Create DNA
One Problem of cell extract, is the stability of linear DNA. In escherichia coli, endogenous and exogenous linear DNA are differentiated by specific proteins, such as the recombinase complex RecBCD. It recognizes genomic double strand breaks via a specific sequence of 8 bases called Chi-site and prepares the DNA for homologous repair. However, foreign DNA lacks the Chi-site and is therefore degraded by RecBCD. For experiments in cell extract expensive and inefficient inhibitors are used. Since a knockout of RecBCD is lethal, we chose to modify the enzyme to enable selective depletion after cell lysis. Therefore, we came up with several depletion strategies:
Create Soup
The financial advantage of producing home-made cell extract for in vitro protein expression is virtually reversed by the fact that it is tedious and time-consuming, with huge batch to batch variations of the resulting product. Therefore, our objective is to optimize the protocol for self-made cell extract from E. coli, by simplifying time consuming steps while eliminating the central sources of variation during the preparation process. The focus of our effort is to determine the influence of cultivation conditions on extract quality and optimizing the cell lysis for speed, protein yield and nal product quality. By implementing novel ways of extract characterization, we aim to gain a deeper understanding of cell-free systems.
Create Phages
Generation of a universal platform for phage engineering: Our TX-TL system is superior to conventional bacterial based phage production in the following aspects:
- Assembly of phages in vitro
- Exchange of phage fibers in vitro
- Establishment of homogeneous phage batches
- Reduction of endotoxins within phage batches We will exemplarily engineer a non lytic fluorescent T7 phage, which targets a non primary E. coli strain.
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"toggle" : n.data(); gt._jQueryInterface.call(t, e) }) }), tt.fn[et] = gt._jQueryInterface, tt.fn[et].Constructor = gt, tt.fn[et].noConflict = function () { return tt.fn[et] = rt, gt._jQueryInterface }, gt), Sn = (pt = "dropdown", Et = "." + (vt = "bs.dropdown"), yt = ".data-api", Tt = (mt = e).fn[pt], Ct = new RegExp("38|40|27"), It = { HIDE: "hide" + Et, HIDDEN: "hidden" + Et, SHOW: "show" + Et, SHOWN: "shown" + Et, CLICK: "click" + Et, CLICK_DATA_API: "click" + Et + yt, KEYDOWN_DATA_API: "keydown" + Et + yt, KEYUP_DATA_API: "keyup" + Et + yt }, At = "disabled", Dt = "show", bt = "dropup", St = "dropright", wt = "dropleft", Nt = "dropdown-menu-right", Ot = "position-static", kt = '[data-toggle="dropdown"]', Pt = ".dropdown form", Lt = ".dropdown-menu", jt = ".navbar-nav", Rt = ".dropdown-menu .dropdown-item:not(.disabled):not(:disabled)", Ht = "top-start", Wt = "top-end", Mt = "bottom-start", xt = "bottom-end", Ut = "right-start", Kt = "left-start", Ft = { offset: 0, flip: !0, boundary: "scrollParent", reference: "toggle", display: "dynamic" }, Vt = { offset: "(number|string|function)", flip: "boolean", boundary: "(string|element)", reference: "(string|element)", display: "string" }, Qt = function () { function l(t, e) { this._element = t, this._popper = null, this._config = this._getConfig(e), this._menu = this._getMenuElement(), this._inNavbar = this._detectNavbar(), this._addEventListeners() } var t = l.prototype; return t.toggle = function () { if (!this._element.disabled && !mt(this._element).hasClass(At)) { var t = l._getParentFromElement(this._element), e = mt(this._menu).hasClass(Dt); if (l._clearMenus(), !e) { var n = { relatedTarget: this._element }, i = mt.Event(It.SHOW, n); if (mt(t).trigger(i), !i.isDefaultPrevented()) { if (!this._inNavbar) { if ("undefined" == typeof c) throw new TypeError("Bootstrap dropdown require Popper.js (https://popper.js.org)"); var r = this._element; "parent" === this._config.reference ? r = t : Cn.isElement(this._config.reference) && (r = this._config.reference, "undefined" != typeof this._config.reference.jquery && (r = this._config.reference[0])), "scrollParent" !