&ĂĐƚŽƌEĞƵƌŽƚƌſĨŝĐŽĞƌŝǀĂĚŽĚĞůĞƌĞďƌŽ͘
E/W͗WƌŽƚĞşŶĂĚĞϭϴ<ƋƵĞ/ŶƚĞƌĂĐĐŝŽŶĂĐŽŶĐůϮͬĚĞŶŽĐŝƌƵƐ͘
'͗ŝƚŽƐŝŶĂͲĚĞŶŝŶĂͲ'ƵĂŶŝŶĂ͘
ĂƐƉĂƐ͗ŝƐƚĞŝŶŝůͲƐƉĂƌƚĂƚŽWƌŽƚĞĂƐĂ͘
ĚŬϱ͗ŝŶĂƐĂĚĞƉĞŶĚŝĞŶƚĞĚĞŝĐůŝŶĂ͕ĚĞƚŝƉŽϱ͘
Ɛ͗ŝĐůŽƐƉŽƌŝŶĂ͘
ϳϳ
d͗ĂĚĞŶĂĚĞdƌĂŶƐƉŽƌƚĞĚĞůĞĐƚƌŽŶĞƐ͘
ǇWͲ͗ŽŵƉůĞũŽŝĐůŽĨŝůŝŶĂ͘
W<͗WƌŽƚĞŝŶͲĐŝŶĂƐĂƐŽĐŝĂĚĂĂůĂDƵĞƌƚĞ͘
&,Ͳ͗ĐĞƚĂƚŽĚĞϮǲ͕ϳǲͲĚŝĐůŽƌŽĚŝŚŝĚƌŽĨůƵŽƌĞƐĐĞşŶĂ͘
ũͲϭ͗>ŽĐƵƐũͲϭĚĞůĂŶĨĞƌŵĞĚĂĚĚĞWĂƌŬŝŶƐŽŶ͘
DDͲ&ϭϮ͗DĞĚŝŽĚĞĂŐůĞŵŽĚŝĨŝĐĂĚŽƉŽƌƵďĞůĐĐŽ͕ĐŽŶĞůĨĂĐƚŽƌ&ϭϮ͘
D^K͗ŝŵĞƚŝůƐƵůĨſǆŝĚŽ͘
ƌƉϭ͗WƌŽƚĞşŶĂƐŝŵŝůĂƌĂůĂĚŝŶĂŵŝŶĂ͕ĚĞƚŝƉŽϭ͘
ƌƉϭͲͬͲ͗ĠůƵůĂƐĚŽďůĞŶĞŐĂƚŝǀŽƉĂƌĂůĂƉƌŽƚĞşŶĂƌƉϭ͘
͗ŶĨĞƌŵĞĚĂĚĚĞůǌŚĞŝŵĞƌ͘
d͗ĐŝĚŽĞƚŝůĞŶĚŝĂŵŝŶŽƚĞƚƌĂĂĐĠƚŝĐŽ͘
'd͗ĐŝĚŽĞƚŝůĞŶŐůŝĐŽůƚĞƚƌĂĂĐĠƚŝĐŽ͘
,͗ŶĨĞƌŵĞĚĂĚĚĞ,ƵŶƚŝŶŐƚŽŶ͘
>/^͗ĞůĂƐƐŝŐůĂƐĚĞůŝŶŐůĠƐĞŶƐĂǇŽƉŽƌŝŶŵƵŶŽĂďƐŽƌĐŝſŶůŝŐĂĚŽĂĞŶǌŝŵĂƐ͘
W͗ŶĨĞƌŵĞĚĂĚĚĞWĂƌŬŝŶƐŽŶ͘
ZK͗ƐƉĞĐŝĞƐZĞĂĐƚŝǀĂƐĚĞůKǆşŐĞŶŽ͘
&^͗^ƵĞƌŽŽǀŝŶŽ&ĞƚĂů͘
&/WϮϬϬ͗ŝŶĂƐĂ&ŽĐĂůĚĞĚŚĞƐŝſŶƋƵĞ/ŶƚĞƌĂĐƚƷĂĐŽŶůĂWƌŽƚĞşŶĂĚĞϮϬϬ<Ă͘
&Zd͗dƌĂŶƐĨĞƌĞŶĐŝĂĚĞŶĞƌŐşĂƉŽƌZĞƐŽŶĂŶĐŝĂĚĞ&ůƵŽƌĞƐĐĞŶĐŝĂ͘
'ZW͗'ĂƐŽĐŝĂĚĂĂůƌĞĐĞƉƚŽƌĚĞůĄĐŝĚŽɶͲĂŵŝŶŽďƵƚşƌŝĐŽƚŝƉŽ͘
'ZZW>ϭ͗WƌŽƚĞşŶĂ^ŝŵŝůĂƌĂ'ZƉĚĞƚŝƉŽϭ
'Wϭ͗WƌŽƚĞşŶĂƐŽĐŝĂĚĂĂůĂŝĨĞƌĞŶĐŝĂĐŝſŶ/ŶĚƵĐŝĚĂƉŽƌ'ĂŶŐůŝſƐŝĚŽƐ͘
'&W͗WƌŽƚĞşŶĂ'ůĂů&ŝďƌŝůĂƌĐşĚŝĐĂ͘
'&W͗WƌŽƚĞşŶĂĚĞ&ůƵŽƌĞƐĐĞŶĐŝĂsĞƌĚĞ͘
'^<ϯď͗ŝŶĂƐĂ'ůŝĐſŐĞŶŽ^ŝŶƚĂƐĂϯď͘
,ϮKϮ͗WĞƌſǆŝĚŽĚĞ,ŝĚƌſŐĞŶŽ͘
ϳϴ
s/͘ďƌĞǀŝĂƚƵƌĂƐ
/Wϯ͗/ŶŽƐŝƚŽůƚƌŝĨŽƐĨĂƚŽ͘
/WϯZ͗ZĞĐĞƚŽƌĂƐŽĐŝĂĚŽĂ/Wϯ͘
<ϯϴ͗ŽŵŝŶĂŶƚĞŶĞŐĂƚŝǀŽĚĞƌƉϭ͘
<&ZY͗WĂŶƚĂƉĠƉƚŝĚŽĨŽƌŵĂĚŽƉŽƌůŝƐŝŶĂ͕ĨĞŶŝůĂůĂŶŝŶĂ͕ĄĐŝĚŽŐůƵƚĄŵŝĐŽ͕ĂƌŐŝŶŝŶĂ
ǇŐůƵƚĂŵŝŶĂ͘
,ϮͲ&Ͳ͗ĐĞƚĂƚŽĚĞϮǲ͕ϳǲͲĚŝĐůŽƌŽĨůƵŽƌĞĐĞşŶĂ͘
,ϮKϮ͗WĞƌſǆŝĚŽĚĞ,ŝĚƌſŐĞŶŽ͘
,ϲ͗,ŝƐƚŽŶĂƐĞƐĂĐĞƚŝůĂƐĂƐƉĞƌƚĞŶĞĐŝĞŶƚĞƐĂůƐƵďƚŝƉŽϲ͘ŶŶƵĞƐƚƌŽƚƌĂďĂũŽ͕
ŶŽƐƌĞĨĞƌŝŵŽƐĐŽŶĐƌĞƚĂŵĞŶƚĞĂůĂƐƉĞƌƚĞŶĞĐŝĞŶƚĞƐĂůĂĐůĂƐĞ//͘
,ϲŝ͗/ŶŚŝďŝĚŽƌĞƐĚĞůĂ,ŝƐƚŽŶĂĞƐĂĐĞƚŝůĂƐĂƉĞƌƚĞŶĞĐŝĞŶƚĞƐĂůƐƵďƚŝƉŽϲ͘
,W^͗ĐŝĚŽϰͲ;ϮͲŚŝĚƌŽǆŝĞƚŝůͿͲϭͲƉŝƉĞƌĂǌŝŶĞƚĂŶŽĐƵůĨſŶŝĐŽ͘
,ƚƚ͗WƌŽƚĞşŶĂ,ƵŶƚŝŶŐƚŝŶĂ͘
/W^͗/ŶŚŝďŝĚŽƌĞƐĚĞůĂƉŽƉƚŽƐŝƐ͘
>DWͲϮ͗WƌŽƚĞşŶĂƐŽĐŝĂĚĂĂůĂDĞŵďƌĂŶĂ>ŝƐŽƐŽŵĂů͕ĚĞƚŝƉŽϮ͘
>DWͲϮ͗WƌŽƚĞşŶĂƐŽĐŝĂĚĂĂůĂDĞŵďƌĂŶĂ>ŝƐŽƐŽŵĂů͕ĚĞƚŝƉŽϮ͘
>ϯ͗ĂĚĞŶĂ>ŝŐĞƌĂ͕ĚĞƚŝƉŽϯ͘
>ϯͲ/͗ĂĚĞŶĂ>ŝŐĞƌĂ͕ĚĞƚŝƉŽϯ͕ƐƵďƚŝƉŽϭ͘
>ϯͲ//͗ĂĚĞŶĂ>ŝŐĞƌĂ͕ĚĞƚŝƉŽϯ͕ƐƵďƚŝƉŽϮ͘
>,͗>ĂĐƚĂƚŽĞƐŚŝĚƌŽŐĞŶĂƐĂ͘
>ͲKW͗>ĞǀŽŽƉĂŵŝŶĂ͘
ůKWϭ͗/ƐŽĨŽƌŵĂůĂƌŐĂĚĞKWϭ͘
DZ,Ͳs͗WƌŽƚĞşŶĂZ/E'Ͳ,,ƵŵĂŶĂƐŽĐŝĂĚĂĂůĂDĞŵďƌĂŶĂ͕ĚĞƚŝƉŽϱ͘
DĚŝǀŝͲϭ͗/ŶŚŝďŝĚŽƌĚĞůĂ&ŝƐŝſŶDŝƚŽĐŽŶĚƌŝĂů͕ĚĞƚŝƉŽϭ͘
D&͗&ŝďƌŽďůĂƐƚŽƐŵďƌŝſŶŝĐŽƐDƵƌŝŶŽƐ͘
D/͗WƌŽƚĞşŶĂĚĞhŶŝſŶĂDŝƚŽĨƵƐŝŶĂ͘
Dŝϰϵ͗WƌŽƚĞşŶĂĚĞůĂŝŶĄŵŝĐĂDŝƚŽĐŽŶĚƌŝĂůĚĞϰϵ<Ă͘
ϳϵ
Dŝϱϭ͗WƌŽƚĞşŶĂĚĞůĂŝŶĄŵŝĐĂDŝƚŽĐŽŶĚƌŝĂůĚĞϱϭ<Ă͘
DŝƚŽW>͗&ŽƐĨŽůŝƉĂƐĂDŝƚŽĐŽŶĚƌŝĂů͘
DĨĨ͗&ĂĐƚŽƌĚĞ&ŝƐŝſŶDŝƚŽĐŽŶĚƌŝĂů͘
DĨŶϭ͗DŝƚŽĨƵƐŝŶĂ͕ĚĞƚŝƉŽϭ͘
DĨŶϮ͗DŝƚŽĨƵƐŝŶĂ͕ĚĞƚŝƉŽϮ͘
DŶdW͗ůŽƌƵƌŽĚĞDŶ;///ͿƚĞƚƌĂŬŝƐ;ϰͲĄĐŝĚŽďĞŶǌſŝĐŽͿƉŽƌĨŝƌŝŶĂ͘
DW&͗&ĂĐƚŽƌWƌŽŵŽƚŽƌĚĞDŝƚŽƐŝƐ͘
DWWн͗ϭͲDĞƚŝůͲϰͲ&ĞŶŝůƉŝƌŝĚŝŶŝŽ͘
ŵƚE͗ĐŝĚŽĞƐŽǆŝƌƌŝďŽŶƵĐůĞŝĐŽDŝƚŽĐŽŶĚƌŝĂů͘
ŵdKZ͗ŝĂŶĂĚĞZĂƉĂŵŝĐŝŶĂĞŶŵĂŵşĨĞƌŽ͘
DdWϭϴ͗WƌŽƚĞşŶĂDŝƚŽĐŽŶĚƌŝĂůĚĞϭϴ<Ă
DdWW͗ϭͲŵĞƚŝůͲϰͲĨĞŶŝůͲϰͲƉƌŽƉŝŽŶƉŝƌŝĚŝŶĂ͘
DdWd͗ϭͲŵĞƚŝůͲϰͲĨĞŶŝůͲϭ͕Ϯ͕ϯ͕ϲͲƚĞƚƌĂŚŝĚƌŽƉŝƌŝĚŝŶĂ͘
Ddd͗ƌŽŵƵƌŽĚĞϯͲ;ϰ͕ϱͲĚŝŵĞƚŝůͲƚŝĂǌŽůͲϮͲŝůͿͲϮ͕ϱͲĚŝĨĞŶŝůͲƚĞƚƌĂǌŽůŝŽͲ
Dh>E͗ĐƚŝǀĂĚŽƌĚĞůĂE&ŬhďŝƋƵŝƚŝŶ>ŝŐĂƐĂ͘
EW,͗EŝĐƌŽƚŝŶĂŵŝĚĂĂĚĞŶŝŶĂĚŝŶƵĐůĞſƚŝĚŽĨŽƐĨĂƚŽ͘
E&Ͳʃ͗ &ĂĐƚŽƌ EƵĐůĞĂƌ ƉŽƚĞŶĐŝĂĚŽƌ ĚĞ ůĂƐ ĐĂĚĞŶĂƐ ůŝŐĞƌĂƐ <ĂƉƉĂ ĚĞ ĠůƵůĂƐ ĂĐƚŝǀĂĚĂƐ͘
K,Ͳ͗ZĂĚŝĐĂů,ŝĚƌŽǆŝůŽ͘
KWϭ͗WƌŽƚĞşŶĂĚĞůĂĂƚƌŽĨŝĂſƉƚŝĐĂĂƵƚŽƐſŵŝĐĂĚŽŵŝŶĂŶƚĞ͕ĚĞƚŝƉŽϭ͘
WĂƌŬŝŶ͗hďŝƋƵŝƚŝŶͲůŝŐĂƐĂϯ͘
WZ>͗WƌĞƐĞůŝŶĂĂƐŽĐŝĂĚĂĂWƌŽƚĞşŶĂƐƐŝŵŝůĂƌĞƐĂůŽƐZŽŵďŽŝĚĞƐ͘
W^͗&ŽƐĨĂƚŽƵĨĨĞƌ^ĂůŝŶŽ͘
WϭϮ͗ >şŶĞĂ ĐĞůƵůĂƌ ŽŶƚĞŶŝĚĂ Ă ƉĂƌƚŝƌ ĚĞ ĨĞŽĐƌŽŵŽĐŝƚŽŵĂ ĚĞ ůĂ ŵĠĚƵůĂ
ƐƵƉƌĂƌƌĞŶĂůĚĞƌĂƚĂƐ͘
W'Ͳϭɲ͗ZĞĐĞƉƚŽƌ'ĂŵŵĂ͕ŽĂĐƚŝǀĂĚŽƌϭͲɲĚĞůĂƉƌŽůŝĨĞƌĂĐŝſŶĚĞWĞƌŽǆŝƐŽŵĂƐ
ĂĐƚŝǀĂĚĂ͘
ϴϬ
s/͘ďƌĞǀŝĂƚƵƌĂƐ
W͗&ŽƐĨĂƚŝĚŝůĞƚĂŶŽůĂŵŝŶĂ͘
W/ϯ<ĚĞĐůĂƐĞ///͗&ŽƐĨĂƚŝŶŝĚĞͲϯͲĐŝŶĂƐĂ͘
WŝŶŬϭ͗ŝŶĂƐĂDŝƚŽĐŽŶĚƌŝĂůWdE/ŶĚƵĐƚŽƌĂĚĞůĂŝŶĂƐĂϭ͘
W<͗WƌŽƚĞŝŶͲĐŝŶĂƐĂĚĞƉĞŶĚŝĞŶƚĞĚĞĐDW͘
WWdD͗WŽƌŽĚĞWĞƌŵĞĂďŝůŝĚĂĚǇdƌĂŶƐŝĐŝſŶDŝƚŽĐŽŶĚƌŝĂů͘
ZĂďϳ͗WƌŽƚĞşŶĂĚĞhŶŝſŶĂ'dW͕ƌĞůĂĐŝŽŶĂĚĂĐŽŶZ^͘
^^ͲW'͗ ůĞĐƚƌŽĨŽƌĞƐŝƐ ĞŶ ŐĞůĞƐ ĚĞ ƉŽůŝĂĐƌŝůĂŵŝĚĂ ĐŽŶ ĚŽĚĞĐŝů ƐƵůĨĂƚŽ ĚĞ
ƐŽĚŝŽ͘
^>WͲϮ͗sĞƌ^ƚŽŵůϮ͘
^K͗^ŽƉĞƌſǆŝĚŽŝƐŵƵƚĂƐĂ͘
ƐKWϭ͗/ƐŽĨŽƌŵĂĐŽƌƚĂĚĞKWϭ͘
^ƚŽŵůϮ͗WƌŽƚĞşŶĂ^ŝŵůŝĂƌĂůĂƐƚŽŵĂƚŝŶĂ͘
d^͗dƌŝƐƵĨĨĞƌ^ĂůŝŶŽ
dDWK>͗ϰͲŚŝĚƌŽǆŝͲϮ͕Ϯ͕ϲ͕ϲͲƚĞƚƌĂŵĞƚŝůƉŝƉĞƌŝĚŝŶĂͲEͲKǆŝů͘
dE&ɲ͗&ĂĐƚŽƌĚĞEĞĐƌŽƐŝƐdƵŵŽƌĂůɲ͘
dƌŝƐ͗dƌŝƐĂŵŝŶŽŵĞƚĂŶŽ͘
dWW͗dƌŝĨĞŶŝůĨŽƐĨŽŶŝŽ͘
d^͗dƌŝĐŽƐƚĂƚŝŶĂ͘
dǁĞĞŶϮϬ͗WŽůŝƐŽƌďĂƚŽϮϬ͘
hWƐ͗WƌŽƚĞşŶĂƐĞƐĂĐŽƉůĂŶƚĞƐ͘
h><ϭ͗DŝĞŵďƌŽƐŝŶŽŽƌĚŝŶĂƌĚĞůĂĨĂŵŝůŝĂϱϭ^ŝŵůŝĂƌĂůĂƐŝŶĂƐĂƐ͕ƚŝƉŽϭ͘
h><Ϯ͗DŝĞŵďƌŽƐŝŶŽŽƌĚŝŶĂƌĚĞůĂĨĂŵŝůŝĂϱϭ^ŝŵůŝĂƌĂůĂƐŝŶĂƐĂƐ͕ƚŝƉŽϮ͘
hs͗ZĂĚŝĂĐŝſŶhůƚƌĂsŝŽůĞƚĂ͘
s͗ĂŶĂůŶŝſŶŝĐŽĞƉĞŶĚŝĞŶƚĞĚĞsŽůƚĂũĞ͘
sͲϮ͗ĂŶĂůŶŝſŶŝĐŽĞƉĞŶĚŝĞŶƚĞĚĞsŽůƚĂũĞ͕ĚĞƚŝƉŽϮ͘
ϴϭ
s///͘ŝďůŝŽŐƌĂĨşĂ
Ǥ A
ďĂĚ͕&͕DĂƌŽƚŽ͕Z͕>ŽƉĞǌ͕D'͕^ĂŶĐŚĞǌͲ'ĂƌĐŝĂ͕W͕'ĂƌĐŝĂ͕';ϭϵϵϱͿWŚĂƌŵĂĐŽůŽŐŝĐĂů
ƉƌŽƚĞĐƚŝŽŶ ĂŐĂŝŶƐƚ ƚŚĞ ĐǇƚŽƚŽǆŝĐŝƚǇ ŝŶĚƵĐĞĚ ďǇ ϲͲŚǇĚƌŽǆǇĚŽƉĂŵŝŶĞ ĂŶĚ ,ϮKϮ ŝŶ
ĐŚƌŽŵĂĨĨŝŶĐĞůůƐ͘Ƶƌ:WŚĂƌŵĂĐŽůϮϵϯ;ϭͿ͗ϱϱͲϲϰ͘
ďŽƵͲ^ůĞŝŵĂŶ͕WD͕DƵƋŝƚ͕DD͕tŽŽĚ͕Et;ϮϬϬϲͿǆƉĂŶĚŝŶŐŝŶƐŝŐŚƚƐŽĨŵŝƚŽĐŚŽŶĚƌŝĂů
ĚǇƐĨƵŶĐƚŝŽŶŝŶWĂƌŬŝŶƐŽŶΖƐĚŝƐĞĂƐĞ͘EĂƚZĞǀEĞƵƌŽƐĐŝϳ;ϯͿ͗ϮϬϳͲϮϭϵ͘
ĚůĂŵ͕s:͕,ĂƌƌŝƐŽŶ͕:͕WŽƌƚĞŽƵƐ͕D͕:ĂŵĞƐ͕D͕^ŵŝƚŚ͕Z͕DƵƌƉŚǇ͕DW͕^ĂŵŵƵƚ͕/
;ϮϬϬϱͿ dĂƌŐĞƚŝŶŐ ĂŶ ĂŶƚŝŽǆŝĚĂŶƚ ƚŽ ŵŝƚŽĐŚŽŶĚƌŝĂ ĚĞĐƌĞĂƐĞƐ ĐĂƌĚŝĂĐ ŝƐĐŚĞŵŝĂͲ
ƌĞƉĞƌĨƵƐŝŽŶŝŶũƵƌǇ͘&^:ϭϵ;ϵͿ͗ϭϬϴϴͲϭϬϵϱ͘
ůĞǆĂŶĚĞƌ͕͕sŽƚƌƵďĂ͕D͕WĞƐĐŚ͕h͕dŚŝƐĞůƚŽŶ͕>͕DĂǇĞƌ͕^͕DŽŽƌĞ͕͕ZŽĚƌŝŐƵĞǌ͕D͕
<ĞůůŶĞƌ͕ h͕ >ĞŽͲ<ŽƚƚůĞƌ͕ ͕ ƵďƵƌŐĞƌ͕ '͕ ŚĂƚƚĂĐŚĂƌǇĂ͕ ^^͕ tŝƐƐŝŶŐĞƌ͕ ;ϮϬϬϬͿ KWϭ͕
ĞŶĐŽĚŝŶŐĂĚǇŶĂŵŝŶͲƌĞůĂƚĞĚ'dWĂƐĞ͕ŝƐŵƵƚĂƚĞĚŝŶĂƵƚŽƐŽŵĂůĚŽŵŝŶĂŶƚŽƉƚŝĐĂƚƌŽƉŚǇ
ůŝŶŬĞĚƚŽĐŚƌŽŵŽƐŽŵĞϯƋϮϴ͘EĂƚ'ĞŶĞƚϮϲ;ϮͿ͗ϮϭϭͲϮϭϱ͘
ůǀĞƐ ĚĂ ŽƐƚĂ͕ ͕ ƵŶǇƐ͕ :͕ ƌĂƵ͕ &͕ tŝůŬ͕ ^͕ ĂƉƉĂŝ͕ Z͕ ŚĞĐůĞƌ͕ & ;ϮϬϬϲͿ ϲͲ
,ǇĚƌŽǆǇĚŽƉĂŵŝŶĞ ďƵƚ ŶŽƚ ϭͲŵĞƚŚǇůͲϰͲƉŚĞŶǇůƉǇƌŝĚŝŶŝƵŵ ĂďŽůŝƐŚĞƐ ĂůƉŚĂͲƐǇŶƵĐůĞŝŶ
ĂŶƚŝͲĂƉŽƉƚŽƚŝĐƉŚĞŶŽƚǇƉĞďǇŝŶŚŝďŝƚŝŶŐŝƚƐƉƌŽƚĞĂƐŽŵĂůĚĞŐƌĂĚĂƚŝŽŶĂŶĚďǇƉƌŽŵŽƚŝŶŐ
ŝƚƐĂŐŐƌĞŐĂƚŝŽŶ͘:ŝŽůŚĞŵϮϴϭ;ϭϰͿ͗ϵϴϮϰͲϵϴϯϭ͘
ŵĞƐ͕ E͕ ^ŚŝŐĞŶĂŐĂ͕ D<͕ ,ĂŐĞŶ͕ dD ;ϭϵϵϯͿ KǆŝĚĂŶƚƐ͕ ĂŶƚŝŽǆŝĚĂŶƚƐ͕ ĂŶĚ ƚŚĞ
ĚĞŐĞŶĞƌĂƚŝǀĞĚŝƐĞĂƐĞƐŽĨĂŐŝŶŐ͘WƌŽĐEĂƚůĐĂĚ^Đŝh^ϵϬ;ϭϳͿ͗ϳϵϭϱͲϳϵϮϮ͘
ŶĚĞƌƐŽŶ͕ :͕ <ǇƉƐŽŶ͕ W͕ ZŽĚƌŝŐƵĞǌ͕ ͕ ŶĚĞƌƐŽŶ͕ ͕ >ĞŚƌ͕ :͕ EĞƵĨĞƌ͕ W ;ϮϬϬϵͿ
^ƵďƐƚƌĂƚĞͲƐƉĞĐŝĨŝĐ ĚĞƌĂŶŐĞŵĞŶƚƐ ŝŶ ŵŝƚŽĐŚŽŶĚƌŝĂů ŵĞƚĂďŽůŝƐŵ ĂŶĚ ƌĞĚŽǆ ďĂůĂŶĐĞ ŝŶ
ƚŚĞĂƚƌŝƵŵŽĨƚŚĞƚǇƉĞϮĚŝĂďĞƚŝĐŚƵŵĂŶŚĞĂƌƚ͘:ŵŽůůĂƌĚŝŽůϱϰ;ϮϬͿ͗ϭϴϵϭͲϭϴϵϴ͘
ŶĚƌĞǁ͕ Z͕ tĂƚƐŽŶ͕ '͕ ĞƐƚ͕ ^͕ DŝĚŐůĞǇ͕ :D͕ tĞŶůŽŶŐ͕ ,͕ WĞƚƚǇ͕ Z< ;ϭϵϵϯͿ dŚĞ
ĚĞƚĞƌŵŝŶĂƚŝŽŶ ŽĨ ŚǇĚƌŽǆǇĚŽƉĂŵŝŶĞƐ ĂŶĚ ŽƚŚĞƌ ƚƌĂĐĞ ĂŵŝŶĞƐ ŝŶ ƚŚĞ ƵƌŝŶĞ ŽĨ
ƉĂƌŬŝŶƐŽŶŝĂŶƉĂƚŝĞŶƚƐĂŶĚŶŽƌŵĂůĐŽŶƚƌŽůƐ͘EĞƵƌŽĐŚĞŵZĞƐϭϴ;ϭϭͿ͗ϭϭϳϱͲϭϭϳϳ͘
ŶƚŝŐŶĂŶŝ͕ ͕ zŽƵůĞ͕ Z: ;ϮϬϬϲͿ ,Žǁ ĚŽ Ăǆ ĂŶĚ ĂŬ ůĞĂĚ ƚŽ ƉĞƌŵĞĂďŝůŝǌĂƚŝŽŶ ŽĨ ƚŚĞ
ŽƵƚĞƌŵŝƚŽĐŚŽŶĚƌŝĂůŵĞŵďƌĂŶĞ͍ƵƌƌKƉŝŶĞůůŝŽůϭϴ;ϲͿ͗ϲϴϱͲϲϴϵ͘
ŶƚƵŶĞƐ͕ &͕ ĂĚĞŶĂƐ͕ ;ϮϬϬϬͿ ƐƚŝŵĂƚŝŽŶ ŽĨ ,ϮKϮ ŐƌĂĚŝĞŶƚƐ ĂĐƌŽƐƐ ďŝŽŵĞŵďƌĂŶĞƐ͘
&^>Ğƚƚϰϳϱ;ϮͿ͗ϭϮϭͲϭϮϲ͘
ƌŶŽůĚ͕ ^͕ 'ŽŐůŝĂ͕ &͕ <ĂĚĞŶďĂĐŚ͕ ;ϭϵϵϴͿ ϯ͕ϱͲŝŝŽĚŽƚŚǇƌŽŶŝŶĞ ďŝŶĚƐ ƚŽ ƐƵďƵŶŝƚ sĂ ŽĨ
ĐǇƚŽĐŚƌŽŵĞͲĐŽǆŝĚĂƐĞĂŶĚĂďŽůŝƐŚĞƐƚŚĞĂůůŽƐƚĞƌŝĐŝŶŚŝďŝƚŝŽŶŽĨƌĞƐƉŝƌĂƚŝŽŶďǇdW͘Ƶƌ:
ŝŽĐŚĞŵϮϱϮ;ϮͿ͗ϯϮϱͲϯϯϬ͘
ϴϯ
ƐĂŶƵŵĂ͕ D͕ ,ŝƌĂƚĂ͕ ,͕ ĂĚĞƚ͕ :> ;ϭϵϵϴͿ ƚƚĞŶƵĂƚŝŽŶ ŽĨ ϲͲŚǇĚƌŽǆǇĚŽƉĂŵŝŶĞͲŝŶĚƵĐĞĚ
ĚŽƉĂŵŝŶĞƌŐŝĐ ŶŝŐƌŽƐƚƌŝĂƚĂů ůĞƐŝŽŶƐ ŝŶ ƐƵƉĞƌŽǆŝĚĞ ĚŝƐŵƵƚĂƐĞ ƚƌĂŶƐŐĞŶŝĐ ŵŝĐĞ͘
EĞƵƌŽƐĐŝĞŶĐĞϴϱ;ϯͿ͗ϵϬϳͲϵϭϳ͘
ƐŚŬƚŽƌĂď͕ ,͕ &ƌĂŶŬ͕ ^͕ <ŚĂůĞĚ͕ Z͕ ƵƌƵŵ͕ ^<͕ <ŝĨůĞ͕ ͕ ^ŵŽŽƚ͕ d ;ϮϬϬϰͿ Ăǆ
ƚƌĂŶƐůŽĐĂƚŝŽŶ ĂŶĚ ŵŝƚŽĐŚŽŶĚƌŝĂů ĨƌĂŐŵĞŶƚĂƚŝŽŶ ŝŶĚƵĐĞĚ ďǇ ,ĞůŝĐŽďĂĐƚĞƌ ƉǇůŽƌŝ͘ 'Ƶƚ
ϱϯ;ϲͿ͗ϴϬϱͲϴϭϯ͘
ĂĐŚ͕͕EĂŽŶ͕͕WŝĐŚ͕^͕^ŽƌŝĂŶŽ͕&y͕sĞŐĂ͕E͕ZŝĞƵƐƐĞƚ͕:͕>ĂǀŝůůĞ͕D͕'ƵŝůůĞƚ͕͕ŽŝƌŝĞ͕
z͕ tĂůůďĞƌŐͲ,ĞŶƌŝŬƐƐŽŶ͕ ,͕ DĂŶĐŽ͕ D͕ ĂůǀĂŶŝ͕ D͕ ĂƐƚĂŐŶĞƚŽ͕ D͕ WĂůĂĐŝŶ͕ D͕
DŝŶŐƌŽŶĞ͕'͕ŝĞƌĂƚŚ͕:Z͕sŝĚĂů͕,͕ŽƌǌĂŶŽ͕;ϮϬϬϱͿǆƉƌĞƐƐŝŽŶŽĨDĨŶϮ͕ƚŚĞŚĂƌĐŽƚͲ
DĂƌŝĞͲdŽŽƚŚ ŶĞƵƌŽƉĂƚŚǇ ƚǇƉĞ Ϯ ŐĞŶĞ͕ ŝŶ ŚƵŵĂŶ ƐŬĞůĞƚĂů ŵƵƐĐůĞ͗ ĞĨĨĞĐƚƐ ŽĨ ƚǇƉĞ Ϯ
ĚŝĂďĞƚĞƐ͕ŽďĞƐŝƚǇ͕ǁĞŝŐŚƚůŽƐƐ͕ĂŶĚƚŚĞƌĞŐƵůĂƚŽƌǇƌŽůĞŽĨƚƵŵŽƌŶĞĐƌŽƐŝƐĨĂĐƚŽƌĂůƉŚĂ
ĂŶĚŝŶƚĞƌůĞƵŬŝŶͲϲ͘ŝĂďĞƚĞƐϱϰ;ϵͿ͗ϮϲϴϱͲϮϲϵϯ͘
ĂĐŚ͕͕WŝĐŚ͕^͕^ŽƌŝĂŶŽ͕&y͕sĞŐĂ͕E͕ĂƵŵŐĂƌƚŶĞƌ͕͕KƌŝŽůĂ͕:͕ĂƵŐĂĂƌĚ͕:Z͕>ůŽďĞƌĂƐ͕
:͕ĂŵƉƐ͕D͕ŝĞƌĂƚŚ͕:Z͕ZĂďĂƐĂͲ>ŚŽƌĞƚ͕Z͕tĂůůďĞƌŐͲ,ĞŶƌŝŬƐƐŽŶ͕,͕>ĂǀŝůůĞ͕D͕WĂůĂĐŝŶ͕
D͕ sŝĚĂů͕ ,͕ ZŝǀĞƌĂ͕ &͕ ƌĂŶĚ͕ D͕ ŽƌǌĂŶŽ͕ ;ϮϬϬϯͿ DŝƚŽĨƵƐŝŶͲϮ ĚĞƚĞƌŵŝŶĞƐ
ŵŝƚŽĐŚŽŶĚƌŝĂůŶĞƚǁŽƌŬĂƌĐŚŝƚĞĐƚƵƌĞĂŶĚŵŝƚŽĐŚŽŶĚƌŝĂůŵĞƚĂďŽůŝƐŵ͘ŶŽǀĞůƌĞŐƵůĂƚŽƌǇ
ŵĞĐŚĂŶŝƐŵĂůƚĞƌĞĚŝŶŽďĞƐŝƚǇ͘:ŝŽůŚĞŵϮϳϴ;ϭϵͿ͗ϭϳϭϵϬͲϭϳϭϵϳ͘
ĂƌŬĂƚƐ͕ D͕ DŝůůĞĐĂŵƉƐ͕ ^͕ ŝůĂŶŐͲůĞƵĞů͕ ͕ DĂůůĞƚ͕ : ;ϮϬϬϮͿ EĞƵƌŽŶĂů ƚƌĂŶƐĨĞƌ ŽĨ ƚŚĞ
ŚƵŵĂŶ ƵͬŶ ƐƵƉĞƌŽǆŝĚĞ ĚŝƐŵƵƚĂƐĞ ŐĞŶĞ ŝŶĐƌĞĂƐĞƐ ƚŚĞ ƌĞƐŝƐƚĂŶĐĞ ŽĨ ĚŽƉĂŵŝŶĞƌŐŝĐ
ŶĞƵƌŽŶƐƚŽϲͲŚǇĚƌŽǆǇĚŽƉĂŵŝŶĞ͘:EĞƵƌŽĐŚĞŵϴϮ;ϭͿ͗ϭϬϭͲϭϬϵ͘
ĂƌƐŽƵŵ͕D:͕zƵĂŶ͕,͕'ĞƌĞŶĐƐĞƌ͕͕>ŝŽƚ͕'͕<ƵƐŚŶĂƌĞǀĂ͕z͕'ƌĂďĞƌ͕^͕<ŽǀĂĐƐ͕/͕>ĞĞ͕
t͕ tĂŐŐŽŶĞƌ͕ :͕ Ƶŝ͕ :͕ tŚŝƚĞ͕ ͕ ŽƐƐǇ͕ ͕ DĂƌƚŝŶŽƵ͕ :͕ zŽƵůĞ͕ Z:͕ >ŝƉƚŽŶ͕ ^͕
ůůŝƐŵĂŶ͕D,͕WĞƌŬŝŶƐ͕'͕ŽƐƐǇͲtĞƚǌĞů͕;ϮϬϬϲͿEŝƚƌŝĐŽǆŝĚĞͲŝŶĚƵĐĞĚŵŝƚŽĐŚŽŶĚƌŝĂů
ĨŝƐƐŝŽŶ ŝƐ ƌĞŐƵůĂƚĞĚ ďǇ ĚǇŶĂŵŝŶͲƌĞůĂƚĞĚ 'dWĂƐĞƐ ŝŶ ŶĞƵƌŽŶƐ͘ DK : Ϯϱ;ϭϲͿ͗ ϯϵϬϬͲ
ϯϵϭϭ͘
ĂƚŝŶŝĐͲ,ĂďĞƌůĞ͕/͕ƵǌǌŽĐƌĞĂ͕^͕ZĞďŽƵĐĂƐ͕:^͕&ĞƌƌĞƌͲ^ƵĞƚĂ͕'͕DĂǌǌŽŶ͕͕ŝWĂŽůĂ͕Z͕
ZĂĚŝ͕Z͕^ƉĂƐŽũĞǀŝĐ͕/͕ĞŶŽǀ͕>͕^ĂůǀĞŵŝŶŝ͕;ϮϬϬϵͿWƵƌĞDŶdWƐĞůĞĐƚŝǀĞůǇƐĐĂǀĞŶŐĞƐ
ƉĞƌŽǆǇŶŝƚƌŝƚĞ ŽǀĞƌ ƐƵƉĞƌŽǆŝĚĞ͗ ĐŽŵƉĂƌŝƐŽŶ ŽĨ ƉƵƌĞ ĂŶĚ ĐŽŵŵĞƌĐŝĂů DŶdW ƐĂŵƉůĞƐ
ƚŽDŶdͲϮͲWǇWŝŶƚǁŽŵŽĚĞůƐŽĨŽǆŝĚĂƚŝǀĞƐƚƌĞƐƐŝŶũƵƌǇ͕ĂŶ^KͲƐƉĞĐŝĨŝĐƐĐŚĞƌŝĐŚŝĂĐŽůŝ
ŵŽĚĞůĂŶĚĐĂƌƌĂŐĞĞŶĂŶͲŝŶĚƵĐĞĚƉůĞƵƌŝƐǇ͘&ƌĞĞZĂĚŝĐŝŽůDĞĚϰϲ;ϮͿ͗ϭϵϮͲϮϬϭ͘
ĂǇƌĂƐǇ͕ ͕ ŚĂďŝ͕ ͕ >ĂŐƵĞƌƌĞ͕ D͕ >ĞĐŽŵƚĞ͕ :͕ :ƵďůĂŶĐ͕ ͕ sŝůůĞŶĞƵǀĞ͕ W͕ tƌƵƚŶŝĂŬͲ
ĂďĞůůŽ͕ ͕ ĂďĞůůŽ͕ ' ;ϮϬϭϯͿ ŽŽƐƚŝŶŐ ŶƚŝŽǆŝĚĂŶƚƐ ďǇ >ŝƉŽƉŚŝůŝǌĂƚŝŽŶ͗ ^ƚƌĂƚĞŐǇ ƚŽ
/ŶĐƌĞĂƐĞĞůůhƉƚĂŬĞĂŶĚdĂƌŐĞƚDŝƚŽĐŚŽŶĚƌŝĂ͘WŚĂƌŵZĞƐ͘
ĞĂů͕D&;ϮϬϬϳͿDŝƚŽĐŚŽŶĚƌŝĂĂŶĚŶĞƵƌŽĚĞŐĞŶĞƌĂƚŝŽŶ͘EŽǀĂƌƚŝƐ&ŽƵŶĚ^ǇŵƉϮϴϳ͗ϭϴϯͲ
ϭϵϮ͖ĚŝƐĐƵƐƐŝŽŶϭϵϮͲϭϴϲ͘
ĞĂů͕ D& ;ϭϵϵϴͿ DŝƚŽĐŚŽŶĚƌŝĂů ĚǇƐĨƵŶĐƚŝŽŶ ŝŶ ŶĞƵƌŽĚĞŐĞŶĞƌĂƚŝǀĞ ĚŝƐĞĂƐĞƐ͘ ŝŽĐŚŝŵ
ŝŽƉŚǇƐĐƚĂϭϯϲϲ;ϭͲϮͿ͗ϮϭϭͲϮϮϯ͘
ϴϰ
ĞŐƌŝĐŚĞ͕ <͕ DĂƐƐĂƌƚ͕ :͕ ZŽďŝŶ͕ D͕ ŽŶŶĞƚ͕ &͕ &ƌŽŵĞŶƚǇ͕ ;ϮϬϭϯͿ DŝƚŽĐŚŽŶĚƌŝĂů
ĂĚĂƉƚĂƚŝŽŶƐĂŶĚĚǇƐĨƵŶĐƚŝŽŶƐŝŶŶŽŶĂůĐŽŚŽůŝĐĨĂƚƚǇůŝǀĞƌĚŝƐĞĂƐĞ͘,ĞƉĂƚŽůŽŐǇ͘
ĞũĂƌĂŶŽ͕͕ƵĞƌǀŽ͕D;ϮϬϭϬͿŚĂƉĞƌŽŶĞͲŵĞĚŝĂƚĞĚĂƵƚŽƉŚĂŐǇ͘WƌŽĐŵdŚŽƌĂĐ^ŽĐ
ϳ;ϭͿ͗ϮϵͲϯϵ͘
ĞƌĞŝƚĞƌͲ,ĂŚŶ͕ :͕ :ĞŶĚƌĂĐŚ͕ D ;ϮϬϭϬͿ DŝƚŽĐŚŽŶĚƌŝĂů ĚǇŶĂŵŝĐƐ͘ /Ŷƚ ZĞǀ Ğůů DŽů ŝŽů
Ϯϴϰ͗ϭͲϲϱ͘
ĞƚĂƌďĞƚ͕Z͕^ŚĞƌĞƌ͕d͕'ƌĞĞŶĂŵǇƌĞ͕:d;ϮϬϬϮͿŶŝŵĂůŵŽĚĞůƐŽĨWĂƌŬŝŶƐŽŶΖƐĚŝƐĞĂƐĞ͘
ŝŽĞƐƐĂǇƐϮϰ;ϰͿ͗ϯϬϴͲϯϭϴ͘
ŝŶĚŽĨĨ͕ >͕ ŝƌĐŚͲDĂĐŚŝŶ͕ D͕ ĂƌƚůŝĚŐĞ͕ E͕ WĂƌŬĞƌ͕ t͕ :ƌ͕͘ dƵƌŶďƵůů͕ D ;ϭϵϴϵͿ
DŝƚŽĐŚŽŶĚƌŝĂůĨƵŶĐƚŝŽŶŝŶWĂƌŬŝŶƐŽŶΖƐĚŝƐĞĂƐĞ͘>ĂŶĐĞƚϮ;ϴϲϱϯͿ͗ϰϵ͘
ŝƐǁĂƐ͕ ^͕ ZǇƵ͕ ͕ WĂƌŬ͕ ͕ DĂůĂŐĞůĂĚĂ͕ ͕ 'ƌĞĞŶĞ͕ > ;ϮϬϬϱͿ WƵŵĂ ĂŶĚ Ɖϱϯ ƉůĂǇ
ƌĞƋƵŝƌĞĚ ƌŽůĞƐ ŝŶ ĚĞĂƚŚ ĞǀŽŬĞĚ ŝŶ Ă ĐĞůůƵůĂƌ ŵŽĚĞů ŽĨ WĂƌŬŝŶƐŽŶ ĚŝƐĞĂƐĞ͘ EĞƵƌŽĐŚĞŵ
ZĞƐϯϬ;ϲͲϳͿ͗ϴϯϵͲϴϰϱ͘
ũŽƌŬůƵŶĚ͕>D͕^ĂŶĐŚĞǌͲWĞƌŶĂƵƚĞ͕Z͕ŚƵŶŐ͕^͕ŶĚĞƌƐƐŽŶ͕d͕ŚĞŶ͕/z͕DĐEĂƵŐŚƚ͕<^͕
ƌŽǁŶĞůů͕ >͕ :ĞŶŬŝŶƐ͕ '͕ tĂŚůĞƐƚĞĚƚ͕ ͕ <ŝŵ͕ <^͕ /ƐĂĐƐŽŶ͕ K ;ϮϬϬϮͿ ŵďƌǇŽŶŝĐ ƐƚĞŵ
ĐĞůůƐĚĞǀĞůŽƉŝŶƚŽĨƵŶĐƚŝŽŶĂůĚŽƉĂŵŝŶĞƌŐŝĐŶĞƵƌŽŶƐĂĨƚĞƌƚƌĂŶƐƉůĂŶƚĂƚŝŽŶŝŶĂWĂƌŬŝŶƐŽŶ
ƌĂƚŵŽĚĞů͘WƌŽĐEĂƚůĐĂĚ^Đŝh^ϵϵ;ϰͿ͗ϮϯϰϰͲϮϯϰϵ͘
ůĂŶĚŝŶŝ͕&͕ƌŵĞŶƚĞƌŽ͕Dd͕DĂƌƚŝŐŶŽŶŝ͕;ϮϬϬϴͿdŚĞϲͲŚǇĚƌŽǆǇĚŽƉĂŵŝŶĞŵŽĚĞů͗ŶĞǁƐ
ĨƌŽŵƚŚĞƉĂƐƚ͘WĂƌŬŝŶƐŽŶŝƐŵZĞůĂƚŝƐŽƌĚϭϰ^ƵƉƉůϮ͗^ϭϮϰͲϭϮϵ͘
ůƵŵ͕͕dŽƌĐŚ͕^͕EŝƐƐŽƵ͕D&͕ĞŶĂďŝĚ͕>͕sĞƌŶĂ͕:D;ϮϬϬϬͿǆƚƌĂĐĞůůƵůĂƌƚŽǆŝĐŝƚǇŽĨϲͲ
ŚǇĚƌŽǆǇĚŽƉĂŵŝŶĞŽŶWϭϮĐĞůůƐ͘EĞƵƌŽƐĐŝ>ĞƚƚϮϴϯ;ϯͿ͗ϭϵϯͲϭϵϲ͘
ŽŐĂĞƌƚƐ͕ s͕ dŚĞƵŶƐ͕ :͕ ǀĂŶ ƌŽĞĐŬŚŽǀĞŶ͕ ;ϮϬϬϴͿ 'ĞŶĞƚŝĐ ĨŝŶĚŝŶŐƐ ŝŶ WĂƌŬŝŶƐŽŶΖƐ
ĚŝƐĞĂƐĞ ĂŶĚ ƚƌĂŶƐůĂƚŝŽŶ ŝŶƚŽ ƚƌĞĂƚŵĞŶƚ͗ Ă ůĞĂĚŝŶŐ ƌŽůĞ ĨŽƌ ŵŝƚŽĐŚŽŶĚƌŝĂ͍ 'ĞŶĞƐ ƌĂŝŶ
ĞŚĂǀϳ;ϮͿ͗ϭϮϵͲϭϱϭ͘
ŽŶŝĨĂƚŝ͕s͕ZŝǌǌƵ͕W͕ǀĂŶĂƌĞŶ͕D:͕^ĐŚĂĂƉ͕K͕ƌĞĞĚǀĞůĚ͕':͕<ƌŝĞŐĞƌ͕͕ĞŬŬĞƌ͕D͕
^ƋƵŝƚŝĞƌŝ͕&͕/ďĂŶĞǌ͕W͕:ŽŽƐƐĞ͕D͕ǀĂŶŽŶŐĞŶ͕:t͕sĂŶĂĐŽƌĞ͕E͕ǀĂŶ^ǁŝĞƚĞŶ͕:͕ƌŝĐĞ͕
͕DĞĐŽ͕'͕ǀĂŶƵŝũŶ͕D͕KŽƐƚƌĂ͕͕,ĞƵƚŝŶŬ͕W;ϮϬϬϯͿDƵƚĂƚŝŽŶƐŝŶƚŚĞ:ͲϭŐĞŶĞ
ĂƐƐŽĐŝĂƚĞĚǁŝƚŚĂƵƚŽƐŽŵĂůƌĞĐĞƐƐŝǀĞĞĂƌůǇͲŽŶƐĞƚƉĂƌŬŝŶƐŽŶŝƐŵ͘^ĐŝĞŶĐĞϮϵϵ;ϱϲϬϰͿ͗ϮϱϲͲ
Ϯϱϵ͘
ŽƌůŽŶŐĂŶ͕s͕<ŽƵƚŽƵǌŝƐ͕d<͕^ĂŶďĞƌŐ͕WZ;ϭϵϵϳͿϯͲEŝƚƌŽƉƌŽƉŝŽŶŝĐĂĐŝĚĂŶŝŵĂůŵŽĚĞů
ĂŶĚ,ƵŶƚŝŶŐƚŽŶΖƐĚŝƐĞĂƐĞ͘EĞƵƌŽƐĐŝŝŽďĞŚĂǀZĞǀϮϭ;ϯͿ͗ϮϴϵͲϮϵϯ͘
ŽƐƐǇͲtĞƚǌĞů͕ ͕ WĞƚƌŝůůŝ͕ ͕ <ŶŽƚƚ͕ ;ϮϬϬϴͿ DƵƚĂŶƚ ŚƵŶƚŝŶŐƚŝŶ ĂŶĚ ŵŝƚŽĐŚŽŶĚƌŝĂů
ĚǇƐĨƵŶĐƚŝŽŶ͘dƌĞŶĚƐEĞƵƌŽƐĐŝϯϭ;ϭϮͿ͗ϲϬϵͲϲϭϲ͘
ϴϱ
ŽƵƐŚĞů͕Z͕'ŶĂŝŐĞƌ͕͕^ĐŚũĞƌůŝŶŐ͕W͕^ŬŽǀďƌŽ͕D͕<ƌĂƵŶƐŽĞ͕Z͕ĞůĂ͕&;ϮϬϬϳͿWĂƚŝĞŶƚƐ
ǁŝƚŚ ƚǇƉĞ Ϯ ĚŝĂďĞƚĞƐ ŚĂǀĞ ŶŽƌŵĂů ŵŝƚŽĐŚŽŶĚƌŝĂů ĨƵŶĐƚŝŽŶ ŝŶ ƐŬĞůĞƚĂů ŵƵƐĐůĞ͘
ŝĂďĞƚŽůŽŐŝĂϱϬ;ϰͿ͗ϳϵϬͲϳϵϲ͘
ŽǀĞ͕:͕WĞƌŝĞƌ͕;ϮϬϭϮͿEĞƵƌŽƚŽǆŝŶͲďĂƐĞĚŵŽĚĞůƐŽĨWĂƌŬŝŶƐŽŶΖƐĚŝƐĞĂƐĞ͘EĞƵƌŽƐĐŝĞŶĐĞ
Ϯϭϭ͗ϱϭͲϳϲ͘
ŽǀĞƌŝƐ͕;ϭϵϵϴͿŝŽĐŚĞŵŝƐƚƌǇŽĨĨƌĞĞƌĂĚŝĐĂůƐ͗ĨƌŽŵĞůĞĐƚƌŽŶƐƚŽƚŝƐƐƵĞƐ͘DĞĚŝĐŝŶĂ;
ŝƌĞƐͿϱϴ;ϰͿ͗ϯϱϬͲϯϱϲ͘
ƌĂĂŬ͕ ,͕ ƌĂĂŬ͕ ͕ zŝůŵĂǌĞƌ͕ ͕ ^ĐŚƵůƚǌ͕ ͕ ĚĞ sŽƐ͕ Z͕ :ĂŶƐĞŶ͕ E ;ϭϵϵϱͿ EŝŐƌĂů ĂŶĚ
ĞǆƚƌĂŶŝŐƌĂůƉĂƚŚŽůŽŐǇŝŶWĂƌŬŝŶƐŽŶΖƐĚŝƐĞĂƐĞ͘:EĞƵƌĂůdƌĂŶƐŵ^ƵƉƉůϰϲ͗ϭϱͲϯϭ͘
ƌĂŶĚƚ͕ :͕ ǇůƐŵĂ͕ &t͕ 'ƌŽƐƐ͕ Z͕ ^ƚŝŶĞ͕ K͕ ZĂŶĞŶ͕ E͕ ZŽƐƐ͕ ;ϭϵϵϲͿ dƌŝŶƵĐůĞŽƚŝĚĞ
ƌĞƉĞĂƚ ůĞŶŐƚŚ ĂŶĚ ĐůŝŶŝĐĂů ƉƌŽŐƌĞƐƐŝŽŶ ŝŶ ,ƵŶƚŝŶŐƚŽŶΖƐ ĚŝƐĞĂƐĞ͘ EĞƵƌŽůŽŐǇ ϰϲ;ϮͿ͗ ϱϮϳͲ
ϱϯϭ͘
ƌĂƐ͕ D͕ YƵĞĞŶĂŶ͕ ͕ ^ƵƐŝŶ͕ ^ ;ϮϬϬϱͿ WƌŽŐƌĂŵŵĞĚ ĐĞůů ĚĞĂƚŚ ǀŝĂ ŵŝƚŽĐŚŽŶĚƌŝĂ͗
ĚŝĨĨĞƌĞŶƚŵŽĚĞƐŽĨĚǇŝŶŐ͘ŝŽĐŚĞŵŝƐƚƌǇ;DŽƐĐͿϳϬ;ϮͿ͗ϮϯϭͲϮϯϵ͘
ƌĂƐ͕ D͕ zƵƐƚĞ͕ s:͕ ZŽƵĞ͕ '͕ ĂƌďŝĞƌ͕ ^͕ ^ĂŶĐŚŽ͕ W͕ sŝƌĞůǇ͕ ͕ ZƵďŝŽ͕ D͕ ĂƵĚĞƚ͕ ^͕
ƐƋƵĞƌĚĂ͕ :͕ DĞƌůĞͲĞƌĂů͕ ,͕ ^ĂƌĨĂƚŝ͕ D͕ ^ƵƐŝŶ͕ ^ ;ϮϬϬϳͿ ƌƉϭ ŵĞĚŝĂƚĞƐ ĐĂƐƉĂƐĞͲ
ŝŶĚĞƉĞŶĚĞŶƚƚǇƉĞ///ĐĞůůĚĞĂƚŚŝŶŶŽƌŵĂůĂŶĚůĞƵŬĞŵŝĐĐĞůůƐ͘DŽůĞůůŝŽůϮϳ;ϮϬͿ͗ϳϬϳϯͲ
ϳϬϴϴ͘
ƌĂƐĐŚŝ͕ ͕ 'ŽǇŽŶ͕ s͕ ƵŶŝŶŽ͕ Z͕ DŽŚĂŶƚǇ͕ ͕ yƵ͕ >͕ DĐƌŝĚĞ͕ ,D ;ϮϬϭϬͿ sƉƐϯϱ
ŵĞĚŝĂƚĞƐ ǀĞƐŝĐůĞ ƚƌĂŶƐƉŽƌƚ ďĞƚǁĞĞŶ ƚŚĞ ŵŝƚŽĐŚŽŶĚƌŝĂ ĂŶĚ ƉĞƌŽǆŝƐŽŵĞƐ͘ Ƶƌƌ ŝŽů
ϮϬ;ϭϰͿ͗ϭϯϭϬͲϭϯϭϱ͘
ƌĂƐĐŚŝ͕ ͕ ƵŶŝŶŽ͕ Z͕ DĐƌŝĚĞ͕ ,D ;ϮϬϬϵͿ DW> ŝƐ Ă ŶĞǁ ŵŝƚŽĐŚŽŶĚƌŝĂů ^hDK ϯ
ůŝŐĂƐĞƚŚĂƚƌĞŐƵůĂƚĞƐŵŝƚŽĐŚŽŶĚƌŝĂůĨŝƐƐŝŽŶ͘DKZĞƉϭϬ;ϳͿ͗ϳϰϴͲϳϱϰ͘
ƌĂƵůƚ͕ ͕ >ĞǀǇ͕ W>͕ ĂƌƚŽƐĐŚ͕ ;ϮϬϭϯͿ ,ĞƉĂƚŝƚŝƐ ǀŝƌƵƐͲŝŶĚƵĐĞĚ ŵŝƚŽĐŚŽŶĚƌŝĂů
ĚǇƐĨƵŶĐƚŝŽŶƐ͘sŝƌƵƐĞƐϱ;ϯͿ͗ϵϱϰͲϵϴϬ͘
ƌĞŶŶĂŶ͕t͕:ƌ͕͘ŝƌĚ͕͕ƉƌŝůůĞ͕:Z;ϭϵϴϱͿZĞŐŝŽŶĂůŵŝƚŽĐŚŽŶĚƌŝĂůƌĞƐƉŝƌĂƚŽƌǇĂĐƚŝǀŝƚǇ
ŝŶ,ƵŶƚŝŶŐƚŽŶΖƐĚŝƐĞĂƐĞďƌĂŝŶ͘:EĞƵƌŽĐŚĞŵϰϰ;ϲͿ͗ϭϵϰϴͲϭϵϱϬ͘
ƌŝŶŬŵĂŶ͕ZZ͕DĞǌĞŝ͕DD͕dŚĞŝůŵĂŶŶ͕:͕ůŵƋǀŝƐƚ͕͕,ĂǇĚĞŶ͕DZ;ϭϵϵϳͿdŚĞůŝŬĞůŝŚŽŽĚ
ŽĨďĞŝŶŐĂĨĨĞĐƚĞĚǁŝƚŚ,ƵŶƚŝŶŐƚŽŶĚŝƐĞĂƐĞďǇĂƉĂƌƚŝĐƵůĂƌĂŐĞ͕ĨŽƌĂƐƉĞĐŝĨŝĐ'ƐŝǌĞ͘
ŵ:,Ƶŵ'ĞŶĞƚϲϬ;ϱͿ͗ϭϮϬϮͲϭϮϭϬ͘
ƌŽƵŝůůĞƚ͕ ͕ 'ƵǇŽƚ͕ D͕ DŝƚƚŽƵǆ͕ s͕ ůƚĂŝƌĂĐ͕ ^͕ ŽŶĚĞ͕ &͕ WĂůĨŝ͕ ^͕ ,ĂŶƚƌĂǇĞ͕ W ;ϭϵϵϴͿ
WĂƌƚŝĂů ŝŶŚŝďŝƚŝŽŶ ŽĨ ďƌĂŝŶ ƐƵĐĐŝŶĂƚĞ ĚĞŚǇĚƌŽŐĞŶĂƐĞ ďǇ ϯͲŶŝƚƌŽƉƌŽƉŝŽŶŝĐ ĂĐŝĚ ŝƐ
ƐƵĨĨŝĐŝĞŶƚƚŽŝŶŝƚŝĂƚĞƐƚƌŝĂƚĂůĚĞŐĞŶĞƌĂƚŝŽŶŝŶƌĂƚ͘:EĞƵƌŽĐŚĞŵϳϬ;ϮͿ͗ϳϵϰͲϴϬϱ͘
ƌŽƵŝůůĞƚ͕͕:ĂĐƋƵĂƌĚ͕͕ŝǌĂƚ͕E͕ůƵŵ͕;ϮϬϬϱͿϯͲEŝƚƌŽƉƌŽƉŝŽŶŝĐĂĐŝĚ͗ĂŵŝƚŽĐŚŽŶĚƌŝĂů
ϴϲ
ƚŽǆŝŶ ƚŽ ƵŶĐŽǀĞƌ ƉŚǇƐŝŽƉĂƚŚŽůŽŐŝĐĂů ŵĞĐŚĂŶŝƐŵƐ ƵŶĚĞƌůǇŝŶŐ ƐƚƌŝĂƚĂů ĚĞŐĞŶĞƌĂƚŝŽŶ ŝŶ
,ƵŶƚŝŶŐƚŽŶΖƐĚŝƐĞĂƐĞ͘:EĞƵƌŽĐŚĞŵϵϱ;ϲͿ͗ϭϱϮϭͲϭϱϰϬ͘
ƌŽǁŶĞ͕ ^͕ ŽǁůŝŶŐ͕ ͕ DĂĐ'ĂƌǀĞǇ͕ h͕ ĂŝŬ͕ D:͕ ĞƌŐĞƌ͕ ^͕ DƵƋŝƚ͕ DD͕ ŝƌĚ͕ ͕
ĞĂů͕D&;ϭϵϵϳͿKǆŝĚĂƚŝǀĞĚĂŵĂŐĞĂŶĚŵĞƚĂďŽůŝĐĚǇƐĨƵŶĐƚŝŽŶŝŶ,ƵŶƚŝŶŐƚŽŶΖƐĚŝƐĞĂƐĞ͗
ƐĞůĞĐƚŝǀĞǀƵůŶĞƌĂďŝůŝƚǇŽĨƚŚĞďĂƐĂůŐĂŶŐůŝĂ͘ŶŶEĞƵƌŽůϰϭ;ϱͿ͗ϲϰϲͲϲϱϯ͘
ƌŽǁŶĞ͕ ^͕ &ĞƌƌĂŶƚĞ͕ Z:͕ ĞĂů͕ D& ;ϭϵϵϵͿ KǆŝĚĂƚŝǀĞ ƐƚƌĞƐƐ ŝŶ ,ƵŶƚŝŶŐƚŽŶΖƐ ĚŝƐĞĂƐĞ͘
ƌĂŝŶWĂƚŚŽůϵ;ϭͿ͗ϭϰϳͲϭϲϯ͘
ƵƌĚŽŶ͕ Z,͕ ZŝĐĞͲǀĂŶƐ͕ ;ϭϵϴϵͿ &ƌĞĞ ƌĂĚŝĐĂůƐ ĂŶĚ ƚŚĞ ƌĞŐƵůĂƚŝŽŶ ŽĨ ŵĂŵŵĂůŝĂŶ ĐĞůů
ƉƌŽůŝĨĞƌĂƚŝŽŶ͘&ƌĞĞZĂĚŝĐZĞƐŽŵŵƵŶϲ;ϲͿ͗ϯϰϱͲϯϱϴ͘
ĂĚĞŶĂƐ͕ ͕ ĂǀŝĞƐ͕ <: ;ϮϬϬϬͿ DŝƚŽĐŚŽŶĚƌŝĂů ĨƌĞĞ ƌĂĚŝĐĂů ŐĞŶĞƌĂƚŝŽŶ͕ ŽǆŝĚĂƚŝǀĞ ƐƚƌĞƐƐ͕
ĂŶĚĂŐŝŶŐ͘&ƌĞĞZĂĚŝĐŝŽůDĞĚϮϵ;ϯͲϰͿ͗ϮϮϮͲϮϯϬ͘
ĂĚĞƚ͕ :>͕ <Ăƚǌ͕ D͕ :ĂĐŬƐŽŶͲ>ĞǁŝƐ͕ s͕ &ĂŚŶ͕ ^ ;ϭϵϴϵͿ sŝƚĂŵŝŶ ĂƚƚĞŶƵĂƚĞƐ ƚŚĞ ƚŽǆŝĐ
ĞĨĨĞĐƚƐ ŽĨ ŝŶƚƌĂƐƚƌŝĂƚĂů ŝŶũĞĐƚŝŽŶ ŽĨ ϲͲŚǇĚƌŽǆǇĚŽƉĂŵŝŶĞ ;ϲͲK,Ϳ ŝŶ ƌĂƚƐ͗ ďĞŚĂǀŝŽƌĂů
ĂŶĚďŝŽĐŚĞŵŝĐĂůĞǀŝĚĞŶĐĞ͘ƌĂŝŶZĞƐϰϳϲ;ϭͿ͗ϭϬͲϭϱ͘
ĂŵƉĞůůŽ͕ ^͕ >ĂĐĂůůĞ͕ Z͕ ĞƚƚĞůůĂ͕ D͕ DĂŶĞƐ͕ ^͕ ^ĐŽƌƌĂŶŽ͕ >͕ sŝŽůĂ͕ ;ϮϬϬϲͿ
KƌĐŚĞƐƚƌĂƚŝŽŶ ŽĨ ůǇŵƉŚŽĐǇƚĞ ĐŚĞŵŽƚĂǆŝƐ ďǇ ŵŝƚŽĐŚŽŶĚƌŝĂů ĚǇŶĂŵŝĐƐ͘ : ǆƉ DĞĚ
ϮϬϯ;ϭϯͿ͗ϮϴϳϵͲϮϴϴϲ͘
ĂŶŶŽŶ͕ :Z͕ 'ƌĞĞŶĂŵǇƌĞ͕ :d ;ϮϬϭϬͿ EĞƵƌŽƚŽǆŝĐ ŝŶ ǀŝǀŽ ŵŽĚĞůƐ ŽĨ WĂƌŬŝŶƐŽŶΖƐ ĚŝƐĞĂƐĞ
ƌĞĐĞŶƚĂĚǀĂŶĐĞƐ͘WƌŽŐƌĂŝŶZĞƐϭϴϰ͗ϭϳͲϯϯ͘
ĂƉŽƌŽƐƐŝ͕͕ŝĂĨƌĞ͕^͕WŝƚƚĂůƵŐĂ͕D͕^ĂǀŝŶŝ͕/͕&ĂƌĂĐĞ͕D';ϮϬϬϯͿĞůůƵůĂƌƌĞƐƉŽŶƐĞƐƚŽ
,;ϮͿK;ϮͿĂŶĚďůĞŽŵǇĐŝŶͲŝŶĚƵĐĞĚŽǆŝĚĂƚŝǀĞƐƚƌĞƐƐŝŶ>ϲϱƌĂƚŵǇŽďůĂƐƚƐ͘&ƌĞĞZĂĚŝĐŝŽů
DĞĚϯϱ;ϭϭͿ͗ϭϯϱϱͲϭϯϲϰ͘
ĂƐƐŝĚǇͲ^ƚŽŶĞ͕͕ŚŝƉƵŬ͕:͕/ŶŐĞƌŵĂŶ͕͕^ŽŶŐ͕͕zŽŽ͕͕<ƵǁĂŶĂ͕d͕<ƵƌƚŚ͕D:͕^ŚĂǁ͕
:d͕,ŝŶƐŚĂǁ͕:͕'ƌĞĞŶ͕Z͕EƵŶŶĂƌŝ͕:;ϮϬϬϴͿŚĞŵŝĐĂůŝŶŚŝďŝƚŝŽŶŽĨƚŚĞŵŝƚŽĐŚŽŶĚƌŝĂů
ĚŝǀŝƐŝŽŶĚǇŶĂŵŝŶƌĞǀĞĂůƐŝƚƐƌŽůĞŝŶĂǆͬĂŬͲĚĞƉĞŶĚĞŶƚŵŝƚŽĐŚŽŶĚƌŝĂůŽƵƚĞƌŵĞŵďƌĂŶĞ
ƉĞƌŵĞĂďŝůŝǌĂƚŝŽŶ͘ĞǀĞůůϭϰ;ϮͿ͗ϭϵϯͲϮϬϰ͘
ĞƌĞŐŚĞƚƚŝ͕'D͕^ƚĂŶŐŚĞƌůŝŶ͕͕DĂƌƚŝŶƐĚĞƌŝƚŽ͕K͕ŚĂŶŐ͕Z͕ůĂĐŬƐƚŽŶĞ͕͕ĞƌŶĂƌĚŝ͕
W͕^ĐŽƌƌĂŶŽ͕>;ϮϬϬϴͿĞƉŚŽƐƉŚŽƌǇůĂƚŝŽŶďǇĐĂůĐŝŶĞƵƌŝŶƌĞŐƵůĂƚĞƐƚƌĂŶƐůŽĐĂƚŝŽŶŽĨƌƉϭ
ƚŽŵŝƚŽĐŚŽŶĚƌŝĂ͘WƌŽĐEĂƚůĐĂĚ^Đŝh^ϭϬϱ;ϰϭͿ͗ϭϱϴϬϯͲϭϱϴϬϴ͘
ĞƌǀĞŶǇ͕ <>͕ DĐĂĨĨĞƌǇ͕ :D͕ :ĞŶƐĞŶ͕ Z ;ϮϬϬϭͿ ŝǀŝƐŝŽŶ ŽĨ ŵŝƚŽĐŚŽŶĚƌŝĂ ƌĞƋƵŝƌĞƐ Ă
ŶŽǀĞůDEϭͲŝŶƚĞƌĂĐƚŝŶŐƉƌŽƚĞŝŶ͕EĞƚϮƉ͘DŽůŝŽůĞůůϭϮ;ϮͿ͗ϯϬϵͲϯϮϭ͘
ŝƉŽůĂƚ͕^͕DĂƌƚŝŶƐĚĞƌŝƚŽ͕K͕ĂůŝůŝŽ͕͕^ĐŽƌƌĂŶŽ͕>;ϮϬϬϰͿKWϭƌĞƋƵŝƌĞƐŵŝƚŽĨƵƐŝŶ
ϭƚŽƉƌŽŵŽƚĞŵŝƚŽĐŚŽŶĚƌŝĂůĨƵƐŝŽŶ͘WƌŽĐEĂƚůĐĂĚ^Đŝh^ϭϬϭ;ϰϱͿ͗ϭϱϵϮϳͲϭϱϵϯϮ͘
ϴϳ
ŝƉŽůĂƚ͕ ^͕ ZƵĚŬĂ͕ d͕ ,ĂƌƚŵĂŶŶ͕ ͕ ŽƐƚĂ͕ s͕ ^ĞƌŶĞĞůƐ͕ >͕ ƌĂĞƐƐĂĞƌƚƐ͕ <͕ DĞƚǌŐĞƌ͕ <͕
&ƌĞǌǌĂ͕ ͕ ŶŶĂĞƌƚ͕ t͕ ΖĚĂŵŝŽ͕ >͕ ĞƌŬƐ͕ ͕ ĞũĂĞŐĞƌĞ͕ d͕ WĞůůĞŐƌŝŶŝ͕ >͕ Ζ,ŽŽŐĞ͕ Z͕
^ĐŽƌƌĂŶŽ͕>͕Ğ^ƚƌŽŽƉĞƌ͕;ϮϬϬϲͿDŝƚŽĐŚŽŶĚƌŝĂůƌŚŽŵďŽŝĚWZ>ƌĞŐƵůĂƚĞƐĐǇƚŽĐŚƌŽŵĞ
Đ ƌĞůĞĂƐĞ ĚƵƌŝŶŐ ĂƉŽƉƚŽƐŝƐ ǀŝĂ KWϭͲĚĞƉĞŶĚĞŶƚ ĐƌŝƐƚĂĞ ƌĞŵŽĚĞůŝŶŐ͘ Ğůů ϭϮϲ;ϭͿ͗ ϭϲϯͲ
ϭϳϱ͘
ŽŶŶĞƌ͕ '͕ ^ĂůĂƚŚĞ͕ D͕ &ŽƌƚĞǌĂ͕ Z ;ϮϬϬϮͿ >ĂĐƚŽƉĞƌŽǆŝĚĂƐĞ ĂŶĚ ŚǇĚƌŽŐĞŶ ƉĞƌŽǆŝĚĞ
ŵĞƚĂďŽůŝƐŵŝŶƚŚĞĂŝƌǁĂǇ͘ŵ:ZĞƐƉŝƌƌŝƚĂƌĞDĞĚϭϲϲ;ϭϮWƚϮͿ͗^ϱϳͲϲϭ͘
ŽƌƌĞŝĂ͕^͕^ĂŶƚŽƐ͕Zy͕WĞƌƌǇ͕'͕ŚƵ͕y͕DŽƌĞŝƌĂ͕W/͕^ŵŝƚŚ͕D;ϮϬϭϮͿDŝƚŽĐŚŽŶĚƌŝĂů
ŝŵƉŽƌƚĂŶĐĞ ŝŶ ůǌŚĞŝŵĞƌΖƐ͕ ,ƵŶƚŝŶŐƚŽŶΖƐ ĂŶĚ WĂƌŬŝŶƐŽŶΖƐ ĚŝƐĞĂƐĞƐ͘ Ěǀ ǆƉ DĞĚ ŝŽů
ϳϮϰ͗ϮϬϱͲϮϮϭ͘
ŽƐƚĂ͕s͕'ŝĂĐŽŵĞůůŽ͕D͕,ƵĚĞĐ͕Z͕>ŽƉƌĞŝĂƚŽ͕Z͕ƌŵĂŬ͕'͕>ŝŵ͕͕DĂůŽƌŶŝ͕t͕ĂǀŝĞƐ͕
<:͕ĂƌĂĨŽůŝ͕͕^ĐŽƌƌĂŶŽ͕>;ϮϬϭϬͿDŝƚŽĐŚŽŶĚƌŝĂůĨŝƐƐŝŽŶĂŶĚĐƌŝƐƚĂĞĚŝƐƌƵƉƚŝŽŶŝŶĐƌĞĂƐĞ
ƚŚĞ ƌĞƐƉŽŶƐĞ ŽĨ ĐĞůů ŵŽĚĞůƐ ŽĨ ,ƵŶƚŝŶŐƚŽŶΖƐ ĚŝƐĞĂƐĞ ƚŽ ĂƉŽƉƚŽƚŝĐ ƐƚŝŵƵůŝ͘ DK DŽů
DĞĚϮ;ϭϮͿ͗ϰϵϬͲϱϬϯ͘
ƌŝďďƐ͕ :d͕ ^ƚƌĂĐŬ͕ ^ ;ϮϬϬϳͿ ZĞǀĞƌƐŝďůĞ ƉŚŽƐƉŚŽƌǇůĂƚŝŽŶ ŽĨ ƌƉϭ ďǇ ĐǇĐůŝĐ DWͲ
