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HydroPaCe: uma metodologia para análise de inibição cruzada em serino proteases através de centroides de regiões hidrofóbicas

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Academic year: 2017

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❱❆▲❉❊❚❊ ▼❆❘■❆ ●❖◆➬❆▲❱❊❙ ❉❊ ❆▲▼❊■❉❆

❍❨❉❘❖P❆❈❊✿ ❯▼❆ ▼❊❚❖❉❖▲❖●■❆ P❆❘❆

❆◆➪▲■❙❊ ❉❊ ■◆■❇■➬➹❖ ❈❘❯❩❆❉❆ ❊▼ ❙❊❘■◆❖

P❘❖❚❊❆❙❊❙ ❆❚❘❆❱➱❙ ❉❊ ❈❊◆❚❘❖■❉❊❙ ❉❊

❘❊●■Õ❊❙ ❍■❉❘❖❋Ó❇■❈❆❙

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❯♥✐✈❡rs✐❞❛❞❡ ❋❡❞❡r❛❧ ❞❡ ▼✐♥❛s ●❡r❛✐s

■♥st✐t✉t♦ ❞❡ ❈✐ê♥❝✐❛s ❇✐♦❧ó❣✐❝❛s

Pr♦❣r❛♠❛ ❞❡ Pós✲●r❛❞✉❛çã♦ ❡♠ ❇✐♦✐♥❢♦r♠át✐❝❛

❍❨❉❘❖P❆❈❊✿ ❯▼❆ ▼❊❚❖❉❖▲❖●■❆ P❆❘❆

❆◆➪▲■❙❊ ❉❊ ■◆■❇■➬➹❖ ❈❘❯❩❆❉❆ ❊▼ ❙❊❘■◆❖

P❘❖❚❊❆❙❊❙ ❆❚❘❆❱➱❙ ❉❊ ❈❊◆❚❘❖■❉❊❙ ❉❊

❘❊●■Õ❊❙ ❍■❉❘❖❋Ó❇■❈❆❙

❚❡s❡ ❛♣r❡s❡♥t❛❞❛ ❛♦ ❈✉rs♦ ❞❡ Pós✲ ●r❛❞✉❛çã♦ ❡♠ ❇✐♦✐♥❢♦r♠át✐❝❛ ❞❛ ❯♥✐✲ ✈❡rs✐❞❛❞❡ ❋❡❞❡r❛❧ ❞❡ ▼✐♥❛s ●❡r❛✐s ❝♦♠♦ r❡q✉✐s✐t♦ ♣❛r❝✐❛❧ ♣❛r❛ ❛ ♦❜t❡♥çã♦ ❞♦ ❣r❛✉ ❞❡ ❉♦✉t♦r ❡♠ ❇✐♦✐♥❢♦r♠át✐❝❛✳

❱❆▲❉❊❚❊ ▼❆❘■❆ ●❖◆➬❆▲❱❊❙ ❉❊ ❆▲▼❊■❉❆

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❯◆■❱❊❘❙■❉❆❉❊ ❋❊❉❊❘❆▲ ❉❊ ▼■◆❆❙ ●❊❘❆■❙

❍②❞r♦P❛❈❡✿ ✉♠❛ ♠❡t♦❞♦❧♦❣✐❛ ♣❛r❛ ❛♥á❧✐s❡ ❞❡ ✐♥✐❜✐çã♦ ❝r✉③❛❞❛

❡♠ s❡r✐♥♦ ♣r♦t❡❛s❡s ❛tr❛✈és ❞❡ ❝❡♥tr♦✐❞❡s ❞❡ r❡❣✐õ❡s ❤✐❞r♦❢ó❜✐❝❛s

❱❆▲❉❊❚❊ ▼❆❘■❆ ●❖◆➬❆▲❱❊❙ ❉❊ ❆▲▼❊■❉❆

P❤✳ ❉✳ ▼❛r❝❡❧♦ ▼❛t♦s ❙❛♥t♦r♦ ✕ ❖r✐❡♥t❛❞♦r ❯♥✐✈❡rs✐❞❛❞❡ ❋❡❞❡r❛❧ ❞❡ ▼✐♥❛s ●❡r❛✐s

P❤✳ ❉✳ ❘❛q✉❡❧ ❈✳ ❞❡ ▼❡❧♦ ▼✐♥❛r❞✐ ✕ ❈♦✲♦r✐❡♥t❛❞♦r ❯♥✐✈❡rs✐❞❛❞❡ ❋❡❞❡r❛❧ ❞❡ ▼✐♥❛s ●❡r❛✐s

P❤✳ ❉✳ ❈❛r❧♦s ❍❡♥r✐q✉❡ ❞❛ ❙✐❧✈❡✐r❛ ✕ ❈♦✲♦r✐❡♥t❛❞♦r ❯♥✐✈❡rs✐❞❛❞❡ ❋❡❞❡r❛❧ ❞❡ ■t❛❥✉❜á

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❘❡s✉♠♦

■♥t❡r❢❛❝❡s ❞❡ ✐♥t❡r❛çõ❡s ♣r♦t❡í♥❛✲♣r♦t❡í♥❛ ❝♦♥tê♠ ✐♥❢♦r♠❛çõ❡s ✐♠♣♦rt❛♥t❡s s♦❜r❡ ♦ r❡✲ ❝♦♥❤❡❝✐♠❡♥t♦ ♠♦❧❡❝✉❧❛r✳ ❊st❡ tr❛❜❛❧❤♦ ✈❡rs❛ s♦❜r❡ ❛ ❞❡s❝♦❜❡rt❛ ❞❡ ♣❛❞rõ❡s ❝♦♥s❡r✈❛❞♦s ♥❡st❛ r❡❣✐ã♦✳ ◆ós ❡♥t❡♥❞❡♠♦s q✉❡ é ❡ss❡♥❝✐❛❧ ❝♦♠♣r❡❡♥❞❡r ❝♦♠♦ s✉❜str❛t♦s ❡ ✐♥✐❜✐❞♦r❡s sã♦ ❧✐❣❛❞♦s ♦✉ ♣❛r❛ ♣r❡❞✐③❡r ❛ ❧✐❣❛çã♦ ♠♦❧❡❝✉❧❛r✳ ◗✉❛♥❞♦ ✉♠ ✐♥✐❜✐❞♦r ❧✐❣❛✲s❡ ❛ ❡♥③✐♠❛s ❝♦♠ ❡str✉t✉r❛s✱ s❡q✉ê♥❝✐❛s ♦✉ ♠❡❝❛♥✐s♠♦s ❞✐❢❡r❡♥t❡s✱ ♥ós ❝❤❛♠❛♠♦s ❡st❛ ❢❛❧t❛ ❞❡ ❡s♣❡❝✐✲ ✜❝✐❞❛❞❡ ❞❡ ■♥✐❜✐çã♦ ❈r✉③❛❞❛✳ ❆ ✐❞❡♥t✐✜❝❛çã♦ ❞❡ ✈❛r✐❛♥t❡s é ✉♠ t❛r❡❢❛ ❞✐❢í❝✐❧ ♥♦ q✉❛❧ ♦s ♠ét♦❞♦s tr❛❞✐❝✐♦♥❛✐s ♣♦❞❡♠ ❢❛❧❤❛r✳ P❛r❛ ❡♥t❡♥❞❡r ❝♦♠♦ ❛ ✐♥✐❜✐çã♦ ❝r✉③❛❞❛ ♦❝♦rr❡✱ ♥ós ♠♦❞❡❧❛♠♦s ♦ ♣r♦❜❧❡♠❛ ❡ ♣r♦♣♦♠♦s ✉♠❛ ♠❡t♦❞♦❧♦❣✐❛✱ ♥❛ q✉❛❧ ❝❤❛♠❛♠♦s ❞❡ ❍②❞r♦P❛❈❡ ✭❍②❞r♦❢♦❜✐❝ P❛t❝❤ ❈❡♥tr♦✐❞✮ ❡ ❛✈❛❧✐❛♠♦s✱ ♣♦r ♠❡✐♦ ❞❡ ♠étr✐❝❛ ❞❡ ❝♦❜❡rt✉r❛ ♣❡♥❛❧✐③❛❞❛ P❘▼ ✭P❡♥❛❧✐③❡❞ ❘❡❝❛❧❧ ▼❡tr✐❝✮✱ ♣❛r❛ ❞❡t❡❝t❛r ♣❛❞rõ❡s ❝♦♥s❡r✈❛❞♦s✳ ❖s át♦♠♦s ❤✐❞r♦✲ ❢ó❜✐❝♦s q✉❡ ❝♦♠♣õ❡♠ ❛ ✐♥t❡r❢❛❝❡ ❢♦r❛♠ ♠♦❞❡❧❛❞♦s ❝♦♠♦ ❣r❛❢♦s ❞❡ ✐♥t❡r❛çõ❡s ❛♣♦❧❛r❡s ❡ ♦s ♣❛t❝❤❡s ♦✉ r❡❣✐õ❡s ❝♦♥❡❝t❛❞❛s ❢♦r❛♠ ❝♦♠♣✉t❛❞❛s ❡ s✉♠❛r✐③❛❞❛s ❡♠ ❝❡♥tr♦✐❞❡s ❣❡♦♠é✲ tr✐❝♦s ✭❍P✲❝❡♥tr♦✐❞❡s✮✱ ❡ s✉❛ ❝♦♥s❡r✈❛çã♦ ❢♦✐ ❞❡t❡❝t❛❞❛✳ ◆ós ❛♥❛❧✐s❛♠♦s ❞♦✐s ❝❛s♦s ❞❡ ✐♥✐❜✐çã♦ ❝r✉③❛❞❛✱ s❡♥❞♦ ✉♠ ❝♦♠ ♦ ✐♥✐❜✐❞♦r ❖✈♦♠♦✈♦✐❞❡ ✭✺ ❝♦♠♣❧❡①♦s ♥ã♦ r❡❞✉♥❞❛♥t❡s✮ ❡ ♦✉tr♦ ❝♦♠ ♦ ✐♥✐❜✐❞♦r ❊❣❧✐♥❛ ❈ ✭✹ ❝♦♠♣❧❡①♦s ♥ã♦ r❡❞✉♥❞❛♥t❡s✮✳ ❆❧é♠ ❞✐ss♦✱ ❞✉❛s ❢❛♠í❧✐❛s ❞❡ s❡r✐♥♦ ♣r♦t❡❛s❡s✱ ❛s ❚✐♣♦ ❚r✐♣s✐♥❛ ✭✸✺ ❡str✉t✉r❛s ♥ã♦ r❡❞✉♥❞❛♥t❡s✮ ❡ ❚✐♣♦ ❙✉❜t✐❧✐s✐♥❛ ✭✾ ❡str✉t✉r❛s ♥ã♦ r❡❞✉♥❞❛♥t❡s✮✱ ❝♦♠ ❝❛❞❡✐❛s s✐♠♣❧❡s ❢♦r❛♠ ❛♥❛❧✐s❛❞❛s✱ ✉s❛♥❞♦ té❝♥✐❝❛ ❞❡ ♣r♦❥❡çã♦ ❞❛ ✐♥t❡r❢❛❝❡✳ ❖s ♣❛❞rõ❡s ❡♥❝♦♥tr❛❞♦s ♥❛s ✐♥t❡r❢❛❝❡s ❞❛s ✐♥✐❜✐çõ❡s ❝r✉③❛❞❛s ❢♦r❛♠ ❡♥❝♦♥tr❛❞♦s ♥❛ ♠❛✐♦r✐❛ ❞❛s ❡♥③✐♠❛s ❞❡st❛s ❢❛♠í❧✐❛s✳ ❆❝r❡❞✐t❛♠♦s q✉❡ ♥♦ss❛ ♠❡t♦❞♦❧♦❣✐❛ ❛t✐♥❣✐✉ ✉♠ ♥í✈❡❧ ❞❡ ❛❜str❛çã♦ ♣❛r❛ ♦❜t❡r ♣r♦♣r✐❡❞❛❞❡s ✐♥✈❛r✐❛♥t❡s ❡♠ ✐♥✐❜✐çã♦ ❝r✉③❛❞❛✳ ◆ós ♠♦str❛♠♦s ❡①❡♠♣❧♦s ♦♥❞❡ ♦s ❍P✲❝❡♥tr♦✐❞❡s ❢♦r❛♠ ♣r❡❞✐t♦s ❝♦♠ s✉❝❡ss♦ ❡♠ ❡♥③✐♠❛s ♣♦r ✐♥✐❜✐❞♦r❡s ❥á ❡st✉❞❛❞♦s✱ ❞❡ ❛❝♦r❞♦ ❝♦♠ ❛ ❜❛s❡ ❞❡ ❞❛❞♦s ❇❘❊◆❉❆✳ P♦r ✜♠✱ ♥ós ❞✐s✲ ♣♦♥✐❜✐❧✐③❛♠♦s t♦❞♦s ♦s ❝ó❞✐❣♦s✱ ✉s❛❞♦s ♥♦s ♣❛ss♦s ♠❡t♦❞♦❧ó❣✐❝♦s✱ ❜❡♠ ❝♦♠♦✱ t✉t♦r✐❛✐s ❡

