Έλληνας επιστήμονας εφηύρε μικροσκοπικές «χειροβομβίδες» κατά του καρκίνου

Πώς θα αποφύγουν διπλή φορολογία οι ομογενείς
November 23, 2015
Η Γενέθλιος ημέρα του Μακαριωτάτου Πάπα & Πατριάρχη Αλεξανδρείας & πάσης Αφρικής
November 26, 2015
Εμφάνιση όλων

Έλληνας επιστήμονας εφηύρε μικροσκοπικές «χειροβομβίδες» κατά του καρκίνου

ΚωσταρέλλοςΘερμικές νανο-χειροβομβίδες που εκρήγνυνται πάνω στους όγκους και απελευθερώνουν τις αντικαρκινικές ουσίες τους, είναι το «όπλο» του μέλλοντος στη μάχη κατά του καρκίνου, το οποίο σχεδίασε ένας Έλληνας επιστήμονας της διασποράς. Ο καθηγητής Κώστας Κωσταρέλλος, επικεφαλής του Εργαστηρίου Νανοϊατρικής του Πανεπιστημίου του Μάντσεστερ στη Βρετανία, παρουσίασε το ερευνητικό επίτευγμά του σε συνέδριο του Εθνικού Ινστιτούτου Ερευνών για τον Καρκίνο, σύμφωνα με το BBC και τη βρετανική «Telegraph».

Το πολλά υποσχόμενο νανο-όπλο συνίσταται σε μικροσκοπικές φυσαλίδες ή σφαιρίδια λίπους (γνωστά και ως λιποσώματα), που μεταφέρουν στο εσωτερικό τους αντικαρκινικά φάρμακα και μπορούν να κατευθυνθούν οπουδήποτε μέσα στο σώμα του ασθενούς. Μάλιστα, δεν προκαλούν τις παρενέργειες άλλων τοξικών αντικαρκινικών χημειοθεραπειών, επειδή είναι δυνατό να σταλούν στοχευμένα στα σημεία όπου βρίσκονται μόνο οι όγκοι. Η τεχνολογία έχει ήδη δοκιμασθεί με επιτυχία σε πειραματόζωα (ποντίκια). Η δυσκολία ήταν με ποιό τρόπο είναι δυνατό να απελευθερωθεί το φάρμακο από τη στιγμή που η φυσαλίδα που το περιέχει, φθάσει στο στόχο της. Το «τρικ» που βρήκε η ομάδα του Κωσταρέλλου, είναι ότι στην κανονική θερμοκρασία του σώματος (37 βαθμοί Κελσίου) τα θερμικά νανο-σφαιρίδια παραμένουν υδατοστεγή, αλλά αν η θερμοκρασία τους ανέβει στους 42 βαθμούς, τότε ξαφνικά, σαν να εκρήγνυνται, απελευθερώνουν το φορτίο τους.

Ο Έλληνας επιστήμονας δήλωσε ότι για επιφανειακούς όγκους (δέρματος, λαιμού, κεφαλιού κ.α.) η τοπική άνοδος της θερμοκρασίας μπορεί να γίνει με ζεστά επιθέματα. Για τους όγκους που είναι βαθιά μέσα στο σώμα, η θερμοκρασία τους θα μπορούσε να αυξηθεί με την αποστολή άλλων ειδικών νανο-συσκευών ή μέσω υπερήχων. Η στόχευση του φαρμάκου επιτυγχάνεται, επειδή οι φυσαλίδες έλκονται από εκείνα τα σημεία του σώματος όπου είναι αυξημένη η θερμοκρασία. Όπως δήλωσε ο κ. Κωσταρέλλος, «τα ευαίσθητα στη θερμοκρασία λιποσώματα μπορούν να ταξιδέψουν με ασφάλεια στο σώμα, μεταφέροντας το επιθυμητό αντικαρκινικό φάρμακο. Μόλις φθάσουν στο ‘καυτό’ σημείο των καρκινικών κυττάρων που έχουν θερμανθεί, μια ‘σκανδάλη’ πυροδοτείται και το φάρμακο απελευθερώνεται. Αυτό επιτρέπει την αποτελεσματικότερη μεταφορά των φαρμάκων στους όγκους και έτσι μειώνει τις παράπλευρες απώλειες στα υγιή κύτταρα». Αν και η σχετική έρευνα βρίσκεται ακόμη σε αρχικά στάδια, οι μελέτες του κ. Κωσταρέλλου ανοίγουν νέους δρόμους στη νανοϊατρική.