ĚĞƉĞŶĚĞŶƚ ƉƌŽƚĞŝŶ ŬŝŶĂƐĞ ĂŶĚ ĐĂůĐŝŶĞƵƌŝŶ ƌĞŐƵůĂƚĞƐ ŵŝƚŽĐŚŽŶĚƌŝĂů ĨŝƐƐŝŽŶ ĂŶĚ ĐĞůů
ĚĞĂƚŚ͘DKZĞƉϴ;ϭϬͿ͗ϵϯϵͲϵϰϰ͘
Ƶŝ͕D͕dĂŶŐ͕y͕ŚƌŝƐƚŝĂŶ͕ts͕zŽŽŶ͕z͕dŝĞƵ͕<;ϮϬϭϬͿWĞƌƚƵƌďĂƚŝŽŶƐŝŶŵŝƚŽĐŚŽŶĚƌŝĂů
ĚǇŶĂŵŝĐƐ ŝŶĚƵĐĞĚ ďǇ ŚƵŵĂŶ ŵƵƚĂŶƚ W/E<ϭ ĐĂŶ ďĞ ƌĞƐĐƵĞĚ ďǇ ƚŚĞ ŵŝƚŽĐŚŽŶĚƌŝĂů
ĚŝǀŝƐŝŽŶŝŶŚŝďŝƚŽƌŵĚŝǀŝͲϭ͘:ŝŽůŚĞŵϮϴϱ;ϭϱͿ͗ϭϭϳϰϬͲϭϭϳϱϮ͘
ƵŶŶŝĨĨ͕ ͕ ĞŶƐŽŶ͕ <͕ ^ƚƵŵƉĨĨ͕ :͕ EĞǁŝĐŬ͕ <͕ ,ĞůĚ͕ W͕ dĂĂƚũĞƐ͕ ͕ :ŽƐĞƉŚ͕ :͕
<ĂůǇĂŶĂƌĂŵĂŶ͕ ͕ ,ĞŝŶƚǌ͕ E, ;ϮϬϭϯͿ DŝƚŽĐŚŽŶĚƌŝĂůͲƚĂƌŐĞƚĞĚ ŶŝƚƌŽǆŝĚĞƐ ĚŝƐƌƵƉƚ
ŵŝƚŽĐŚŽŶĚƌŝĂů ĂƌĐŚŝƚĞĐƚƵƌĞ ĂŶĚ ŝŶŚŝďŝƚ ĞǆƉƌĞƐƐŝŽŶ ŽĨ ƉĞƌŽǆŝƌĞĚŽǆŝŶ ϯ ĂŶĚ &KyDϭ ŝŶ
ŵĂůŝŐŶĂŶƚŵĞƐŽƚŚĞůŝŽŵĂĐĞůůƐ͘:ĞůůWŚǇƐŝŽůϮϮϴ;ϰͿ͗ϴϯϱͲϴϰϱ͘
ƵƌƚŝƵƐ͕ ,͕ tŽůĨĞŶƐďĞƌŐĞƌ͕ D͕ ^ƚĞŝŶŵĂŶŶ͕ ͕ ZĞĚǁĞŝŬ͕ h͕ ^ŝĞŐĨƌŝĞĚ͕ : ;ϭϵϳϰͿ DĂƐƐ
ĨƌĂŐŵĞŶƚŽŐƌĂƉŚǇ ŽĨ ĚŽƉĂŵŝŶĞ ĂŶĚ ϲͲŚǇĚƌŽǆǇĚŽƉĂŵŝŶĞ͘ ƉƉůŝĐĂƚŝŽŶ ƚŽ ƚŚĞ
ĚĞƚĞƌŵŝŶĂƚŝŽŶ ŽĨ ĚŽƉĂŵŝŶĞ ŝŶ ŚƵŵĂŶ ďƌĂŝŶ ďŝŽƉƐŝĞƐ ĨƌŽŵ ƚŚĞ ĐĂƵĚĂƚĞ ŶƵĐůĞƵƐ͘ :
ŚƌŽŵĂƚŽŐƌϵϵ;ϬͿ͗ϱϮϵͲϱϰϬ͘
ŚĂŶ͕,͕WĂƵƌ͕,͕sĞƌŶŽŶ͕͕ĂďĂƌƐŬǇ͕s͕ĂƚůĂ͕<W͕ƌŽƵĐŚĞƌ͕D:͕ĞǆƚĞƌ͕d;ϮϬϭϬͿ
EĞƵƌŽƉƌŽƚĞĐƚŝŽŶ ĂŶĚ &ƵŶĐƚŝŽŶĂů ZĞĐŽǀĞƌǇ ƐƐŽĐŝĂƚĞĚ ǁŝƚŚ ĞĐƌĞĂƐĞĚ DŝĐƌŽŐůŝĂů
ĐƚŝǀĂƚŝŽŶ&ŽůůŽǁŝŶŐ^ĞůĞĐƚŝǀĞĐƚŝǀĂƚŝŽŶŽĨŵ'ůƵZϮͬϯZĞĐĞƉƚŽƌƐŝŶĂZŽĚĞŶƚDŽĚĞůŽĨ
WĂƌŬŝŶƐŽŶΖƐŝƐĞĂƐĞ͘WĂƌŬŝŶƐŽŶƐŝƐϮϬϭϬ͘
ŚĂŶĚƌĂŶ͕ <͕ ŐŐĂƌǁĂů͕ ͕ DŝŐƌŝŶŽ͕ ZY͕ :ŽƐĞƉŚ͕ :͕ DĐůůŝƐƚĞƌ͕ ͕ <ŽŶŽƌĞǀ͕ ͕
ŶƚŚŽůŝŶĞ͕ t͕ ŝĞůŽŶŬĂ͕ :͕ ^ƌŝŶŝǀĂƐĂŶ͕ ^͕ ǀĂĚŚĂŶŝ͕ E'͕ <ĂůǇĂŶĂƌĂŵĂŶ͕ ;ϮϬϬϵͿ
ŽǆŽƌƵďŝĐŝŶ ŝŶĂĐƚŝǀĂƚĞƐŵǇŽĐĂƌĚŝĂů ĐǇƚŽĐŚƌŽŵĞĐ ŽǆŝĚĂƐĞ ŝŶ ƌĂƚƐ͗ ĐĂƌĚŝŽƉƌŽƚĞĐƚŝŽŶ ďǇ
DŝƚŽͲY͘ŝŽƉŚǇƐ:ϵϲ;ϰͿ͗ϭϯϴϴͲϭϯϵϴ͘
ŚĂŶŐ͕Z͕ůĂĐŬƐƚŽŶĞ͕;ϮϬϬϳͿǇĐůŝĐDWͲĚĞƉĞŶĚĞŶƚƉƌŽƚĞŝŶŬŝŶĂƐĞƉŚŽƐƉŚŽƌǇůĂƚŝŽŶ
ϴϴ
ŽĨ ƌƉϭ ƌĞŐƵůĂƚĞƐ ŝƚƐ 'dWĂƐĞ ĂĐƚŝǀŝƚǇ ĂŶĚ ŵŝƚŽĐŚŽŶĚƌŝĂů ŵŽƌƉŚŽůŽŐǇ͘ : ŝŽů ŚĞŵ
ϮϴϮ;ϯϬͿ͗ϮϭϱϴϯͲϮϭϱϴϳ͘
ŚĂŶŐ͕ Z͕ ůĂĐŬƐƚŽŶĞ͕ ;ϮϬϭϬͿ ǇŶĂŵŝĐ ƌĞŐƵůĂƚŝŽŶ ŽĨ ŵŝƚŽĐŚŽŶĚƌŝĂů ĨŝƐƐŝŽŶ ƚŚƌŽƵŐŚ
ŵŽĚŝĨŝĐĂƚŝŽŶŽĨƚŚĞĚǇŶĂŵŝŶͲƌĞůĂƚĞĚƉƌŽƚĞŝŶƌƉϭ͘ŶŶEzĐĂĚ^ĐŝϭϮϬϭ͗ϯϰͲϯϵ͘
ŚĂŶŐ͕ d͕ ZĞǇŶŽůĚƐ͕ /: ;ϮϬϬϲĂͿ ŝĨĨĞƌĞŶĐĞƐ ŝŶ ŵŝƚŽĐŚŽŶĚƌŝĂů ŵŽǀĞŵĞŶƚ ĂŶĚ
ŵŽƌƉŚŽůŽŐǇ ŝŶ ǇŽƵŶŐ ĂŶĚ ŵĂƚƵƌĞ ƉƌŝŵĂƌǇ ĐŽƌƚŝĐĂů ŶĞƵƌŽŶƐ ŝŶ ĐƵůƚƵƌĞ͘ EĞƵƌŽƐĐŝĞŶĐĞ
ϭϰϭ;ϮͿ͗ϳϮϳͲϳϯϲ͘
ŚĂŶŐ͕d͕ZŝŶƚŽƵů͕'>͕WĂŶĚŝƉĂƚŝ͕^͕ZĞǇŶŽůĚƐ͕/:;ϮϬϬϲďͿDƵƚĂŶƚŚƵŶƚŝŶŐƚŝŶĂŐŐƌĞŐĂƚĞƐ
ŝŵƉĂŝƌ ŵŝƚŽĐŚŽŶĚƌŝĂů ŵŽǀĞŵĞŶƚ ĂŶĚ ƚƌĂĨĨŝĐŬŝŶŐ ŝŶ ĐŽƌƚŝĐĂů ŶĞƵƌŽŶƐ͘ EĞƵƌŽďŝŽů ŝƐ
ϮϮ;ϮͿ͗ϯϴϴͲϰϬϬ͘
ŚĞŶ͕ D ;ϮϬϭϭͿ DŝƚŽĐŚŽŶĚƌŝĂů ĚǇƐĨƵŶĐƚŝŽŶ͕ ŵĞƚĂďŽůŝĐ ĚĞĨŝĐŝƚƐ͕ ĂŶĚ ŝŶĐƌĞĂƐĞĚ
ŽǆŝĚĂƚŝǀĞƐƚƌĞƐƐŝŶ,ƵŶƚŝŶŐƚŽŶΖƐĚŝƐĞĂƐĞ͘ŚĂŶŐ'ƵŶŐDĞĚ:ϯϰ;ϮͿ͗ϭϯϱͲϭϱϮ͘
ŚĞŶ͕D͕tƵ͕zZ͕ŚĞŶŐ͕D>͕>ŝƵ͕:>͕>ĞĞ͕zD͕>ĞĞ͕Wt͕^ŽŽŶŐ͕t͕ŚŝƵ͕d;ϮϬϬϳĂͿ
/ŶĐƌĞĂƐĞĚ ŽǆŝĚĂƚŝǀĞ ĚĂŵĂŐĞ ĂŶĚ ŵŝƚŽĐŚŽŶĚƌŝĂů ĂďŶŽƌŵĂůŝƚŝĞƐ ŝŶ ƚŚĞ ƉĞƌŝƉŚĞƌĂů ďůŽŽĚ
ŽĨ,ƵŶƚŝŶŐƚŽŶΖƐĚŝƐĞĂƐĞƉĂƚŝĞŶƚƐ͘ŝŽĐŚĞŵŝŽƉŚǇƐZĞƐŽŵŵƵŶϯϱϵ;ϮͿ͗ϯϯϱͲϯϰϬ͘
ŚĞŶ͕/;ϮϬϭϮͿDŝƚŽĐŚŽŶĚƌŝĂůĚǇƐĨƵŶĐƚŝŽŶĂŶĚĐĂŶĐĞƌŵĞƚĂƐƚĂƐŝƐ͘:ŝŽĞŶĞƌŐŝŽŵĞŵďƌ
ϰϰ;ϲͿ͗ϲϭϵͲϲϮϮ͘
ŚĞŶ͕,͕ŚĂŶ͕;ϮϬϬϱĂͿŵĞƌŐŝŶŐĨƵŶĐƚŝŽŶƐŽĨŵĂŵŵĂůŝĂŶŵŝƚŽĐŚŽŶĚƌŝĂůĨƵƐŝŽŶĂŶĚ
ĨŝƐƐŝŽŶ͘,ƵŵDŽů'ĞŶĞƚϭϰ^ƉĞĐEŽ͘Ϯ͗ZϮϴϯͲϮϴϵ͘
ŚĞŶ͕ ,͕ ŚĂŶ͕ ;ϮϬϬϵͿ DŝƚŽĐŚŽŶĚƌŝĂů ĚǇŶĂŵŝĐƐͲͲĨƵƐŝŽŶ͕ ĨŝƐƐŝŽŶ͕ ŵŽǀĞŵĞŶƚ͕ ĂŶĚ
ŵŝƚŽƉŚĂŐǇͲͲŝŶŶĞƵƌŽĚĞŐĞŶĞƌĂƚŝǀĞĚŝƐĞĂƐĞƐ͘,ƵŵDŽů'ĞŶĞƚϭϴ;ZϮͿ͗ZϭϲϵͲϭϳϲ͘
ŚĞŶ͕ ,͕ ŚŽŵǇŶ͕ ͕ ŚĂŶ͕ ;ϮϬϬϱďͿ ŝƐƌƵƉƚŝŽŶ ŽĨ ĨƵƐŝŽŶ ƌĞƐƵůƚƐ ŝŶ ŵŝƚŽĐŚŽŶĚƌŝĂů
ŚĞƚĞƌŽŐĞŶĞŝƚǇĂŶĚĚǇƐĨƵŶĐƚŝŽŶ͘:ŝŽůŚĞŵϮϴϬ;ϮϴͿ͗ϮϲϭϴϱͲϮϲϭϵϮ͘
ŚĞŶ͕ ,͕ ĞƚŵĞƌ͕ ^͕ ǁĂůĚ͕ :͕ 'ƌŝĨĨŝŶ͕ ͕ &ƌĂƐĞƌ͕ ^͕ ŚĂŶ͕ ;ϮϬϬϯͿ DŝƚŽĨƵƐŝŶƐ
DĨŶϭ ĂŶĚ DĨŶϮ ĐŽŽƌĚŝŶĂƚĞůǇ ƌĞŐƵůĂƚĞ ŵŝƚŽĐŚŽŶĚƌŝĂů ĨƵƐŝŽŶ ĂŶĚ ĂƌĞ ĞƐƐĞŶƚŝĂů ĨŽƌ
ĞŵďƌǇŽŶŝĐĚĞǀĞůŽƉŵĞŶƚ͘:ĞůůŝŽůϭϲϬ;ϮͿ͗ϭϴϵͲϮϬϬ͘
ŚĞŶ͕ ^͕ KǁĞŶƐ͕ '͕ ƌŽƐƐŝŶ͕ <>͕ ĚĞůŵĂŶ͕ ;ϮϬϬϳďͿ ^ĞƌŽƚŽŶŝŶ ƐƚŝŵƵůĂƚĞƐ
ŵŝƚŽĐŚŽŶĚƌŝĂůƚƌĂŶƐƉŽƌƚŝŶŚŝƉƉŽĐĂŵƉĂůŶĞƵƌŽŶƐ͘DŽůĞůůEĞƵƌŽƐĐŝϯϲ;ϰͿ͗ϰϳϮͲϰϴϯ͘
ŚĞŶ͕z͕<ůŝŽŶƐŬǇ͕:;ϮϬϭϭͿdŚĞƌĞŐƵůĂƚŝŽŶŽĨĂƵƚŽƉŚĂŐǇͲƵŶĂŶƐǁĞƌĞĚƋƵĞƐƚŝŽŶƐ͘:Ğůů
^ĐŝϭϮϰ;WƚϮͿ͗ϭϲϭͲϭϳϬ͘
ŚĞƵŶŐ͕͕DĐƌŝĚĞ͕,D͕^ůĂĐŬ͕Z^;ϮϬϬϳͿDŝƚŽĐŚŽŶĚƌŝĂůĚǇŶĂŵŝĐƐŝŶƚŚĞƌĞŐƵůĂƚŝŽŶŽĨ
ŶĞƵƌŽŶĂůĐĞůůĚĞĂƚŚ͘ƉŽƉƚŽƐŝƐϭϮ;ϱͿ͗ϵϳϵͲϵϵϮ͘
ϴϵ
ŚŽŝ͕ t^͕ zŽŽŶ͕ ^z͕ KŚ͕ d,͕ ŚŽŝ͕ :͕ KΖDĂůůĞǇ͕ <>͕ KŚ͕ z: ;ϭϵϵϵͿ dǁŽ ĚŝƐƚŝŶĐƚ
ŵĞĐŚĂŶŝƐŵƐ ĂƌĞ ŝŶǀŽůǀĞĚ ŝŶ ϲͲŚǇĚƌŽǆǇĚŽƉĂŵŝŶĞͲ ĂŶĚ DWWнͲŝŶĚƵĐĞĚ ĚŽƉĂŵŝŶĞƌŐŝĐ
ŶĞƵƌŽŶĂůĐĞůůĚĞĂƚŚ͗ƌŽůĞŽĨĐĂƐƉĂƐĞƐ͕ZK^͕ĂŶĚ:E<͘:EĞƵƌŽƐĐŝZĞƐϱϳ;ϭͿ͗ϴϲͲϵϰ͘
ŚƵŶŐ͕::͕KŬĂŵŽƚŽ͕z͕Žďůŝƚǌ͕͕>ŝ͕D͕YŝƵ͕z͕ ^ŚŝŬĂŶŽ͕^;ϮϬϬϵͿW/ϯ<ͬŬƚƐŝŐŶĂůůŝŶŐͲ
ŵĞĚŝĂƚĞĚ ƉƌŽƚĞŝŶ ƐƵƌĨĂĐĞ ĞǆƉƌĞƐƐŝŽŶ ƐĞŶƐĞĚ ďǇ ϭϰͲϯͲϯ ŝŶƚĞƌĂĐƚŝŶŐ ŵŽƚŝĨ͘ &^ :
Ϯϳϲ;ϭϵͿ͗ϱϱϰϳͲϱϱϱϴ͘
ĂŐĚĂ͕Z<͕ŚƵ͕:͕<ƵůŝĐŚ͕^D͕ŚƵ͕d;ϮϬϬϴͿDŝƚŽĐŚŽŶĚƌŝĂůůǇůŽĐĂůŝǌĞĚZ<ϮƌĞŐƵůĂƚĞƐ
ŵŝƚŽƉŚĂŐǇĂŶĚĂƵƚŽƉŚĂŐŝĐĐĞůůƐƚƌĞƐƐ͗ŝŵƉůŝĐĂƚŝŽŶƐĨŽƌWĂƌŬŝŶƐŽŶΖƐĚŝƐĞĂƐĞ͘ƵƚŽƉŚĂŐǇ
ϰ;ϲͿ͗ϳϳϬͲϳϴϮ͘
ĂŶŝŶŽ͕ ͕ DŽŽŶ͕ <,͕ ,ŝŶƐŚĂǁ͕ : ;ϮϬϬϰͿ ZĂƉŝĚ ĐŽŶƐƚƌŝĐƚŝŽŶ ŽĨ ůŝƉŝĚ ďŝůĂǇĞƌƐ ďǇ ƚŚĞ
ŵĞĐŚĂŶŽĐŚĞŵŝĐĂůĞŶǌǇŵĞĚǇŶĂŵŝŶ͘:^ƚƌƵĐƚŝŽůϭϰϳ;ϯͿ͗ϮϱϵͲϮϲϳ͘
ĂƌůĞǇͲhƐŵĂƌ͕s͕,ĂůůŝǁĞůů͕;ϭϵϵϲͿůŽŽĚƌĂĚŝĐĂůƐ͗ƌĞĂĐƚŝǀĞŶŝƚƌŽŐĞŶƐƉĞĐŝĞƐ͕ƌĞĂĐƚŝǀĞ
ŽǆǇŐĞŶƐƉĞĐŝĞƐ͕ƚƌĂŶƐŝƚŝŽŶŵĞƚĂůŝŽŶƐ͕ĂŶĚƚŚĞǀĂƐĐƵůĂƌƐǇƐƚĞŵ͘WŚĂƌŵZĞƐϭϯ;ϱͿ͗ϲϰϵͲ
ϲϲϮ͘
ĂƵĞƌ͕t͕WƌǌĞĚďŽƌƐŬŝ͕^;ϮϬϬϯͿWĂƌŬŝŶƐŽŶΖƐĚŝƐĞĂƐĞ͗ŵĞĐŚĂŶŝƐŵƐĂŶĚŵŽĚĞůƐ͘EĞƵƌŽŶ
ϯϵ;ϲͿ͗ϴϴϵͲϵϬϵ͘
ĂǀŝĞƐ͕^t͕dƵƌŵĂŝŶĞ͕D͕ŽǌĞŶƐ͕͕ŝ&ŝŐůŝĂ͕D͕^ŚĂƌƉ͕,͕ZŽƐƐ͕͕^ĐŚĞƌǌŝŶŐĞƌ͕͕
tĂŶŬĞƌ͕ ͕ DĂŶŐŝĂƌŝŶŝ͕ >͕ ĂƚĞƐ͕ 'W ;ϭϵϵϳͿ &ŽƌŵĂƚŝŽŶ ŽĨ ŶĞƵƌŽŶĂů ŝŶƚƌĂŶƵĐůĞĂƌ
ŝŶĐůƵƐŝŽŶƐ ƵŶĚĞƌůŝĞƐ ƚŚĞ ŶĞƵƌŽůŽŐŝĐĂů ĚǇƐĨƵŶĐƚŝŽŶ ŝŶ ŵŝĐĞ ƚƌĂŶƐŐĞŶŝĐ ĨŽƌ ƚŚĞ ,
ŵƵƚĂƚŝŽŶ͘ĞůůϵϬ;ϯͿ͗ϱϯϳͲϱϰϴ͘
ĂǇ͕:͕ƌĂƉŽ͕:;ϭϵϵϲͿŵĞƚĂůůŽƉŽƌƉŚǇƌŝŶƐƵƉĞƌŽǆŝĚĞĚŝƐŵƵƚĂƐĞŵŝŵĞƚŝĐƉƌŽƚĞĐƚƐ
ĂŐĂŝŶƐƚƉĂƌĂƋƵĂƚͲŝŶĚƵĐĞĚůƵŶŐŝŶũƵƌǇŝŶǀŝǀŽ͘dŽǆŝĐŽůƉƉůWŚĂƌŵĂĐŽůϭϰϬ;ϭͿ͗ϵϰͲϭϬϬ͘
ĂǇ͕ :͕ ^ŚĂǁĞŶ͕ ^͕ >ŝŽĐŚĞǀ͕ ^/͕ ƌĂƉŽ͕ : ;ϭϵϵϱͿ ŵĞƚĂůůŽƉŽƌƉŚǇƌŝŶ ƐƵƉĞƌŽǆŝĚĞ
ĚŝƐŵƵƚĂƐĞŵŝŵĞƚŝĐƉƌŽƚĞĐƚƐĂŐĂŝŶƐƚƉĂƌĂƋƵĂƚͲŝŶĚƵĐĞĚĞŶĚŽƚŚĞůŝĂůĐĞůůŝŶũƵƌǇ͕ŝŶǀŝƚƌŽ͘:
WŚĂƌŵĂĐŽůǆƉdŚĞƌϮϳϱ;ϯͿ͗ϭϮϮϳͲϭϮϯϮ͘
ĞƵǀĞ͕;ϭϵϲϯͿdŚĞůǇƐŽƐŽŵĞ͘^ĐŝŵϮϬϴ͗ϲϰͲϳϮ͘
ĚĞ >ĂƵ͕ >D͕ ƌĞƚĞůĞƌ͕ DD ;ϮϬϬϲͿ ƉŝĚĞŵŝŽůŽŐǇ ŽĨ WĂƌŬŝŶƐŽŶΖƐ ĚŝƐĞĂƐĞ͘ >ĂŶĐĞƚ EĞƵƌŽů
ϱ;ϲͿ͗ϱϮϱͲϱϯϱ͘
ĞsŽƐ͕<:͕ůůĂŶ͕s:͕'ƌŝĞƌƐŽŶ͕:͕^ŚĞĞƚǌ͕DW;ϮϬϬϱͿDŝƚŽĐŚŽŶĚƌŝĂůĨƵŶĐƚŝŽŶĂŶĚĂĐƚŝŶ
ƌĞŐƵůĂƚĞ ĚǇŶĂŵŝŶͲƌĞůĂƚĞĚ ƉƌŽƚĞŝŶ ϭͲĚĞƉĞŶĚĞŶƚ ŵŝƚŽĐŚŽŶĚƌŝĂů ĨŝƐƐŝŽŶ͘ Ƶƌƌ ŝŽů ϭϱ;ϳͿ͗
ϲϳϴͲϲϴϯ͘
ĞůĂǀĂůůĞĞ͕ >͕ ĂďŽŶ͕ >͕ 'ĂůĂŶͲDĂůŽ͕ W͕ >ŽƌĞŶǌŽ͕ ,<͕ ^ƵƐŝŶ͕ ^ ;ϮϬϭϭͿ /&ͲŵĞĚŝĂƚĞĚ
ĐĂƐƉĂƐĞͲŝŶĚĞƉĞŶĚĞŶƚŶĞĐƌŽƉƚŽƐŝƐ͗ĂŶĞǁĐŚĂŶĐĞĨŽƌƚĂƌŐĞƚĞĚƚŚĞƌĂƉĞƵƚŝĐƐ͘/hD>ŝĨĞ
ϲϯ;ϰͿ͗ϮϮϭͲϮϯϮ͘
ϵϬ
ĞůĞƚƚƌĞ͕͕>ĞŶĂĞƌƐ͕'͕'ƌŝĨĨŽŝŶ͕:D͕'ŝŐĂƌĞů͕E͕>ŽƌĞŶǌŽ͕͕ĞůĞŶŐƵĞƌ͕W͕WĞůůŽƋƵŝŶ͕>͕
'ƌŽƐŐĞŽƌŐĞ͕ :͕ dƵƌĐͲĂƌĞů͕ ͕ WĞƌƌĞƚ͕ ͕ ƐƚĂƌŝĞͲĞƋƵĞŬĞƌ͕ ͕ >ĂƐƋƵĞůůĞĐ͕ >͕ ƌŶĂƵĚ͕ ͕
ƵĐŽŵŵƵŶ͕ ͕ <ĂƉůĂŶ͕ :͕ ,ĂŵĞů͕ W ;ϮϬϬϬͿ EƵĐůĞĂƌ ŐĞŶĞ KWϭ͕ ĞŶĐŽĚŝŶŐ Ă
ŵŝƚŽĐŚŽŶĚƌŝĂů ĚǇŶĂŵŝŶͲƌĞůĂƚĞĚ ƉƌŽƚĞŝŶ͕ ŝƐ ŵƵƚĂƚĞĚ ŝŶ ĚŽŵŝŶĂŶƚ ŽƉƚŝĐ ĂƚƌŽƉŚǇ͘ EĂƚ
'ĞŶĞƚϮϲ;ϮͿ͗ϮϬϳͲϮϭϬ͘
ĞŶŐũĞů͕ :͕ <ƌŝƐƚĞŶƐĞŶ͕ Z͕ ŶĚĞƌƐĞŶ͕ :^ ;ϮϬϬϴͿ KƌĚĞƌĞĚ ďƵůŬ ĚĞŐƌĂĚĂƚŝŽŶ ǀŝĂ
ĂƵƚŽƉŚĂŐǇ͘ƵƚŽƉŚĂŐǇϰ;ϴͿ͗ϭϬϱϳͲϭϬϱϵ͘
ĞǀĂƐĂŐĂǇĂŵ͕ dW͕dŝůĂŬ͕:͕ ŽůŽŽƌ͕ <<͕ ^ĂŶĞ͕ <^͕ 'ŚĂƐŬĂĚďŝ͕ ^^͕ >ĞůĞ͕ Z ;ϮϬϬϰͿ &ƌĞĞ
ƌĂĚŝĐĂůƐĂŶĚĂŶƚŝŽǆŝĚĂŶƚƐŝŶŚƵŵĂŶŚĞĂůƚŚ͗ĐƵƌƌĞŶƚƐƚĂƚƵƐĂŶĚĨƵƚƵƌĞƉƌŽƐƉĞĐƚƐ͘:ƐƐŽĐ
WŚǇƐŝĐŝĂŶƐ/ŶĚŝĂϱϮ͗ϳϵϰͲϴϬϰ͘
ŚĂŶĂƐĞŬĂƌĂŶ͕ ͕ <ŽƚĂŵƌĂũƵ͕ ^͕ <ĂƌƵŶĂŬĂƌĂŶ͕ ͕ <ĂůŝǀĞŶĚŝ͕ ^s͕ dŚŽŵĂƐ͕ ^͕ :ŽƐĞƉŚ͕ :͕
<ĂůǇĂŶĂƌĂŵĂŶ͕;ϮϬϬϱͿDŝƚŽĐŚŽŶĚƌŝĂƐƵƉĞƌŽǆŝĚĞĚŝƐŵƵƚĂƐĞŵŝŵĞƚŝĐŝŶŚŝďŝƚƐƉĞƌŽǆŝĚĞͲ
ŝŶĚƵĐĞĚŽǆŝĚĂƚŝǀĞĚĂŵĂŐĞĂŶĚĂƉŽƉƚŽƐŝƐ͗ƌŽůĞŽĨŵŝƚŽĐŚŽŶĚƌŝĂůƐƵƉĞƌŽǆŝĚĞ͘&ƌĞĞZĂĚŝĐ
ŝŽůDĞĚϯϵ;ϱͿ͗ϱϲϳͲϱϴϯ͘
ŝ&ŝŐůŝĂ͕D͕^ĂƉƉ͕͕ŚĂƐĞ͕<K͕ĂǀŝĞƐ͕^t͕ĂƚĞƐ͕'W͕sŽŶƐĂƚƚĞů͕:W͕ƌŽŶŝŶ͕E;ϭϵϵϳͿ
ŐŐƌĞŐĂƚŝŽŶŽĨŚƵŶƚŝŶŐƚŝŶŝŶŶĞƵƌŽŶĂůŝŶƚƌĂŶƵĐůĞĂƌŝŶĐůƵƐŝŽŶƐĂŶĚĚǇƐƚƌŽƉŚŝĐŶĞƵƌŝƚĞƐ
ŝŶďƌĂŝŶ͘^ĐŝĞŶĐĞϮϳϳ;ϱϯϯϰͿ͗ϭϵϵϬͲϭϵϵϯ͘
ŝŶŐ͕ &͕ ^ŚĂŽ͕ t͕ zĂŶŐ͕ ^,͕ tƵ͕ Y͕ 'ĂŽ͕ &͕ yŝŽŶŐ͕ >D ;ϮϬϭϮͿ ZŽůĞ ŽĨ ŵŝƚŽĐŚŽŶĚƌŝĂů
ƉĂƚŚǁĂǇŝŶĐŽŵƉƌĞƐƐŝŽŶͲŝŶĚƵĐĞĚĂƉŽƉƚŽƐŝƐŽĨŶƵĐůĞƵƐƉƵůƉŽƐƵƐĐĞůůƐ͘ƉŽƉƚŽƐŝƐ͘
ƌŽŐĞ͕t;ϮϬϬϮͿ&ƌĞĞƌĂĚŝĐĂůƐŝŶƚŚĞƉŚǇƐŝŽůŽŐŝĐĂůĐŽŶƚƌŽůŽĨĐĞůůĨƵŶĐƚŝŽŶ͘WŚǇƐŝŽůZĞǀ
ϴϮ;ϭͿ͗ϰϳͲϵϱ͘
ƵƌĂŶ͕͕>ŝŶĂƌĞƐ͕:&͕'ĂůǀĞǌ͕^͕tŝŬĞŶŚĞŝƐĞƌ͕<͕&ůŽƌĞƐ͕:D͕ŝĂǌͲDĞĐŽ͕Dd͕DŽƐĐĂƚ͕:
;ϮϬϬϴͿ dŚĞ ƐŝŐŶĂůŝŶŐ ĂĚĂƉƚŽƌ ƉϲϮ ŝƐ ĂŶ ŝŵƉŽƌƚĂŶƚ E&ͲŬĂƉƉĂ ŵĞĚŝĂƚŽƌ ŝŶ
ƚƵŵŽƌŝŐĞŶĞƐŝƐ͘ĂŶĐĞƌĞůůϭϯ;ϰͿ͗ϯϰϯͲϯϱϰ͘
ƵƌĂŶ͕ ͕ ^ĞƌƌĂŶŽ͕ D͕ >ĞŝƚŐĞƐ͕ D͕ &ůŽƌĞƐ͕ :D͕ WŝĐĂƌĚ͕ ^͕ ƌŽǁŶ͕ :W͕ DŽƐĐĂƚ͕ :͕ ŝĂǌͲ
DĞĐŽ͕Dd;ϮϬϬϰͿdŚĞĂƚǇƉŝĐĂůW<ͲŝŶƚĞƌĂĐƚŝŶŐƉƌŽƚĞŝŶƉϲϮŝƐĂŶŝŵƉŽƌƚĂŶƚŵĞĚŝĂƚŽƌŽĨ
ZE<ͲĂĐƚŝǀĂƚĞĚŽƐƚĞŽĐůĂƐƚŽŐĞŶĞƐŝƐ͘ĞǀĞůůϲ;ϮͿ͗ϯϬϯͲϯϬϵ͘
ĐŚƚĂǇ͕<^͕DƵƌƉŚǇ͕DW͕^ŵŝƚŚ͕Z͕dĂůďŽƚ͕͕ƌĂŶĚ͕D;ϮϬϬϮͿ^ƵƉĞƌŽǆŝĚĞĂĐƚŝǀĂƚĞƐ
ŵŝƚŽĐŚŽŶĚƌŝĂů ƵŶĐŽƵƉůŝŶŐ ƉƌŽƚĞŝŶ Ϯ ĨƌŽŵ ƚŚĞ ŵĂƚƌŝǆ ƐŝĚĞ͘ ^ƚƵĚŝĞƐ ƵƐŝŶŐ ƚĂƌŐĞƚĞĚ
ĂŶƚŝŽǆŝĚĂŶƚƐ͘:ŝŽůŚĞŵϮϳϳ;ϰϵͿ͗ϰϳϭϮϵͲϰϳϭϯϱ͘
ŐĂŶ͕&͕^ŚĂĐŬĞůĨŽƌĚ͕͕DŝŚĂǇůŽǀĂ͕DD͕'ĞůŝŶŽ͕^͕<ŽŚŶǌ͕Z͕DĂŝƌ͕t͕sĂƐƋƵĞǌ͕^͕
:ŽƐŚŝ͕͕'ǁŝŶŶ͕D͕dĂǇůŽƌ͕Z͕ƐĂƌĂ͕:D͕&ŝƚǌƉĂƚƌŝĐŬ͕:͕ŝůůŝŶ͕͕sŝŽůůĞƚ͕͕<ƵŶĚƵ͕D͕
,ĂŶƐĞŶ͕ D͕ ^ŚĂǁ͕ Z: ;ϮϬϭϭͿ WŚŽƐƉŚŽƌǇůĂƚŝŽŶ ŽĨ h><ϭ ;Śd'ϭͿ ďǇ DWͲĂĐƚŝǀĂƚĞĚ
ƉƌŽƚĞŝŶŬŝŶĂƐĞĐŽŶŶĞĐƚƐĞŶĞƌŐǇƐĞŶƐŝŶŐƚŽŵŝƚŽƉŚĂŐǇ͘^ĐŝĞŶĐĞϯϯϭ;ϲϬϭϲͿ͗ϰϱϲͲϰϲϭ͘
ůŵŽƌĞ͕^W͕YŝĂŶ͕d͕'ƌŝƐƐŽŵ͕^&͕>ĞŵĂƐƚĞƌƐ͕::;ϮϬϬϭͿdŚĞŵŝƚŽĐŚŽŶĚƌŝĂůƉĞƌŵĞĂďŝůŝƚǇ
ƚƌĂŶƐŝƚŝŽŶŝŶŝƚŝĂƚĞƐĂƵƚŽƉŚĂŐǇŝŶƌĂƚŚĞƉĂƚŽĐǇƚĞƐ͘&^:ϭϱ;ϭϮͿ͗ϮϮϴϲͲϮϮϴϳ͘
ϵϭ
ƵƌĂ͕ z͕ /ƐŚŝŚĂƌĂ͕ E͕ zŽŬŽƚĂ͕ ^͕ DŝŚĂƌĂ͕ < ;ϮϬϬϯͿ dǁŽ ŵŝƚŽĨƵƐŝŶ ƉƌŽƚĞŝŶƐ͕ ŵĂŵŵĂůŝĂŶ
ŚŽŵŽůŽŐƵĞƐŽĨ&K͕ǁŝƚŚĚŝƐƚŝŶĐƚĨƵŶĐƚŝŽŶƐĂƌĞďŽƚŚƌĞƋƵŝƌĞĚĨŽƌŵŝƚŽĐŚŽŶĚƌŝĂůĨƵƐŝŽŶ͘
:ŝŽĐŚĞŵϭϯϰ;ϯͿ͗ϯϯϯͲϯϰϰ͘
ǀĂŶƐ͕;ϭϵϬϳͿKŶƚŚĞĂƚĂůǇƚŝĐĞĐŽŵƉŽƐŝƚŝŽŶŽĨ,ǇĚƌŽŐĞŶWĞƌŽǆŝĚĞďǇƚŚĞĂƚĂůĂƐĞ
ŽĨůŽŽĚ͘ŝŽĐŚĞŵ:Ϯ;ϰͿ͗ϭϯϯͲϭϱϱ͘
&ĂĞƐ͕>͕ĂůůĞǁĂĞƌƚ͕';ϮϬϭϭͿDŝƚŽĐŚŽŶĚƌŝĂůĚǇƐĨƵŶĐƚŝŽŶŝŶĨĂŵŝůŝĂůĂŵǇŽƚƌŽƉŚŝĐůĂƚĞƌĂů
ƐĐůĞƌŽƐŝƐ͘:ŝŽĞŶĞƌŐŝŽŵĞŵďƌϰϯ;ϲͿ͗ϱϴϳͲϱϵϮ͘
&ĂƌŝƐƐ͕Dt͕ŚĂŶ͕͕WĂƚĞů͕D͕sĂŶ,ŽƵƚĞŶ͕͕KƌƌĞŶŝƵƐ͕^;ϮϬϬϱͿZŽůĞŽĨŵŝƚŽĐŚŽŶĚƌŝĂ
ŝŶƚŽǆŝĐŽǆŝĚĂƚŝǀĞƐƚƌĞƐƐ͘DŽů/ŶƚĞƌǀϱ;ϮͿ͗ϵϰͲϭϭϭ͘
&ĞƌŶĂŶĚĞǌͲ'ŽŵĞǌ͕&:͕'ĂůŝŶĚŽ͕D&͕'ŽŵĞǌͲ>ĂǌĂƌŽ͕D͕zƵƐƚĞ͕s:͕ŽŵĞůůĂ͕:y͕ŐƵŝƌƌĞ͕
E͕ :ŽƌĚĂŶ͕ : ;ϮϬϬϱͿ DĂůŽŶĂƚĞ ŝŶĚƵĐĞƐ ĐĞůů ĚĞĂƚŚ ǀŝĂ ŵŝƚŽĐŚŽŶĚƌŝĂů ƉŽƚĞŶƚŝĂů ĐŽůůĂƉƐĞ
ĂŶĚĚĞůĂǇĞĚƐǁĞůůŝŶŐƚŚƌŽƵŐŚĂŶZK^ͲĚĞƉĞŶĚĞŶƚƉĂƚŚǁĂǇ͘ƌ:WŚĂƌŵĂĐŽůϭϰϰ;ϰͿ͗ϱϮϴͲ
ϱϯϳ͘
&ĞƌŶĂŶĚĞǌͲ'ŽŵĞǌ͕ &:͕ WĂƐƚŽƌ͕ D͕ 'ĂƌĐŝĂͲDĂƌƚŝŶĞǌ͕ D͕ DĞůĞƌŽͲ&ĞƌŶĂŶĚĞǌ ĚĞ DĞƌĂ͕
Z͕ 'ŽƵͲ&ĂďƌĞŐĂƐ͕ D͕ 'ŽŵĞǌͲ>ĂǌĂƌŽ͕ D͕ ĂůǀŽ͕ ^͕ ^ŽůĞƌ͕ ZD͕ 'ĂůŝŶĚŽ͕ D&͕ :ŽƌĚĂŶ͕ :
;ϮϬϬϲͿ WǇƌƵǀĂƚĞ ƉƌŽƚĞĐƚƐ ĐĞƌĞďĞůůĂƌ ŐƌĂŶƵůĂƌ ĐĞůůƐ ĨƌŽŵ ϲͲŚǇĚƌŽǆǇĚŽƉĂŵŝŶĞͲŝŶĚƵĐĞĚ
ĐǇƚŽƚŽǆŝĐŝƚǇ ďǇ ĂĐƚŝǀĂƚŝŶŐ ƚŚĞ Ŭƚ ƐŝŐŶĂůŝŶŐ ƉĂƚŚǁĂǇ ĂŶĚ ŝŶĐƌĞĂƐŝŶŐ ŐůƵƚĂƚŚŝŽŶĞ
ƉĞƌŽǆŝĚĂƐĞĞǆƉƌĞƐƐŝŽŶ͘EĞƵƌŽďŝŽůŝƐϮϰ;ϮͿ͗ϮϵϲͲϯϬϳ͘
&ĞƌƌĂƌŝ͕ >&͕ ŚƵŵ͕ ͕ ŽŐĞŶ͕ K͕ ZĞŝĐŚůŝŶŐ͕ ͕ >ĞǀŝŶĞ͕ : ;ϮϬϭϭͿ ZŽůĞ ŽĨ ƌƉϭ͕ Ă ŬĞǇ
ŵŝƚŽĐŚŽŶĚƌŝĂůĨŝƐƐŝŽŶƉƌŽƚĞŝŶ͕ŝŶŶĞƵƌŽƉĂƚŚŝĐƉĂŝŶ͘:EĞƵƌŽƐĐŝϯϭ;ϯϭͿ͗ϭϭϰϬϰͲϭϭϰϭϬ͘
&ŝŶŬĞů͕d;ϭϵϵϴͿKǆǇŐĞŶƌĂĚŝĐĂůƐĂŶĚƐŝŐŶĂůŝŶŐ͘ƵƌƌKƉŝŶĞůůŝŽůϭϬ;ϮͿ͗ϮϰϴͲϮϱϯ͘
&ŝƐŬƵŵ͕ '͕ ^ƚĂƌŬŽǀ͕ ͕ WŽůƐƚĞƌ͕ D͕ ŚŝŶŽƉŽƵůŽƐ͕ ;ϮϬϬϯͿDŝƚŽĐŚŽŶĚƌŝĂůŵĞĐŚĂŶŝƐŵƐ
ŽĨŶĞƵƌĂůĐĞůůĚĞĂƚŚĂŶĚŶĞƵƌŽƉƌŽƚĞĐƚŝǀĞŝŶƚĞƌǀĞŶƚŝŽŶƐŝŶWĂƌŬŝŶƐŽŶΖƐĚŝƐĞĂƐĞ͘ŶŶEz
ĐĂĚ^Đŝϵϵϭ͗ϭϭϭͲϭϭϵ͘
&ƌĂŶŬ͕ ^͕ 'ĂƵŵĞ͕ ͕ ĞƌŐŵĂŶŶͲ>ĞŝƚŶĞƌ͕ ^͕ >ĞŝƚŶĞƌ͕ tt͕ ZŽďĞƌƚ͕ '͕ ĂƚĞǌ͕ &͕ ^ŵŝƚŚ͕
>͕zŽƵůĞ͕Z:;ϮϬϬϭͿdŚĞƌŽůĞŽĨĚǇŶĂŵŝŶͲƌĞůĂƚĞĚƉƌŽƚĞŝŶϭ͕ĂŵĞĚŝĂƚŽƌŽĨŵŝƚŽĐŚŽŶĚƌŝĂů
ĨŝƐƐŝŽŶ͕ŝŶĂƉŽƉƚŽƐŝƐ͘ĞǀĞůůϭ;ϰͿ͗ϱϭϱͲϱϮϱ͘
&ƵŬƵƐŚŝŵĂ͕ E,͕ ƌŝƐĐŚ͕ ͕ <ĞĞŐĂŶ͕ Z͕ ůĞĂǌĂƌĚ͕ t͕ ^ŚĂǁ͕ :D ;ϮϬϬϭͿ dŚĞ 'dWĂƐĞ
ĞĨĨĞĐƚŽƌĚŽŵĂŝŶƐĞƋƵĞŶĐĞŽĨƚŚĞŶŵϭƉ'dWĂƐĞƌĞŐƵůĂƚĞƐƐĞůĨͲĂƐƐĞŵďůǇĂŶĚĐŽŶƚƌŽůƐ
ĂƌĂƚĞͲůŝŵŝƚŝŶŐƐƚĞƉŝŶŵŝƚŽĐŚŽŶĚƌŝĂůĨŝƐƐŝŽŶ͘DŽůŝŽůĞůůϭϮ;ϵͿ͗ϮϳϱϲͲϮϳϲϲ͘
&ƵůĚĂ͕^͕ĞďĂƚŝŶ͕<D;ϮϬϬϲͿǆƚƌŝŶƐŝĐǀĞƌƐƵƐŝŶƚƌŝŶƐŝĐĂƉŽƉƚŽƐŝƐƉĂƚŚǁĂǇƐŝŶĂŶƚŝĐĂŶĐĞƌ
ĐŚĞŵŽƚŚĞƌĂƉǇ͘KŶĐŽŐĞŶĞϮϱ;ϯϰͿ͗ϰϳϵϴͲϰϴϭϭ͘
'ĂůĂƐ͕ D͕ ŝǌĂƚ͕ E͕ ƵǀĞůŝĞƌ͕ >͕ ĂŶƚƵďƵŶŐŝ͕ <͕ ƌŽƵŝůůĞƚ͕ ͕ ^ĐŚŝĨĨŵĂŶŶ͕ Ê͕ ůƵŵ͕ ;ϮϬϬϰͿĞĂƚŚŽĨĐŽƌƚŝĐĂůĂŶĚƐƚƌŝĂƚĂůŶĞƵƌŽŶƐŝŶĚƵĐĞĚďǇŵŝƚŽĐŚŽŶĚƌŝĂůĚĞĨĞĐƚŝŶǀŽůǀĞƐ
ϵϮ
ĚŝĨĨĞƌĞŶƚŝĂůŵŽůĞĐƵůĂƌŵĞĐŚĂŶŝƐŵƐ͘EĞƵƌŽďŝŽůŝƐϭϱ;ϭͿ͗ϭϱϮͲϭϱϵ͘
'ĂůŝŶĚŽ͕ D&͕ :ŽƌĚĂŶ͕ :͕ 'ŽŶǌĂůĞǌͲ'ĂƌĐŝĂ͕ ͕ ĞŶĂ͕ s ;ϮϬϬϯͿ ŚƌŽŵĂĨĨŝŶ ĐĞůů ĚĞĂƚŚ
ŝŶĚƵĐĞĚďǇϲͲŚǇĚƌŽǆǇĚŽƉĂŵŝŶĞŝƐŝŶĚĞƉĞŶĚĞŶƚŽĨŵŝƚŽĐŚŽŶĚƌŝĂůƐǁĞůůŝŶŐĂŶĚĐĂƐƉĂƐĞ
ĂĐƚŝǀĂƚŝŽŶ͘:EĞƵƌŽĐŚĞŵϴϰ;ϱͿ͗ϭϬϲϲͲϭϬϳϯ͘
'ĂůůƵǌǌŝ͕ >͕ <ĞƉƉ͕ K͕ dƌŽũĞůͲ,ĂŶƐĞŶ͕ ͕ <ƌŽĞŵĞƌ͕ ' ;ϮϬϭϮͿ EŽŶͲĂƉŽƉƚŽƚŝĐ ĨƵŶĐƚŝŽŶƐ ŽĨ
ĂƉŽƉƚŽƐŝƐͲƌĞŐƵůĂƚŽƌǇƉƌŽƚĞŝŶƐ͘DKZĞƉ͘
'ĂƐƐĞŶ͕D͕WŝŶĐŚĂƐŝ͕͕zŽƵĚŝŵ͕D;ϭϵϵϴͿƉŽŵŽƌƉŚŝŶĞŝƐĂƉŽƚĞŶƚƌĂĚŝĐĂůƐĐĂǀĞŶŐĞƌ
ĂŶĚ ƉƌŽƚĞĐƚƐ ĐƵůƚƵƌĞĚ ƉŚĞŽĐŚƌŽŵŽĐǇƚŽŵĂ ĐĞůůƐ ĨƌŽŵ ϲͲK, ĂŶĚ ,ϮKϮͲŝŶĚƵĐĞĚ ĐĞůů
ĚĞĂƚŚ͘ĚǀWŚĂƌŵĂĐŽůϰϮ͗ϯϮϬͲϯϮϰ͘
'ĞĞ͕ W͕ ĂǀŝƐŽŶ͕ : ;ϭϵϴϵͿ /ŶƚĞƌŵĞĚŝĂƚĞƐ ŝŶ ƚŚĞ ĂĞƌŽďŝĐ ĂƵƚŽǆŝĚĂƚŝŽŶ ŽĨ ϲͲ
ŚǇĚƌŽǆǇĚŽƉĂŵŝŶĞ͗ƌĞůĂƚŝǀĞŝŵƉŽƌƚĂŶĐĞƵŶĚĞƌĚŝĨĨĞƌĞŶƚƌĞĂĐƚŝŽŶĐŽŶĚŝƚŝŽŶƐ͘&ƌĞĞZĂĚŝĐ
ŝŽůDĞĚϲ;ϯͿ͗ϮϳϭͲϮϴϰ͘
'ĞŝƐůĞƌ͕ ^͕ ,ŽůŵƐƚƌŽŵ͕ <D͕ ^ŬƵũĂƚ͕ ͕ &ŝĞƐĞů͕ &͕ ZŽƚŚĨƵƐƐ͕ K͕ <ĂŚůĞ͕ W:͕ ^ƉƌŝŶŐĞƌ͕ t
;ϮϬϭϬͿ W/E<ϭͬWĂƌŬŝŶͲŵĞĚŝĂƚĞĚ ŵŝƚŽƉŚĂŐǇ ŝƐ ĚĞƉĞŶĚĞŶƚ ŽŶ sϭ ĂŶĚ ƉϲϮͬ^Y^dDϭ͘
EĂƚĞůůŝŽůϭϮ;ϮͿ͗ϭϭϵͲϭϯϭ͘
'ĞŶĂ͕ W͕ &ĂŶĞůůŝ͕ ͕ ƌĞŶŶĞƌ͕ ͕ ^ǀĞůƚŽ͕ D͕ ĂůĂŵŝƚĂ͕ ' ;ϮϬϬϵͿ EĞǁƐ ĂŶĚ ǀŝĞǁƐ ŽŶ
ŵŝƚŽĐŚŽŶĚƌŝĂůǁĂƚĞƌƚƌĂŶƐƉŽƌƚ͘&ƌŽŶƚŝŽƐĐŝϭϰ͗ϰϭϴϵͲϰϭϵϴ͘
'ĞƌŵĂŝŶ͕ D͕ DĂƚŚĂŝ͕ :W͕ DĐƌŝĚĞ͕ ,D͕ ^ŚŽƌĞ͕ ' ;ϮϬϬϱͿ ŶĚŽƉůĂƐŵŝĐ ƌĞƚŝĐƵůƵŵ /<
ŝŶŝƚŝĂƚĞƐZWϭͲƌĞŐƵůĂƚĞĚƌĞŵŽĚĞůůŝŶŐŽĨŵŝƚŽĐŚŽŶĚƌŝĂůĐƌŝƐƚĂĞĚƵƌŝŶŐĂƉŽƉƚŽƐŝƐ͘DK
:Ϯϰ;ϴͿ͗ϭϱϰϲͲϭϱϱϲ͘
'ŚŽďƌŝĂů͕ /D͕ tŝƚǌŝŐ͕ d͕ ĚũĞŝ͕ ;ϮϬϬϱͿ dĂƌŐĞƚŝŶŐ ĂƉŽƉƚŽƐŝƐ ƉĂƚŚǁĂǇƐ ŝŶ ĐĂŶĐĞƌ
ƚŚĞƌĂƉǇ͘ĂŶĐĞƌ:ůŝŶϱϱ;ϯͿ͗ϭϳϴͲϭϵϰ͘
'ŝǀǀŝŵĂŶŝ͕^͕DƵŶũĂů͕͕dǇĂŐŝ͕E͕^ĞŶ͕h͕DĞƚƌĞǀĞůŝ͕E͕dǇĂŐŝ͕^;ϮϬϭϮͿDŝƚŽĐŚŽŶĚƌŝĂů
ĚŝǀŝƐŝŽŶͬŵŝƚŽƉŚĂŐǇ ŝŶŚŝďŝƚŽƌ ;DĚŝǀŝͿ ĂŵĞůŝŽƌĂƚĞƐ ƉƌĞƐƐƵƌĞ ŽǀĞƌůŽĂĚ ŝŶĚƵĐĞĚ ŚĞĂƌƚ
ĨĂŝůƵƌĞ͘W>Ž^KŶĞϳ;ϯͿ͗ĞϯϮϯϴϴ͘
'ůŝŶŬĂ͕ z͕ 'ĂƐƐĞŶ͕ D͕ zŽƵĚŝŵ͕ D ;ϭϵϵϳͿ DĞĐŚĂŶŝƐŵ ŽĨ ϲͲŚǇĚƌŽǆǇĚŽƉĂŵŝŶĞ
ŶĞƵƌŽƚŽǆŝĐŝƚǇ͘:EĞƵƌĂůdƌĂŶƐŵ^ƵƉƉůϱϬ͗ϱϱͲϲϲ͘
'ůŝŶŬĂ͕ z͕ dŝƉƚŽŶ͕ <&͕ zŽƵĚŝŵ͕ D ;ϭϵϵϴͿ DĞĐŚĂŶŝƐŵ ŽĨ ŝŶŚŝďŝƚŝŽŶ ŽĨ ŵŝƚŽĐŚŽŶĚƌŝĂů
ƌĞƐƉŝƌĂƚŽƌǇ ĐŽŵƉůĞǆ / ďǇ ϲͲŚǇĚƌŽǆǇĚŽƉĂŵŝŶĞ ĂŶĚ ŝƚƐ ƉƌĞǀĞŶƚŝŽŶ ďǇ ĚĞƐĨĞƌƌŝŽǆĂŵŝŶĞ͘
Ƶƌ:WŚĂƌŵĂĐŽůϯϱϭ;ϭͿ͗ϭϮϭͲϭϮϵ͘
'ůŝŶŬĂ͕ z͕ dŝƉƚŽŶ͕ <&͕ zŽƵĚŝŵ͕ D ;ϭϵϵϲͿ EĂƚƵƌĞ ŽĨ ŝŶŚŝďŝƚŝŽŶ ŽĨ ŵŝƚŽĐŚŽŶĚƌŝĂů
ƌĞƐƉŝƌĂƚŽƌǇĐŽŵƉůĞǆ/ďǇϲͲ,ǇĚƌŽǆǇĚŽƉĂŵŝŶĞ͘:EĞƵƌŽĐŚĞŵϲϲ;ϱͿ͗ϮϬϬϰͲϮϬϭϬ͘
ϵϯ
'ŽŵĞƐ͕ >͕ ŝ ĞŶĞĚĞƚƚŽ͕ '͕ ^ĐŽƌƌĂŶŽ͕ > ;ϮϬϭϭͿ ƵƌŝŶŐ ĂƵƚŽƉŚĂŐǇ ŵŝƚŽĐŚŽŶĚƌŝĂ
ĞůŽŶŐĂƚĞ͕ ĂƌĞ ƐƉĂƌĞĚ ĨƌŽŵ ĚĞŐƌĂĚĂƚŝŽŶ ĂŶĚ ƐƵƐƚĂŝŶ ĐĞůů ǀŝĂďŝůŝƚǇ͘ EĂƚ Ğůů ŝŽů ϭϯ;ϱͿ͗
ϱϴϵͲϱϵϴ͘
'ŽŵĞǌͲ>ĂǌĂƌŽ͕ D͕ ŽŶĞŬĂŵƉ͕ E͕ 'ĂůŝŶĚŽ͕ D&͕ :ŽƌĚĂŶ͕ :͕ ^ĐŚƌĂĚĞƌ͕ D ;ϮϬϬϴĂͿ ϲͲ
,ǇĚƌŽǆǇĚŽƉĂŵŝŶĞ;ϲͲK,ͿŝŶĚƵĐĞƐƌƉϭͲĚĞƉĞŶĚĞŶƚŵŝƚŽĐŚŽŶĚƌŝĂůĨƌĂŐŵĞŶƚĂƚŝŽŶŝŶ
^,Ͳ^zϱzĐĞůůƐ͘&ƌĞĞZĂĚŝĐŝŽůDĞĚϰϰ;ϭϭͿ͗ϭϵϲϬͲϭϵϲϵ͘
'ŽŵĞǌͲ>ĂǌĂƌŽ͕ D͕ 'ĂůŝŶĚŽ͕ D&͕ ŽŶĐĂŶŶŽŶ͕ '͕ ^ĞŐƵƌĂ͕ D&͕ &ĞƌŶĂŶĚĞǌͲ'ŽŵĞǌ͕ &:͕
>ůĞĐŚĂ͕E͕ŽŵĞůůĂ͕:y͕WƌĞŚŶ͕:,͕:ŽƌĚĂŶ͕:;ϮϬϬϴďͿϲͲ,ǇĚƌŽǆǇĚŽƉĂŵŝŶĞĂĐƚŝǀĂƚĞƐƚŚĞ
ŵŝƚŽĐŚŽŶĚƌŝĂů ĂƉŽƉƚŽƐŝƐ ƉĂƚŚǁĂǇ ƚŚƌŽƵŐŚ Ɖϯϴ DW<ͲŵĞĚŝĂƚĞĚ͕ ƉϱϯͲŝŶĚĞƉĞŶĚĞŶƚ
ĂĐƚŝǀĂƚŝŽŶŽĨĂǆĂŶĚWhD͘:EĞƵƌŽĐŚĞŵϭϬϰ;ϲͿ͗ϭϱϵϵͲϭϲϭϮ͘
'ŽŶǌĂůĞǌͲWŽůŽ͕ Z͕ ƌĂǀŽͲ^ĂŶ WĞĚƌŽ͕ :D͕ 'ŽŵĞǌͲ^ĂŶĐŚĞǌ͕ Z͕ WŝǌĂƌƌŽͲƐƚƌĞůůĂ͕ ͕ EŝƐŽͲ
^ĂŶƚĂŶŽ͕ D͕ &ƵĞŶƚĞƐ͕ :D ;ϮϬϭϮͿ ƵƚŽƉŚĂŐǇ͕ ŵŝƚŽĐŚŽŶĚƌŝĂ ĂŶĚ ϯͲŶŝƚƌŽƉƌŽƉŝŽŶŝĐ ĂĐŝĚ
ũŽŝŶĞĚŝŶƚŚĞƐĂŵĞŵŽĚĞů͘ƌ:WŚĂƌŵĂĐŽůϭϲϴ;ϭͿ͗ϲϬͲϲϮ͘
'ŽŶǌĂůĞǌͲWŽůŽ͕Z͕&ƵĞŶƚĞƐ͕:D͕EŝƐŽͲ^ĂŶƚĂŶŽ͕D͕ůǀĂƌĞǌͲƌǀŝƚŝ͕>;ϮϬϭϯͿ/ŵƉůŝĐĂƚŝŽŶŽĨ
ĂƵƚŽƉŚĂŐǇŝŶWĂƌŬŝŶƐŽŶΖƐĚŝƐĞĂƐĞ͘WĂƌŬŝŶƐŽŶƐŝƐϮϬϭϯ͗ϰϯϲϰϴϭ͘
'ŽƐǁĂŵŝ͕͕ŝŬƐŚŝƚ͕W͕DŝƐŚƌĂ͕͕DƵůŚĞƌŬĂƌ͕^͕EƵŬŝŶĂ͕E͕:ĂŶĂ͕EZ;ϮϬϬϲͿKǆŝĚĂƚŝǀĞ
ƐƚƌĞƐƐƉƌŽŵŽƚĞƐŵƵƚĂŶƚŚƵŶƚŝŶŐƚŝŶĂŐŐƌĞŐĂƚŝŽŶĂŶĚŵƵƚĂŶƚŚƵŶƚŝŶŐƚŝŶͲĚĞƉĞŶĚĞŶƚĐĞůů
ĚĞĂƚŚ ďǇ ŵŝŵŝĐŬŝŶŐ ƉƌŽƚĞĂƐŽŵĂů ŵĂůĨƵŶĐƚŝŽŶ͘ ŝŽĐŚĞŵ ŝŽƉŚǇƐ ZĞƐ ŽŵŵƵŶ ϯϰϮ;ϭͿ͗
ϭϴϰͲϭϵϬ͘
'ƌĂŚĂŵ͕ ' ;ϭϵϳϴͿ KǆŝĚĂƚŝǀĞ ƉĂƚŚǁĂǇƐ ĨŽƌ ĐĂƚĞĐŚŽůĂŵŝŶĞƐ ŝŶ ƚŚĞ ŐĞŶĞƐŝƐ ŽĨ
ŶĞƵƌŽŵĞůĂŶŝŶĂŶĚĐǇƚŽƚŽǆŝĐƋƵŝŶŽŶĞƐ͘DŽůWŚĂƌŵĂĐŽůϭϰ;ϰͿ͗ϲϯϯͲϲϰϯ͘
'ƌĂŚĂŵ͕ '͕ dŝĨĨĂŶǇ͕ ^D͕ Ğůů͕ tZ͕ :ƌ͕͘ 'ƵƚŬŶĞĐŚƚ͕ t& ;ϭϵϳϴͿ ƵƚŽǆŝĚĂƚŝŽŶ ǀĞƌƐƵƐ
ĐŽǀĂůĞŶƚ ďŝŶĚŝŶŐ ŽĨ ƋƵŝŶŽŶĞƐ ĂƐ ƚŚĞ ŵĞĐŚĂŶŝƐŵ ŽĨ ƚŽǆŝĐŝƚǇ ŽĨ ĚŽƉĂŵŝŶĞ͕ ϲͲ
ŚǇĚƌŽǆǇĚŽƉĂŵŝŶĞ͕ĂŶĚƌĞůĂƚĞĚĐŽŵƉŽƵŶĚƐƚŽǁĂƌĚϭϯϬϬŶĞƵƌŽďůĂƐƚŽŵĂĐĞůůƐŝŶǀŝƚƌŽ͘
DŽůWŚĂƌŵĂĐŽůϭϰ;ϰͿ͗ϲϰϰͲϲϱϯ͘
'ƌĞĞŶĂŵǇƌĞ͕ :d͕ ,ĂƐƚŝŶŐƐ͕ d' ;ϮϬϬϰͿ ŝŽŵĞĚŝĐŝŶĞ͘ WĂƌŬŝŶƐŽŶΖƐͲͲĚŝǀĞƌŐĞŶƚ ĐĂƵƐĞƐ͕
ĐŽŶǀĞƌŐĞŶƚŵĞĐŚĂŶŝƐŵƐ͘^ĐŝĞŶĐĞϯϬϰ;ϱϲϳϰͿ͗ϭϭϮϬͲϭϭϮϮ͘
'ƌŝŶŝƵƐ͕ >>͕ :ĂƐĂŝƚŝƐ͕ ͕ <ĂĚǌŝĂƵƐŬĂƐ͕ zW͕ >ŝďĞƌŵĂŶ͕ ͕ ^ŬƵůĂĐŚĞǀ͕ sW͕ dŽƉĂůŝ͕ sW͕
dƐŽĨŝŶĂ͕ >D͕ sůĂĚŝŵŝƌŽǀĂ͕ D ;ϭϵϳϬͿ ŽŶǀĞƌƐŝŽŶ ŽĨ ďŝŽŵĞŵďƌĂŶĞͲƉƌŽĚƵĐĞĚ ĞŶĞƌŐǇ
ŝŶƚŽĞůĞĐƚƌŝĐĨŽƌŵ͘/͘^ƵďŵŝƚŽĐŚŽŶĚƌŝĂůƉĂƌƚŝĐůĞƐ͘ŝŽĐŚŝŵŝŽƉŚǇƐĐƚĂϮϭϲ;ϭͿ͗ϭͲϭϮ͘
'ƌŝƉĂƌŝĐ͕ >͕ <ĂŶĂǌĂǁĂ͕ d͕ ǀĂŶ ĚĞƌ ůŝĞŬ͕ D ;ϮϬϬϳͿ ZĞŐƵůĂƚŝŽŶ ŽĨ ƚŚĞ ŵŝƚŽĐŚŽŶĚƌŝĂů
ĚǇŶĂŵŝŶͲůŝŬĞƉƌŽƚĞŝŶKƉĂϭďǇƉƌŽƚĞŽůǇƚŝĐĐůĞĂǀĂŐĞ͘:ĞůůŝŽůϭϳϴ;ϱͿ͗ϳϱϳͲϳϲϰ͘
'Ƶ͕ D͕ 'ĂƐŚ͕ Dd͕ DĂŶŶ͕ sD͕ :ĂǀŽǇͲŐŝĚ͕ &͕ ŽŽƉĞƌ͕ :D͕ ^ĐŚĂƉŝƌĂ͕ , ;ϭϵϵϲͿ
DŝƚŽĐŚŽŶĚƌŝĂůĚĞĨĞĐƚŝŶ,ƵŶƚŝŶŐƚŽŶΖƐĚŝƐĞĂƐĞĐĂƵĚĂƚĞŶƵĐůĞƵƐ͘ŶŶEĞƵƌŽůϯϵ;ϯͿ͗ϯϴϱͲ
ϯϴϵ͘
ϵϰ
'ƵŽ͕>͕^Ƶŝ͕͕tĂŶŐ͕yz͕tĞŝ͕zz͕,ƵĂŶŐ͕:͕ŚĞŶ͕:͕tƵ͕^y͕>ŝ͕zY͕tĂŶŐ͕zz͕zĂŶŐ͕
z>;ϮϬϭϯͿ^ŝŐŶŝĨŝĐĂŶƚĐŚĂŶŐĞƐŝŶŵŝƚŽĐŚŽŶĚƌŝĂůĚŝƐƚƌŝďƵƚŝŽŶŝŶĚŝĨĨĞƌĞŶƚƉĂŝŶŵŽĚĞůƐŽĨ
ŵŝĐĞ͘DŝƚŽĐŚŽŶĚƌŝŽŶ͘
,Ă͕ :,͕ EŽŚ͕ ,^͕ ^ŚŝŶ͕ /t͕ ,ĂŚŵ͕ :Z͕ <ŝŵ͕ Z ;ϮϬϭϮͿ DŝƚŝŐĂƚŝŽŶ ŽĨ ,ϮKϮͲŝŶĚƵĐĞĚ
ĂƵƚŽƉŚĂŐŝĐĐĞůůĚĞĂƚŚďǇƉƌŽƉŽĨŽůŝŶ,ϵĐϮĐĂƌĚŝŽŵǇŽĐǇƚĞƐ͘ĞůůŝŽůdŽǆŝĐŽůϮϴ;ϭͿ͗ϭϵͲ
Ϯϵ͘
,ĂĂƐ͕ Z,͕ EĂƐŝƌŝĂŶ͕ &͕ EĂŬĂŶŽ͕ <͕ tĂƌĚ͕ ͕ WĂǇ͕ D͕ ,ŝůů͕ Z͕ ^ŚƵůƚƐ͕ t ;ϭϵϵϱͿ >Žǁ
ƉůĂƚĞůĞƚ ŵŝƚŽĐŚŽŶĚƌŝĂů ĐŽŵƉůĞǆ / ĂŶĚ ĐŽŵƉůĞǆ //ͬ/// ĂĐƚŝǀŝƚǇ ŝŶ ĞĂƌůǇ ƵŶƚƌĞĂƚĞĚ
WĂƌŬŝŶƐŽŶΖƐĚŝƐĞĂƐĞ͘ŶŶEĞƵƌŽůϯϳ;ϲͿ͗ϳϭϰͲϳϮϮ͘
,ĂŵĂƐĂŬŝ͕ D͕ &ƵƌƵƚĂ͕ E͕ DĂƚƐƵĚĂ͕ ͕ EĞǌƵ͕ ͕ zĂŵĂŵŽƚŽ͕ ͕ &ƵũŝƚĂ͕ E͕ KŽŵŽƌŝ͕ ,͕
EŽĚĂ͕ d͕ ,ĂƌĂŐƵĐŚŝ͕ d͕ ,ŝƌĂŽŬĂ͕ z͕ ŵĂŶŽ͕ ͕ zŽƐŚŝŵŽƌŝ͕ d ;ϮϬϭϯͿ ƵƚŽƉŚĂŐŽƐŽŵĞƐ
ĨŽƌŵĂƚZͲŵŝƚŽĐŚŽŶĚƌŝĂĐŽŶƚĂĐƚƐŝƚĞƐ͘EĂƚƵƌĞϰϵϱ;ϳϰϰϭͿ͗ϯϴϵͲϯϵϯ͘
,ĂŶƌŽƚƚ͕ <͕ 'ƵĚŵƵŶƐĞŶ͕ >͕ KΖEĞŝůů͕ D:͕ tŽŶŶĂĐŽƚƚ͕ ^ ;ϮϬϬϲͿ ϲͲŚǇĚƌŽǆǇĚŽƉĂŵŝŶĞͲ
ŝŶĚƵĐĞĚ ĂƉŽƉƚŽƐŝƐ ŝƐ ŵĞĚŝĂƚĞĚ ǀŝĂ ĞǆƚƌĂĐĞůůƵůĂƌ ĂƵƚŽͲŽǆŝĚĂƚŝŽŶ ĂŶĚ ĐĂƐƉĂƐĞ ϯͲ
ĚĞƉĞŶĚĞŶƚĂĐƚŝǀĂƚŝŽŶŽĨƉƌŽƚĞŝŶŬŝŶĂƐĞĚĞůƚĂ͘:ŝŽůŚĞŵϮϴϭ;ϵͿ͗ϱϯϳϯͲϱϯϴϮ͘
,ĂƌĚĞƌ͕ ͕ ƵŶŝŶŽ͕ Z͕ DĐƌŝĚĞ͕ , ;ϮϬϬϰͿ ^ƵŵŽϭ ĐŽŶũƵŐĂƚĞƐ ŵŝƚŽĐŚŽŶĚƌŝĂů ƐƵďƐƚƌĂƚĞƐ
ĂŶĚƉĂƌƚŝĐŝƉĂƚĞƐŝŶŵŝƚŽĐŚŽŶĚƌŝĂůĨŝƐƐŝŽŶ͘ƵƌƌŝŽůϭϰ;ϰͿ͗ϯϰϬͲϯϰϱ͘
,ĂƚĂŶŽ͕z͕>ŝ͕z͕^ĂƚŽ͕<͕ƐĂŬĂǁĂ͕^͕zĂŵĂŵƵƌĂ͕z͕dŽŵŝǇĂŵĂ͕,͕zŽƐŚŝŶŽ͕,͕ƐĂŚŝŶĂ͕
D͕ <ŽďĂǇĂƐŚŝ͕ ^͕ ,ĂƐƐŝŶͲĂĞƌ͕ ^͕ >Ƶ͕ ^͕ EŐ͕ Z͕ ZŽƐĂůĞƐ͕ Z>͕ ^ŚŝŵŝǌƵ͕ E͕ dŽĚĂ͕ d͕
DŝǌƵŶŽ͕z͕,ĂƚƚŽƌŝ͕E;ϮϬϬϰͿEŽǀĞůW/E<ϭŵƵƚĂƚŝŽŶƐŝŶĞĂƌůǇͲŽŶƐĞƚƉĂƌŬŝŶƐŽŶŝƐŵ͘ŶŶ
EĞƵƌŽůϱϲ;ϯͿ͗ϰϮϰͲϰϮϳ͘
,Z' ;ϭϵϵϯͿ ŶŽǀĞů ŐĞŶĞ ĐŽŶƚĂŝŶŝŶŐ Ă ƚƌŝŶƵĐůĞŽƚŝĚĞ ƌĞƉĞĂƚ ƚŚĂƚ ŝƐ ĞǆƉĂŶĚĞĚ ĂŶĚ
ƵŶƐƚĂďůĞ ŽŶ ,ƵŶƚŝŶŐƚŽŶΖƐ ĚŝƐĞĂƐĞ ĐŚƌŽŵŽƐŽŵĞƐ͘ dŚĞ ,ƵŶƚŝŶŐƚŽŶΖƐ ŝƐĞĂƐĞ
ŽůůĂďŽƌĂƚŝǀĞZĞƐĞĂƌĐŚ'ƌŽƵƉ͘ĞůůϳϮ;ϲͿ͗ϵϳϭͲϵϴϯ͘
,Ğ͕ ͕ <ůŝŽŶƐŬǇ͕ : ;ϮϬϬϵͿ ZĞŐƵůĂƚŝŽŶ ŵĞĐŚĂŶŝƐŵƐ ĂŶĚ ƐŝŐŶĂůŝŶŐ ƉĂƚŚǁĂǇƐ ŽĨ
