• Odgaard Raahauge posted an update a month ago

    Eribulin is a novel microtubule inhibitor that, similar to other types of microtubule inhibitors, induces apoptosis by inhibiting the mitotic division of cells. Besides this direct effect on tumor cells, previous studies have shown that eribulin has the potential to induce tumor vascular remodeling in several different cancers; however, the mechanisms underlying this phenomenon remain unclear. In the present study, we aimed to elucidate whether eribulin is effective against synovial sarcoma, a relatively rare sarcoma that often affects adolescents and young adults, and to histologically investigate the microstructure of tumor vessels after the administration of eribulin. We found that eribulin exhibits potent antitumor activity against synovial sarcoma in a tumor xenograft model and that tumor vessels frequently have intervascular pillars, a hallmark of intussusceptive angiogenesis (IA), after the administration of eribulin. IA is a distinct form of angiogenesis that is involved in normal developmental processes as well as pathological conditions. Our data indicate that IA is potentially involved in eribulin-induced vascular remodeling and thereby suggest previously unacknowledged role of IA in regulating the tumor vasculature after eribulin administration.The lack of a simple, fast and efficient method for protein delivery is limiting the widespread application of in-cell experiments, which are crucial for understanding the cellular function. We present here an innovative strategy to deliver proteins into both prokaryotic and eukaryotic cells, exploiting thermal vesiculation. This method allows to internalize substantial amounts of proteins, with different molecular weight and conformation, without compromising the structural properties and cell viability. Characterizing proteins in a physiological environment is essential as the environment can dramatically affect the conformation and dynamics of biomolecules as shown by in-cell EPR spectra vs those acquired in buffer solution. Considering its versatility, this method opens the possibility to scientists to study proteins directly in living cells through a wide range of techniques.During the first year of life, infants undergo a process known as perceptual narrowing, which reduces their sensitivity to classes of stimuli which the infants do not encounter in their environment. It has been proposed that perceptual narrowing for faces and speech may be driven by shared domain-general processes. To investigate this theory, our study longitudinally tested 50 German Caucasian infants with respect to these domains first at 6 months of age followed by a second testing at 9 months of age. We used an infant-controlled habituation-dishabituation paradigm to test the infants’ ability to discriminate among other-race Asian faces and non-native Cantonese speech tones, as well as same-race Caucasian faces as a control. We found that while at 6 months of age infants could discriminate among all stimuli, by 9 months of age they could no longer discriminate among other-race faces or non-native tones. However, infants could discriminate among same-race stimuli both at 6 and at 9 months of age. These results demonstrate that the same infants undergo perceptual narrowing for both other-race faces and non-native speech tones between the ages of 6 and 9 months. This parallel development of perceptual narrowing occurring in both the face and speech perception modalities over the same period of time lends support to the domain-general theory of perceptual narrowing in face and speech perception.

    Infant massage, in which mothers stroke their infant’s skin slowly and gently, can cause pleasant sensations in the infant that can be affected by the velocity of massage. However, the massage velocity at which infants feel the most pleasant sensations remains unclear.

    To investigate the effects of massage velocity on heart rate (HR) and HR variability (HRV) in healthy infants.

    Twenty-two infant-mother dyads two to seven months of age were recruited. Mothers stroked their infant’s skin at three massage velocities (5.0, 7.5, and 10.0 cm/s) in a randomized order for 15 min. The rhythm of massage velocity was calculated according to the length of three body areas. The massage velocity of the mothers was regulated using a metronome. HR and HRV (high frequency [HF] and low frequency [LF]) were measured at rest and during massage for each velocity. AICAR phosphate The effects on pleasantness were evaluated using percent change in median baseline value compared with median values for the three massage velocities. Statistical analysis was performed using analysis of variance mixed effect models to exclude “period” and “carryover” effects during massage.

    When measuring HF, massage (7.5 cm/s) caused a significant increase in pleasantness compared with 10.0 cm/s (p = 0.04). The HR and LF/HF ratio were not significantly changed between velocities.

    Results of this study suggested that a massage velocity of 7.5 cm/s was the most pleasant for infants. Future research should investigate the relationship between an infant massage by optimal velocity and infant development in longitudinal studies.