Ποιος είναι ο Κώστας Κωσταρέλλος

Ο Κώστας Κωσταρέλλος σπούδασε χημικός μηχανικός στο Imperial College του Λονδίνου, από όπου πήρε και το διδακτορικό του. Έκανε μεταδιδακτορική έρευνα στις ΗΠΑ, όπου έγινε επίκουρος καθηγητής στο Ιατρικό Κολέγιο του Πανεπιστημίου Κορνέλ. Το 2002 επέστρεψε στη Βρετανία, όπου αρχικά δίδαξε και διεξήγαγε νανοϊατρική έρευνα στη Φαρμακευτική Σχολή του University College του Λονδίνου. Το 2013 μετακινήθηκε στο Πανεπιστήμιο του Μάντσεστερ ως καθηγητής και επικεφαλής του Εργαστηρίου Νανοϊατρικής. Θεωρείται σήμερα ένας από τους κορυφαίους επιστήμονες στον κόσμο στον τομέα της νανοϊατρικής.

(Πηγή: http://www.zougla.gr)

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browserState=()=>{var e,t,n,i,s;const{screen:{width:a,height:o},self:r,top:d,matchMedia:c,opener:l}=window,{documentElement:{clientWidth:h,clientHeight:u}}=document;let p;try{p=(new Date).getTimezoneOffset()/60*-1}catch(e){p=null}return{popup:!(!l||l===window),timezone_offset:p,user_preference:null===(e=null===Intl||void 0===Intl?void 0:Intl.DateTimeFormat())||void 0===e?void 0:e.resolvedOptions(),user_using_darkmode:Boolean(c&&c("(prefers-color-scheme: dark)").matches),user_supports_darkmode:Boolean(c),window_resolution:{width:null!=h?h:0,height:null!=u?u:0},screen_resolution:{width:null!=a?a:0,height:null!=o?o:0},frame:d===r?null:{innerWidth:null!==(t=null==r?void 0:r.innerWidth)&&void 0!==t?t:0,innerHeight:null!==(n=null==r?void 0:r.innerHeight)&&void 0!==n?n:0,outerWidth:null!==(i=null==r?void 0:r.outerWidth)&&void 0!==i?i:0,outerHeight:null!==(s=null==r?void 0:r.outerHeight)&&void 0!==s?s:0}}},CAFKey="caf",ClickKey="click",NoCacheKey="nc",SessionKey="session",TRACKING_URL="_tr",buildSignature=({callbacks:e,context:t},n)=>{var i,s,a,o;return Object.assign({ad_loaded_callback:null==e?void 0:e.adLoadedCallback,app_version:version,caf_client_id:null===(i=null==t?void 0:t.pageOptions)||void 0===i?void 0:i.pubId,caf_timed_out:null==e?void 0:e.cafTimedOut,caf_loaded_ms:null==e?void 0:e.cafLoadedMs,channel:null===(s=null==t?void 0:t.pageOptions)||void 0===s?void 0:s.channel,desktop:t.desktop,terms:null===(a=null==t?void 0:t.pageOptions)||void 0===a?void 0:a.terms,fd_server_datetime:t.fd_server_datetime,fd_server:t.fd_server,flex_rule:t.flex_rule,host:t.host,ip:t.ip,ivt:null===(o=null==t?void 0:t.pageOptions)||void 0===o?void 0:o.ivt,js_error:t.js_error,mobile:t.mobile,no_ads_redirect:t.noAdsRedirect,page_headers:t.page_headers,page_loaded_callback:null==e?void 0:e.pageLoadedCallback,page_method:t.page_method,page_request:t.page_request,page_time:t.page_time,page_url:t.page_url,reportable_channel:t.reportableChannel,reportable_style_id:t.reportableStyleId,tablet:t.tablet,template_id:t.templateId,type:n,user_has_ad_blocker:t.user_has_ad_blocker,user_id:t.userId,uuid:t.uuid,zeroclick:t.zeroClick},browserState())},trackVisit=({callbacks:e,context:t},n,i="")=>{const s=`${i}/${TRACKING_URL}`,a=i?"include":"same-origin",o=buildSignature({callbacks:e,context:t},n);let r={};"click"===n&&(r={[ClickKey]:"true",[SessionKey]:t.uuid,[NoCacheKey]:Date.now().toString()}),fetch(s,{method:"POST",headers:{Accept:"application/json","Content-Type":"application/json"},credentials:a,body:JSON.stringify(Object.assign({signature:encode(o)},r))})};var State$1;!function(){if(!window.CustomEvent){function