ĂƵƚŽƉŚĂŐǇ͘ŶŶƵZĞǀ'ĞŶĞƚϰϯ͗ϲϳͲϵϯ͘
,ĞŶĐŚĐůŝĨĨĞ͕͕ĞĂů͕D&;ϮϬϬϴͿDŝƚŽĐŚŽŶĚƌŝĂůďŝŽůŽŐǇĂŶĚŽǆŝĚĂƚŝǀĞƐƚƌĞƐƐŝŶWĂƌŬŝŶƐŽŶ
ĚŝƐĞĂƐĞƉĂƚŚŽŐĞŶĞƐŝƐ͘EĂƚůŝŶWƌĂĐƚEĞƵƌŽůϰ;ϭϭͿ͗ϲϬϬͲϲϬϵ͘
,ĞŶŐĂƌƚŶĞƌ͕DK;ϮϬϬϬͿdŚĞďŝŽĐŚĞŵŝƐƚƌǇŽĨĂƉŽƉƚŽƐŝƐ͘EĂƚƵƌĞϰϬϳ;ϲϴϬϱͿ͗ϳϳϬͲϳϳϲ͘
,ĞŶƐŽŶ͕ WD͕ ƌĂƚƚŽŶ͕ >͕ &ĂĚŽŬ͕ s ;ϮϬϬϭͿ ƉŽƉƚŽƚŝĐ ĐĞůů ƌĞŵŽǀĂů͘ Ƶƌƌ ŝŽů ϭϭ;ϭϵͿ͗
ZϳϵϱͲϴϬϱ͘
,ĞŶǌĞ͕ <͕ DĂƌƚŝŶ͕ t ;ϮϬϬϯͿ ǀŽůƵƚŝŽŶĂƌǇ ďŝŽůŽŐǇ͗ ĞƐƐĞŶĐĞ ŽĨ ŵŝƚŽĐŚŽŶĚƌŝĂ͘ EĂƚƵƌĞ
ϰϮϲ;ϲϵϲϯͿ͗ϭϮϳͲϭϮϴ͘
ϵϱ
,ĞƌŶĂŶĚĞǌͲZĞƐĞŶĚŝǌ͕ ^͕ ƵĞůŶĂͲŚŽŶƚĂů͕ D͕ ŽƌƌĞĂ͕ &͕ ĂǌƵĞƚĂ͕ ;ϮϬϭϯͿ dĂƌŐĞƚŝŶŐ
DŝƚŽĐŚŽŶĚƌŝĂĨŽƌĂƌĚŝĂĐWƌŽƚĞĐƚŝŽŶ͘ƵƌƌƌƵŐdĂƌŐĞƚƐ͘
,ŽŝĚĂů͕:Z;ϮϬϬϭͿZĞĂĐƚŝǀĞŽǆǇŐĞŶƐƉĞĐŝĞƐĂŶĚĐĞůůƐŝŐŶĂůŝŶŐ͘ŵ:ZĞƐƉŝƌĞůůDŽůŝŽů
Ϯϱ;ϲͿ͗ϲϲϭͲϲϲϯ͘
,ŽůůĞŶďĞĐŬ͕ W:͕ ^ĂǆƚŽŶ͕ tD ;ϮϬϬϱͿ dŚĞ ĂǆŽŶĂů ƚƌĂŶƐƉŽƌƚ ŽĨ ŵŝƚŽĐŚŽŶĚƌŝĂ͘ : Ğůů ^Đŝ
ϭϭϴ;WƚϮϯͿ͗ϱϰϭϭͲϱϰϭϵ͘
,ŽŶŐ͕ ͕ <ƵƚƚǇ͕ ^͕ dŽƚŚ͕ Wd͕ DĂƌƐďŽŽŵ͕ '͕ ,ĂŵŵĞů͕ :D͕ ŚĂŵďĞƌůĂŝŶ͕ ͕ ZǇĂŶ͕ ::͕
ŚĂŶŐ͕ ,:͕ ^ŚĂƌƉ͕ tt͕ DŽƌƌŽǁ͕ D͕ dƌŝǀĞĚŝ͕ <͕ tĞŝƌ͕ <͕ ƌĐŚĞƌ͕ ^> ;ϮϬϭϮͿ ZŽůĞ ŽĨ
ǇŶĂŵŝŶ ZĞůĂƚĞĚ WƌŽƚĞŝŶ ϭ ;ƌƉϭͿͲDĞĚŝĂƚĞĚDŝƚŽĐŚŽŶĚƌŝĂů &ŝƐƐŝŽŶ ŝŶ KǆǇŐĞŶͲ^ĞŶƐŝŶŐ
ĂŶĚŽŶƐƚƌŝĐƚŝŽŶŽĨƚŚĞƵĐƚƵƐƌƚĞƌŝŽƐƵƐ͘ŝƌĐZĞƐ͘
,ŽƉƉŝŶƐ͕ ^͕ >ĂĐŬŶĞƌ͕ >͕ EƵŶŶĂƌŝ͕ : ;ϮϬϬϳͿ dŚĞ ŵĂĐŚŝŶĞƐ ƚŚĂƚ ĚŝǀŝĚĞ ĂŶĚ ĨƵƐĞ
ŵŝƚŽĐŚŽŶĚƌŝĂ͘ŶŶƵZĞǀŝŽĐŚĞŵϳϲ͗ϳϱϭͲϳϴϬ͘
,ƵĂŶŐ͕ D>͕ >ĂŶĞ͕ :͕ ZŝĐŚĂƌĚƐŽŶ͕ Z ;ϮϬϭϭͿ DŝƚŽĐŚŽŶĚƌŝĂů ŵĂǇŚĞŵ͗ ƚŚĞ
ŵŝƚŽĐŚŽŶĚƌŝŽŶ ĂƐ Ă ŵŽĚƵůĂƚŽƌ ŽĨ ŝƌŽŶ ŵĞƚĂďŽůŝƐŵ ĂŶĚ ŝƚƐ ƌŽůĞ ŝŶ ĚŝƐĞĂƐĞ͘ ŶƚŝŽǆŝĚ
ZĞĚŽǆ^ŝŐŶĂůϭϱ;ϭϮͿ͗ϯϬϬϯͲϯϬϭϵ͘
/ůŝũŝĐ͕ ͕ 'ƵǌŵĂŶ͕ :E͕ ^ƵƌŵĞŝĞƌ͕ : ;ϮϬϭϭͿ dŚĞ >ͲƚǇƉĞ ĐŚĂŶŶĞů ĂŶƚĂŐŽŶŝƐƚ ŝƐƌĂĚŝƉŝŶĞ ŝƐ
ŶĞƵƌŽƉƌŽƚĞĐƚŝǀĞ ŝŶ Ă ŵŽƵƐĞ ŵŽĚĞů ŽĨ WĂƌŬŝŶƐŽŶΖƐ ĚŝƐĞĂƐĞ͘ EĞƵƌŽďŝŽů ŝƐ ϰϯ;ϮͿ͗ ϯϲϰͲ
ϯϳϭ͘
/ůůĂƌŝŽƐŚŬŝŶ͕ Ê͕ /ŐĂƌĂƐŚŝ͕ ^͕ KŶŽĚĞƌĂ͕ K͕ DĂƌŬŽǀĂ͕ ͕ EŝŬŽůƐŬĂǇĂ͕ EE͕ dĂŶĂŬĂ͕ ,͕
ŚĂďƌĂƐŚǁŝůŝ͕ d͕ /ŶƐĂƌŽǀĂ͕ E'͕ ŶĚŽ͕ <͕ /ǀĂŶŽǀĂͲ^ŵŽůĞŶƐŬĂǇĂ͕ /͕ Ğƚ Ăů͘ ;ϭϵϵϰͿ
dƌŝŶƵĐůĞŽƚŝĚĞ ƌĞƉĞĂƚ ůĞŶŐƚŚ ĂŶĚ ƌĂƚĞ ŽĨ ƉƌŽŐƌĞƐƐŝŽŶ ŽĨ ,ƵŶƚŝŶŐƚŽŶΖƐ ĚŝƐĞĂƐĞ͘ ŶŶ
EĞƵƌŽůϯϲ;ϰͿ͗ϲϯϬͲϲϯϱ͘
/ŶŐĞƌŵĂŶ͕͕WĞƌŬŝŶƐ͕D͕DĂƌŝŶŽ͕D͕DĞĂƌƐ͕:͕DĐĂĨĨĞƌǇ͕:D͕,ŝŶƐŚĂǁ͕:͕EƵŶŶĂƌŝ͕:
;ϮϬϬϱͿŶŵϭĨŽƌŵƐƐƉŝƌĂůƐƚŚĂƚĂƌĞƐƚƌƵĐƚƵƌĂůůǇƚĂŝůŽƌĞĚƚŽĨŝƚŵŝƚŽĐŚŽŶĚƌŝĂ͘:ĞůůŝŽů
ϭϳϬ;ϳͿ͗ϭϬϮϭͲϭϬϮϳ͘
/ƋďĂů͕<͕'ƌƵŶĚŬĞͲ/ƋďĂů͕/;ϮϬϭϬͿůǌŚĞŝŵĞƌΖƐĚŝƐĞĂƐĞ͕ĂŵƵůƚŝĨĂĐƚŽƌŝĂůĚŝƐŽƌĚĞƌƐĞĞŬŝŶŐ
ŵƵůƚŝƚŚĞƌĂƉŝĞƐ͘ůǌŚĞŝŵĞƌƐĞŵĞŶƚϲ;ϱͿ͗ϰϮϬͲϰϮϰ͘
/ƐŚŝŚĂƌĂ͕ E͕ ƵƌĂ͕ z͕ DŝŚĂƌĂ͕ < ;ϮϬϬϰͿ DŝƚŽĨƵƐŝŶ ϭ ĂŶĚ Ϯ ƉůĂǇ ĚŝƐƚŝŶĐƚ ƌŽůĞƐ ŝŶ
ŵŝƚŽĐŚŽŶĚƌŝĂůĨƵƐŝŽŶƌĞĂĐƚŝŽŶƐǀŝĂ'dWĂƐĞĂĐƚŝǀŝƚǇ͘:Ğůů^Đŝϭϭϳ;WƚϮϲͿ͗ϲϱϯϱͲϲϱϰϲ͘
/ƐŚŝŚĂƌĂ͕E͕&ƵũŝƚĂ͕z͕KŬĂ͕d͕DŝŚĂƌĂ͕<;ϮϬϬϲͿZĞŐƵůĂƚŝŽŶŽĨŵŝƚŽĐŚŽŶĚƌŝĂůŵŽƌƉŚŽůŽŐǇ
ƚŚƌŽƵŐŚƉƌŽƚĞŽůǇƚŝĐĐůĞĂǀĂŐĞŽĨKWϭ͘DK:Ϯϱ;ϭϯͿ͗ϮϵϲϲͲϮϵϳϳ͘
/ƐŚŝŚĂƌĂ͕E͕EŽŵƵƌĂ͕D͕:ŽĨƵŬƵ͕͕<ĂƚŽ͕,͕^ƵǌƵŬŝ͕^K͕DĂƐƵĚĂ͕<͕KƚĞƌĂ͕,͕EĂŬĂŶŝƐŚŝ͕
z͕ EŽŶĂŬĂ͕ /͕ 'ŽƚŽ͕ z͕ dĂŐƵĐŚŝ͕ E͕ DŽƌŝŶĂŐĂ͕ ,͕ DĂĞĚĂ͕ D͕ dĂŬĂǇĂŶĂŐŝ͕ Z͕ zŽŬŽƚĂ͕ ^͕
DŝŚĂƌĂ͕ < ;ϮϬϬϵͿ DŝƚŽĐŚŽŶĚƌŝĂů ĨŝƐƐŝŽŶ ĨĂĐƚŽƌ ƌƉϭ ŝƐ ĞƐƐĞŶƚŝĂů ĨŽƌ ĞŵďƌǇŽŶŝĐ
ĚĞǀĞůŽƉŵĞŶƚĂŶĚƐǇŶĂƉƐĞĨŽƌŵĂƚŝŽŶŝŶŵŝĐĞ͘EĂƚĞůůŝŽůϭϭ;ϴͿ͗ϵϱϴͲϵϲϲ͘
ϵϲ
/ǌƵŵŝ͕ z͕ ^ĂǁĂĚĂ͕ ,͕ ^ĂŬŬĂ͕ E͕ zĂŵĂŵŽƚŽ͕ E͕ <ƵŵĞ͕ d͕ <ĂƚƐƵŬŝ͕ ,͕ ^ŚŝŵŽŚĂŵĂ͕ ^͕
ŬĂŝŬĞ͕ ;ϮϬϬϱͿ ƉͲYƵŝŶŽŶĞ ŵĞĚŝĂƚĞƐ ϲͲŚǇĚƌŽǆǇĚŽƉĂŵŝŶĞͲŝŶĚƵĐĞĚ ĚŽƉĂŵŝŶĞƌŐŝĐ
ŶĞƵƌŽŶĂůĚĞĂƚŚĂŶĚĨĞƌƌŽƵƐŝƌŽŶĂĐĐĞůĞƌĂƚĞƐƚŚĞĐŽŶǀĞƌƐŝŽŶŽĨƉͲƋƵŝŶŽŶĞŝŶƚŽŵĞůĂŶŝŶ
ĞǆƚƌĂĐĞůůƵůĂƌůǇ͘:EĞƵƌŽƐĐŝZĞƐϳϵ;ϲͿ͗ϴϰϵͲϴϲϬ͘
:ĂďƐ͕d;ϭϵϵϵͿZĞĂĐƚŝǀĞŽǆǇŐĞŶŝŶƚĞƌŵĞĚŝĂƚĞƐĂƐŵĞĚŝĂƚŽƌƐŽĨƉƌŽŐƌĂŵŵĞĚĐĞůůĚĞĂƚŚ
ŝŶƉůĂŶƚƐĂŶĚĂŶŝŵĂůƐ͘ŝŽĐŚĞŵWŚĂƌŵĂĐŽůϱϳ;ϯͿ͗ϮϯϭͲϮϰϱ͘
:ĂŚĂŶŝͲƐů͕ ͕ ŚĞƵŶŐ͕ ͕ EĞƵƐƉŝĞů͕ D͕ DĂĐ>ĂƵƌŝŶ͕ :'͕ &ŽƌƚŝŶ͕ ͕ WĂƌŬ͕ ^͕ DĐƌŝĚĞ͕
,D͕ ^ůĂĐŬ͕ Z^ ;ϮϬϬϳͿ DŝƚŽĨƵƐŝŶ Ϯ ƉƌŽƚĞĐƚƐ ĐĞƌĞďĞůůĂƌ ŐƌĂŶƵůĞ ŶĞƵƌŽŶƐ ĂŐĂŝŶƐƚ ŝŶũƵƌǇͲ
ŝŶĚƵĐĞĚĐĞůůĚĞĂƚŚ͘:ŝŽůŚĞŵϮϴϮ;ϯϯͿ͗ϮϯϳϴϴͲϮϯϳϵϴ͘
:ĂŚĂŶŝͲƐů͕͕'ĞƌŵĂŝŶ͕D͕^ůĂĐŬ͕Z^;ϮϬϬϵͿDŝƚŽĐŚŽŶĚƌŝĂ͗:ŽŝŶŝŶŐĨŽƌĐĞƐƚŽƚŚǁĂƌƚĐĞůů
ĚĞĂƚŚ͘ŝŽĐŚŝŵŝŽƉŚǇƐĐƚĂ͘
:ĞŶŶĞƌ͕W;ϮϬϬϯͿKǆŝĚĂƚŝǀĞƐƚƌĞƐƐŝŶWĂƌŬŝŶƐŽŶΖƐĚŝƐĞĂƐĞ͘ŶŶEĞƵƌŽůϱϯ^ƵƉƉůϯ͗^ϮϲͲϯϲ͖
ĚŝƐĐƵƐƐŝŽŶ^ϯϲͲϮϴ͘
:ŝĂŶŐ͕,͕:ĂĐŬƐŽŶͲ>ĞǁŝƐ͕s͕DƵƚŚĂŶĞ͕h͕ŽůůŝƐŽŶ͕͕&ĞƌƌĞŝƌĂ͕D͕ƐƉŝŶŽƐĂ͕͕WĂƌƐŽŶƐ͕
͕WƌǌĞĚďŽƌƐŬŝ͕^;ϭϵϵϯͿĚĞŶŽƐŝŶĞƌĞĐĞƉƚŽƌĂŶƚĂŐŽŶŝƐƚƐƉŽƚĞŶƚŝĂƚĞĚŽƉĂŵŝŶĞƌĞĐĞƉƚŽƌ
ĂŐŽŶŝƐƚͲŝŶĚƵĐĞĚ ƌŽƚĂƚŝŽŶĂů ďĞŚĂǀŝŽƌ ŝŶ ϲͲŚǇĚƌŽǆǇĚŽƉĂŵŝŶĞͲůĞƐŝŽŶĞĚ ƌĂƚƐ͘ ƌĂŝŶ ZĞƐ
ϲϭϯ;ϮͿ͗ϯϰϳͲϯϱϭ͘
:ŽŚƌŝ͕ ͕ ĞĂů͕ D& ;ϮϬϭϮͿ DŝƚŽĐŚŽŶĚƌŝĂů ĚǇƐĨƵŶĐƚŝŽŶ ŝŶ ŶĞƵƌŽĚĞŐĞŶĞƌĂƚŝǀĞ ĚŝƐĞĂƐĞƐ͘ :
WŚĂƌŵĂĐŽůǆƉdŚĞƌϯϰϮ;ϯͿ͗ϲϭϵͲϲϯϬ͘
:ŽŶƐƐŽŶ͕ '͕ ^ĂĐŚƐ͕ ;ϭϵϳϭͿ hƉƚĂŬĞ ĂŶĚ ĂĐĐƵŵƵůĂƚŝŽŶ ŽĨ ϯ ,ͲϲͲŚǇĚƌŽǆǇĚŽƉĂŵŝŶĞ ŝŶ
ĂĚƌĞŶĞƌŐŝĐŶĞƌǀĞƐ͘Ƶƌ:WŚĂƌŵĂĐŽůϭϲ;ϭͿ͗ϱϱͲϲϮ͘
:ŽƌĚĂŶ͕:͕ĞŶĂ͕s͕WƌĞŚŶ͕:,;ϮϬϬϯͿDŝƚŽĐŚŽŶĚƌŝĂůĐŽŶƚƌŽůŽĨŶĞƵƌŽŶĚĞĂƚŚĂŶĚŝƚƐƌŽůĞ
ŝŶŶĞƵƌŽĚĞŐĞŶĞƌĂƚŝǀĞĚŝƐŽƌĚĞƌƐ͘:WŚǇƐŝŽůŝŽĐŚĞŵϱϵ;ϮͿ͗ϭϮϵͲϭϰϭ͘
:ŽƌĚĂŶ͕ :͕ 'ĂůŝŶĚŽ͕ D&͕ dŽƌŶĞƌŽ͕ ͕ 'ŽŶǌĂůĞǌͲ'ĂƌĐŝĂ͕ ͕ ĞŶĂ͕ s ;ϮϬϬϰͿ ĐůͲǆ > ďůŽĐŬƐ
ŵŝƚŽĐŚŽŶĚƌŝĂů ŵƵůƚŝƉůĞ ĐŽŶĚƵĐƚĂŶĐĞ ĐŚĂŶŶĞů ĂĐƚŝǀĂƚŝŽŶ ĂŶĚ ŝŶŚŝďŝƚƐ ϲͲK,ͲŝŶĚƵĐĞĚ
ĚĞĂƚŚŝŶ^,Ͳ^zϱzĐĞůůƐ͘:EĞƵƌŽĐŚĞŵϴϵ;ϭͿ͗ϭϮϰͲϭϯϯ͘
<ĂďĞǇĂ͕ z͕ DŝǌƵƐŚŝŵĂ͕ E͕ hĞŶŽ͕ d͕ zĂŵĂŵŽƚŽ͕ ͕ <ŝƌŝƐĂŬŽ͕ d͕ EŽĚĂ͕ d͕ <ŽŵŝŶĂŵŝ͕ ͕
KŚƐƵŵŝ͕ z͕ zŽƐŚŝŵŽƌŝ͕ d ;ϮϬϬϬͿ >ϯ͕ Ă ŵĂŵŵĂůŝĂŶ ŚŽŵŽůŽŐƵĞ ŽĨ ǇĞĂƐƚ ƉŐϴƉ͕ ŝƐ
ůŽĐĂůŝǌĞĚŝŶĂƵƚŽƉŚĂŐŽƐŽŵĞŵĞŵďƌĂŶĞƐĂĨƚĞƌƉƌŽĐĞƐƐŝŶŐ͘DK:ϭϵ;ϮϭͿ͗ϱϳϮϬͲϱϳϮϴ͘
<ĂďĞǇĂ͕z͕DŝǌƵƐŚŝŵĂ͕E͕zĂŵĂŵŽƚŽ͕͕KƐŚŝƚĂŶŝͲKŬĂŵŽƚŽ͕^͕KŚƐƵŵŝ͕z͕zŽƐŚŝŵŽƌŝ͕d
;ϮϬϬϰͿ>ϯ͕'ZWĂŶĚ'dϭϲůŽĐĂůŝǌĞƚŽĂƵƚŽƉŚĂŐŽƐŽŵĂůŵĞŵďƌĂŶĞĚĞƉĞŶĚŝŶŐ
ŽŶĨŽƌŵͲ//ĨŽƌŵĂƚŝŽŶ͘:Ğůů^Đŝϭϭϳ;WƚϭϯͿ͗ϮϴϬϱͲϮϴϭϮ͘
ϵϳ
<ĂďƵƚŽ͕ ,͕ zŽŬŽŝ͕ /͕ /ǁĂƚĂͲ/ĐŚŝŬĂǁĂ͕ ͕ KŐĂǁĂ͕ E ;ϭϵϵϵͿ WͲ<ϭ͕ Ă ŚǇĚƌŽǆǇů ƌĂĚŝĐĂů
ƐĐĂǀĞŶŐĞƌ͕ ƉƌĞǀĞŶƚƐ ϲͲŚǇĚƌŽǆǇĚŽƉĂŵŝŶĞͲŝŶĚƵĐĞĚ ĚŽƉĂŵŝŶĞ ĚĞƉůĞƚŝŽŶ ŝŶ ƚŚĞ ŵŽƵƐĞ
ƐƚƌŝĂƚƵŵďǇƵƉͲƌĞŐƵůĂƚŝŽŶŽĨĐĂƚĂůĂƐĞĂĐƚŝǀŝƚǇ͘EĞƵƌŽĐŚĞŵZĞƐϮϰ;ϭϮͿ͗ϭϱϰϯͲϭϱϰϴ͘
<ĂŶƚŚĂƐĂŵǇ͕͕:ŝŶ͕,͕DĞŚƌŽƚƌĂ͕^͕DŝƐŚƌĂ͕Z͕ZĂŶĂ͕;ϮϬϭϬͿEŽǀĞůĐĞůůĚĞĂƚŚƐŝŐŶĂůŝŶŐ
ƉĂƚŚǁĂǇƐ ŝŶ ŶĞƵƌŽƚŽǆŝĐŝƚǇ ŵŽĚĞůƐ ŽĨ ĚŽƉĂŵŝŶĞƌŐŝĐ ĚĞŐĞŶĞƌĂƚŝŽŶ͗ ƌĞůĞǀĂŶĐĞ ƚŽ
ŽǆŝĚĂƚŝǀĞƐƚƌĞƐƐĂŶĚŶĞƵƌŽŝŶĨůĂŵŵĂƚŝŽŶŝŶWĂƌŬŝŶƐŽŶΖƐĚŝƐĞĂƐĞ͘EĞƵƌŽƚŽǆŝĐŽůŽŐǇϯϭ;ϱͿ͗
ϱϱϱͲϱϲϭ͘
<ĂƌďŽǁƐŬŝ͕ D͕ :ĞŽŶŐ͕ ^z͕ zŽƵůĞ͕ Z: ;ϮϬϬϰͿ ŶĚŽƉŚŝůŝŶ ϭ ŝƐ ƌĞƋƵŝƌĞĚ ĨŽƌ ƚŚĞ
ŵĂŝŶƚĞŶĂŶĐĞŽĨŵŝƚŽĐŚŽŶĚƌŝĂůŵŽƌƉŚŽůŽŐǇ͘:ĞůůŝŽůϭϲϲ;ϳͿ͗ϭϬϮϳͲϭϬϯϵ͘
<ĂƌďŽǁƐŬŝ͕ D͕ EĞƵƚǌŶĞƌ͕ ͕ zŽƵůĞ͕ Z: ;ϮϬϬϳͿ dŚĞ ŵŝƚŽĐŚŽŶĚƌŝĂů ϯ ƵďŝƋƵŝƚŝŶ ůŝŐĂƐĞ
DZ,ϱŝƐƌĞƋƵŝƌĞĚĨŽƌƌƉϭĚĞƉĞŶĚĞŶƚŵŝƚŽĐŚŽŶĚƌŝĂůĚŝǀŝƐŝŽŶ͘:ĞůůŝŽůϭϳϴ;ϭͿ͗ϳϭͲ
ϴϰ͘
<ĂƌƌĞŶ͕ D͕ ŽŽŶƌŽĚ͕ D͕ ŶĚĞƌƐŽŶ͕ d<͕ ^ŚĂǁ͕ :D ;ϮϬϬϱͿ dŚĞ ƌŽůĞ ŽĨ &ŝƐϭƉͲDĚǀϭƉ
ŝŶƚĞƌĂĐƚŝŽŶƐŝŶŵŝƚŽĐŚŽŶĚƌŝĂůĨŝƐƐŝŽŶĐŽŵƉůĞǆĂƐƐĞŵďůǇ͘:ĞůůŝŽůϭϳϭ;ϮͿ͗ϮϵϭͲϯϬϭ͘
<ĂǌƵŶŽ͕ ͕ DƵŶĂŬĂƚĂ͕ <͕ EĂŐĂŝ͕ d͕ ^ŚŝŵŽǌŽŶŽ͕ ^͕ dĂŶĂŬĂ͕ D͕ zŽŶĞĚĂ͕ D͕ <ĂƚŽ͕ E͕
DŝǇĂǁĂŬŝ͕ ͕ <ĂƚŽ͕ d ;ϮϬϬϲͿ /ĚĞŶƚŝĨŝĐĂƚŝŽŶ ŽĨ ŵŝƚŽĐŚŽŶĚƌŝĂů E ƉŽůǇŵŽƌƉŚŝƐŵƐ ƚŚĂƚ
ĂůƚĞƌ ŵŝƚŽĐŚŽŶĚƌŝĂů ŵĂƚƌŝǆ Ɖ, ĂŶĚ ŝŶƚƌĂĐĞůůƵůĂƌ ĐĂůĐŝƵŵ ĚǇŶĂŵŝĐƐ͘ W>Ž^ 'ĞŶĞƚ Ϯ;ϴͿ͗
ĞϭϮϴ͘
<ĞůƐŽ͕ '&͕ WŽƌƚĞŽƵƐ͕ D͕ ŽƵůƚĞƌ͕ s͕ ,ƵŐŚĞƐ͕ '͕ WŽƌƚĞŽƵƐ͕ t<͕ >ĞĚŐĞƌǁŽŽĚ͕ ͕
^ŵŝƚŚ͕ Z͕ DƵƌƉŚǇ͕ DW ;ϮϬϬϭͿ ^ĞůĞĐƚŝǀĞ ƚĂƌŐĞƚŝŶŐ ŽĨ Ă ƌĞĚŽǆͲĂĐƚŝǀĞ ƵďŝƋƵŝŶŽŶĞ ƚŽ
ŵŝƚŽĐŚŽŶĚƌŝĂ ǁŝƚŚŝŶ ĐĞůůƐ͗ ĂŶƚŝŽǆŝĚĂŶƚ ĂŶĚ ĂŶƚŝĂƉŽƉƚŽƚŝĐ ƉƌŽƉĞƌƚŝĞƐ͘ : ŝŽů ŚĞŵ
Ϯϳϲ;ϳͿ͗ϰϱϴϴͲϰϱϵϲ͘
<ĞŶŶĂĚǇ͕W<͕KƌŵĞƌŽĚ͕D'͕^ŝŶŐŚ͕^͕WĂŶĚĞ͕';ϮϬϬϰͿsĂƌŝĂƚŝŽŶŽĨŵŝƚŽĐŚŽŶĚƌŝĂůƐŝǌĞ
ĚƵƌŝŶŐ ƚŚĞ ĐĞůů ĐǇĐůĞ͗ ŵƵůƚŝƉĂƌĂŵĞƚĞƌ ĨůŽǁ ĐǇƚŽŵĞƚƌŝĐ ĂŶĚ ŵŝĐƌŽƐĐŽƉŝĐ ƐƚƵĚǇ͘
ǇƚŽŵĞƚƌǇϲϮ;ϮͿ͗ϵϳͲϭϬϴ͘
<Ğƌƌ͕:&͕tǇůůŝĞ͕,͕ƵƌƌŝĞ͕Z;ϭϵϳϮͿƉŽƉƚŽƐŝƐ͗ĂďĂƐŝĐďŝŽůŽŐŝĐĂůƉŚĞŶŽŵĞŶŽŶǁŝƚŚ
ǁŝĚĞͲƌĂŶŐŝŶŐŝŵƉůŝĐĂƚŝŽŶƐŝŶƚŝƐƐƵĞŬŝŶĞƚŝĐƐ͘ƌ:ĂŶĐĞƌϮϲ;ϰͿ͗ϮϯϵͲϮϱϳ͘
<ŝŵ͕ /͕ >ĞŵĂƐƚĞƌƐ͕ :: ;ϮϬϭϬͿ DŝƚŽĐŚŽŶĚƌŝĂů ĚĞŐƌĂĚĂƚŝŽŶ ďǇ ĂƵƚŽƉŚĂŐǇ ;ŵŝƚŽƉŚĂŐǇͿ ŝŶ
'&WͲ>ϯƚƌĂŶƐŐĞŶŝĐŚĞƉĂƚŽĐǇƚĞƐĚƵƌŝŶŐŶƵƚƌŝĞŶƚĚĞƉƌŝǀĂƚŝŽŶ͘ŵ:WŚǇƐŝŽůĞůůWŚǇƐŝŽů
ϯϬϬ;ϮͿ͗ϯϬϴͲϯϭϳ͘
<ŝŵ͕Z;ϮϬϬϱͿhŶŬŶŽƚƚŝŶŐƚŚĞƌŽůĞƐŽĨĐůͲϮĂŶĚĐůͲǆ>ŝŶĐĞůůĚĞĂƚŚ͘ŝŽĐŚĞŵŝŽƉŚǇƐ
ZĞƐŽŵŵƵŶϯϯϯ;ϮͿ͗ϯϯϲͲϯϰϯ͘
<ŝŵ͕ Z,͕ ŽĂƚĞƐ͕ :D͕ ŽǁůĞƐ͕ d>͕ DĐEĞƌŶĞǇ͕ 'W͕ ^ƵƚĐůŝĨĨĞ͕ :͕ :ƵŶŐ͕ :h͕ 'ĂŶĚŽƵƌͲ
ĚǁĂƌĚƐ͕ Z͕ ŚƵĂŶŐ͕ &z͕ ŽůĚ͕ Z:͕ <ƵŶŐ͕ ,: ;ϮϬϬϵͿ ƌŐŝŶŝŶĞ ĚĞŝŵŝŶĂƐĞ ĂƐ Ă ŶŽǀĞů
ƚŚĞƌĂƉǇ ĨŽƌ ƉƌŽƐƚĂƚĞ ĐĂŶĐĞƌ ŝŶĚƵĐĞƐ ĂƵƚŽƉŚĂŐǇ ĂŶĚ ĐĂƐƉĂƐĞͲŝŶĚĞƉĞŶĚĞŶƚ ĂƉŽƉƚŽƐŝƐ͘
ĂŶĐĞƌZĞƐϲϵ;ϮͿ͗ϳϬϬͲϳϬϴ͘
ϵϴ
<ŝŶŐ͕ ͕ ^ĞůĂŬ͕ D͕ 'ŽƚƚůŝĞď͕ ;ϮϬϬϲͿ ^ƵĐĐŝŶĂƚĞ ĚĞŚǇĚƌŽŐĞŶĂƐĞ ĂŶĚ ĨƵŵĂƌĂƚĞ
ŚǇĚƌĂƚĂƐĞ͗ůŝŶŬŝŶŐŵŝƚŽĐŚŽŶĚƌŝĂůĚǇƐĨƵŶĐƚŝŽŶĂŶĚĐĂŶĐĞƌ͘KŶĐŽŐĞŶĞϮϱ;ϯϰͿ͗ϰϲϳϱͲϰϲϴϮ͘
<ŝƌŝŬ͕͕'ĞŽƌŐŝĞǀƐŬĂ͕͕ ƵƌŐĞƌ͕͕tŝŶŬůĞƌ͕͕DƵǌǇĐǌŬĂ͕E͕DĂŶĚĞů͕Z:͕ũŽƌŬůƵŶĚ͕
;ϮϬϬϮͿZĞǀĞƌƐĂůŽĨŵŽƚŽƌŝŵƉĂŝƌŵĞŶƚƐŝŶƉĂƌŬŝŶƐŽŶŝĂŶƌĂƚƐďǇĐŽŶƚŝŶƵŽƵƐŝŶƚƌĂƐƚƌŝĂƚĂů
ĚĞůŝǀĞƌǇŽĨ>ͲĚŽƉĂƵƐŝŶŐƌsͲŵĞĚŝĂƚĞĚŐĞŶĞƚƌĂŶƐĨĞƌ͘WƌŽĐEĂƚůĐĂĚ^Đŝh^ϵϵ;ϳͿ͗
ϰϳϬϴͲϰϳϭϯ͘
<ŝƚĂĚĂ͕d͕ƐĂŬĂǁĂ͕^͕,ĂƚƚŽƌŝ͕E͕DĂƚƐƵŵŝŶĞ͕,͕zĂŵĂŵƵƌĂ͕z͕DŝŶŽƐŚŝŵĂ͕^͕zŽŬŽĐŚŝ͕
D͕ DŝǌƵŶŽ͕ z͕ ^ŚŝŵŝǌƵ͕ E ;ϭϵϵϴͿ DƵƚĂƚŝŽŶƐ ŝŶ ƚŚĞ ƉĂƌŬŝŶ ŐĞŶĞ ĐĂƵƐĞ ĂƵƚŽƐŽŵĂů
ƌĞĐĞƐƐŝǀĞũƵǀĞŶŝůĞƉĂƌŬŝŶƐŽŶŝƐŵ͘EĂƚƵƌĞϯϵϮ;ϲϲϳϲͿ͗ϲϬϱͲϲϬϴ͘
<ŶŽƚƚ͕ ͕ ŽƐƐǇͲtĞƚǌĞů͕ ;ϮϬϬϴĂͿ /ŵƉĂŝƌŝŶŐ ƚŚĞ ŵŝƚŽĐŚŽŶĚƌŝĂů ĨŝƐƐŝŽŶ ĂŶĚ ĨƵƐŝŽŶ
ďĂůĂŶĐĞ͗ĂŶĞǁŵĞĐŚĂŶŝƐŵŽĨŶĞƵƌŽĚĞŐĞŶĞƌĂƚŝŽŶ͘ŶŶEzĐĂĚ^Đŝϭϭϰϳ͗ϮϴϯͲϮϵϮ͘
<ŶŽƚƚ͕ ͕ WĞƌŬŝŶƐ͕ '͕ ^ĐŚǁĂƌǌĞŶďĂĐŚĞƌ͕ Z͕ ŽƐƐǇͲtĞƚǌĞů͕ ;ϮϬϬϴďͿ DŝƚŽĐŚŽŶĚƌŝĂů
ĨƌĂŐŵĞŶƚĂƚŝŽŶŝŶŶĞƵƌŽĚĞŐĞŶĞƌĂƚŝŽŶ͘EĂƚZĞǀEĞƵƌŽƐĐŝϵ;ϳͿ͗ϱϬϱͲϱϭϴ͘
<ŽĐŚ͕ ͕ dŚŝĞŵĂŶŶ͕ D͕ 'ƌĂďĞŶďĂƵĞƌ͕ D͕ zŽŽŶ͕ z͕ DĐEŝǀĞŶ͕ D͕ ^ĐŚƌĂĚĞƌ͕ D ;ϮϬϬϯͿ
ǇŶĂŵŝŶͲůŝŬĞ ƉƌŽƚĞŝŶ ϭ ŝƐ ŝŶǀŽůǀĞĚ ŝŶ ƉĞƌŽǆŝƐŽŵĂů ĨŝƐƐŝŽŶ͘ : ŝŽů ŚĞŵ Ϯϳϴ;ϭϬͿ͗ ϴϱϵϳͲ
ϴϲϬϱ͘
<ŽĐŚ͕͕zŽŽŶ͕z͕ŽŶĞŬĂŵƉ͕E͕DĐEŝǀĞŶ͕D͕^ĐŚƌĂĚĞƌ͕D;ϮϬϬϱͿƌŽůĞĨŽƌ&ŝƐϭŝŶ
ďŽƚŚ ŵŝƚŽĐŚŽŶĚƌŝĂůĂŶĚƉĞƌŽǆŝƐŽŵĂůĨŝƐƐŝŽŶ ŝŶ ŵĂŵŵĂůŝĂŶ ĐĞůůƐ͘ DŽů ŝŽů Ğůů ϭϲ;ϭϭͿ͗
ϱϬϳϳͲϱϬϴϲ͘
<ŽŵĂƚƐƵ͕ D͕ tĂŐƵƌŝ͕ ^͕ <ŽŝŬĞ͕ D͕ ^ŽƵ͕ z^͕ hĞŶŽ͕ d͕ ,ĂƌĂ͕ d͕ DŝǌƵƐŚŝŵĂ͕ E͕ /ǁĂƚĂ͕ :͕
ǌĂŬŝ͕ :͕ DƵƌĂƚĂ͕ ^͕ ,ĂŵĂǌĂŬŝ͕ :͕ EŝƐŚŝƚŽ͕ z͕ /ĞŵƵƌĂ͕ ^͕ EĂƚƐƵŵĞ͕ d͕ zĂŶĂŐĂǁĂ͕ d͕
hǁĂǇĂŵĂ͕ :͕ tĂƌĂďŝ͕ ͕ zŽƐŚŝĚĂ͕ ,͕ /ƐŚŝŝ͕ d͕ <ŽďĂǇĂƐŚŝ͕ ͕ zĂŵĂŵŽƚŽ͕ D͕ zƵĞ͕ ͕
hĐŚŝǇĂŵĂ͕ z͕ <ŽŵŝŶĂŵŝ͕ ͕ dĂŶĂŬĂ͕ < ;ϮϬϬϳͿ ,ŽŵĞŽƐƚĂƚŝĐ ůĞǀĞůƐ ŽĨ ƉϲϮ ĐŽŶƚƌŽů
ĐǇƚŽƉůĂƐŵŝĐ ŝŶĐůƵƐŝŽŶ ďŽĚǇ ĨŽƌŵĂƚŝŽŶ ŝŶ ĂƵƚŽƉŚĂŐǇͲĚĞĨŝĐŝĞŶƚ ŵŝĐĞ͘ Ğůů ϭϯϭ;ϲͿ͗ ϭϭϰϵͲ
ϭϭϲϯ͘
<ŽŶŐĂƌĂ͕ ^͕ <ĂƌĂŶƚǌĂ͕ s ;ϮϬϭϮͿ dŚĞ ŝŶƚĞƌƉůĂǇ ďĞƚǁĞĞŶ ĂƵƚŽƉŚĂŐǇ ĂŶĚ ZK^ ŝŶ
ƚƵŵŽƌŝŐĞŶĞƐŝƐ͘&ƌŽŶƚKŶĐŽůϮ͗ϭϳϭ͘
<ŽƐĞŽŐůƵ͕^͕ŝůŬƐ͕:Z͕WĞƚĞƌƐ͕'͕&ŝƚĐŚͲdĞǁĨŝŬ͕:>͕&ĂĚĞů͕E͕:ĂƐƵũĂ͕Z͕/ƚĂůŝĂŶŽ͕:͕:ƌ͕͘
,ĂǇŶĞƐ͕ >͕ &ůĂƵŵĞŶŚĂĨƚ͕ Z ;ϮϬϭϯͿ ǇŶĂŵŝŶͲƌĞůĂƚĞĚ ƉƌŽƚĞŝŶͲϭ ĐŽŶƚƌŽůƐ ĨƵƐŝŽŶ ƉŽƌĞ
ĚǇŶĂŵŝĐƐĚƵƌŝŶŐƉůĂƚĞůĞƚŐƌĂŶƵůĞĞǆŽĐǇƚŽƐŝƐ͘ƌƚĞƌŝŽƐĐůĞƌdŚƌŽŵďsĂƐĐŝŽůϯϯ;ϯͿ͗ϰϴϭͲ
ϰϴϴ͘
<ŽƐŚŝďĂ͕d͕ĞƚŵĞƌ͕^͕<ĂŝƐĞƌ͕:d͕ŚĞŶ͕,͕DĐĂĨĨĞƌǇ͕:D͕ŚĂŶ͕;ϮϬϬϰͿ^ƚƌƵĐƚƵƌĂů
ďĂƐŝƐŽĨŵŝƚŽĐŚŽŶĚƌŝĂůƚĞƚŚĞƌŝŶŐďǇŵŝƚŽĨƵƐŝŶĐŽŵƉůĞǆĞƐ͘^ĐŝĞŶĐĞϯϬϱ;ϱϲϴϱͿ͗ϴϱϴͲϴϲϮ͘
<ŽƐƚƌǌĞǁĂ͕ ZD͕ :ĂĐŽďŽǁŝƚǌ͕ D ;ϭϵϳϰͿ WŚĂƌŵĂĐŽůŽŐŝĐĂů ĂĐƚŝŽŶƐ ŽĨ ϲͲ
ŚǇĚƌŽǆǇĚŽƉĂŵŝŶĞ͘WŚĂƌŵĂĐŽůZĞǀϮϲ;ϯͿ͗ϭϵϵͲϮϴϴ͘
ϵϵ
<ŽǁĂůƚŽǁƐŬŝ͕:͕ĚĞ^ŽƵǌĂͲWŝŶƚŽ͕E͕ĂƐƚŝůŚŽ͕Z&͕sĞƌĐĞƐŝ͕;ϮϬϬϵͿDŝƚŽĐŚŽŶĚƌŝĂĂŶĚ
ƌĞĂĐƚŝǀĞŽǆǇŐĞŶƐƉĞĐŝĞƐ͘&ƌĞĞZĂĚŝĐŝŽůDĞĚϰϳ;ϰͿ͗ϯϯϯͲϯϰϯ͘
<ƌĂǇƚƐďĞƌŐ͕ z͕ <ƵĚƌǇĂǀƚƐĞǀĂ͕ ͕ DĐ<ĞĞ͕ ͕ 'ĞƵůĂ͕ ͕ <ŽǁĂůů͕ Et͕ <ŚƌĂƉŬŽ͕ < ;ϮϬϬϲͿ
DŝƚŽĐŚŽŶĚƌŝĂů E ĚĞůĞƚŝŽŶƐ ĂƌĞ ĂďƵŶĚĂŶƚ ĂŶĚ ĐĂƵƐĞ ĨƵŶĐƚŝŽŶĂů ŝŵƉĂŝƌŵĞŶƚ ŝŶ ĂŐĞĚ
ŚƵŵĂŶƐƵďƐƚĂŶƚŝĂŶŝŐƌĂŶĞƵƌŽŶƐ͘EĂƚ'ĞŶĞƚϯϴ;ϱͿ͗ϱϭϴͲϱϮϬ͘
<ƌŝƐƚĞŶƐĞŶ͕ Z͕ ^ĐŚĂŶĚŽƌĨĨ͕ ^͕ ,ŽǇĞƌͲ,ĂŶƐĞŶ͕ D͕ EŝĞůƐĞŶ͕DK͕ :ĂĂƚƚĞůĂ͕D͕ ĞŶŐũĞů͕ :͕
ŶĚĞƌƐĞŶ͕ :^ ;ϮϬϬϴͿ KƌĚĞƌĞĚ ŽƌŐĂŶĞůůĞ ĚĞŐƌĂĚĂƚŝŽŶ ĚƵƌŝŶŐ ƐƚĂƌǀĂƚŝŽŶͲŝŶĚƵĐĞĚ
ĂƵƚŽƉŚĂŐǇ͘DŽůĞůůWƌŽƚĞŽŵŝĐƐϳ;ϭϮͿ͗ϮϰϭϵͲϮϰϮϴ͘
<ƌŽĞŵĞƌ͕ '͕ 'ĂůůƵǌǌŝ͕ >͕ sĂŶĚĞŶĂďĞĞůĞ͕ W͕ ďƌĂŵƐ͕ :͕ ůŶĞŵƌŝ͕ ^͕ ĂĞŚƌĞĐŬĞ͕ ,͕
ůĂŐŽƐŬůŽŶŶǇ͕ Ds͕ ůͲĞŝƌǇ͕ t^͕ 'ŽůƐƚĞŝŶ͕ W͕ 'ƌĞĞŶ͕ Z͕ ,ĞŶŐĂƌƚŶĞƌ͕ D͕ <ŶŝŐŚƚ͕ Z͕
<ƵŵĂƌ͕^͕>ŝƉƚŽŶ͕^͕DĂůŽƌŶŝ͕t͕EƵŶĞǌ͕'͕WĞƚĞƌ͕D͕dƐĐŚŽƉƉ͕:͕zƵĂŶ͕:͕WŝĂĐĞŶƚŝŶŝ͕
D͕ ŚŝǀŽƚŽǀƐŬǇ͕ ͕ DĞůŝŶŽ͕ ' ;ϮϬϬϵͿ ůĂƐƐŝĨŝĐĂƚŝŽŶ ŽĨ ĐĞůů ĚĞĂƚŚ͗ ƌĞĐŽŵŵĞŶĚĂƚŝŽŶƐ ŽĨ
ƚŚĞEŽŵĞŶĐůĂƚƵƌĞŽŵŵŝƚƚĞĞŽŶĞůůĞĂƚŚϮϬϬϵ͘ĞůůĞĂƚŚŝĨĨĞƌϭϲ;ϭͿ͗ϯͲϭϭ͘
<ƌŽĞŵĞƌ͕ '͕ ZĞĞĚ͕ : ;ϮϬϬϬͿ DŝƚŽĐŚŽŶĚƌŝĂů ĐŽŶƚƌŽů ŽĨ ĐĞůů ĚĞĂƚŚ͘ EĂƚ DĞĚ ϲ;ϱͿ͗ ϱϭϯͲ
ϱϭϵ͘
<ƵůŝĐŚ͕ ^D͕ ŚƵ͕ d ;ϮϬϬϯͿ ZŽůĞ ŽĨ ƌĞĂĐƚŝǀĞ ŽǆǇŐĞŶ ƐƉĞĐŝĞƐ ŝŶ ĞǆƚƌĂĐĞůůƵůĂƌ ƐŝŐŶĂůͲ
ƌĞŐƵůĂƚĞĚƉƌŽƚĞŝŶŬŝŶĂƐĞƉŚŽƐƉŚŽƌǇůĂƚŝŽŶĂŶĚϲͲŚǇĚƌŽǆǇĚŽƉĂŵŝŶĞĐǇƚŽƚŽǆŝĐŝƚǇ͘:ŝŽƐĐŝ
Ϯϴ;ϭͿ͗ϴϯͲϴϵ͘
<ƵůŝĐŚ͕ ^D͕ ,ŽƌďŝŶƐŬŝ͕ ͕ WĂƚĞů͕ D͕ ŚƵ͕ d ;ϮϬϬϳͿ ϲͲ,ǇĚƌŽǆǇĚŽƉĂŵŝŶĞ ŝŶĚƵĐĞƐ
ŵŝƚŽĐŚŽŶĚƌŝĂůZ<ĂĐƚŝǀĂƚŝŽŶ͘&ƌĞĞZĂĚŝĐŝŽůDĞĚϰϯ;ϯͿ͗ϯϳϮͲϯϴϯ͘
<ƵŵĂƌ͕ Z͕ ŐĂƌǁĂů͕ <͕ ^ĞƚŚ͕ W< ;ϭϵϵϱͿ &ƌĞĞ ƌĂĚŝĐĂůͲŐĞŶĞƌĂƚĞĚ ŶĞƵƌŽƚŽǆŝĐŝƚǇ ŽĨ ϲͲ
ŚǇĚƌŽǆǇĚŽƉĂŵŝŶĞ͘:EĞƵƌŽĐŚĞŵϲϰ;ϰͿ͗ϭϳϬϯͲϭϳϬϳ͘
<ƵŵĂƌŝ͕ h͕ zĂ :ƵŶ͕ t͕ ,ƵĂƚ ĂǇ͕ ͕ >ǇĂŬŚŽǀŝĐŚ͕ ;ϮϬϭϯͿ ǀŝĚĞŶĐĞ ŽĨ ŵŝƚŽĐŚŽŶĚƌŝĂů
ĚǇƐĨƵŶĐƚŝŽŶ ĂŶĚ ŝŵƉĂŝƌĞĚ ZK^ ĚĞƚŽǆŝĨǇŝŶŐ ŵĂĐŚŝŶĞƌǇ ŝŶ &ĂŶĐŽŶŝ ŶĞŵŝĂ ĐĞůůƐ͘
KŶĐŽŐĞŶĞ͘
>ĂďƌŽƵƐƐĞ͕ D͕ ĂƉƉĂƚĞƌƌĂ͕ D͕ ZƵďĞ͕ ͕ ǀĂŶ ĚĞƌ ůŝĞŬ͕ D ;ϭϵϵϵͿ ͘ ĞůĞŐĂŶƐ
ĚǇŶĂŵŝŶͲƌĞůĂƚĞĚ ƉƌŽƚĞŝŶ ZWͲϭ ĐŽŶƚƌŽůƐ ƐĞǀĞƌŝŶŐ ŽĨ ƚŚĞ ŵŝƚŽĐŚŽŶĚƌŝĂů ŽƵƚĞƌ
ŵĞŵďƌĂŶĞ͘DŽůĞůůϰ;ϱͿ͗ϴϭϱͲϴϮϲ͘
>Ăŝ͕d͕zƵ͕W,;ϭϵϵϳͿŽƉĂŵŝŶĞͲĂŶĚ>ͲďĞƚĂͲϯ͕ϰͲĚŝŚǇĚƌŽǆǇƉŚĞŶǇůĂůĂŶŝŶĞŚǇĚƌŽĐŚůŽƌŝĚĞ
;>ͲŽƉĂͿͲŝŶĚƵĐĞĚĐǇƚŽƚŽǆŝĐŝƚǇƚŽǁĂƌĚƐĐĂƚĞĐŚŽůĂŵŝŶĞƌŐŝĐŶĞƵƌŽďůĂƐƚŽŵĂ^,Ͳ^zϱzĐĞůůƐ͘
ĨĨĞĐƚƐ ŽĨ ŽǆŝĚĂƚŝǀĞ ƐƚƌĞƐƐ ĂŶĚ ĂŶƚŝŽǆŝĚĂƚŝǀĞ ĨĂĐƚŽƌƐ͘ ŝŽĐŚĞŵ WŚĂƌŵĂĐŽů ϱϯ;ϯͿ͗ ϯϲϯͲ
ϯϳϮ͘
>ĂŝŐŚƚ͕t͕ŶĚƌĞǁƐ͕d:͕,ĂũͲzĞŚŝĂ͕/͕ĂƌƌŝĞƌ͕D:͕ŶŐŐĂƌĚ͕;ϭϵϵϳͿDŝĐƌŽĂƐƐĂǇŽĨ
ƐƵƉĞƌŽǆŝĚĞĂŶŝŽŶƐĐĂǀĞŶŐŝŶŐĂĐƚŝǀŝƚǇŝŶǀŝƚƌŽ͘ŶǀŝƌŽŶdŽǆŝĐŽůWŚĂƌŵĂĐŽůϯ;ϭͿ͗ϲϱͲϲϴ͘
ϭϬϬ
>ĂŶĚĞƐ͕d͕DĂƌƚŝŶŽƵ͕:;ϮϬϭϭͿDŝƚŽĐŚŽŶĚƌŝĂůŽƵƚĞƌŵĞŵďƌĂŶĞƉĞƌŵĞĂďŝůŝǌĂƚŝŽŶĚƵƌŝŶŐ
ĂƉŽƉƚŽƐŝƐ͗ƚŚĞƌŽůĞŽĨŵŝƚŽĐŚŽŶĚƌŝĂůĨŝƐƐŝŽŶ͘ŝŽĐŚŝŵŝŽƉŚǇƐĐƚĂϭϴϭϯ;ϰͿ͗ϱϰϬͲϱϰϱ͘
>ĂŶŐƐƚŽŶ͕ :t͕ ĂůůĂƌĚ͕ W͕ dĞƚƌƵĚ͕ :t͕ /ƌǁŝŶ͕ / ;ϭϵϴϯͿ ŚƌŽŶŝĐ WĂƌŬŝŶƐŽŶŝƐŵ ŝŶ ŚƵŵĂŶƐ
ĚƵĞƚŽĂƉƌŽĚƵĐƚŽĨŵĞƉĞƌŝĚŝŶĞͲĂŶĂůŽŐƐǇŶƚŚĞƐŝƐ͘^ĐŝĞŶĐĞϮϭϵ;ϰϱϴϳͿ͗ϵϳϵͲϵϴϬ͘
>ĂŶŶŝ͕ ͕ DŽƌĞŶŽ͕ D͕ >ŽŵďĂƌĚŝ͕ ͕ ĚĞ >ĂŶŐĞ͕ W͕ 'ŽŐůŝĂ͕ & ;ϮϬϬϭͿ ŽŶƚƌŽů ŽĨ ĞŶĞƌŐǇ
ŵĞƚĂďŽůŝƐŵďǇŝŽĚŽƚŚǇƌŽŶŝŶĞƐ͘:ŶĚŽĐƌŝŶŽů/ŶǀĞƐƚϮϰ;ϭϭͿ͗ϴϵϳͲϵϭϯ͘
>ĞĞ͕E͕ŚŽŝ͕zt͕<ŝŵ͕,<͕WĂƌŬ͕:<͕<ŝŵ͕,:͕<ŝŵ͕D:͕>ĞĞ͕,t͕<ŝŵ͕<,͕ĂĞ͕^^͕<ŝŵ͕
^͕ zŽŽŶ͕ ^ ;ϮϬϭϭͿ ŚůŽƌŽĨŽƌŵ ĞǆƚƌĂĐƚ ŽĨ ĂŐĞĚ ďůĂĐŬ ŐĂƌůŝĐ ĂƚƚĞŶƵĂƚĞƐ dE&ͲĂůƉŚĂͲ
ŝŶĚƵĐĞĚZK^ŐĞŶĞƌĂƚŝŽŶ͕sDͲϭĞǆƉƌĞƐƐŝŽŶ͕E&ͲŬĂƉƉĂĂĐƚŝǀĂƚŝŽŶĂŶĚĂĚŚĞƐŝǀĞŶĞƐƐ
ĨŽƌŵŽŶŽĐǇƚĞƐŝŶŚƵŵĂŶƵŵďŝůŝĐĂůǀĞŝŶĞŶĚŽƚŚĞůŝĂůĐĞůůƐ͘WŚǇƚŽƚŚĞƌZĞƐϮϱ;ϭͿ͗ϵϮͲϭϬϬ͘
>ĞĞ͕ :͕ 'ŝŽƌĚĂŶŽ͕ ^͕ ŚĂŶŐ͕ : ;ϮϬϭϮͿ ƵƚŽƉŚĂŐǇ͕ ŵŝƚŽĐŚŽŶĚƌŝĂ ĂŶĚ ŽǆŝĚĂƚŝǀĞ ƐƚƌĞƐƐ͗
ĐƌŽƐƐͲƚĂůŬĂŶĚƌĞĚŽǆƐŝŐŶĂůůŝŶŐ͘ŝŽĐŚĞŵ:ϰϰϭ;ϮͿ͗ϱϮϯͲϱϰϬ͘
>ĞĞ͕ ^͕ :ĞŽŶŐ͕ ^z͕ >ŝŵ͕ t͕ <ŝŵ͕ ^͕ WĂƌŬ͕ zz͕ ^ƵŶ͕ y͕ zŽƵůĞ͕ Z:͕ ŚŽ͕ , ;ϮϬϬϳͿ
DŝƚŽĐŚŽŶĚƌŝĂů ĨŝƐƐŝŽŶ ĂŶĚ ĨƵƐŝŽŶ ŵĞĚŝĂƚŽƌƐ͕ Ś&ŝƐϭ ĂŶĚ KWϭ͕ ŵŽĚƵůĂƚĞ ĐĞůůƵůĂƌ
ƐĞŶĞƐĐĞŶĐĞ͘:ŝŽůŚĞŵϮϴϮ;ϯϭͿ͗ϮϮϵϳϳͲϮϮϵϴϯ͘
>ĞĞ͕ ^:͕ ŚŽ͕ <^͕ <ŽŚ͕:z ;ϮϬϬϵͿ KǆŝĚĂƚŝǀĞ ŝŶũƵƌǇƚƌŝŐŐĞƌƐ ĂƵƚŽƉŚĂŐǇ ŝŶ ĂƐƚƌŽĐǇƚĞƐ͗ƚŚĞ
ƌŽůĞŽĨĞŶĚŽŐĞŶŽƵƐǌŝŶĐ͘'ůŝĂϱϳ;ϭϮͿ͗ϭϯϱϭͲϭϯϲϭ͘
>ĞĞ͕z:͕:ĞŽŶŐ͕^z͕<ĂƌďŽǁƐŬŝ͕D͕^ŵŝƚŚ͕>͕zŽƵůĞ͕Z:;ϮϬϬϰͿZŽůĞƐŽĨƚŚĞŵĂŵŵĂůŝĂŶ
ŵŝƚŽĐŚŽŶĚƌŝĂůĨŝƐƐŝŽŶĂŶĚĨƵƐŝŽŶŵĞĚŝĂƚŽƌƐ&ŝƐϭ͕ƌƉϭ͕ĂŶĚKƉĂϭŝŶĂƉŽƉƚŽƐŝƐ͘DŽůŝŽů
Ğůůϭϱ;ϭϭͿ͗ϱϬϬϭͲϱϬϭϭ͘
>ĞŐĞƐƐĞͲDŝůůĞƌ͕ ͕ DĂƐƐŽů͕ Z,͕ <ŝƌĐŚŚĂƵƐĞŶ͕ d ;ϮϬϬϯͿ ŽŶƐƚƌŝĐƚŝŽŶ ĂŶĚ ŶŵϭƉ
ƌĞĐƌƵŝƚŵĞŶƚ ĂƌĞ ĚŝƐƚŝŶĐƚƉƌŽĐĞƐƐĞƐ ŝŶ ŵŝƚŽĐŚŽŶĚƌŝĂů ĨŝƐƐŝŽŶ͘ DŽů ŝŽů Ğůů ϭϰ;ϱͿ͗ ϭϵϱϯͲ
ϭϵϲϯ͘
>ĞŐƌŽƐ͕&͕>ŽŵďĞƐ͕͕&ƌĂĐŚŽŶ͕W͕ZŽũŽ͕D;ϮϬϬϮͿDŝƚŽĐŚŽŶĚƌŝĂůĨƵƐŝŽŶŝŶŚƵŵĂŶĐĞůůƐŝƐ
ĞĨĨŝĐŝĞŶƚ͕ƌĞƋƵŝƌĞƐƚŚĞŝŶŶĞƌŵĞŵďƌĂŶĞƉŽƚĞŶƚŝĂů͕ĂŶĚŝƐŵĞĚŝĂƚĞĚďǇŵŝƚŽĨƵƐŝŶƐ͘DŽů
ŝŽůĞůůϭϯ;ϭϮͿ͗ϰϯϰϯͲϰϯϱϰ͘
>ĞŐƌŽƐ͕&͕DĂůŬĂ͕&͕&ƌĂĐŚŽŶ͕W͕>ŽŵďĞƐ͕͕ZŽũŽ͕D;ϮϬϬϰͿKƌŐĂŶŝǌĂƚŝŽŶĂŶĚĚǇŶĂŵŝĐƐ
ŽĨŚƵŵĂŶŵŝƚŽĐŚŽŶĚƌŝĂůE͘:Ğůů^Đŝϭϭϳ;WƚϭϯͿ͗ϮϲϱϯͲϮϲϲϮ͘
>ĞŵĂƐƚĞƌƐ͕ :: ;ϮϬϬϱͿ ^ĞůĞĐƚŝǀĞ ŵŝƚŽĐŚŽŶĚƌŝĂů ĂƵƚŽƉŚĂŐǇ͕ Žƌ ŵŝƚŽƉŚĂŐǇ͕ ĂƐ Ă ƚĂƌŐĞƚĞĚ
ĚĞĨĞŶƐĞ ĂŐĂŝŶƐƚ ŽǆŝĚĂƚŝǀĞ ƐƚƌĞƐƐ͕ ŵŝƚŽĐŚŽŶĚƌŝĂů ĚǇƐĨƵŶĐƚŝŽŶ͕ ĂŶĚ ĂŐŝŶŐ͘ ZĞũƵǀĞŶĂƚŝŽŶ
ZĞƐϴ;ϭͿ͗ϯͲϱ͘
>ĞŵŝĞƵǆ͕,͕,ŽƉƉĞů͕>;ϮϬϬϵͿDŝƚŽĐŚŽŶĚƌŝĂŝŶƚŚĞŚƵŵĂŶŚĞĂƌƚ͘:ŝŽĞŶĞƌŐŝŽŵĞŵďƌ
ϰϭ;ϮͿ͗ϵϵͲϭϬϲ͘
ϭϬϭ
>ĞŵŝĞƵǆ͕ ,͕ ^ĞŵƐƌŽƚŚ͕ ^͕ ŶƚƌĞƚƚĞƌ͕ ,͕ ,ŽĨĞƌ͕ ͕ 'ŶĂŝŐĞƌ͕ ;ϮϬϭϭͿ DŝƚŽĐŚŽŶĚƌŝĂů
ƌĞƐƉŝƌĂƚŽƌǇĐŽŶƚƌŽůĂŶĚĞĂƌůǇĚĞĨĞĐƚƐŽĨŽǆŝĚĂƚŝǀĞƉŚŽƐƉŚŽƌǇůĂƚŝŽŶŝŶƚŚĞĨĂŝůŝŶŐŚƵŵĂŶ
ŚĞĂƌƚ͘/Ŷƚ:ŝŽĐŚĞŵĞůůŝŽůϰϯ;ϭϮͿ͗ϭϳϮϵͲϭϳϯϴ͘
>ĞǀĞŶƚŚĂů͕ >͕ ^ŽƌƚǁĞůů͕ ͕ ,ĂŶďƵƌǇ͕ Z͕ ŽůůŝĞƌ͕ d:͕ <ŽƌĚŽǁĞƌ͕ :,͕ WĂůĨŝ͕ ^ ;ϮϬϬϬͿ
ǇĐůŽƐƉŽƌŝŶƉƌŽƚĞĐƚƐƐƚƌŝĂƚĂůŶĞƵƌŽŶƐŝŶǀŝƚƌŽĂŶĚŝŶǀŝǀŽĨƌŽŵϯͲŶŝƚƌŽƉƌŽƉŝŽŶŝĐĂĐŝĚ
ƚŽǆŝĐŝƚǇ͘:ŽŵƉEĞƵƌŽůϰϮϱ;ϰͿ͗ϰϳϭͲϰϳϴ͘
>ŝ͕t͕ĞŶŐƚƐŽŶ͕D,͕hůďƌŝĐŚ͕͕DĂƚƐƵĚĂ͕͕ZĞĚĚǇ͕s͕KƌƚŚ͕͕ŚĂŶĚĂ͕^<͕ĂƚĂůŽǀ͕
^͕:ŽĂǌĞŝƌŽ͕;ϮϬϬϴͿ'ĞŶŽŵĞͲǁŝĚĞĂŶĚĨƵŶĐƚŝŽŶĂůĂŶŶŽƚĂƚŝŽŶŽĨŚƵŵĂŶϯƵďŝƋƵŝƚŝŶ
ůŝŐĂƐĞƐ ŝĚĞŶƚŝĨŝĞƐ Dh>E͕ Ă ŵŝƚŽĐŚŽŶĚƌŝĂů ϯ ƚŚĂƚ ƌĞŐƵůĂƚĞƐ ƚŚĞ ŽƌŐĂŶĞůůĞΖƐ ĚǇŶĂŵŝĐƐ
ĂŶĚƐŝŐŶĂůŝŶŐ͘W>Ž^KŶĞϯ;ϭͿ͗Ğϭϰϴϳ͘
>ŝ͕ ͕ KŬĂŵŽƚŽ͕ <͕ ,ĂǇĂƐŚŝ͕ z͕ ^ŚĞŶŐ͕ D ;ϮϬϬϰͿ dŚĞ ŝŵƉŽƌƚĂŶĐĞ ŽĨ ĚĞŶĚƌŝƚŝĐ
ŵŝƚŽĐŚŽŶĚƌŝĂŝŶƚŚĞŵŽƌƉŚŽŐĞŶĞƐŝƐĂŶĚƉůĂƐƚŝĐŝƚǇŽĨƐƉŝŶĞƐĂŶĚƐǇŶĂƉƐĞƐ͘Ğůůϭϭϵ;ϲͿ͗
ϴϳϯͲϴϴϳ͘
>ŝ͕͕yƵ͕y͕,ƵĂŶŐ͕z͕ŝŶŐ͕>͕tĂŶŐ͕͕zƵ͕'͕yƵ͕͕>ŝ͕t͕dŽŶŐ͕;ϮϬϭϮͿ^ǁĂŝŶƐŽŶŝŶĞ
ĐƚŝǀĂƚĞƐDŝƚŽĐŚŽŶĚƌŝĂͲŵĞĚŝĂƚĞĚƉŽƉƚŽƚŝĐWĂƚŚǁĂǇŝŶ,ƵŵĂŶ>ƵŶŐĂŶĐĞƌϱϰϵĞůůƐ
ĂŶĚZĞƚĂƌĚƐƚŚĞ'ƌŽǁƚŚŽĨ>ƵŶŐĂŶĐĞƌyĞŶŽŐƌĂĨƚƐ͘/Ŷƚ:ŝŽů^Đŝϴ;ϯͿ͗ϯϵϰͲϰϬϱ͘
>ŝĞƐĂ͕D͕WĂůĂĐŝŶ͕D͕ŽƌǌĂŶŽ͕;ϮϬϬϵͿDŝƚŽĐŚŽŶĚƌŝĂůĚǇŶĂŵŝĐƐŝŶŵĂŵŵĂůŝĂŶŚĞĂůƚŚ
ĂŶĚĚŝƐĞĂƐĞ͘WŚǇƐŝŽůZĞǀϴϵ;ϯͿ͗ϳϵϵͲϴϰϱ͘
>ŝŶ͕ Dd͕ ĞĂů͕ D& ;ϮϬϬϲͿ DŝƚŽĐŚŽŶĚƌŝĂů ĚǇƐĨƵŶĐƚŝŽŶ ĂŶĚ ŽǆŝĚĂƚŝǀĞ ƐƚƌĞƐƐ ŝŶ
ŶĞƵƌŽĚĞŐĞŶĞƌĂƚŝǀĞĚŝƐĞĂƐĞƐ͘EĂƚƵƌĞϰϰϯ;ϳϭϭϯͿ͗ϳϴϳͲϳϵϱ͘
>ŝŽƚ͕'͕ŽƐƐǇ͕͕>Ƶďŝƚǌ͕^͕<ƵƐŚŶĂƌĞǀĂ͕z͕^ĞũďƵŬ͕E͕ŽƐƐǇͲtĞƚǌĞů͕;ϮϬϬϵͿŽŵƉůĞǆ//
ŝŶŚŝďŝƚŝŽŶďǇϯͲEWĐĂƵƐĞƐŵŝƚŽĐŚŽŶĚƌŝĂůĨƌĂŐŵĞŶƚĂƚŝŽŶĂŶĚŶĞƵƌŽŶĂůĐĞůůĚĞĂƚŚǀŝĂĂŶ
EDͲĂŶĚZK^ͲĚĞƉĞŶĚĞŶƚƉĂƚŚǁĂǇ͘ĞůůĞĂƚŚŝĨĨĞƌϭϲ;ϲͿ͗ϴϵϵͲϵϬϵ͘
>ŝƵ͕ y͕ tĞĂǀĞƌ͕ ͕ ^ŚŝƌŝŚĂŝ͕ K͕ ,ĂũŶŽĐǌŬǇ͕ ' ;ϮϬϬϵͿ DŝƚŽĐŚŽŶĚƌŝĂů ΖŬŝƐƐͲĂŶĚͲƌƵŶΖ͗
ŝŶƚĞƌƉůĂǇďĞƚǁĞĞŶŵŝƚŽĐŚŽŶĚƌŝĂůŵŽƚŝůŝƚǇĂŶĚĨƵƐŝŽŶͲĨŝƐƐŝŽŶĚǇŶĂŵŝĐƐ͘DK:Ϯϴ;ϮϬͿ͗
ϯϬϳϰͲϯϬϴϵ͘
>ƵŽ͕z͕ŽƵ͕W͕ŽƵ͕:͕tĂŶŐ͕:͕ŚŽƵ͕͕>ŝƵ͕>;ϮϬϭϭͿƵƚŽƉŚĂŐǇƌĞŐƵůĂƚĞƐZK^ͲŝŶĚƵĐĞĚ
ĐĞůůƵůĂƌ ƐĞŶĞƐĐĞŶĐĞ ǀŝĂ ƉϮϭ ŝŶ Ă Ɖϯϴ DW<ĂůƉŚĂ ĚĞƉĞŶĚĞŶƚ ŵĂŶŶĞƌ͘ ǆƉ 'ĞƌŽŶƚŽů
ϰϲ;ϭϭͿ͗ϴϲϬͲϴϲϳ͘
>ƵƚŚŵĂŶ͕ :͕ &ƌĞĚƌŝŬƐƐŽŶ͕ ͕ >ĞǁĂŶĚĞƌ͕ d͕ :ŽŶƐƐŽŶ͕ '͕ ƌĐŚĞƌ͕ d ;ϭϵϴϵͿ ĨĨĞĐƚƐ ŽĨ ĚͲ
ĂŵƉŚĞƚĂŵŝŶĞ ĂŶĚ ŵĞƚŚǇůƉŚĞŶŝĚĂƚĞ ŽŶ ŚǇƉĞƌĂĐƚŝǀŝƚǇ ƉƌŽĚƵĐĞĚ ďǇ ŶĞŽŶĂƚĂů ϲͲ
ŚǇĚƌŽǆǇĚŽƉĂŵŝŶĞƚƌĞĂƚŵĞŶƚ͘WƐǇĐŚŽƉŚĂƌŵĂĐŽůŽŐǇ;ĞƌůͿϵϵ;ϰͿ͗ϱϱϬͲϱϱϳ͘
DĂĐŝƉ͕ ^͕ /ŐĂƌĂƐŚŝ͕ D͕ ĞƌŐŐƌĞŶ͕ W͕ zƵ͕ :͕ >ĞĞ͕ ^t͕ ĂƌŽŶƐŽŶ͕ ^ ;ϮϬϬϯͿ /ŶĨůƵĞŶĐĞ ŽĨ
ŝŶĚƵĐĞĚ ƌĞĂĐƚŝǀĞ ŽǆǇŐĞŶ ƐƉĞĐŝĞƐ ŝŶ ƉϱϯͲŵĞĚŝĂƚĞĚ ĐĞůů ĨĂƚĞ ĚĞĐŝƐŝŽŶƐ͘ DŽů Ğůů ŝŽů
Ϯϯ;ϮϯͿ͗ϴϱϳϲͲϴϱϴϱ͘
ϭϬϮ
DĂĚĂŵĂŶĐŚŝ͕ EZ͕ ZƵŶŐĞ͕ D^ ;ϮϬϭϯͿ ZĞĚŽǆ ^ŝŐŶĂůŝŶŐ ŝŶ ĂƌĚŝŽǀĂƐĐƵůĂƌ ,ĞĂůƚŚ ĂŶĚ
ŝƐĞĂƐĞ͘&ƌĞĞZĂĚŝĐŝŽůDĞĚ͘
DĂůŬĂ͕ &͕ 'ƵŝůůĞƌǇ͕ K͕ ŝĨƵĞŶƚĞƐͲŝĂǌ͕ ͕ 'ƵŝůůŽƵ͕ ͕ ĞůĞŶŐƵĞƌ͕ W͕ >ŽŵďĞƐ͕ ͕ ZŽũŽ͕ D