    Results of this study suggested that a massage velocity of 7.5 cm/s was the most pleasant for infants. Future research should investigate the relationship between an infant massage by optimal velocity and infant development in longitudinal studies.

    Secretory immunoglobulin A (sIgA) is important for mucosal immunity due to the inhibition of pathogen infection. The submandibular gland is known to secrete more sIgA than the parotid and sublingual glands. In this study, we focused on the relationship between the secretion of accumulated intracellular sIgA and β-adrenergic receptor stimulation, and clarified the autonomic regulatory mechanism of sIgA secretion in submandibular gland cells using dispersed gland cells.

    Sprague-Dawley rats (male, 6 weeks old, 200-250 g) were euthanized and their submandibular glands were removed. Dispersed submandibular gland cells placed in Krebs-Ringer-Bicarbonate solution were stimulated by autonomic nerve agonists. The concentration of secreted sIgA was measured using a rat IgA ELISA kit. The results were analysed using ANOVA and Tukey’s test.

    Cells stimulated with the non-selective β-adrenoreceptor agonist, isoprenaline, secreted significantly more sIgA compared with the unstimulated control. The β2-adrenoreceptor agonist, fenoterol, caused significantly more sIgA secretion than the control, and more sIgA secretion than the β1-adrenoreceptor agonist, xamoterol.