❡①❡♠♣❧♦s ❡♠ ✇✇✇✳❞❝❝✳✉❢♠❣✳❜r✴∼r❛q✉❡❧❝♠✴❤②❞r♦♣❛❝❡✳

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❆❜str❛❝t

■♥t❡r❢❛❝❡s ♦❢ ♣r♦t❡✐♥✲♣r♦t❡✐♥ ✐♥t❡r❛❝t✐♦♥s ❝♦♥t❛✐♥ ✐♠♣♦rt❛♥t ✐♥❢♦r♠❛t✐♦♥ ❛❜♦✉t ♠♦❧❡❝✉✲ ❧❛r r❡❝♦❣♥✐t✐♦♥✳ ❚❤✐s ✇♦r❦ ❛✐♠s ❛t t❤❡ ❞✐s❝♦✈❡r② ♦❢ ❝♦♥s❡r✈❡❞ ♣❛tt❡r♥s ✐♥ t❤✐s r❡❣✐♦♥✳ ❲❡ ❜❡❧✐❡✈❡ ✐t ✐s ❡ss❡♥t✐❛❧ t♦ ✉♥❞❡rst❛♥❞ ❤♦✇ s✉❜str❛t❡s ❛♥❞ ✐♥❤✐❜✐t♦rs ❛r❡ ❜♦✉♥❞ ❛♥❞ ❢♦r ♣r❡✲ ❞✐❝t✐♥❣ ♠♦❧❡❝✉❧❛r ❜✐♥❞✐♥❣✳ ❲❤❡♥ ❛♥ ✐♥❤✐❜✐t♦r ❜✐♥❞s t♦ ❡♥③②♠❡s ✇✐t❤ ❞✐✛❡r❡♥t str✉❝t✉r❡s✱ s❡q✉❡♥❝❡s ♦r ♠❡❝❤❛♥✐s♠s✱ ✇❡ ❝❛❧❧ t❤✐s ❧❛❝❦ ♦❢ s♣❡❝✐✜❝✐t② ♦❢ ❈r♦ss✲■♥❤✐❜✐t✐♦♥✳ ❚❤❡ ✐❞❡♥t✐✜✲ ❝❛t✐♦♥ ♦❢ ✈❛r✐❛♥ts ✐s ❛ ❞✐✣❝✉❧t t❛s❦ ❢♦r ✇❤✐❝❤ tr❛❞✐t✐♦♥❛❧ ♠❡t❤♦❞s ♠❛② ❢❛✐❧✳ ❚♦ ✉♥❞❡rst❛♥❞ ❤♦✇ t❤❡ ❝r♦ss✲✐♥❤✐❜✐t✐♦♥ ♦❝❝✉rs✱ ✇❡ ♠♦❞❡❧ t❤❡ ♣r♦❜❧❡♠ ❛♥❞ ♣r♦♣♦s❡ ❛ ♠❡t❤♦❞♦❧♦❣②✱ ✇❤✐❝❤ ✇❡ ❝❛❧❧ ❍②❞r♦P❛❈❡✭❍②❞r♦❢♦❜✐❝P❛t❝❤ ❈❡♥tr♦✐❞✮ ❛♥❞ ✇❡ ❡✈❛❧✉❛t❡✱ t❤r♦✉❣❤ ♣❡♥❛❧✐③❡❞ r❡❝❛❧❧ ♠❡tr✐❝ ✲ P❘▼✱ t♦ ❞❡t❡❝t ♣r❡s❡r✈❡❞ ♣❛tt❡r♥s✳ ❚❤❡ ❤②❞r♦♣❤♦❜✐❝ ❛t♦♠s t❤❛t ❜❡❧♦♥❣ t♦ t❤❡ ✐♥t❡r❢❛❝❡ ✇❡r❡ ♠♦❞❡❧❡❞ ❛s ❣r❛♣❤s ♦❢ ❛♣♦❧❛r ✐♥t❡r❛❝t✐♦♥s ❛♥❞ ❤②❞r♦❢♦❜✐❝ ❝♦♥♥❡❝t❡❞ r❡❣✐♦♥s ♦r ♣❛t❝❤❡s ✇❡r❡ ❝♦♠♣✉t❡❞ ❛♥❞ s✉♠♠❛r✐③❡❞ ❜② ❣❡♦♠❡tr✐❝ ❝❡♥tr♦✐❞s ✭❍P✲❝❡♥tr♦✐❞s✮✱ ❛♥❞ t❤❡✐r ❝♦♥s❡r✈❛t✐♦♥ ✐s ❞❡t❡❝t❡❞✳ ❲❡ ❛♥❛❧②③❡ t✇♦ ❝❛s❡s ♦❢ ❝r♦ss✲✐♥❤✐❜✐t✐♦♥✱ ♦♥❡ ✇✐t❤ t❤❡ ✐♥❤✐✲ ❜✐t♦r ❖✈♦♠♦✈♦✐❞ ✭✺ ♥♦♥✲r❡❞✉♥❞❛♥t ❝♦♠♣❧❡①❡s✮ ❛♥❞ ❛♥♦t❤❡r ✇✐t❤ t❤❡ ✐♥❤✐❜✐t♦r ❊❣❧✐♥ ❈ ✭✹ ♥♦♥✲r❡❞✉♥❞❛♥t ❝♦♠♣❧❡①❡s✮✳ ■♥ ❛❞❞✐t✐♦♥✱ t✇♦ ❢❛♠✐❧✐❡s ♦❢ s❡r✐♥❡ ♣r♦t❡❛s❡s ✇✐t❤ s✐♥❣❧❡ ❝❤❛✐♥ ✭❛♣♦✲❡♥③②♠❡s✮ ✇❡r❡ ❛♥❛❧②③❡❞ ✉s✐♥❣ ♣r♦❥❡❝t✐♦♥ ♦❢ t❤❡ ✐♥t❡r❢❛❝❡ t❡❝❤♥✐q✉❡✿ ❚❤❡ ❚r②♣s✐♥✲❧✐❦❡ ✭✸✺ ♥♦♥✲r❡❞✉♥❞❛♥t str✉❝t✉r❡s✮ ❛♥❞ t❤❡ ❙✉❜t✐❧✐s✐♥✲❧✐❦❡ ✭✾ ♥♦♥✲r❡❞✉♥❞❛♥t str✉❝t✉r❡s✮✳ ❚❤❡ ♣❛tt❡r♥s ❢♦✉♥❞ ✐♥ t❤❡ ✐♥t❡r❢❛❝❡s ♦❢ ❝r♦ss✲✐♥❤✐❜✐t✐♦♥s ✇❡r❡ ❢♦✉♥❞ ✐♥ ♠♦st ❡♥③②♠❡s t❤❡s❡ ❢❛♠✐❧✐❡s✳ ❲❡ ❜❡❧✐❡✈❡ t❤❛t ♦✉r ♠❡t❤♦❞♦❧♦❣② ❛❝❤✐❡✈❡s ❛♥ ❛♣♣r♦♣r✐❛t❡ ❧❡✈❡❧ ♦❢ ❛❜str❛❝t✐♦♥ t♦ ♦❜t❛✐♥ ✐♥✈❛r✐❛♥t ♣r♦♣❡rt✐❡s ✐♥ ❝r♦ss✲✐♥❤✐❜✐t✐♦♥✳ ❲❡ s❤♦✇ ❡①❛♠♣❧❡s ✐♥ ✇❤✐❝❤ ❍P✲❝❡♥tr♦✐❞s s✉❝❝❡ss❢✉❧❧② ♣r❡❞✐❝t❡❞ ❡♥③②♠❡s t❤❛t ❝♦✉❧❞ ❜❡ ✐♥❤✐❜✐t❡❞ ❜② t❤❡ st✉❞✐❡❞ ✐♥❤✐❜✐t♦rs ❛❝❝♦r❞✐♥❣ t♦ ❇❘❊◆❉❆ ❞❛t❛❜❛s❡✳ ❋✐♥❛❧❧②✱ ✇❡ ♣r♦✈✐❞❡ ❛❧❧ ❝♦❞❡s ✉s❡❞ ✐♥ t❤❡ ♠❡t❤♦❞♦❧♦❣✐❝❛❧ st❡♣s✱ ❛s

✇❡❧❧ ❛s t✉t♦r✐❛❧s ❛♥❞ ❡①❛♠♣❧❡s ✐♥ ✇✇✇✳❞❝❝✳✉❢♠❣✳❜r✴∼r❛q✉❡❧❝♠✴❤②❞r♦♣❛❝❡✳

(6)

✧✳✳✳✳✳◗✉❛❧q✉❡r ❝♦✐s❛ q✉❡ ✈♦❝ê ♣♦ss❛ ❢❛③❡r ♦✉ s♦♥❤❛r✱ ✈♦❝ê ♣♦❞❡ ❝♦♠❡ç❛r✳ ❆ ❝♦r❛❣❡♠ ❝♦♥té♠ ❡♠ s✐ ♠❡s♠❛✱ ♣♦❞❡r✱ ♦ ❣ê♥✐♦ ❡ ♠❛❣✐❛✳✧

●♦❡t❤❡

(7)

❆❣r❛❞❡❝✐♠❡♥t♦s

❆❣r❛❞❡ç♦ ❛ ❉❡✉s ♣❡❧❛ ✈✐❞❛✳

❆♦ ♠❡✉ ♣❛✐ ❖s✈❛❧❞♦ q✉❡ ♠❡ ❡♥❝♦r❛❥♦✉ ♥♦ ✐♥í❝✐♦ ❞❡st❛ ❥♦r♥❛❞❛✱ ❝♦♠ s✉❛s s✐♠♣❧❡s ♣❛❧❛✈r❛s ❞❡ ✐♥❝❡♥t✐✈♦✳ P❛✐✱ s❡✐ q✉❡ ❤♦❥❡ ✈♦❝ê ♥ã♦ ❡stá ♠❛✐s ❡♥tr❡ ♥ós✱ ♠❛s ❛❝r❡❞✐t♦ q✉❡ s❡♠♣r❡ ❡st❛rá ♦❧❤❛♥❞♦ ♣♦r ♠✐♠✳ ❆ ♠✐♥❤❛ ♠ã❡ ▼❛r✐❛ ♣♦r s❡♠♣r❡ ♠❡ ✐♥❝❧✉✐r ❡♠ s✉❛s ♦r❛çõ❡s ❡ ♣♦r t✉❞♦ q✉❡ ♥ã♦ ❤á ❝♦♠♦ ❝✐t❛r ♦✉ ❞❡s❝r❡✈❡r ❛♦ ❧♦♥❣♦ ❞❡ ♠✐♥❤❛ ❡①✐stê♥❝✐❛✳

❆❣r❛❞❡ç♦ ❛♦ ❋❡r♥❛♥❞♦✱ ♠❡✉ ♠❛r✐❞♦ ❡ ❝♦♠♣❛♥❤❡✐r♦✱ ♣❡❧♦ ❝❛r✐♥❤♦ ❡ ❛♣♦✐♦ ✐♥❝♦♥❞✐❝✐♦♥❛❧ ♣❛r❛ q✉❡ ❡✉ ✜③❡ss❡ ❡st❡ ❞♦✉t♦r❛❞♦✳ ❋❡r♥❛♥❞♦✱ ✈♦❝ê ♠❡ ❡♥s✐♥♦✉ q✉❡ ❛ t♦❧❡râ♥❝✐❛ ❡ ❛ ♣❛❝✐ê♥❝✐❛ sã♦ ❣r❛♥❞❡s ✈✐rt✉❞❡s✳ ❆ ✈♦❝ê ❡✉ ❞❡❞✐❝♦ t♦❞♦ ♠❡✉ ❛♠♦r✳

❆ ♠✐♥❤❛s ✐r♠ãs ❊❞✐❛♥❡ ❡ ❘♦s✐❧❡♥❡✱ ♣❡❧♦ ❛♣♦✐♦✱ ❝❛r✐♥❤♦ ❡ ❞❡❞✐❝❛çã♦ ♥♦s ♠♦♠❡♥t♦s ❞✐❢í❝❡✐s✳ ❆❣r❛❞❡ç♦ t❛♠❜é♠ ❛♦s ♠❡✉s s♦❜r✐♥❤♦s ❏♦ã♦ ❱✐t♦r ❡ ▲✉ís ❋❡❧✐♣❡ ♣❡❧❛ ❛❧❡❣r✐❛ ❡ ❡♥❡r❣✐❛ ❞❛ ✐♥❢â♥❝✐❛ q✉❡ s❡♠♣r❡ ♠❡ ❢❛③ ❢❡❧✐③✳

❆ ♠✐♥❤❛ s♦❣r❛ ❆♥❛ q✉❡ ❞♦ s❡✉ ❥❡✐t✐♥❤♦ s❡♠♣r❡ t♦r❝❡✉ ♣♦r ♠✐♠✳ ❆♦s ❝✉♥❤❛❞♦s ❘♦❣ér✐♦✱ ❘♦❞r✐❣♦ ❡ ❆♥❞ré✐❛ ❡ ❛s s♦❜r✐♥❤❛s ▼❛r✐❛♥❛✱ ❆♥❛ ❏ú❧✐❛✱ ❲❛♥❡ss❛✱ ❏éss✐❝❛ ❡ ❊st❡❢❛♥✐ ♣❡❧♦ ❛♣♦✐♦ ❡♠ t♦❞♦s ♦s ♠♦♠❡♥t♦s✳

❆♦s ♣r♦❢❡ss♦r❡s ❡ ♠❡str❡s ▼❛r❝❡❧♦ ❙❛♥t♦r♦✱ ❈❛r❧♦s ❍❡♥r✐q✉❡ ❡ ❲❛❣♥❡r ▼❡✐r❛✱ q✉❡✱ ♠❛✐s q✉❡ ♦r✐❡♥t❛❞♦r❡s✱ ❢♦r❛♠ ❛♠✐❣♦s q✉❡ ♦❢❡r❡❝❡r❛♠ s✉❛ ❣r❛♥❞❡ ✐♥t❡❧✐❣ê♥❝✐❛ ❡ ❝❛♣❛❝✐❞❛❞❡ ♣❛r❛ q✉❡ ❡✉ ♣✉❞❡ss❡ ❝♦♥❝❧✉✐r ❡st❡ ❞♦✉t♦r❛❞♦✳

❆ ♣r♦❢❡ss♦r❛ ❘❛q✉❡❧ ▼✐♥❛r❞✐ q✉❡ ❢♦✐ ♠❛✐s q✉❡ ✉♠❛ ♦r✐❡♥t❛❞♦r❛✱ ❢♦✐ ✉♠❛ ❛♠✐❣❛ ❡ ❝♦♥s❡❧❤❡✐r❛✱ q✉❡ ♦❢❡r❡❝❡✉ s❡✉ t❛❧❡♥t♦ ♣❛r❛ ♠❡ ❝♦♥❞✉③✐r✳ ❘❛q✉❡❧✱ ♥ã♦ t❡♥❤♦ ♣❛❧❛✈r❛s ♣❛r❛ ❛❣r❛❞❡❝❡r ♦ q✉❛♥t♦ ✈♦❝ê ❝♦♥tr✐❜✉✐✉ ❝♦♠ ❡st❡ tr❛❜❛❧❤♦✳

❆♦ ❣r❛♥❞❡ ❛♠✐❣♦ ❉♦✉❣❧❛s P✐r❡s q✉❡ s❡♠♣r❡ ♠❡ ❛♣♦✐♦✉ ♥♦s ♠♦♠❡♥t♦s ♠❛✐s ❞✐❢í❝❡✐s✱ ✉s❛♥❞♦ ❞❡ s✉❛ ❝❛♣❛❝✐❞❛❞❡ ✐♥t❡❧❡❝t✉❛❧ ♣❛r❛ ♠❡ ❛❥✉❞❛r ♥♦s ♣r♦❜❧❡♠❛s ♠❡t♦❞♦❧ó❣✐❝♦s✳ ❉♦✉✲ ❣❧❛s✱ ♣❛r❛ ✈♦❝ê ♠❡✉ ✐r♠ã♦③✐♥❤♦ ❞♦ ❝♦r❛çã♦✱ ♠❡✉ ♠✉✐t♦ ♦❜r✐❣❛❞❛✳ ❈♦♥t❡ s❡♠♣r❡ ❝♦♠✐❣♦✳