;ϮϬϬϱͿ^ĞƉĂƌĂƚĞĨƵƐŝŽŶŽĨŽƵƚĞƌĂŶĚŝŶŶĞƌŵŝƚŽĐŚŽŶĚƌŝĂůŵĞŵďƌĂŶĞƐ͘DKZĞƉϲ;ϵͿ͗
ϴϱϯͲϴϱϵ͘
DĂŶĐǌĂŬ͕ D͕ ĂůŬŝŶƐ͕ D:͕ ZĞĚĚǇ͕ W, ;ϮϬϭϭͿ /ŵƉĂŝƌĞĚ ŵŝƚŽĐŚŽŶĚƌŝĂů ĚǇŶĂŵŝĐƐ ĂŶĚ
ĂďŶŽƌŵĂůŝŶƚĞƌĂĐƚŝŽŶŽĨĂŵǇůŽŝĚďĞƚĂǁŝƚŚŵŝƚŽĐŚŽŶĚƌŝĂůƉƌŽƚĞŝŶƌƉϭŝŶŶĞƵƌŽŶƐĨƌŽŵ
ƉĂƚŝĞŶƚƐǁŝƚŚůǌŚĞŝŵĞƌΖƐĚŝƐĞĂƐĞ͗ŝŵƉůŝĐĂƚŝŽŶƐĨŽƌŶĞƵƌŽŶĂůĚĂŵĂŐĞ͘,ƵŵDŽů'ĞŶĞƚ
ϮϬ;ϭϯͿ͗ϮϰϵϱͲϮϱϬϵ͘
DĂŶĐǌĂŬ͕D͕DĂŽ͕W͕ĂůŬŝŶƐ͕D:͕ŽƌŶĞĂ͕͕ZĞĚĚǇ͕W͕DƵƌƉŚǇ͕DW͕^ǌĞƚŽ͕,,͕WĂƌŬ͕
͕ZĞĚĚǇ͕W,;ϮϬϭϬͿDŝƚŽĐŚŽŶĚƌŝĂͲƚĂƌŐĞƚĞĚĂŶƚŝŽǆŝĚĂŶƚƐƉƌŽƚĞĐƚĂŐĂŝŶƐƚĂŵǇůŽŝĚͲďĞƚĂ
ƚŽǆŝĐŝƚǇŝŶůǌŚĞŝŵĞƌΖƐĚŝƐĞĂƐĞŶĞƵƌŽŶƐ͘:ůǌŚĞŝŵĞƌƐŝƐϮϬ^ƵƉƉůϮ͗^ϲϬϵͲϲϯϭ͘
DĂƌĂǌǌŝƚŝ͕͕ĂƌŽŶŝ͕^͕WŝĐĐŚĞƚƚŝ͕D͕>ĂŶĚŝ͕W͕^ŝůǀĞƐƚƌŝ͕^͕sĂƚƚĞƌŽŶŝ͕͕ĂƚĞŶĂĞůůΖKƐƐŽ͕
D ;ϮϬϭϮͿ WƐǇĐŚŝĂƚƌŝĐ ĚŝƐŽƌĚĞƌƐ ĂŶĚ ŵŝƚŽĐŚŽŶĚƌŝĂů ĚǇƐĨƵŶĐƚŝŽŶƐ͘ Ƶƌ ZĞǀ DĞĚ
WŚĂƌŵĂĐŽů^Đŝϭϲ;ϮͿ͗ϮϳϬͲϮϳϱ͘
DĂƌƚŝŶ͕ : ;ϭϵϴϮͿ ,ƵŶƚŝŶŐƚŽŶΖƐ ĚŝƐĞĂƐĞ͗ ŐĞŶĞƚŝĐĂůůǇ ƉƌŽŐƌĂŵŵĞĚ ĐĞůů ĚĞĂƚŚ ŝŶ ƚŚĞ
ŚƵŵĂŶĐĞŶƚƌĂůŶĞƌǀŽƵƐƐǇƐƚĞŵ͘EĂƚƵƌĞϮϵϵ;ϱϴϴϬͿ͗ϮϬϱͲϮϬϲ͘
DĂƌƚŝŶĚĂůĞ͕:>͕,ŽůďƌŽŽŬ͕E:;ϮϬϬϮͿĞůůƵůĂƌƌĞƐƉŽŶƐĞƚŽŽǆŝĚĂƚŝǀĞƐƚƌĞƐƐ͗ƐŝŐŶĂůŝŶŐĨŽƌ
ƐƵŝĐŝĚĞĂŶĚƐƵƌǀŝǀĂů͘:ĞůůWŚǇƐŝŽůϭϵϮ;ϭͿ͗ϭͲϭϱ͘
DĂƌƚŝŶŽƵ͕ :͕ zŽƵůĞ͕ Z: ;ϮϬϭϭͿ DŝƚŽĐŚŽŶĚƌŝĂ ŝŶ ĂƉŽƉƚŽƐŝƐ͗ ĐůͲϮ ĨĂŵŝůǇ ŵĞŵďĞƌƐ ĂŶĚ
ŵŝƚŽĐŚŽŶĚƌŝĂůĚǇŶĂŵŝĐƐ͘ĞǀĞůůϮϭ;ϭͿ͗ϵϮͲϭϬϭ͘
DĂƌƚŝŶŽƵ͕ :͕ zŽƵůĞ͕ Z: ;ϮϬϬϲͿ tŚŝĐŚ ĐĂŵĞ ĨŝƌƐƚ͕ ƚŚĞ ĐǇƚŽĐŚƌŽŵĞ Đ ƌĞůĞĂƐĞ Žƌ ƚŚĞ
ŵŝƚŽĐŚŽŶĚƌŝĂůĨŝƐƐŝŽŶ͍ĞůůĞĂƚŚŝĨĨĞƌϭϯ;ϴͿ͗ϭϮϵϭͲϭϮϵϱ͘
DĂƚŚĞǁ͕ Z͕ <ĂƌƉ͕ D͕ ĞĂƵĚŽŝŶ͕ ͕ sƵŽŶŐ͕ E͕ ŚĞŶ͕ '͕ ŚĞŶ͕ ,z͕ ƌĂǇ͕ <͕ ZĞĚĚǇ͕ ͕
ŚĂŶŽƚ͕'͕'ĞůŝŶĂƐ͕͕ŝƉĂŽůĂ͕Z^͕<ĂƌĂŶƚǌĂͲtĂĚƐǁŽƌƚŚ͕s͕tŚŝƚĞ͕;ϮϬϬϵͿƵƚŽƉŚĂŐǇ
ƐƵƉƉƌĞƐƐĞƐƚƵŵŽƌŝŐĞŶĞƐŝƐƚŚƌŽƵŐŚĞůŝŵŝŶĂƚŝŽŶŽĨƉϲϮ͘Ğůůϭϯϳ;ϲͿ͗ϭϬϲϮͲϭϬϳϱ͘
DĂƚƚƐŽŶ͕ DW ;ϮϬϬϬͿ ƉŽƉƚŽƐŝƐ ŝŶŶĞƵƌŽĚĞŐĞŶĞƌĂƚŝǀĞ ĚŝƐŽƌĚĞƌƐ͘ EĂƚ ZĞǀ DŽů Ğůů ŝŽů
ϭ;ϮͿ͗ϭϮϬͲϭϮϵ͘
DĂƚǌ͕Ds͕&ƌĂĚŬŽǀ͕&͕>ĂďĂƐ͕z͕^ĂǀŝƚƐŬǇ͕W͕ĂƌĂŝƐŬǇ͕'͕DĂƌŬĞůŽǀ͕D>͕>ƵŬǇĂŶŽǀ͕
^ ;ϭϵϵϵͿ &ůƵŽƌĞƐĐĞŶƚ ƉƌŽƚĞŝŶƐ ĨƌŽŵ ŶŽŶďŝŽůƵŵŝŶĞƐĐĞŶƚ ŶƚŚŽǌŽĂ ƐƉĞĐŝĞƐ͘ EĂƚ
ŝŽƚĞĐŚŶŽůϭϳ;ϭϬͿ͗ϵϲϵͲϵϳϯ͘
DĂǌǌŝŽ͕ ͕ ZĞĂŵƐ͕ ZZ͕ ^ŽůŝŵĂŶ͕ <& ;ϮϬϬϰͿ dŚĞ ƌŽůĞ ŽĨ ŽǆŝĚĂƚŝǀĞ ƐƚƌĞƐƐ͕ ŝŵƉĂŝƌĞĚ
ŐůǇĐŽůǇƐŝƐ ĂŶĚ ŵŝƚŽĐŚŽŶĚƌŝĂů ƌĞƐƉŝƌĂƚŽƌǇ ƌĞĚŽǆ ĨĂŝůƵƌĞ ŝŶ ƚŚĞ ĐǇƚŽƚŽǆŝĐ ĞĨĨĞĐƚƐ ŽĨ ϲͲ
ŚǇĚƌŽǆǇĚŽƉĂŵŝŶĞŝŶǀŝƚƌŽ͘ƌĂŝŶZĞƐϭϬϬϰ;ϭͲϮͿ͗ϮϵͲϰϰ͘
ϭϬϯ
DĐƌŝĚĞ͕ ,D͕ EĞƵƐƉŝĞů͕ D͕ tĂƐŝĂŬ͕ ^ ;ϮϬϬϲͿ DŝƚŽĐŚŽŶĚƌŝĂ͗ ŵŽƌĞ ƚŚĂŶ ũƵƐƚ Ă
ƉŽǁĞƌŚŽƵƐĞ͘ƵƌƌŝŽůϭϲ;ϭϰͿ͗ZϱϱϭͲϱϲϬ͘
DĞĞƵƐĞŶ͕^͕ĞsĂǇ͕Z͕ůŽĐŬ͕:͕ĂƐƐŝĚǇͲ^ƚŽŶĞ͕͕tĂǇƐŽŶ͕^͕DĐĂĨĨĞƌǇ͕:D͕EƵŶŶĂƌŝ͕:
;ϮϬϬϲͿ DŝƚŽĐŚŽŶĚƌŝĂů ŝŶŶĞƌͲŵĞŵďƌĂŶĞ ĨƵƐŝŽŶ ĂŶĚ ĐƌŝƐƚĂ ŵĂŝŶƚĞŶĂŶĐĞ ƌĞƋƵŝƌĞƐ ƚŚĞ
ĚǇŶĂŵŝŶͲƌĞůĂƚĞĚ'dWĂƐĞDŐŵϭ͘ĞůůϭϮϳ;ϮͿ͗ϯϴϯͲϯϵϱ͘
DĞĞƵƐĞŶ͕ ^͕ DĐĂĨĨĞƌǇ͕ :D͕ EƵŶŶĂƌŝ͕ : ;ϮϬϬϰͿ DŝƚŽĐŚŽŶĚƌŝĂů ĨƵƐŝŽŶ ŝŶƚĞƌŵĞĚŝĂƚĞƐ
ƌĞǀĞĂůĞĚŝŶǀŝƚƌŽ͘^ĐŝĞŶĐĞϯϬϱ;ϱϲϵϭͿ͗ϭϳϰϳͲϭϳϱϮ͘
DĞůŝŶŽ͕'͕ĞƌŶĂƐƐŽůĂ͕&͕ZĂŶĂůůŝ͕D͕zĞĞ͕<͕ŽŶŐ͕ty͕ŽƌĂǌǌĂƌŝ͕D͕<ŶŝŐŚƚ͕Z͕'ƌĞĞŶ͕
Z͕dŚŽŵƉƐŽŶ͕͕sŽƵƐĚĞŶ͕<,;ϮϬϬϰͿƉϳϯ/ŶĚƵĐĞƐĂƉŽƉƚŽƐŝƐǀŝĂWhDƚƌĂŶƐĂĐƚŝǀĂƚŝŽŶ
ĂŶĚĂǆŵŝƚŽĐŚŽŶĚƌŝĂůƚƌĂŶƐůŽĐĂƚŝŽŶ͘:ŝŽůŚĞŵϮϳϵ;ϵͿ͗ϴϬϳϲͲϴϬϴϯ͘
DĞŶǌŝĞƐ͕&D͕ŽŽŬƐŽŶ͕DZ͕dĂǇůŽƌ͕Zt͕dƵƌŶďƵůů͕D͕ŚƌǌĂŶŽǁƐŬĂͲ>ŝŐŚƚŽǁůĞƌƐ͕D͕
ŽŶŐ͕ >͕ &ŝŐůĞǁŝĐǌ͕ ͕ ^ŚĂǁ͕ W: ;ϮϬϬϮͿ DŝƚŽĐŚŽŶĚƌŝĂů ĚǇƐĨƵŶĐƚŝŽŶ ŝŶ Ă ĐĞůů ĐƵůƚƵƌĞ
ŵŽĚĞůŽĨĨĂŵŝůŝĂůĂŵǇŽƚƌŽƉŚŝĐůĂƚĞƌĂůƐĐůĞƌŽƐŝƐ͘ƌĂŝŶϭϮϱ;WƚϳͿ͗ϭϱϮϮͲϭϱϯϯ͘
DĞƌǌ͕ ^͕ ,ĂŵŵĞƌŵĞŝƐƚĞƌ͕ D͕ ůƚŵĂŶŶ͕ <͕ Ƶƌƌ͕ D͕ tĞƐƚĞƌŵĂŶŶ͕ ;ϮϬϬϳͿ DŽůĞĐƵůĂƌ
ŵĂĐŚŝŶĞƌǇŽĨŵŝƚŽĐŚŽŶĚƌŝĂůĚǇŶĂŵŝĐƐŝŶǇĞĂƐƚ͘ŝŽůŚĞŵϯϴϴ;ϵͿ͗ϵϭϳͲϵϮϲ͘
DĞƵĞƌ͕ <͕ ^ƵƉƉĂŶǌ͕ /͕ >ŝŶŐŽƌ͕ W͕ WůĂŶĐŚĂŵƉ͕ s͕ 'ŽƌŝĐŬĞ͕ ͕ &ŝĐŚƚŶĞƌ͕ >͕ ƌĂƵƐ͕ ',͕
ŝĞƚǌ͕ 'W͕ :ĂŬŽďƐ͕ ^͕ ĂŚƌ͕ D͕ tĞŝƐŚĂƵƉƚ͕ :, ;ϮϬϬϳͿ ǇĐůŝŶͲĚĞƉĞŶĚĞŶƚ ŬŝŶĂƐĞ ϱ ŝƐ ĂŶ
ƵƉƐƚƌĞĂŵ ƌĞŐƵůĂƚŽƌ ŽĨ ŵŝƚŽĐŚŽŶĚƌŝĂů ĨŝƐƐŝŽŶ ĚƵƌŝŶŐ ŶĞƵƌŽŶĂů ĂƉŽƉƚŽƐŝƐ͘ Ğůů ĞĂƚŚ
ŝĨĨĞƌϭϰ;ϰͿ͗ϲϱϭͲϲϲϭ͘
DŝĐŚĞů͕ WW͕ ,ĞĨƚŝ͕ & ;ϭϵϵϬͿ dŽǆŝĐŝƚǇ ŽĨ ϲͲŚǇĚƌŽǆǇĚŽƉĂŵŝŶĞ ĂŶĚ ĚŽƉĂŵŝŶĞ ĨŽƌ
ĚŽƉĂŵŝŶĞƌŐŝĐŶĞƵƌŽŶƐŝŶĐƵůƚƵƌĞ͘:EĞƵƌŽƐĐŝZĞƐϮϲ;ϰͿ͗ϰϮϴͲϰϯϱ͘
DŝũĂůũŝĐĂ͕ ͕ WƌĞƐĐŽƚƚ͕ D͕ ĞǀĞŶŝƐŚ͕ Z: ;ϮϬϭϭͿ DŝĐƌŽĂƵƚŽƉŚĂŐǇ ŝŶ ŵĂŵŵĂůŝĂŶ ĐĞůůƐ͗
ƌĞǀŝƐŝƚŝŶŐĂϰϬͲǇĞĂƌͲŽůĚĐŽŶƵŶĚƌƵŵ͘ƵƚŽƉŚĂŐǇϳ;ϳͿ͗ϲϳϯͲϲϴϮ͘
DŝƚĐŚĞůů͕ :͕ ^ĂŵƵŶŝ͕ ͕ <ƌŝƐŚŶĂ͕ D͕ Ğ'ƌĂĨĨ͕ t'͕ ŚŶ͕ D^͕ ^ĂŵƵŶŝ͕ h͕ ZƵƐƐŽ͕ ;ϭϵϵϬͿ ŝŽůŽŐŝĐĂůůǇ ĂĐƚŝǀĞ ŵĞƚĂůͲŝŶĚĞƉĞŶĚĞŶƚ ƐƵƉĞƌŽǆŝĚĞ ĚŝƐŵƵƚĂƐĞ ŵŝŵŝĐƐ͘
ŝŽĐŚĞŵŝƐƚƌǇϮϵ;ϭϭͿ͗ϮϴϬϮͲϮϴϬϳ͘
DŽĐŚŝǌƵŬŝ͕ ,͕ ,ĂǇĂŬĂǁĂ͕ ,͕ DŝŐŝƚĂ͕ D͕ ^ŚŝďĂƚĂ͕ D͕ dĂŶĂŬĂ͕ Z͕ ^ƵǌƵŬŝ͕ ͕ ^ŚŝŵŽͲ
EĂŬĂŶŝƐŚŝ͕ z͕ hƌĂďĞ͕ d͕ zĂŵĂĚĂ͕ D͕ dĂŵĂǇŽƐĞ͕ <͕ ^ŚŝŵĂĚĂ͕ d͕ DŝƵƌĂ͕ D͕ DŝǌƵŶŽ͕ z
;ϮϬϬϭͿŶsͲĚĞƌŝǀĞĚƉĂĨͲϭĚŽŵŝŶĂŶƚŶĞŐĂƚŝǀĞŝŶŚŝďŝƚŽƌƉƌĞǀĞŶƚƐDWdWƚŽǆŝĐŝƚǇĂƐ
ĂŶƚŝĂƉŽƉƚŽƚŝĐ ŐĞŶĞ ƚŚĞƌĂƉǇ ĨŽƌ WĂƌŬŝŶƐŽŶΖƐ ĚŝƐĞĂƐĞ͘ WƌŽĐ EĂƚů ĐĂĚ ^Đŝ h ^ ϵϴ;ϭϵͿ͗
ϭϬϵϭϴͲϭϬϵϮϯ͘
DŽŶƚĞƐƐƵŝƚ͕ ^͕ ^ŽŵĂƐĞŬŚĂƌĂŶ͕ ^W͕ dĞƌƌŽŶĞƐ͕ K͕ >ƵĐŬĞŶͲƌĚũŽŵĂŶĚĞ͕ ^͕ ,ĞƌǌŝŐ͕ ^͕
^ĐŚǁĂƌǌĞŶďĂĐŚĞƌ͕Z͕DĂŶƐƚĞŝŶ͕:͕ŽƐƐǇͲtĞƚǌĞů͕͕ĂƐĂŶĞǌ͕'͕DĞĚĂ͕W͕DĂƌƚŝŶŽƵ͕:
;ϮϬϭϬͿDĞŵďƌĂŶĞƌĞŵŽĚĞůŝŶŐŝŶĚƵĐĞĚďǇƚŚĞĚǇŶĂŵŝŶͲƌĞůĂƚĞĚƉƌŽƚĞŝŶƌƉϭƐƚŝŵƵůĂƚĞƐ
ĂǆŽůŝŐŽŵĞƌŝǌĂƚŝŽŶ͘ĞůůϭϰϮ;ϲͿ͗ϴϴϵͲϵϬϭ͘
ϭϬϰ
DŽŶƚŝ͕͕ŽǀĂ͕͕'ƵŝĚŽ͕͕DŽƌĞůůŝ͕Z͕KůŝǀĂ͕;ϭϵϵϲͿWƌŽƚĞĐƚŝǀĞĞĨĨĞĐƚŽĨƚŚĞŶŝƚƌŽǆŝĚĞ
ƚĞŵƉŽůĂŐĂŝŶƐƚƚŚĞĐĂƌĚŝŽƚŽǆŝĐŝƚǇŽĨĂĚƌŝĂŵǇĐŝŶ͘&ƌĞĞZĂĚŝĐŝŽůDĞĚϮϭ;ϰͿ͗ϰϲϯͲϰϳϬ͘
DŽƉĞƌƚ͕ <͕ ,ĂũĞŬ͕ W͕ &ƌĂŶŬ͕ ^͕ ŚĞŶ͕ ͕ <ĂƵĨŵĂŶŶ͕ :͕ ^ĂŶƚĞů͕ ;ϮϬϬϵͿ >ŽƐƐ ŽĨ ƌƉϭ
ĨƵŶĐƚŝŽŶ ĂůƚĞƌƐ KWϭ ƉƌŽĐĞƐƐŝŶŐ ĂŶĚ ĐŚĂŶŐĞƐ ŵŝƚŽĐŚŽŶĚƌŝĂů ŵĞŵďƌĂŶĞ ŽƌŐĂŶŝǌĂƚŝŽŶ͘
ǆƉĞůůZĞƐϯϭϱ;ϭϯͿ͗ϮϭϲϱͲϮϭϴϬ͘
DŽƌĂŶ͕ :D͕ KƌƚŝǌͲKƌƚŝǌ͕ D͕ ZƵŝǌͲDĞƐĂ͕ >D͕ &ƵĞŶƚĞƐ͕ :D ;ϮϬϭϬͿ EŝƚƌŝĐ ŽǆŝĚĞ ŝŶ
ƉĂƌĂƋƵĂƚͲŵĞĚŝĂƚĞĚƚŽǆŝĐŝƚǇ͗ƌĞǀŝĞǁ͘:ŝŽĐŚĞŵDŽůdŽǆŝĐŽůϮϰ;ϲͿ͗ϰϬϮͲϰϬϵ͘
DŽƌƚŝŵŽƌĞ͕ '͕ ,ƵƚƐŽŶ͕ E:͕ ^ƵƌŵĂĐǌ͕ ;ϭϵϴϯͿ YƵĂŶƚŝƚĂƚŝǀĞ ĐŽƌƌĞůĂƚŝŽŶ ďĞƚǁĞĞŶ
ƉƌŽƚĞŽůǇƐŝƐ ĂŶĚ ŵĂĐƌŽͲ ĂŶĚ ŵŝĐƌŽĂƵƚŽƉŚĂŐǇ ŝŶ ŵŽƵƐĞ ŚĞƉĂƚŽĐǇƚĞƐ ĚƵƌŝŶŐ ƐƚĂƌǀĂƚŝŽŶ
ĂŶĚƌĞĨĞĞĚŝŶŐ͘WƌŽĐEĂƚůĐĂĚ^Đŝh^ϴϬ;ϴͿ͗ϮϭϳϵͲϮϭϴϯ͘
DŽƌƚŝŵŽƌĞ͕ '͕ >ĂƌĚĞƵǆ͕ Z͕ ĚĂŵƐ͕ ;ϭϵϴϴͿ ZĞŐƵůĂƚŝŽŶ ŽĨ ŵŝĐƌŽĂƵƚŽƉŚĂŐǇ ĂŶĚ
ďĂƐĂůƉƌŽƚĞŝŶƚƵƌŶŽǀĞƌŝŶƌĂƚůŝǀĞƌ͘ĨĨĞĐƚƐŽĨƐŚŽƌƚͲƚĞƌŵƐƚĂƌǀĂƚŝŽŶ͘:ŝŽůŚĞŵϮϲϯ;ϱͿ͗
ϮϱϬϲͲϮϱϭϮ͘
DŽƐĐĂƚ͕:͕ŝĂǌͲDĞĐŽ͕Dd;ϮϬϬϵͿƉϲϮĂƚƚŚĞĐƌŽƐƐƌŽĂĚƐŽĨĂƵƚŽƉŚĂŐǇ͕ĂƉŽƉƚŽƐŝƐ͕ĂŶĚ
ĐĂŶĐĞƌ͘Ğůůϭϯϳ;ϲͿ͗ϭϬϬϭͲϭϬϬϰ͘
DŽƵůŝ͕ W<͕ dǁŝŐ͕ '͕ ^ŚŝƌŝŚĂŝ͕ K^ ;ϮϬϬϵͿ &ƌĞƋƵĞŶĐǇ ĂŶĚ ƐĞůĞĐƚŝǀŝƚǇ ŽĨ ŵŝƚŽĐŚŽŶĚƌŝĂů
ĨƵƐŝŽŶĂƌĞŬĞǇƚŽŝƚƐƋƵĂůŝƚǇŵĂŝŶƚĞŶĂŶĐĞĨƵŶĐƚŝŽŶ͘ŝŽƉŚǇƐ:ϵϲ;ϵͿ͗ϯϱϬϵͲϯϱϭϴ͘
DŽǌĚǇ͕ ͕ DĐĂĨĨĞƌǇ͕ :D͕ ^ŚĂǁ͕ :D ;ϮϬϬϬͿ ŶŵϭƉ 'dWĂƐĞͲŵĞĚŝĂƚĞĚ ŵŝƚŽĐŚŽŶĚƌŝĂů
ĨŝƐƐŝŽŶŝƐĂŵƵůƚŝͲƐƚĞƉƉƌŽĐĞƐƐƌĞƋƵŝƌŝŶŐƚŚĞŶŽǀĞůŝŶƚĞŐƌĂůŵĞŵďƌĂŶĞĐŽŵƉŽŶĞŶƚ&ŝƐϭƉ͘
:ĞůůŝŽůϭϱϭ;ϮͿ͗ϯϲϳͲϯϴϬ͘
DƵĂŶŐƉĂŝƐĂŶ͕ t͕ DĂƚŚĞǁƐ͕ ͕ ,Žƌŝ͕ ,͕ ^ĞŝĚĞů͕ ;ϮϬϭϭͿ ƐǇƐƚĞŵĂƚŝĐ ƌĞǀŝĞǁ ŽĨ ƚŚĞ
ǁŽƌůĚǁŝĚĞ ƉƌĞǀĂůĞŶĐĞ ĂŶĚ ŝŶĐŝĚĞŶĐĞ ŽĨ WĂƌŬŝŶƐŽŶΖƐ ĚŝƐĞĂƐĞ͘ : DĞĚ ƐƐŽĐ dŚĂŝ ϵϰ;ϲͿ͗
ϳϰϵͲϳϱϱ͘
DƵŶŽǌͲWŝŶĞĚŽ͕ ;ϮϬϭϮͿ ^ŝŐŶĂůŝŶŐ WĂƚŚǁĂǇƐ ƚŚĂƚ ZĞŐƵůĂƚĞ >ŝĨĞ ĂŶĚ Ğůů ĞĂƚŚ͗
ǀŽůƵƚŝŽŶŽĨƉŽƉƚŽƐŝƐŝŶƚŚĞŽŶƚĞǆƚŽĨ^ĞůĨͲĞĨĞŶƐĞ͘ĚǀǆƉDĞĚŝŽůϳϯϴ͗ϭϮϰͲϭϰϯ͘
DƵƌƉŚǇ͕DW;ϮϬϬϴͿdĂƌŐĞƚŝŶŐůŝƉŽƉŚŝůŝĐĐĂƚŝŽŶƐƚŽŵŝƚŽĐŚŽŶĚƌŝĂ͘ŝŽĐŚŝŵŝŽƉŚǇƐĐƚĂ
ϭϳϳϳ;ϳͲϴͿ͗ϭϬϮϴͲϭϬϯϭ͘
DƵƌƉŚǇ͕DW͕^ŵŝƚŚ͕Z;ϮϬϬϬͿƌƵŐĚĞůŝǀĞƌǇƚŽŵŝƚŽĐŚŽŶĚƌŝĂ͗ƚŚĞŬĞǇƚŽŵŝƚŽĐŚŽŶĚƌŝĂů
ŵĞĚŝĐŝŶĞ͘ĚǀƌƵŐĞůŝǀZĞǀϰϭ;ϮͿ͗ϮϯϱͲϮϱϬ͘
EĂŶĐĞ͕D;ϭϵϵϳͿůŝŶŝĐĂůĂƐƉĞĐƚƐŽĨ'ƌĞƉĞĂƚĚŝƐĞĂƐĞƐ͘ƌĂŝŶWĂƚŚŽůϳ;ϯͿ͗ϴϴϭͲϵϬϬ͘
EĂŶŐĂŬƵ͕ D͕ ^ĂƚŽͲzŽƐŚŝƚĂŬĞ͕ Z͕ KŬĂĚĂ͕ z͕ EŽĚĂ͕ z͕ dĂŬĞŵƵƌĂ͕ Z͕ zĂŵĂǌĂŬŝ͕ ,͕
,ŝƌŽŬĂǁĂ͕ E ;ϭϵϵϰͿ </&ϭ͕ Ă ŶŽǀĞů ŵŝĐƌŽƚƵďƵůĞ ƉůƵƐ ĞŶĚͲĚŝƌĞĐƚĞĚ ŵŽŶŽŵĞƌŝĐ ŵŽƚŽƌ
ƉƌŽƚĞŝŶĨŽƌƚƌĂŶƐƉŽƌƚŽĨŵŝƚŽĐŚŽŶĚƌŝĂ͘Ğůůϳϵ;ϳͿ͗ϭϮϬϵͲϭϮϮϬ͘
ϭϬϱ
EĂƉŽůŝƚĂŶŽ͕ D͕ ĞŶƚŽŶǌĞ͕ ͕ 'ƵďĞůůŝŶŝ͕ W͕ ZŽƐƐŝ͕ ^͕ ^ƉŝĞǌŝĂ͕ ^͕ ĞƌŶĂƌĚŝ͕ '͕ 'ƵůŝŶŽ͕ ͕
ĂůĂďƌĞƐŝ͕ W ;ϮϬϬϰͿ /ŶŚŝďŝƚŝŽŶŽĨ ŵŝƚŽĐŚŽŶĚƌŝĂů ĐŽŵƉůĞǆ // ĂůƚĞƌƐ ƐƚƌŝĂƚĂůĞǆƉƌĞƐƐŝŽŶŽĨ
ŐĞŶĞƐŝŶǀŽůǀĞĚŝŶŐůƵƚĂŵĂƚĞƌŐŝĐĂŶĚĚŽƉĂŵŝŶĞƌŐŝĐƐŝŐŶĂůŝŶŐ͗ƉŽƐƐŝďůĞŝŵƉůŝĐĂƚŝŽŶƐĨŽƌ
,ƵŶƚŝŶŐƚŽŶΖƐĚŝƐĞĂƐĞ͘EĞƵƌŽďŝŽůŝƐϭϱ;ϮͿ͗ϰϬϳͲϰϭϰ͘
EĂƌĞŶĚƌĂ͕ ͕ dĂŶĂŬĂ͕ ͕ ^ƵĞŶ͕ &͕ zŽƵůĞ͕ Z: ;ϮϬϬϴͿ WĂƌŬŝŶ ŝƐ ƌĞĐƌƵŝƚĞĚ ƐĞůĞĐƚŝǀĞůǇ ƚŽ
ŝŵƉĂŝƌĞĚŵŝƚŽĐŚŽŶĚƌŝĂĂŶĚƉƌŽŵŽƚĞƐƚŚĞŝƌĂƵƚŽƉŚĂŐǇ͘:ĞůůŝŽůϭϴϯ;ϱͿ͗ϳϵϱͲϴϬϯ͘
EĞƵƐƉŝĞů͕D͕^ĐŚĂƵƐƐ͕͕ƌĂƐĐŚŝ͕͕ƵŶŝŶŽ͕Z͕ZŝƉƉƐƚĞŝŶ͕W͕ZĂĐŚƵďŝŶƐŬŝ͕Z͕ŶĚƌĂĚĞͲ
EĂǀĂƌƌŽ͕D͕DĐƌŝĚĞ͕,D;ϮϬϬϴͿĂƌŐŽͲƐĞůĞĐƚĞĚƚƌĂŶƐƉŽƌƚĨƌŽŵƚŚĞŵŝƚŽĐŚŽŶĚƌŝĂƚŽ
ƉĞƌŽǆŝƐŽŵĞƐŝƐŵĞĚŝĂƚĞĚďǇǀĞƐŝĐƵůĂƌĐĂƌƌŝĞƌƐ͘ƵƌƌŝŽůϭϴ;ϮͿ͗ϭϬϮͲϭϬϴ͘
EŝĞ͕ '͕ ĂŽ͕ z͕ ŚĂŽ͕ ;ϮϬϬϮͿ WƌŽƚĞĐƚŝǀĞ ĞĨĨĞĐƚƐ ŽĨ ŐƌĞĞŶ ƚĞĂ ƉŽůǇƉŚĞŶŽůƐ ĂŶĚ ƚŚĞŝƌ
ŵĂũŽƌ ĐŽŵƉŽŶĞŶƚ͕ ;ͲͿͲĞƉŝŐĂůůŽĐĂƚĞĐŚŝŶͲϯͲŐĂůůĂƚĞ ;''Ϳ͕ ŽŶ ϲͲŚǇĚƌŽǆǇĚŽƉĂŵŝŶĞͲ
ŝŶĚƵĐĞĚĂƉŽƉƚŽƐŝƐŝŶWϭϮĐĞůůƐ͘ZĞĚŽǆZĞƉϳ;ϯͿ͗ϭϳϭͲϭϳϳ͘
EŽƵƌĂŝŶŝ͕ ^͕ ^ŝǆ͕ ͕ DĂƚƐƵǇĂŵĂ͕ ^͕ <ƌĂũĞǁƐŬŝ͕ ^͕ ZĞĞĚ͕ : ;ϮϬϬϬͿ dŚĞ ƉƵƚĂƚŝǀĞ ƉŽƌĞͲ
ĨŽƌŵŝŶŐ ĚŽŵĂŝŶ ŽĨ Ăǆ ƌĞŐƵůĂƚĞƐ ŵŝƚŽĐŚŽŶĚƌŝĂů ůŽĐĂůŝǌĂƚŝŽŶ ĂŶĚ ŝŶƚĞƌĂĐƚŝŽŶ ǁŝƚŚ ĐůͲ
y;>Ϳ͘DŽůĞůůŝŽůϮϬ;ϱͿ͗ϭϲϬϰͲϭϲϭϱ͘
KĐŚƵ͕ ͕ ZŽƚŚǁĞůů͕ E:͕ tĂƚĞƌƐ͕ D ;ϭϵϵϴͿ ĂƐƉĂƐĞƐ ŵĞĚŝĂƚĞ ϲͲŚǇĚƌŽǆǇĚŽƉĂŵŝŶĞͲ
ŝŶĚƵĐĞĚĂƉŽƉƚŽƐŝƐďƵƚŶŽƚŶĞĐƌŽƐŝƐŝŶWϭϮĐĞůůƐ͘:EĞƵƌŽĐŚĞŵϳϬ;ϲͿ͗ϮϲϯϳͲϮϲϰϬ͘
KĞƚƚŝŶŐŚĂƵƐ͕ ͕ >ŝĐĐŝ͕ D͕ ^ĐŽƌƌĂŶŽ͕ >͕ &ƌĂŶŬ͕ ^ ;ϮϬϭϮͿ >ĞƐƐ ƚŚĂŶ ƉĞƌĨĞĐƚ ĚŝǀŽƌĐĞƐ͗
ĚǇƐƌĞŐƵůĂƚĞĚ ŵŝƚŽĐŚŽŶĚƌŝĂů ĨŝƐƐŝŽŶ ĂŶĚ ŶĞƵƌŽĚĞŐĞŶĞƌĂƚŝŽŶ͘ ĐƚĂ EĞƵƌŽƉĂƚŚŽů ϭϮϯ;ϮͿ͗
ϭϴϵͲϮϬϯ͘
KŬĂŵŽƚŽ͕ <͕ ^ŚĂǁ͕ :D ;ϮϬϬϱͿ DŝƚŽĐŚŽŶĚƌŝĂů ŵŽƌƉŚŽůŽŐǇ ĂŶĚ ĚǇŶĂŵŝĐƐ ŝŶ ǇĞĂƐƚ ĂŶĚ
ŵƵůƚŝĐĞůůƵůĂƌĞƵŬĂƌǇŽƚĞƐ͘ŶŶƵZĞǀ'ĞŶĞƚϯϵ͗ϱϬϯͲϱϯϲ͘
KŶŽ͕ d͕ /ƐŽďĞ͕ <͕ EĂŬĂĚĂ͕ <͕ ,ĂǇĂƐŚŝ͕ :/ ;ϮϬϬϭͿ ,ƵŵĂŶ ĐĞůůƐ ĂƌĞ ƉƌŽƚĞĐƚĞĚ ĨƌŽŵ
ŵŝƚŽĐŚŽŶĚƌŝĂů ĚǇƐĨƵŶĐƚŝŽŶ ďǇ ĐŽŵƉůĞŵĞŶƚĂƚŝŽŶ ŽĨ E ƉƌŽĚƵĐƚƐ ŝŶ ĨƵƐĞĚ
ŵŝƚŽĐŚŽŶĚƌŝĂ͘EĂƚ'ĞŶĞƚϮϴ;ϯͿ͗ϮϳϮͲϮϳϱ͘
Kƌƌ͕ >͕ >ŝ͕ ^͕ tĂŶŐ͕ ͕ >ŝ͕ ,͕ tĂŶŐ͕ :͕ ZŽŶŐ͕ :͕ yƵ͕ y͕ DĂƐƚƌŽďĞƌĂƌĚŝŶŽ͕ W'͕
'ƌĞĞŶĂŵǇƌĞ͕ :d͕ >ŝ͕ y: ;ϮϬϬϴͿ EͲƚĞƌŵŝŶĂů ŵƵƚĂŶƚ ŚƵŶƚŝŶŐƚŝŶ ĂƐƐŽĐŝĂƚĞƐ ǁŝƚŚ
ŵŝƚŽĐŚŽŶĚƌŝĂĂŶĚŝŵƉĂŝƌƐŵŝƚŽĐŚŽŶĚƌŝĂůƚƌĂĨĨŝĐŬŝŶŐ͘:EĞƵƌŽƐĐŝϮϴ;ϭϭͿ͗ϮϳϴϯͲϮϳϵϮ͘
KƌƚŚ͕ D͕ ^ĐŚĂƉŝƌĂ͕ , ;ϮϬϬϮͿ DŝƚŽĐŚŽŶĚƌŝĂů ŝŶǀŽůǀĞŵĞŶƚ ŝŶ WĂƌŬŝŶƐŽŶΖƐ ĚŝƐĞĂƐĞ͘
EĞƵƌŽĐŚĞŵ/ŶƚϰϬ;ϲͿ͗ϱϯϯͲϱϰϭ͘
KƚĞƌĂ͕,͕DŝŚĂƌĂ͕<;ϮϬϭϮͿDŝƚŽĐŚŽŶĚƌŝĂůĚǇŶĂŵŝĐƐ͗ĨƵŶĐƚŝŽŶĂůůŝŶŬǁŝƚŚĂƉŽƉƚŽƐŝƐ͘/Ŷƚ:
ĞůůŝŽůϮϬϭϮ͗ϴϮϭϲϳϲ͘
KƚĞƌĂ͕ ,͕ tĂŶŐ͕ ͕ ůĞůĂŶĚ͕ DD͕ ^ĞƚŽŐƵĐŚŝ͕ <͕zŽŬŽƚĂ͕ ^͕ zŽƵůĞ͕ Z:͕ DŝŚĂƌĂ͕ < ;ϮϬϭϬͿ
DĨĨŝƐĂŶĞƐƐĞŶƚŝĂůĨĂĐƚŽƌĨŽƌŵŝƚŽĐŚŽŶĚƌŝĂůƌĞĐƌƵŝƚŵĞŶƚŽĨƌƉϭĚƵƌŝŶŐŵŝƚŽĐŚŽŶĚƌŝĂů
ĨŝƐƐŝŽŶŝŶŵĂŵŵĂůŝĂŶĐĞůůƐ͘:ĞůůŝŽůϭϵϭ;ϲͿ͗ϭϭϰϭͲϭϭϱϴ͘
ϭϬϲ
KƚƐƵŐĂ͕ ͕ <ĞĞŐĂŶ͕ Z͕ ƌŝƐĐŚ͕ ͕ dŚĂƚĐŚĞƌ͕ :t͕ ,ĞƌŵĂŶŶ͕ ':͕ ůĞĂǌĂƌĚ͕ t͕ ^ŚĂǁ͕ :D
;ϭϵϵϴͿ dŚĞ ĚǇŶĂŵŝŶͲƌĞůĂƚĞĚ 'dWĂƐĞ͕ ŶŵϭƉ͕ ĐŽŶƚƌŽůƐ ŵŝƚŽĐŚŽŶĚƌŝĂů ŵŽƌƉŚŽůŽŐǇ ŝŶ
ǇĞĂƐƚ͘:ĞůůŝŽůϭϰϯ;ϮͿ͗ϯϯϯͲϯϰϵ͘
WĂůŵĞƌ͕ ^͕ KƐĞůůĂŵĞ͕ >͕ ^ƚŽũĂŶŽǀƐŬŝ͕ ͕ ZǇĂŶ͕ Dd ;ϮϬϭϭͿ dŚĞ ƌĞŐƵůĂƚŝŽŶ ŽĨ
ŵŝƚŽĐŚŽŶĚƌŝĂů ŵŽƌƉŚŽůŽŐǇ͗ ŝŶƚƌŝĐĂƚĞ ŵĞĐŚĂŶŝƐŵƐ ĂŶĚ ĚǇŶĂŵŝĐ ŵĂĐŚŝŶĞƌǇ͘ Ğůů ^ŝŐŶĂů
Ϯϯ;ϭϬͿ͗ϭϱϯϰͲϭϱϰϱ͘
WĂŶŬŝǀ͕^͕ůĂƵƐĞŶ͕d,͕>ĂŵĂƌŬ͕d͕ƌĞĐŚ͕͕ƌƵƵŶ͕:͕KƵƚǌĞŶ͕,͕KǀĞƌǀĂƚŶ͕͕ũŽƌŬŽǇ͕
'͕:ŽŚĂŶƐĞŶ͕d;ϮϬϬϳͿƉϲϮͬ^Y^dDϭďŝŶĚƐĚŝƌĞĐƚůǇƚŽƚŐϴͬ>ϯƚŽĨĂĐŝůŝƚĂƚĞĚĞŐƌĂĚĂƚŝŽŶ
ŽĨƵďŝƋƵŝƚŝŶĂƚĞĚƉƌŽƚĞŝŶĂŐŐƌĞŐĂƚĞƐďǇĂƵƚŽƉŚĂŐǇ͘:ŝŽůŚĞŵϮϴϮ;ϯϯͿ͗ϮϰϭϯϭͲϮϰϭϰϱ͘
WĂŶŽǀ͕ s͕ 'ƵƚĞŬƵŶƐƚ͕ ͕ >ĞĂǀŝƚƚ͕ Z͕ ,ĂǇĚĞŶ͕ DZ͕ ƵƌŬĞ͕ :Z͕ ^ƚƌŝƚƚŵĂƚƚĞƌ͕ t:͕
'ƌĞĞŶĂŵǇƌĞ͕:d;ϮϬϬϮͿĂƌůǇŵŝƚŽĐŚŽŶĚƌŝĂůĐĂůĐŝƵŵĚĞĨĞĐƚƐŝŶ,ƵŶƚŝŶŐƚŽŶΖƐĚŝƐĞĂƐĞĂƌĞ
ĂĚŝƌĞĐƚĞĨĨĞĐƚŽĨƉŽůǇŐůƵƚĂŵŝŶĞƐ͘EĂƚEĞƵƌŽƐĐŝϱ;ϴͿ͗ϳϯϭͲϳϯϲ͘
WĂƌŬĞƌ͕ t͕ :ƌ͕͘ ŽǇƐŽŶ͕ ^:͕ WĂƌŬƐ͕ :< ;ϭϵϴϵͿ ďŶŽƌŵĂůŝƚŝĞƐ ŽĨ ƚŚĞ ĞůĞĐƚƌŽŶ ƚƌĂŶƐƉŽƌƚ
ĐŚĂŝŶŝŶŝĚŝŽƉĂƚŚŝĐWĂƌŬŝŶƐŽŶΖƐĚŝƐĞĂƐĞ͘ŶŶEĞƵƌŽůϮϲ;ϲͿ͗ϳϭϵͲϳϮϯ͘
WĞƌĞǌͲůǀĂƌĞǌ͕^͕^ŽůĞƐŝŽ͕D͕DĂŶǌĂŶĂƌĞƐ͕:͕:ŽƌĚĂŶ͕:͕'ĂůŝŶĚŽ͕D&;ϮϬϬϵͿ>ĂĐƚĂĐǇƐƚŝŶ
ƌĞƋƵŝƌĞƐ ƌĞĂĐƚŝǀĞ ŽǆǇŐĞŶ ƐƉĞĐŝĞƐ ĂŶĚ Ăǆ ƌĞĚŝƐƚƌŝďƵƚŝŽŶ ƚŽ ŝŶĚƵĐĞ ŵŝƚŽĐŚŽŶĚƌŝĂͲ
ŵĞĚŝĂƚĞĚĐĞůůĚĞĂƚŚ͘ƌ:WŚĂƌŵĂĐŽůϭϱϴ;ϰͿ͗ϭϭϮϭͲϭϭϯϬ͘
WĞƌŝĞƌ͕ ͕ ŽǀĞ͕ :͕ tƵ͕ ͕ ĞŚĂǇ͕ ͕ ŚŽŝ͕ <͕ :ĂĐŬƐŽŶͲ>ĞǁŝƐ͕ s͕ ZĂƚŚŬĞͲ,ĂƌƚůŝĞď͕ ^͕
ŽƵŝůůĞƚ͕ W͕ ^ƚƌĂƐƐĞƌ͕ ͕ ^ĐŚƵůǌ͕ :͕ WƌǌĞĚďŽƌƐŬŝ͕ ^͕ sŝůĂ͕ D ;ϮϬϬϳͿ dǁŽ ŵŽůĞĐƵůĂƌ
ƉĂƚŚǁĂǇƐ ŝŶŝƚŝĂƚĞ ŵŝƚŽĐŚŽŶĚƌŝĂͲĚĞƉĞŶĚĞŶƚ ĚŽƉĂŵŝŶĞƌŐŝĐ ŶĞƵƌŽĚĞŐĞŶĞƌĂƚŝŽŶ ŝŶ
ĞǆƉĞƌŝŵĞŶƚĂůWĂƌŬŝŶƐŽŶΖƐĚŝƐĞĂƐĞ͘WƌŽĐEĂƚůĐĂĚ^Đŝh^ϭϬϰ;ϭϵͿ͗ϴϭϲϭͲϴϭϲϲ͘
WĞƌŝĞƌ͕͕dŝĞƵ͕<͕'ƵĞŐĂŶ͕͕ĂƐƉĞƌƐĞŶ͕͕:ĂĐŬƐŽŶͲ>ĞǁŝƐ͕s͕ĂƌĞůůŝ͕s͕DĂƌƚŝŶƵǌǌŝ͕͕
,ŝƌĂŶŽ͕D͕WƌǌĞĚďŽƌƐŬŝ͕^͕sŝůĂ͕D;ϮϬϬϱͿŽŵƉůĞǆ/ĚĞĨŝĐŝĞŶĐǇƉƌŝŵĞƐĂǆͲĚĞƉĞŶĚĞŶƚ
ŶĞƵƌŽŶĂůĂƉŽƉƚŽƐŝƐƚŚƌŽƵŐŚŵŝƚŽĐŚŽŶĚƌŝĂůŽǆŝĚĂƚŝǀĞĚĂŵĂŐĞ͘WƌŽĐEĂƚůĐĂĚ^Đŝh^
ϭϬϮ;ϱϮͿ͗ϭϵϭϮϲͲϭϵϭϯϭ͘
WĞƌƵŵĂů͕ ^͕ 'ŽƉĂů͕ s͕ dŽƌĚǌƌŽ͕ t<͕ ŽŽƉĞƌ͕ d͕ ĂĚĞƚ͕ :> ;ϭϵϵϮͿ sŝƚĂŵŝŶ ĂƚƚĞŶƵĂƚĞƐƚŚĞƚŽǆŝĐĞĨĨĞĐƚƐŽĨϲͲŚǇĚƌŽǆǇĚŽƉĂŵŝŶĞŽŶĨƌĞĞƌĂĚŝĐĂůƐĐĂǀĞŶŐŝŶŐƐǇƐƚĞŵƐ
ŝŶƌĂƚďƌĂŝŶ͘ƌĂŝŶZĞƐƵůůϮϵ;ϱͿ͗ϲϵϵͲϳϬϭ͘
WŝĂŶƚĂĚŽƐŝ͕;ϮϬϭϭͿZĞŐƵůĂƚŝŽŶŽĨŵŝƚŽĐŚŽŶĚƌŝĂůƉƌŽĐĞƐƐĞƐďǇƉƌŽƚĞŝŶ^ͲŶŝƚƌŽƐǇůĂƚŝŽŶ͘
ŝŽĐŚŝŵŝŽƉŚǇƐĐƚĂ͘
WŽůŝĚŽƌŝ͕D͕DĞĐŽĐĐŝ͕W͕ƌŽǁŶĞ͕^͕^ĞŶŝŶ͕h͕ĞĂů͕D&;ϭϵϵϵͿKǆŝĚĂƚŝǀĞĚĂŵĂŐĞƚŽ
ŵŝƚŽĐŚŽŶĚƌŝĂůEŝŶ,ƵŶƚŝŶŐƚŽŶΖƐĚŝƐĞĂƐĞƉĂƌŝĞƚĂůĐŽƌƚĞǆ͘EĞƵƌŽƐĐŝ>ĞƚƚϮϳϮ;ϭͿ͗ϱϯͲϱϲ͘
WŽůǇŵĞƌŽƉŽƵůŽƐ͕D,͕>ĂǀĞĚĂŶ͕͕>ĞƌŽǇ͕͕/ĚĞ͕^͕ĞŚĞũŝĂ͕͕ƵƚƌĂ͕͕WŝŬĞ͕͕ZŽŽƚ͕
,͕ ZƵďĞŶƐƚĞŝŶ͕ :͕ ŽǇĞƌ͕ Z͕ ^ƚĞŶƌŽŽƐ͕ ^͕ ŚĂŶĚƌĂƐĞŬŚĂƌĂƉƉĂ͕ ^͕ ƚŚĂŶĂƐƐŝĂĚŽƵ͕ ͕
WĂƉĂƉĞƚƌŽƉŽƵůŽƐ͕ d͕ :ŽŚŶƐŽŶ͕ t'͕ >ĂǌǌĂƌŝŶŝ͕ D͕ ƵǀŽŝƐŝŶ͕ Z͕ ŝ /ŽƌŝŽ͕ '͕ 'ŽůďĞ͕ >/͕
ϭϬϳ
EƵƐƐďĂƵŵ͕Z>;ϭϵϵϳͿDƵƚĂƚŝŽŶŝŶƚŚĞĂůƉŚĂͲƐǇŶƵĐůĞŝŶŐĞŶĞŝĚĞŶƚŝĨŝĞĚŝŶĨĂŵŝůŝĞƐǁŝƚŚ
WĂƌŬŝŶƐŽŶΖƐĚŝƐĞĂƐĞ͘^ĐŝĞŶĐĞϮϳϲ;ϱϯϮϭͿ͗ϮϬϰϱͲϮϬϰϳ͘
WƌŝŶŐƐŚĞŝŵ͕ d͕ tŝůƚƐŚŝƌĞ͕ <͕ ĂǇ͕ >͕ ǇŬĞŵĂŶ͕ :͕ ^ƚĞĞǀĞƐ͕ d͕ :ĞƚƚĞ͕ E ;ϮϬϭϮͿ dŚĞ
ŝŶĐŝĚĞŶĐĞ ĂŶĚ ƉƌĞǀĂůĞŶĐĞ ŽĨ ,ƵŶƚŝŶŐƚŽŶΖƐ ĚŝƐĞĂƐĞ͗ Ă ƐǇƐƚĞŵĂƚŝĐ ƌĞǀŝĞǁ ĂŶĚ ŵĞƚĂͲ
ĂŶĂůǇƐŝƐ͘DŽǀŝƐŽƌĚϮϳ;ϵͿ͗ϭϬϴϯͲϭϬϵϭ͘
Yŝ͕y͕Yǀŝƚ͕E͕^Ƶ͕z͕DŽĐŚůǇͲZŽƐĞŶ͕;ϮϬϭϮͿEŽǀĞůƌƉϭŝŶŚŝďŝƚŽƌĚŝŵŝŶŝƐŚĞƐĂďĞƌƌĂŶƚ
ŵŝƚŽĐŚŽŶĚƌŝĂůĨŝƐƐŝŽŶĂŶĚŶĞƵƌŽƚŽǆŝĐŝƚǇ͘:Ğůů^Đŝ͘
YŝĂŶŐ͕t͕tĞŝƋŝĂŶŐ͕<͕YŝŶŐ͕͕WĞŶŐũƵ͕͕zŝ͕>;ϮϬϬϳͿŐŝŶŐŝŵƉĂŝƌƐŝŶƐƵůŝŶͲƐƚŝŵƵůĂƚĞĚ
ŐůƵĐŽƐĞƵƉƚĂŬĞŝŶƌĂƚƐŬĞůĞƚĂůŵƵƐĐůĞǀŝĂƐƵƉƉƌĞƐƐŝŶŐDW<ĂůƉŚĂ͘ǆƉDŽůDĞĚϯϵ;ϰͿ͗
ϱϯϱͲϱϰϯ͘
ZĂĚĂ͕͕>ĞƚŽ͕d>;ϮϬϬϴͿKǆŝĚĂƚŝǀĞŝŶŶĂƚĞŝŵŵƵŶĞĚĞĨĞŶƐĞƐďǇEŽǆͬƵŽǆĨĂŵŝůǇEW,
ŽǆŝĚĂƐĞƐ͘ŽŶƚƌŝďDŝĐƌŽďŝŽůϭϱ͗ϭϲϰͲϭϴϳ͘
ZĂŵďŽůĚ͕ ^͕ <ŽƐƚĞůĞĐŬǇ͕ ͕ ůŝĂ͕ E͕ >ŝƉƉŝŶĐŽƚƚͲ^ĐŚǁĂƌƚǌ͕ : ;ϮϬϭϭͿ dƵďƵůĂƌ ŶĞƚǁŽƌŬ
ĨŽƌŵĂƚŝŽŶ ƉƌŽƚĞĐƚƐ ŵŝƚŽĐŚŽŶĚƌŝĂ ĨƌŽŵ ĂƵƚŽƉŚĂŐŽƐŽŵĂů ĚĞŐƌĂĚĂƚŝŽŶ ĚƵƌŝŶŐ ŶƵƚƌŝĞŶƚ
ƐƚĂƌǀĂƚŝŽŶ͘WƌŽĐEĂƚůĐĂĚ^Đŝh^ϭϬϴ;ϮϱͿ͗ϭϬϭϵϬͲϭϬϭϵϱ͘
ZĞďŽƵĐĂƐ͕:^͕Ğ&ƌĞŝƚĂƐͲ^ŝůǀĂ͕'͕^ƉĂƐŽũĞǀŝĐ͕/͕/ĚĞŵŽƌŝ͕zD͕ĞŶŽǀ͕>͕ĂƚŝŶŝĐͲ,ĂďĞƌůĞ͕/
;ϮϬϬϴĂͿ /ŵƉĂĐƚ ŽĨ ĞůĞĐƚƌŽƐƚĂƚŝĐƐ ŝŶ ƌĞĚŽǆ ŵŽĚƵůĂƚŝŽŶ ŽĨ ŽǆŝĚĂƚŝǀĞ ƐƚƌĞƐƐ ďǇ DŶ
ƉŽƌƉŚǇƌŝŶƐ͗ ƉƌŽƚĞĐƚŝŽŶ ŽĨ ^KͲĚĞĨŝĐŝĞŶƚ ƐĐŚĞƌŝĐŚŝĂ ĐŽůŝ ǀŝĂ ĂůƚĞƌŶĂƚŝǀĞ ŵĞĐŚĂŶŝƐŵ
ǁŚĞƌĞDŶƉŽƌƉŚǇƌŝŶĂĐƚƐĂƐĂDŶĐĂƌƌŝĞƌ͘&ƌĞĞZĂĚŝĐŝŽůDĞĚϰϱ;ϮͿ͗ϮϬϭͲϮϭϬ͘
ZĞďŽƵĐĂƐ͕:^͕^ƉĂƐŽũĞǀŝĐ͕/͕ĂƚŝŶŝĐͲ,ĂďĞƌůĞ͕/;ϮϬϬϴďͿWƵƌĞŵĂŶŐĂŶĞƐĞ;///Ϳϱ͕ϭϬ͕ϭϱ͕ϮϬͲ
ƚĞƚƌĂŬŝƐ;ϰͲďĞŶǌŽŝĐ ĂĐŝĚͿƉŽƌƉŚǇƌŝŶ ;DŶdWͿ ŝƐ ŶŽƚ Ă ƐƵƉĞƌŽǆŝĚĞ ĚŝƐŵƵƚĂƐĞ ŵŝŵŝĐ ŝŶ
ĂƋƵĞŽƵƐƐǇƐƚĞŵƐ͗ĂĐĂƐĞŽĨƐƚƌƵĐƚƵƌĞͲĂĐƚŝǀŝƚǇƌĞůĂƚŝŽŶƐŚŝƉĂƐĂǁĂƚĐŚĚŽŐŵĞĐŚĂŶŝƐŵŝŶ
ĞǆƉĞƌŝŵĞŶƚĂůƚŚĞƌĂƉĞƵƚŝĐƐĂŶĚďŝŽůŽŐǇ͘:ŝŽů/ŶŽƌŐŚĞŵϭϯ;ϮͿ͗ϮϴϵͲϯϬϮ͘
ZĞĚĚǇ͕ W, ;ϮϬϬϴͿ DŝƚŽĐŚŽŶĚƌŝĂů ŵĞĚŝĐŝŶĞ ĨŽƌ ĂŐŝŶŐ ĂŶĚ ŶĞƵƌŽĚĞŐĞŶĞƌĂƚŝǀĞ ĚŝƐĞĂƐĞƐ͘
EĞƵƌŽŵŽůĞĐƵůĂƌDĞĚϭϬ;ϰͿ͗ϮϵϭͲϯϭϱ͘
ZĞĚĚǇ͕W,͕ZĞĚĚǇ͕dW͕DĂŶĐǌĂŬ͕D͕ĂůŬŝŶƐ͕D:͕^ŚŝƌĞŶĚĞď͕h͕DĂŽ͕W;ϮϬϭϭͿǇŶĂŵŝŶͲ
ƌĞůĂƚĞĚ ƉƌŽƚĞŝŶ ϭ ĂŶĚ ŵŝƚŽĐŚŽŶĚƌŝĂů ĨƌĂŐŵĞŶƚĂƚŝŽŶ ŝŶ ŶĞƵƌŽĚĞŐĞŶĞƌĂƚŝǀĞ ĚŝƐĞĂƐĞƐ͘
ƌĂŝŶZĞƐZĞǀϲϳ;ϭͲϮͿ͗ϭϬϯͲϭϭϴ͘
ZĞŝƐ͕ <͕ &ƌĂŶƐƐŽŶ͕ ͕ ƐƉĞŶƐƚƌŽŵ͕ W ;ϮϬϬϵͿ dŚĞ DŝƌŽ 'dWĂƐĞƐ͗ Ăƚ ƚŚĞ ŚĞĂƌƚ ŽĨ ƚŚĞ
ŵŝƚŽĐŚŽŶĚƌŝĂůƚƌĂŶƐƉŽƌƚŵĂĐŚŝŶĞƌǇ͘&^>Ğƚƚϱϴϯ;ϵͿ͗ϭϯϵϭͲϭϯϵϴ͘
ZĞǇŶŽůĚƐ͕/:͕DĂůĂŝǇĂŶĚŝ͕>D͕ŽĂƐŚ͕D͕ZŝŶƚŽƵů͕'>;ϮϬϬϰͿDŝƚŽĐŚŽŶĚƌŝĂůƚƌĂĨĨŝĐŬŝŶŐŝŶ
ŶĞƵƌŽŶƐ͗ĂŬĞǇǀĂƌŝĂďůĞŝŶŶĞƵƌŽĚĞŐĞŶĞƌĂƚŝŽŶ͍:ŝŽĞŶĞƌŐŝŽŵĞŵďƌϯϲ;ϰͿ͗ϮϴϯͲϮϴϲ͘
ZĞǌŶŝĐŬ͕ZD͕ŽŶŐ͕,͕>ŝ͕:͕DŽƌŝŶŽ͕<͕DŽŽƌĞ͕/<͕zƵ͕,:͕>ŝƵ͕y͕ŽŶŐ͕:͕DƵƐƚĂƌĚ͕<:͕
,ĂǁůĞǇ͕^͕ĞĨƌŽǇ͕͕WǇƉĂĞƌƚ͕D͕,ĂƌĚŝĞ͕'͕zŽƵŶŐ͕>,͕^ŚƵůŵĂŶ͕'/;ϮϬϬϳͿŐŝŶŐͲ
ĂƐƐŽĐŝĂƚĞĚ ƌĞĚƵĐƚŝŽŶƐ ŝŶ DWͲĂĐƚŝǀĂƚĞĚ ƉƌŽƚĞŝŶ ŬŝŶĂƐĞ ĂĐƚŝǀŝƚǇ ĂŶĚ ŵŝƚŽĐŚŽŶĚƌŝĂů
ϭϬϴ
ďŝŽŐĞŶĞƐŝƐ͘ĞůůDĞƚĂďϱ;ϮͿ͗ϭϱϭͲϭϱϲ͘
ZŝĐŚƚĞƌ͕͕WĂƌŬ͕:t͕ŵĞƐ͕E;ϭϵϴϴͿEŽƌŵĂůŽǆŝĚĂƚŝǀĞĚĂŵĂŐĞƚŽŵŝƚŽĐŚŽŶĚƌŝĂůĂŶĚ
ŶƵĐůĞĂƌEŝƐĞǆƚĞŶƐŝǀĞ͘WƌŽĐEĂƚůĐĂĚ^Đŝh^ϴϱ;ϭϳͿ͗ϲϰϲϱͲϲϰϲϳ͘
ZŝĞƐƐ͕ K͕ <ƌƵŐĞƌ͕ Z ;ϭϵϵϵͿ WĂƌŬŝŶƐŽŶΖƐ ĚŝƐĞĂƐĞͲͲĂ ŵƵůƚŝĨĂĐƚŽƌŝĂů ŶĞƵƌŽĚĞŐĞŶĞƌĂƚŝǀĞ
ĚŝƐŽƌĚĞƌ͘:EĞƵƌĂůdƌĂŶƐŵ^ƵƉƉůϱϲ͗ϭϭϯͲϭϮϱ͘
ZŝĞƵƐƐĞƚ͕ : ;ϮϬϭϭͿ DŝƚŽĐŚŽŶĚƌŝĂ ĂŶĚ ĞŶĚŽƉůĂƐŵŝĐ ƌĞƚŝĐƵůƵŵ͗ ŵŝƚŽĐŚŽŶĚƌŝĂͲ
ĞŶĚŽƉůĂƐŵŝĐƌĞƚŝĐƵůƵŵŝŶƚĞƌƉůĂǇŝŶƚǇƉĞϮĚŝĂďĞƚĞƐƉĂƚŚŽƉŚǇƐŝŽůŽŐǇ͘/Ŷƚ:ŝŽĐŚĞŵĞůů
ŝŽůϰϯ;ϵͿ͗ϭϮϱϳͲϭϮϲϮ͘
ZŝǌǌƵƚŽ͕Z͕ƌŝŶŝ͕D͕WŝǌǌŽ͕W͕DƵƌŐŝĂ͕D͕WŽǌǌĂŶ͕d;ϭϵϵϱͿŚŝŵĞƌŝĐŐƌĞĞŶĨůƵŽƌĞƐĐĞŶƚ
ƉƌŽƚĞŝŶĂƐĂƚŽŽůĨŽƌǀŝƐƵĂůŝǌŝŶŐƐƵďĐĞůůƵůĂƌŽƌŐĂŶĞůůĞƐŝŶůŝǀŝŶŐĐĞůůƐ͘ƵƌƌŝŽůϱ;ϲͿ͗ϲϯϱͲ
ϲϰϮ͘
ZŽǇ͕ E^͕ ůĞƌĞŶ͕ ͕ ^ŝŶŐŚ͕ ^<͕ zĂŶŐ͕ >͕ ĞĂů͕ D&͕ 'ŽůĚŵĂŶ͕ ^ ;ϮϬϬϲͿ &ƵŶĐƚŝŽŶĂů
ĞŶŐƌĂĨƚŵĞŶƚ ŽĨ ŚƵŵĂŶ ^ ĐĞůůͲĚĞƌŝǀĞĚ ĚŽƉĂŵŝŶĞƌŐŝĐ ŶĞƵƌŽŶƐ ĞŶƌŝĐŚĞĚ ďǇ ĐŽĐƵůƚƵƌĞ
ǁŝƚŚƚĞůŽŵĞƌĂƐĞͲŝŵŵŽƌƚĂůŝǌĞĚŵŝĚďƌĂŝŶĂƐƚƌŽĐǇƚĞƐ͘EĂƚDĞĚϭϮ;ϭϭͿ͗ϭϮϱϵͲϭϮϲϴ͘
ZƵďŝŶƐǌƚĞŝŶ͕͕>ĞŐŐŽ͕:͕ŽůĞƐ͕Z͕ůŵƋǀŝƐƚ͕͕ŝĂŶĐĂůĂŶĂ͕s͕ĂƐƐŝŵĂŶ͕::͕ŚŽƚĂŝ͕<͕
ŽŶŶĂƌƚǇ͕ D͕ ƌĂƵĨŽƌĚ͕ ͕ ƵƌƚŝƐ͕ ͕ ƵƌƚŝƐ͕ ͕ ĂǀŝĚƐŽŶ͕ D:͕ ŝĨĨĞƌ͕ D͕ ŽĚĞ͕ ͕
ŽĚŐĞ͕͕&ƌŽŶƚĂůŝ͕D͕ZĂŶĞŶ͕E'͕^ƚŝŶĞ͕K͕^ŚĞƌƌ͕D͕ďďŽƚƚ͕D,͕&ƌĂŶǌ͕D>͕'ƌĂŚĂŵ͕
͕,ĂƌƉĞƌ͕W^͕,ĞĚƌĞĞŶ͕:͕,ĂǇĚĞŶ͕DZ͕ĞƚĂů͘;ϭϵϵϲͿWŚĞŶŽƚǇƉŝĐĐŚĂƌĂĐƚĞƌŝǌĂƚŝŽŶŽĨ
ŝŶĚŝǀŝĚƵĂůƐ ǁŝƚŚ ϯϬͲϰϬ ' ƌĞƉĞĂƚƐ ŝŶ ƚŚĞ ,ƵŶƚŝŶŐƚŽŶ ĚŝƐĞĂƐĞ ;,Ϳ ŐĞŶĞ ƌĞǀĞĂůƐ ,
ĐĂƐĞƐ ǁŝƚŚ ϯϲ ƌĞƉĞĂƚƐ ĂŶĚ ĂƉƉĂƌĞŶƚůǇ ŶŽƌŵĂů ĞůĚĞƌůǇ ŝŶĚŝǀŝĚƵĂůƐ ǁŝƚŚ ϯϲͲϯϵ ƌĞƉĞĂƚƐ͘
ŵ:,Ƶŵ'ĞŶĞƚϱϵ;ϭͿ͗ϭϲͲϮϮ͘
^ĂŐĂŶ͕>;ϭϵϲϳͿKŶƚŚĞŽƌŝŐŝŶŽĨŵŝƚŽƐŝŶŐĐĞůůƐ͘:dŚĞŽƌŝŽůϭϰ;ϯͿ͗ϮϱϱͲϮϳϰ͘
^ĂŚƵ͕ Z͕ <ĂƵƐŚŝŬ͕ ^͕ ůĞŵĞŶƚ͕ ͕ ĂŶŶŝǌǌŽ͕ ^͕ ^ĐŚĂƌĨ͕ ͕ &ŽůůĞŶǌŝ͕ ͕ WŽƚŽůŝĐĐŚŝŽ͕ /͕
EŝĞǀĞƐ͕ ͕ ƵĞƌǀŽ͕ D͕ ^ĂŶƚĂŵďƌŽŐŝŽ͕ > ;ϮϬϭϭͿ DŝĐƌŽĂƵƚŽƉŚĂŐǇ ŽĨ ĐǇƚŽƐŽůŝĐ ƉƌŽƚĞŝŶƐ
ďǇůĂƚĞĞŶĚŽƐŽŵĞƐ͘ĞǀĞůůϮϬ;ϭͿ͗ϭϯϭͲϭϯϵ͘
^ĂŝƚŽ͕z͕EŝƐŚŝŽ͕<͕KŐĂǁĂ͕z͕<ŝŶƵŵŝ͕d͕zŽƐŚŝĚĂ͕z͕DĂƐƵŽ͕z͕EŝŬŝ͕;ϮϬϬϳͿDŽůĞĐƵůĂƌ
ŵĞĐŚĂŶŝƐŵƐŽĨϲͲŚǇĚƌŽǆǇĚŽƉĂŵŝŶĞͲŝŶĚƵĐĞĚĐǇƚŽƚŽǆŝĐŝƚǇŝŶWϭϮĐĞůůƐ͗ŝŶǀŽůǀĞŵĞŶƚŽĨ
ŚǇĚƌŽŐĞŶ ƉĞƌŽǆŝĚĞͲĚĞƉĞŶĚĞŶƚ ĂŶĚ ͲŝŶĚĞƉĞŶĚĞŶƚ ĂĐƚŝŽŶ͘ &ƌĞĞ ZĂĚŝĐ ŝŽů DĞĚ ϰϮ;ϱͿ͗
ϲϳϱͲϲϴϱ͘
^ĂŵƵŶŝ͕͕<ƌŝƐŚŶĂ͕D͕DŝƚĐŚĞůů͕:͕ŽůůŝŶƐ͕Z͕ZƵƐƐŽ͕;ϭϵϵϬͿ^ƵƉĞƌŽǆŝĚĞƌĞĂĐƚŝŽŶ
ǁŝƚŚŶŝƚƌŽǆŝĚĞƐ͘&ƌĞĞZĂĚŝĐZĞƐŽŵŵƵŶϵ;ϯͲϲͿ͗ϮϰϭͲϮϰϵ͘
^ĂŶĞƌ͕͕dŚŽĞŶĞŶ͕,;ϭϵϳϭͿDŽĚĞůĞǆƉĞƌŝŵĞŶƚƐŽŶƚŚĞŵŽůĞĐƵůĂƌŵĞĐŚĂŶŝƐŵŽĨĂĐƚŝŽŶ
ŽĨϲͲŚǇĚƌŽǆǇĚŽƉĂŵŝŶĞ͘DŽůWŚĂƌŵĂĐŽůϳ;ϮͿ͗ϭϰϳͲϭϱϰ͘
ϭϬϵ
^ĂŶƚĞů͕ ͕ &ƌĂŶŬ͕ ^͕ 'ĂƵŵĞ͕ ͕ ,ĞƌƌůĞƌ͕ D͕ zŽƵůĞ͕ Z:͕ &ƵůůĞƌ͕ Dd ;ϮϬϬϯͿ DŝƚŽĨƵƐŝŶͲϭ
ƉƌŽƚĞŝŶŝƐĂŐĞŶĞƌĂůůǇĞǆƉƌĞƐƐĞĚŵĞĚŝĂƚŽƌŽĨŵŝƚŽĐŚŽŶĚƌŝĂůĨƵƐŝŽŶŝŶŵĂŵŵĂůŝĂŶĐĞůůƐ͘:
Ğůů^Đŝϭϭϲ;WƚϭϯͿ͗ϮϳϲϯͲϮϳϳϰ͘
^ĂŶƚĞů͕ ͕ &ƵůůĞƌ͕ Dd ;ϮϬϬϭͿ ŽŶƚƌŽů ŽĨ ŵŝƚŽĐŚŽŶĚƌŝĂů ŵŽƌƉŚŽůŽŐǇ ďǇ Ă ŚƵŵĂŶ
ŵŝƚŽĨƵƐŝŶ͘:Ğůů^Đŝϭϭϰ;WƚϱͿ͗ϴϲϳͲϴϳϰ͘
^ĂƌŬĂƌ͕&,͕ZĂŚŵĂŶ͕<D͕>ŝ͕z;ϮϬϬϯͿĂǆƚƌĂŶƐůŽĐĂƚŝŽŶƚŽŵŝƚŽĐŚŽŶĚƌŝĂŝƐĂŶŝŵƉŽƌƚĂŶƚ
ĞǀĞŶƚ ŝŶ ŝŶĚƵĐŝŶŐ ĂƉŽƉƚŽƚŝĐ ĐĞůů ĚĞĂƚŚ ďǇ ŝŶĚŽůĞͲϯͲĐĂƌďŝŶŽů ;/ϯͿ ƚƌĞĂƚŵĞŶƚ ŽĨ ďƌĞĂƐƚ
ĐĂŶĐĞƌĐĞůůƐ͘:EƵƚƌϭϯϯ;ϳ^ƵƉƉůͿ͗Ϯϰϯϰ^ͲϮϰϯϵ^͘