!function(e,t){"object"==typeof exports&&"undefined"!=typeof module?t(exports):"function"==typeof define&&define.amd?define(["exports"],t):t((e="undefined"!=typeof globalThis?globalThis:e||self).version={})}(this,(function(exports){"use strict";function __awaiter(e,t,n,i){return new(n||(n=Promise))((function(s,a){function o(e){try{d(i.next(e))}catch(e){a(e)}}function r(e){try{d(i.throw(e))}catch(e){a(e)}}function d(e){var t;e.done?s(e.value):(t=e.value,t instanceof n?t:new n((function(e){e(t)}))).then(o,r)}d((i=i.apply(e,t||[])).next())}))}var Blocking;"function"==typeof SuppressedError&&SuppressedError,function(e){e.PENDING="pending",e.NONE="none",e.BLOCKED="blocked",e.ALLOWED="allowed"}(Blocking||(Blocking={}));class Adblock{constructor(e){this.state=Blocking.PENDING,this._mocked=!1,e?(this.state=e,this._mocked=!0):this.state=Blocking.ALLOWED}inject(){return __awaiter(this,void 0,void 0,(function*(){}))}hasAdblocker(){if(void 0===window.google)return!0;const e=document.querySelectorAll("style");return Array.from(e).some((e=>!!e.innerHTML.includes("adblockkey")))}handleAdblocked(){this.removeAdblockKey(),this.state=Blocking.BLOCKED}removeAdblockKey(){var e;null===(e=document.documentElement.dataset)||void 0===e||delete e.adblockkey}get isBlocked(){return this.state===Blocking.BLOCKED}get isAllowed(){return this.state===Blocking.ALLOWED}toContext(){return{user_has_ad_blocker:null,is_ad_blocked:null}}}const OBFUSCATING_BASE_64_PREFIX="UxFdVMwNFNwN0wzODEybV",encode=e=>OBFUSCATING_BASE_64_PREFIX+btoa(unescape(encodeURIComponent(JSON.stringify(e))));function decode$1(e){return JSON.parse(decodeURIComponent(escape(atob(e.replace(OBFUSCATING_BASE_64_PREFIX,"")))))}var version="0.8.1";const APP_ENV="production",TRACKING_DOMAIN="https://click-use1.bodis.com/",SALES_JS_URL="https://parking.bodiscdn.com/js/inquiry.js",GOOGLE_CAF_TIMEOUT_SCRIPTS="0",GOOGLE_CAF_TIMEOUT_CALLBACKS="0",GOOGLE_MV3_URL_PARAMS="abp=1&bodis=true",APP_VERSION=version,COOKIE_CONSENT_JS_URL="",AFD_CHEQ_LOAD_PERCENTAGE="30",isLocal=(e=!0)=>"production"!==APP_ENV;function log(...e){}const FIND_DOMAIN_URL="_fd",getFindDomain=(e="",t=!1,n="")=>{const i=n||window.location.search,s=`${e}/${FIND_DOMAIN_URL}${i}`,a=e?"include":"same-origin",o=Object.assign({Accept:"application/json","Content-Type":"application/json"},t?{"X-HOST":window.location.host}:{});return fetch(s,{method:"POST",headers:o,credentials:a}).then((e=>e.text())).then(decode$1)};var ZeroClickReasons;!function(e){e.CAF_TIMEDOUT="caf_timedout",e.CAF_ADLOAD_FAIL_RS="caf_adloadfail_rs",e.CAF_ADLOAD_FAIL_ADS="caf_adloadfail_ads",e.DISABLED_GB="disabled_gb",e.DISABLED_AB="disabled_ab",e.DISABLED_DS="disabled_ds",e.AD_BLOCKED="ad_blocked",e.PREFERRED="preferred"}(ZeroClickReasons||(ZeroClickReasons={}));const getZeroClick=e=>__awaiter(void 0,void 0,void 0,(function*(){const t=Object.assign(Object.assign({},e),{type:"zc_fetch"});return fetch("/_zc",{method:"POST",body:JSON.stringify({signature:encode(t)}),headers:{Accept:"application/json","Content-Type":"application/json"}}).then((e=>__awaiter(void 0,void 0,void 0,(function*(){try{return decode$1(yield e.text())}catch(e){return{}}}))))})),waiter=(e,t)=>new Promise((n=>{t(e),e<=0&&n();let i=e;const s=()=>{i>0?(i-=1,t(i),setTimeout(s,1e3)):n()};s()})),decode=()=>JSON.parse(atob(window.park||""));var PAGE_STYLES='* {\n font-smoothing: antialiased;\n -webkit-font-smoothing: antialiased;\n -moz-osx-font-smoothing: grayscale;\n}\n\nhtml, body {\n width: 100%;\n margin: 0;\n}\n\nhtml {\n background-color: #2B2B2B;\n height: 100%;\n}\n\nbody {\n min-height: 90%;\n font-family: Arial, sans-serif;\n letter-spacing: 1.2px;\n color: #ccc;\n text-align: center;\n}\n\n/* App Target - This starts hidden until we apply a class to "activate" it */\n\n#target {\n opacity: 0;\n visibility: hidden;\n}\n\n/* Status Messages - These are displayed when