❆♦ ❛♠✐❣♦ ❆♥❣❡❧♦ ❇r✉♥♦ ❡ ❛ t♦❞♦s ♦s ❛♠✐❣♦s q✉❡ ❝♦♥❤❡❝✐ ❛♦ ❧♦♥❣♦ ❞❡ss❡s q✉❛tr♦ ❛♥♦s❀ ♦s ❛♠✐❣♦s ❞❛ ❇✐♦✐♥❢♦r♠át✐❝❛✱ ♦s ❛♠✐❣♦s ❜✐ó❧♦❣♦s✱ ❛ t♦❞♦s ✈♦❝ês ♠❡✉ ❛❜r❛ç♦ ❛♣❡rt❛❞♦✳

❆ t♦❞♦s ♦s ♣r♦❢❡ss♦r❡s q✉❡ ❡st✐✈❡r❛♠ ♣r❡s❡♥t❡s ❞✉r❛♥t❡ ❡ss❡ ❞♦✉t♦r❛❞♦ ❡ q✉❡ ❝♦♥tr✐✲ ❜✉ír❛♠ ♠✉✐t♦ ❝♦♠ s❡✉s ❝♦♥❤❡❝✐♠❡♥t♦s✳

❆♦s ❛♠✐❣♦s ❞♦ ▲❇❙✱ ♣❡❧❛ tr♦❝❛ ❞❡ ❝♦♥❤❡❝✐♠❡♥t♦s ❡ ✐♥❡sq✉❡❝í✈❡✐s ♠♦♠❡♥t♦s ❞❡ ❞❡s❝♦♥✲ tr❛çã♦ q✉❡ t♦r♥❛r❛♠ ❡st❛ ❥♦r♥❛❞❛ ♠❛✐s s✉❛✈❡✳

❆ ✐♥st✉✐çã♦ ❞❡ ❢♦♠❡♥t♦ ❈❆P❊❙ ♣❡❧♦ ❛♣ó✐♦ ✜♥❛♥❝❡✐r♦ ♣❛r❛ q✉❡ ❡✉ ♣✉❞❡ss❡ ♠❡ ❞❡❞✐❝❛r ❡①❝❧✉s✐✈❛♠❡♥t❡ à ♣❡sq✉✐s❛✳

(8)

❙✉♠ár✐♦

▲✐st❛ ❞❡ ❆❜r❡✈✐❛çõ❡s ✶

✶ ■♥tr♦❞✉çã♦ ✷

✷ ❋✉♥❞❛♠❡♥t❛çã♦ ❚❡ór✐❝❛ ✺

✷✳✶ Pr♦t❡❛s❡s ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✺ ✷✳✶✳✶ ❈❧❛ss✐✜❝❛çã♦ ❞❡ ♣r♦t❡❛s❡s ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✼ ✷✳✷ ❇❛s❡ ❞❡ ❞❛❞♦s ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✶✵ ✷✳✷✳✶ P❋❆▼ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✶✵ ✷✳✷✳✷ ❇❘❊◆❉❆ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✶✶ ✷✳✸ s❡r✐♥♦ ♣r♦t❡❛s❡s ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✶✶ ✷✳✸✳✶ ❚✐♣♦ ❙✉❜t✐❧✐s✐♥❛ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✶✷ ✷✳✸✳✷ ❚✐♣♦ ❚r✐♣s✐♥❛ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✶✸ ✷✳✹ ❈♦♥✈❡r❣ê♥❝✐❛ ❡✈♦❧✉t✐✈❛ ❡♠ ❢❛♠í❧✐❛s ❞❡ s❡r✐♥♦ ♣r♦t❡❛s❡s ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✶✹ ✷✳✺ ■♥✐❜✐❞♦r❡s ❞❡ s❡r✐♥♦ ♣r♦t❡❛s❡s ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✶✻ ✷✳✺✳✶ ❙❡r♣✐♥❛s ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✶✼ ✷✳✺✳✷ ■♥✐❜✐❞♦r❡s ❝❛♥ô♥✐❝♦s ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✶✼ ✷✳✺✳✸ ■♥✐❜✐❞♦r❡s ♥ã♦ ❝❛♥ô♥✐❝♦s ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✶✽ ✷✳✻ ■♥✐❜✐çã♦ ❈r✉③❛❞❛ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✶✾ ✷✳✼ ▼♦❞❡❧❛❣❡♠ ✈✐❛ ❣r❛❢♦s ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✷✵

✸ ❖❜❥❡t✐✈♦s ✷✷

✸✳✶ ❖❜❥❡t✐✈♦ ●❡r❛❧ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✷✷ ✸✳✶✳✶ ❖❜❥❡t✐✈♦s ❡s♣❡❝í✜❝♦s ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✷✷

✹ ▼❛t❡r✐❛✐s ❡ ▼ét♦❞♦s ✷✸

✹✳✶ ❙❡❧❡çã♦ ❞♦s ❞❛❞♦s ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✷✸ ✹✳✷ Pr❡♣❛r❛çã♦ ❞♦s ❞❛❞♦s ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✷✺ ✹✳✷✳✶ ◆♦r♠❛❧✐③❛çã♦ ❡ ❛❧✐♥❤❛♠❡♥t♦ ❞❛s ❡str✉t✉r❛s ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✷✻ ✹✳✷✳✷ ■♥t❡r❢❛❝❡ ▼♦❧❡❝✉❧❛r ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✷✼ ✹✳✸ ❈♦♥str✉çã♦ ❞♦s ❣r❛❢♦s ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✷✽ ✹✳✸✳✶ ❉✐❛❣r❛♠❛ ❞❡ ❱♦r♦♥♦✐ ❡ ❚❡ss❡❧❛çã♦ ❞❡ ❉❡❧❛✉♥❛② ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✷✾

(9)

✹✳✹ ▼♦❞❡❧❛❣❡♠ ❞♦ ♣r♦❜❧❡♠❛ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✸✷ ✹✳✺ ❆❧❣♦r✐t♠♦s ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✸✷ ✹✳✺✳✶ ❆❜♦r❞❛❣❡♠ ❞❡ ❣r❛♥✉❧❛r✐❞❛❞❡ ❣r♦ss❛ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✸✸ ✹✳✺✳✷ ❆❜♦r❞❛❣❡♠ ❞❡ ❣r❛♥✉❧❛r✐❞❛❞❡ ✜♥❛ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✸✸ ✹✳✺✳✸ ❈♦♠♣❛r❛çã♦ ❞♦s ❍P✲❝❡♥tr♦✐❞❡s ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✸✺ ✹✳✻ ❆✈❛❧✐❛çã♦ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✸✼

✺ ❘❡s✉❧t❛❞♦s ❡ ❞✐s❝✉ssã♦ ✸✾

✺✳✶ ❆♥á❧✐s❡ ❞❛s ✐♥✐❜✐çõ❡s ❝r✉③❛❞❛s ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✸✾ ✺✳✶✳✶ ■♥✐❜✐❞♦r ❊❣❧✐♥❛ ❈ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✹✵ ✺✳✶✳✷ ■♥✐❜✐❞♦r ❖✈♦♠✉❝♦✐❞❡ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✹✺ ✺✳✷ ❯s♦ ❞❡ ❍P✲❝❡♥tr♦✐❞❡s ♣❛r❛ ♣r❡❞✐çã♦ ❞❡ ✐♥✐❜✐çã♦ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✺✵ ✺✳✷✳✶ ❋❛♠í❧✐❛ ❚✐♣♦ ❚r✐♣s✐♥❛ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✺✷ ✺✳✷✳✷ ❋❛♠í❧✐❛ ❚✐♣♦ ❙✉❜t✐❧✐s✐♥❛ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✺✻ ✺✳✸ ❈♦♥s✐❞❡r❛çõ❡s ✜♥❛✐s ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✺✾

✻ ❈♦♥❝❧✉sã♦ ✻✶

✼ P❡rs♣❡❝t✐✈❛s ❡ tr❛❜❛❧❤♦s ❢✉t✉r♦s ✻✸

✼✳✶ P❡rs♣❡❝t✐✈❛s ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✻✸ ✼✳✷ ❚r❛❜❛❧❤♦s ❢✉t✉r♦s ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✻✹

❆ ❆rt✐❣♦ s✉❜♠❡t✐❞♦ ✻✺

❇ ▼❛t❡r✐❛❧ ❙✉♣❧❡♠❡♥t❛r ✽✸

❈ ❙✐t❡ ✭✇✇✇✳❞❝❝✳✉❢♠❣✳❜r✴∼r❛q✉❡❧❝♠✴❤②❞r♦♣❛❝❡✮ ✶✵✷

❉ ◆♦ss❛ ❊q✉✐♣❡ ✶✵✸

❘❡❢❡rê♥❝✐❛s ❇✐❜❧✐♦❣rá✜❝❛s ✶✵✹

(10)

▲✐st❛ ❞❡ ❋✐❣✉r❛s

✷✳✶ ❙✉❜❞✐✈✐sã♦ ❞❛s ❡♥③✐♠❛s ♣r♦t❡♦❧ít✐❝❛s✳❊♠ ✭❛✮✱ t❡♠♦s ❛ r❡♣r❡s❡♥t❛çã♦ ❞♦s t✐♣♦s ❞❡ ♣r♦t❡❛s❡s ❡①✐st❡♥t❡s ❝♦♠ s❡✉s s✐♥ô♥✐♠♦s ❡ ❡♠ ✭❜✮✱ t❡♠♦s ❛ r❡♣r❡s❡♥t❛çã♦ ❞♦ ♠♦❞♦ ❞❡ ❛çã♦✱ s❡♥❞♦ q✉❡ ♦s tr❛ç♦s ✐♥❞✐❝❛♠ ♦ ❧♦❝❛❧ ❞❛ ❝❧✐✈❛❣❡♠✳ ❋✐❣✉r❛ ❛❞❛♣t❛❞❛ ❞❡ ❬❇❡②♥♦♥ ❡ ❇♦♥❞ ✭✷✵✵✶✮❪ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✼ ✷✳✷ ●rá✜❝♦ r❡♣r❡s❡♥t❛t✐✈♦ ❞♦ ♥ú♠❡r♦ ❞❡ ❢❛♠í❧✐❛s ✐♥s❡r✐❞❛s ❞❡♥tr♦ ❞❡ ❝❛❞❛ ❝❧ã ▼❊✲

❘❖P❙✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✾ ✷✳✸ ❊str✉t✉r❛ tr✐❞✐♠❡♥s✐♦♥❛❧ ❞❛s ❚✐♣♦ ❙✉❜t✐❧✐s✐♥❛ ✭P❉❇ ■❉✿✶●❈■✮ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✶✸ ✷✳✹ ❊str✉t✉r❛ tr✐❞✐♠❡♥s✐♦♥❛❧ ❞❡ ❚✐♣♦ ❚r✐♣s✐♥❛ ✭P❉❇ ■❉✿ ✶❍❏✽✮ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✶✸ ✷✳✺ ❙❡♠❡❧❤❛♥ç❛ ♥❛ t♦♣♦❧♦❣✐❛ ❞♦s r❡sí❞✉♦s ❞❛ trí❛❞❡ ❝❛t❛❧ít✐❝❛ ❞❡ ❚✐♣♦ ❙✉❜t✐❧✐s✐♥❛

❡ ❚✐♣♦ ❚r✐♣s✐♥❛✳ ❊♠ ✭❛✮✱ t❡♠♦s ❚✐♣♦ ❙✉❜t✐❧✐s✐♥❛ ✶❘✵❘ ❡ s✉❛ trí❛❞❡ ❝❛t❛❧ít✐❝❛ ❡ ❡♠ ✭❜✮✱ t❡♠♦s ❚✐♣♦ ❚r✐♣s✐♥❛ ✶PP❋ ❡ s✉❛ trí❛❞❡ ❝❛t❛❧ít✐❝❛✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✶✺ ✷✳✻ ❆❧✐♥❤❛♠❡♥t♦ ❞❛s s❡q✉ê♥❝✐❛s ❞❛ ❚✐♣♦ ❙✉❜t✐❧✐s✐♥❛ ✭✶❘✵❘✮ ❡ tr✐♣s✐♥❛ ✭✶PP❋✮ ✳ ✳ ✶✺ ✷✳✼ ❊str✉t✉r❛s tr✐❞✐♠❡♥s✐♦♥❛✐s ❞❡ ✐♥✐❜✐❞♦r❡s ❞❛ ❝❧❛ss❡ ❙❡r♣✐♥❛✳ ✭❛✮ r❡♣r❡s❡♥t❛ ❛

❡str✉t✉r❛ ❞❡ α✶✲❆♥t✐tr✐♣s✐♥❛ ✭✶P❙■✮✱ ✭❜✮ r❡♣r❡s❡♥t❛ ❛ ❡str✉t✉r❛ ❞❡ ✉♠❛ ❆♥✲ t✐tr♦♠❜✐♥❛ ✭✶❆◆❚✮ ❡ ✭❝✮ r❡♣r❡s❡♥t❛ ❛ ❡str✉t✉r❛ ❞❡ P❧❛s♠✐♥♦❣ê♥✐♦ ❆t✐✈❛❞♦r ■♥✐❜✐t♦r✲✶❆ ✭✶❉❱◆✮✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✶✼ ✷✳✽ ❊str✉t✉r❛s tr✐❞✐♠❡♥s✐♦♥❛✐s ❞❡ ✐♥✐❜✐❞♦r❡s ❝❛♥ô♥✐❝♦s ❞❡ s❡r✐♥♦ ♣r♦t❡❛s❡s✳ ✭❛✮

r❡♣r❡s❡♥t❛ ❛ ❡str✉t✉r❛ ❞♦ ❇P❚■ ✭✶❇P■✮✱ ❡①tr❛í❞♦ ❞❡ ❇♦s t❛✉r✉s✱ ✭❜✮ r❡♣r❡s❡♥t❛ ❛ ❡str✉t✉r❛ ❞❡ ✐♥✐❜✐❞♦r t✐♣♦ ❜❛t❛t❛ ■ ✭✶▼■❚✮✱ ❡①tr❛í❞♦ ❞❡ ❈✉❝úr❜✐t❛ ♠á①✐♠❛✱ ✭❝✮ r❡♣r❡s❡♥t❛ ❛ ❡str✉t✉r❛ ❞♦ ✐♥✐❜✐❞♦r t✐♣♦ ❜❛t❛t❛ ■■ ✭✶❚■❍✮✱ ❡①tr❛í❞♦ ❞❡ ◆✐❝♦t✐❛♥❛ ❛❧❛t❛ ❡ ✭❞✮ r❡♣r❡s❡♥t❛ ❛ ❡str✉t✉r❛ ❞❡ ❙❚■ ✭✶❆❱❯✮✱ ❡①tr❛í❞♦ ❞❛ ●❧②❝✐♥❡ ♠❛①✳ ✳ ✶✽ ✷✳✾ ❊①❡♠♣❧♦ ❞❡ ❡str✉t✉r❛ tr✐❞✐♠❡♥s✐♦♥❛❧ ❞❡ ✉♠ ✐♥✐❜✐❞♦r ♥ã♦ ❝❛♥ô♥✐❝♦ ❞❡ s❡r✐♥♦