^ĂƐĂŬŝ͕ ,͕ >ŝŶ͕ >Z͕ zŽŬŽǇĂŵĂ͕ d͕ ^ĞǀŝůůĂ͕ D͕ ZĞĚĚǇ͕ sE͕ 'ŝďůŝŶ͕ &: ;ϭϵϵϴͿ dDWK>
ƉƌŽƚĞĐƚƐ ĂŐĂŝŶƐƚ ůĞŶƐ E ƐƚƌĂŶĚ ďƌĞĂŬƐ ĂŶĚ ĐĂƚĂƌĂĐƚ ŝŶ ƚŚĞ ǆͲƌĂǇĞĚ ƌĂďďŝƚ͘ /ŶǀĞƐƚ
KƉŚƚŚĂůŵŽůsŝƐ^Đŝϯϵ;ϯͿ͗ϱϰϰͲϱϱϮ͘
^ĐŚĂƉŝƌĂ͕ ,͕ ŽŽƉĞƌ͕ :D͕ ĞǆƚĞƌ͕ ͕ ůĂƌŬ͕ :͕ :ĞŶŶĞƌ͕ W͕ DĂƌƐĚĞŶ͕ ;ϭϵϵϬͿ
DŝƚŽĐŚŽŶĚƌŝĂů ĐŽŵƉůĞǆ / ĚĞĨŝĐŝĞŶĐǇ ŝŶ WĂƌŬŝŶƐŽŶΖƐ ĚŝƐĞĂƐĞ͘ : EĞƵƌŽĐŚĞŵ ϱϰ;ϯͿ͗ ϴϮϯͲ
ϴϮϳ͘
^ĐŚĞƌǌͲ^ŚŽƵǀĂů͕Z͕^ŚǀĞƚƐ͕͕&ĂƐƐ͕͕^ŚŽƌĞƌ͕,͕'ŝů͕>͕ůĂǌĂƌ͕;ϮϬϬϳͿZĞĂĐƚŝǀĞŽǆǇŐĞŶ
ƐƉĞĐŝĞƐĂƌĞĞƐƐĞŶƚŝĂůĨŽƌĂƵƚŽƉŚĂŐǇĂŶĚƐƉĞĐŝĨŝĐĂůůǇƌĞŐƵůĂƚĞƚŚĞĂĐƚŝǀŝƚǇŽĨƚŐϰ͘DK
:Ϯϲ;ϳͿ͗ϭϳϰϵͲϭϳϲϬ͘
^ĐŚŽďĞƌ͕;ϮϬϬϰͿůĂƐƐŝĐƚŽǆŝŶͲŝŶĚƵĐĞĚĂŶŝŵĂůŵŽĚĞůƐŽĨWĂƌŬŝŶƐŽŶΖƐĚŝƐĞĂƐĞ͗ϲͲK,
ĂŶĚDWdW͘ĞůůdŝƐƐƵĞZĞƐϯϭϴ;ϭͿ͗ϮϭϱͲϮϮϰ͘
^ĐŚǁĂƌƚŝŶŐ͕Z<͕,ƵƐƚŽŶ͕:W;ϭϵϵϲĂͿdŚĞƵŶŝůĂƚĞƌĂůϲͲŚǇĚƌŽǆǇĚŽƉĂŵŝŶĞůĞƐŝŽŶŵŽĚĞůŝŶ
ďĞŚĂǀŝŽƌĂů ďƌĂŝŶ ƌĞƐĞĂƌĐŚ͘ ŶĂůǇƐŝƐ ŽĨ ĨƵŶĐƚŝŽŶĂů ĚĞĨŝĐŝƚƐ͕ ƌĞĐŽǀĞƌǇ ĂŶĚ ƚƌĞĂƚŵĞŶƚƐ͘
WƌŽŐEĞƵƌŽďŝŽůϱϬ;ϮͲϯͿ͗ϮϳϱͲϯϯϭ͘
^ĐŚǁĂƌƚŝŶŐ͕ Z<͕ ,ƵƐƚŽŶ͕ :W ;ϭϵϵϲďͿ hŶŝůĂƚĞƌĂů ϲͲŚǇĚƌŽǆǇĚŽƉĂŵŝŶĞ ůĞƐŝŽŶƐ ŽĨ ŵĞƐŽͲ
ƐƚƌŝĂƚĂůĚŽƉĂŵŝŶĞŶĞƵƌŽŶƐĂŶĚƚŚĞŝƌƉŚǇƐŝŽůŽŐŝĐĂůƐĞƋƵĞůĂĞ͘WƌŽŐEĞƵƌŽďŝŽůϰϵ;ϯͿ͗ϮϭϱͲ
Ϯϲϲ͘
^ĞŬŚĂƌĂŵ͕D͕dƌŽƚƚŝ͕͕ƵŶŶŝĐŬ͕:D͕tƵ͕:;ϭϵϵϴͿ^ƵƉƉƌĞƐƐŝŽŶŽĨĨŝďƌŽďůĂƐƚĐĞůůĐǇĐůĞ
ƉƌŽŐƌĞƐƐŝŽŶŝŶ'ϭƉŚĂƐĞďǇEͲĂĐĞƚǇůĐǇƐƚĞŝŶĞ͘dŽǆŝĐŽůƉƉůWŚĂƌŵĂĐŽůϭϰϵ;ϮͿ͗ϮϭϬͲϮϭϲ͘
^ĞŽ͕ z͕ :ŽƐĞƉŚ͕ D͕ ƵƚƚĂ͕ ͕ ,ǁĂŶŐ͕ :͕ ƌŝƐ͕ :W͕ >ĞĞƵǁĞŶďƵƌŐŚ͕ ;ϮϬϭϬͿ EĞǁ
ŝŶƐŝŐŚƚƐŝŶƚŽƚŚĞƌŽůĞŽĨŵŝƚŽĐŚŽŶĚƌŝĂŝŶĂŐŝŶŐ͗ŵŝƚŽĐŚŽŶĚƌŝĂůĚǇŶĂŵŝĐƐĂŶĚŵŽƌĞ͘:Ğůů
^ĐŝϭϮϯ;WƚϭϱͿ͗ϮϱϯϯͲϮϱϰϮ͘
^ĞƚŚ͕Z͕^ƵŶ͕>͕Ă͕<͕ŚĞŶ͕:;ϮϬϬϱͿ/ĚĞŶƚŝĨŝĐĂƚŝŽŶĂŶĚĐŚĂƌĂĐƚĞƌŝǌĂƚŝŽŶŽĨDs^͕Ă
ŵŝƚŽĐŚŽŶĚƌŝĂů ĂŶƚŝǀŝƌĂů ƐŝŐŶĂůŝŶŐ ƉƌŽƚĞŝŶ ƚŚĂƚ ĂĐƚŝǀĂƚĞƐ E&ͲŬĂƉƉĂ ĂŶĚ /Z& ϯ͘ Ğůů
ϭϮϮ;ϱͿ͗ϲϲϵͲϲϴϮ͘
^ŚĂƉŽǀĂůŽǀ͕ z͕ ,ŽĨĨŵĂŶ͕ ͕ ƵĐŚ͕ ͕ ĚĞ DĞƐǇ ĞŶƚůĞǇ͕ <>͕ ůŝƐĞĞǀ͕ Z ;ϮϬϭϭͿ
DŝƚŽĐŚŽŶĚƌŝĂůĚǇƐĨƵŶĐƚŝŽŶŝŶĐĂŶĐĞƌĐĞůůƐĚƵĞƚŽĂďĞƌƌĂŶƚŵŝƚŽĐŚŽŶĚƌŝĂůƌĞƉůŝĐĂƚŝŽŶ͘:
ϭϭϬ
ŝŽůŚĞŵϮϴϲ;ϮϱͿ͗ϮϮϯϯϭͲϮϮϯϯϴ͘
^ŚŝŵŝǌƵ͕͕,ĂƐŚŝŵŽƚŽ͕<͕<ŽŵĂƚƐƵ͕E͕/ǇŽ͕D;ϮϬϬϮͿZŽůĞƐŽĨĞŶĚŽŐĞŶŽƵƐŐůƵƚĂƚŚŝŽŶĞ
ůĞǀĞůƐ ŽŶ ϲͲŚǇĚƌŽǆǇĚŽƉĂŵŝŶĞͲŝŶĚƵĐĞĚ ĂƉŽƉƚŽƚŝĐ ŶĞƵƌŽŶĂů ĐĞůů ĚĞĂƚŚ ŝŶ ŚƵŵĂŶ
ŶĞƵƌŽďůĂƐƚŽŵĂ^<ͲEͲ^,ĐĞůůƐ͘EĞƵƌŽƉŚĂƌŵĂĐŽůŽŐǇϰϯ;ϯͿ͗ϰϯϰͲϰϰϯ͘
^ŚƵůƚƐ͕t;ϮϬϬϲͿ>ĞǁǇďŽĚŝĞƐ͘WƌŽĐEĂƚůĐĂĚ^Đŝh^ϭϬϯ;ϲͿ͗ϭϲϲϭͲϭϲϲϴ͘
^ŝŐĂƵĚ͕^͕ǀĞůƐŽŶ͕W͕'ŽŶǌĂůĞǌͲ&ůĞĐŚĂ͕;ϮϬϬϱͿ,ϮKϮͲŝŶĚƵĐĞĚƉƌŽůŝĨĞƌĂƚŝŽŶŽĨƉƌŝŵĂƌǇ
ĂůǀĞŽůĂƌĞƉŝƚŚĞůŝĂůĐĞůůƐŝƐŵĞĚŝĂƚĞĚďǇDWŬŝŶĂƐĞƐ͘ŶƚŝŽǆŝĚZĞĚŽǆ^ŝŐŶĂůϳ;ϭͲϮͿ͗ϲͲϭϯ͘
^ŝŵĂŶƚŽǀ͕Z͕ůŝŶĚĞƌ͕͕ZĂƚŽǀŝƚƐŬŝ͕d͕dĂƵďĞƌ͕D͕'ĂďďĂǇ͕D͕WŽƌĂƚ͕^;ϭϵϵϲͿŽƉĂŵŝŶĞͲ
ŝŶĚƵĐĞĚĂƉŽƉƚŽƐŝƐŝŶŚƵŵĂŶŶĞƵƌŽŶĂůĐĞůůƐ͗ŝŶŚŝďŝƚŝŽŶďǇŶƵĐůĞŝĐĂĐŝĚƐĂŶƚŝƐĞŶƐĞƚŽƚŚĞ
ĚŽƉĂŵŝŶĞƚƌĂŶƐƉŽƌƚĞƌ͘EĞƵƌŽƐĐŝĞŶĐĞϳϰ;ϭͿ͗ϯϵͲϱϬ͘
^ŝŶŐĞƌ͕ ;ϮϬϭϮͿ ŽŵƉƌĞŚĞŶƐŝǀĞ ƚƌĞĂƚŵĞŶƚ ŽĨ ,ƵŶƚŝŶŐƚŽŶ ĚŝƐĞĂƐĞ ĂŶĚ ŽƚŚĞƌ ĐŚŽƌĞŝĐ
ĚŝƐŽƌĚĞƌƐ͘ůĞǀĞůŝŶ:DĞĚϳϵ^ƵƉƉůϮ͗^ϯϬͲϯϰ͘
^ŝƚĂŝůŽ͕>͕dŝďƵĚĂŶ͕^^͕ĞŶŶŝŶŐ͕D&;ϮϬϬϮͿĐƚŝǀĂƚŝŽŶŽĨĐĂƐƉĂƐĞͲϵŝƐƌĞƋƵŝƌĞĚĨŽƌhsͲ
ŝŶĚƵĐĞĚĂƉŽƉƚŽƐŝƐŽĨŚƵŵĂŶŬĞƌĂƚŝŶŽĐǇƚĞƐ͘:ŝŽůŚĞŵϮϳϳ;ϮϮͿ͗ϭϵϯϰϲͲϭϵϯϱϮ͘
^ŬƵůĂĐŚĞǀ͕ sW ;ϮϬϬϭͿ DŝƚŽĐŚŽŶĚƌŝĂů ĨŝůĂŵĞŶƚƐ ĂŶĚ ĐůƵƐƚĞƌƐ ĂƐ ŝŶƚƌĂĐĞůůƵůĂƌ ƉŽǁĞƌͲ
ƚƌĂŶƐŵŝƚƚŝŶŐĐĂďůĞƐ͘dƌĞŶĚƐŝŽĐŚĞŵ^ĐŝϮϲ;ϭͿ͗ϮϯͲϮϵ͘
^ŵĂŝůŝ͕ ^^͕ ,ƐƵ͕ zd͕ ^ĂŶĚĞƌƐ͕ <D͕ ZƵƐƐĞůů͕ :d͕ zŽƵůĞ͕ Z: ;ϮϬϬϭͿ Ăǆ ƚƌĂŶƐůŽĐĂƚŝŽŶ ƚŽ
ŵŝƚŽĐŚŽŶĚƌŝĂ ƐƵďƐĞƋƵĞŶƚ ƚŽ Ă ƌĂƉŝĚ ůŽƐƐ ŽĨ ŵŝƚŽĐŚŽŶĚƌŝĂů ŵĞŵďƌĂŶĞ ƉŽƚĞŶƚŝĂů͘ Ğůů
ĞĂƚŚŝĨĨĞƌϴ;ϵͿ͗ϵϬϵͲϵϮϬ͘
^ŵŝƌŶŽǀĂ͕ ͕ 'ƌŝƉĂƌŝĐ͕ >͕ ^ŚƵƌůĂŶĚ͕ >͕ ǀĂŶ ĚĞƌ ůŝĞŬ͕ D ;ϮϬϬϭͿ ǇŶĂŵŝŶͲƌĞůĂƚĞĚ
ƉƌŽƚĞŝŶ ƌƉϭ ŝƐ ƌĞƋƵŝƌĞĚ ĨŽƌ ŵŝƚŽĐŚŽŶĚƌŝĂů ĚŝǀŝƐŝŽŶ ŝŶ ŵĂŵŵĂůŝĂŶ ĐĞůůƐ͘ DŽů ŝŽů Ğůů
ϭϮ;ϴͿ͗ϮϮϰϱͲϮϮϱϲ͘
^ŵŝƌŶŽǀĂ͕͕^ŚƵƌůĂŶĚ͕>͕ZǇĂǌĂŶƚƐĞǀ͕Ê͕ǀĂŶĚĞƌůŝĞŬ͕D;ϭϵϵϴͿŚƵŵĂŶĚǇŶĂŵŝŶͲ
ƌĞůĂƚĞĚƉƌŽƚĞŝŶĐŽŶƚƌŽůƐƚŚĞĚŝƐƚƌŝďƵƚŝŽŶŽĨŵŝƚŽĐŚŽŶĚƌŝĂ͘:ĞůůŝŽůϭϰϯ;ϮͿ͗ϯϱϭͲϯϱϴ͘
^ŵŝƚŚ͕ Z͕ ,ĂƌƚůĞǇ͕ Z͕ DƵƌƉŚǇ͕ DW ;ϮϬϭϭĂͿ DŝƚŽĐŚŽŶĚƌŝĂͲƚĂƌŐĞƚĞĚ ƐŵĂůů ŵŽůĞĐƵůĞ
ƚŚĞƌĂƉĞƵƚŝĐƐĂŶĚƉƌŽďĞƐ͘ŶƚŝŽǆŝĚZĞĚŽǆ^ŝŐŶĂůϭϱ;ϭϮͿ͗ϯϬϮϭͲϯϬϯϴ͘
^ŵŝƚŚ͕ Z͕ DƵƌƉŚǇ͕ DW ;ϮϬϭϬͿ ŶŝŵĂů ĂŶĚ ŚƵŵĂŶ ƐƚƵĚŝĞƐ ǁŝƚŚ ƚŚĞ ŵŝƚŽĐŚŽŶĚƌŝĂͲ
ƚĂƌŐĞƚĞĚĂŶƚŝŽǆŝĚĂŶƚDŝƚŽY͘ŶŶEzĐĂĚ^ĐŝϭϮϬϭ͗ϵϲͲϭϬϯ͘
^ŵŝƚŚ͕ Z͕ DƵƌƉŚǇ͕ DW ;ϮϬϭϭďͿ DŝƚŽĐŚŽŶĚƌŝĂͲƚĂƌŐĞƚĞĚ ĂŶƚŝŽǆŝĚĂŶƚƐ ĂƐ ƚŚĞƌĂƉŝĞƐ͘
ŝƐĐŽǀDĞĚϭϭ;ϱϳͿ͗ϭϬϲͲϭϭϰ͘
^ŵŝƚŚ͕ Z͕ WŽƌƚĞŽƵƐ͕ D͕ 'ĂŶĞ͕ D͕ DƵƌƉŚǇ͕ DW ;ϮϬϬϯͿ ĞůŝǀĞƌǇ ŽĨ ďŝŽĂĐƚŝǀĞ
ŵŽůĞĐƵůĞƐƚŽŵŝƚŽĐŚŽŶĚƌŝĂŝŶǀŝǀŽ͘WƌŽĐEĂƚůĐĂĚ^Đŝh^ϭϬϬ;ϵͿ͗ϱϰϬϳͲϱϰϭϮ͘
ϭϭϭ
^Ž͕ ͕ ,ƐŝŶŐ͕ ,͕ >ŝĂŶŐ͕ ,͕ tƵ͕ Ê ;ϮϬϭϮͿ dŚĞ ĂĐƚŝŽŶƐ ŽĨ ŵĚŝǀŝͲϭ͕ ĂŶ ŝŶŚŝďŝƚŽƌ ŽĨ
ŵŝƚŽĐŚŽŶĚƌŝĂů ĨŝƐƐŝŽŶ͕ ŽŶ ƌĂƉŝĚůǇ ĂĐƚŝǀĂƚŝŶŐ ĚĞůĂǇĞĚͲƌĞĐƚŝĨŝĞƌ <;нͿ ĐƵƌƌĞŶƚ ĂŶĚ
ŵĞŵďƌĂŶĞƉŽƚĞŶƚŝĂůŝŶ,>ͲϭŵƵƌŝŶĞĂƚƌŝĂůĐĂƌĚŝŽŵǇŽĐǇƚĞƐ͘Ƶƌ:WŚĂƌŵĂĐŽůϲϴϯ;ϭͲϯͿ͗
ϭͲϵ͘
^ŽďƌŝĚŽ͕D:͕ŝĂƐͲ^ŝůǀĂ͕:͘:͕͘YƵŝŶƚĄŶƐ͕͘;ϮϬϬϵͿdƌĂŶƐƚŽƌŶŽƐĚĞůĐŽŵƉŽƌƚĂŵŝĞŶƚŽĞŶůĂ
ĞŶĨĞƌŵĞĚĂĚĚĞWĂƌŬŝŶƐŽŶ͘ƐƉĞĐƚŽƐŐĞŶĠƚŝĐŽƐ͕ĨĂƌŵĂĐŽůſŐŝĐŽƐǇŵĠĚŝĐŽͲůĞŐĂůĞƐ͘͘ZĞǀ
EĞƵƌŽůϰϴ͗^ϰϯͲ^ϰϴ͘
^ŽŶŐ͕ ͕ ŚĞŶ͕ ,͕ &ŝŬĞƚ͕ D͕ ůĞǆĂŶĚĞƌ͕ ͕ ŚĂŶ͕ ;ϮϬϬϳͿ KWϭ ƉƌŽĐĞƐƐŝŶŐ ĐŽŶƚƌŽůƐ
ŵŝƚŽĐŚŽŶĚƌŝĂů ĨƵƐŝŽŶ ĂŶĚ ŝƐ ƌĞŐƵůĂƚĞĚ ďǇ ŵZE ƐƉůŝĐŝŶŐ͕ ŵĞŵďƌĂŶĞ ƉŽƚĞŶƚŝĂů͕ ĂŶĚ
zŵĞϭ>͘:ĞůůŝŽůϭϳϴ;ϱͿ͗ϳϰϵͲϳϱϱ͘
^ŽŶŐ͕͕'ŚŽĐŚĂŶŝ͕D͕DĐĂĨĨĞƌǇ͕:D͕&ƌĞǇ͕d'͕ŚĂŶ͕;ϮϬϬϵͿDŝƚŽĨƵƐŝŶƐĂŶĚKWϭ
ŵĞĚŝĂƚĞ ƐĞƋƵĞŶƚŝĂů ƐƚĞƉƐ ŝŶ ŵŝƚŽĐŚŽŶĚƌŝĂů ŵĞŵďƌĂŶĞ ĨƵƐŝŽŶ͘ DŽů ŝŽů Ğůů ϮϬ;ϭϱͿ͗
ϯϱϮϱͲϯϱϯϮ͘
^ƚĂƌŬƐƚĞŝŶ͕ ^͕ ƌŽĐŬŵĂŶ͕ ^͕ ,ĂǇŚŽǁ͕ ;ϮϬϭϮͿ WƐǇĐŚŝĂƚƌŝĐ ƐǇŶĚƌŽŵĞƐ ŝŶ WĂƌŬŝŶƐŽŶΖƐ
ĚŝƐĞĂƐĞ͘ƵƌƌKƉŝŶWƐǇĐŚŝĂƚƌǇϮϱ;ϲͿ͗ϰϲϴͲϰϳϮ͘
^ƚŽũĂŶŽǀƐŬŝ͕͕<ŽƵƚƐŽƉŽƵůŽƐ͕K^͕KŬĂŵŽƚŽ͕<͕ZǇĂŶ͕Dd;ϮϬϬϰͿ>ĞǀĞůƐŽĨŚƵŵĂŶ&ŝƐϭ
Ăƚ ƚŚĞ ŵŝƚŽĐŚŽŶĚƌŝĂů ŽƵƚĞƌ ŵĞŵďƌĂŶĞ ƌĞŐƵůĂƚĞ ŵŝƚŽĐŚŽŶĚƌŝĂů ŵŽƌƉŚŽůŽŐǇ͘ : Ğůů ^Đŝ
ϭϭϳ;WƚϳͿ͗ϭϮϬϭͲϭϮϭϬ͘
^ƚŽŶĞ͕ :Z͕ ŽůůŝŶƐ͕ d ;ϮϬϬϮͿ dŚĞ ƌŽůĞ ŽĨ ŚǇĚƌŽŐĞŶ ƉĞƌŽǆŝĚĞ ŝŶĞŶĚŽƚŚĞůŝĂů ƉƌŽůŝĨĞƌĂƚŝǀĞ
ƌĞƐƉŽŶƐĞƐ͘ŶĚŽƚŚĞůŝƵŵϵ;ϰͿ͗ϮϯϭͲϮϯϴ͘
^ƚŽŶĞ͕ :Z͕ zĂŶŐ͕ ^ ;ϮϬϬϲͿ ,ǇĚƌŽŐĞŶ ƉĞƌŽǆŝĚĞ͗ Ă ƐŝŐŶĂůŝŶŐ ŵĞƐƐĞŶŐĞƌ͘ ŶƚŝŽǆŝĚ ZĞĚŽǆ
^ŝŐŶĂůϴ;ϯͲϰͿ͗ϮϰϯͲϮϳϬ͘
^ƚŽƌĐŚ͕ ͕ <ĂĨƚĂŶ͕ ͕ ƵƌŬŚĂƌĚƚ͕ <͕ ^ĐŚǁĂƌǌ͕ : ;ϮϬϬϬͿ ϲͲ,ǇĚƌŽǆǇĚŽƉĂŵŝŶĞ ƚŽǆŝĐŝƚǇ
ƚŽǁĂƌĚƐ ŚƵŵĂŶ ^,Ͳ^zϱz ĚŽƉĂŵŝŶĞƌŐŝĐ ŶĞƵƌŽďůĂƐƚŽŵĂ ĐĞůůƐ͗ ŝŶĚĞƉĞŶĚĞŶƚ ŽĨ
ŵŝƚŽĐŚŽŶĚƌŝĂůĞŶĞƌŐǇŵĞƚĂďŽůŝƐŵ͘:EĞƵƌĂůdƌĂŶƐŵϭϬϳ;ϯͿ͗ϮϴϭͲϮϵϯ͘
^ƚƌĂƵƐƐ͕<D͕DĂƌƚŝŶƐ͕>D͕WůƵŶͲ&ĂǀƌĞĂƵ͕,͕DĂƌǆ͕&W͕<ĂƵƚǌŵĂŶŶ͕^͕ĞƌŐ͕͕'ĂƐƐĞƌ͕d͕
tƐǌŽůĞŬ͕ ͕ DƵůůĞƌ͕ d͕ ŽƌŶĞŵĂŶŶ͕ ͕ tŽůďƵƌŐ͕ ,͕ ŽǁŶǁĂƌĚ͕ :͕ ZŝĞƐƐ͕ K͕ ^ĐŚƵůǌ͕ :͕
<ƌƵŐĞƌ͕ Z ;ϮϬϬϱͿ >ŽƐƐ ŽĨ ĨƵŶĐƚŝŽŶ ŵƵƚĂƚŝŽŶƐ ŝŶ ƚŚĞ ŐĞŶĞ ĞŶĐŽĚŝŶŐ Kŵŝͬ,ƚƌϮ ŝŶ
WĂƌŬŝŶƐŽŶΖƐĚŝƐĞĂƐĞ͘,ƵŵDŽů'ĞŶĞƚϭϰ;ϭϱͿ͗ϮϬϵϵͲϮϭϭϭ͘
^ƵďƌĂŵĂŶŝĂŶ͕ ^͕ <ĂůǇĂŶĂƌĂŵĂŶ͕ ͕ DŝŐƌŝŶŽ͕ ZY ;ϮϬϭϬͿ DŝƚŽĐŚŽŶĚƌŝĂůůǇ ƚĂƌŐĞƚĞĚ
ĂŶƚŝŽǆŝĚĂŶƚƐĨŽƌƚŚĞƚƌĞĂƚŵĞŶƚŽĨĐĂƌĚŝŽǀĂƐĐƵůĂƌĚŝƐĞĂƐĞƐ͘ZĞĐĞŶƚWĂƚĂƌĚŝŽǀĂƐĐƌƵŐ
ŝƐĐŽǀϱ;ϭͿ͗ϱϰͲϲϱ͘
^ǌĂďĂĚŬĂŝ͕'͕^ŝŵŽŶŝ͕D͕ŝĂŶĐŚŝ͕<͕Ğ^ƚĞĨĂŶŝ͕͕>ĞŽ͕^͕tŝĞĐŬŽǁƐŬŝ͕DZ͕ZŝǌǌƵƚŽ͕Z
;ϮϬϬϲͿ DŝƚŽĐŚŽŶĚƌŝĂů ĚǇŶĂŵŝĐƐ ĂŶĚ ĂϮн ƐŝŐŶĂůŝŶŐ͘ ŝŽĐŚŝŵ ŝŽƉŚǇƐ ĐƚĂ ϭϳϲϯ;ϱͲϲͿ͗
ϰϰϮͲϰϰϵ͘
ϭϭϮ
^ǌĂďŽ͕ ͕ ^ĂůǌŵĂŶ͕ > ;ϭϵϵϲͿ /ŶŚŝďŝƚŝŽŶ ŽĨ dWͲĂĐƚŝǀĂƚĞĚ ƉŽƚĂƐƐŝƵŵ ĐŚĂŶŶĞůƐ ĞǆĞƌƚƐ
ƉƌĞƐƐŽƌ ĞĨĨĞĐƚƐ ĂŶĚ ŝŵƉƌŽǀĞƐ ƐƵƌǀŝǀĂů ŝŶ Ă ƌĂƚ ŵŽĚĞů ŽĨ ƐĞǀĞƌĞ ŚĞŵŽƌƌŚĂŐŝĐ ƐŚŽĐŬ͘
^ŚŽĐŬϱ;ϲͿ͗ϯϵϭͲϯϵϰ͘
dĂďƌŝǌŝ͕ ^:͕ ůĞĞƚĞƌ͕ Dt͕ yƵĞƌĞď͕ :͕ dĂĂŶŵĂŶ͕ :t͕ ŽŽƉĞƌ͕ :D͕ ^ĐŚĂƉŝƌĂ͕ , ;ϭϵϵϵͿ
ŝŽĐŚĞŵŝĐĂůĂďŶŽƌŵĂůŝƚŝĞƐĂŶĚĞǆĐŝƚŽƚŽǆŝĐŝƚǇŝŶ,ƵŶƚŝŶŐƚŽŶΖƐĚŝƐĞĂƐĞďƌĂŝŶ͘ŶŶEĞƵƌŽů
ϰϱ;ϭͿ͗ϮϱͲϯϮ͘
dĂŐƵĐŚŝ͕E͕/ƐŚŝŚĂƌĂ͕E͕:ŽĨƵŬƵ͕͕KŬĂ͕d͕DŝŚĂƌĂ͕<;ϮϬϬϳͿDŝƚŽƚŝĐƉŚŽƐƉŚŽƌǇůĂƚŝŽŶŽĨ
ĚǇŶĂŵŝŶͲƌĞůĂƚĞĚ 'dWĂƐĞ ƌƉϭ ƉĂƌƚŝĐŝƉĂƚĞƐ ŝŶ ŵŝƚŽĐŚŽŶĚƌŝĂů ĨŝƐƐŝŽŶ͘ : ŝŽů ŚĞŵ
ϮϴϮ;ϭϱͿ͗ϭϭϱϮϭͲϭϭϱϮϵ͘
dĂŝƚ͕ ^t͕ 'ƌĞĞŶ͕ Z ;ϮϬϭϬͿ DŝƚŽĐŚŽŶĚƌŝĂ ĂŶĚ ĐĞůů ĚĞĂƚŚ͗ ŽƵƚĞƌ ŵĞŵďƌĂŶĞ
ƉĞƌŵĞĂďŝůŝǌĂƚŝŽŶĂŶĚďĞǇŽŶĚ͘EĂƚZĞǀDŽůĞůůŝŽůϭϭ;ϵͿ͗ϲϮϭͲϲϯϮ͘
dĂŵƵƌĂ͕ d͕ /ƐŚŝŚĂƌĂ͕ D͕ >ĂŵƉŚŝĞƌ͕ D^͕ dĂŶĂŬĂ͕ E͕ KŝƐŚŝ͕ /͕ ŝǌĂǁĂ͕ ^͕ DĂƚƐƵǇĂŵĂ͕ d͕
DĂŬ͕ dt͕ dĂŬŝ͕ ^͕ dĂŶŝŐƵĐŚŝ͕ d ;ϭϵϵϱͿ Ŷ /Z&ͲϭͲĚĞƉĞŶĚĞŶƚ ƉĂƚŚǁĂǇ ŽĨ E ĚĂŵĂŐĞͲ
ŝŶĚƵĐĞĚĂƉŽƉƚŽƐŝƐŝŶŵŝƚŽŐĞŶͲĂĐƚŝǀĂƚĞĚdůǇŵƉŚŽĐǇƚĞƐ͘EĂƚƵƌĞϯϳϲ;ϲϱϰϭͿ͗ϱϵϲͲϱϵϵ͘
dĂŶĂŬĂ͕ ͕ zŽƵůĞ͕ Z: ;ϮϬϬϴͿ ĐŚĞŵŝĐĂů ŝŶŚŝďŝƚŽƌ ŽĨ ZWϭ ƵŶĐŽƵƉůĞƐ ŵŝƚŽĐŚŽŶĚƌŝĂů
ĨŝƐƐŝŽŶĂŶĚĂƉŽƉƚŽƐŝƐ͘DŽůĞůůϮϵ;ϰͿ͗ϰϬϵͲϰϭϬ͘
dĂŶĂŬĂ͕ z͕ <ĂŶĂŝ͕ z͕ KŬĂĚĂ͕ z͕ EŽŶĂŬĂ͕ ^͕ dĂŬĞĚĂ͕ ^͕ ,ĂƌĂĚĂ͕ ͕ ,ŝƌŽŬĂǁĂ͕ E ;ϭϵϵϴͿ
dĂƌŐĞƚĞĚ ĚŝƐƌƵƉƚŝŽŶ ŽĨ ŵŽƵƐĞ ĐŽŶǀĞŶƚŝŽŶĂů ŬŝŶĞƐŝŶ ŚĞĂǀǇ ĐŚĂŝŶ͕ ŬŝĨϱ͕ ƌĞƐƵůƚƐ ŝŶ
ĂďŶŽƌŵĂůƉĞƌŝŶƵĐůĞĂƌĐůƵƐƚĞƌŝŶŐŽĨŵŝƚŽĐŚŽŶĚƌŝĂ͘Ğůůϵϯ;ϳͿ͗ϭϭϰϳͲϭϭϱϴ͘
dĂŶŐ͕t͕ŚĞŶ͕͕tƵ͕t͕YŝƵ͕,͕Ž͕,͕ŚĂŶŐ͕>͕&Ƶ͕W;ϮϬϭϯͿZĞŶĂůWƌŽƚĞĐƚŝǀĞĨĨĞĐƚƐ
ŽĨ ĂƌůǇ ŽŶƚŝŶƵŽƵƐ sĞŶŽǀĞŶŽƵƐ ,ĞŵŽĨŝůƚƌĂƚŝŽŶ ŝŶ ZŚĂďĚŽŵǇŽůǇƐŝƐ͗ /ŵƉƌŽǀĞĚ ZĞŶĂů
DŝƚŽĐŚŽŶĚƌŝĂůǇƐĨƵŶĐƚŝŽŶĂŶĚ/ŶŚŝďŝƚĞĚƉŽƉƚŽƐŝƐ͘ƌƚŝĨKƌŐĂŶƐ͘
dĂŶŝĚĂ͕ /͕ hĞŶŽ͕ d͕ <ŽŵŝŶĂŵŝ͕ ;ϮϬϬϰͿ >ϯ ĐŽŶũƵŐĂƚŝŽŶ ƐǇƐƚĞŵ ŝŶ ŵĂŵŵĂůŝĂŶ
ĂƵƚŽƉŚĂŐǇ͘/Ŷƚ:ŝŽĐŚĞŵĞůůŝŽůϯϲ;ϭϮͿ͗ϮϱϬϯͲϮϱϭϴ͘
dŝĂŶ͕ ͕ DƵƌƌŝŶ͕ >͕ ŚĞŶŐ͕ : ;ϮϬϬϵͿ DŝƚŽĐŚŽŶĚƌŝĂů ĨƌĂŐŵĞŶƚĂƚŝŽŶ ŝƐ ŝŶǀŽůǀĞĚ ŝŶ
ŵĞƚŚĂŵƉŚĞƚĂŵŝŶĞͲŝŶĚƵĐĞĚĐĞůůĚĞĂƚŚŝŶƌĂƚŚŝƉƉŽĐĂŵƉĂůŶĞƵƌĂůƉƌŽŐĞŶŝƚŽƌĐĞůůƐ͘W>Ž^
KŶĞϰ;ϱͿ͗Ğϱϱϰϲ͘
dŝĞƵ͕<;ϮϬϭϭͿŐƵŝĚĞƚŽŶĞƵƌŽƚŽǆŝĐĂŶŝŵĂůŵŽĚĞůƐŽĨWĂƌŬŝŶƐŽŶΖƐĚŝƐĞĂƐĞ͘ŽůĚ^ƉƌŝŶŐ
,ĂƌďWĞƌƐƉĞĐƚDĞĚϭ;ϭͿ͗ĂϬϬϵϯϭϲ͘
dŝĨĨĂŶǇͲĂƐƚŝŐůŝŽŶŝ͕ ͕ ^ĂŶĞƚŽ͕ ZW͕ WƌŽĐƚŽƌ͕ W,͕ WĞƌĞǌͲWŽůŽ͕ :Z ;ϭϵϴϮͿ WĂƌƚŝĐŝƉĂƚŝŽŶ ŽĨ
ĂĐƚŝǀĞ ŽǆǇŐĞŶ ƐƉĞĐŝĞƐ ŝŶ ϲͲŚǇĚƌŽǆǇĚŽƉĂŵŝŶĞ ƚŽǆŝĐŝƚǇ ƚŽ Ă ŚƵŵĂŶ ŶĞƵƌŽďůĂƐƚŽŵĂ ĐĞůů
ůŝŶĞ͘ŝŽĐŚĞŵWŚĂƌŵĂĐŽůϯϭ;ϮͿ͗ϭϴϭͲϭϴϴ͘
dŝǁĂƌŝ͕D;ϮϬϭϮͿƉŽƉƚŽƐŝƐĂŶĚƐƵƌǀŝǀĂů͘/ŶĚŝĂŶ:,Ƶŵ'ĞŶĞƚϭϳ;ϯͿ͗ϭϮϬͲϭϮϱ͘
ϭϭϯ
dŽŶĚĞƌĂ͕͕'ƌĂŶĚĞŵĂŶŐĞ͕^͕:ŽƵƌĚĂŝŶ͕͕<ĂƌďŽǁƐŬŝ͕D͕DĂƚƚĞŶďĞƌŐĞƌ͕z͕,ĞƌǌŝŐ͕^͕Ă
ƌƵǌ͕^͕ůĞƌĐ͕W͕ZĂƐĐŚŬĞ͕/͕DĞƌŬǁŝƌƚŚ͕͕ŚƐĞƐ͕^͕<ƌĂƵƐĞ͕&͕ŚĂŶ͕͕ůĞǆĂŶĚĞƌ͕͕
ĂƵĞƌ͕͕zŽƵůĞ͕Z͕>ĂŶŐĞƌ͕d͕DĂƌƚŝŶŽƵ͕:;ϮϬϬϵͿ^>WͲϮŝƐƌĞƋƵŝƌĞĚĨŽƌƐƚƌĞƐƐͲŝŶĚƵĐĞĚ
ŵŝƚŽĐŚŽŶĚƌŝĂůŚǇƉĞƌĨƵƐŝŽŶ͘DK:Ϯϴ;ϭϭͿ͗ϭϱϴϵͲϭϲϬϬ͘
dŽƌŶĞƌŽ͕͕ĞŶĂ͕s͕'ŽŶǌĂůĞǌͲ'ĂƌĐŝĂ͕͕:ŽƌĚĂŶ͕:;ϮϬϬϮͿdŚĞƌŽůĞŽĨƚŚĞŵŝƚŽĐŚŽŶĚƌŝĂů
ƉĞƌŵĞĂďŝůŝƚǇ ƚƌĂŶƐŝƚŝŽŶ ƉŽƌĞ ŝŶ ŶĞƵƌŽĚĞŐĞŶĞƌĂƚŝǀĞ ƉƌŽĐĞƐƐĞƐ͘ ZĞǀ EĞƵƌŽů ϯϱ;ϰͿ͗ ϯϱϰͲ
ϯϲϭ͘
dƌŝŵŵĞƌ͕ W͕ ŽƌůĂŶĚ͕ D< ;ϮϬϬϱͿ ŝĨĨĞƌĞŶƚŝĂƚĞĚ ůǌŚĞŝŵĞƌΖƐ ĚŝƐĞĂƐĞ
ƚƌĂŶƐŵŝƚŽĐŚŽŶĚƌŝĂů ĐǇďƌŝĚ ĐĞůů ůŝŶĞƐ ĞǆŚŝďŝƚ ƌĞĚƵĐĞĚ ŽƌŐĂŶĞůůĞ ŵŽǀĞŵĞŶƚ͘ ŶƚŝŽǆŝĚ
ZĞĚŽǆ^ŝŐŶĂůϳ;ϵͲϭϬͿ͗ϭϭϬϭͲϭϭϬϵ͘
dƌŽƚƚŝĞƌ͕z͕ŝĂŶĐĂůĂŶĂ͕s͕DĂŶĚĞů͕:>;ϭϵϵϰͿ/ŶƐƚĂďŝůŝƚǇŽĨ'ƌĞƉĞĂƚƐŝŶ,ƵŶƚŝŶŐƚŽŶΖƐ
ĚŝƐĞĂƐĞ͗ ƌĞůĂƚŝŽŶ ƚŽ ƉĂƌĞŶƚĂů ƚƌĂŶƐŵŝƐƐŝŽŶ ĂŶĚ ĂŐĞ ŽĨ ŽŶƐĞƚ͘ : DĞĚ 'ĞŶĞƚ ϯϭ;ϱͿ͗ ϯϳϳͲ
ϯϴϮ͘
dƵƌƌĞŶƐ͕:&;ϮϬϬϯͿDŝƚŽĐŚŽŶĚƌŝĂůĨŽƌŵĂƚŝŽŶŽĨƌĞĂĐƚŝǀĞŽǆǇŐĞŶƐƉĞĐŝĞƐ͘:WŚǇƐŝŽůϱϱϮ;Wƚ
ϮͿ͗ϯϯϱͲϯϰϰ͘
dǁŝŐ͕'͕ůŽƌǌĂ͕͕DŽůŝŶĂ͕:͕DŽŚĂŵĞĚ͕,͕tŝŬƐƚƌŽŵ͕:͕tĂůǌĞƌ͕'͕^ƚŝůĞƐ͕>͕,ĂŝŐŚ͕
^͕<Ăƚǌ͕^͕>ĂƐ͕'͕ůƌŽǇ͕:͕tƵ͕D͕WǇ͕&͕zƵĂŶ͕:͕ĞĞŶĞǇ͕:d͕ŽƌŬĞǇ͕͕^ŚŝƌŝŚĂŝ͕K^
;ϮϬϬϴͿ &ŝƐƐŝŽŶ ĂŶĚ ƐĞůĞĐƚŝǀĞ ĨƵƐŝŽŶ ŐŽǀĞƌŶ ŵŝƚŽĐŚŽŶĚƌŝĂů ƐĞŐƌĞŐĂƚŝŽŶ ĂŶĚ ĞůŝŵŝŶĂƚŝŽŶ
ďǇĂƵƚŽƉŚĂŐǇ͘DK:Ϯϳ;ϮͿ͗ϰϯϯͲϰϰϲ͘
hŶŐĞƌƐƚĞĚƚ͕ h ;ϭϵϲϴͿ ϲͲ,ǇĚƌŽǆǇͲĚŽƉĂŵŝŶĞ ŝŶĚƵĐĞĚ ĚĞŐĞŶĞƌĂƚŝŽŶ ŽĨ ĐĞŶƚƌĂů
ŵŽŶŽĂŵŝŶĞŶĞƵƌŽŶƐ͘Ƶƌ:WŚĂƌŵĂĐŽůϱ;ϭͿ͗ϭϬϳͲϭϭϬ͘
hŽ͕ d͕ ǁŽƌǌĂŬ͕ :͕ <ŝŶŽƐŚŝƚĂ͕ ͕ /ŶŵĂŶ͕ D͕ <ŝŶŽƐŚŝƚĂ͕ z͕ ,ŽƌŶĞƌ͕ W:͕ DŽƌƌŝƐŽŶ͕ Z^
;ϮϬϬϵͿ ƌƉϭ ůĞǀĞůƐ ĐŽŶƐƚŝƚƵƚŝǀĞůǇ ƌĞŐƵůĂƚĞ ŵŝƚŽĐŚŽŶĚƌŝĂů ĚǇŶĂŵŝĐƐ ĂŶĚ ĐĞůů ƐƵƌǀŝǀĂů ŝŶ
ĐŽƌƚŝĐĂůŶĞƵƌŽŶƐ͘ǆƉEĞƵƌŽůϮϭϴ;ϮͿ͗ϮϳϰͲϮϴϱ͘
sĂůĞŶƚĞ͕ D͕ ďŽƵͲ^ůĞŝŵĂŶ͕ WD͕ ĂƉƵƚŽ͕ s͕ DƵƋŝƚ͕ DD͕ ,ĂƌǀĞǇ͕ <͕ 'ŝƐƉĞƌƚ͕ ^͕ ůŝ͕ ͕
Ğů dƵƌĐŽ͕ ͕ ĞŶƚŝǀŽŐůŝŽ͕ Z͕ ,ĞĂůǇ͕ '͕ ůďĂŶĞƐĞ͕ ͕ EƵƐƐďĂƵŵ͕ Z͕ 'ŽŶǌĂůĞǌͲ
DĂůĚŽŶĂĚŽ͕ Z͕ ĞůůĞƌ͕ d͕ ^Ăůǀŝ͕ ^͕ ŽƌƚĞůůŝ͕ W͕ 'ŝůŬƐ͕ tW͕ >ĂƚĐŚŵĂŶ͕ ^͕ ,ĂƌǀĞǇ͕ Z:͕
ĂůůĂƉŝĐĐŽůĂ͕ ͕ ƵďƵƌŐĞƌ͕ '͕ tŽŽĚ͕ Et ;ϮϬϬϰͿ ,ĞƌĞĚŝƚĂƌǇ ĞĂƌůǇͲŽŶƐĞƚ WĂƌŬŝŶƐŽŶΖƐ
ĚŝƐĞĂƐĞĐĂƵƐĞĚďǇŵƵƚĂƚŝŽŶƐŝŶW/E<ϭ͘^ĐŝĞŶĐĞϯϬϰ;ϱϲϳϰͿ͗ϭϭϱϴͲϭϭϲϬ͘
sĂůĞŶǌƵĞůĂͲ&ĞƌŶĂŶĚĞǌ͕͕ĂďƌĞƌŽ͕:Z͕^ĞƌƌĂĚŽƌ͕:D͕^ĂŶĐŚĞǌͲDĂĚƌŝĚ͕&;ϮϬϬϴͿ,ϲ͗
ĂŬĞǇƌĞŐƵůĂƚŽƌŽĨĐǇƚŽƐŬĞůĞƚŽŶ͕ĐĞůůŵŝŐƌĂƚŝŽŶĂŶĚĐĞůůͲĐĞůůŝŶƚĞƌĂĐƚŝŽŶƐ͘dƌĞŶĚƐĞůůŝŽů
ϭϴ;ϲͿ͗ϮϵϭͲϮϵϳ͘
sĂŶ >ĂĂƌ͕ s^͕ ĞƌŵĂŶ͕ ^ ;ϮϬϬϵͿ DŝƚŽĐŚŽŶĚƌŝĂů ĚǇŶĂŵŝĐƐ ŝŶ WĂƌŬŝŶƐŽŶΖƐ ĚŝƐĞĂƐĞ͘ ǆƉ
EĞƵƌŽůϮϭϴ;ϮͿ͗ϮϰϳͲϮϱϲ͘
sĂƌĂĚŝ͕ ͕ :ŽŚŶƐŽŶͲĂĚǁĞůů͕ >/͕ ŝƌƵůůŝ͕ s͕ zŽŽŶ͕ z͕ ůůĂŶ͕ s:͕ ZƵƚƚĞƌ͕ ' ;ϮϬϬϰͿ
ǇƚŽƉůĂƐŵŝĐ ĚǇŶĞŝŶ ƌĞŐƵůĂƚĞƐ ƚŚĞ ƐƵďĐĞůůƵůĂƌ ĚŝƐƚƌŝďƵƚŝŽŶ ŽĨ ŵŝƚŽĐŚŽŶĚƌŝĂ ďǇ
ϭϭϰ
ĐŽŶƚƌŽůůŝŶŐ ƚŚĞ ƌĞĐƌƵŝƚŵĞŶƚ ŽĨ ƚŚĞ ĨŝƐƐŝŽŶ ĨĂĐƚŽƌ ĚǇŶĂŵŝŶͲƌĞůĂƚĞĚ ƉƌŽƚĞŝŶͲϭ͘ : Ğůů ^Đŝ
ϭϭϳ;WƚϭϵͿ͗ϰϯϴϵͲϰϰϬϬ͘
sŝůĂ͕D͕:ĂĐŬƐŽŶͲ>ĞǁŝƐ͕s͕sƵŬŽƐĂǀŝĐ͕^͕ũĂůĚĞƚƚŝ͕Z͕>ŝďĞƌĂƚŽƌĞ͕'͕KĨĨĞŶ͕͕<ŽƌƐŵĞǇĞƌ͕
^:͕WƌǌĞĚďŽƌƐŬŝ͕^;ϮϬϬϭͿĂǆĂďůĂƚŝŽŶƉƌĞǀĞŶƚƐĚŽƉĂŵŝŶĞƌŐŝĐŶĞƵƌŽĚĞŐĞŶĞƌĂƚŝŽŶŝŶƚŚĞ
ϭͲŵĞƚŚǇůͲ ϰͲƉŚĞŶǇůͲϭ͕Ϯ͕ϯ͕ϲͲƚĞƚƌĂŚǇĚƌŽƉǇƌŝĚŝŶĞ ŵŽƵƐĞ ŵŽĚĞů ŽĨ WĂƌŬŝŶƐŽŶΖƐ ĚŝƐĞĂƐĞ͘
WƌŽĐEĂƚůĐĂĚ^Đŝh^ϵϴ;ϱͿ͗ϮϴϯϳͲϮϴϰϮ͘
sŝŶĐĞŶƚ͕,<͕/ŶŶĞƐ͕<͕sŝŶĐĞŶƚ͕<Z;ϮϬϬϳͿKǆŝĚĂƚŝǀĞƐƚƌĞƐƐĂŶĚƉŽƚĞŶƚŝĂůŝŶƚĞƌǀĞŶƚŝŽŶƐ
ƚŽƌĞĚƵĐĞŽǆŝĚĂƚŝǀĞƐƚƌĞƐƐŝŶŽǀĞƌǁĞŝŐŚƚĂŶĚŽďĞƐŝƚǇ͘ŝĂďĞƚĞƐKďĞƐDĞƚĂďϵ;ϲͿ͗ϴϭϯͲ
ϴϯϵ͘
sŝƐ͕ :͕ sĞƌďĞĞŬ͕ DD͕ Ğ tĂĂů͕ ZD͕ dĞŶ ŽŶŬĞůĂĂƌ͕ ,:͕ <ƌĞŵĞƌ͕ ,W ;ϭϵϵϵͿ ϯͲ
EŝƚƌŽƉƌŽƉŝŽŶŝĐĂĐŝĚŝŶĚƵĐĞƐĂƐƉĞĐƚƌƵŵŽĨ,ƵŶƚŝŶŐƚŽŶΖƐĚŝƐĞĂƐĞͲůŝŬĞŶĞƵƌŽƉĂƚŚŽůŽŐǇŝŶ
ƌĂƚƐƚƌŝĂƚƵŵ͘EĞƵƌŽƉĂƚŚŽůƉƉůEĞƵƌŽďŝŽůϮϱ;ϲͿ͗ϱϭϯͲϱϮϭ͘
sŝǀĞƐͲĂƵǌĂ͕͕ĚĞsƌŝĞƐ͕Z>͕dŽĐŝůĞƐĐƵ͕D͕WƌǌĞĚďŽƌƐŬŝ͕^;ϮϬϬϵͿ/ƐƚŚĞƌĞĂƉĂƚŚŽŐĞŶŝĐ
ƌŽůĞ ĨŽƌ ŵŝƚŽĐŚŽŶĚƌŝĂ ŝŶ WĂƌŬŝŶƐŽŶΖƐ ĚŝƐĞĂƐĞ͍ WĂƌŬŝŶƐŽŶŝƐŵ ZĞůĂƚ ŝƐŽƌĚ ϭϱ ^ƵƉƉů ϯ͗
^ϮϰϭͲϮϰϰ͘
sŝǀĞƐͲĂƵǌĂ͕ ͕ WƌǌĞĚďŽƌƐŬŝ͕ ^ ;ϮϬϭϭͿ DŝƚŽƉŚĂŐǇ͗ ƚŚĞ ůĂƚĞƐƚ ƉƌŽďůĞŵ ĨŽƌ WĂƌŬŝŶƐŽŶΖƐ
ĚŝƐĞĂƐĞ͘dƌĞŶĚƐDŽůDĞĚϭϳ;ϯͿ͗ϭϱϴͲϭϲϱ͘
ǀŽŶŽĞůůŶ͕Z͕<ƵŐůĞƌ͕^͕ĂŚƌ͕D͕tĞůůĞƌ͕D͕ŝĐŚŐĂŶƐ͕:͕^ĐŚƵůǌ͕:;ϮϬϬϭͿZĞƐĐƵĞĨƌŽŵ
ĚĞĂƚŚ ďƵƚ ŶŽƚ ĨƌŽŵ ĨƵŶĐƚŝŽŶĂů ŝŵƉĂŝƌŵĞŶƚ͗ ĐĂƐƉĂƐĞ ŝŶŚŝďŝƚŝŽŶ ƉƌŽƚĞĐƚƐ ĚŽƉĂŵŝŶĞƌŐŝĐ
ĐĞůůƐ ĂŐĂŝŶƐƚ ϲͲŚǇĚƌŽǆǇĚŽƉĂŵŝŶĞͲŝŶĚƵĐĞĚ ĂƉŽƉƚŽƐŝƐ ďƵƚ ŶŽƚ ĂŐĂŝŶƐƚ ƚŚĞ ůŽƐƐ ŽĨ ƚŚĞŝƌ
ƚĞƌŵŝŶĂůƐ͘:EĞƵƌŽĐŚĞŵϳϳ;ϭͿ͗ϮϲϯͲϮϳϯ͘
sŽŶƐĂƚƚĞů͕ :W͕ ŝ&ŝŐůŝĂ͕D ;ϭϵϵϴͿ ,ƵŶƚŝŶŐƚŽŶĚŝƐĞĂƐĞ͘ : EĞƵƌŽƉĂƚŚŽů ǆƉ EĞƵƌŽů ϱϳ;ϱͿ͗
ϯϲϵͲϯϴϰ͘
tĂŬĂďĂǇĂƐŚŝ͕:͕ŚĂŶŐ͕͕tĂŬĂďĂǇĂƐŚŝ͕E͕dĂŵƵƌĂ͕z͕&ƵŬĂǇĂ͕D͕<ĞŶƐůĞƌ͕dt͕/ŝũŝŵĂ͕
D͕^ĞƐĂŬŝ͕,;ϮϬϬϵͿdŚĞĚǇŶĂŵŝŶͲƌĞůĂƚĞĚ'dWĂƐĞƌƉϭŝƐƌĞƋƵŝƌĞĚĨŽƌĞŵďƌǇŽŶŝĐĂŶĚ
ďƌĂŝŶĚĞǀĞůŽƉŵĞŶƚŝŶŵŝĐĞ͘:ĞůůŝŽůϭϴϲ;ϲͿ͗ϴϬϱͲϴϭϲ͘
tĂůŬŝŶƐŚĂǁ͕ '͕ tĂƚĞƌƐ͕ D ;ϭϵϵϰͿ EĞƵƌŽƚŽǆŝŶͲŝŶĚƵĐĞĚ ĐĞůů ĚĞĂƚŚ ŝŶ ŶĞƵƌŽŶĂů WϭϮ
ĐĞůůƐŝƐŵĞĚŝĂƚĞĚďǇŝŶĚƵĐƚŝŽŶŽĨĂƉŽƉƚŽƐŝƐ͘EĞƵƌŽƐĐŝĞŶĐĞϲϯ;ϰͿ͗ϵϳϱͲϵϴϳ͘
tĂŶŐ͕y͕^Ƶ͕͕&ƵũŝŽŬĂ͕,͕ŚƵ͕y;ϮϬϬϴĂͿǇŶĂŵŝŶͲůŝŬĞƉƌŽƚĞŝŶϭƌĞĚƵĐƚŝŽŶƵŶĚĞƌůŝĞƐ
ŵŝƚŽĐŚŽŶĚƌŝĂůŵŽƌƉŚŽůŽŐǇĂŶĚĚŝƐƚƌŝďƵƚŝŽŶĂďŶŽƌŵĂůŝƚŝĞƐŝŶĨŝďƌŽďůĂƐƚƐĨƌŽŵƐƉŽƌĂĚŝĐ
ůǌŚĞŝŵĞƌΖƐĚŝƐĞĂƐĞƉĂƚŝĞŶƚƐ͘ŵ:WĂƚŚŽůϭϳϯ;ϮͿ͗ϰϳϬͲϰϴϮ͘
tĂŶŐ͕ y͕ ^Ƶ͕ ͕ ^ŝĞĚůĂŬ͕ ^>͕ DŽƌĞŝƌĂ͕ W/͕ &ƵũŝŽŬĂ͕ ,͕ tĂŶŐ͕ z͕ ĂƐĂĚĞƐƵƐ͕ '͕ ŚƵ͕ y
;ϮϬϬϴďͿ ŵǇůŽŝĚͲďĞƚĂ ŽǀĞƌƉƌŽĚƵĐƚŝŽŶ ĐĂƵƐĞƐ ĂďŶŽƌŵĂů ŵŝƚŽĐŚŽŶĚƌŝĂů ĚǇŶĂŵŝĐƐ ǀŝĂ
ĚŝĨĨĞƌĞŶƚŝĂůŵŽĚƵůĂƚŝŽŶŽĨŵŝƚŽĐŚŽŶĚƌŝĂůĨŝƐƐŝŽŶͬĨƵƐŝŽŶƉƌŽƚĞŝŶƐ͘WƌŽĐEĂƚůĐĂĚ^Đŝh^
ϭϬϱ;ϰϵͿ͗ϭϵϯϭϴͲϭϵϯϮϯ͘
ϭϭϱ
tĂƐŝĂŬ͕^͕ƵŶŝŶŽ͕Z͕DĐƌŝĚĞ͕,D;ϮϬϬϳͿĂǆͬĂŬƉƌŽŵŽƚĞƐƵŵŽǇůĂƚŝŽŶŽĨZWϭĂŶĚ
ŝƚƐƐƚĂďůĞĂƐƐŽĐŝĂƚŝŽŶǁŝƚŚŵŝƚŽĐŚŽŶĚƌŝĂĚƵƌŝŶŐĂƉŽƉƚŽƚŝĐĐĞůůĚĞĂƚŚ͘:ĞůůŝŽůϭϳϳ;ϯͿ͗
ϰϯϵͲϰϱϬ͘
tĂƐŝůĞǁƐŬŝ͕ D͕ ^ĐŽƌƌĂŶŽ͕ > ;ϮϬϬϵͿ dŚĞ ĐŚĂŶŐŝŶŐ ƐŚĂƉĞ ŽĨ ŵŝƚŽĐŚŽŶĚƌŝĂů ĂƉŽƉƚŽƐŝƐ͘
dƌĞŶĚƐŶĚŽĐƌŝŶŽůDĞƚĂďϮϬ;ϲͿ͗ϮϴϳͲϮϵϰ͘
tĞŝ͕D͕ŽŶŐ͕ty͕ŚĞŶŐ͕,͕>ŝŶĚƐƚĞŶ͕d͕WĂŶŽƵƚƐĂŬŽƉŽƵůŽƵ͕s͕ZŽƐƐ͕:͕ZŽƚŚ͕<͕
DĂĐ'ƌĞŐŽƌ͕ 'Z͕ dŚŽŵƉƐŽŶ͕ ͕ <ŽƌƐŵĞǇĞƌ͕ ^: ;ϮϬϬϭͿ WƌŽĂƉŽƉƚŽƚŝĐ y ĂŶĚ <͗ Ă
ƌĞƋƵŝƐŝƚĞ ŐĂƚĞǁĂǇ ƚŽ ŵŝƚŽĐŚŽŶĚƌŝĂů ĚǇƐĨƵŶĐƚŝŽŶ ĂŶĚ ĚĞĂƚŚ͘ ^ĐŝĞŶĐĞ ϮϵϮ;ϱϱϭϳͿ͗ ϳϮϳͲ
ϳϯϬ͘
tĞƐƚĞƌŵĂŶŶ͕ ;ϮϬϬϮͿ DĞƌŐŝŶŐ ŵŝƚŽĐŚŽŶĚƌŝĂ ŵĂƚƚĞƌƐ͗ ĐĞůůƵůĂƌ ƌŽůĞ ĂŶĚ ŵŽůĞĐƵůĂƌ
ŵĂĐŚŝŶĞƌǇŽĨŵŝƚŽĐŚŽŶĚƌŝĂůĨƵƐŝŽŶ͘DKZĞƉϯ;ϲͿ͗ϱϮϳͲϱϯϭ͘
tĞƐƚĞƌŵĂŶŶ͕;ϮϬϭϬͿDŝƚŽĐŚŽŶĚƌŝĂůĨƵƐŝŽŶĂŶĚĨŝƐƐŝŽŶŝŶĐĞůůůŝĨĞĂŶĚĚĞĂƚŚ͘EĂƚZĞǀ
DŽůĞůůŝŽůϭϭ;ϭϮͿ͗ϴϳϮͲϴϴϰ͘
tŝŬƐƚƌŽŵ͕:͕dǁŝŐ͕'͕^ŚŝƌŝŚĂŝ͕K^;ϮϬϬϵͿtŚĂƚĐĂŶŵŝƚŽĐŚŽŶĚƌŝĂůŚĞƚĞƌŽŐĞŶĞŝƚǇƚĞůů
ƵƐĂďŽƵƚŵŝƚŽĐŚŽŶĚƌŝĂůĚǇŶĂŵŝĐƐĂŶĚĂƵƚŽƉŚĂŐǇ͍/Ŷƚ:ŝŽĐŚĞŵĞůůŝŽůϰϭ;ϭϬͿ͗ϭϵϭϰͲ
ϭϵϮϳ͘
tŝůĨůŝŶŐ͕ &͕ tĞďĞƌ͕ ͕ WŽƚƚŚŽĨĨ͕ ^͕ sŽŐƚůĞ͕ &E͕ DĞŝƐŝŶŐĞƌ͕ ͕ WĂƐĐŚĞŶ͕ ^͕ ,ĂĐŬĞƌ͕ '
;ϮϬϭϮͿ,ϯͲŽŶůǇƉƌŽƚĞŝŶƐĂƌĞƚĂŝůͲĂŶĐŚŽƌĞĚŝŶƚŚĞŽƵƚĞƌŵŝƚŽĐŚŽŶĚƌŝĂůŵĞŵďƌĂŶĞĂŶĚ
ĐĂŶŝŶŝƚŝĂƚĞƚŚĞĂĐƚŝǀĂƚŝŽŶŽĨĂǆ͘ĞůůĞĂƚŚŝĨĨĞƌ͘
tŽŽĚͲ<ĂĐǌŵĂƌ͕ ͕ 'ĂŶĚŚŝ͕ ^͕ zĂŽ͕ ͕ ďƌĂŵŽǀ͕ z͕ DŝůũĂŶ͕ ͕ <ĞĞŶ͕ '͕ ^ƚĂŶǇĞƌ͕ >͕
,ĂƌŐƌĞĂǀĞƐ͕/͕<ůƵƉƐĐŚ͕<͕ĞĂƐ͕͕ŽǁŶǁĂƌĚ͕:͕DĂŶƐĨŝĞůĚ͕>͕:Ăƚ͕W͕dĂǇůŽƌ͕:͕,ĞĂůĞƐ͕^͕
ƵĐŚĞŶ͕ DZ͕ >ĂƚĐŚŵĂŶ͕ ͕ dĂďƌŝǌŝ͕ ^:͕ tŽŽĚ͕ Et ;ϮϬϬϴͿ W/E<ϭ ŝƐ ŶĞĐĞƐƐĂƌǇ ĨŽƌ ůŽŶŐ
ƚĞƌŵ ƐƵƌǀŝǀĂů ĂŶĚ ŵŝƚŽĐŚŽŶĚƌŝĂů ĨƵŶĐƚŝŽŶ ŝŶ ŚƵŵĂŶ ĚŽƉĂŵŝŶĞƌŐŝĐ ŶĞƵƌŽŶƐ͘ W>Ž^ KŶĞ
ϯ;ϲͿ͗ĞϮϰϱϱ͘
tƵ͕ ^͕ ŚŽƵ͕ &͕ ŚĂŶŐ͕ ͕ yŝŶŐ͕ ;ϮϬϭϭͿ Ăǆ ŝƐ ĞƐƐĞŶƚŝĂů ĨŽƌ ƌƉϭͲŵĞĚŝĂƚĞĚ
ŵŝƚŽĐŚŽŶĚƌŝĂů ĨŝƐƐŝŽŶ ďƵƚ ŶŽƚ ĨŽƌ ŵŝƚŽĐŚŽŶĚƌŝĂů ŽƵƚĞƌ ŵĞŵďƌĂŶĞ ƉĞƌŵĞĂďŝůŝǌĂƚŝŽŶ
ĐĂƵƐĞĚďǇƉŚŽƚŽĚǇŶĂŵŝĐƚŚĞƌĂƉǇ͘:ĞůůWŚǇƐŝŽůϮϮϲ;ϮͿ͗ϱϯϬͲϱϰϭ͘
yƵ͕ :y ;ϮϬϬϰͿ ZĂĚŝĐĂů ŵĞƚĂďŽůŝƐŵ ŝƐ ƉĂƌƚŶĞƌ ƚŽ ĞŶĞƌŐǇ ŵĞƚĂďŽůŝƐŵ ŝŶ ŵŝƚŽĐŚŽŶĚƌŝĂ͘
ŶŶEzĐĂĚ^ĐŝϭϬϭϭ͗ϱϳͲϲϬ͘
zĂĨĨĞ͕ DW ;ϭϵϵϵͿ dŚĞ ŵĂĐŚŝŶĞƌǇ ŽĨ ŵŝƚŽĐŚŽŶĚƌŝĂů ŝŶŚĞƌŝƚĂŶĐĞ ĂŶĚ ďĞŚĂǀŝŽƌ͘ ^ĐŝĞŶĐĞ
Ϯϴϯ;ϱϰϬϳͿ͗ϭϰϵϯͲϭϰϵϳ͘
zĂŬĞƐ͕ &D͕ sĂŶ ,ŽƵƚĞŶ͕ ;ϭϵϵϳͿ DŝƚŽĐŚŽŶĚƌŝĂů E ĚĂŵĂŐĞ ŝƐ ŵŽƌĞ ĞǆƚĞŶƐŝǀĞ ĂŶĚ
ƉĞƌƐŝƐƚƐ ůŽŶŐĞƌ ƚŚĂŶ ŶƵĐůĞĂƌ E ĚĂŵĂŐĞ ŝŶ ŚƵŵĂŶ ĐĞůůƐ ĨŽůůŽǁŝŶŐ ŽǆŝĚĂƚŝǀĞ ƐƚƌĞƐƐ͘
WƌŽĐEĂƚůĐĂĚ^Đŝh^ϵϰ;ϮͿ͗ϱϭϰͲϱϭϵ͘
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ƉĂƌŬŝŶƐŽŶŝƐŵǁŝƚŚƉůĞŽŵŽƌƉŚŝĐƉĂƚŚŽůŽŐǇ͘EĞƵƌŽŶϰϰ;ϰͿ͗ϲϬϭͲϲϬϳ͘
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ŶŝƚƌŝĐ ŽǆŝĚĞͲŵĞĚŝĂƚĞĚ ĚĞůĂǇĞĚ ǀĂƐĐƵůĂƌ ĨĂŝůƵƌĞ ŝŶ ĞŶĚŽƚŽǆŝĐ ƐŚŽĐŬ͗ ƉŽƚĞŶƚŝĂů
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ϭϭϳ
Hindawi Publishing Corporation
Parkinson’s Disease
Volume 2012, Article ID 131058, 8 pages
doi:10.1155/2012/131058
Review Article
Mitochondrial Dynamics and Mitophagy in the
6-Hydroxydopamine Preclinical Model of Parkinson’s Disease
Maria F. Galindo,1 Maria E. Solesio,1 Sandra Atienzar-Aroca,2
Maria J. Zamora,1, 2 and Joaquı́n Jordán Bueso2
1 Unidad
de Neuropsicofarmacologı́a Traslacional, Complejo Hospitalario Universitario de Albacete,
C/Hermanos Falcó 37, 02006 Albacete, Spain
2 Grupo de Neurofarmacologı́a, Departamento Ciencias Médicas, Facultad de Medicina de Albacete,
Universidad Castilla-La Mancha, IDINE, 02006 Albacete, Spain
Correspondence should be addressed to Maria F. Galindo, [email protected] and
Joaquı́n Jordán Bueso, [email protected]
Received 27 June 2012; Accepted 18 July 2012
Academic Editor: José Manuel Fuentes Rodrı́guez
Copyright © 2012 Maria F. Galindo et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
We discuss the participation of mitochondrial dynamics and autophagy in the 6-hydroxidopamine-induced Parkinson’s disease