e(e,t){t=t||{bubbles:!1,cancelable:!1,detail:void 0};const n=document.createEvent("CustomEvent");return n.initCustomEvent(e,t.bubbles,t.cancelable,t.detail),n}e.prototype=window.Event.prototype,window.CustomEvent=e}}(),function(e){e[e.Pending=0]="Pending",e[e.Loaded=1]="Loaded",e[e.Failed=2]="Failed"}(State$1||(State$1={}));class Provider{get providerCtor(){return this.constructor}constructor(e){this.state=new Map,this.injectedAt=new Map,this.timeoutAt=new Map,this.timeoutSeconds=5,this.handlePixelEvent=e=>{this.keys.forEach((t=>{switch(this.state.get(t)){case State$1.Failed:break;case State$1.Pending:setTimeout((()=>this.handlePixelEvent(e)),100);break;case State$1.Loaded:this.onPixelEvent(e,t)}}))},this.watch=e=>{switch(this.state.get(e)){case State$1.Loaded:case State$1.Failed:break;case State$1.Pending:this.isLoaded(e)?this.state.set(e,State$1.Loaded):this.isTimedOut(e)?this.state.set(e,State$1.Failed):setTimeout((()=>this.watch(e)),50)}},this.config=e,this.keys.length>0?this.keys.forEach((e=>{this.state.set(e,State$1.Pending);const t=new Date;t.setSeconds(t.getSeconds()+this.timeoutAfter()),this.timeoutAt.set(e,t),this.injectPixel(e)})):this.state.set("",State$1.Failed)}get keys(){return this.config?Object.keys(this.config):[]}getPixelEvents(e){var t,n;return null===(n=null===(t=this.config)||void 0===t?void 0:t[e])||void 0===n?void 0:n.pixel_events}injectPixel(e){this.injectedAt.has(e)||(this.injectedAt.set(e,new Date),this.inject(e),this.watch(e))}inject(e){if(!this.providerCtor.scriptInjected){const e=document.createElement("script");e.text=this.getScript(),document.head.appendChild(e),this.providerCtor.scriptInjected=!0}this.init(e)}isTimedOut(e){return+new Date>=+(this.timeoutAt.get(e)||0)}timeoutAfter(){return this.timeoutSeconds}selectPixelEvents(e,t){const n=this.getPixelEvents(t);if(Array.isArray(n))return n.filter((t=>"term-view"===t.trigger&&"visit"===e||(!(!["term-click","ad-view"].includes(t.trigger)||"ctr"!==e)||"ad-click"===t.trigger&&"click"===e)))}}class Facebook extends Provider{getScript(){return"!function(f,b,e,v,n,t,s){if(f.fbq)return;n=f.fbq=function(){n.callMethod?n.callMethod.apply(n,arguments):n.queue.push(arguments)};if(!f._fbq)f._fbq=n;n.push=n;n.loaded=!0;n.version='2.0';n.queue=[];t=b.createElement(e);t.async=!0;t.src=v;s=b.getElementsByTagName(e)[0];s.parentNode.insertBefore(t,s)}(window, document,'script','https://connect.facebook.net/en_US/fbevents.js');"}init(e){window.fbq&&window.fbq("init",e)}onPixelEvent(e,t){const n=this.selectPixelEvents(e,t);n&&n.forEach((e=>{e&&(e.custom?window.fbq("trackSingleCustom",t,e.event):window.fbq("trackSingle",t,e.event))}))}isLoaded(e){return!!window.fbq&&window.fbq.getState&&window.fbq.getState(e)}}Facebook.scriptInjected=!1;class Outbrain extends Provider{getScript(){return`!function(_window, _document) { var OB_ADV_ID = ${JSON.stringify(this.keys)}; if (_window.obApi) { var toArray = function(object) { return Object.prototype.toString.call(object) === '[object Array]' ? object : [object]; }; _window.obApi.marketerId = toArray(_window.obApi.marketerId).concat(toArray(OB_ADV_ID)); return; } var api = _window.obApi = function() { api.dispatch ? api.dispatch.apply(api, arguments) : api.queue.push(arguments); }; api.version = '1.1'; api.loaded = true; api.marketerId = OB_ADV_ID; api.queue = []; var tag = _document.createElement('script'); tag.async = true; tag.src = '//amplify.outbrain.com/cp/obtp.js'; tag.type = 'text/javascript'; var script = _document.getElementsByTagName('script')[0]; script.parentNode.insertBefore(tag, script); }(window, document);`}init(e){}onPixelEvent(e,t){const n=this.selectPixelEvents(e,t);n&&n.forEach((e=>{e&&window.obApi("track",e.event)}))}isLoaded(e){return!!window.obApi}}Outbrain.scriptInjected=!1;class Revcontent extends Provider{getScript(){return"var script=document.createElement('script');script.src='https://assets.revcontent.com/master/rev.js';document.head.appendChild(script);"}init(e){}onPixelEvent(e,t){const n=this.selectPixelEvents(e,t);n&&n.forEach((e=>{e&&window.rev("event",e.event)}))}isLoaded(e){return!!window.rev}}Revcontent.scriptInjected=!1;class Taboola extends Provider{getScript(){return`window._tfa = window._tfa || [];!function (t, f, a, x) {if (!document.getElementById(x)) {t.async = 1;t.src = a;t.id=x;f.parentNode.insertBefore(t, f);}}(document.createElement('script'),document.getElementsByTagName('script')[0],'//cdn.taboola.com/libtrc/unip/${this.keys[0]}/tfa.js','tb_tfa_script');`}init(e){}onPixelEvent(e,t){const n=this.selectPixelEvents(e,t);n&&n.forEach((e=>{if(e){const n=parseInt(t,10);window._tfa.push({notify:"event",name:e.event,id:n})}}))}isLoaded(e){return Array.isArray(window._tfa)}}Taboola.scriptInjected=!1;class Tiktok extends Provider{getScript(){return'!function (w, d, t) {w.TiktokAnalyticsObject=t;var ttq=w[t]=w[t]||[];ttq.methods=["page","track","identify","instances","debug","on","off","once","ready","alias","group","enableCookie","disableCookie"],ttq.setAndDefer=function(t,e){t[e]=function(){t.push([e].concat(Array.prototype.slice.call(arguments,0)))}};for(var i=0;i{e&&window.ttq.instance(t).track(e.event)}))}isLoaded(){return!!window.ttq}}Tiktok.scriptInjected=!1;class GoogleAds extends Provider{getScript(){return`var s=document.createElement('script');s.async=1;s.src='https://www.googletagmanager.com/gtag/js?id=${this.keys[0]}';document.head.appendChild(s);window.dataLayer=window.dataLayer||[];function gtag(){dataLayer.push(arguments)}gtag('set','allow_ad_personalization_signals',false);gtag('js',new Date);`}init(e){window.gtag&&window.gtag("config",e)}onPixelEvent(e,t){const n=this.selectPixelEvents(e,t);n&&n.forEach((e=>{e&&window.gtag("event","conversion",{send_to:`${t}/${e.event}`})}))}isLoaded(e){return!!window.gtag}}GoogleAds.scriptInjected=!1;const ADS_PARAM$1=CAFKey,MESSAGE_PREFIX="FSXDC,.aCS:",ALLOWED_ORIGINS=["https://www.google.com","https://www.adsensecustomsearchads.com","https://syndicatedsearch.goog","https://googleadservices.com"];class Pixels{static build(e){const t=unpackPHPArrayObject(e,"pixel_tracking_data");if(t)return t.useAltTikTokEventsForAdsPlatformUser=e.is_ads,new Pixels(t)}constructor(e){this.onPixelEvent=e=>{const{detail:{type:t}}=e;switch(t){case"visit":case"ctr":case"click":this.providers.forEach((e=>e.handlePixelEvent(t)))}},this.providers=[],e.facebook&&Object.keys(e.facebook).forEach((t=>{this.providers.push(new Facebook({[t]:e.facebook[t]}))})),e.tiktok&&Object.keys(e.tiktok).forEach((t=>{this.providers.push(new Tiktok({[t]:e.tiktok[t]}))})),e.taboola&&Object.keys(e.taboola).forEach((t=>{this.providers.push(new