== this._config.boundary && mt(t).addClass(Ot), this._popper = new c(r, this._menu, this._getPopperConfig()) } "ontouchstart" in document.documentElement && 0 === mt(t).closest(jt).length && mt(document.body).children().on("mouseover", null, mt.noop), this._element.focus(), this._element.setAttribute("aria-expanded", !0), mt(this._menu).toggleClass(Dt), mt(t).toggleClass(Dt).trigger(mt.Event(It.SHOWN, n)) } } } }, t.dispose = function () { mt.removeData(this._element, vt), mt(this._element).off(Et), this._element = null, (this._menu = null) !== this._popper && (this._popper.destroy(), this._popper = null) }, t.update = function () { this._inNavbar = this._detectNavbar(), null !== this._popper && this._popper.scheduleUpdate() }, t._addEventListeners = function () { var e = this; mt(this._element).on(It.CLICK, function (t) { t.preventDefault(), t.stopPropagation(), e.toggle() }) }, t._getConfig = function (t) { return t = h({}, this.constructor.Default, mt(this._element).data(), t), Cn.typeCheckConfig(pt, t, this.constructor.DefaultType), t }, t._getMenuElement = function () { if (!this._menu) { var t = l._getParentFromElement(this._element); this._menu = mt(t).find(Lt)[0] } return this._menu }, t._getPlacement = function () { var t = mt(this._element).parent(), e = Mt; return t.hasClass(bt) ? (e = Ht, mt(this._menu).hasClass(Nt) && (e = Wt)) : t.hasClass(St) ? e = Ut : t.hasClass(wt) ? e = Kt : mt(this._menu).hasClass(Nt) && (e = xt), e }, t._detectNavbar = function () { return 0 < mt(this._element).closest(".navbar").length }, t._getPopperConfig = function () { var e = this, t = {}; "function" == typeof this._config.offset ? t.fn = function (t) { return t.offsets = h({}, t.offsets, e._config.offset(t.offsets) || {}), t } : t.offset = this._config.offset; var n = { placement: this._getPlacement(), modifiers: { offset: t, flip: { enabled: this._config.flip }, preventOverflow: { boundariesElement: this._config.boundary } } }; return "static" === this._config.display && (n.modifiers.applyStyle = { enabled: !1 }), n }, l._jQueryInterface = function (e) { return this.each(function () { var t = mt(this).data(vt); if (t || (t = new l(this, "object" == typeof e ? e : null), mt(this).data(vt, t)), "string" == typeof e) { if ("undefined" == typeof t[e]) throw new TypeError('No method named "' + e + '"'); t[e]() } }) }, l._clearMenus = function (t) { if (!t || 3 !== t.which && ("keyup" !== t.type || 9 === t.which)) for (var e = mt.makeArray(mt(kt)), n = 0; n < e.length; n++) { var i = l._getParentFromElement(e[n]), r = mt(e[n]).data(vt), s = { relatedTarget: e[n] }; if (r) { var o = r._menu; if (mt(i).hasClass(Dt) && !(t && ("click" === t.type && /input|textarea/i.test(t.target.tagName) || "keyup" === t.type && 9 === t.which) && mt.contains(i, t.target))) { var a = mt.Event(It.HIDE, s); mt(i).trigger(a), a.isDefaultPrevented() || ("ontouchstart" in document.documentElement && mt(document.body).children().off("mouseover", null, mt.noop), e[n].setAttribute("aria-expanded", "false"), mt(o).removeClass(Dt), mt(i).removeClass(Dt).trigger(mt.Event(It.HIDDEN, s))) } } } }, l._getParentFromElement = function (t) { var e, n = Cn.getSelectorFromElement(t); return n && (e = mt(n)[0]), e || t.parentNode }, l._dataApiKeydownHandler = function (t) { if ((/input|textarea/i.test(t.target.tagName) ? !(32 === t.which || 27 !== t.which && (40 !== t.which && 38 !== t.which || mt(t.target).closest(Lt).length)) : Ct.test(t.which)) && (t.preventDefault(), t.stopPropagation(), !this.disabled && !mt(this).hasClass(At))) { var e = l._getParentFromElement(this), n = mt(e).hasClass(Dt); if ((n || 27 === t.which && 32 === t.which) && (!n || 27 !== t.which && 32 !