♣r♦t❡❛s❡s ✭P❉❇ ■❉ ✶❚❖❈✮ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✶✾

✹✳✶ ❉✐❛❣r❛♠❛ ❞❡ ✢✉①♦ ❞❛ ♠❡t♦❞♦❧♦❣✐❛ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✷✺ ✹✳✷ ❊①❡♠♣❧♦s ❞❡ ❛❧✐♥❤❛♠❡♥t♦ ❞❛s ❡str✉t✉r❛s✳ ❊♠ ✭❛✮✱ t❡♠♦s ❡①❡♠♣❧♦ ❞❡ ❛❧✐♥❤❛✲

♠❡♥t♦ ♣❡❧♦ ❝❛❞❡✐❛ ❞♦ ✐♥✐❜✐❞♦r ❡ ❡♠ ✭❜✮✱ t❡♠♦s ❡①❡♠♣❧♦s ❞❡ ❛❧✐♥❤❛♠❡♥t♦ ♣❡❧❛ ❝❛❞❡✐❛ ❞❛s ❛♣♦ ❡♥③✐♠❛s ✭s❡♠ ❝♦♠♣❧❡①♦s✮ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✷✼ ✹✳✸ ❊①❡♠♣❧♦s ❞❡ ✐♥t❡r❢❛❝❡ ♠♦❧❡❝✉❧❛r✳ ❊♠ ✭❛✮✱ ❚✐♣♦ ❙✉❜t✐❧✐s✐♥❛ P❉❇ ■❉ ✶❚❊❈✿❊

❡ ❡♠ ✭❜✮✱ ❚✐♣♦ ❚r✐♣s✐♥❛ P❉❇ ■❉ ✶❆❈❇✿❊✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✷✼ ✹✳✹ ❊♠ ✭❛✮✱ t❡♠♦s ❉❱ ✭❧✐♥❤❛s ♣♦♥t✐❧❤❛❞❛s✮ ❡ ❚❉ ✭❧✐♥❤❛s só❧✐❞❛s✮ ❡ ❡♠ ✭❜✮ t❡♠♦s

(11)

✹✳✺ ❊①❡♠♣❧♦s ❞❡ ❚❡ss❡❧❛çã♦ ❞❡ ❉❡❧❛✉♥❛② ♥❛ ✐♥t❡r❢❛❝❡ ♠♦❧❡❝✉❧❛r ❞❡ ❡♥③✐♠❛s✳ ❊♠ ✭❛✮✱ P❉❇ ■❉ ✶❚❊❈✿❊ ❡ ❡♠ ✭❜✮✱ P❉❇ ■❉ ✶❆❈❇✿❊ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✸✵ ✹✳✻ ❊①❡♠♣❧♦s ❞❡ ❝♦♠♣♦♥❡♥t❡s ❝♦♥❡①♦s ♥❛ ✐♥t❡r❢❛❝❡ ♠♦❧❡❝✉❧❛r ❞❡ ❡♥③✐♠❛s✳ ❊♠ ✭❛✮✱

P❉❇ ■❉ ✶❚❊❈✿❊ ❡ ❡♠ ✭❜✮✱ P❉❇ ■❉ ✶❆❈❇✿❊ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✸✶ ✹✳✼ ❊①❡♠♣❧♦s ❞❡ ❍P✲❝❡♥tr♦✐❞❡s ♣❛r❛ ❈❈❈✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✸✸ ✹✳✽ ❊①❡♠♣❧♦s ❞❡ ❍P✲❝❡♥tr♦✐❞❡s ♣❛r❛ ❊❇❈❈ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✸✹ ✹✳✾ ❊①❡♠♣❧♦s ❞❡ ❍P✲❝❡♥tr♦✐❞❡s ♣❛r❛ ❙●❈❈ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✸✺

✺✳✶ ❊①❡♠♣❧♦s ❞❡ ✐♥✐❜✐çã♦ ❝r✉③❛❞❛ ❝♦♠ ♦ ✐♥✐❜✐❞♦r ❊❣❧✐♥❛ ❈✳ ❊♠ ✭❛✮✱ ❚✐♣♦ ❙✉❜t✐❧✐✲ s✐♥❛ P❉❇ ■❉ ✶❚❊❈ ❡ ❡♠ ✭❜✮✱ ❚✐♣♦ ❚r✐♣s✐♥❛ P❉❇ ■❉ ✶❆❈❇✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✹✵ ✺✳✷ ❊❣❧✐♥❛ ❈ ✭❛❜♦r❞❛❣❡♠ ❈❈❈✮✿ ❘❡❧❛çã♦ ❡♥tr❡ ♦ ♥ú♠❡r♦ ❞❡ ❣r✉♣♦s✱ ❛s ❞✐stâ♥❝✐❛s

♠é❞✐❛s ❞♦s ❍P✲❝❡♥tr♦✐❞❡s ✐♥tr❛✲❣r✉♣♦s ❡ ♦s ✈❛❧♦r❡s ❞❛ P❘▼ ♠é❞✐❛ ✭❣rá✜❝♦ ❞❛ ❡sq✉❡r❞❛✮ ❡ ♦s ✈❛❧♦r❡s ❞❛ ♠étr✐❝❛ P❘▼ ♣❛r❛ ❝❛❞❛ ❣r✉♣♦ ✭❣rá✜❝♦ ❞❛ ❞✐r❡✐t❛✮ ✳ ✹✶ ✺✳✸ ❊❣❧✐♥❛ ❈ ✭❛❜♦r❞❛❣❡♠ ❙●❈❈✮✳ ❘❡❧❛çã♦ ❡♥tr❡ ♦ ♥ú♠❡r♦ ❞❡ ❣r✉♣♦s✱ ❛s ❞✐stâ♥❝✐❛s

♠é❞✐❛s ❞♦s ❍P✲❝❡♥tr♦✐❞❡s ✐♥tr❛✲❣r✉♣♦s ❡ ♦s ✈❛❧♦r❡s ❞❛ P❘▼ ♠é❞✐❛ ✭❣rá✜❝♦ ❞❛ ❡sq✉❡r❞❛✮ ❡ ♦s ✈❛❧♦r❡s ❞❛ ♠étr✐❝❛ P❘▼ ♣❛r❛ ❝❛❞❛ ❣r✉♣♦ ✭❣rá✜❝♦ ❞❛ ❞✐r❡✐t❛✮ ✳ ✹✷ ✺✳✹ ❊❣❧✐♥❛ ❈ ✭❛❜♦r❞❛❣❡♠ ❊❇❈❈✮✳ ❘❡❧❛çã♦ ❡♥tr❡ ♦ ♥ú♠❡r♦ ❞❡ ❣r✉♣♦s✱ ❛s ❞✐stâ♥❝✐❛s

♠é❞✐❛s ❞♦s ❍P✲❝❡♥tr♦✐❞❡s ✐♥tr❛✲❣r✉♣♦s ❡ ♦s ✈❛❧♦r❡s ❞❛ P❘▼ ♠é❞✐❛ ✭❣rá✜❝♦ ❞❛ ❡sq✉❡r❞❛✮ ❡ ♦s ✈❛❧♦r❡s ❞❛ ♠étr✐❝❛ P❘▼ ♣❛r❛ ❝❛❞❛ ❣r✉♣♦ ✭❣rá✜❝♦ ❞❛ ❞✐r❡✐t❛✮ ✳ ✹✸ ✺✳✺ P❛t❝❤❡s ❤✐❞r♦❢ó❜✐❝♦s ♣❛r❛ ✐♥✐❜✐çã♦ ❝r✉③❛❞❛ ❝♦♠ ♦ ✐♥✐❜✐❞♦r ❊❣❧✐♥❛ ❈ ✳ ✳ ✳ ✳ ✳ ✳ ✹✺ ✺✳✻ ❊①❡♠♣❧♦s ❞❡ ✐♥✐❜✐çã♦ ❝r✉③❛❞❛ ❝♦♠ ✐♥✐❜✐❞♦r ❖✈♦♠✉❝♦✐❞❡✳ ❊♠ ✭❛✮✱ ❚✐♣♦ ❙✉❜t✐✲

❧✐s✐♥❛ P❉❇ ■❉ ✶❘✵❘ ❡ ❡♠ ✭❜✮✱ ❚✐♣♦ ❚r✐♣s✐♥❛ P❉❇ ■❉ ✶PP❋✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✹✻ ✺✳✼ ❖✈♦♠✉❝♦✐❞❡ ✭❛❜♦r❞❛❣❡♠ ❈❈❈✮✳ ❘❡❧❛çã♦ ❡♥tr❡ ♦ ♥ú♠❡r♦ ❞❡ ❣r✉♣♦s✱ ❛s ❞✐stâ♥✲

❝✐❛s ♠é❞✐❛s ❞♦s ❍P✲❝❡♥tr♦✐❞❡s ✐♥tr❛✲❣r✉♣♦s ❡ ♦s ✈❛❧♦r❡s ❞❛ P❘▼ ♠é❞✐❛ ✭❣rá✜❝♦ ❞❛ ❡sq✉❡r❞❛✮ ❡ ♦s ✈❛❧♦r❡s ❞❛ ♠étr✐❝❛ P❘▼ ♣❛r❛ ❝❛❞❛ ❣r✉♣♦ ✭❣rá✜❝♦ ❞❛ ❞✐r❡✐t❛✮ ✹✻ ✺✳✽ ❖✈♦♠✉❝♦✐❞❡ ✭❛❜♦r❞❛❣❡♠ ❙●❈❈✮✳ ❘❡❧❛çã♦ ❡♥tr❡ ♦ ♥ú♠❡r♦ ❞❡ ❣r✉♣♦s✱ ❛s ❞✐s✲

tâ♥❝✐❛s ♠é❞✐❛s ❞♦s ❍P✲❝❡♥tr♦✐❞❡s ✐♥tr❛✲❣r✉♣♦s ❡ ❛s ♠é❞✐❛s ❞❛ P❘▼ ✭❣rá✜❝♦ ❞❛ ❡sq✉❡r❞❛✮✳ ❖s ✈❛❧♦r❡s ❞❛ ♠étr✐❝❛ P❘▼ ♣❛r❛ ❝❛❞❛ ❣r✉♣♦ ❡stã♦ ♥♦ ❣rá✜❝♦ ❞❛ ❞✐r❡✐t❛ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✹✼ ✺✳✾ ❖✈♦♠✉❝♦✐❞❡ ✭❛❜♦r❞❛❣❡♠ ❊❇❈❈✮✳ ❘❡❧❛çã♦ ❡♥tr❡ ♦ ♥ú♠❡r♦ ❞❡ ❣r✉♣♦s✱ ❛s ❞✐s✲

tâ♥❝✐❛s ♠é❞✐❛s ❞♦s ❍P✲❝❡♥tr♦✐❞❡s ✐♥tr❛✲❣r✉♣♦s ❡ ❛s ♠é❞✐❛s ❞❛ P❘▼ ✭❣rá✜❝♦ ❞❛ ❡sq✉❡r❞❛✮✳ ❖s ✈❛❧♦r❡s ❞❛ ♠étr✐❝❛ P❘▼ ♣❛r❛ ❝❛❞❛ ❣r✉♣♦ ❡stã♦ ♥♦ ❣rá✜❝♦ ❞❛ ❞✐r❡✐t❛ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✹✽ ✺✳✶✵ P❛t❝❤❡s ❤✐❞r♦❢ó❜✐❝♦s ♣❛r❛ ✐♥✐❜✐çã♦ ❝r✉③❛❞❛ ♣❡❧♦ ✐♥✐❜✐❞♦r ❖✈♦♠✉❝♦✐❞❡ ✳ ✳ ✳ ✳ ✳ ✺✵ ✺✳✶✶ Pr❡❞✐çã♦ ❞❛ ■❋❘s ❡ ❍P✲❝❡♥tr♦✐❞❡s ❡♥❝♦♥tr❛❞♦s ♥❛s ✐♥✐❜✐çõ❡s ❝r✉③❛❞❛s ❝♦♠

✐♥✐❜✐❞♦r ❖✈♦♠✉❝♦✐❞❡ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✺✷ ✺✳✶✷ ❚✐♣♦ ❚r✐♣s✐♥❛ ✭❛❜♦r❞❛❣❡♠ ❈❈❈✮✳ ❘❡❧❛çã♦ ❡♥tr❡ ♦ ♥ú♠❡r♦ ❞❡ ❣r✉♣♦s✱ ❛s ❞✐s✲

tâ♥❝✐❛s ♠é❞✐❛s ❞♦s ❍P✲❝❡♥tr♦✐❞❡s ✐♥tr❛✲❣r✉♣♦s ❡ ❛s ♠é❞✐❛s ❞❛ P❘▼ ✭❣rá✜❝♦ ❞❛ ❡sq✉❡r❞❛✮✳ ❖s ✈❛❧♦r❡s ❞❛ ♠étr✐❝❛ P❘▼ ♣❛r❛ ❝❛❞❛ ❣r✉♣♦ sã♦ ♠♦str❛❞♦s ♥♦ ❣rá✜❝♦ ❞❛ ❞✐r❡✐t❛ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✺✸