we are not rendering ad blocks or Related Search */\n\n#pk-status-message {\n height: 75vh;\n width: 100%;\n display: flex;\n flex-direction: column;\n align-items: center;\n justify-content: center;\n}\n\n/* Sales Box - Default State */\n\n#sales-box {\n display: block;\n width: 100%;\n padding: 3px;\n text-align: center;\n text-decoration: none;\n color: #8EABC0;\n}\n\n#sales-box a {\n display: block;\n width: 100%;\n text-decoration: inherit;\n color: #8EABC0;\n cursor: pointer;\n}\n\n/* Sales Box - Highlighted State */\n\n#sales-box.is-highlighted {\n position: relative;\n z-index: 1;\n background: #032438 linear-gradient(to top, #044368 0%, #000 100%);\n box-shadow: 0 0 15px 0 #000;\n border-bottom: 3px solid #262626;\n}\n\n#sales-box.is-highlighted a {\n line-height: 1.3;\n display: inline-block;\n font-size: 18px;\n color: #fff;\n text-shadow: 1px 1px 0 rgba(0, 0, 0, 0.5);\n background: none;\n}\n\n/* Ellipsis Loader */\n\n.pk-loader {\n display: inline-block;\n position: relative;\n width: 80px;\n height: 80px;\n}\n\n.pk-loader div {\n position: absolute;\n top: 33px;\n width: 13px;\n height: 13px;\n border-radius: 50%;\n background: #ccc;\n animation-timing-function: cubic-bezier(0, 1, 1, 0);\n}\n\n.pk-loader div:nth-child(1) {\n left: 8px;\n animation: pk-anim-1 0.6s infinite;\n}\n\n.pk-loader div:nth-child(2) {\n left: 8px;\n animation: pk-anim-2 0.6s infinite;\n}\n\n.pk-loader div:nth-child(3) {\n left: 32px;\n animation: pk-anim-2 0.6s infinite;\n}\n\n.pk-loader div:nth-child(4) {\n left: 56px;\n animation: pk-anim-1 0.6s infinite;\n animation-direction: reverse;\n}\n\n.pk-loader-text {\n position: fixed;\n font-size: 12px;\n right: 20px;\n bottom: 20px;\n font-weight: lighter;\n}\n\n/* Utilities */\n\n.pk-message-title {\n font-size: 2em;\n font-weight: bold;\n}\n\n.pk-page-ready {\n opacity: 1 !important;\n visibility: visible !important;\n}\n\n.hide-sales-banner > #sales-banner {\n display: none;\n}\n\n@media only screen and (max-width: 600px) {\n .hidden-xs {\n opacity: 0;\n visibility: hidden;\n }\n}\n\n/* Animation */\n\n@keyframes pk-anim-1 {\n 0% {\n transform: scale(0);\n }\n 100% {\n transform: scale(1);\n }\n}\n\n@keyframes pk-anim-2 {\n 0% {\n transform: translate(0, 0);\n }\n 100% {\n transform: translate(24px, 0);\n }\n}\n';const APP_TARGET="#target",MESSAGE_TARGET="main",MESSAGE_SELECTOR="#pk-status-message",PAGE_READY_CLASS="pk-page-ready",MESSAGE_TEMPLATE='
';class Renderer{constructor(e){this._domIsReady=!1,this.revealPage=()=>{this.domNode&&this.domNode.classList.add(PAGE_READY_CLASS)},this.hideSalesBanner=()=>{this.domNode.classList.add("hide-sales-banner")},this.revealSalesBanner=()=>{this.domNode.classList.remove("hide-sales-banner")},this.injectMetaDescription=e=>{if(!e||0===e.length)return;window.document.title=e;const t=document.createElement("meta");t.setAttribute("name","description"),t.setAttribute("content",`See relevant content for ${e}`),document.getElementsByTagName("head")[0].appendChild(t)},this.domNode=document.querySelector(e)}get domIsReady(){return this._domIsReady}set domIsReady(e){this._domIsReady=e,e&&this.injectStyles(PAGE_STYLES)}message(e,t=""){if(this.injectMessage(MESSAGE_TEMPLATE),this.domNode){const t=this.domNode.querySelector(MESSAGE_SELECTOR);t&&(t.innerHTML=e)}t&&this.injectMetaDescription(t)}injectMessage(e){const t=document.querySelector(MESSAGE_TARGET);t?t.innerHTML=e:this.domNode&&(this.domNode.innerHTML=e)}salesBanner(e){if(!e)return;const{href:t,position:n,message:i,theme:s,status:a}=e,o=document.createElement("div"),r=n||"",d="HIGHLIGHT"===s?"is-highlighted":"";o.innerHTML=t?`\n
\n ${i}\n
\n `:`\n
\n ${i}\n
\n `,"BOTTOM"===n?(o.style.marginTop="30px",document.body.appendChild(o)):document.body.prepend(o)}loading(e){let t="a few";e>0&&(t=`${e}`),this.message(`\n
\n
\n
\n
\n
\n
\n \n `)}adBlockMessage(){this.message("\n