model. The regulation of dynamic mitochondrial processes such as fusion, fission, and mitophagy has been shown to be an
important mechanism controlling cellular fate. An imbalance in mitochondrial dynamics may contribute to both familial and
sporadic neurodegenerative diseases including Parkinson’s disease. With special attention we address the role of second messengers
as the role of reactive oxygen species and the mitochondria as the headquarters of cell death. The role of molecular signaling
pathways, for instance, the participation of Dynamin-related protein 1(Drp1), will also be addressed. Furthermore evidence
demonstrates the therapeutic potential of small-molecule inhibitors of mitochondrial division in Parkinson’s disease. For instance,
pharmacological inhibition of Drp1, through treatment with the mitochondrial division inhibitor-1, results in the abrogation
of mitochondrial fission and in a decrease of the number of autophagic cells. Deciphering the signaling cascades that underlie
mitophagy triggered by 6-OHDA, as well as the mechanisms that determine the selectivity of this response, will help to better
understand this process and may have impact on human treatment strategies of Parkinson’s disease.
1. Introduction
Parkinson’s disease (PD) is progressive neurodegenerative
condition that is characterized by the presence of motor
and nonmotor symptoms, of which the etiology remains
poorly understood. Nevertheless, a broad range of studies
conducted over the past few decades have collectively
identified a number of molecular/cellular events that might
underlie PD pathogenesis. In particular, the participation of
mitochondrial-mediated pathways has provided tremendous
insights into the molecular pathways underlying dopaminergic neurodegeneration. Mitochondria can be considered
as headquarters where the cell controls signaling pathways
that under some circumstances can lead to cell death [1, 2].
Mitochondrial membrane permeabilization is a critical event
during apoptosis and represents the point of no return of
this lethal process [3]. For instance, the permeabilization of
the mitochondrial outer membrane (MOMP), which allows
the release of mitochondrial death factors, facilitates or
triggers different signaling cascades that ultimately cause the
execution of cell death. In many PD experimental models,
including the addition of parkinsonian neurotoxins to cell
cultures, the participation of MOMP has been described,
resulting in the release of cytochrome c from mitochondria
[4].
In the past, mitochondria have been suggested to be
filamentous, rigid, and static organelles incrusted into the
cytosol with the only function of being the main source or
energy to the cell in the form of ATP. In fact, mitochondria
are dynamic and mobile organelles that constantly undergo
membrane remodeling through repeated cycles of fusion
and fission. In addition, regulated turnover occurs via a
2
specialized lysosome-mediated degradation pathway known
as “mitophagy,” a term originally coined by Lemasters [5].
6-Hydroxydopamine (6-OHDA), also known as oxidopamine or 2,4,5-trihydroxyphenethylamine (C8 H11 NO3 ),
is a toxic oxidative metabolite of dopamine and is detected in
the brains and urine of Parkinson’s disease (PD) patients. It
has been applied broadly to generate experimental models of
Parkinson’s disease. There is accumulating evidence from in
vitro and in vivo studies, implicating cell death in the etiology
of the 6-OHDA model of PD [6–9].
2. 6-OHDA and Mitochondrial Dynamics
The regulation of mitochondrial dynamics processes such as
fusion, fission, and mitophagy, signifies an important mechanism controlling cellular fate [10]. Mitochondrial fission
and fusion are antagonistic activities. Their fundamental
roles are to create a compartment that is a connected conductor, which is able to mix its contents. Also, they function
to have access to mtDNA and its products in order to be
distributed to distant cellular destinations through transport
via actin or microtubule networks. The importance of
mitochondrial dynamics to cellular function is perhaps best
appreciated in neurons. These postmitotic cells, particularly
those with vast axonal field, require high energy to support
their operations, which include the active transportation of
components (including mitochondria) toward metabolically
demanding synaptic terminals that are distally located.
An imbalance in mitochondrial dynamics may contribute to both familial and sporadic neurodegenerative
diseases including PD [11–14]. Evidence exists suggesting
that an amplification of fission events can cause pathogenesis
of human PD. Stress stimuli that are used to study PD,
such as rotenone [15], annonacin [16], and 6-OHDA
[17], are capable of inducing mitochondrial fission. Also,
human fibroblasts from PD patients exhibit elevated levels
of fragmented mitochondria [18].
Evidence has been presented showing that tipping
the equilibrium toward continuous mitochondrial fission
can evoke a neurodegenerative cascade [19]. Intriguingly,
inherited loss-of-function mutations of MFN2 or OPA1
cause progressive neuropathies in humans. MFN2 mutations
cause Charcot-Marie-Tooth type 2A (CMT-2A), a peripheral
neuropathy characterized by motor and sensory neuron
loss [20]. OPA1 mutations cause autosomal dominant optic
atrophy, which is characterized by retinal ganglion cell and
optic nerve degeneration [21].
In the dopaminergic cell line SH-SY5Y, using immunofluorescence studies with antibodies raised against the
mitochondrial matrix protein MnSOD, we have shown that
in untreated cells mitochondria exhibited a predominantly
elongated and filamentous morphology. Strikingly, after
addition of 50 µM 6-OHDA mitochondria formed short
and spherical structures, due to the fragmentation of single
filamentous mitochondria into multiple isolated organelles
[17]. Furthermore, time-lapse fluorescence microscopy
revealed that 6-OHDA-induced mitochondrial fragmentation occurred rapidly and synchronous within 15 min after
6-OHDA addition and was visible in approximately 80%
of the cells after 3 h. Thus, mitochondrial fragmentation
appears to be an early event in 6-OHDA-induced cell
death. Nevertheless, significant changes in the chromatin
structure were not detected early on. 6-OHDA (50 µM) had
to be present more than 9 h to initiate significant changes
in mitochondrial membrane potential in SH-SY5Y cells,
placing mitochondrial alterations in an early stage of 6OHDA-activated pathways.
Mitochondrial fission is highly regulated process and is
mediated by a defined set of proteins [22–25]. One of these
proteins, Dynamin-related protein 1 (Drp1), is a member of
the dynamin family of large GTPases and mediates the scission of mitochondrial membranes through GTP hydrolysis.
Drp1 predominantly is a cytoplasmic protein and associates
with mitochondrial fission sites upon oligomerization [26,
27]. How Drp1 mediates outer membrane scission is unclear
but it has been proposed that, similar to Dynamin, it
may act as a mechanoenzyme [28]. Upon activation by an
unknown mechanism, Drp1 assembles via Fis1 [29] into
large complexes at future scission sites (cut sites) on the
inner mitochondrial membrane [30]. Overexpression of Fis1
can induce directly both mitochondrial fragmentation and
apoptosis [29]. However, Fis1 or mitochondrial fission is
not requisites for apoptosis since cytochrome c release is
prevented in cells overexpressing Fis1 when proapoptotic
Bax/Bak are inactivated [31, 32].
Indicating that mitochondrial fission process may be
important for apoptosis, dominant-negative forms of Drp1
that antagonize mitochondrial division delay the release of
cytochrome c and the onset of cell death [33], although,
not as potently as some antiapoptotic Bcl-2 family members, such as Bcl-xL. Moreover, ectopic Mfn2, Opa1, and
mutant forms of Opa1 can also confer protection against
programmed cell death [34–36].
We have revealed that 6-OHDA requires the dynaminlike GTPase Drp1 to induce mitochondrial division. We have
also observed that Drp1 translocated to mitochondria 3 h
after addition of 50 µM 6-OHDA, although the levels of
total Drp1 were unchanged in cellular extracts [37]. When
SH-SY5Y cells were transfected with Drp1 siRNA duplexes
to silence Drp1, 6-OHDA-induced mitochondrial fragmentation was inhibited. Furthermore, 6-OHDA-induced cell
death was reduced after silencing of Drp1. In line with these
findings, inhibition of Drp1 function in other experimental
models has also been shown to prevent mitochondrial fission
and cell death [33, 38, 39]. In a recent report, a block in mitochondrial fission by the expression of dominant-negative
Drp1 or wild-type Mfn1 prevented mitochondrial fragmentation and rescued neurons from nitric- oxide- (NO-)
induced degeneration and cell death.
Nowadays we have the pharmacological possibility of
inhibiting Drp1 activity. For instance, Cassidy-Stone and
colleagues [40] have identified an inhibitor of mitochondrial
division, called mitochondrial division inhibitor-1 (mdivi1), using yeast screens of chemical libraries. Mdivi-1 reduces
mitochondrial fission after several insults [40, 41]. Mdivi1 inhibits Dnm1 assembly and GTPase activity in vitro.
Examining the activity of a series of mdivi-1 analogs shows
a correlation between the degree of inhibition of GTPase
activity and the extent of inhibition of yeast mitochondrial
fission. Recently, another group identified an inhibitor of
Dynamin-1, Dynamin-2, and DRP1, called Dynasore, which
binds the GTPase domain and inhibits GTPase activity [42].
Mdivi-1 appears to be more selective than Dynasore, as it
affects neither the activity of the Dynamin-1 GTPase in vitro
nor that of the two mitochondrial dynamin family members
mediating yeast mitochondrial fusion, Fzo1 or Mgm1. This
is because mdivi-1 does not inhibit mitochondrial fusion
in vivo. This specificity has been proposed to stem from
mdivi-1 binding outside the GTPase domain to a surface
that is involved in oligomeric assembly, thereby inhibiting
Dnm1/DRP1 GTPase activation. Mechanistically, mdivi-1
acts as a mixed-type inhibitor to attenuate the early stages
of division DRP assembly by preventing the polymerization
of higher-order structures. Mdivi-1 selectively targets the
unassembled pool of the mitochondrial division dynamin,
and its binding creates and/or stabilizes an assemblydeficient conformation [43]. Furthermore, inhibiting mitochondrial division with mdivi-1 in Parkinson’s disease cell
culture models or a dominant negative form of Drp1 in
Alzheimer’s and Huntington’s disease cell culture models
attenuates disease-associated phenotypes [44]. For a review
see [43].
Alternatively, mitochondrial dynamics may be initiated
by insertion of the protooncogene Bcl-2 family into the
MOM. The Bcl-2 family is composed of about 25 key regulators of apoptotic processes. These proteins are structural
and functional homologs of the nematode protein CED9 and are localized in the mitochondrial membrane. They
contain up to four regions with a high homology to Bcl-2
(regions BH 1 to 4) [45]. Members containing only the BH3
region are proapoptotic proteins, and among them are Bax
(X Bcl-2-associated protein), Bak (Bcl-2-antagonist/killer),
BIM, and BID. Inactive Bax resides in the cytosol or is
anchored to the laxly face of the membranes of various
organelles [46]. Recently, several members of Bcl-2 family,
including both, pro- and antiapoptotic proteins, have been
shown to play a role in mitochondrial morphogenesis in
healthy cells [37, 47]. Finding that Bax and Bak promote
mitochondrial fusion in healthy cells [47] was unanticipated,
as Bax and Bak form foci that colocalize with ectopic Mfn2
and Drp1 at the sites of mitochondrial division to promote
mitochondrial fission during apoptosis [47]. After a cell
death signal, the Bax protein acquires a homooligomeric
shape and is incorporated into the outer mitochondrial
membrane. Postmortem studies indicated that the presence
of Bax and its translocation to the outer mitochondrial
membrane may contribute to the death of dopaminergic
neurons in PD [48]. In addition, the proapoptotic Bax protein colocalized to scission sites on mitochondria, suggesting
that the mitochondrial fission machinery cooperates with the
cell death machinery [49]. We have shown that Bax actively
participates in the 6-OHDA preclinical model of PD [4, 17].
Furthermore, in our experimental model, mitochondrial Bax
translocation took place after mitochondrial fragmentation
and Drp1 translocation. SH-SY5Y cells consistently showed
3
mitochondrial Bax localization 6 h after 6-OHDA addition.
We were unable to find mitochondrial Bax-aggregation
loci at the very early time points where mitochondrial
fragmentation was already evident (<3 h of treatment).
On the other hand, 6-OHDA-induced mitochondrial Bax
translocation was independent of Drp1 and mitochondrial
fission. Thus, Mdivi-1 failed to abrogate the translocation
of Bax to the mitochondria upon 6-OHDA additions. In
agreement with this, in Drp1−/− cells [50] or in cells that were
transfected with a dominant negative allele, DrpK38A, that is
defective in GTP binding [33, 39, 49, 51], Bax translocates to
the mitochondria with kinetics similar to those observed in
wild-type cells.
In addition, several studies have reported that preventing
mitochondrial fission during apoptosis leads to a partial
inhibition of cytochrome c release [33, 35, 36, 38, 51]. Mitochondrial fission is not required for cell death. However, this
does not exclude that fragmentation of the mitochondrial
network might potentiate cell death.
Mitochondrial dynamics has also been proposed to play a
role in the quality control of the organelle. During a division
event, functionally asymmetric daughter mitochondria with
different membrane potentials can be produced. The functional daughter, which retains a high membrane potential,
can refuse with the mitochondrial network, whereas the
dysfunctional daughter cannot refuse due to the low membrane potential and is subsequently flagged for autophagic
degradation [52, 53].
3. 6-OHDA Inductors of Autophagy
The mitochondrial quality control hypothesis postulates that
dysfunctional mitochondria are susceptible to degradation
[53]. Autophagy is a stress-induced catabolic process involving the lysosome (or, in yeast, the analogous vacuole),
which is conserved in all eukaryotes [54, 55]. According to
the different pathways by which cargo is delivered to the
lysosome or vacuole, autophagy is divided into three main
types: chaperone-mediated autophagy, microautophagy, and
macroautophagy [56]. Among the three main forms of
autophagy, macroautophagy is the most widely studied
and best characterized process. Macroautophagy, hereafter
referred to as autophagy, is characterized by the formation
of a cytosolic double-membrane vesicle, the autophagosome.
During autophagy, cytoplasmic proteins, organelles or other
materials are surrounded by phagophores, which expand
and close to form autophagosomes. These autophagosomes
fuse with lysosomes (or vacuoles) to form autolysosomes,
in which the cytoplasmic cargos are degraded by resident
hydrolases. The resulting degradation products are then
transported back into the cytosol through the activity of
membrane permeases for reuse [57]. Although autophagy
is generally considered to be nonspecific, there are many
examples of selective autophagy, including mitophagy (for
mitochondria), ribophagy (for ribosomes), pexophagy (for
peroxisomes), and reticulophagy (for the endoplasmic reticulum, ER) [58].