Taboola({[t]:e.taboola[t]}))})),e.revcontent&&Object.keys(e.revcontent).forEach((t=>{this.providers.push(new Revcontent({[t]:e.revcontent[t]}))})),e.outbrain&&this.providers.push(new Outbrain(e.outbrain)),e.googleads&&Object.keys(e.googleads).forEach((t=>{this.providers.push(new GoogleAds({[t]:e.googleads[t]}))}))}listenForEvents(){document.addEventListener("pixel",(e=>{this.onPixelEvent(e)}));window.onmessage=e=>{const{origin:t,data:n}=e;ALLOWED_ORIGINS.includes(t)&&"string"==typeof n&&(null==n?void 0:n.startsWith(MESSAGE_PREFIX))&&new URLSearchParams(window.location.search).has(ADS_PARAM$1)&&document.dispatchEvent(new CustomEvent("pixel",{detail:{type:"click"}}))}}listenForPixelEvents(){document.addEventListener("pixel",(e=>{this.onPixelEvent(e)}))}dispatchEvent(e){document.dispatchEvent(new CustomEvent("pixel",{detail:e}))}}var State;!function(e){e[e.Pending=0]="Pending",e[e.Loaded=1]="Loaded",e[e.Failure=2]="Failure",e[e.TimedOut=3]="TimedOut",e[e.Errored=4]="Errored"}(State||(State={}));const CAF_SCRIPT_SRC=`https://www.google.com/adsense/domains/caf.js?${GOOGLE_MV3_URL_PARAMS}`,TIMEOUT_SCRIPTS=Number(GOOGLE_CAF_TIMEOUT_SCRIPTS),TIMEOUT_CALLBACKS=Number(GOOGLE_CAF_TIMEOUT_CALLBACKS);class StateMachine{constructor(){this.state=State.Pending}transitionTo(e){this.state=e}transitionFromPendingTo(e){this.done||(this.state=e)}get loaded(){return this.state===State.Loaded}get timedOut(){return this.state===State.TimedOut}get done(){return this.state!==State.Pending}}class Ads{constructor(e,t){this.state={script:new StateMachine,blocks:new StateMachine},this.blocksLoaded=[],this.injectScriptTags=()=>__awaiter(this,void 0,void 0,(function*(){return new Promise((e=>{const t=document.createElement("script");t.type="text/javascript",t.src=CAF_SCRIPT_SRC,t.addEventListener("load",(()=>e(!0))),t.addEventListener("error",(()=>e(!1))),document.body.appendChild(t),TIMEOUT_SCRIPTS>0&&setTimeout((()=>e(!1)),TIMEOUT_SCRIPTS)}))})),this.onPageLoaded=(e,t)=>{if(this.pageLoaded={requestAccepted:e,status:t},this.state.script.done)return;const n=null==t?void 0:t.error_code;n?(this.state.script.transitionTo(State.Failure),this.failureReason=`caf_pageloaderror_${n}`):this.state.script.transitionTo(State.Loaded)},this.onBlockLoaded=(e,t,n,i)=>{this.blocksLoaded.push({containerName:e,adsLoaded:t,isExperimentVariant:n,callbackOptions:i}),this.state.blocks.done||(t?this.state.blocks.transitionTo(State.Loaded):this.blocksLoaded.length>=this.blocks.length&&(this.state.blocks.transitionTo(State.Failure),this.failureReason=`caf_adloadfail_${e}`))},this.onTimeout=()=>{this.state.script.transitionFromPendingTo(State.TimedOut),this.state.blocks.transitionFromPendingTo(State.TimedOut)},this.blocks=e,this.options=t}get loaded(){return this.state.script.loaded&&!this.blocksLoaded.map((e=>e.adsLoaded)).includes(!1)}waitForBlocks(){return __awaiter(this,void 0,void 0,(function*(){return new Promise((e=>{const t=()=>{const n=performance.now();if(this.state.blocks.done)return this.cafLoadTime=Math.round(n-this.cafStartTime),void e();const i=this.blocksLoaded.map((e=>e.adsLoaded));i.includes(!1)||i.length>=this.blocks.length?e():setTimeout(t,50)};t()}))}))}inject(){return __awaiter(this,void 0,void 0,(function*(){try{const e=yield this.injectScriptTags();return this.cafStartTime=performance.now(),e&&void 0!