Ad block detected

\n Please disable your ad blocker and reload the page.\n ")}errorParkingUnavailable(){this.message("\n

An Error Occurred

\n

Parking is currently unavailable. We'll be right back.

\n ")}errorParkingServicesDisabled(){this.message("\n

An Error Occurred

\n

Services for this domain name have been disabled.

\n ")}errorParkingNoSponsors(e){this.message(`\n
\n No sponsors\n
\n \n ${window.location.hostname} currently does not have any sponsors for you.\n \n `,e)}imprint(e){if(!e)return;const t=document.querySelector("#imprint-text");t&&(t.innerHTML=e.replace(/(?:\r\n|\r|\n)/g,"
"))}injectStyles(e){if(!e)return;const t=document.createElement("style");t.innerHTML=e.toString(),document.head.appendChild(t)}injectScript(e){if(!e)return;const t=document.createElement("script");t.type="text/javascript",t.src=e,document.body.appendChild(t)}injectJS(js){js&&0!==js.length&&eval(js)}injectHTML(e){this.domNode?(e&&(this.domNode.innerHTML=e),this.domIsReady=!0):(this.domIsReady=!1,console.error("An error occurred when trying to render this page. DOM node not found."))}prerender(e){this.injectMetaDescription(e.domain),e.bannerAdblockerOnly&&this.hideSalesBanner(),this.injectHTML(e.html)}template(e){var t;this.domIsReady||this.prerender(e),this.injectStyles(e.stylesheet),this.imprint(e.imprint),this.salesBanner(e.salesBanner),e.bannerAdblockerOnly||this.injectJS(e.javascript),null===(t=e.scripts)||void 0===t||t.forEach((e=>{this.injectScript(e)}))}}const Render=new Renderer(APP_TARGET);var Type;!function(e){e[e.Failed=0]="Failed",e[e.Disabled=1]="Disabled",e[e.Redirect=2]="Redirect",e[e.Parking=3]="Parking",e[e.Sales=4]="Sales"}(Type||(Type={}));let State$2=class{get trackingType(){return this._trackingType}set trackingType(e){this._trackingType=e}get track(){return!!this.trackingType}};class Disabled extends State$2{constructor(){super(...arguments),this.type=Type.Disabled}static build(e,t){let n;switch(t===Blocking.BLOCKED&&(n="adblocker"),e.cannotPark){case"disabled_mr":case"disabled_rc":n=e.cannotPark}if(n){const t=new Disabled;return t.reason=n,t.domain=e.domainName,t}}get message(){switch(this.reason){case"adblocker":return"

Content blocked

Please turn off your ad blocker.";case"disabled_mr":return`

Invalid URL

Referral traffic for ${this.domain} does not meet requirements.`;default:return`

No sponsors

${this.domain} currently does not have any sponsors for you.`}}get trackingType(){switch(this.reason){case"adblocker":return"ad_blocked_message";case"disabled_mr":return"invalid_referral";case"disabled_rc":return"revenue_cap_reached";default:return"no_sponsors_message"}}toContext(){return{cannotPark:this.reason}}}class Failed extends State$2{constructor(){super(...arguments),this.type=Type.Failed}static cannotPark({cannotPark:e}){switch(e){case"disabled_b":case"prohibited_ua":case"disabled_fr":case"revenue_cap_reached":case"disabled_mr":case"disabled_rc":case"disabled_cp":case"invalid_domain":{const t=new Failed;return t.reason=e,t}}}static noSponsors({cannotLoadAds:e}){if(e){const e=new Failed;return e.reason="no_sponsors",e}}static fromError(e){const t=new Failed;return t.reason="js_error",t.error=e,t}get track(){return!!this.trackingType}get message(){switch(this.reason){case"disabled_fr":case"disabled_rc":case"no_sponsors":return`\n

No Sponsors

\n

${this.domain} currently does not have any sponsors for you.

`;case"disabled_mr":return`\n

Invalid URL

\n

Referral traffic for ${this.domain} does not meet requirements.

`;case"js_error":return"\n

An Error Occurred

\n

Parking is currently unavailable. We'll be right back.

\n ";default:return"\n

An Error Occurred

\n

Services for this domain name have been disabled.