4
p-quinones
H2 O2
6-OHDA
•OH−
•O2 −
Drp1
ROS
PTP
ROS
Fis
Autophagy
Bax
Cyt c
Atg5-12-16
LC3-I
Apoptosome
Caspases
LC3-II
Cell death
Lysosome
Figure 1: Mitochondrial fission and autophagy events are activated after 6-OHDA addition. Drp1 and Bax translocate from the cytosol to
mitochondria. Drp1 has been proposed to encircle mitochondria to mediate constriction and this is followed by scission, which results in the
formation of two separate mitochondria. Mitochondrial fission may play a role in the removal of dysfunctional mitochondria with reduced
mitochondrial membrane potential, through an autophagy-lysosomal pathway named “mitophagy.”
The primary role of autophagy is to protect cells under
stress conditions such as starvation. During periods of starvation, autophagy degrades cytoplasmic materials to produce
amino acids and fatty acids that can be used to synthesize
new proteins or are oxidized by mitochondria to produce
ATP for cell survival [59]. However, when autophagy is
excessively induced, it can result in autophagic cell death, socalled type II programmed cell death [60, 61] (Figure 1). In
addition to stress management, autophagy is involved in normal development [60], senescence [62], lifespan extension
[63], immunity, and defense against microbial invasion [64].
In particular, autophagy has been observed to be deregulated
in PD brains [65]. Consistent with these observations,
suppression of basal autophagy causes neurodegeneration in
mice [66]. Moreover, rapamycin, a well-known autophagic
inducer, protects from PD toxins [67].
Unfortunately, to date it remains unknown what the
underlying mechanisms of autophagy are in terms of procell
survival versus procell death effects. Therefore, mechanisms
that underlie these dual functions of autophagy (cell survival
and cell death) need to be explored in the future. There are
several hypotheses. The procell death effect of autophagy
could be related to the activation of apoptosis, which would
imply that autophagy is an upstream event of apoptosis
[68]. For the cytoprotective effect of autophagy against stress,
one possible mechanism for autophagic cell death could
involve the autophagic degradation of a negative effector
of apoptosis. This is supported by a recent demonstration
that autophagic degradation of the Drosophila inhibitor of
apoptosis (IAP) dBruce controls apoptotic cell death in nurse
cells during late Drosophila melanogaster oogenesis [68].
Alternatively, autophagic degradation of active caspase-8, a
positive effector of apoptosis, may also be responsible for the
inhibition of apoptotic cell death in mammalian cells [69].
Autophagy is induced by 6-OHDA treatment. The 6OHDA-induced autophagy correlated with an increase in the
LC3-II protein level and with the accumulation of autophagic
vacuoles in the cytoplasm and the activation of lysosomes
[70]. It remains to be determined whether the induction of
autophagy by 6-OHDA is related to cell death or to a cytoprotective response, which is activated by dying cells in order
to cope with stress. In a previous study, tyrosine hydrolasepositive neurons in substantia nigra were protected from 6OHDA-induced cell death when they were pretreated with
the autophagy inhibitor 3-methyladenine [70]. On the other
hand, experiments using neuron-specific knockout mouse
models have demonstrated that autophagy deficiency leads
to protein aggregation and neurodegeneration, even in the
absence of disease-related aggregate-prone proteins [58].
4. ROS as Second Messengers in
6-OHDA-Induced Pathways
Reactive oxygen species (ROS) are important for execution
of physiological functions. However, excessive production of
ROS is detrimental to the cell. Following an increase in ROS
production, the cell’s redox equilibrium is shifted to a more
oxidized state, affecting both the structure and the function
of different molecules. This may lead to specific toxic
processes, which compromise the redox status of the cell and
can cause cell death. Due to high levels of polyunsaturated
fatty acids in their membranes and the relatively low activity
of endogenous antioxidant enzymes, cells in the brain are
particularly susceptible to oxidative damage.
On the other hand, ROS are able to induce pore opening
[71]. Exposure of mitochondria to these species causes a
decrease in the content of thiol residues in the membrane.
It also leads to a collapse of the mitochondrial electrical
transmembrane potential [72], which is prevented by the
presence of antioxidant drugs like vitamin E and glutathione.
Under physiological conditions, 6-OHDA is rapidly and
nonenzymatically oxidized by molecular oxygen to form
1,4-para-quinone and its degradation products [73], along
with production of ROS such as hydrogen peroxide (H2 O2 ),
superoxide radical (O2 − ) and hydroxyl radical (• OH− ).
Quinones react with nucleotic groups of macromolecules,
leading to inactive or destroyed quinoproteins, which do not
seem to contribute significantly to the observed cytotoxic
effects of 6-OHDA. H2 O2 can enter the cells and reacts with
trace metals to form highly reactive • OH− [74]. This can
oxidatively damage proteins, lipids, and DNA [75]. We have
shown that 6-OHDA concentrations that were nontoxic to
cell cultures did not significantly increase H2 O2 production
[76]. Moreover, H2 O2 addition to cultures produced a
pattern of cell death similar to 6-OHDA.
In addition to the non-enzymatic self-auto-oxidation
process, microinjection of 6-OHDA into the striatum may
lead to the generation of H2 O2 via a mitochondrial enzymatic oxidation process. Inhibition of complex I of
the electron transport chain also stimulated mitochondrial
production of superoxide radicals. These superoxide radicals
were then catalyzed to H2 O2 by superoxide dismutase
and, subsequently, • OH− may arise from the breakdown
of H2 O2 . This may be associated with the mitochondrial
dysfunction seen in our experiments, because • OH− rapidly
attacks other biological molecules. The radicals produced in
molecules such as lipids and proteins may also interact with
mitochondrial enzymes to cause degradation.
In the signaling pathways that are involved in 6-OHDAinduced mitochondrial fission and autophagy, evidence
revealed a key role for ROS. Our data demonstrated a relationship between ROS and 6-OHDA-induced mitochondrial
fission and, subsequently, mitophagy. Intriguingly, 6-OHDA
increases H2 O2 between the cells. We made this observation
using the dye CM-H2 DCFDA to measure peroxide-like
5
formation. This specific tool allows us to ascertain the role
of ROS in the mitochondrial dynamics process. Given that
the inhibition of this dynamic process, using mdivi-1, did
no block mitochondrial H2 O2 production upon 6-OHDA
treatments, H2 O2 production is upstream of mitochondrial
fission. In addition, TEMPOL and MnTBAP, two wellknown antioxidant drugs, abolished translocation of Drp1
to mitochondria and, consequently, 6-OHDA-induced mitochondrial fission. In keeping with this interpretation, oxidative stress might be responsible for induced mitochondrial
fission in several processes, including PD, perhaps due to a
posttranslational redox change in the Drp1 protein [77, 78].
In addition, nitric oxide induces profound mitochondrial
fission [44]. Cultured cerebrocortical neurons exposed to the
physiological NO donor, S-nitrosocysteine, induced SNODrp1 formation and led to the accumulation of excessively fragmented mitochondria. SNO-Drp1-induced mitochondrial fragmentation caused synaptic damage, an early
characteristic feature of AD and, subsequently, apoptotic
neuronal cell death. Importantly, blockade of Drp1 nitrosylation (using the Drp1 (C644A) mutant) prevented A-βmediated mitochondrial fission, synaptic loss, and neuronal
cell death, suggesting that the posttranslational modification
(S-nitrosylation) of Drp1 contributes to the pathogenesis
of AD. Thus, SNO-Drp1 may represent a potential new
therapeutic target for protecting neurons and their synapses
in sporadic AD. Multiple groups have now reported on Snitrosylation and subsequent activation of dynamin family
members, including Drp1 [79–82].
In conclusion, although we await further clarifications
on the role of mitochondrial fission and mitophagy in PD,
we consider this pathway as a promising new and attractive
pharmacological target. Interestingly, recent evidence has
identified new molecules involved in PD such as Parkin and
PINK1, key regulators of mitophagy.
Acknowledgments
This work was supported by SAF2008-05143-C03-1 from
Ministerio de Ciencia e Innovación and PI2007/55 Consejerı́a de Sanidad from Junta de Comunidades de CastillaLa Mancha (to J. Jordán) and by “Incorporación de grupos
emergentes” FIS CARLOS III (EMER07/023) and FISFEDER (PI080693; PI-2008/21) (to M. F. Galindo). M. E.
Solesio is a FIS-FEDER grant fellow.
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Biochimica et Biophysica Acta 1832 (2013) 174–182
Contents lists available at SciVerse ScienceDirect
Biochimica et Biophysica Acta
journal homepage: www.elsevier.com/locate/bbadis
The mitochondria-targeted anti-oxidant MitoQ reduces aspects of mitochondrial
fission in the 6-OHDA cell model of Parkinson's disease
María E. Solesio a, Tracy A. Prime b, Angela Logan b, Michael P. Murphy b, María del Mar Arroyo-Jimenez c,
Joaquín Jordán d, María F. Galindo a,⁎
a
Unidad de Neuropsicofarmacología Traslacional, Complejo Hospitalario Universitario de Albacete, Albacete, Spain
MRC Mitochondrial Biology Unit, Wellcome Trust/MRC Building, Hills Road, Cambridge, CB2 0XY, UK
c
Grupo de Neuroanatomía Humana, Dpto. Ciencias Médicas, Universidad Castilla-La Mancha, CRIB, Albacete, Spain
d
Grupo de Neurofarmacología, Dpto. Ciencias Médicas, Fac. de Medicina de Albacete, Universidad Castilla-La Mancha, IDINE, Albacete, Spain
b
a r t i c l e
i n f o
Article history:
Received 12 March 2012
Received in revised form 15 July 2012
Accepted 23 July 2012
Available online 28 July 2012
Keywords:
Mitochondrial dynamics
Fission
ROS
Bax
Drp1
a b s t r a c t
Parkinson's disease (PD) is a neurodegenerative disorder for which available treatments provide symptom
relief but do not stop disease progression. Mitochondria, and in particular mitochondrial dynamics, have
been postulated as plausible pharmacological targets. Mitochondria-targeted antioxidants have been developed to prevent mitochondrial oxidative damage, and to alter the involvement of reactive oxygen species
(ROS) in signaling pathways. In this study, we have dissected the effect of MitoQ, which is produced by
covalent attachment of ubiquinone to a triphenylphosphonium lipophilic cation by a ten carbon alkyl
chain. MitoQ was tested in an in vitro PD model which involves addition of 6-hydroxydopamine (6-OHDA)
to SH-SY5Y cell cultures. At sublethal concentrations of 50 μM, 6-OHDA did not induce increases in protein
carbonyl, mitochondrial lipid peroxidation or mitochondrial DNA damage. However, after 3 h of treatment,
6-OHDA disrupts the mitochondrial morphology and activates the machinery of mitochondrial fission, but
not fusion. Addition of 6-OHDA did not increase the levels of fission 1, mitofusins 1 and 2 or optic atrophy
1 proteins, but does lead to the translocation of dynamin related protein 1 from the cytosol to the mitochondria. Pre-treatment with MitoQ (50 nM, 30 min) results in the inhibition of the mitochondrial translocation
of Drp1. Furthermore, MitoQ also inhibited the translocation of the pro-apoptotic protein Bax to the mitochondria. These findings provide mechanistic evidence for a role for redox events contributing to mitochondrial fission and suggest the potential of mitochondria-targeted therapeutics in diseases that involve
mitochondrial fragmentation due to oxidative stress.
© 2012 Elsevier B.V. All rights reserved.
1. Introduction
Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder. At present, common medications provide some
dramatic relief of the symptoms but fail to abrogate disease development. Unfortunately, efforts to find effective agents that provide protection against neurodegeneration have been rather unsuccessful [1].
Oxidative stress, resulting from an imbalance between generation of
reactive oxygen species (ROS) and antioxidant mechanisms, is an important factor in the etiology and pathogenesis of degenerative diseases. Besides their importance for bioenergetics, mitochondria are
involved in oxidative damage and cell signaling leading to cell death
through the generation of ROS. Therefore, mitochondrial dysfunction
is central to a broad range of pathologies [2–5].
⁎ Corresponding author at: Unidad de Neurofarmacología Traslacional, Complejo
Hospitalario Universitario de Albacete, C/Hermanos Falcó 37, 02006 Albacete, Spain.
Tel.: +34 967 597477; fax: +34 967 597173.
E-mail address: [email protected] (M.F. Galindo).
0925-4439/$ – see front matter © 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.bbadis.2012.07.009
There are a series of mitochondrial antioxidant defenses for intercepting ROS and minimizing oxidative damage. But, excessive production of ROS or disruption of the antioxidant defenses leads to
extensive oxidative damage of the mitochondria [6]. Pathology, toxicology, and genetics suggest mitochondrial oxidative stress as an etiological cause in PD [7,8]. A plausible general therapeutic approach thus
could be the reduction of mitochondrial oxidative damage [6,9]. A number of mitochondria-targeted therapies are being developed [10], in particular antioxidants conjugated to triphenylphosphonium cation (TPP)
such as mitoquinone, mitovitamin E and mitophenyltertbutyline [11].
The best characterized mitochondria-targeted antioxidant is MitoQ
([10-(4,5-dimethoxy-2-methyl-3,6-dioxo-1,4-cyclohexadien-1-yl)decyl]
triphenylphosphonium), which consists of a ubiquinone moiety that is
linked to a TPP cation by a 10-carbon alkyl chain [12]. MitoQ accumulates
within the mitochondria and, once it is there, is continually recycled to
the active ubiquinol antioxidant by complex II of the respiratory chain
[12,13]. MitoQ has been used to prevent mitochondrial oxidative
damage and to block the involvement of ROS in signaling pathways
[12,13]. MitoQ functions most likely through its direct antioxidant action,
M.E. Solesio et al. / Biochimica et Biophysica Acta 1832 (2013) 174–182
although concomitant antiinflammatory and antihypoxic properties have
been shown [14–16]. MitoQ has been developed as a therapy for humans
and has undergone clinical trials [17,18].
Different experimental models have proved effective in the search
for clues to the underlying cause of Parkinson's Disease (PD) [19], for
instance, the administration of 6-hydroxydopamine (6-OHDA) to experimental animals or cell cultures [20]. However the mechanisms by
which 6-OHDA elicits its neurotoxic effects have yet to be fully elucidated, although a role for oxidative stress (reviewed in [2]) and the
participation of mitochondrially-mediated cell death [21], including
morphological alterations of mitochondria such as fragmentation
[22] are likely.
Mitochondria undergo continuous fission, fusion and movement referred to as mitochondrial dynamics. Major neurodegenerative diseases,
including PD, involve disruption of mitochondrial dynamics. These
structural abnormalities are caused by an imbalance in highly conserved
GTPase genes, which are essential for mitochondrial fission and fusion.
GTPase dynamin-related protein-1 (Drp1), fission 1 (Fis1), mitofusins
1 and 2 (Mfn1, Mfn2), and optic atrophy 1 (Opa1) proteins —regulate,
maintain and remodel mammalian mitochondria [23,24]. Remarkably,
in several disease models, the manipulation of mitochondrial fusion or
fission can partially rescue disease phenotypes [23,25]. Therefore, interference with those early processes may yield a neuroprotective approach. Recent studies reported that impaired mitochondrial dynamics
involve the participation of Drp1 in different neurodegenerative disease,
including Alzheimer's [25,26] and Huntington's [24,27]. In addition, in a
previous study, we have shown that in an in vitro pharmacological
model of Parkinson's disease, 6-OHDA disrupts mitochondrial dynamics
by inducing mitochondrial fragmentation. In this case activation of the
mitochondrial fission machinery was monitored by assaying the translocation of Drp1 from the cytosol to the mitochondria [22]. The translocation of Drp1 to the mitochondria took place very early in the process,
before apoptotic hallmarks such as collapse of the mitochondrial membrane potential or cytochrome c release become apparent, and was accompanied by formation of Bax foci on the mitochondrial surface [21].
In the present study we found that MitoQ dramatically diminished
6-OHDA-induced mitochondrial fragmentation. Through its capacity to
alter mitochondrial redox processes MitoQ seems to exert its effects
by preventing the migration of Drp1 and Bax to mitochondria.
2. Material and methods
2.1. Reagents and plasmids
DMEM-F12, penicillin–streptomycin, gentamicin and fetal bovine
serum (FBS) were purchased from Gibco-Invitrogen. 6-OHDA from
SIGMA. The BCA protein assay kit from PIERCE. The pDsRed2-mito vector was provided by Clontech, Drp1-GFP was provided by T. Wilson and
Dr. S. Strack, Dept. Pharmacology, University of Iowa Carver College of
Medicine. GFP-Bax was a gift from Dr. J.H.M. Prehn (Department of
Physiology and RCSI Neuroscience Research Centre, Royal College of
Surgeons, Ireland).
2.2. Cell culture and drug treatment procedures
SH-SY5Y cell lines were obtained from the American Type Culture Collection (ATCC). Cell cultures were grown as described previously [28] in
Dulbecco's modified Eagle's medium (DMEM-F12) supplemented with
2 mM L-glutamine, 20 units·mL−1 penicillin-streptomycin, 5 mg·mL−1
gentamicin and 15% (v/v) FBS. Cells were grown in a humidified cell incubator at 37 °C under a 5% CO2 atmosphere. Cells were plated 24 h before
transfection at a density of 5.3×104 cells cm−2, on μ-dish-35 mm Ibidi
GmbH (Munich, Germany). 6-OHDA was added to culture medium at a
final concentration of 50 μM. Duration of pre-treatment with MitoQ and
TPP was 30 min and were maintained during the whole experiments.
175
2.3. Transfections
Twenty-four hours before transfection, cells were plated at a density of 5.3 × 10 4 cells cm −2 on μ-dish-35 mm Ibidi GmbH (Munich,
Germany). Transfection was achieved using Lipofectamine reagent
(Invitrogen, Carlsbad, CA, USA) according to the manufacturer's protocol. Cells were transfected with plasmids encoding pDsRed2,
Drp1-GFP, and Bax-GFP. After 4 h of incubation the transfection mixture was removed and replaced with fresh complete medium. To
allow protein expression, further experiments were performed 24 h
after transfection.
2.4. Image acquisition and processing
Micrographs were processed with Huygens Deconvolution Software (Scientific Volume Imaging) and Adobe Photoshop. For quantitative analysis of mitochondrial morphology, the three patterns of
mitochondrial morphology (filamentous, punctuate or intermediate)
were recorded in at least 100 cells per coverslip observed on adjacent
fields at magnification 63 ×. We assessed the robustness of this classification by comparing data obtained with separate cover slips from
the same experiment and from successive passages. In addition, the
monitoring of the mitochondrial morphology was performed by two
independent examiners on three different cultures. The proportions
observed were similar in all these experiments demonstrating that
mitochondrial morphology could be reliably analyzed and did not
vary within and between experiments under basal culture conditions.
We performed the experiments using a “blind” counter.
2.5. Analysis of mitochondrial morphology
Cells were transfected with pDsRed2-Mito, which leads to the expression of fluorescent DsRed2 in mitochondria, thereby labeling the
organelles. The transfected cells are then subjected to experimental
treatments to evaluate mitochondrial morphology by fluorescence
microscopy. For quantification, the percentage of cells with abnormal
mitochondrial morphologies was determined and taken as a measure
of the proportion of cells with fragmented mitochondria. Most of the
cells had either fragmented or filamentous mitochondria, whereas a
small percentage (b10%) of the cells contained both fragmented and
filamentous mitochondria. In case of the latter, the mitochondrial
morphology was classified according to the majority (>70%) of the
mitochondria.
2.6. Protein carbonyl determination
SH-SY5Y cells were cultured in 150 mm Dish plates until they
were confluent. Then, cells were scraped off, resuspended in cold
PBS, and centrifuged in Eppendorf tubes for 5 min at 12,000 rpm.
After this, supernatants were discarded and the pellets were
resuspended in 300 μL of cold PBS and sonicated. Protein Carbonyls
were assayed by ELISA, using a commercial kit (BioCell Corp., New
Zealand) and following the manufacturer's instructions. Protein was
quantified with the BCA Protein Assay Reagent (Pierce). Samples
were assayed in triplicate using protein carbonyl and BSA protein
standards that are supplied with the kit.
2.7. Measurement of mtDNA damage and copy number
SH-SY5Y cells were grown in 6-well plates at a confluence of
700,000 cells well−1. The following day, cells were exposed to drugs
for 3 h after which the spent medium was removed and cells were
scraped off, resuspended in 0.5 mL of cold PBS, and transferred to
Eppendorf tubes. The cell suspensions were centrifugated for 3 min at
12,000 rpm, and the pellet was resuspended in 200 μL of cold PBS.
Total DNA was isolated from these cells using the Qiagen DNeasy
176
by 10 min at 75 °C. For the long mtDNA target the conditions were:
1 min at 94 °C, followed by 19 cycles of 15 s at 74 °C and 12 min at
64 °C followed by a final extension step of 10 min at 72 °C. PCR products were quantified by the PicoGreen assay. Amplification linearity
was tested by adding controls with 25% or 50% of the amount of
DNA template. The reaction was considered linear if the amplification
obtained in the controls was between 40% and 60%. All samples
were amplified in duplicate and corrected for the control without
template.
Blood and Tissue kit. For DNA quantification we used the PicoGreen
dsDNA assay kit (Invitrogen) and a SpectraMax fluorimetric plate reader (excitation wavelength 488 nm, emission wavelength 515 nm). DNA
was then diluted to 3 ng/μL in TE buffer (10 mM Tris, 1 mM EDTA,
pH 7.5) and stored at −20 °C.
Damage to mtDNA was assayed using a PCR method which measures the amplification of a very long (∼ 10 kb) section of mtDNA.
Damage to the mtDNA (e.g. strand breaks, abasic sites, and certain
types of oxidative lesions) blocks the progression of the DNA polymerase, thus decreasing amplification. To control for mtDNA copy
number, amplification of the long DNA target was normalized to
that of a short (126 bp) mtDNA region. Amplification of a short
mtDNA target is ∼ 100-fold less likely to be affected by random damage, allowing for comparison of DNA damage between different
samples.
PCR primers were modified from published ones. The long mtDNA
target encompasses nt 3278 to nt 13343 (10,065 bp; ND1 to ND5).
The forward primer was 5′‐TCTAAGCCTCCTTATTCGAGCCGA‐3′ and
the reverse primer was 5′‐TTTCATCATGCGGAGATGTTGGATGG‐3′.
The short DNA target for amplification spans the region from nt
3278 to nt 3404 (126 bp; ND1). The reverse primer was the same as
for the long mtDNA target and the forward primer was 5′‐
CCCCACAAACCCCATTACTAAACCCA‐3′. Primers were synthesized by
Sigma-Genosys, diluted to 10 μM in TE buffer, and stored as aliquots
at − 20 °C. PCRs were performed using the GeneAmp XL PCR kit
(Applied Biosystems) in a total volume of 50 μL, consisting of 15 ng
DNA template, 1 U rTth DNA polymerase XL, and 35 μL PCR master
mix containing 5 μg BSA, 200 μM dNTPs, 20 pmol forward primer,
20 pmol reverse primer, and 1.0 mM magnesium acetate (0.9 mM
for the short mtDNA target). The PCR was initiated with a manual
hot start by heating the mixture to 75 °C before adding the DNA polymerase. The PCR parameters were, for the short mtDNA target,
18 cycles of 30 s at 94 °C, 45 s at 60 °C, and 45 s at 72 °C followed
Cells were washed with ice-cold PBS, left on ice for 10 min, and then
resuspended in isotonic homogenization buffer (250 mM sucrose,
10 mM KCl, 1.5 mM MgCl2, 1 mM sodium-EDTA, 1 mM sodium-EGTA,
1 mM dithiothreitol, 0.1 mM phenylmethylsulfonyl fluoride, and
10 mM Tris–HCl, pH 7.4) containing a proteinase inhibitor mixture
(Roche, Basel, Switzerland). After 40 strokes in a Dounce homogenizer,
the unbroken cells were spun down at 30 g for 5 min. The mitochondrial fractions were fractionated at 750 g for 10 min and 14,000 g for
20 min, respectively, and separated from the supernatant (cytosolic
fraction).
2.9. Western blotting
For measurements of cellular concentrations of Mfn1, Mfn2, Opa1,
Fis1, Drp1 and Bax, cells were washed with PBS and lysed for 5 min in
30 μL office-cold lysis buffer, consisting of 80 mM KCl, 250 mM sucrose,
500 μg/mL digitonin, and 1 μg/mL each of the protease inhibitors
leupeptin, aprotinin, pepstatin, and 0.1 mM PMSF in PBS. Cell lysates
were centrifuged for 5 min at 10,000 g. Protein concentrations were
quantified spectrophotometrically (Micro BCA Protein Reagent Kit;
Pierce, Rockford, IL), and equal amounts of protein (30 μg) were loaded
B
A
Control
0.6
0.5
0.4
0.3
0.2
0.1
6-OHDA
1.75
1.50
1.25
1.00
0.75
0.50
0.25
0.00
0.0
C
Control
6-OHDA
Relative amplification
(Normalised RFU)
Protein Cabonyls
(nmol Protein Cabonyls/mg protein)
2.8. Preparation of mitochondrial fractions
Control
dTPP
MitoQ
Control
dTPP
MitoQ
Ratio
/
590
520
3
2
***
1
0
0
50
100
6-OHDA (µM)
Fig. 1. 6-OHDA does not induce large scale mitochondrial oxidative damage. A. Protein carbonyl levels in total cellular extracts of SH-SY5Y upon a 3 h treatment with 50 μM 6-OHDA.
B. MtDNA integrity following a 3 h treatment with 6-OHDA was determined by semi-quantitative PCR. C. After 3 h of 6-OHDA treatment the levels of mitochondrial phospholipid peroxidation was determined by calculating the oxidation of MitoPerOx within cells. The concentration of 100 μM 6-OHDA was used as positive control. The ratio of emission at 520 nm to
590 nm is shown in the bar graph. Given values are the mean±SEM of five independent experiments that were performed in quadruplicate. (*pb 0.05; ** pb 0.001; one-way ANOVA
post hoc Tukey).
onto 10% SDS-PAGE gels. After electrophoresis, proteins were transferred to polyvinylidene difluoride membranes (Immobilon; Millipore
Corporation, Billerica, MA). Nonspecific protein binding was blocked
with Blotto (4% w/v nonfat dried milk, 4% bovine serum albumin
(Sigma), and 0.1% Tween 20 (Sigma)) in PBS for 1 h. The membranes
were incubated with anti-Fis1 (Atlas Antibodies 1:500), antiMfn1(Santa Cruz; 1:1000 dilution), anti-; Mfn2 (abcam;1:1000 dilution), anti-Opa1(BD; 1:1000 dilution), anti-Bax (Cell Signaling 1:1000
dilution), anti-COX IV (Cell signaling; 1:1000dilution), anti-αTubuline (Santa Cruz; 1:1000) and anti-Drp1 (BD Biosciences 1:1,000
dilution) overnight at 4 °C. After washing with Blotto, the membranes
were incubated with a secondary antibody (1:5000 dilution of a
peroxidase-conjugated from Promega, Madison, WI) in Blotto. The
177
signal was detected using an enhanced chemiluminescence detection
kit (GE Healthcare, Little Chalfont, Buckinghamshire, UK).
2.10. Mitochondrial viability
Mitochondrial viability was assessed in the SH-SY5y cells from control and experimental treatments (n= 3) the mitochondrial-dependent
reduction of 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetraz9olium
bromide (MTT) to formazan. Briefly, in this reduction SH-SY5Y cells
were seeded in 48-well plates at a density of 10 5 cells per well. After
treatments, MTT (5 mg/mL in PBS) was added to the plates, and the
cells (control and experimental) were incubated for 1 h. The medium
was then replaced with DMSO, and MTT absorption was measured at
Control
B
6-OHDA
C
dTPP
D
6-OHDA+dTPP
E
MitoQ
F
6-OHDA+MitoQ
G
Cell with fragmended
mitochondria (%)
A
Control
70
60
6-OHDA
**
***
n/s
50
40
30
20
10
0
Control
dTPP
MitoQ
Fig. 2. MitoQ reduces 6-OHDA-induced alterations of mitochondrial morphology. SH-SY5Y cells were transfected with the pDsRed2-mito vector. Twenty-four hours later cells were
pre-treated (or not) with 5 nM of dTPP or MitoQ for 30 min, followed by a 3 h treatment with 50 μM 6-OHDA. Representative confocal images of mitochondrial morphology under
the different conditions are shown in A–F. Scale bar, 10 μm. G. Proportions of cells with fragmented mitochondrial patterns were determined after a 3 h treatment with 6-OHDA.
Data in histograms are the mean ± SEM of four independent experiments. Statistical significance was determined by a two-tailed Student's test: n/s, p > 0.05; **p b 0.01; ***p b 0.001.
178
570 nm. Results were expressed as the percentage of MTT reduction, assuming that the absorbance of the control SH-SY5Y cells was 100%.
2.11. Intracellular lipid peroxidation measurement
SH-SY5Y cells were plated at a density of 5.3 104 cells/cm2 on μ-dish
35 mm plates obtained from IBIDI GmbH, (Munich, Germany).
Twenty-four hours later, the cells were treated with 6-OHDA, (100 or
50 μM) for 2.5 h after which the medium was refreshed by adding
fresh medium with the same concentration of 6-OHDA plus 100 nM
MitoPerOx [29], and incubating the plates for 30 min at 37 °C in the
dark. Then, plates were washed three times with 1× PBS and 1 mL
HEPES was added. Cells were visualized with a Zeiss Confocal Microscope, using a 63× oil-immersion objective. In each field, two different
photos were taken: one at 520 nm and one at 590 nm. We analyzed significant regions of interest from all the photos, using ImageJ, and calculated the 520/590 nm ratio, which is a good measure of lipid peroxidation
production. In the presence of intracellular lipid peroxidation, there is
an increment in the 520 nm emission while 590 nm decreases.
cells with mitochondrial morphology alterations, being 24% (pb 0.001)
after 3 h of treatment (Fig. 2B, G).
In order to ascertain the role of mitochondrial oxidative events in
this process, we used the mitochondria-targeted antioxidant MitoQ.
First, we tested if the presence of the control compound dTPP,
which has the same mitochondria-targeting motif as MitoQ but
which lacks its antioxidant properties, has any effect on mitochondrial morphology. Control cell cultures expressing DsRed2 did not show
mitochondrial alterations after 3 h of dTPP (50 nM) treatment
(Fig. 2C, G). In addition, a 30 min pre-treatment with 50 nM of
dTPP did not decrease the percentage of cells showing fragmented
mitochondria after 3 h of treatment with 6-OHDA (Fig. 2C, G). Furthermore, the mitochondrial morphology of cells under control conditions was unaffected by the addition of 50 nM MitoQ (Fig. 2E, G).
Subsequently, cell cultures that were pre-treated for 30 min with
50 nM MitoQ were challenged with 50 μM 6-OHDA. Upon 3 h of
6-OHDA treatment, MitoQ significantly decreased the number of
cells with fragmented mitochondria (Fig. 2F, G).
3. Results
3.3. 6-OHDA activates fission but not fusion of mitochondria
Addition of 6-OHDA to SH-SY5Y cell cultures is an in vitro experimental model of PD. In this study, we have determined the effect of
the mitochondria-targeted antioxidant MitoQ on mitochondrial fragmentation in this model. We chose 50 μM 6-OHDA because 3 h of
treatment with this concentration is non-lethal but does alter mitochondrial morphology [22].
Mitochondrial fusion is controlled by three dynamin-related
GTPases: Mfn1 and Mfn2, in the outer mitochondrial membrane,
and Opa1 in the inner mitochondrial membrane. To determine
whether the change in mitochondrial morphology was due to an increase in mitochondrial fusion, we explored the protein expression
levels of these three GTPases. Lysates from SH-SY5Y cells that had
been challenged with 50 μM 6-OHDA were compared with control
cells analyzed by immunoblotting. After 3 h of treatment, all the
GTPase proteins assayed had similar expression levels under both
conditions (Fig. 3A–C).
In the next set of experiments, we ascertained the role of Fis1 and
Drp1, two proteins that are involved in mitochondrial fission, in this
model. Levels of the outer mitochondrial membrane protein Fis1
were unaltered upon a 3 h treatment with 50 μM 6-OHDA (Fig. 3D).
Drp1 is a cytosolic protein that migrates to mitochondria to induce
mitochondrial fission [30]. SH-SY5Y cells were transfected with the
fluorescent chimeric protein GFP-Drp1, which enables us to monitor
the intracellular localization of Drp1 using confocal microscopy.
Untreated cells showed cytosolic localization of GFP-Drp1 (Fig. 4A).
Upon a 3 h treatment with 50 μM 6-OHDA, a punctuated distribution
3.1. 6-OHDA has minimal effects on mitochondrial oxidative damage
Oxidative stress is a condition in which ROS production overwhelms
antioxidant defenses. Its occurrence can be detected by determining the
levels of protein carbonyl groups or the presence of oxidative mitochondrial DNA damage. The levels of protein carbonyl groups were determined in SH-SY5Y cells that had been challenged with 6-OHDA
(50 μM, 3 h). 6-OHDA did not increase the total cellular levels of protein
carbonyl groups (Fig. 1A). In addition, we determined the effect on
mtDNA damage and deletion. Again, 6-OHDA did not disrupt mtDNA
(Fig. 1B). Taken together, we conclude that SH-SY5Y cells that were
challenged for 3 h with 50 μM 6-OHDA present do not undergo extensive oxidative damage. In a third approach we used the ratiometric fluorescent probe MitoPerOx for assessing mitochondrial phospholipid
peroxidation within living cells [29]. Three hours after 6-OHDA addition, no significant differences were found between cell cultures challenged or not with 50 μM 6-OHDA (Fig. 1C). Of note, when we
performed similar experiments with a higher concentration of 100 μM
6-OHDA, increases in all the oxidative hallmarks mentioned above
were found. Taken together, we conclude that SH-SY5Y cells that
were challenged for 3 h with 50 μM 6-OHDA present do not undergo
extensive oxidative damage and suggest that a relatively mild redox signaling process can initiate mitochondrial fission. In addition, 3 h after
treatment, 50 μM 6-OHDA did not compromise the mitochondrial viability of SH-SY5Y cells, as measured using the MTT assay (data not
shown).
3.2. MitoQ abrogates 6-OHDA-induced mitochondrial fission
Our previous work has shown that 6-OHDA induces mitochondrial
fission in SH-SY5Y cell cultures [22]. In the current study, to be able to
determine mitochondrial morphology, we have used the pDsRed2mito plasmid to express the mitochondrial protein DsRed2 (Fig. 2). As
expected, control cells contained elongated mitochondria. Addition of
50 μM 6-OHDA resulted in morphologically altered mitochondria, with
apparently shorter filaments (Fig. 2B, also see [22]). Quantitative analysis revealed that 6-OHDA resulted in an increase in the proportion of
A
C
6-OHDA
B
C
Opa1
Mfn 1
α Tubulin
α Tubulin
C
C
6-OHDA
D
C
Mfn 2
hFis
α Tubulin
α Tubulin
6-OHDA
6-OHDA
Fig. 3. 6-OHDA does not induce mitochondrial fusion. Protein expression levels of Opa1
(A) Mfn1 (B), Mfn2 (C), and Fish1 (D) in lysates prepared from total cellular extracts
were subjected to immunoblotting. Equal amounts of protein (30 μg/lane) were loaded
on the gels. α-Tubulin levels were used as an index of total cell load. The immunoblots
shown are representative of three independent experiments.
179
A
Control
B
6-OHDA
C
dTPP
D
6-OHDA+dTPP
E
MitoQ
F
6-OHDA+MitoQ
Punctated GFP-Drp-1
(% cell transfected with Drp-1)
G
80
70
60
50
40
30
20
10
0
Control
6-OHDA
***
***
Control
dTPP
MitoQ
Fig. 4. MitoQ reduces the 6-OHDA-induced mitochondrial translocation of Drp1. SH-SY5Y cells were transfected with GFP-Drp1 vector for 24 h, and pre-treated (or not) with 50 nM
of dTPP or MitoQ for 30 min, followed by a 3 h treatment with 50 μM 6-OHDA. Representative confocal images of mitochondrial morphology under the different conditions are
shown in A–F. Scale bar, 10 μm. G. Percentages of cells with punctuate Drp1 distribution were determined 3 h after addition of 6-OHDA. Results shown are the mean ± SEM of
at least three experiments, each performed in triplicate. Statistical significance was determined by a two-tailed Student's test: ***p b 0.001.
of GFP-Drp1 was observed, indicating that Drp1 was efficiently
translocated to the mitochondria (Fig. 4B, G).
3.4. MitoQ reduces 6-OHDA-induced mitochondrial translocation of Drp1
Next, we determined the percentage of cells with a punctate distribution of Drp1 following pre-treatment for 30 min with 50 nM MitoQ before challenge with 50 μM 6-OHDA. MitoQ reduced the number of cells
with a punctate appearance of Drp1 by about 74% in 6-OHDAchallenged SH-SY5Y cell cultures (Fig. 4F, G). In addition, 50 nM dTPP
failed to induce Drp1 translocation in control cultures, and did not prevent the 6-OHDA-induced effect on Drp1 localization (Fig. 4D, G).
3.5. MitoQ reduces 6-OHDA-induced mitochondrial translocation of Bax
Previously, we have reported that the intracellular localization of
the pro-apoptotic protein Bax changes after 12 h treatment with
6-OHDA [21]. In the next set of experiments, we investigated if this
effect is modulated by MitoQ. Cell cultures were transfected with
GFP-Bax, and 24 h later they were pre-treated with either 50 nM
dTPP or MitoQ for 30 min, followed by addition of 50 μM 6-OHDA
(Fig. 5). After 12 h of 6-OHDA treatment, we determined the percentage of cells with punctate GFP-Bax distribution (Fig. 5G). The addition
of dTPP did not modify the cellular localization of Bax in control cultures, and did not abrogate the effects of 6-OHDA (Fig. 5C–D, G).
However, MitoQ reduced the number of cells with a punctate
180
appearance of Bax in cell cultures that were challenged with 50 μM
6-OHDA (Fig. 5F,G). In addition, we corroborated the inhibitory effect
of MitoQ on 6-OHDA-induced translocation from mitochondrial fractions by immunoblotting (Fig. 5H).
4. Discussion
In the present study, we have focused on assessing the effect of MitoQ
on cellular pathways that contribute to 6-OHDA-induced mitochondrial
fission in SH-SY5Y cells. We utilized a sublethal 6-OHDA concentration
of 50 μM, which is able to induce mitochondrial morphological alterations. We did not observe an increase in total protein carbonyls or in
oxidative damage to mtDNA, suggesting that these levels of 6-OHDA
did not act by extensive oxidative damage but rather by relative mild
redox effects. Notably, MitoQ reduced the mitochondrial morphology alterations induced by 6-OHDA. This suggests that a mild mitochondrial
redox process induced by 6-OHDA that can be prevented by MitoQ is
an early event in the change in mitochondrial morphology caused by
6HD. In addition, MitoQ prevented the 6-OHDA-induced translocation
of both Drp1 and Bax to mitochondria.
Pathology, toxicology, and genetics suggest that mitochondrial oxidative stress is an etiological factor in PD [7,8]. Under physiological
conditions, 6-OHDA is rapidly and non-enzymatically oxidized to
form ROS. Previous work in our group and elsewhere has shown an
A
Control
B
6-OHDA
C
dTPP
D
6-OHDA+dTPP
E
MitoQ
F
6-OHDA+MitoQ
Punctated GFP-Bax
(% cell transfected with Bax)
G
80
70
60
50
40
30
20
10
0
Control
6-OHDA
H
6-OHDA
**
C
n/s
6-OHDA dTPP
MitoQ
**
Bax
COX IV
Control
dTPP
MitoQ
Fig. 5. MitoQ reduces the 6-OHDA-induced mitochondrial translocation of Bax. SH-SY5Y cells were transfected for 24 h with GFP-Bax vector, and were pre-treated (or not) with
50 nM dTPP or MitoQ for 30 min, followed by a 12 h treatment with 50 μM 6-OHDA. Representative confocal images of mitochondrial morphology under the different conditions
are shown in A–F. Scale bar, 10 μm. G Percentages of cells with punctuate Bax distribution were determined 12 h after addition of 6-OHDA. Results shown are the mean ± SEM of at
least three experiments, each performed in triplicate. Statistical significance was determined by a two-tailed Student's test: n/s, p > 0.05; **p b 0.01. H. Representative immunoblot
analysis of Bax levels in mitochondrial fractions obtained from SH-SY5Y cells. Cell cultures were pre-treated with 50 nM dTPP or MitoQ for 30 min, followed by a 12 h treatment
with 50 μM 6-OHDA. Equal amounts of protein (30 μg/lane) were loaded on the gels. COX-IV was used as an index of mitochondrial load. The immunoblots shown are representative of three independent experiments.
181
defined set of proteins [39–43]. Our data support the notion that
MitoQ blocks the activation of the mitochondrial fission machinery by
preventing mitochondrial translocation of Drp1, a large GTPase of the
dynamin family. Drp1 is cytosolic, but a subpopulation of the protein
migrates to mitochondria and accumulates at sites of future fission,
forming discrete spots [44,45]. According to in vitro studies, Drp1 assembles into rings around mitochondria and constricts their membranes. This results in degradation of the organelles in a GTP
hydrolysis-dependent manner [40]. In our study, 6-OHDA recruited
Drp1 to mitochondria. Confocal microscopy analysis of cell cultures
overexpressing Drp1-GFP revealed that addition of 6-OHDA modified
the cytosolic and diffuse distribution of Drp1, leading to a punctate mitochondrial distribution. Administration of 50 nM MitoQ was sufficient
to inhibit 6-OHDA-induced Drp1 mitochondrial translocation in
SH-SY5Y cells. This observation can be explained by the fact that
MitoQ is preventing posttranscriptional changes in Drp1. Accordingly,
redox modification of Drp1 may link excessive mitochondrial fission
to neuronal injury in neurodegeneration [24,26]. In line with these observations, using a neurodegenerative model that monitors amyloid-β
toxicity to N2a cells, Manczak et al. have reported how MitoQ appears
to protect mitochondrial structure by preventing mitochondrial genes
from abnormal expression [25].
In addition, MitoQ abrogates the 6-OHDA-induced mitochondrial
translocation of Bax in SH-SY5Y cells. We and other groups have described that Bax actively participates in neurodegenerative processes
[21,46]. Bax co-localized with Drp1 and Mfn2 at mitochondrial fission
sites in apoptotic cells [47], and has been suggested to participate directly
in apoptotic mitochondrial fission. Previously, in a different neurodegenerative model using MEF cell cultures from mice which lack Bax, we
have shown that this protein is not required for 6-OHDA-induced mitochondrial fragmentation [22]. Interestingly, MitoQ also mediates protection against cardiac ischemia–reperfusion injury, diabetic nephropathy,
adriamycin-induced cardiotoxicity, and hepatitis C-induced liver injury
[17,36–38] and whether prevention of mitochondrial fission contributes
to these processes will be an area of future activity (Fig. 6).
increase in H2O2 in cell cultures challenged with 6-OHDA [31–34]. As
the 6-OHDA concentration used in our study was sublethal, and we
chose an early time point, SH-SY5Y cells challenged with 6-OHDA
did not present hallmarks of oxidative stress. Neither total protein
carbonyl group levels nor oxidative mtDNA damage levels were significantly modified by 6-OHDA. This suggests that the effects on the
cell were relatively mild redox signals probably originating in the mitochondrial matrix in response to 6-OHDA oxidative stress, and this
was abrogated by pretreatment with MitoQ. In addition, we corroborated the lack of excessive oxidative stress in these conditions using
the ratiometric fluorescent probe MitoPerOx for assessing mitochondrial phospholipid peroxidation.
Several classes of small molecular antioxidant mimetics have been
shown to protect against central nervous system injuries such as dopaminergic neuron degeneration [25,35–38]. Neurons are metabolically active cells with high energy demands at locations distant
from the cell body. Because of this, these cells are particularly dependent on mitochondrial function, as reflected by the observation that
mitochondrial-dysfunction diseases often have a neurodegenerative
component [23].
In vivo, MitoQ is taken up rapidly and extensively by mitochondria, where it is reduced to the active antioxidant ubiquinol form
[10]. MitoQ is nontoxic and orally bioavailable in animal models and
humans [14,18]. MitoQ protects mitochondria by decreasing oxidative damage to mitochondrial proteins, lipids, and DNA [11,12]. It
also has been shown to decrease mitochondrial damage and to
lower the levels of mitochondrial ROS in a range of animal models
(reviewed in [13]).
MitoQ blocks 6-OHDA induced mitochondrial fission. By intervening
in this process, MitoQ modulates mitochondrial function. It enables mitochondrial recruitment to critical subcellular compartments, content
exchange between mitochondria, mitochondrial shape control, communication with the cytosol, and mitochondrial quality control. When
mitochondrial dynamics is disrupted, cellular dysfunction ensues. Mitochondrial fission is a highly regulated process, and is mediated by a
6-OHDA
p-quinones
H2O2
H2O2
Drp1
Bax
MitoQ
H2O2
Mitochondrial
fission
Fig. 6. Schematic diagram of the MitoQ-modulated abrogation of mitochondrial morphology alterations in the 6-OHDA PD model. Auto-oxidation of 6-OHDA leads to the formation
of H2O2, either extracellularly or within the cell, and this is able to reach the mitochondrial matrix. Mitochondrial fission induced by 6-OHDA-mediated stress is an early event. H2O2
may activate the mitochondrial fission machinery, including the mitochondrial translocation of either Drp1 or Bax. MitoQ accumulated in the mitochondrial membrane may block
H2O2 increases in the mitochondrial matrix. MitoQ is effective at concentrations that do not lead to induction of detectable oxidative stress hallmarks. MitoQ seems to prevent the
activation of the mitochondrial fission machinery by preventing Drp1 translocation to the mitochondria. In addition, MitoQ also blocked the formation of mitochondrial Bax foci in
response to 6-OHDA in SH-SY5Y cell cultures.
182
In conclusion, our data suggest that 6-OHDA treatment leads to mitochondrial fragmentation by inducing a mild redox stress on mitochondria that is sufficient to induce a translocation of Drp1 to the
mitochondria and thereby increase mitochondrial fission. This fragmentation can be largely prevented by the mitochondria-targeted antioxidant MitoQ, consistent with a mitochondrial redox signaling event
leading to Drp1 recruitment. Furthermore, these data suggest that
mitochondria-targeted antioxidants may be worth exploring as potential therapies in pathologies involving mitochondrial fragmentation.
Acknowledgements
We thank Carlos Garrido for technical help, and T. Wilson, Dr. S.
Strack and Dr. J.H.M. Prehn for providing vectors. This work was
supported by SAF2008-05143-C03-1 from Ministerio de Ciencia e
Innovación and PI2007/55 Consejería de Sanidad from Junta de
Comunidades de Castilla-La Mancha (to J.J.) and by ‘Incorporación
de grupos emergentes’ FIS CARLOS III (EMER07/023) and FIS-FEDER
(PI080693; PI-2008/21) (to M.F.G.). M.E.S. is a FIS-FEDER grant fellow.
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doi:10.1093/toxsci/kfs218
Advance Access publication July 21, 2012
TOXICOLOGICAL SCIENCES
Characterization of Mitophagy in the 6-Hydoxydopamine Parkinson’s
Disease Model
Maria E. Solesio,* Sara Saez-Atienzar,† Joaquin Jordán,†,1 and Maria F. Galindo*
*Unidad de Neuropsicofarmacología Traslacional, Complejo Hospitalario Universitario de Albacete, Albacete, Spain; and
†Grupo de Neurofarmacología, Dpto. Ciencias Médicas, Fac. de Medicina de Albacete, Universidad Castilla-La Mancha, IDINE, Albacete, Spain
1
To whom correspondence should be addressed. Fax: +34-967599327. E-mail: [email protected].
In the present study, the activation of autophagy and its interaction with the mitochondrial fission machinery was investigated
in an experimental model of Parkinson’s disease. The addition of
50µM 6-hydroxydopamine (6-OHDA) to the dopaminergic cell line
SH-SY5Y profoundly stimulated formation of autophagosomes
within 12 h. Under these conditions, mitochondrial fission was
also activated in a sustained manner, but this occurred at earlier
time points (after 3 h). Upon 6-OHDA treatment, dynamin-related
protein 1 (Drp1) transiently translocated to mitochondria, with
increased levels of mitochondrial Drp1 being observed after 3 and
9 h. Pharmacological inhibition of Drp1, through treatment with
the mitochondrial-division inhibitor-1 (mdivi-1), resulted in the
abrogation of mitochondrial fission and in a decrease of the number of autophagic cells. In addition, 6-OHDA failed to induce the
expression of the proapoptotic protein Bax in total cellular extracts
although it did induce its migration to mitochondria. In our model,
Bax migrated later than Drp1. However, Drp1 inhibition did not
block Bax migration. These results show that reactive oxygen species but not quinone derivates act as mediators of autophagy at
an early stage of the process. 6-OHDA induces hydrogen peroxide
production, which was placed upstream of mitochondrial fission,
given that mdivi-1 did not abrogate this increase. Furthermore, the
6-OHDA–induced activation of autophagy was also suppressed by
addition of the free radical scavengers TEMPOL and MnTBAP.
This effect could be reproduced by the addition of hydrogen peroxide, but not with aged 6-OHDA. To our knowledge, this is the
first detailed study highlighting the various mediators that are
implicated in mitochondrial alterations and autophagy of cells in
response to 6-OHDA.
Key Words: Parkinson’s disease; mitochondrial dynamics;
Drp1; Bax; mdivi-1; hydrogen peroxide.
The regulation of dynamic mitochondrial processes such as
fusion, fission, and mitophagy has been shown to be an important mechanism controlling cellular fate (Liesa et al., 2009).
An imbalance in mitochondrial dynamics may contribute to
both familial and sporadic neurodegenerative diseases including Parkinson’s disease (PD), a progressive neurodegenerative condition that is characterized by the presence of motor
and nonmotor symptoms (Cho et al., 2010; Lees et al., 2009;
Su et al., 2010; Thomas and Beal, 2007). Evidence exists
suggesting that an amplification of fission events can cause
pathogenesis of human PD. Stress stimuli that are used to
study PD, such as rotenone (De Palma et al., 2010), annonacin (Escobar-Khondiker et al., 2007), and 6-hydroxydopamine
(6-OHDA) (Gomez-Lazaro et al., 2008a), are capable of inducing mitochondrial fission. Also, human fibroblasts from PD
patients exhibit elevated levels of fragmented mitochondria
(Exner et al., 2007).
Human cells contain a number of intracellular mechanisms
that are essential for the removal of damaged or energy-deficient
mitochondria. Macroautophagy, here simply referred to as
autophagy, is one of the most prominent of these processes
(Yorimitsu and Klionsky, 2005) and is important to maintain
cellular homeostasis. Through the delivery of nonfunctional
cytosolic proteins and organelles to lysosomes for degradation,
autophagy yields a continuous turnover of cellular components
(Cuervo, 2004). Undoubtedly, there are multiple connections
between autophagic and apoptotic processes, which jointly can
determine the fate of cells (Leber and Andrews, 2010).
Mitochondrial fission and autophagy are highly regulated
process and are mediated by a defined set of proteins (Cerveny
et al., 2001; Karbowski et al., 2004; Mozdy et al., 2000; Otsuga
et al., 1998). One of these proteins, dynamin-related protein 1
(Drp1), is a member of the dynamin family of large GTPases
and mediates the scission of mitochondrial membranes
through GTP hydrolysis. Drp1 predominantly is a cytoplasmic
protein that associates with mitochondrial fission sites upon
oligomerization (Labrousse et al., 1999; Legesse-Miller et al.,
2003). In addition, the proapoptotic Bax protein has been
© The Author 2012. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved.
For permissions, please email: [email protected]
Downloaded from http://toxsci.oxfordjournals.org/ at INSERM on November 7, 2012
Received April 10, 2012; accepted June 27, 2012
412
SOLESIO ET AL.
MATERIAL AND METHODS
Reagents and plasmids. Dulbecco’s modified Eagle medium
(DMEM)-F12, penicillin-streptomycin, gentamicin, and fetal bovine serum
(FBS) were purchased from Gibco Invitrogen, and 6-hydroxydopmaine
(6-OHDA) was purchased from Sigma-Aldrich. MnTBAP and TEMPOL
(4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl) were purchased from
Calbiochem. The BCA protein assay was from Pierce, and the pDsRed2-mito
vector was provided by Clontech. GFP-Bax was a gift from Dr J.H.M.
Prehn (Department of Physiology and RCSI Neuroscience Research Centre,
Royal College of Surgeons, Ireland), and Drp1-GFP was kindly provided by
T. Wilson and Dr S. Strack (Department of Pharmacology, University of Iowa
Carver College of Medicine).
Cell culture and drug treatment procedures. SH-SY5Y cell lines were
obtained from the American Type Culture Collection. Cell cultures were grown
in a humidified cell incubator at 37°C under a 5% CO2 atmosphere in DMEM-F12
supplemented with 2mM L-glutamine, 20 units·ml−1 penicillin-streptomycin, 5
mg·ml−1 gentamicin, and 15% (v/v) FBS, as described previously (Jordan et al.,
2004). 6-OHDA was added to culture medium at final concentrations of 50µM.
Duration of pretreatment with the antioxidant drugs TEMPOL (0.2μM) and
MnTBAP (10nM) was 30 min. For both compounds, we have verified that the
treatment was not inducing cell death in control cells.
Transfections. Twenty-four hours before transfection, cells were plated at
a density of 5.3 × 104 cells/cm2 on IDIBI-coated glass dishes. Transfection was
achieved using Lipofectamine reagent (Invitrogen, Carlsbad, CA) according
to the manufacturer’s protocol. Cells were transfected with plasmids encoding
pDsRed2, Drp1-GFP, and Bax-GFP (see Solesio et al., forthcoming). After 4 h
of incubation, the transfection mixture was removed and replaced with fresh
complete medium. Experiments were performed 24 h after transfection to allow
protein expression.
Analysis of mitochondrial morphology. Cells were transfected with
pDsRed2-Mito, which leads to the expression of fluorescent DsRed2 in mitochondria, thereby labeling the organelles. The transfected cells were subjected
to experimental treatments, and mitochondrial morphology was evaluated by
fluorescence microscopy. For quantification, the percentage of cells with abnormal mitochondrial morphologies was determined and taken as a measure of
the proportion of cells with fragmented mitochondria. Most of the cells had
either fragmented or filamentous mitochondria, whereas a small percentage
(< 10%) of the cells contained both fragmented and filamentous mitochondria.
In case of the latter, the mitochondrial morphology was classified according to
the majority (> 70%) of the mitochondria.
Reactive oxygen species measurement. Reactive oxygen species (ROS)
in SH-SY5Ycells were detected using 2′,7′-dichlorofluorescin diacetate
(H2-DCF-DA; Molecular Probes, Eugene, OR). H2-DCF-DA is a nonpolar
compound that rapidly diffuses into cells, where it is hydrolyzed to the fluorescent polar derivative DCF and gets trapped within the cells. H2-DCF-DA
(10μM) was added to the cells. After incubation for 30 min at 37°C, the liquid
was removed and KREBS was added. Intracellular ROS accumulation in cells
with or without 6-OHDA treatment was measured in a Spectra Max Gemini
XS (Molecular Devices). The relative level of ROS production was determined
by calculating the average value from four wells in at least three independent
cultures.
Image acquisition and processing. Micrographs were processed with
Huygens Deconvolution Software (Scientific Volume Imaging) and Adobe
Photoshop. For quantitative analysis of mitochondrial morphology, the three
patterns of mitochondrial morphology (filamentous, punctuate, or intermediate) were recorded in at least 100 cells per coverslip observed on adjacent
fields at magnification 63×. We assessed the robustness of this classification by
comparing data obtained with separate cover slips from the same experiment
and from successive passages. In addition, monitoring of the mitochondrial
morphology was performed by two independent examiners on three different
cultures. The proportions observed were similar in all these experiments, demonstrating that mitochondrial morphology could be reliably analyzed and did
not vary within and between experiments under basal culture conditions. We
performed the experiments using a “blind” counter.
Determination of subcellular concentrations of Drp1 and Bax. For measurements of subcellular concentrations of Drp1 and Bax, cells were washed
with PBS and lysed for 5 min in 30 μl office-cold lysis buffer, consisting of
80mM KCl, 250mM sucrose, 500 μg/ml digitonin, and 1 μg/ml each of the protease inhibitors leupeptin, aprotinin, and pepstatin, and 0.1mM PMSF in PBS.
Cell lysates were centrifuged for 5 min at 10,000 g. Protein concentrations were
quantified spectrophotometrically (Micro BCA Protein Reagent Kit; Pierce,
Rockford, IL), and equal amounts of protein (30 μg) were loaded onto 10%
sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE) gels.
After electrophoresis, proteins were transferred to polyvinylidene difluoride
membranes (Immobilon; Millipore Corporation, Billerica, MA). Nonspecific
protein binding was blocked with Blotto (4% wt/vol nonfat dried milk, 4%
bovine serum albumin [Sigma], and 0.1% Tween 20 [Sigma]) in PBS for 1 h.
The membranes were incubated with anti-Bax (1:1000 dilution of an anti-rabbit
polyclonal, Cell Signaling) and anti-Drp1 (1:1000 dilution of anti-mouse monoclonal from BD Biosciences) overnight at 4°C. After washing with Blotto, the
membranes were incubated with a secondary antibody (1:5000 dilution of a
peroxidase-conjugated anti-mouse polyclonal from Promega, Madison, WI) in
Blotto. The signal was detected using an enhanced chemiluminescence detection kit (GE Healthcare, Little Chalfont, Buckinghamshire, UK).
Statistics. Statistically significant differences between groups were determined by ANOVA followed by a Newman-Keuls post hoc analysis. The cutoff
level of statistical significance was set at p < 0.05.
RESULTS
Autophagy is Activated by 6-OHDA Treatment
The protein LC3 has been used as a specific marker for quantification of autophagosomes, and overexpression of GFP-LC3
is a well-accepted, straightforward, and specific assessment
colocalized to scission sites on mitochondria, suggesting that
the mitochondrial fission machinery cooperates with the cell
death machinery (Karbowski et al., 2002). In previous studies,
we have shown that both proteins actively participate in the
6-OHDA preclinical model of PD (Gomez-Lazaro et al.,
2008a,b).
nonenzymatically oxidized by molecular oxygen to form
1,4-para-quinone and its degradation products(Gee and
Davison, 1989), along with production of ROS such as hydrogen peroxide (H2O2). Quinones react with nucleotic groups of
macromolecules, leading to inactive or destroyed quinoproteins. H2O2 is central to mitochondrial oxidative damage and
redox signaling, which acts as a direct redox signal independent
of the accumulation of oxidative damage (Janssen-Heininger
et al., 2008).
Hitherto, no direct observations have been reported on
the effect of 6-OHDA–induced mitochondrial fission and
autophagy. In the present study, we found that 6-OHDA dramatically induced mitochondrial fragmentation, resulting in an
increase in autophagy through a mechanism that was meditated
by reactive oxygen species and Drp1 but not by Bax.
MITOPHAGY IN THE 6-HYDOXYDOPAMINE PARKINSON’S DISEASE MODEL
(Fig. 1D). The increase of LC3-II immunoreactivity correlated
with a decrease of LC3-I, suggesting that autophagy occurred
at a very high rate (Fig. 1D). Withdrawal of serum from the
medium was used as a positive control of this event (Fig. 1D).
Drp1 Mediates 6-OHDA–Induced Mitochondrial Fission
At this point, the question arose whether autophagy is activated by mitochondrial fission. Our previous work has shown
that 6-OHDA induces mitochondrial fission in SH-SY5Y cell
cultures (Gomez-Lazaro et al., 2008a). In our current study, we
have used a new approach, exploiting the pDsRed2-mito plasmid to express the mitochondrial protein DsRed2. As expected,
untreated cells present mitochondria with a longitudinal aspect.
Addition of 50µM 6-OHDA results in morphologically altered
mitochondria, with apparently shorter filaments (Supplementary
fig. 1, also see Gomez-Lazaro et al., 2008b). Quantitative analysis revealed that addition of 6-OHDA resulted in an increase
in the proportion of cells with mitochondrial morphology
FIG. 1. 6-OHDA induces autophagy in SH-SY5Y cells. (A) Proportions of autophagic SH-SY5Y cells in cell cultures that were challenged with 0 (untreated),
25, 50, and 100µM 6-OHDA for different periods of time. Data represent mean ± SEM of four independent experiments. Significant differences between
6-OHDA–treated and untreated cells are indicated (*p < 0.05; ***p < 0.001; t-test). (B and C) Induction of autophagosome formation by 6-OHDA. Representative
confocal fluorescent microscopy images of SH-SY5Y cells transfected with GFP-LC3 cDNA and challenged (C) or not (B) with 50µM 6-OHDA for 12 h. The
punctuated distribution of green fluorescence indicates the formation of autophagosomes. (D) LC3b-II is induced by 6-OHDA. SH-SY5Y cell cultures were pretreated (or not) with 10µM mdivi-1 for 30 min before adding 50µM 6-OHDA. Serum withdrawal was used as positive control for accumulation of LC3b-II levels.
Twelve hours after 50µM 6-OHDA addition, total cellular extracts were collected. Equal amounts of protein (30 μg/lane) were loaded on the gels. The immunoblot
shown is representative of three independent experiments. Histograms: Quantitative analysis of the ratio of LC3-II to LC3-I (n = 3) (*p < 0.05; t-test).
of autophagosome formation. Upon induction of autophagy,
LC3 is conjugated to phosphatidylethanolamine and targeted
to autophagic membranes. We transfected SH-SY5Y cells with
GFP-LC3 and allowed its expression for 24 h prior to further
treatments. When these cells were cultured in regular DMEM
supplemented with 10% FBS, only a small number of GFP-LC3
dots were observed (4 ± 0.23 cell−1) (Figs. 1A and B). Next, 25,
50, and 100µM 6-OHDA was added to SH-SY5Y cell cultures, and autophagosome formation was quantified at different
time points. Cells with more than five autophagosomes were
counted as autophagic cells. 6-OHDA induced and increased
the number of GFP-LC3 dots per cell in a concentration- and
time-dependent manner (Fig. 1A).