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✺✳✶✸ ❚✐♣♦ ❚r✐♣s✐♥❛ ✭❛❜♦r❞❛❣❡♠ ❙●❈❈✮✳ ❘❡❧❛çã♦ ❡♥tr❡ ♦ ♥ú♠❡r♦ ❞❡ ❣r✉♣♦s✱ ❛s ❞✐s✲ tâ♥❝✐❛s ♠é❞✐❛s ❞♦s ❍P✲❝❡♥tr♦✐❞❡s ✐♥tr❛✲❣r✉♣♦s ❡ ❛s ♠é❞✐❛s ❞❛ P❘▼ ✭❣rá✜❝♦ ❞❛ ❡sq✉❡r❞❛✮✳ ❖s ✈❛❧♦r❡s ❞❛ ♠étr✐❝❛ P❘▼ ♣❛r❛ ❝❛❞❛ ❣r✉♣♦ sã♦ ❞❡♠♦♥str❛❞♦s ♥♦ ❣rá✜❝♦ ❞❛ ❞✐r❡✐t❛ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✺✹ ✺✳✶✹ ❚✐♣♦ ❚r✐♣s✐♥❛ ✭❛❜♦r❞❛❣❡♠ ❊❇❈❈✳ ❘❡❧❛çã♦ ❡♥tr❡ ♦ ♥ú♠❡r♦ ❞❡ ❣r✉♣♦s✱ ❛s ❞✐s✲

tâ♥❝✐❛s ♠é❞✐❛s ❞♦s ❍P✲❝❡♥tr♦✐❞❡s ✐♥tr❛✲❣r✉♣♦s ❡ ❛s P❘▼ ♠é❞✐❛s ✭❣rá✜❝♦ ❞❛ ❡sq✉❡r❞❛✮✳ ❖s ✈❛❧♦r❡s ❞❛ ♠étr✐❝❛ P❘▼ ♣❛r❛ ❝❛❞❛ ❣r✉♣♦ sã♦ ❡①✐❜✐❞♦s ♥♦ ❣rá✜❝♦ ❞❛ ❞✐r❡✐t❛ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✺✺ ✺✳✶✺ ❚✐♣♦ ❙✉❜t✐❧✐s✐♥❛ ✭❛❜♦r❞❛❣❡♠ ❈❈❈✮✳ ❘❡❧❛çã♦ ❡♥tr❡ ♦ ♥ú♠❡r♦ ❞❡ ❣r✉♣♦s✱ ❛s

❞✐stâ♥❝✐❛s ♠é❞✐❛s ❞♦s ❍P✲❝❡♥tr♦✐❞❡s ✐♥tr❛✲❣r✉♣♦s ❡ ❛s ♠é❞✐❛s ❞❛ P❘▼ ✭❣rá✜❝♦ ❞❛ ❡sq✉❡r❞❛✮✳ ❖s ✈❛❧♦r❡s ❞❛ ♠étr✐❝❛ P❘▼ ♣❛r❛ ❝❛❞❛ ❣r✉♣♦ sã♦ ❡①✐❜✐❞♦s ♥♦ ❣rá✜❝♦ ❞❛ ❞✐r❡✐t❛ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✺✻ ✺✳✶✻ ❚✐♣♦ ❙✉❜t✐❧✐s✐♥❛ ✭❛❜♦r❞❛❣❡♠ ❙●❈❈✮✳ ❘❡❧❛çã♦ ❡♥tr❡ ♦ ♥ú♠❡r♦ ❞❡ ❣r✉♣♦s✱ ❛s

❞✐stâ♥❝✐❛s ♠é❞✐❛s ❞♦s ❍P✲❝❡♥tr♦✐❞❡s ✐♥tr❛✲❣r✉♣♦s ❡ ❛s ♠é❞✐❛s ❞❛ P❘▼ ✭❣rá✜❝♦ ❞❛ ❡sq✉❡r❞❛✮✳ ❖s ✈❛❧♦r❡s ❞❛ ♠étr✐❝❛ P❘▼ ♣❛r❛ ❝❛❞❛ ❣r✉♣♦ sã♦ ❡①✐❜✐❞♦s ♥♦ ❣rá✜❝♦ ❞❛ ❞✐r❡✐t❛ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✺✼ ✺✳✶✼ ❚✐♣♦ ❙✉❜t✐❧✐s✐♥❛ ✭❛❜♦r❞❛❣❡♠ ❊❇❈❈✮✳ ❘❡❧❛çã♦ ❡♥tr❡ ♦ ♥ú♠❡r♦ ❞❡ ❣r✉♣♦s✱ ❛s

❞✐stâ♥❝✐❛s ♠é❞✐❛s ❞♦s ❍P✲❝❡♥tr♦✐❞❡s ✐♥tr❛✲❣r✉♣♦s ❡ ❛s ♠é❞✐❛s ❞❛ P❘▼ ✭❣rá✜❝♦ ❞❛ ❡sq✉❡r❞❛✮✳ ❖s ✈❛❧♦r❡s ❞❛ ♠étr✐❝❛ P❘▼ ♣❛r❛ ❝❛❞❛ ❣r✉♣♦ sã♦ ❡①✐❜✐❞♦s ♥♦ ❣rá✜❝♦ ❞❛ ❞✐r❡✐t❛ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✺✽

❇✳✶ ❊①❡♠♣❧♦ ❞❡ ❝♦♠♣❧❡♠❡♥t❛r✐❞❛❞❡✲ ❝♦♠♣❧❡①♦ ✶❚❊❈ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✽✸

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▲✐st❛ ❞❡ ❚❛❜❡❧❛s

✷✳✶ ❖ s✐st❡♠❛ ❊❈ ❞❡ ❝❧❛ss✐✜❝❛çã♦ ❞❡ ♣❡♣t✐❞❛s❡s✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✽ ✷✳✷ ❋❛♠í❧✐❛s ❞❡ ✐♥✐❜✐❞♦r❡s ❞❡ s❡r✐♥♦ ♣r♦t❡❛s❡s ❝♦♠ ❡str✉t✉r❛ ❝r✐st❛❧✐♥❛ r❡s♦❧✈✐❞❛✳

■♥✐❜✐❞♦r❡s ❞❡ ♦r✐❣❡♠a❛♥✐♠❛❧✱ ❞❡b♣❧❛♥t❛s ❡ ❞❡ c♠✐❝r♦✲♦r❣❛♥✐s♠♦s✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✶✽

✹✳✶ ❚❛❜❡❧❛ ❞❡ ✐♥✐❜✐çã♦ ❝r✉③❛❞❛ ❝♦♠ ❊❣❧✐♥❛ ❈ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✷✸ ✹✳✷ ❚❛❜❡❧❛ ❞❡ ✐♥✐❜✐çã♦ ❝r✉③❛❞❛ ❝♦♠ ❖✈♦♠✉❝♦✐❞❡ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✷✸ ✹✳✸ ❚❛❜❡❧❛ ❞❡ ❛♣♦ ❡♥③✐♠❛s ❞♦ ❚✐♣♦ ❚r✐♣s✐♥❛ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✷✹ ✹✳✹ ❚❛❜❡❧❛ ❞❡ ❛♣♦ ❡♥③✐♠❛s ❞♦ ❚✐♣♦ ❙✉❜t✐❧✐s✐♥❛ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✷✹ ✹✳✺ ❚❛❜❡❧❛ ❞❡ ❝❧❛ss✐✜❝❛çã♦ ❞❡ át♦♠♦s ❡♠ ❝♦♥❞✐çõ❡s ❤✐❞r♦❢ó❜✐❝❛s ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✸✶

✺✳✶ ❆♥á❧✐s❡ ❈❈❈ ♣❛r❛ ❊❣❧✐♥❛ ❈ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✹✷ ✺✳✷ ❆♥á❧✐s❡ ❙●❈❈ ♣❛r❛ ❊❣❧✐♥❛ ❈ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✹✸ ✺✳✸ ❆♥á❧✐s❡ ❊❇❈❈ ♣❛r❛ ❊❣❧✐♥❛ ❈ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✹✹ ✺✳✹ ❈♦♠♣❛r❛çã♦ q✉❛♥t✐t❛t✐✈❛ ❡♥tr❡ ❛s ❛❜♦r❞❛❣❡♥s ♣r♦♣♦st❛s ♣❛r❛ ❊❣❧✐♥❛ ❈ ✳ ✳ ✳ ✳ ✹✹ ✺✳✺ ❆♥á❧✐s❡ ❈❈❈ ♣❛r❛ ❖✈♦♠✉❝♦✐❞❡ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✹✼ ✺✳✻ ❆♥á❧✐s❡ ❙●❈❈ ♣❛r❛ ❖✈♦♠✉❝♦✐❞❡ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✹✽ ✺✳✼ ❆♥á❧✐s❡ ❊❇❈❈ ♣❛r❛ ❖✈♦♠✉❝♦✐❞❡ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✹✾ ✺✳✽ ❈♦♠♣❛r❛çã♦ q✉❛♥t✐t❛t✐✈❛ ❡♥tr❡ ❛s ❛❜♦r❞❛❣❡♥s ♣r♦♣♦st❛s ♣❛r❛ ❖✈♦♠✉❝♦✐❞❡ ✳ ✳ ✹✾ ✺✳✾ ❆♥á❧✐s❡ ❈❈❈✿ ♣r❡❞✐çã♦ ■❋❘ ❚✐♣♦ ❚r✐♣s✐♥❛ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✺✸ ✺✳✶✵ ❆♥á❧✐s❡ ❙●❈❈✿ ♣r❡❞✐çã♦ ■❋❘ ❚✐♣♦ ❚r✐♣s✐♥❛ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✺✹ ✺✳✶✶ ❆♥á❧✐s❡ ❊❇❈❈✿ ♣r❡❞✐çã♦ ■❋❘ ❚✐♣♦ ❚r✐♣s✐♥❛ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✺✺ ✺✳✶✷ ❈♦♠♣❛r❛çã♦ q✉❛♥t✐t❛t✐✈❛ ❡♥tr❡ ❛s ❛❜♦r❞❛❣❡♥s ♣r♦♣♦st❛s ♣❛r❛ ♣r❡❞✐çã♦ ❞❛s

■❋❘s ❞❛s ❡♥③✐♠❛s ❞♦ ❚✐♣♦ ❚r✐♣s✐♥❛ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✺✺ ✺✳✶✸ ❆♥á❧✐s❡ ❈❈❈✿ ♣r❡❞✐çã♦ ■❋❘ ❚✐♣♦ ❙✉❜t✐❧✐s✐♥❛ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✺✼ ✺✳✶✹ ❆♥á❧✐s❡ ❙●❈❈✿ ♣r❡❞✐çã♦ ■❋❘ ❚✐♣♦ ❙✉❜t✐❧✐s✐♥❛ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✺✽ ✺✳✶✺ ❆♥á❧✐s❡ ❊❇❈❈✿ ♣r❡❞✐çã♦ ■❋❘ ❚✐♣♦ ❙✉❜t✐❧✐s✐♥❛ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✺✾ ✺✳✶✻ ❈♦♠♣❛r❛çã♦ q✉❛♥t✐t❛t✐✈❛ ❡♥tr❡ ❛s ❛❜♦r❞❛❣❡♥s ♣r♦♣♦st❛s ♣❛r❛ ♣r❡❞✐çã♦ ❞❛s

■❋❘s ❞❛s ❡♥③✐♠❛s ❞♦ ❚✐♣♦ ❙✉❜t✐❧✐s✐♥❛ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✳ ✺✾