==window.google?(new window.google.ads.domains.Caf(Object.assign(Object.assign({},this.options),{pageLoadedCallback:this.onPageLoaded,adLoadedCallback:this.onBlockLoaded}),...this.blocks),TIMEOUT_CALLBACKS>0&&setTimeout(this.onTimeout,TIMEOUT_CALLBACKS),yield new Promise((e=>{const t=()=>{this.state.script.done?e():setTimeout(t,10)};t()}))):void this.state.script.transitionTo(State.Failure)}catch(e){return void(this.error=e.toString())}}))}toCallbacks(){return{adLoadedCallback:this.blocksLoaded.slice(-1)[0],pageLoadedCallback:this.pageLoaded,cafTimedOut:this.state.script.timedOut||this.state.blocks.timedOut,cafLoadedMs:this.cafLoadTime,googleAdsFailure:!!this.failureReason}}toContext(){const e={cafScriptWasLoaded:this.state.script.loaded,cafScriptLoadTime:this.cafLoadTime,callbacks:this.toCallbacks};return this.error&&(e.js_error={message:this.error}),this.state.script.loaded||(e.zeroclick={reason:"googleAdsFailure"}),e}mockFailedState(){this.state.blocks.transitionTo(State.Failure),this.state.script.transitionTo(State.Failure)}}class TagManager{constructor(e){this.injected=!1,this.identifier=e}inject(){if(this.injected)return;if(!this.identifier)return;if("TEST"===this.identifier)return;const e=document.createElement("script");e.setAttribute("src",`https://www.googletagmanager.com/gtag/js?id=${this.identifier}`),document.head.appendChild(e),this.track(),this.injected=!0}track(){this.push("js",new Date),this.push("config",this.identifier)}push(e,t){window.dataLayer||(window.dataLayer=[]),window.dataLayer.push(arguments)}}const ADS_PARAM=CAFKey,ADS_TRACKING_URL="_tr",BLOCKS_TYPE="ads",BLOCKS_CONTAINER="rs",KNOWN_CAF_PARAMS=["caf","query","afdToken","pcsa","nb","nm","nx","ny","is","clkt"];class Google{static build({pageOptions:e,preferredLanguage:t,blocks:n,googleAnalytics:i},s,a,o){let r={};e&&(r=Object.assign({},e),r.hl||(r.hl=t));let d=null==e?void 0:e.resultsPageBaseUrl;d||(d=window.location.origin);return new Google(s.uuid,n,r,i,d,o)}constructor(e,t,n,i,s,a){this._blocks=t,this._pageOptions=n,this.uuid=e,this._baseURL=new URL(s),this._signature=a,this.ads=new Ads(this.blocks,this.pageOptions),this.tagManager=new TagManager(i)}injectTagManager(){this.tagManager.inject()}injectAds(){return __awaiter(this,void 0,void 0,(function*(){yield this.ads.inject()}))}waitForBlocks(){return __awaiter(this,void 0,void 0,(function*(){return this.ads.waitForBlocks()}))}get blocks(){return(this._blocks||[]).filter((e=>this.wantsToServeAds?e.type===BLOCKS_TYPE:e.container===BLOCKS_CONTAINER)).map((e=>{const t=this.baseURL;new URLSearchParams(window.location.search).forEach(((e,n)=>{t.searchParams.has(n)||t.searchParams.append(n,e)}));const n=Object.assign({},e);if(n.resultsPageBaseUrl=t.toString(),this.wantsToServeAds){const e=new URLSearchParams;e.append("click","true"),e.append("session",this.uuid);const t=Object.assign({},this._signature);delete t.ad_loaded_callback,delete t.caf_loaded_ms,delete t.caf_timed_out,delete t.flex_rule,delete t.frame,delete t.js_error,delete t.no_ads_redirect,delete t.page_headers,delete t.page_request,delete t.page_loaded_callback,delete t.popup,delete t.screen_resolution,delete t.user_has_ad_blocker,delete t.user_preference,delete t.user_supports_darkmode,delete t.user_using_darkmode,delete t.zeroclick,e.append("signature",encode(t)),n.clicktrackUrl=`${TRACKING_DOMAIN}${ADS_TRACKING_URL}?