\n "}}get trackingType(){switch(this.reason){case"disabled_rc":return"revenue_cap_reached";case"disabled_mr":return"invalid_referral";case"adblock":return"ad_blocked_message";case"no_sponsors":return"no_sponsors_message"}}get domain(){return window.location.hostname}toContext(){return{cannotPark:this.reason}}}function unpackPHPArrayObject(e,t){const n=e[t];if(n&&!Array.isArray(n))return n}class Parking extends State$2{constructor(){super(...arguments),this.type=Type.Parking}static build(e,t){const n=new Parking;n.domain=e.domainName,n.html=e.template,n.scripts=e.scripts||[],n.javascript=e.inlineJs,n.stylesheet=e.styles,n.imprint=e.imprintText;const i=unpackPHPArrayObject(e,"salesSettings");n.bannerAdblockerOnly=null==i?void 0:i.banner_adblocker_only;const s=(null==i?void 0:i.status)&&"NOT_FOR_SALE"!==(null==i?void 0:i.status);if(s){const{status:e,location:t,message:s,link:a,type:o}=i;n.salesBanner={message:s,href:a,position:t,theme:o,status:e}}return t.wantsToServeAds?n.trackingType="ctr":s&&window.location.pathname.startsWith("/listing")?n.trackingType="sales":n.trackingType="visit",n}toContext(){return{}}}class Sales extends State$2{constructor(){super(...arguments),this.type=Type.Sales}static build(e){const t=unpackPHPArrayObject(e,"salesSettings");if(!t)return;const{status:n}=t;return["NOT_FOR_SALE","EXTERNAL_MARKET","URL"].includes(n)?void 0:window.location.pathname.startsWith("/listing")?new Sales:void 0}toContext(){return{}}get trackingType(){return"sales"}init(e){window.context=e;const t=document.createElement("script");t.type="text/javascript",t.src=SALES_JS_URL,document.head.append(t)}}class Redirect extends State$2{constructor(){super(...arguments),this.type=Type.Redirect}static build(e,t,n){const i=unpackPHPArrayObject(e,"salesSettings"),{zeroClickDelay:s,skenzoRedirect:a,skenzoUrl:o,showInquiryForm:r,canZeroClick:d,cannotPark:c}=e;if(window.location.pathname.startsWith("/listing")&&["EXTERNAL_MARKET","URL"].includes(null==i?void 0:i.status)){if(null==i?void 0:i.external)return Redirect.toState(i.external,"sales");if(null==i?void 0:i.link)return Redirect.toState(i.link,"sales")}if(n.cannotLoadAds&&n.wantsToServeAds)return Redirect.toState(n.noAdsRedirectUrl,"no_ads_redirect");if(d&&(null==t?void 0:t.reason)){if(null==t?void 0:t.redirect)return Redirect.toState(t.redirect,"zc_redirect",s);if(a&&o)return Redirect.toState(o,"skenzo_redirect")}return(null==i?void 0:i.status)&&"NOT_FOR_SALE"!==(null==i?void 0:i.status)&&!(null==i?void 0:i.banner_adblocker_only)&&(n.cannotLoadAds||n.cannotLoadAds&&!d||r)?Redirect.toState(`${window.location.origin}/listing`):void 0}static toState(e,t,n=0){const i=new Redirect;return i.url=e,i.delay=n,i.trackingType=t,i}toContext(){return{}}}const 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,n){return __awaiter(this,void 0,void 0,(function*(){if(!n||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;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 n=Parking.build(this.findDomainResponse,this.google);Render.prerender(n),this.cheq=new Cheq(AFD_CHEQ_LOAD_PERCENTAGE),this.cheq.inject(this.parkResponse.uuid,this.findDomainResponse.userId,this.findDomainResponse.referral),this.cookieConsentManager=new CookieConsentManager,yield this.cookieConsentManager.inject();let i=Failed.cannotPark(this.findDomainResponse);if(i)return void(yield this.transitionToFailed(i,n));yield this.google.injectAds();let s=Disabled.build(this.findDomainResponse,this.adblock.state);if(s)return void(yield this.transitionToDisabled(s,n));const a=this.adblock.hasAdblocker();a&&this.adblock.handleAdblocked();const o=Sales.build(this.findDomainResponse);if(o)return void(yield this.transitionToSales(o));this.eligibleForZeroClick&&(this.zeroClickResponse=yield getZeroClick(this.context));const r=Redirect.build(this.findDomainResponse,this.zeroClickResponse,this.google);if(r)yield this.transitionToRedirect(r);else{if(a)return s=Disabled.build(this.findDomainResponse,this.adblock.state),void(yield this.transitionToDisabled(s,n));i=Failed.noSponsors(this.google),i?yield this.transitionToFailed(i,n):yield this.transitionToParking(n)}}))}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}));
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