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▲✐st❛ ❞❡ ❆❜r❡✈✐❛çõ❡s

❆❆✿ ❆❣r✉♣❛♠❡♥t♦ ❆❣❧♦♠❡r❛t✐✈♦

❆❙❆✿ ❆❝❝❡ss✐❜✐❧✐t② ❙♦❧✈❡♥t ❆r❡❛

❇❘❊◆❉❆✿ ❇❘❛✉♥s❝❤✇❡✐❣ ❊◆③②♠❡ ❉❛t❛❜❛s❡

❈❈❈✿ ❈❡♥tró✐❞❡ ❞❡ ❈♦♠♣♦♥❡♥t❡ ❈♦♥❡①♦

❉❈✿ ❉❡♣❡♥❞❡♥t❡ ❞❡ ❈♦rt❡

❉❱✿ ❉✐❛❣r❛♠❛ ❞❡ ❱♦r♦♥♦✐

❊❇❈❈✿ ❈❡♥tró✐❞❡ ❞❡ ❈♦♠✉♥✐❞❛❞❡ ❜❛s❡❛❞♦ ♥♦ ♠ét♦❞♦ ❊❞❣❡ ❇❡t✇❡❡♥❡ss

❊❈✿ ❊♥③②♠❡ ❈❧❛ss✐✜❝❛t✐♦♥

❍P✲❝❡♥tr♦✐❞❡✿ ❍②❞r♦❢♦❜✐❝ P❛t❝❤ ❈❡♥tr♦✐❞❡

❍②❞r♦P❛❈❡✿ ❍②❞r♦❢♦❜✐❝ P❛t❝❤ ❈❡♥tr♦✐❞

■❈✿ ■♥❞❡♣❡♥❞❡♥t❡ ❞❡ ❈♦rt❡

■❋❘✿ ■♥t❡r❢❛❝❡ ❋♦r♠✐♥❣ ❘❡s✐❞✉❡

■❯❇▼❇✿ ■♥t❡r♥❛t✐♦♥❛❧ ❯♥✐♦♥ ♦❢ ❇✐♦❝❤❡♠✐str② ❛♥❞ ▼♦❧❡❝✉❧❛r ❇✐♦❧♦❣②

▼❖✿ ▼♦❞❡❧♦ ❞❡ ❖t✐♠✐③❛çã♦

P❉❇✿ Pr♦t❡✐♥ ❉❛t❛ ❇❛♥❦

P❉❇❡st✿ P❉❇ ❊♥❤❛♥❝❡❞ ❙tr✉❝t✉r❡ ❚♦♦❧❦✐t

P❘▼✿ P❡♥❛❧✐③❡❞ ❘❡❝❛❧❧ ▼❡tr✐❝

❘❈▲✿ ❘❡❛t✐✈❡ ❈❡♥tr❡ ▲♦♦♣

❙❈❖P✿ ❙tr✉❝t✉r❛❧ ❈❧❛ss✐✜❝❛t✐♦♥ ♦❢ Pr♦t❡✐♥s

❙●❈❈✿ ❈❡♥tró✐❞❡ ❞❡ ❈♦♠✉♥✐❞❛❞❡ ❜❛s❡❛❞♦ ♥♦ ♠ét♦❞♦ ❙♣✐♥ ●❧❛ss

❙▼❙✿ ❙❚■◆● ▼✐❧❧❡♥♥✐✉♠ ❙✉✐t❡

❚❉✿ ❚❡ss❡❧❛çã♦ ❞❡ ❉❡❧❛✉♥❛②

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❈❛♣ít✉❧♦ ✶

■♥tr♦❞✉çã♦

■♥✐❜✐çã♦ ❡♥③✐♠át✐❝❛ ♦❝♦rr❡ q✉❛♥❞♦ ✉♠❛ ♠♦❧é❝✉❧❛ ❧✐❣❛✲s❡ ❛ ✉♠❛ ❡♥③✐♠❛ ❞✐♠✐♥✉✐♥❞♦ ❛ s✉❛ ❛t✐✈✐❞❛❞❡✱ ♣♦❞❡♥❞♦ s❡r r❡✈❡rsí✈❡❧ ♦✉ ✐rr❡✈❡rsí✈❡❧✳ ❊❧❛ é ✉♠ ❢❡♥ô♠❡♥♦ ❝♦♠♣❧❡①♦ q✉❡ ❡♥✈♦❧✈❡ r❡❝♦♥❤❡❝✐♠❡♥t♦ ♠♦❧❡❝✉❧❛r ❡ ✐♥t❡r❛çõ❡s ❬❇❛❤❛❞✉r ❡ ❩❛❝❤❛r✐❛s ✭✷✵✵✽✮❀ ❙❤✉❧♠❛♥✲ P❡❧❡❣ ❡t ❛❧✳ ✭✷✵✵✼✮❀ ❈❛✛r❡② ❡t ❛❧✳ ✭✷✵✵✹✮❀ ❚✉♥❝❜❛❣ ❡t ❛❧✳ ✭✷✵✶✶✮❀ ❈s❡r♠❡❧② ✭✷✵✵✽✮❪✳ ➱ ✉♠ ♠❡❝❛♥✐s♠♦ ✐♠♣♦rt❛♥t❡ ❡♥✈♦❧✈❡♥❞♦ r❡❣✉❧❛çõ❡s ♠❡t❛❜ó❧✐❝❛s ✐♥t❡r ❡ ✐♥tr❛ ❝❡❧✉❧❛r✱ ♣r♦❝❡ss♦s ✐♥✢❛♠❛tór✐♦s ❡ ✐♠✉♥♦❧ó❣✐❝♦s✱ r❡♣❧✐❝❛çã♦ ❞❡ ✈ír✉s ❡ ♠✉✐t❛s ♦✉tr❛s ❢✉♥çõ❡s ❜✐♦❧ó❣✐❝❛s ❬ ❘❛✲ ✇❧✐♥❣s ❡t ❛❧✳ ✭✷✵✵✹✮❪✳ ❯♠❛ ✈❡③ q✉❡ ❡ss❡ ❢❡♥ô♠❡♥♦ ♥❛t✉r❛❧ é ❝♦rr❡t❛♠❡♥t❡ ❡♥t❡♥❞✐❞♦✱ ❡❧❡ ♣♦❞❡ s❡r ✉s❛❞♦ ❝♦♠ ♣r♦♣ós✐t♦s ❜✐♦t❡❝♥♦❧ó❣✐❝♦s ♥♦ ❞❡s❡♥✈♦❧✈✐♠❡♥t♦ ❞❡ ♥♦✈♦s ❢ár♠❛❝♦s✱ ✐♥s❡t✐❝✐❞❛s✱ ♣❡st✐❝✐❞❛s✱ ❡♥tr❡ ♦✉tr♦s✳

❖s ✐♥✐❜✐❞♦r❡s ❡♥③✐♠át✐❝♦s ♣♦❞❡♠ s❡r ♣r♦t❡✐❝♦s ♦✉ ♥ã♦ ♣r♦t❡✐❝♦s ❡ ❡❧❡s ♣♦❞❡♠ ❞✐♠✐♥✉✐r ❛ ❤❛❜✐❧✐❞❛❞❡ ❞❡ ✉♠❛ ❡♥③✐♠❛ ♣❛r❛ ❡♥❝♦♥tr❛r s✉❜str❛t♦s✱ ❞✐♠✐♥✉✐r ❛ ❛t✐✈✐❞❛❞❡ ❝❛t❛❧ít✐❝❛ ♦✉ ❛ ❝♦♠❜✐♥❛çã♦ ❞❡ ❛♠❜♦s✳ ❆ ✐♥✐❜✐çã♦ ♣♦❞❡ ♦❝♦rr❡r ❞❡ três ♠❛♥❡✐r❛s ❞✐❢❡r❡♥t❡s✳ ❆ ♣r✐♠❡✐r❛ é ❛ ✐♥✐❜✐çã♦ ❝♦♠♣❡t✐t✐✈❛ ❡ ♦❝♦rr❡ q✉❛♥❞♦ ♦ ✐♥✐❜✐❞♦r t❡♠ ✉♠❛ ❛✜♥✐❞❛❞❡ ♣❡❧♦ sít✐♦ ❛t✐✈♦✱ ❞✐s♣✉t❛♥❞♦ ♦ ❛❝❡ss♦ ❝♦♠ ♦ s✉❜str❛t♦✳ ❆ s❡❣✉♥❞❛ é ❛ ✐♥✐❜✐çã♦ ♥ã♦ ❝♦♠♣❡t✐t✐✈❛ ❡ ♦❝♦rr❡ q✉❛♥❞♦ ♦ ♣r♦❝❡ss♦ ❞❡ ✐♥✐❜✐çã♦ ♥ã♦ ❛❢❡t❛ ❛ ❧✐❣❛çã♦ ♥♦ s✉❜str❛t♦✱ ♠❛s r❡❞✉③ ❛ ❛t✐✈✐❞❛❞❡ ❡♥③✐♠át✐❝❛✳ ❆ t❡r❝❡✐r❛ é ❛ ❝♦♠❜✐♥❛çã♦ ❞♦s ❞♦✐s ♣r✐♠❡✐r♦s t✐♣♦s ❡ ♦❝♦rr❡ q✉❛♥❞♦ ♦ ✐♥✐❜✐❞♦r ❡ ♦ s✉❜str❛t♦ ❧✐❣❛♠✲s❡ ❛♦ ♠❡s♠♦ t❡♠♣♦ ♥❛ ❡♥③✐♠❛ ❡ ♦ ♣r✐♠❡✐r♦ ❛❢❡t❛ ❛ ❧✐❣❛çã♦ ❞♦ ú❧t✐♠♦✳ ❯♠ ❝❛s♦ ♣❛rt✐❝✉❧❛r é ❛ ✐♥✐❜✐çã♦ ❞❡ ♣r♦t❡❛s❡s ❡✱ ♥❡st❡ ❝♦♥t❡①t♦✱ ❛ ❜❛s❡ ❞❡ ❞❛❞♦s ▼❊✲ ❘❖P❙ é ❛t✉❛❧♠❡♥t❡ ✉♠ ❞♦s ♠❛✐s ✐♠♣♦rt❛♥t❡s r❡♣♦s✐tór✐♦s ❬ ❘❛✇❧✐♥❣s ❡t ❛❧✳ ✭✷✵✵✽✮❪✳ ❊❧❡ ❛❣r✉♣❛ ❤✐❡r❛rq✉✐❝❛♠❡♥t❡ ♣r♦t❡❛s❡s ❡ ✐♥✐❜✐❞♦r❡s ❡♠ ❢❛♠í❧✐❛s ✭❡♥t✐❞❛❞❡s r❡❧❛❝✐♦♥❛❞❛s ♣❡❧❛ s❡q✉ê♥❝✐❛✮ ❡ ❝❧ãs ✭❡♥t✐❞❛❞❡s r❡❧❛❝✐♦♥❛❞❛s ♣❡❧❛ ❡str✉t✉r❛✮✳ ❯♠❛ ❝r✐t❡r✐♦s❛ ❜✉s❝❛ ♥❛ ❜❛s❡ ❞❡ ❞❛❞♦s ▼❊❘❖P❙ r❡ss❛❧t❛ ✉♠ ❜❡♠ ❝♦♥❤❡❝✐❞♦✱ ♠❛s ✐♥tr✐❣❛♥t❡ ❢❡♥ô♠❡♥♦✿ ❛ ❢❛❧t❛ ❞❡ ❡s♣❡❝✐✜❝✐❞❛❞❡ ❞❡ ❛❧❣✉♥s ✐♥✐❜✐❞♦r❡s✱ ❡♥✈♦❧✈❡♥❞♦ ❡str✉t✉r❛s tr✐❞✐♠❡♥s✐♦♥❛✐s ❡ ♠❡❝❛♥✐s♠♦s ❝❛t❛❧ít✐❝♦s ❞✐❢❡r❡♥t❡s✳ P♦r ❡①❡♠♣❧♦✿ ♦s ✐♥✐❜✐❞♦r❡s ❖✈♦♠✉❝♦✐❞❡ ❡ ❊❣❧✐♥❛ ❈ ❛❣❡♠ ❡♠ ❞✐✲

❢❡r❡♥t❡s ❝❧ãs ❞❡ ♣r♦t❡❛s❡s✱ ❝♦♠♦ P❆✭❙✮ ✭❚✐♣♦ ❚r✐♣s✐♥❛✿ ❡♥♦✈❡❧❛♠❡♥t♦ ❞♦ t✐♣♦ ❛❧❧ β✮✶

❡ ❙❇ ✭❚✐♣♦ ❙✉❜t✐❧✐s✐♥❛✿ ❡♥♦✈❡❧❛♠❡♥t♦ ❞♦ t✐♣♦ α/β✮✷❀ ♦ ✐♥✐❜✐❞♦r ❑✉♥✐t③ ❞❡ ❚r✐♣s✐♥❛ ❞❛ ✶ ❛❧❧ β✿ ❡str✉t✉r❛ ❢♦r♠❛❞❛ q✉❛s❡ ❡①❝❧✉s✐✈❛♠❡♥t❡ ♣♦r ❢♦❧❤❛s β✱ ❛♣r❡s❡♥t❛❞❛s ❡♠ ✉♠ ❛rr❛♥❥♦ q✉❛s❡ ♦✉

❝♦♠♣❧❡t❛♠❡♥t❡ ❛♥t✐✲♣❛r❛❧❡❧♦

(16)

✶✳ ■♥tr♦❞✉çã♦ ✸

s♦❥❛ ❞❡❝❛✐ ❛ ❛t✐✈✐❞❛❞❡ ♣r♦t❡♦❧ít✐❝❛ t❛♥t♦ ❡♠ s❡r✐♥♦ q✉❛♥t♦ ❡♠ ♠❡t❛❧♦ ♣r♦t❡❛s❡s✱ q✉❡ tê♠ ♠❡❝❛♥✐s♠♦s ❡♥③✐♠át✐❝♦s ♠✉✐t♦ ❞✐❢❡r❡♥t❡s✳ ◆ós ❝❤❛♠❛♠♦s ❡st❛ ❢❛❧t❛ ❞❡ ❡s♣❡❝✐✜❝✐❞❛❞❡ ❞♦ ✐♥✐❜✐❞♦r ❞❡ ■♥✐❜✐çã♦ ❈r✉③❛❞❛✳ ◆♦ss♦ ♣r✐♥❝✐♣❛❧ ❞❡s❛✜♦ é ❞❡s❡♥✈♦❧✈❡r ✉♠❛ ♠❡t♦❞♦❧♦❣✐❛ q✉❡ ♣♦❞❡ ❛❥✉❞❛r ❛ ❡♥t❡♥❞❡r ❡ ♣r❡❞✐③❡r ❡ss❡ ❢❡♥ô♠❡♥♦✳

❖ r❡❝♦♥❤❡❝✐♠❡♥t♦ ❡ ❛ ❧✐❣❛çã♦ ❡♥tr❡ ❡♥③✐♠❛ ❡ ✐♥✐❜✐❞♦r é ❞❡t❡r♠✐♥❛❞♦ ♣❡❧❛ ♦r❣❛♥✐③❛çã♦ ❝♦♠♣❧❡①❛ ❞❛s ✐♥t❡r❛çõ❡s q✉í♠✐❝❛s ❡ ❢❛t♦r❡s ❡♥tró♣✐❝♦s ❡♥✈♦❧✈❡♥❞♦ ♦ s✐st❡♠❛ ♣r♦t❡❛s❡✲ ✐♥✐❜✐❞♦r✲s♦❧✈❡♥t❡✳ ❋❡❧✐③♠❡♥t❡✱ ❛ ❡♥❡r❣✐❛ ❡①♣❡r✐♠❡♥t❛❧ ❞❛ ❧✐❣❛çã♦ ❞❡ ♠✉✐t♦s ❝♦♠♣❧❡①♦s ✐♥✐✲ ❜✐❞♦r❡s ❡ ♣r♦t❡❛s❡s ❥á ❢♦✐ t❡r♠♦❞✐♥❛♠✐❝❛♠❡♥t❡ ❞❡t❡r♠✐♥❛❞❛✳ ➱ ❝♦♥❤❡❝✐❞♦✱ ♣♦r ❡①❡♠♣❧♦✱ q✉❡ ❛ ❧✐❣❛çã♦ ❞❡ ❖✈♦♠✉❝♦✐❞❡ ❡ ❊❧❛st❛s❡✱ ❡♠ 25◦C✱ é ❝❛r❛❝t❡r✐③❛❞❛ ♣♦r ✉♠❛ ❡♥❡r❣✐❛ ❧✐✈r❡ ❞❡ ●✐❜❜s ♥❡❣❛t✐✈❛✱ ♥❛ q✉❛❧✱ ❛ ✈❛r✐❛çã♦ ❞❛ ❡♥t❛❧♣✐❛ é q✉❛s❡ ✐♥s✐❣♥✐✜❝❛♥t❡✱ ♠❛s ❛ ♠✉❞❛♥ç❛ ❞❡ ❡♥tr♦♣✐❛ é ❛♠♣❧❛♠❡♥t❡ ♣♦s✐t✐✈❛ ❬❇❛❦❡r ❡ ▼✉r♣❤② ✭✶✾✾✼✮❪✳ ■ss♦ ♥♦s ❞❡✉ ❢♦rt❡s ✐♥❞í❝✐♦s ❞❡ q✉❡ ❞❡✈❡♠♦s ❝♦♥❝❡♥tr❛r ❛ ♥♦ss❛ ❛t❡♥çã♦✱ ❡s♣❡❝✐❛❧♠❡♥t❡ ♥❛ ❜✉s❝❛ ♣♦r ♣❛❞rõ❡s ❞❡ ✐♥t❡✲ r❛çõ❡s ❤✐❞r♦❢ó❜✐❝❛s ❝♦♥s❡r✈❛❞❛s✳ ◆ós ❞❡✜♥✐♠♦s ❡ss❡s ♣❛❞rõ❡s ❝♦♠♦ r❡❣✐õ❡s ❤✐❞r♦❢ó❜✐❝❛s ✐♥✈❛r✐á✈❡✐s ♦✉ ♣❛t❝❤❡s q✉❡ ❡stã♦ ❡♠ ❝♦♥t❛t♦ ❝♦♠ ❛s ♠❡s♠❛s r❡❣✐õ❡s ❞♦ ✐♥✐❜✐❞♦r✳