${e.toString()}`}return n}))}get baseURL(){const e=new URL(this._baseURL.origin);return e.searchParams.append(ADS_PARAM,"1"),this._baseURL.searchParams.forEach(((t,n)=>{e.searchParams.append(n,t)})),e}get pageOptions(){const e=Object.assign({},this._pageOptions);return Object.keys(this._pageOptions).forEach((t=>{t.startsWith("bodis")&&delete e[t]})),e}get cannotLoadAds(){return!this.ads.loaded}get wantsToServeAds(){return new URLSearchParams(window.location.search).has(ADS_PARAM)}get adsMode(){return this.ads.loaded&&this.wantsToServeAds}get adsReady(){return this.wantsToServeAds&&!this.cannotLoadAds}get noAdsRedirectUrl(){const e=new URLSearchParams(window.location.search);return KNOWN_CAF_PARAMS.forEach((t=>e.delete(t))),`${window.location.origin}?${e.toString()}`}get callbacks(){return this.ads.toCallbacks()}toContext(){return Object.assign({blocks:this.blocks,pageOptions:this.pageOptions},this.ads.toContext())}}class CookieConsentManager{constructor(){this.injectScriptTag=()=>__awaiter(this,void 0,void 0,(function*(){return new Promise((e=>{const t=document.createElement("script");t.setAttribute("src",COOKIE_CONSENT_JS_URL),t.addEventListener("load",(()=>this.awaitConsent(e))),t.addEventListener("error",(()=>e(!1))),document.head.appendChild(t)}))}))}inject(){return __awaiter(this,void 0,void 0,(function*(){this.injected||!COOKIE_CONSENT_JS_URL||isLocal()||(this.injected=yield this.injectScriptTag())}))}awaitConsent(e){let t=0;const n=setInterval((()=>{t+=1,20===t&&(clearInterval(n),e(!0)),void 0!==window.__tcfapi&&(window.addEventListener("ConsentActivity",(t=>{const{detail:{status:n}}=t;n&&e(!0)})),clearInterval(n))}),50)}}class Cheq{constructor(e){let t;if(t="string"==typeof e?parseInt(e,10):e,t<0||t>100)throw new Error("Load percentage must be between 0 and 100");this.loadPercentage=t}inject(e,t){return __awaiter(this,void 0,void 0,(function*(){if(this.injected)return;100*Math.random()<=this.loadPercentage&&(this.injected=this.injectScriptTag(e,t))}))}injectScriptTag(e,t){const n=document.createElement("script");return n.type="text/javascript",n.async=!0,n.setAttribute("src","https://ob.forseasky.com/i/148870ae21863d775c347e8893c985af.js"),n.setAttribute("data-ch","cheq4ppc"),n.setAttribute("data-uvid",e),n.setAttribute("data-utm-campaign",t.toString()),n.className="ct_clicktrue_73521",document.head.appendChild(n),!0}}class App{main(){var e,t,n;return __awaiter(this,void 0,void 0,(function*(){if(this.parkResponse=decode(),this.findDomainResponse=yield getFindDomain(),!this.findDomainResponse)throw new Error("Domain failed to load.");this.pixels=Pixels.build(this.findDomainResponse),null===(e=this.pixels)||void 0===e||e.listenForEvents(),this.adblock=new Adblock,yield this.adblock.inject(),this.google=Google.build(this.findDomainResponse,this.parkResponse,this.adblock,buildSignature({context:this.context,callbacks:null===(t=this.google)||void 0===t?void 0:t.callbacks},"click")),this.google.injectTagManager();const i=Parking.build(this.findDomainResponse,this.google);Render.prerender(i);const s=(null===(n=this.findDomainResponse)||void 0===n?void 0:n.referral)?AFD_REFERRAL_CHEQ_LOAD_PERCENTAGE:AFD_ORGANIC_CHEQ_LOAD_PERCENTAGE;this.cheq=new Cheq(s),this.cheq.inject(this.parkResponse.uuid,this.findDomainResponse.userId),this.cookieConsentManager=new