The unconjugated (LC3-I) and conjugated forms (LC3-II)
of LC3 can be separated by SDS-PAGE. Immunoblot analysis showed that mock-treated SH-SY5Y cells barely contained
detectable levels of LC3b-II during the 12 h of the experiment.
In contrast, treatment with 50µM 6-OHDA–induced accumulation of LC3b-II, which was detectable after 12 h of treatment
413
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SOLESIO ET AL.
Bax Does Not Participate in 6-OHDA–Induced Autophagy
Previously, we have shown that Bax is a proapoptotic protein
that is involved in the 6-OHDA–induced PD model (GomezLazaro et al., 2008b). Now, we investigated the significance of
Bax in 6-OHDA–induced autophagy. 6-OHDA did not induce
an increase of Bax protein levels in total cellular extracts.
However, we observed mitochondrial Bax recruitment 9 h
after addition of 50µM 6-OHDA (Fig. 4; see Gomez-Lazaro
et al., 2008b). Furthermore, using the fluorescent protein BaxGFP, we observed that upon 6-OHDA treatment its appearance
changed from diffuse fluorescence in the cytoplasm to a more
punctuated distribution (Fig. 4A; see Gomez-Lazaro et al.,
2008b). These results place Bax translocation downstream of
mitochondrial fission in the 6-OHDA–induced PD model.
Subsequently, we analyzed whether Drp1 inhibition would
modulate 6-OHDA–induced Bax translocation. Cell cultures
were pretreated with mdivi-1 for 30 min prior to the addition of
50µM 6-OHDA. Twelve hours after 6-OHDA addition, mdivi-1
pretreated cell cultures presented a comparable number of cells
with a punctuated GFP-Bax distribution as mdivi-1-untreated
control cells (Fig. 4D).
Next, we studied the significance of Bax in 6-OHDA–
induced autophagy. Mouse embryonic fibroblasts (MEFs)
from wild-type and Bax knockout animals (Bax−/−MEFs) were
transfected with GFP-LC3 plasmid, 24 h before exposure to
50µM 6-OHDA. As shown in Figure 4E, the lack of Bax did not
decrease the percentage of autophagic cells in Bax knockout
animals 12 h after 6-OHDA addition compared with wild-type
MEF cells.
ROS Participate in 6-OHDA–Induced Autophagy
nonenzymatically oxidized to form 1,4-para-quinone and its
degradation products (Gee and Davison, 1989), along with
production of ROS such as H2O2. To determine whether ROS
participate in our model, we used the dye CM-H2DCF-DA to
measure peroxide-like formation. Differences in cellular H2O2
during different treatments were examined by comparing the
2ʹ,7ʹ-dichlorofluorescein (DCF) formation in cells challenged
or not with 6-OHDA (Fig. 5A). There was significant increase
in DCF fluorescence levels by 3 h after treatment. Furthermore,
the pretreatment with mitochondrial fission inhibitor mdivi-1
did not decrease this rise in ROS production. (Fig. 5A).
The role of ROS in our model was approached using two
broad spectrum antioxidant drugs, TEMPOL and MnTBAP.
Both ROS-scavenger drugs abrogated the increase in the number of 6-OHDA–induced autophagic cells, 12 h after 6-OHDA
treatments (Fig. 5B). Furthermore, we challenged the cell cultures with 100µM H2O2. After 12 h of treatment, H2O2 induced
a robust increase in autophagy (Fig. 5B).
We used aged 6-OHDA, which has lost the ROS-inductor
capacity, to investigate the role of quinone derivates. Cell
cultures were treated with 50µM aged 6-OHDA, and autophagy
activation was assayed. As shown in histograms, aged 6-OHDA
failed to induce an increase in the number autophagosomes per
cell (Fig. 5B).
DISCUSSION
A number of studies have investigated mitochondrial
dynamics in different PD models. However, none of these
have directly compared the activation of mitochondrial fission
and autophagy in the human neuroblastoma cell model of PD
as a consequence 6-OHDA addition. We took advantage of
alterations, being 24% (p < 0.05) after 3 h and 46% (p < 0.01)
after 12 h of treatment. The increase in the number of cells with
mitochondrial morphology alterations was already noticeable
at early time points.
Drp1 is a cytosolic protein that migrates to mitochondria to
induce mitochondrial fission (Lee et al., 2004). To gain insight
in the relevance of mitochondrial fission for 6-OHDA–induced
autophagy, the participation of this protein in autophagy was
assayed. First, using immunoblot analysis, we demonstrated
that the cellular levels of total Drp1 remained unchanged after
6-OHDA treatments, at all of the time points that were assayed
(3–24 h; Fig. 2A). However, immunoblots with mitochondrial
fractions revealed recruitment of Drp1 to mitochondria in
SH-SY5Y cell cultures that were challenged with 6-OHDA
(Fig. 2B). This effect was evident after 3 h of treatment, sustained at 9 h, and levels of mitochondrial Drp1 returned to basal
levels after 24 h of treatment (Fig. 2B).
Second, SH-SY5Y cells were transfected with the fluorescent chimeric protein GFP-Drp1, which enables us to
identify the intracellular localization of Drp1 using confocal
microscopy. Untreated cells showed cytosolic localization of
GFP-Drp1 (Fig. 2C). Upon treatment with 50µM 6-OHDA, a
punctuated distribution of GFP-Drp1 was observed, indicating
that Drp1 was efficiently translocated to the mitochondria in a
time-dependent manner (Figs. 2D and E). The proportion of
cells with a punctuated appearance of Drp1 rose to about 40%
after 3 h of 6-OHDA treatment.
Next, in a pharmacological approach to investigate the
relevance of this protein for autophagy, we used the Drp1inhibitor drug mitochondria-division inhibitor-1 (mdivi-1).
Incubation with mdivi-1 (10µM) led to increased length and
interconnectivity of the mitochondrial network in SH-SY5Y
cell cultures (Fig. 3B) and prevented 6-OHDA–induced
mitochondrial fission (Fig. 3E). Subsequently, we determined
the number of autophagic cells in cultures that were pretreated
for 30 min with 10µM mdivi-1 before being challenged
with 50µM 6-OHDA. After 12 h of 6-OHDA treatment, we
determined the percentage of autophagic cells. Exposure to
mdivi-1 decreased the number of autophagic cells by about
73.5% (Fig. 3F). In addition, mdivi-1 pretreatment significantly
inhibited the 6-OHDA–induced accumulation of LC3b-II levels
in SH-SY5Y cells after 12 h of treatment (Fig. 1D).
415
FIG. 2. Drp1 participates in 6-OHDA–induced mitochondrial fragmentation. (A and B) Immunoblot analysis showing Drp1 levels in total cellular extracts
(A) and mitochondrial fractions (B) of SH-SY5Y cells that were challenged with 50µM 6-OHDA for the indicated periods of time. Equal amounts of protein
(30 μg/lane) were loaded on the gels. α-Tubulin levels were used as an index of total cell load, COX-IV was used as an index of mitochondrial load. The immunoblots shown are representative of three independent experiments. Histograms: Variation of Drp1 levels normalized to α-Tubulin or COX is shown. Results are
expressed as mean ± SEM (n = 3). (C and D) Confocal imaging of SH-SY5Y cells that were transfected with Drp1-GFP and treated (D) or not (C) with 50µM
6-OHDA for 3 h. Images shown are representative of four independent experiments. In each case, several cells were examined. Scale bars: 10 µm. (E) Percentages
of cells with punctuate Drp1 distribution. Results shown are the mean ± SEM of at least three experiments, each performed in triplicate. Significant differences
between 6-OHDA–treated cells and controls are indicated (**p < 0.01).
416
SOLESIO ET AL.
GFP-fusions to Drp1, Bax, and LC3 to study mitochondrial
morphology alterations, Bax translocation, and autophagy
in time-course experiments, and we used a pharmacological
approach to elucidate plausible interrelationships between
these events.
Consistent with our previous observations (Gomez-Lazaro
et al., 2008a), SH-SY5Y cell cultures showed a significant
increase in the percentage of cells with truncated or fragmented
mitochondria upon 6-OHDA treatment. This process was
dependent on the mitochondrial fission factor Drp1. Drp1 is a
cytosolic protein that forms oligomers, which are recruited to
the outer mitochondrial membrane and constrict the organelle
in a GTPase-dependent manner (Fukushima et al., 2001; Zhu
et al., 2004). We observed that Drp1 translocated to mitochondria 3 h after addition of 50µM 6-OHDA although the levels
of total Drp1 were unchanged in cellular extracts. The relevance of this protein for mitochondrial fission was evidenced
further by pretreating the cells with the mdivi-1. mdivi-1 prevents docking of Drp1 at the mitochondrial outer membrane
and, consequently, reduces mitochondrial fission after several
insults (Cassidy-Stone et al., 2008; Cereghetti et al., 2008).
Consistent with this, we observed that mdivi-1 significantly
attenuated 6-OHDA–induced mitochondrial fission.
After 6-OHDA addition, the proapoptotic protein Bax also
translocated from the cytosol to the mitochondria in SH-SY5Y
cells. In our experimental model, this process took place after
mitochondrial fragmentation and Drp1 translocation. SH-SY5Y
cells consistently showed mitochondrial Bax localization 6 h
after 6-OHDA addition. We were unable to find mitochondrial Bax-aggregation loci at the very early time points where
FIG. 3. Drp1 inhibition blocks 6-OHDA–induced mitochondrial morphology alteration and autophagy. (A–D) Representative confocal images of SH-SY5Y
cells that were transfected with the pDsRed2-mito vector. Cells were pretreated (B and D) or not (A and C) with 10µM mdivi-1 prior to a 3 h treatment with 50µM
6-OHDA (C and D). Scale bars: 10 µm. (E) Proportions of cells with fragmented mitochondrial patterns were determined after a 3 h treatment with 6-OHDA. (F)
Proportions of autophagic cells in parallel cell cultures after 12 h of 6-OHDA treatment. Data in histograms are the mean ± SEM of four independent experiments
(**p < 0.01; one way ANOVA post hoc Tukey).
417
FIG. 4.
6-OHDA induces autophagy in a Bax-independent manner. (A and B) Immunoblot analysis of Bax protein levels in total cellular extracts (A) and
mitochondrial fractions (B) of SH-SY5Y cells that were challenged with 50µM 6-OHDA for the periods of time indicated. Equal amounts of protein (30 μg per
lane) were loaded on the gels. The immunoblots shown are representative of three independent experiments. Histograms: Variation of Bax levels normalized to
COX or α-Tubulin is shown. Results are expressed as mean ± SEM (n = 3). (C) Percentages of cells with punctuate Bax distribution upon a 12 h treatment with
50µM 6-OHDA. (D) Drp1 inhibition failed to block Bax translocation. Cell cultures overexpressing Bax-GFP were pretreated (or not) with mdivi-1 for 30 min
prior to the addition of 50µM 6-OHDA. After 12 h of 6-OHDA treatment, the percentages of cells with punctuate Bax-GFP distribution were determined. (E)
Lack of Bax protein expression does not affect the autophagosome formation that is triggered by 6-OHDA. Percentages of autophagic cells, determined as the
proportions of MEF cells expressing LC3-GFP, upon a 12 h treatment with 50µM 6-OHDA. Cells with more than 5 LC3-GFP dots were considered positive. In
C–E, data are the mean ± SEM of at least three independent experiments, each performed in triplicate. Significant differences between treated cells and controls
are indicated (**p < 0.01).
mitochondrial fragmentation was already evident (< 3 h of
treatment). mdivi-1 failed to abrogate the translocation of Bax
to the mitochondria upon 6-OHDA additions. Consequently,
the 6-OHDA–induced mitochondrial Bax translocation was
independent of Drp1 and mitochondrial fission. In agreement
with this, in Drp1−/− cells (Ishihara et al., 2009) or in cells that
were transfected with a dominant negative allele, DrpK38A,
that is defective in GTP binding (Frank et al., 2001; Germain
418
SOLESIO ET AL.
et al., 2005; Karbowski et al., 2002; Lee et al., 2004), Bax
translocates to the mitochondria with kinetics similar to those
observed in wild-type cells. Moreover, mitochondrial release of
proapoptotic proteins, as Smac/DIABLO, is not affected by the
absence of Drp1 (Estaquier and Arnoult, 2007; Parone et al.,
2006). Accordingly, Bax is dispensable for mitochondrial fission in the 6-OHDA model (Gomez-Lazaro et al., 2008a) but
also when fission is induced by hFis1 or by a widely used
intrinsic apoptotic stimulus (Gomez-Lazaro et al., 2008a).
Our results showed that autophagy is induced by 6-OHDA
treatment. The 6-OHDA–induced autophagy correlated with an
increase in the LC3-II protein level and with the accumulation of
autophagic vacuoles in the cytoplasm. Consistent with our data,
accumulation of autophagic vacuoles and activation of lysosomes
have been observed in nigral rat neurons that had been treated
with 6-OHDA (Li et al., 2011). Autophagy seems to be involved
in mitochondrial quality control by promoting the removal of
damaged mitochondria. Our data indicate the involvement
of autophagy in the degradation of altered mitochondria. To
establish this further, we monitored autophagosome formation
in cells that were coexpressing GFP-LC3 and the mitochondrial
protein DsRed2. Among the total mitochondrial population,
autophagosomes appeared to associate specifically with
fragmented mitochondria. In 6-OHDA–challenged SH-SY5Y
cells, the formation of autophagosomes took place distant
from the mitochondria and in a time-dependent manner.
The autophagosomes specifically approach fragmented
mitochondria, as indicated by the observed colocalization at
the later time points of 6-OHDA treatment. Consistent with our
data, the mitochondrial quality control hypothesis postulates
that dysfunctional mitochondria are susceptible to degradation
(Twig et al., 2008) and that mitochondrial elongation serves
to protect mitochondria from mitophagy (Gomes et al., 2011;
Rambold et al., 2011). Another study has shown that cytoplasmic
components are degraded during the initial period of starvation
(0–6 h), whereas mitochondria become a substrate of lysosomes
much later (Kristensen et al., 2008). It remains to be determined
whether the induction of autophagy by 6-OHDA is related to cell
death or to a cytoprotective response, which is activated by dying
cells in order to cope with stress. In a previous study, tyrosine
hydrolase–positive neurons in substantia nigra were protected
from 6-OHDA–induced cell death when they were pretreated
with the autophagy inhibitor 3-methyladenine (Li et al., 2011).
On the other hand, experiments using neuron-specific knockout
mouse models have demonstrated that autophagy deficiency
leads to protein aggregation and neurodegeneration, even in the
absence of disease-related aggregate-prone proteins (He and
Klionsky, 2006).
Further, we investigated the signaling pathways that are
involved in 6-OHDA–induced mitochondrial fission and
autophagy, which revealed a key role for ROS. Our data
demonstrated a relationship between ROS and 6-OHDA–
induced mitochondrial fission and, subsequently, mitophagy.
Intriguingly, 6-OHDA increases H2O2 between the cells. We
reach this observation using the dye CM-H2DCF-DA to measure peroxide-like formation. This specific toll allows us ascertain the role of ROS into the mitochondrial dynamic process.
Thus, H2O2 production is upstream of mitochondrial fission,
given that the inhibition of this dynamic process, by mdivi-1,
did not block mitochondrial H2O2 after 6-OHDA treatments.
In addition, TEMPOL and MnTBAP, two well-known antioxidant drugs, abolished translocation of Drp1 to mitochondria
and, consequently, 6-OHDA–induced mitochondrial fission.
In keeping with this interpretation, oxidative stress might be
FIG. 5. ROS function as second messengers in 6-OHDA–induced mitochondrial fragmentation and autophagy. (A) Effect of 6-OHDA on the MitoP/MitoB
ratio in SH-SY5Y cells. Cells that had been incubated with MitoB were incubated under 50µM 6-OHDA for 3 h, and then the MitoP/MitoB ratio was determined.
Data are means ± SEM of three replicates. (B) Proportions of autophagic cells were determined in at least six different cultures under basal conditions (control) and
after 12 h of treatments. Cell cultures overexpressing GFP-LC3 protein were challenged either with 50µM aged 6-OHDA or with 100µM H2O2. Parallel cultures
were preincubated with 0.2µM TEMPOL or 10nM MnTBAP for 30 min prior to treatment with 6-OHDA. Given values are the mean ± SEM of five independent
experiments that were performed in quadruplicate. (*p < 0.05; **p < 0.001; one-way ANOVA post hoc Tukey; p > 0.05).
responsible for induced mitochondrial fission in several processes, including PD, perhaps due to a redox posttranslational
change in Drp1 protein (Nakamura and Lipton, 2010, 2011).
In conclusion, our findings show that 6-OHDA induces
autophagy in human SH-SY5Y cells, which is mediated
in part by the mitochondrial fission signaling pathways.
Furthermore, ROS contribute to fission and autophagy in this
neurodegenerative disease model. Deciphering the signaling
cascades that underlie mitophagy triggered by 6-OHDA in
SH-SY5Y cell cultures, as well as the mechanisms that determine the selectivity of this response, will help to better understand this process and may have impact on human treatment
strategies of PD.
Supplementary data are available online at http://toxsci.
oxfordjournals.org/.
ACKNOWLEDGMENTS
We thank Carlos Garrido for technical help, and T. Wilson,
Dr S. Strack and Dr J.H.M. Prehn for providing vectors.
FUNDING
This work was supported by SAF2008-05143-C03-1 from
Ministerio de Ciencia e Innovación and PI2007/55 Consejería
de Sanidad from Junta de Comunidades de Castilla-La Mancha
(to J.J.) and by ‘Incorporación de grupos emergentes’ FIS
CARLOS III (EMER07/023) and FIS-FEDER (PI080693;
PI-2008/21 to M.F.G.). M.E.S. is a FIS-FEDER grant fellow.
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BJP
British Journal of
Pharmacology
DOI:10.1111/j.1476-5381.2012.01994.x
www.brjpharmacol.org
RESEARCH PAPER
bph_1994
Correspondence
63..75
3-Nitropropionic acid
induces autophagy by
forming mitochondrial
permeability transition
pores rather than activatiing
the mitochondrial fission
pathway
María F Galindo, Unidad de
Neurofarmacología Traslacional,
Complejo Hospitalario
Universitario de Albacete, C/
Hermanos Falcó 37, 02006
Albacete. Spain. E-mail:
[email protected]
----------------------------------------------------------------
Keywords
Huntington’s disease;
mitochondrial dynamics; MPTP;
Drp1; Bax; Mdivi-1;
mitochondrial swelling
----------------------------------------------------------------
Received
5 December 2011
Revised
19 March 2012
Accepted
26 March 2012
Maria E Solesio1, Sara Saez-Atienzar2, Joaquin Jordan2 and
Maria F Galindo1
1
Unidad de Neuropsicofarmacología Traslacional, Complejo Hospitalario Universitario de
Albacete, Albacete, Spain, and 2Grupo de Neurofarmacología, Dpto. Ciencias Médicas, Fac. de
Medicina de Albacete, Universidad Castilla-La Mancha, IDINE, Albacete, Spain
BACKGROUND AND PURPOSE
Huntington’s disease is a neurodegenerative process associated with mitochondrial alterations. Inhibitors of the electron–
transport channel complex II, such as 3-nitropropionic acid (3NP), are used to study the molecular and cellular pathways
involved in this disease. We studied the effect of 3NP on mitochondrial morphology and its involvement in macrophagy.
EXPERIMENTAL APPROACH
Pharmacological and biochemical methods were used to characterize the effects of 3NP on autophagy and mitochondrial
morphology. SH-SY5Y cells were transfected with GFP-LC3, GFP-Drp1 or GFP-Bax to ascertain their role and intracellular
localization after 3NP treatment using confocal microscopy.
KEY RESULTS
Untreated SH-SY5Y cells presented a long, tubular and filamentous net of mitochondria. After 3NP (5 mM) treatment,
mitochondria became shorter and rounder. 3NP induced formation of mitochondrial permeability transition pores, both in cell
cultures and in isolated liver mitochondria, and this process was inhibited by cyclosporin A. Participation of the mitochondrial
fission pathway was excluded because 3NP did not induce translocation of the dynamin-related protein 1 (Drp1) to the
mitochondria. The Drp1 inhibitor Mdivi-1 did not affect the observed changes in mitochondrial morphology. Finally,
scavengers of reactive oxygen species failed to prevent mitochondrial alterations, while cyclosporin A, but not Mdivi-1,
prevented the generation of ROS.
CONCLUSIONS AND IMPLICATIONS
There was a direct correlation between formation of mitochondrial permeability transition pores and autophagy induced by
3NP treatment. Activation of autophagy preceded the apoptotic process and was mediated, at least partly, by formation of
reactive oxygen species and mitochondrial permeability transition pores.
LINKED ARTICLE
This article is commented on by González-Polo et al., pp. 60–62 of this issue. To view this commentary visit
http://dx.doi.org/10.1111/j.1476-5381.2012.02203.x
Abbreviations
3NP, 3-nitropropionic acid; CsA, cyclosporin A; DCFH-DA, 2′,7′′-dichlorodihydrofluorescein diacetate; Drp1, Dynaminrelated protein 1; Mdivi-1, mitochondrial division inhibitor-1; MnTBAP, Mn(III)tetrakis (4-benzoic acid)porphyrin
© 2012 The Authors
British Journal of Pharmacology © 2012 The British Pharmacological Society
British Journal of Pharmacology (2013) 168 63–75 63
BJP
ME Solesio et al.
chloride; MOMP, mitochondrial outer membrane permeabilization; MPTP, mitochondrial permeability transition pore;
ROS, reactive oxygen species; TEMPOL, 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl; TMRM, tetramethylrhodamine
methyl ester
Introduction
Macrophagy, here simply referred to as autophagy, is associated with cell death. The term autophagic (or type 2) cell
death is also used frequently. In some circumstances, apoptosis and autophagy seem to be, positively or negatively interconnected, referring to the ‘molecular switches’ between
them (Xue et al., 1999; Yu et al., 2006; Leber and Andrews,
2010). Undoubtedly, there are multiple connections between
apoptotic and autophagic processes, which jointly can determine the fate of cells (Leber and Andrews, 2010). Autophagy
plays a physiological role that is important for cellular homeostasis, and this requires a continuous turnover of nonfunctional proteins and organelles (Cuervo, 2004).
Mitochondria are considered multifunctional organelles
of changing morphology. Cells continually adjust the rate of
mitochondrial fission and fusion in response to changing
energy demands and to facilitate the distribution of mitochondria (Detmer and Chan, 2007). These events are especially
relevant within neurons where mitochondria need to be very
active to meet the high energy demands. Mitochondrial malfunctioning has been observed in several neurodegenerative
disorders, and inhibitors of mitochondrial respiration are frequently used to mimic neurodegenerative disorders (Browne
and Beal, 2002). For instance, the succinate dehydrogenase
inhibitor 3-nitropropionic acid (3NP) is commonly used to
develop experimental models of Huntington’s disease (Bove
et al., 2005) Extensive behavioural and neuropathological
evaluations have shown that a partial but prolonged energy
impairment induced by 3NP is sufficient to produce most of
the clinical and pathophysiological hallmarks of Huntington’s
disease (Beal et al., 1993; Brouillet et al., 1999; Bove et al.,
2005). The molecular mechanisms involved in 3NP-induced
neurotoxicity remains unclear. Nevertheless, participation
of the intrinsic apoptosis pathway, which is critically dependent on mitochondrial outer membrane permeabilization
(MOMP), and the consequent release of cell-death-mediating
mitochondrial intermembrane space proteins, such as cytochrome c, has been described (Chipuk et al., 2008). Before
releasing apoptotic factors, mitochondria often display a dramatic morphological transformation, namely a thread-grain
transition, which is mediated by mitochondrial fission proteins (Skulachev et al., 2004; Gomez-Lazaro et al., 2008a).
Swollen mitochondria have been observed in the context of
neurodegenerative diseases (Menzies et al., 2002; Ferreirinha
et al., 2004), and this has been related to the involvement of
the mitochondrial permeability transition pore (MPTP)
(Crompton, 1999). Under in vitro , pseudopathological, conditions of oxidative stress, with relatively high levels of reactive oxygen species (ROS), Ca2+ and low ATP, the complex
flickers into an open-pore state, allowing free diffusion of
solutes across the inner membrane (Crompton, 1999). On the
other hand, Bcl-2 family members, such as Bax, can form
ion-selective channels and larger diameter pores, resulting in
the release of pro-apoptotic proteins (Antignani and Youle,
2006). Recent studies have proposed that mitochondrial
fission is an additional or alternative mechanism in the
64
British Journal of Pharmacology (2013) 168 63–75
mitochondrial pathway of apoptosis (Frank et al., 2001; BossyWetzel et al., 2003; James et al., 2003; Karbowski and Youle,
2003; Lee et al., 2004; Gomez-Lazaro et al., 2008a).
The knowledge of upstream modulators of mitochondrial
dynamics is still not complete. Mitochondrial fission is a
highly regulated process mediated by a defined set of protein
factors (Otsuga et al., 1998; Mozdy et al., 2000; Cerveny et al.,
2001; Karbowski et al., 2004). One of these proteins,
dynamin-related protein 1 (Drp1) in mammals, is a member
of the dynamin family of large GTPases and mediates the
scission of mitochondrial membranes through GTP hydrolysis. Drp1 is predominantly a cytoplasmic protein that associates with mitochondrial fission sites upon oligomerization
(Labrousse et al., 1999; Legesse-Miller et al., 2003). In addition, Drp1 and the pro-apoptotic Bax protein have been
co-localized to scission sites on mitochondria, suggesting that
the mitochondrial fission machinery cooperates with the cell
death machinery (Karbowski et al., 2002).
Consistent with this, autophagy contributes to mitochondrial dysfunction-induced neurodegeneration (Puyal et al.,
2011) and in vivo administration of 3NP activates autophagy
(Zhang et al., 2009). How 3NP regulates autophagy, and how
this is related to mitochondrial morphology is an important
question. Therefore, in the present study, we investigated the
contribution of the mitochondrial morphology pathway to
autophagy activation as induced by 3NP. Our data show that
5 mM 3NP induced autophagy and resulted in mitochondrial
changes. The mitochondrial morphology changed from elongated, tubular, interconnected structures to disintegrated
punctate structures, due to an irreversible mitochondrial
swelling. The 3NP effect was inhibited by the MPTP inhibitor
cyclosporin A (CsA) but was independent of the molecular
fission machinery, as revealed by the use of the Drp1 inhibitor, Mdivi-1. The participation of the Bax protein and ROS
was also addressed.
Methods
Cell culture and drug treatment procedures
SH-SY5Y cell lines were obtained from the American Type
Culture Collection (ATCC), and mouse embryonic fibroblasts
(MEFs) (WT, Bax–/–) were kindly provided by Dr M Serrano,
(CNIO, Spain). Cell cultures were grown as described previously (Jordan et al., 2004) in DMEM-F12 supplemented with
2 mM L-glutamine, 20 units·mL-1 penicillin-streptomycin,
5 mg·mL-1 gentamicin and 15% (v/v) FBS. Cells were grown
in a humidified cell incubator at 37°C under a 5% CO2 atmosphere. Cells were plated 24 h before transfection at a density
of 5.3 ¥ 104 cells cm-2, on 35 mm m-dish (Ibidi GmbH,
Munich, Germany). 3NP was added to culture medium at a
final concentration of 5 mM. Duration of pretreatment with
TEMPOL (0.2 mM) and MnTBAP (10 nM) was 30 min.
Transfections
Twenty-four hours before transfection, cells were plated at a
density of 5.3 ¥ 104 cells cm-2 on poly-L-lysine-coated glass
3NP and mitochondrial morphology
slides. Transfection was achieved using Lipofectamine 2000
reagent (Invitrogen, Carlsbad, CA, USA) according to the
manufacturer’s protocol. Cells were transfected with the following plasmids encoding pDsRed2, Drp1-GFP and Bax-GFP.
After 4 h of incubation, the transfection mixture was
removed and replaced with fresh complete medium. The
experiments were performed 24 h after transfection to allow
protein expression.
Cell fixation, chromatin state and
cell viability
Cells were fixed with 4% paraformaldehyde in PBS and 5%
glucose-sucrose in PBS for 20 min at 37°C and washed three
times with PBS. For assessment of chromatin state, the
SH-SY5Y cells were plated on poly-L-lysine-coated glass slides.
Nuclei were stained with Hoechst 33342 (0.5 mg·mL-1) at RT
for 5 min. Uniformly stained nuclei were scored as healthy,
viable cells. Condensed or fragmented nuclei were scored as
apoptotic. Cell viability after 3NP addition was assessed by
measurement of LDH activity according to the protocol provided by the manufacturer (Promega, Madison, WI, USA).
Briefly, the reaction mixture was added to conditioned media
and removed from 24-well plates after centrifugation at 250¥
g for 10 min. After 30 min of incubation at room temperature, absorbance of samples at 490 nm was measured in a
microplate reader (Bio-Rad, Hercules, CA, USA).
Image acquisition and processing
Micrographs were processed with Huygens Deconvolution
Software (Scientific Volume Imaging, Hilversum, The Netherlands) and Adobe Photoshop. For quantitative analysis of
mitochondrial morphology, the three patterns of mitochondrial morphology (filamentous, punctuate or intermediate)
were recorded in at least 100 cells per coverslip observed on
adjacent fields at magnification 63¥. We assessed the robustness of this classification by comparing the proportions
obtained with separate coverslips from the same experiment
and from successive passages, as well as the proportions
obtained by two independent examiners on three different
cultures. The proportions observed were similar in all these
experiments demonstrating that mitochondrial morphology
could be reliably analysed and did not vary within and
between experiments under basal culture conditions. Morphology was assessed by an examiner, unaware of the treatment administered.
Mitochondrial isolation
All animal care and experimental procedures complied with
the Guiding Principles for Research Involving Animals and
Human Beings of the American Physiological Society, the
Guidelines of the European Union Council (86/609/CEE) and
the Spanish regulations (BOE 67/8509-12, 1988) for the use of
laboratory animals, and were approved by the Scientific Committee of the University of Castilla-La Mancha. All studies
involving animals are reported in accordance with the ARRIVE
guidelines for reporting experiments involving animals
(McGrath et al., 2010). A total of 4 rats were used in the
experiments described here. All animals were housed at 22°C
with 12 h light/12 h dark cycles and with full access to water
and food. Liver mitochondria were isolated from adult male
BJP
Wistar rats (300–350 g). Rat livers were homogenized with an
automatic homogenizer (Heidolph®, Heidolph Instruments
GmbH & Co., Schwabach, Germany). in a buffer containing
210 mM mannitol, 70 mM sucrose,1.0 mM EGTA, 0,1% BSA
and 5 mM HEPES, pH 7.40, using 4 mL of medium per gram of
tissue. Subsequently, differential centrifugation was applied.
Briefly, the homogenate was centrifuged at 1000¥ g for 10 min
and the supernatant at 10 000 ¥ g for 10 min to precipitate
mitochondria that were washed under the same conditions.
The mitochondrial suspensions thus obtained (about 40 mg
protein mL-1) were used immediately after isolation.
Permeability transition pore activity in
isolated mitochondria
Permeability transition pore opening was assayed spectrophotometrically as previously described (Galindo et al.,
2003). Specifically, mitochondria were suspended in 200 mL
of solution containing 125 mM KCl, 20 mM HEPES, 2 mM
KH2PO4, 1 mM EGTA, 1 mM MgCl2, 5 mM malate and 5 mM
glutamate with the pH adjusted to 7.08 with KOH to yield a
final protein concentration of 1 mg·mL-1. Changes in absorbance at 540 nm (A540), indicating mitochondrial swelling as a
result of MPTP opening, were determined after addition of
different compounds using a microtitre plate reader (Bio-Rad,
Hercules, CA, USA). Minor differences in the loading of the
wells were normalized by presenting the values measured at a
given time as the fraction of the initial A540 absorbance (~0.8).
Detection of mitochondrial permeability
transition pore (MPTP) using
calcein fluorescence
To demonstrate induction of the MPTPs, calcein fluorescence
studies were carried out following the method of Petronilli
et al. (1999). This method allows the direct visualization of
permeability changes in mitochondria in situ (Perez-Alvarez
et al., 2010). Calcein/acetoxymethyl ester enters the cells and
becomes fluorescent upon de-esterification. Co-loading of
cells with cobalt chloride quenches the fluorescence in the
cell, except in mitochondria, because mitochondrial membranes are impermeable to cobalt. However, during induction
of the MPTPs, cobalt enters mitochondria and is able to
quench the mitochondrial calcein fluorescence. Cultures
were washed in Krebs–HEPES (K-H) buffer with the following
ionic composition (in mol·L-1): NaCl 140, KCl 5.9, MgCl2 1.2,
HEPES 15, glucose 10 and CaCl2 2.5, pH 7.4, and incubated in
fresh K–H containing calcein/acetoxymethyl ester (1 mM) and
cobalt chloride (1 mM) for 30 min at 22–25°C. Following
cobalt quenching, cultures were washed with K–H buffer, and
images were collected with a confocal microscope within
5 min. This method was validated in cultured SH-SY5Y cells
by the addition of 500 mmol·L-1 CaCl2 along with the calcium
ionophore A23187 (3 mmol·L-1), which was pre-loaded with
calcein and Co2+. The addition of calcium caused a significant
decrease in the mitochondrial calcein fluorescence in a timedependent manner.
Mitochondrial potential
The effects of 3NP treatment on the mitochondrial potential
(DY) in intact SH-SY5Y cells were determined in cells that
were loaded with the DY-sensitive probe tetramethylrhodamBritish Journal of Pharmacology (2013) 168 63–75 65
BJP
ME Solesio et al.
ine methyl ester (TMRM). Briefly, SH-SY5Y cells were loaded
with 10 nM TMRM for 10 min, washed with a standard external medium and challenged with 5 mM 3NP. Images were
collected with a confocal microscope each 15 min during
180 min. Further details have been reported previously
(Garcia-Martinez et al., 2010).
Preparation of cytosolic and
mitochondrial fractions
Cells were washed with ice-cold PBS, left on ice for 10 min and
then re-suspended in isotonic homogenization buffer
(250 mM sucrose, 10 mM KCl, 1.5 mM MgCl2, 1 mM sodiumEDTA, 1 mM sodium-EGTA, 1 mM dithiothreitol, 0.1 mM
PMSF and 10 mM Tris–HCl, pH 7.4) containing a proteinase
inhibitor mixture (Roche, Basel, Switzerland). After 40 strokes
in a Dounce homogenizer, the unbroken cells were spun down
at 30¥ g for 5 min. The mitochondria fractions were fractionated at 750 g for 10 min and 14 000¥ g for 20 min, respectively,
and separated from the supernatant (cytosolic fraction).
Western blotting
The protein concentration from each condition was quantified spectrophotometrically (Micro BCA Protein Reagent Kit,
Pierce), and an equal amount of protein (30 mg) was loaded
onto 10% SDS-PAGE gels. After electrophoresis, proteins were
transferred to PVDF membranes (Immobilon; Millipore Corporation, Billerica, MA, USA). Non-specific protein binding
was blocked with Blotto [4% w/v nonfat dried milk, 4% BSA
(Sigma), and 0.1% Tween 20 (Sigma)] in PBS for 1 h. The
membranes were incubated with a 1:1000 dilution of rabbit
polyclonal anti-Bax antiserum (Cell Signalling, Beverly, MA,
USA), anti-cytochrome C oxidase subunit IV (COX-IV; BD
Biosciences, San José, CA, USA) or a 1:1000 dilution of a
mouse anti-Drp1 monoclonal antibody (BD Biosciences)
overnight at 4°C. After washing with Blotto, the membranes
were incubated with peroxidase-labelled anti-mouse or antirabbit secondary antibodies (Promega) in Blotto. The signal
was detected using an enhanced chemiluminescence detection kit (GE Healthcare, Little Chalfont, Buckinghamshire,
UK). Immunoblots were developed by exposure to X-ray film
(Eastman Kodak, Rochester, NY, USA). Band intensity was
estimated densitometrically on a GS-800 calibrated densitometer (Bio-Rad Quantity One, Hercules, CA, USA).
Intracellular generation of ROS
The
oxidation-sensitive
fluorescent
dye
2′,7′dichlorodihydrofluorescein diacetate (DCFH-DA) was used to
measure the production of ROS, mainly hydrogen peroxide
and hydroxyl radicals, as previously described (FernandezGomez et al., 2005). This non-fluorescent ester is converted by
ROS into DCF, which can easily be visualized by strong fluorescence at 530 nm when excited at 485 nm. Cells seeded in
96-well culture plates were incubated with DCFH-DA
(10 mg·mL-1) for 15 min, before adding either 3NP or vehicle
and 30 min later fluorescence intensity was measured in a
Spectra Max Gemini XS (Molecular Devices, Sunnyvale, CA,
USA). The average relative percentage of ROS production in
four wells from at least three separate cultures was determined.
Statistics
Data shown are means 6 SEM, unless otherwise stated. Statistical significance of differences between groups was deter66
mined by ANOVA followed by a Newman–Keul’s post hoc
analysis. The level of statistical significance was set at P < 0.05.
Materials
DMEM-F12, penicillin-streptomycin, gentamicin and FBS
were purchased from Gibco-Invitrogen (Carlsbad, CA, USA).
The LDH kit (Citotox 96) is from Promega (Madison, WI,
USA); poly-l-lysine, 3NP, Mdivi-1, Hoechst 33342 were
obtained from Sigma-Aldrich (St. Louis, MO, USA). Mn(III)tetrakis (4-benzoic acid)porphyrin chloride (MnTBAP) and
4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPOL)
were purchased from Calbiochem (Darmstadt, Germany); the
BCA protein assay kit from Pierce (Rockford, IL, USA). The
pDsRed2-mito vector was provided by Clontech (Mountain
View, CA, USA), Drp1-GFP was provided by T Wilson and Dr
S Strack (Department Pharmacology, University of Iowa
Carver College of Medicine), and GFP-Bax was a gift from Dr
JHM Prehn (Department of Physiology and RCSI Neuroscience Research Centre, Royal College of Surgeons, Ireland).
The stock solutions of 3NP (5 M in PBS), TEMPOL (0.2 mM in
DMSO) and MnTBAP (10 nM in DMSO) were stored at -20°C.
Results
3NP induces autophagy in SH-SY5Y cells
The protein LC3 has been used as a specific marker for the
quantification of autophagosomes. Overexpression of GFPLC3 is a well-accepted, straightforward and specific assessment
of autophagosome formation. SH-SY5Y cells were transfected
with GFP-LC3 and kept for 24 h before treatment with 3NP.
When these cells are cultured in regular DMEM medium
supplemented with 10% FBS, only a small number of GFP-LC3
dots were detected (4 6 0.2 per cell) (Figure 1A, C), and the
chimeric protein was homogeneously distributed within the
cytosol. The number of these LC3-GFP dots increased to 17 6
1.2 per cell after 3 h treatment with 5 mM 3NP (Figure 1B, C).
Cells with more than five autophagosomes were counted as
autophagic cells. The number of autophagic cells in untreated
conditions was about 16%, whereas in the presence of 3NP,
this number increased to 85 % (Figure 1D).
3NP disrupts mitochondrial morphology
To study the mitochondrial morphology, SH-SY5Y cells were
transfected with pDsRed2-mito plasmid to express the mitochondrial DsRed2 protein. After 24 h of transfection,
untreated cultures present mitochondria with a long and
tubular morphology (Figure 2A), which became dramatically
shorter and rounder in response to 3 h of treatment with
5 mM 3NP (Figure 2B). Cell counting of the different mitochondrial morphologies (filamentous, mixed and fragmented)
indicated that 3NP induced mitochondrial fragmentation and
the formation of swollen, ball-shaped mitochondria in about
40% of the cells (Figure 2C). These changes in shape took place
during the first hour of treatment because, when we examined
the effect of a short-term (1 h) exposure to 3NP by replacing
the culture medium with fresh medium lacking inhibitor and
then examining the mitochondrial morphology, the morphological changes were not reversed (Figure 2D).
To examine if a collapse of the mitochondrial transmembrane potential accompanies mitochondrial fragmentation,
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Figure 1
3NP induces autophagy. (A–B) Confocal images of SH-SY5Y cells 24 h after transfection with the LC3-GFP vector. Representative non-treated cells
(control, A) or incubated for 3 h in 5 mM 3NP (B). Scale bar, 10 mm. (C) Number of cytosolic LC3-GFP vacuoles per cell were determined in at
least six different cultures under basal conditions (control) and after 3 h treatment with 5 mM 3NP. (D) Proportions of autophagic cells in cell
cultures challenged or not with 5 mM 3NP cells for 3 h. Data represent mean 6 SEM of four independent experiments (***P < 0.001, significantly
different from Control, t-test. (E) Left representative Western blot showing LC3-I and II; p62 and tubulin protein bands from total cellular extracts
of SH-SY5Y cells challenged or not with 5 mM 3NP for 3 h. Histograms: Quantitative analysis of the ratio of LC3II to LC3I (n = 4) and (lower graph)
of p62 levels normalized to tubulin (n = 4). Results are expressed as mean 6 SEM (n = 5). ***P < 0.001, significantly different from Control, t-test.
SH-SY5Y cells were incubated with TMRM, a fluorescent dye
that accumulates rapidly and selectively within mitochondria. Uptake of TMRM depends on and is directly proportional to the membrane potential. Statistical analysis of the
TMRM fluorescence intensity showed differences between
controls and cells treated with 5 mM 3NP, after 45 min of
treatment (36 6 2.3% of TMRM fluorescence level of controls,
P < 0.01, n = 5).
Furthermore, these events took place before the appearance of any marker of cell death. After 3 h, cells kept the
capacity to retain LDH intracellularly (Figure 2E, 3 h of total
treatment time). But, consistent with the well-known toxicity
of this inhibitor and the fact that we were using toxic concentrations, cell cultures lost viability when they were cultured for an additional 21 h (Figure 2E; 24 h of total
treatment time).
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ME Solesio et al.
Figure 2
3NP disrupts mitochondrial morphology. (A–B) Confocal images of SH-SY5Y cells 24 h after transfection with the pDsRed2-mito vector.
Representative mitochondrial morphology in non-treated cells (control, A) or incubated for 3 h in 5 mM 3NP (B). Scale bar, 10 mm. (C) Proportions
of cells with filamentous, mixed or fragmented mitochondrial patterns were determined in at least six different cultures under basal conditions
(untreated) and after 3 h treatment with 5 mM 3NP (*P < 0.05, significant effects of 3NP, t-test. (D) 3NP does not induce reversible morphological
changes. Proportions of cells with fragmented mitochondrial patterns were determined after 3 h (untreated), or 1 h and 2 h after removal of the
inhibitor from cell cultures challenged for 1 h with 3NP. (E) Cell viability studies of cell cultures that were exposed for 3 or 24 h to 5 mM 3NP. Data
represent mean 6 SEM of four independent experiments *P < 0.05, significantly different as indicated, t-test.
Mitochondrial permeability transition pore
(MPTP) formation due to 3NP
Under certain conditions, mitochondria respond to cytotoxic
stimuli by forming MPTPs. This results in the swelling of the
organelle (Crompton, 1999). First, we used the calcein
staining/Co2+-quenching technique to image the formation
of MPTPs. Confocal microscopy analysis revealed that as early
as 30 min after 5 mM 3NP addition, a decrease in mitochondrial calcein fluorescence was evident (Figure 3A–E). To elucidate if this phenomenon was due to a direct effect on
mitochondria, we isolated mitochondria from rat livers and
68
measured changes in absorbance at 540 mm, which is an
indicator of organelle swelling. 3NP induced a significant
decrease in the A540 (Figure 3F), indicating that exposure to
3NP induced mitochondrial swelling. The role of MPTP formation on 3NP-induced autophagy was then assessed. Cell
cultures were pre-treated for 30 min with the MPTP inhibitor
CsA (1 mM) and then challenged with 5 mM 3NP. The inhibition of MPTP blocked 3NP-induced autophagy (24.6 6
2.4% autophagic cells in the presence of CsA vs. 84.6 6 5.4%
in the absence of CsA; P < 0.001, n = 5 independent cultures).
Furthermore, CsA prevented the mitochondrial changes
induced by 3NP (Figure 4D).
BJP
Figure 3
MPTP participation in 3NP-induced mitochondrial alteration. (A–D) Changes in mitochondrial fluorescence of calcein. SH-SY5Y cells loaded with
calcein/Co2+ were treated with 5 mM 3NP. Representative confocal images of calcein fluorescence in SH-SY5Y cells, before (left) or 30 min after
(right) treatment. (E) Fluorescence intensity normalized to the initial value. Data represent mean 6 SEM of four independent experiments. (F) 3NP
induces mitochondrial swelling. Mitochondrial suspensions were exposed to 5 mM 3NP, and A540 was recorded. Ca2+ (75 mM) was used as a
positive control for mitochondrial swelling. Data represent mean 6 SEM of four independent experiments. ***P< 0.001 significantly different from
vehicle, t-test.
BJP
ME Solesio et al.
Figure 4
Drp1 displays cytosolic localization after 3NP treatment. (A) Confocal imaging of SH-SY5Y cells transfected with Drp1-GFP and treated with 5 mM
3NP. Drp1-GFP demonstrated primarily diffuse staining in control (left) and after 3 h treatment with 3NP (right). Images shown are representative
of four separate experiments, each performed in triplicate. (B) Number of cells with punctuate Drp1-GFP distribution were counted and expressed
as percentage of the total number of cells expressing Drp1-GFP. Data shown are the mean 6 SEM. of at least three experiments, each performed
in triplicate. (C) Levels of Drp1 were determined in mitochondrial fraction (M) and soluble extracts (S) from SH-SY5Y control cells and cells treated
with 5 mM 3NP. COX-IV protein levels (lower panel) were used as an index of mitochondrial contamination. Equal amounts of protein
(30 mg/lane) were loaded onto the gels. The immunoblots shown are representative of three independent experiments. Fold variation of Drp1
levels normalized to COX are shown at the bottom of each line. Data shown are mean 6 SEM (n = 5). (D) Effects of Mdivi-1 and CsA on
3NP-induced changes in mitochondrial morphology. SH-SY5Y cells transfected with pDsRed2-mito vector were co-treated with either 10 mM
Mdivi-1 or CsA and 5 mM 3NP. Proportions of cells with filamentous, mixed or fragmented mitochondrial patterns were determined in at least
six different cultures under basal conditions (control) and after 3 h treatment with 5 mM 3NP. **P < 0.01, significantly different as indicated,
one-way ANOVA with Tukey’s post hoc test. (E)Mdivi-1 effects on 3NP-induced autophagy. SH-SY5Y cells transfected with LC3-GFP vector and
co-treated with 10 mM Mdivi-1 and 5 mM 3NP. Proportions of autophagic cells in cell cultures challenged or not with 5 mM 3NP cells for 3 h. Data
shown are the mean 6 SEM of four independent experiments.
3NP did not activate mitochondrial Drp1
translocation
Translocation of the cytosolic protein Drp1 to the mitochondria has been associated with mitochondrial fission. To evaluate the effects of 3NP on Drp1 cellular localization, cell
cultures overexpressing Drp1-GFP were used. In untreated
cultures, Drp1-GFP distribution was cytosolic (Figure 4A).
70
Treatment of the cells with 3NP (5 mM, 3 h) did not induce
changes in Drp1-GFP distribution (Figure 4B). We also
assayed the localization of this protein using immunoblotting of cellular subfractions isolated from cell cultures. Consistent with the above results, 3NP did not induce the
translocation of Drp1 from the cytosol to the mitochondria
(Figure 4C).
To evaluate the role of Drp1 in 3NP-induced autophagy,
the mitochondrial division inhibitor Mdivi-1 was used
(Cassidy-Stone et al., 2008; Tanaka and Youle, 2008). Cell
cultures were pre-treated for 30 min with Mdivi-1 (10 mM)
before being challenged with 5 mM 3NP. Furthermore,
Mdivi-1 (10 mM) treatment resulted in extensive budding and
elongation of the mitochondrial network, but did not inhibit
the mitochondrial fragmentation caused by 3NP (Figure 4D).
Furthermore, the inhibition of Drp1 did not block 3NPinduced autophagy (Figure 4E).
Bax translocates to the mitochondria after
3NP addition
Bax is a pro-apoptotic protein that participates in cell death
and mitochondrial fission. To study whether the 3NP treatment induced Bax translocation, we analysed cells overexpressing GFP-Bax and performed immunoblotting of cellular
subfractions isolated from cell cultures. As shown in Figure 5,
both approaches revealed translocation of Bax to the mitochondria in cell cultures challenged with 5 mM 3NP. 3NP
induced an increase in the number of cells with a punctuate
distribution of Bax-GFP (Figure 5A–C), and immunoblotting
revealed an increase of the levels of the protein in the cytosol
(S, Figure 5C) as well as in mitochondrial subfractions (M,
Figure 5C).
To investigate if inhibition of Drp1 modulated the translocation of Bax to the mitochondria, SH-SY5Y cells transfected
Bax-GFP were co-treated with Mdivi-1 and 3NP. After 3 h, the
number of cells with Bax-GFP punctuated distribution was
determined. As shown in Figure 5D, 10 mM Mdivi-1 failed to
affect 3NP-induced Bax-GFP translocation to mitochondria.
Next, we aimed to elucidate the role of Bax protein in
3NP-induced mitochondrial morphology alterations. To this
end, we used embryonic fibroblasts from Bax–/– mice. Lack of
Bax protein expression neither prevented 3NP-induced MPTP
formation, evaluated after 45 min of 3NP treatment using a
confocal microscopy calcein technique (Figure 5E), nor did it
affect the alterations in mitochondrial morphology, measured 3 h later (Figure 5F).
Role of ROS
To further delineate the physiological consequences of 3NP
addition, we also considered the role of ROS. In this study, we
used DCFH-DA, a redox-sensitive probe, to demonstrate if
3NP increased intracellular levels of ROS. After 3 h of treatment, we found that cells challenged with 3NP displayed a
significant increase in DFA fluorescence emission intensity
(Figure 6A, vehicle). Next, we determined the effect of ROS
scavenger drugs on 3NP-induced effects. Cells were preincubated with the antioxidants TEMPOL (0.2 mM) or
MnTBAP (10 nM) 30 min before 3NP treatments. Confocal
microscopy analysis of cell cultures overexpressing LC3-GFP
protein revealed that both scavengers failed to inhibit the
formation of autophagic cells by 3NP (Figure 6B). Furthermore, both these drugs failed to prevent 3NP-induced
changes in mitochondrial morphology (Figure 6C).
Finally, we assessed the relationship between changes in
mitochondrial morphology and 3NP-induced ROS by pretreating cell cultures with either Mdivi-1 or CsA and measuring ROS production 3 h after 3NP addition. As shown in
BJP
Figure 6A, only 1 mM CsA, but not Mdivi-1, was able to block
3NP-induced ROS production.
Discussion
In this study, SH-SY5Y cells were used to investigate the effect
of 3NP on autophagy and its relationship with alterations
in mitochondrial morphology. We demonstrated that 3NP
provoked autophagy through irreversible mitochondrial
changes. This involved organelle swelling by the formation of
MPTPs rather than activation of the fission program.
Autophagy is emerging as a pathway relevant to physiology and alterations in this process contribute to several diseases (Kroemer and Levine, 2008). At 3 h after addition of
5 mM 3NP, SY-SY5Y cell cultures presented an increased
number of autophagosomes, which is characteristic of
autophagy. Consistent with this observation, morphological
and biochemical analyses of rat striatum treated with 3NP by
stereotaxic injection showed activation of autophagy in striatal cells (Zhang et al., 2009). By this time point, cell cultures
exposed to 3NP showed clear changes in mitochondrial morphology, but not clear signs of cell death. The organelles
presented a markedly shorter and rounder morphology, compared with those from untreated cultures. To observe this we
used a fluorescent protein, pDsRed2-mito, targeted to the
mitochondria. pDsRed2-mito is efficiently localized to both
wild-type and respiratory-deficient mitochondria, allowing
studies of mitochondrial morphology in compromised conditions such as the addition of 3NP, well-known to inhibit
complex II. Although we mostly evaluated morphological
alterations at 3 h after 3NP addition, mitochondrial alterations take place during the early stages of treatment. In preliminary studies, we were able to detect mitochondria with
altered morphology as early as 1 h after 3NP addition. Moreover, if we treated cells only for 1 h and analysed the mitochondrial morphology 3 h later, the effects on mitochondrial
morphology were similar to those seen after 3h exposure to
3NP. However, these effects could be a consequence of nonreversible inhibition of complex II by 3NP. On the other hand,
supporting our hypothesis are the data from the analysis of
MPTP formation both in vivo and in isolated mitochondria.
The influence of mitochondrial dynamics on cellular
functioning is perhaps best appreciated in neurons, as these
cells have a high energy requirement to support distantly
located and metabolically demanding synaptic terminals.
Strong evidence has been presented, indicating that mitochondrial malfunction plays a crucial part in the pathogenesis of Huntington’s disease. Mitochondria isolated from
lymphocytes of Huntington’s disease patients have decreased
Ca2+-buffering capacity Moreover, possibly due to a direct
interaction between the poly-glutamine stretch in mutant
huntingtin and the mitochondria, their mitochondrial membrane potential depolarizes earlier at lower Ca2+ concentrations (Panov et al., 2002).
We observed depletion in calcein fluorescence during the
first 30 min after 3NP addition. In isolated mitochondria,
3NP induced mitochondrial swelling by CsA-sensitive classic
MPTP formation. Consistent with This observation was
consistent with that of Nishimura et al. (2008) who described
how 3NP-induced functional changes of mitochondria were
BJP
ME Solesio et al.
Figure 5
3NP induces Bax translocation to the mitochondria but does not mediate alterations in mitochondrial morphology. (A) Confocal imaging of
SH-SY5Y cells that were transfected with Bax-GFP, incubated for 24 h to allow sufficient Bax-GFP expression and treated with 5 mM 3NP. After 3 h
exposure the cells were fixed in 4% paraformaldehyde, and confocal images were captured using a 63¥ oil immersion lens. Bax-GFP demonstrated
primarily diffuse staining in control (left), whereas 3 h after 3NP treatment a punctuate pattern is evident. Images shown are representative of four
separate experiments, each performed in triplicate. (B) The numbers of cells with punctuate Bax-GFP distribution were counted and expressed as
percentage of the total number of cells. Data shown are the mean 6 SEM of at least three experiments, each performed in triplicate. *P < 0.05,
significantly different from control, t-test. (C) Levels of Bax were determined in mitochondrial fraction (M) and soluble extracts (S) from SH-SY5Y
cells treated with or without 5 mM 3NP. COX-IV protein levels (lower panel) were used as an index of mitochondrial contamination. Equal
amounts of protein (30 mg/lane) were loaded onto the gels. An immunoblot from SH-SY5Y cell cultures, representative of five independent
experiments, is shown. Fold variation of Bax levels (mean 6 SEM; n = 5) normalized to control, are shown at the top of each line. . (D) Drp1
inhibition does not modify Bax-GFP translocation. SH-SY5Y cells transfected with Bax-GFP plasmid were co-treated with 10 mM Mdivi-1 and with
5 mM 3NP. After 3 h of treatment, proportions of cells with diffuse or punctuate GFP-distribution patterns were determined in at least six different
cultures. Data represent mean 6 SEM of four independent experiments. (E) Confocal calcein fluorescence intensity in MEF from Bax–/– mice 45 min
after 5 mM 3NP treatments. Values were normalized to the initial value. Data represent mean 6 SEM of four independent experiments. (F) MEF
from Bax–/– mice were transfected with pDsRed2-mito vector and treated with 5 mM 3NP. Proportions of cells with fragmented mitochondrial
patterns were determined in at least six different cultures under basal conditions (control) and after 3 h treatment with 5 mM 3NP (3NP, n/s
P > 0.05; **P < 0.01, significantly different as indicated; one-way ANOVA with Tukey’s post hoc test.
72
BJP
Figure 6
ROS do not function as second messengers in 3NP-induced mitochondrial fragmentation. (A) 3NP induces the production of peroxides. Cell
cultures were pre-treated with 10 mM Mdivi-1, 1 mM CsA or vehicle for 30 min before the addition of 5 mM 3NP, and production of peroxide-like
ROS was measured 3 h after 3NP addition. Data were normalized to vehicle-treated cells, and values shown are the mean 6 SEM of five
independent experiments performed in quadruplicate. *P < 0.05, **P < 0.001, significantly different as indicated, one-way ANOVA with Tukey’s post
hoc test; ns, P > 0.05). (B) TEMPOL (0.2 mM) or MnTBAP(10 nM) effects on 3NP-induced autophagy. SH-SY5Y cells were transfected with LC3-GFP
vector and pre-incubated with 0.2 mM TEMPOL or 10 nM MnTBAP for 30 min prior to treatment with 5 mM 3NP. Proportions of autophagic cells
in cell cultures that were challenged or not with 5 mM 3NP cells for 3 h. Data represent mean 6 SEM of four independent experiments. (C)
Confocal microscopy analysis of mitochondrial morphology of cell cultures overexpressing pDsRed2-mito protein and pre-incubated with 0.2 mM
TEMPOL or 10 nM MnTBAP 30 min before treatment with 5 mM 3NP. Proportions of cells with filamentous, mixed or fragmented mitochondrial
patterns were determined in at least six different cultures under basal conditions (control) and after 3 h of treatment with inhibitors. Data represent
mean 6 SEM of four independent experiments.
caused by the CsA-sensitive classic MPTP. Furthermore, Leventhal et al. (2000) showed that the neuroprotective properties of CsA are mediated by its ability to prevent MPTP
opening during exposure to high levels of calcium or oxidative stress in 3NP-lesioned rats.
Our data support the notion that mitochondrial fission
did not actively participate in the 3NP-induced morphological changes we observed. Mitochondrial fission requires
Drp1, a large GTPase of the dynamin family. Drp1 is cytosolic
but a subpool of the protein concentrates in discrete spots on
mitochondria at sites of future fission (Labrousse et al., 1999;
Legesse-Miller et al., 2003) and assembles into rings around
mitochondria and constricts their membranes, breaking
down the organelles in a GTP hydrolysis-dependent mechanism (Ingerman et al., 2005). In our study, 3NP did not recruit
Drp1 to mitochondria. We reach this conclusion from several
kinds of experiments that included assaying the levels of
Drp1 protein in cytosolic and mitochondrial subcellular fractions, which failed to detect increases in either fraction. In
addition, confocal microscopy of cell cultures overexpressing
Drp1-GFP revealed that addition of 3NP did not modify the
cytosolic and diffuse distribution of Drp1. A similar conclusion was reached when we analysed the capacity of 3NP to
induce mitochondrial morphological alterations in cell cultures where Drp1 was inhibited using Mdivi-1. Mdivi-1 selectively inhibits the activity of mitochondrial division
dynamin-related proteins by binding to an allosteric site that
does not exclusively act through the GTPase domain
(Cassidy-Stone et al., 2008). The concentration of Mdivi-1
used in our study (10 mM) was sufficient to inhibit Drp1 as
was shown by extensive budding and elongation of the mitochondrial network in the SH-SY5Y cell cultures.
After 3NP addition, Bax translocated to the mitochondria
in SH-SY5Y cells. The participation of Bax in mitochondrial
fission is controversial (Antignani and Youle, 2006). Bax was
found to co-localize with Drp1 and Mfn2 at mitochondrial
fission sites in apoptotic cells (Karbowski et al., 2002) and has
been suggested to participate directly in apoptotic mitochondrial fission. Consistent with this, Drp1 or Fis1 knockdown
resulted in a reduced accumulation of Bax in mitochondria
BJP
ME Solesio et al.
(Lee et al., 2004). However, in SH-SY5Y cells, Bax translocation occurred in a non-concatenate process of mitochondrial
fission after 3NP treatment. Indeed, by the time that mitochondria were already fragmented (1–3 h), Bax had not yet
translocated to the mitochondria. Moreover, and in support
of a different activation route, 3NP-induced Bax translocation
was not inhibited by Mdivi-1. Our observations were In agreement withealier studies in which Drp1 knockdown or a
mutant Drp1K38A exhibited no effect on Bax dynamics
(Frank et al., 2001; Lee et al., 2004). We have already shown,
in a different neurodegenerative model using MEF cell cultures from mice lacking Bax, that this protein is not required
for 6-OHDA-induced mitochondrial fragmentation (GomezLazaro et al., 2008a). Thus, the function of Bax might be
related to MOMP in 3NP-treated cells. Consistent with this
hypothesis, mitochondrial energization associated with
apoptosis promotes Bax translocation to mitochondria
(Smaili et al., 2001; Gomez-Lazaro et al., 2008b; Perez-Alvarez
et al., 2009), and we and others have found that Bax actively
participates in neurodegenerative process (Gomez-Lazaro
et al., 2008b; Perez-Alvarez et al., 2009). Indeed, 3NP, in striatal neurons, produced distribution of pro-apoptotic proteins
including Bad and Bax (Galas et al., 2004).
We also addressed the function of ROS in 3NP-activated
pathways. Our data indicate that, although 3NP increased
intracellular ROS, the ROS did not appear to be a significant
signalling link between 3NP and the mitochondrial fragmentation machinery. When ROS were scavenged, a slight, nonsignificant, inhibition of autophagy and mitochondrial
alteration was observed. However, ROS induction was
blocked when we inhibited mitochondrial swelling using
CsA. Again, and consistent with the notion that mitochondrial fission does not play a role in our model, Mdivi-1 did
not modulate 3NP-induced ROS production. An explanation
for this observation can be found in the results of Liot et al.
(2009) who placed mitochondrial fragmentation upstream of
ROS production. These authors observed that 3NP induced an
initial wave of ROS formation, which was not related to
mitochondrial fragmentation or cell death.
Our data show a direct correlation between MPTP formation and autophagy induced by 3NP treatment. Activation of
autophagy preceded the apoptotic process and was mediated,
at least partly, by ROS and MPTP formation. Further elucidation of beneficial and detrimental roles of autophagy in
neurodegenerative diseases will shed new light on the pathogenesis of neurodegenerative diseases that involve mitochondrial dysfunction.
CARLOS III (EMER07/023) and FIS-FEDER (PI080693) and
PI11/00736 (to MFG). MES is a FIS-FEDER grant fellow.
Conflicts of interest
None.
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Acknowledgements
We thank Joaquín Soriano (UCLM) and Manuel Izquierdo
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Buendia, Noemi Pérez and Carlos Garrido for technical help,
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TESIS Solesio Torregrosa - Ruidera - Universidad de Castilla

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