❊♠❜♦r❛ ❡①✐st❛♠ ♠✉✐t♦s ❡st✉❞♦s ❜✐♦q✉í♠✐❝♦s ❛♥❛❧✐s❛♥❞♦ ❛ ❞✐✈❡rs✐❞❛❞❡ ❞❡ ♣r♦❝❡ss♦s ❞❡ ✐♥✐❜✐çã♦ ❬▲❛s❦♦✇s❦✐ ❡ ◗❛s✐♠ ✭✷✵✵✵❛✮❀ ❇♦❞❡ ❡t ❛❧✳ ✭✶✾✽✻✮❀ ◗❛s✐♠ ❡t ❛❧✳ ✭✶✾✾✼✮❀ ❈❤❛❦r❛❜❛rt✐ ❡ ❏❛♥✐♥ ✭✷✵✵✷❛✮❪✱ ❛ ❝❛r❛❝t❡r✐③❛çã♦ ❡①♣❡r✐♠❡♥t❛❧ ❞❡ ✐♥✐❜✐çã♦ é ✉♠ ♣r♦❝❡ss♦ ❞❡ tr❛❜❛❧❤♦ ✐♥t❡♥s✐✈♦✳ ❆ ❣r❛♥❞❡ q✉❛♥t✐❞❛❞❡ ❞❡ ♣♦ssí✈❡✐s ✐♥✐❜✐❞♦r❡s ♣❛r❛ ✉♠❛ ❞❡t❡r♠✐♥❛❞❛ ❡♥③✐♠❛ ♣♦❞❡♠ ❢❛③❡r ❝♦♠ q✉❡ ❡st❡s t❡st❡s s❡❥❛♠ ❝✉st♦s♦s ❡✱ ♣♦r ✐ss♦✱ ♠ét♦❞♦s ✐♥ s✐❧✐❝♦ ♣♦❞❡♠ ❝♦♥tr✐❜✉✐r ♣❛r❛ ♣r❡❞✐③❡r r❡❝♦♥❤❡❝✐♠❡♥t♦ ❡♥③✐♠❛✲✐♥✐❜✐❞♦r✳

❆♣❡s❛r ❞❡ s✉❛ ✐♠♣♦rtâ♥❝✐❛ ❡✈✐❞❡♥t❡✱ ♥ós ♣❡r❝❡❜❡♠♦s q✉❡ ❤á ✉♠❛ ❢❛❧t❛ ❞❡ ♠♦❞❡❧♦s ❡ ❛❧❣♦r✐t♠♦s ❝❛♣❛③❡s ❞❡ ✐❞❡♥t✐✜❝❛r ♣❛❞rõ❡s ❞❡ r❡❝♦♥❤❡❝✐♠❡♥t♦ ❡ ✐♥t❡r❛çã♦ q✉❡ ♣♦❞❡r✐❛♠ ❛❥✉❞❛r ❛ ❡s❝❧❛r❡❝❡r ❝♦♠♦ ❛ ✐♥✐❜✐çã♦ ❝r✉③❛❞❛ ❛❝♦♥t❡❝❡✳ ◆❡st❡ ❝♦♥t❡①t♦✱ ✉♠ ♣❛❞rã♦ é ✉♠ ❝♦♥❥✉♥t♦ ❞❡ ❛tr✐❜✉t♦s ❝♦♥s❡r✈❛❞♦s✱ ♥❛ ✐♥t❡r❢❛❝❡✱ ✉s❛❞♦s ♣❛r❛ ❡①♣❧✐❝❛r ♦✉ ♣r❡❞✐③❡r ❧✐❣❛çõ❡s✳ ❚r❛❞✐❝✐♦♥❛❧♠❡♥t❡✱ ♠ét♦❞♦s ❞❡ ❝♦♠♣❛r❛çã♦ ❞❡ s❡q✉ê♥❝✐❛s ❡✴♦✉ ❛❧✐♥❤❛♠❡♥t♦ ❡str✉t✉r❛❧ tê♠ s✐❞♦ ✉t✐❧✐③❛❞♦s ♥❛ ❞❡t❡❝çã♦ ❞❡ ❝♦♥s❡r✈❛çã♦ ❬❩❤❛♥❣ ❡t ❛❧✳ ✭✷✵✶✶✮❀ ❘✐❜❡✐r♦ ❡t ❛❧✳ ✭✷✵✶✵✮❀ ▼❡❧♦ ❡t ❛❧✳ ✭✷✵✵✼✮❪✳ ❉❡ ❛❝♦r❞♦ ❝♦♠ ❚✉♥❝❜❛❣ ❡t ❛❧✳ ✭✷✵✶✶✮✱ ❡str✉t✉r❛s sã♦ ♠❛✐s ❝♦♥s❡r✈❛❞❛s ❞♦ q✉❡ ❛s s❡q✉ê♥❝✐❛s ❡ r❡sí❞✉♦s ❞❛ ✐♥t❡r❢❛❝❡ ♦✉ ■❘❋✱ ❞♦ ✐♥❣❧ês ■♥t❡r❢❛❝❡ ❋♦r♠✐♥❣ ❘❡s✐❞✉❡s✱ sã♦ ❛✐♥❞❛ ♠❛✐s ❝♦♥s❡r✈❛❞♦ ❞♦ q✉❡ t♦❞❛ ❛ ❡str✉t✉r❛✳ ◆♦ ❡♥t❛♥t♦✱ ♥❛ ✐♥✐❜✐çã♦ ❝r✉③❛❞❛ ♣♦✲ ❞❡♠♦s ❧✐❞❛r ❝♦♠ s❡q✉ê♥❝✐❛s ♠✉✐t♦ ❞✐❢❡r❡♥t❡s ❡ ❡str✉t✉r❛s tr✐❞✐♠❡♥s✐♦♥❛✐s ❝♦♠♣❧❡t❛♠❡♥t❡ ❞✐ss✐♠✐❧❛r❡s✱ ♦ q✉❡ ❢❛③ ❝♦♠ q✉❡ ♦s ♠ét♦❞♦s ❝❧áss✐❝♦s s❡❥❛♠ ✐♥❛❞❡q✉❛❞♦s✳

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✶✳ ■♥tr♦❞✉çã♦ ✹

♣♦r ❡①❡♠♣❧♦✱ é ❝♦♥s✐❞❡r❛❞♦ ✉♠ r❡sí❞✉♦ ❝❛rr❡❣❛❞♦ ♣♦s✐t✐✈❛♠❡♥t❡ ✭❡♠ ♣❍ ♥❡✉tr♦✮✱ ♠❛s ❤á t❛♠❜é♠ ✈ár✐♦s ❣r✉♣♦s ♠❡t✐s ❤✐❞r♦❢ó❜✐❝♦s✳

❖ r❡❝♦♥❤❡❝✐♠❡♥t♦ ❡♥③✐♠❛✲✐♥✐❜✐❞♦r é ❞❡t❡r♠✐♥❛❞♦ ♣♦r ✉♠❛ r❡❞❡ ❞❡ ✐♥t❡r❛çõ❡s ❡♥tr❡ ♦s át♦♠♦s✱ ♣♦rt❛♥t♦✱ ❛ ♠♦❞❡❧❛❣❡♠ ❡♠ ❣r❛❢♦ é ✉♠❛ ❛❜♦r❞❛❣❡♠ ❞✐r❡t❛✳ ◆ós ♠♦❞❡❧❛♠♦s ♦s át♦♠♦s ❤✐❞r♦❢ó❜✐❝♦s ❝♦♠♦ ✈ért✐❝❡s ❞❡ ✉♠ ❣r❛❢♦ ❡ ♦s ❝♦♥t❛t♦s ❡♥tr❡ ❡❧❡s ❝♦♠♦ ❛s ❛r❡s✲ t❛s✳ ❯s❛♠♦s ♦ ❣r❛❢♦ ♣❛r❛ ♦❜t❡r ♣❛t❝❤❡s ❤✐❞r♦❢ó❜✐❝♦s ❝♦♥s❡r✈❛❞♦s ♦✉✱ ❡♠ ♦✉tr❛s ♣❛❧❛✈r❛s✱ ❝♦♠♣♦♥❡♥t❡s ❝♦♥❡❝t❛❞♦s✳

❙✉♣♦♥❞♦ q✉❡ ❛ ♣r♦♣r✐❡❞❛❞❡ ♠❛✐s ✐♠♣♦rt❛♥t❡ ❞❡ ✉♠ ♣❛t❝❤ ❤✐❞r♦❢ó❜✐❝♦ é ♦♥❞❡ ❡❧❡ ❡stá ♣♦s✐❝✐♦♥❛❞♦ ♣❛r❛ ✐♥t❡r❛❣✐r ❝♦♠ ♦ ❧✐❣❛♥t❡✱ ♥♦s ❛❜str❛í♠♦s ❛ s✉❛ ❝♦♠♣♦s✐çã♦✱ ❢♦r♠❛✱ ✈♦❧✉♠❡ ❡ ❞❡♥s✐❞❛❞❡ ❡ r❡♣r❡s❡♥t❛♠♦s ✉♠ ♣❛t❝❤ ❝♦♠♦ ✉♠ ❝❡♥tr♦✐❞❡ ❣❡♦♠étr✐❝♦✱ q✉❡ ♥ós ❝❤❛♠❛♠♦s ❞❡ ❍P✲❝❡♥tr♦✐❞❡ ✭❍②❞r♦♣❤♦❜✐❝ P❛t❝❤ ❈❡♥tr♦✐❞✮✳ ◆❡st❡ tr❛❜❛❧❤♦✱ ♥ós ♣r♦♣♦♠♦s ✉♠❛ ♥♦✈❛ ♠❡t♦❞♦❧♦❣✐❛ q✉❡ ❡♥✈♦❧✈❡ ♠♦❞❡❧♦s ❡ ❛❧❣♦r✐t♠♦s ♣❛r❛ ❞❡t❡❝t❛r ❍P✲❝❡♥tr♦✐❞❡s ❤✐❞r♦❢ó❜✐❝♦s ❝♦♥s❡r✈❛❞♦s ❡♠ ✐♥✐❜✐çã♦ ❝r✉③❛❞❛✳

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❈❛♣ít✉❧♦ ✷

❋✉♥❞❛♠❡♥t❛çã♦ ❚❡ór✐❝❛

✷✳✶ Pr♦t❡❛s❡s

❆s ♣r♦t❡❛s❡s✱ t❛♠❜é♠ ❝♦♥❤❡❝✐❞❛s ❝♦♠♦ ♣r♦t❡✐♥❛s❡s✱ ♣❡♣t✐❞❛s❡s ♦✉ ❡♥③✐♠❛s ♣r♦t❡♦❧ít✐✲ ❝❛s✱ sã♦ ❝❧❛ss❡s ❞❡ ❡♥③✐♠❛s q✉❡ ❝❛t❛❧✐s❛♠ ❛ ❝❧✐✈❛❣❡♠ ❞❡ ❧✐❣❛çõ❡s ♣❡♣tí❞✐❝❛s ❞❡ ♣r♦t❡í♥❛s✳ ❖ ♣r♦❝❡ss♦ ❞❡ ❝❧✐✈❛❣❡♠✱ ♦✉ s❡❥❛✱ ❛ q✉❡❜r❛ ❞❡ ❧✐❣❛çõ❡s ♣❡♣tí❞✐❝❛s ♥❡❝❡ss✐t❛ ❞♦ ❡♥✈♦❧✈✐♠❡♥t♦ ❞❡ ✉♠❛ ♠♦❧é❝✉❧❛ ❞❡ á❣✉❛✱ s❡♥❞♦ ❝❧❛ss✐✜❝❛❞♦ ❝♦♠♦ ❤✐❞r♦❧❛s❡✳ ▼✉✐t❛s ❞❡ss❛s ❡♥③✐♠❛s ❛❞q✉✐✲ r❡♠ ❛♠♣❧❛s ❛t✐✈✐❞❛❞❡s ❡♥③✐♠át✐❝❛s q✉❛♥❞♦ s❡ ❡♥♦✈❡❧❛♠ ❡s♣♦♥t❛♥❡❛♠❡♥t❡ ❡♠ s✉❛s ❢♦r♠❛s tr✐❞✐♠❡♥s✐♦♥❛✐s ❝❛r❛❝t❡ríst✐❝❛s✱ ♣♦ré♠✱ ♦✉tr❛s sã♦ s✐♥t❡t✐③❛❞❛s ❝♦♠♦ ♣r❡❝✉rs♦r❡s ✐♥❛t✐✈♦s✱ q✉❡ s✉❜s❡q✉❡♥t❡♠❡♥t❡ sã♦ ❛t✐✈❛❞♦s ♣♦r ❝❧✐✈❛❣❡♠ ❞❡ ✉♠❛ ♦✉ ♠❛✐s ❧✐❣❛çõ❡s ♣❡♣tí❞✐❝❛s ❡s✲ ♣❡❝í✜❝❛s✳ ❊st❡s ♣r❡❝✉rs♦r❡s ✐♥❛t✐✈♦s sã♦ ❝❤❛♠❛❞♦s ❞❡ ③✐♠♦❣ê♥✐♦s ♦✉ ♣r♦❡♥③✐♠❛s ❬❇❡r❣ ❡t ❛❧✳ ✭✷✵✵✺✮❪✳

Pr♦t❡❛s❡s sã♦ ✈✐st❛s ❝♦♠♦ ♠♦❧é❝✉❧❛s s✐♥❛❧✐③❛❞♦r❛s ❡①tr❡♠❛♠❡♥t❡ ✐♠♣♦rt❛♥t❡s q✉❡ ❡s✲ tã♦ ❡♥✈♦❧✈✐❞❛s ❡♠ ♥✉♠❡r♦s♦s ♣r♦❝❡ss♦s ✈✐t❛✐s✳ ❊❧❛s sã♦ ❡str✐t❛♠❡♥t❡ r❡❣✉❧❛❞♦r❛s✱ ❡ ❛ ❞❡sr❡❣✉❧❛çã♦ ❞❡ s✉❛s ❛t✐✈✐❞❛❞❡s ♣♦❞❡ ❝♦♥❞✉③✐r ❛ ♣❛t♦❧♦❣✐❛s✱ t❛✐s ❝♦♠♦✱ ❞♦❡♥ç❛s ❝❛r❞✐♦✲ ✈❛s❝✉❧❛r❡s ❡ ✐♥✢❛♠❛tór✐❛s✱ ❝â♥❝❡r✱ ♦st❡♦♣♦r♦s❡ ❡ ❞❡s♦r❞❡♥s ♥❡✉r♦❧ó❣✐❝❛s✳ ❊❧❛s ♦❝♦rr❡♠ ♥❛t✉r❛❧♠❡♥t❡ ❡♠ t♦❞♦s ♦s ♦r❣❛♥✐s♠♦s ❡ ❝♦rr❡s♣♦♥❞❡♠ ❛ ❛♣r♦①✐♠❛❞❛♠❡♥t❡ ✷✪ ♥♦ ❣❡♥♦♠❛ ❤✉♠❛♥♦✳ ❊❧❛s ❡stã♦ ❡♥✈♦❧✈✐❞❛s ❡♠ ✉♠❛ ❣r❛♥❞❡ ✈❛r✐❡❞❛❞❡ ❞❡ r❡❛çõ❡s ♠❡t❛❜ó❧✐❝❛s✱ ❝♦♠♦ ❛ ❞✐❣❡stã♦ ❞❡ ♣r♦t❡í♥❛s ❞♦ ❛❧✐♠❡♥t♦ ❡ ❝❛s❝❛t❛s ❛❧t❛♠❡♥t❡ r❡❣✉❧❛❞❛s✱ ❝♦♠♦✱ ♣♦r ❡①❡♠♣❧♦✱ ❛ ❞❛ ❝♦❛❣✉❧❛çã♦ s❛♥❣✉í♥❡❛✱ ♦ s✐st❡♠❛ ❞♦ ❝♦♠♣❧❡♠❡♥t♦✱ ❛s ✈✐❛s ❞❡ ❛♣♦♣t♦s❡✱ ❛ ❝❛s❝❛t❛ ❛t✐✈❛❞♦r❛ ❞❛ ♣r♦❢❡♥♦❧♦①✐❞❛s❡ ♥♦s ✐♥✈❡rt❡❜r❛❞♦s✱ ❡ r❡♣❧✐❝❛çã♦ ❡ tr❛♥s❝r✐çã♦ ❞♦ ❉◆❆ ❬❚✉r❦ ✭✷✵✵✻✮❪✳