CookieConsentManager,yield this.cookieConsentManager.inject();let a=Failed.cannotPark(this.findDomainResponse);if(a)return void(yield this.transitionToFailed(a,i));yield this.google.injectAds();let o=Disabled.build(this.findDomainResponse,this.adblock.state);if(o)return void(yield this.transitionToDisabled(o,i));const r=this.adblock.hasAdblocker();r&&this.adblock.handleAdblocked();const d=Sales.build(this.findDomainResponse);if(d)return void(yield this.transitionToSales(d));this.eligibleForZeroClick&&(this.zeroClickResponse=yield getZeroClick(this.context));const c=Redirect.build(this.findDomainResponse,this.zeroClickResponse,this.google);if(c)yield this.transitionToRedirect(c);else{if(r)return o=Disabled.build(this.findDomainResponse,this.adblock.state),void(yield this.transitionToDisabled(o,i));a=Failed.noSponsors(this.google),a?yield this.transitionToFailed(a,i):yield this.transitionToParking(i)}}))}transitionToParking(e){return __awaiter(this,void 0,void 0,(function*(){this.state=e,Render.template(e),Render.revealPage(),yield this.google.waitForBlocks(),yield this.track()}))}transitionToRedirect(e){return __awaiter(this,void 0,void 0,(function*(){this.state=e;const t=this.track();Render.revealPage(),yield waiter(e.delay,(e=>Render.loading(e))),yield t,window.location.href=e.url,log(`➡ Redirecting [${e.url}]`)}))}transitionToFailed(e,t){return __awaiter(this,void 0,void 0,(function*(){this.state=e,Render.message(e.message),Render.injectJS(t.javascript),Render.revealPage(),yield this.track()}))}transitionToSales(e){return __awaiter(this,void 0,void 0,(function*(){this.state=e,e.init(this.context),yield this.track()}))}transitionToDisabled(e,t){return __awaiter(this,void 0,void 0,(function*(){this.state=e,Render.message(e.message),Render.injectJS(t.javascript),"adblocker"===e.reason&&t.bannerAdblockerOnly&&Render.revealSalesBanner(),Render.revealPage(),yield this.track()}))}track(){var e;return __awaiter(this,void 0,void 0,(function*(){if(!this.state.track)return Promise.resolve();try{const t=this.state.trackingType;return null===(e=this.pixels)||void 0===e||e.dispatchEvent({type:t}),trackVisit({context:this.context,callbacks:this.google.callbacks},t)}catch(e){return}}))}get eligibleForZeroClick(){const{cannotPark:e,canZeroClick:t,zeroClick:n}=this.findDomainResponse,{cannotLoadAds:i,wantsToServeAds:s}=this.google;return this.adblock.state!==Blocking.BLOCKED&&(!!t&&(!!e||(!(!i||s)||!!(null==n?void 0:n.reason))))}get context(){var e,t,n,i;const s=this.findDomainResponse,a=this.parkResponse,o=null===(e=this.state)||void 0===e?void 0:e.toContext(),r=null===(t=this.adblock)||void 0===t?void 0:t.toContext(),d=null===(n=this.google)||void 0===n?void 0:n.toContext(),c=browserState(),l=Object.assign(Object.assign({},null===(i=this.findDomainResponse)||void 0===i?void 0:i.zeroClick),this.zeroClickResponse);return Object.assign(Object.assign(Object.assign(Object.assign(Object.assign(Object.assign(Object.assign({app_version:APP_VERSION},s),a),r),d),o),c),{zeroClick:l})}init(){return __awaiter(this,void 0,void 0,(function*(){try{window.__parkour=this,yield this.main()}catch(e){console.error("app",e);const t=Failed.fromError(e);this.state=t,Render.message(t.message),Render.revealPage()}}))}}(new App).init(),exports.App=App}));