Pr♦t❡❛s❡s ♣❛rt✐❝✐♣❛♠ ♥♦ ♠❡❝❛♥✐s♠♦ ✐♥✈❛s✐✈♦ ❞❡ t✉♠♦r❡s❀ ✐♥❢❡çõ❡s ❞❡ ♠✐❝r♦✲♦r❣❛♥✐s♠♦s r❡q✉❡r❡♠ ♣r♦t❡❛s❡s ♣❛r❛ r❡♣❧✐❝❛çã♦ ♦✉ ✉s❛♠ ♣r♦t❡❛s❡s ❝♦♠♦ ❢❛t♦r ❞❡ ✈✐r✉❧ê♥❝✐❛✳ ■st♦ t❡♠ ❢❛❝✐❧✐t❛❞♦ ♦ ❞❡s❡♥✈♦❧✈✐♠❡♥t♦ ❞❡ t❡r❛♣✐❛s ❞❡ ♣r♦t❡❛s❡s ❛❧✈♦s ♣❛r❛ ❞♦❡♥ç❛s ❞❡ ❣r❛♥❞❡ r❡❧❡✲ ✈â♥❝✐❛ ♣❛r❛ ❛ ✈✐❞❛ ❤✉♠❛♥❛✱ ❝♦♠♦ ♣♦r ❡①❡♠♣❧♦ ❛ ❆■❉❙✱ t♦r♥❛♥❞♦ ♠✉✐t❛s ♣r♦t❡❛s❡s ❢♦❝♦s ❞❡ ❛t❡♥çã♦ ♣❛r❛ ❛s ✐♥❞ústr✐❛s ❢❛r♠❛❝ê✉t✐❝❛s ❝♦♠♦ ♣♦t❡♥❝✐❛✐s ❛❧✈♦s ♣❛r❛ ❞❡s❡♥✈♦❧✈✐♠❡♥t♦ ❞❡ ♥♦✈♦s ❢ár♠❛❝♦s ♦✉ ❝♦♠♦ ❜✐♦♠❛r❝❛❞♦r❡s ❞❡ ❞✐❛❣♥óst✐❝♦s ❡ ♣r♦❣♥óst✐❝♦s✳ ❊♠ ♣❧❛♥t❛s ❛s ♣r♦t❡❛s❡s t❛♠❜é♠ tê♠ ✉♠ ♣❛♣❡❧ ✐♠♣♦rt❛♥t❡✱ ♣♦✐s ❝♦♥tr✐❜✉❡♠ ♣❛r❛ ♦ ♣r♦❝❡ss❛♠❡♥t♦✱

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✷✳ ❋✉♥❞❛♠❡♥t❛çã♦ ❚❡ór✐❝❛ ✻

♠❛t✉r❛çã♦ ♦✉ ❞❡str✉✐çã♦ ❞❡ ❝♦♥❥✉♥t♦s ❡s♣❡❝í✜❝♦s ❞❡ ♣r♦t❡í♥❛s ❡♠ r❡s♣♦st❛ ❛s ✈❛r✐❛çõ❡s ❞❛s ❝♦♥❞✐çõ❡s ❛♠❜✐❡♥t❛✐s ❬▲ó♣❡③✲❖tí♥ ❡ ❇♦♥❞ ✭✷✵✵✽✮❪✳

❘❡♣r❡s❡♥t❛♥t❡s ❞❡ ❡♥③✐♠❛s ❝♦♠ ✐♠♣♦rt❛♥t❡s ♣❛♣❡✐s ❡♠ ♣r♦❝❡ss♦s ✜s✐♦❧ó❣✐❝♦s✱ ❛s ♣r♦✲ t❡❛s❡s t❛♠❜é♠ tê♠ ❛♣❧✐❝❛çã♦ ❝♦♠❡r❝✐❛❧✱ ❡st❛♥❞♦ ❡♥tr❡ ♦s três ♠❛✐♦r❡s ❣r✉♣♦s ❞❡ ❡♥③✐♠❛s ✐♥❞✉str✐❛✐s✱ s❡♥❞♦ r❡s♣♦♥sá✈❡✐s ♣♦r ✻✵✪ ❞❛ ✈❡♥❞❛ ✐♥t❡r♥❛❝✐♦♥❛❧ ❞❡ ❡♥③✐♠❛s✳ ❙ã♦ t❛♠❜é♠ ✐♠♣♦rt❛♥t❡s ❢❡rr❛♠❡♥t❛s ♥❛s ✐♥❞ústr✐❛s ❞❡ ❜✐♦t❡❝♥♦❧♦❣✐❛✱ ♣♦rq✉❡ tê♠ ✉t✐❧✐❞❛❞❡ ❝♦♠♦ r❡✲ ❛❣❡♥t❡s ♦✉ ♥❛ ❢❛❜r✐❝❛çã♦ ❞❡ ✐♥ú♠❡r♦s ♣r♦❞✉t♦s✳ ➱ ♥♦tá✈❡❧ ❛ ❛♣❧✐❝❛çã♦ ♥❛ ✐♥❞ústr✐❛ ❞❡ ❞❡t❡r❣❡♥t❡s ❡ ❞❡ ❛❧✐♠❡♥t♦s❀ t❡♥❞♦ ❡♠ ✈✐st❛ ♦s r❡❝❡♥t❡s ❛❝♦r❞♦s ♠✉♥❞✐❛✐s ♣❛r❛ ♦ ✉s♦ ❞❡ t❡❝♥♦❧♦❣✐❛s ♥ã♦ ♣♦❧✉❡♥t❡s✱ ❛s ♣r♦t❡❛s❡s ❡stã♦ s✉❜st✐t✉✐♥❞♦ ♦s ❝♦♠♣♦st♦s tó①✐❝♦s ♣♦❧✉❡♥t❡s ❬❇❡②♥♦♥ ❡ ❇♦♥❞ ✭✷✵✵✶✮❪✳

❆s ♣r♦t❡❛s❡s sã♦ ❡♥❝♦♥tr❛❞❛s ❡♠ ♠✐❝r♦✲♦r❣❛♥✐s♠♦s✱ ❝♦♠♦ ✈ír✉s✱ ❜❛❝tér✐❛s✱ ♣r♦t♦③♦á✲ r✐♦s✱ ❧❡✈❡❞✉r❛s ❡ ❢✉♥❣♦s✳ ❖s ♠✐❝r♦✲♦r❣❛♥✐s♠♦s r❡♣r❡s❡♥t❛♠ ✉♠❛ ❡①❝❡❧❡♥t❡ ❢♦♥t❡ ❞❡ ♣r♦✲ t❡❛s❡s✱ ❞❡✈✐❞♦ ❛ s✉❛ ❣r❛♥❞❡ ❞✐✈❡rs✐❞❛❞❡ ❜✐♦q✉í♠✐❝❛ ❡ ❢❛❝✐❧✐❞❛❞❡ ❞❡ ♠❛♥✐♣✉❧❛çã♦ ❣❡♥ét✐❝❛ ❬❘❛♦ ❡t ❛❧✳ ✭✶✾✾✽✮❪✳

❖s sít✐♦s ❝❛t❛❧ít✐❝♦s ❞❡ ✉♠❛ ♣r♦t❡❛s❡ ❡stã♦ ❝♦♠✉♠❡♥t❡ ❧♦❝❛❧✐③❛❞♦s ❡♠ s✉❧❝♦s ♥❛ s✉♣❡r✲ ❢í❝✐❡ ❞❛ ♠♦❧é❝✉❧❛✳ ❖ s✉❜str❛t♦ ❡s♣❡❝í✜❝♦✱ ❞❡t❡r♠✐♥❛❞♦ ♣❡❧❛s ♣r♦♣r✐❡❞❛❞❡s ❞♦s sít✐♦s ❞❡ ❧✐❣❛çã♦✱ sã♦ ❛❝♦♠♦❞❛❞♦s ❛♦ ❧♦♥❣♦ ❞♦s s✉❧❝♦s ♦♥❞❡ ❛❝♦♥t❡❝❡ ❛ ❤✐❞ró❧✐s❡ ❞❛ ❧✐❣❛çã♦ ♣❡♣tí❞✐❝❛✳ ❆s ♣r♦t❡❛s❡s ♣♦❞❡♠ q✉❡❜r❛r ❧✐❣❛çõ❡s ♣❡♣tí❞✐❝❛s ❡♠ s❡q✉ê♥❝✐❛s ❡s♣❡❝í✜❝❛s ❞❡ ❛♠✐♥♦á❝✐❞♦s ✭♣r♦t❡ó❧✐s❡ ❧✐♠✐t❛❞❛✮✱ ❛♦ ♣❛ss♦ q✉❡ ♦✉tr❛s ❞❡❣r❛❞❛♠ ♦ ♣❡♣tí❞❡♦ ✐♥t❡❣r❛❧♠❡♥t❡ ✭♣r♦t❡ó❧✐s❡ ✐❧✐♠✐t❛❞❛✮✳ ❆ ❝❧✐✈❛❣❡♠ ❡s♣❡❝í✜❝❛ ❞❡ ✉♠❛ ♣r♦t❡í♥❛ ♣♦❞❡ t❛♥t♦ ♥❡✉tr❛❧✐③á✲❧❛✱ q✉❛♥t♦ ♣❡r✲ ♠✐t✐r q✉❡ ❡❧❛ ❛ss✉♠❛ ✉♠❛ ❝♦♥❢♦r♠❛çã♦ ❛t✐✈❛✱ ♦ q✉❡ ♣♦❞❡ s❡r✈✐r ❞❡ s✐♥❛❧✐③❛çã♦ ♣❛r❛ ❝✐❝❧♦s ❝❡❧✉❧❛r❡s✳

❆ ❡s♣❡❝✐✜❝✐❞❛❞❡ ❞❡ ✉♠❛ ♣r♦t❡❛s❡ é ❞❡s❝r✐t❛ ♣❡❧♦ ✉s♦ ❞❡ ✉♠ ♠♦❞❡❧♦ ❝♦♥❝❡✐t✉❛❧ ♥♦ q✉❛❧ ❝❛❞❛ s✉❜sít✐♦ ❡s♣❡❝í✜❝♦ é ❝❛♣❛③ ❞❡ ❛❝♦♠♦❞❛r ❛ ❝❛❞❡✐❛ ❧❛t❡r❛❧ ❞❡ ✉♠ r❡sí❞✉♦ ❞❡ ❛♠✐♥♦á❝✐❞♦ s✐♠♣❧❡s✳ ❖s sít✐♦s ❝❛t❛❧ít✐❝♦s ❞❛ ❡♥③✐♠❛ sã♦ ♥✉♠❡r❛❞♦s✱ ❙✶✱ ❙✷✳✳✳❙♥ ♣❛r❛ ♦ ◆✲t❡r♠✐♥❛❧ ❡ ❙✬✶✱ ❙✬✷✳✳✳❙✬♥ ♣❛r❛ ♦ ❈✲t❡r♠✐♥❛❧ ❡ ♦s ❛♠✐♥♦á❝✐❞♦s ❞♦ s✉❜str❛t♦ sã♦ ❛❝♦♠♦❞❛❞♦s ❡ ♥✉♠❡r❛❞♦s P✶✱ P✷✳✳✳P♥✱ ❡ P✬✶✱ P✬✷✳✳✳P✬♥✱ r❡s♣❡❝t✐✈❛♠❡♥t❡✳ ❖s r❡sí❞✉♦s P✶✲P✶✬ ❢♦r♠❛♠ ✉♠❛ ❧✐❣❛çã♦ ❝❤❛♠❛❞❛”s❝✐ss✐❧❡ ❜♦♥❞”♦✉ ❧✐❣❛çã♦ ♣❡♣tí❞✐❝❛ ❞♦ s✉❜str❛t♦ q✉❡ é ❝❧✐✈❛❞❛ ♣❡❧❛ ♣r♦t❡❛s❡ ♥❛ ❤✐❞ró❧✐s❡✱ ❝♦♠♦ ♠♦str❛ ❡sq✉❡♠❛ ❛❜❛✐①♦ ❬❇❡②♥♦♥ ❡ ❇♦♥❞ ✭✷✵✵✶✮❪✳

❖ sít✐♦ ❝❛t❛❧ít✐❝♦ ❞❛ ❡♥③✐♠❛✱ ♠❛r❝❛❞♦ ❝♦♠ ❛st❡r✐s❝♦ ✭✯✮ ✐♥❞✐❝❛ ♦ ❧♦❝❛❧ ❞❛ ❝❛tá❧✐s❡ ❡ ❛ ❧✐❣❛çã♦ ♣❡♣tí❞✐❝❛ q✉❡ é ❝❧✐✈❛❞❛ ♥♦ s✉❜str❛t♦ é ✐♥❞✐❝❛❞❛ ❝♦♠ s✐♥❛❧ ❞❡ ♠❛✐s ✭✰✮✳

❙✉❜str❛t♦✿ ✲P3 ✲ P2 ✲ P1 ✰ P1′ ✲ P2′ ✲ P3′ ✲ ❊♥③✐♠❛✿ ✲S3 ✲ S2 ✲S1 ✯ S1′ ✲S2′ ✲ S3′ ✲

Imagem

Table 1: Comparison of thermodynamic parameters from experimental and empirical estimation for OMTKY3 / PPE complex as
Figure 2 - Plot showing the correlation between solvation entropy change and patch extension
Figure 3 - Hydrophobic interactions between protease Subtilisin-like and inhibitor Eglin C
Fig. 1. HydroPaCe workflow: We searched for three-dimensional structures of subtilisin-like and trypsin-like families in the PDB database
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