== t.which)) { var i = mt(e).find(Rt).get(); if (0 !== i.length) { var r = i.indexOf(t.target); 38 === t.which && 0 < r && r--, 40 === t.which && r < i.length - 1 && r++, r < 0 && (r = 0), i[r].focus() } } else { if (27 === t.which) { var s = mt(e).find(kt)[0]; mt(s).trigger("focus") } mt(this).trigger("click") } } }, o(l, null, [{ key: "VERSION", get: function () { return "4.1.0" } }, { key: "Default", get: function () { return Ft } }, { key: "DefaultType", get: function () { return Vt } }]), l }(), mt(document).on(It.KEYDOWN_DATA_API, kt, Qt._dataApiKeydownHandler).on(It.KEYDOWN_DATA_API, Lt, Qt._dataApiKeydownHandler).on(It.CLICK_DATA_API + " " + It.KEYUP_DATA_API, Qt._clearMenus).on(It.CLICK_DATA_API, kt, function (t) { t.preventDefault(), t.stopPropagation(), Qt._jQueryInterface.call(mt(this), "toggle") }).on(It.CLICK_DATA_API, Pt, function (t) { t.stopPropagation() }), mt.fn[pt] = Qt._jQueryInterface, mt.fn[pt].Constructor = Qt, mt.fn[pt].noConflict = function () { return mt.fn[pt] = Tt, Qt._jQueryInterface }, Qt), wn = (Yt = "modal", qt = "." + (Gt = "bs.modal"), zt = (Bt = e).fn[Yt], Xt = { backdrop: !0, keyboard: !0, focus: !0, show: !0 }, Jt = { backdrop: "(boolean|string)", keyboard: "boolean", focus: "boolean", show: "boolean" }, Zt = { HIDE: "hide" + qt, HIDDEN: "hidden" + qt, SHOW: "show" + qt, SHOWN: "shown" + qt, FOCUSIN: "focusin" + qt, RESIZE: "resize" + qt, CLICK_DISMISS: "click.dismiss" + qt, KEYDOWN_DISMISS: "keydown.dismiss" + qt, MOUSEUP_DISMISS: "mouseup.dismiss" + qt, MOUSEDOWN_DISMISS: "mousedown.dismiss" + qt, CLICK_DATA_API: "click" + qt + ".data-api" }, $t = "modal-scrollbar-measure", te = "modal-backdrop", ee = "modal-open", ne = "fade", ie = "show", re = { DIALOG: ".modal-dialog", DATA_TOGGLE: '[data-toggle="modal"]', DATA_DISMISS: '[data-dismiss="modal"]', FIXED_CONTENT: ".fixed-top, .fixed-bottom, .is-fixed, .sticky-top", STICKY_CONTENT: ".sticky-top", NAVBAR_TOGGLER: ".navbar-toggler" }, se = function () { function r(t, e) { this._config = this._getConfig(e), this._element = t, this._dialog = Bt(t).find(re.DIALOG)[0], this._backdrop = null, this._isShown = !1, this._isBodyOverflowing = !1, this._ignoreBackdropClick = !1, this._scrollbarWidth = 0 } var t = r.prototype; return t.toggle = function (t) { return this._isShown ? this.hide() : this.show(t) }, t.show = function (t) { var e = this; if (!this._isTransitioning && !this._isShown) { Bt(this._element).hasClass(ne) && (this._isTransitioning = !0); var n = Bt.Event(Zt.SHOW, { relatedTarget: t }); Bt(this._element).trigger(n), this._isShown || n.isDefaultPrevented() || (this._isShown = !0, this._checkScrollbar(), this._setScrollbar(), this._adjustDialog(), Bt(document.body).addClass(ee), this._setEscapeEvent(), this._setResizeEvent(), Bt(this._element).on(Zt.CLICK_DISMISS, re.DATA_DISMISS, function (t) { return e.hide(t) }), Bt(this._dialog).on(Zt.MOUSEDOWN_DISMISS, function () { Bt(e._element).one(Zt.MOUSEUP_DISMISS, function (t) { Bt(t.target).is(e._element) && (e._ignoreBackdropClick = !0) }) }), this._showBackdrop(function () { return e._showElement(t) })) } }, t.hide = function (t) { var e = this; if (t && t.preventDefault(), !this._isTransitioning && this._isShown) { var n = Bt.Event(Zt.HIDE); if (Bt(this._element).trigger(n), this._isShown && !n.isDefaultPrevented()) { this._isShown = !1; var i = Bt(this._element).hasClass(ne); if (i && (this._isTransitioning = !0), this._setEscapeEvent(), this._setResizeEvent(), Bt(document).off(Zt.FOCUSIN), Bt(this._element).removeClass(ie), Bt(this._element).off(Zt.CLICK_DISMISS), Bt(this._dialog).off(Zt.MOUSEDOWN_DISMISS), i) { var r = Cn.getTransitionDurationFromElement(this._element); Bt(this._element).one(Cn.TRANSITION_END, function (t) { return e._hideModal(t) }).emulateTransitionEnd(r) } else this._hideModal() } } }, t.dispose = function () { Bt.removeData(this._element, Gt), Bt(window, document, this._element, this._backdrop).off(qt), this._config = null, this._element = null, this._dialog = null, this._backdrop = null, this._isShown = null, this._isBodyOverflowing = null, this._ignoreBackdropClick = null, this._scrollbarWidth = null }, t.handleUpdate = function () { this._adjustDialog() }, t._getConfig = function (t) { return t = h({}, Xt, t), Cn.typeCheckConfig(Yt, t, Jt), t }, t._showElement = function (t) { var e = this, n = Bt(this._element).hasClass(ne); this._element.parentNode && this._element.parentNode.nodeType === Node.ELEMENT_NODE || document.body.appendChild(this._element), this._element.style.display = "block", this._element.removeAttribute("aria-hidden"), this._element.scrollTop = 0, n && Cn.reflow(this._element), Bt(this._element).addClass(ie), this._config.focus && this._enforceFocus(); var i = Bt.Event(Zt.SHOWN, { relatedTarget: t }), r = function () { e._config.focus && e._element.focus(), e._isTransitioning = !1, Bt(e._element).trigger(i) }; if (n) { var s = Cn.getTransitionDurationFromElement(this._element); Bt(this._dialog).one(Cn.TRANSITION_END, r).emulateTransitionEnd(s) } else r() }, t._enforceFocus = function () { var e = this; Bt(document).off(Zt.FOCUSIN).on(Zt.FOCUSIN, function (t) { document !== t.target && e._element !== t.target && 0 === Bt(e._element).has(t.target).length && e._element.focus() }) }, t._setEscapeEvent = function () { var e = this; this._isShown && this._config.keyboard ? Bt(this._element).on(Zt.KEYDOWN_DISMISS, function (t) { 27 === t.which && (t.preventDefault(), e.hide()) }) : this._isShown || Bt(this._element).off(Zt.KEYDOWN_DISMISS) }, t._setResizeEvent = function () { var e = this; this._isShown ? Bt(window).on(Zt.RESIZE, function (t) { return e.handleUpdate(t) }) : Bt(window).off(Zt.RESIZE) }, t._hideModal = function () { var t = this; this._element.style.display = "none", this._element.setAttribute("aria-hidden", !0), this._isTransitioning = !1, this._showBackdrop(function () { Bt(document.body).removeClass(ee), t._resetAdjustments(), t._resetScrollbar(), Bt(t._element).trigger(Zt.HIDDEN) }) }, t._removeBackdrop = function () { this._backdrop && (Bt(this._backdrop).remove(), this._backdrop = null) }, t._showBackdrop = function (t) { var e = this, n = Bt(this._element).hasClass(ne) ? ne : ""; if (this._isShown && this._config.backdrop) { if (this._backdrop = document.createElement("div"), this._backdrop.className = te, n && Bt(this._backdrop).addClass(n), Bt(this._backdrop).appendTo(document.body), Bt(this._element).on(Zt.CLICK_DISMISS, function (t) { e._ignoreBackdropClick ? e._ignoreBackdropClick = !1 : t.target === t.currentTarget && ("static" === e._config.backdrop ? e._element.focus() : e.hide()) }), n && Cn.reflow(this._backdrop), Bt(this._backdrop).addClass(ie), !t) return; if (!n) return void t(); var i = Cn.getTransitionDurationFromElement(this._backdrop); Bt(this._backdrop).one(Cn.TRANSITION_END, t).emulateTransitionEnd(i) } else if (!this._isShown && this._backdrop) { Bt(this._backdrop).removeClass(ie); var r = function () { e._removeBackdrop(), t && t() }; if (Bt(this._element).hasClass(ne)) { var s = Cn.getTransitionDurationFromElement(this._backdrop); Bt(this._backdrop).one(Cn.TRANSITION_END, r).emulateTransitionEnd(s) } else r() } else t && t() }, t._adjustDialog = function () { var t = this._element.scrollHeight > document.documentElement.clientHeight; !this._isBodyOverflowing && t && (this._element.style.paddingLeft = this._scrollbarWidth + "px"), this._isBodyOverflowing && !t && (this._element.style.paddingRight = this._scrollbarWidth + "px") }, t._resetAdjustments = function () { this._element.style.paddingLeft = "", this._element.style.paddingRight = "" }, t._checkScrollbar = function () { var t = document.body.getBoundingClientRect(); this._isBodyOverflowing = t.left + t.right < window.innerWidth, this._scrollbarWidth = this._getScrollbarWidth() }, t._setScrollbar = function () { var r = this; if (this._isBodyOverflowing) { Bt(re.FIXED_CONTENT).each(function (t, e) { var n = Bt(e)[0].style.paddingRight, i = Bt(e).css("padding-right"); Bt(e).data("padding-right", n).css("padding-right", parseFloat(i) + r._scrollbarWidth + "px") }), Bt(re.STICKY_CONTENT).each(function (t, e) { var n = Bt(e)[0].style.marginRight, i = Bt(e).css("margin-right"); Bt(e).data("margin-right", n).css("margin-right", parseFloat(i) - r._scrollbarWidth + "px") }), Bt(re.NAVBAR_TOGGLER).each(function (t, e) { var n = Bt(e)[0].style.marginRight, i = Bt(e).css("margin-right"); Bt(e).data("margin-right", n).css("margin-right", parseFloat(i) + r._scrollbarWidth + "px") }); var t = document.body.style.paddingRight, e = Bt(document.body).css("padding-right"); Bt(document.body).data("padding-right", t).css("padding-right", parseFloat(e) + this._scrollbarWidth + "px") } }, t._resetScrollbar = function () { Bt(re.FIXED_CONTENT).each(function (t, e) { var n = Bt(e).data("padding-right"); "undefined" != typeof n && Bt(e).css("padding-right", n).removeData("padding-right") }), Bt(re.STICKY_CONTENT + ", " + re.NAVBAR_TOGGLER).each(function (t, e) { var n = Bt(e).data("margin-right"); "undefined" != typeof n && Bt(e).css("margin-right", n).removeData("margin-right") }); var t = Bt(document.body).data("padding-right"); "undefined" != typeof t && Bt(document.body).css("padding-right", t).removeData("padding-right") }, t._getScrollbarWidth = function () { var t = document.createElement("div"); t.className = $t, document.body.appendChild(t); var e = t.getBoundingClientRect().width - t.clientWidth; return document.body.removeChild(t), e }, r._jQueryInterface = function (n, i) { return this.each(function () { var t = Bt(this).data(Gt), e = h({}, r.Default, Bt(this).data(), "object" == typeof n && n); if (t || (t = new r(this, e), Bt(this).data(Gt, t)), "string" == typeof n) { if ("undefined" == typeof t[n]) throw new TypeError('No method named "' + n + '"'); t[n](i) } else e.show && t.show(i) }) }, o(r, null, [{ key: "VERSION", get: function () { return "4.1.0" } }, { key: "Default", get: function () { return Xt } }]), r }(), Bt(document).on(Zt.CLICK_DATA_API, re.DATA_TOGGLE, function (t) { var e, n = this, i = Cn.getSelectorFromElement(this); i && (e = Bt(i)[0]); var r = Bt(e).data(Gt) ? "toggle" : h({}, Bt(e).data(), Bt(this).data()); "A" !== this.tagName && "AREA" !== this.tagName || t.preventDefault(); var s = Bt(e).one(Zt.SHOW, function (t) { t.isDefaultPrevented() || s.one(Zt.HIDDEN, function () { Bt(n).is(":visible") && n.focus() }) }); se._jQueryInterface.call(Bt(e), r, this) }), Bt.fn[Yt] = se._jQueryInterface, Bt.fn[Yt].Constructor = se, Bt.fn[Yt].noConflict = function () { return Bt.fn[Yt] = zt, se._jQueryInterface }, se), Nn = (ae = "tooltip", he = "." + (le = "bs.tooltip"), ce = (oe = e).fn[ae], ue = "bs-tooltip", fe = new RegExp("(^|\\s)" + ue + "\\S+", "g"), ge = { animation: !0,template: '
trigger: "hover focus", title: "", delay: 0, html: !(_e = { AUTO: "auto", TOP: "top", RIGHT: "right", BOTTOM: "bottom", LEFT: "left" }), selector: !(de = { animation: "boolean", template: "string", title: "(string|element|function)", trigger: "string", delay: "(number|object)", html: "boolean", selector: "(string|boolean)", placement: "(string|function)", offset: "(number|string)", container: "(string|element|boolean)", fallbackPlacement: "(string|array)", boundary: "(string|element)" }), placement: "top", offset: 0, container: !1, fallbackPlacement: "flip", boundary: "scrollParent" }, pe = "out", ve = { HIDE: "hide" + he, HIDDEN: "hidden" + he, SHOW: (me = "show") + he, SHOWN: "shown" + he, INSERTED: "inserted" + he, CLICK: "click" + he, FOCUSIN: "focusin" + he, FOCUSOUT: "focusout" + he, MOUSEENTER: "mouseenter" + he, MOUSELEAVE: "mouseleave" + he }, Ee = "fade", ye = "show", Te = ".tooltip-inner", Ce = ".arrow", Ie = "hover", Ae = "focus", De = "click", be = "manual", Se = function () { function i(t, e) { if ("undefined" == typeof c) throw new TypeError("Bootstrap tooltips require Popper.js (https://popper.js.org)"); this._isEnabled = !0, this._timeout = 0, this._hoverState = "", this._activeTrigger = {}, this._popper = null, this.element = t, this.config = this._getConfig(e), this.tip = null, this._setListeners() } var t = i.prototype; return t.enable = function () { this._isEnabled = !0 }, t.disable = function () { this._isEnabled = !1 }, t.toggleEnabled = function () { this._isEnabled = !this._isEnabled }, t.toggle = function (t) { if (this._isEnabled) if (t) { var e = this.constructor.DATA_KEY, n = oe(t.currentTarget).data(e); n || (n = new this.constructor(t.currentTarget, this._getDelegateConfig()), oe(t.currentTarget).data(e, n)), n._activeTrigger.click = !n._activeTrigger.click, n._isWithActiveTrigger() ? n._enter(null, n) : n._leave(null, n) } else { if (oe(this.getTipElement()).hasClass(ye)) return void this._leave(null, this); this._enter(null, this) } }, t.dispose = function () { clearTimeout(this._timeout), oe.removeData(this.element, this.constructor.DATA_KEY), oe(this.element).off(this.constructor.EVENT_KEY), oe(this.element).closest(".modal").off("hide.bs.modal"), this.tip && oe(this.tip).remove(), this._isEnabled = null, this._timeout = null, this._hoverState = null, (this._activeTrigger = null) !== this._popper && this._popper.destroy(), this._popper = null, this.element = null, this.config = null, this.tip = null }, t.show = function () { var e = this; if ("none" === oe(this.element).css("display")) throw new Error("Please use show on visible elements"); var t = oe.Event(this.constructor.Event.SHOW); if (this.isWithContent() && this._isEnabled) { oe(this.element).trigger(t); var n = oe.contains(this.element.ownerDocument.documentElement, this.element); if (t.isDefaultPrevented() || !n) return; var i = this.getTipElement(), r = Cn.getUID(this.constructor.NAME); i.setAttribute("id", r), this.element.setAttribute("aria-describedby", r), this.setContent(), this.config.animation && oe(i).addClass(Ee); var s = "function" == typeof this.config.placement ? this.config.placement.call(this, i, this.element) : this.config.placement, o = this._getAttachment(s); this.addAttachmentClass(o); var a = !1 === this.config.container ? document.body : oe(this.config.container); oe(i).data(this.constructor.DATA_KEY, this), oe.contains(this.element.ownerDocument.documentElement, this.tip) || oe(i).appendTo(a), oe(this.element).trigger(this.constructor.Event.INSERTED), this._popper = new c(this.element, i, { placement: o, modifiers: { offset: { offset: this.config.offset }, flip: { behavior: this.config.fallbackPlacement }, arrow: { element: Ce }, preventOverflow: { boundariesElement: this.config.boundary } }, onCreate: function (t) { t.originalPlacement !== t.placement && e._handlePopperPlacementChange(t) }, onUpdate: function (t) { e._handlePopperPlacementChange(t) } }), oe(i).addClass(ye), "ontouchstart" in document.documentElement && oe(document.body).children().on("mouseover", null, oe.noop); var l = function () { e.config.animation && e._fixTransition(); var t = e._hoverState; e._hoverState = null, oe(e.element).trigger(e.constructor.Event.SHOWN), t === pe && e._leave(null, e) }; if (oe(this.tip).hasClass(Ee)) { var h = Cn.getTransitionDurationFromElement(this.tip); oe(this.tip).one(Cn.TRANSITION_END, l).emulateTransitionEnd(h) } else l() } }, t.hide = function (t) { var e = this, n = this.getTipElement(), i = oe.Event(this.constructor.Event.HIDE), r = function () { e._hoverState !== me && n.parentNode && n.parentNode.removeChild(n), e._cleanTipClass(), e.element.removeAttribute("aria-describedby"), oe(e.element).trigger(e.constructor.Event.HIDDEN), null !== e._popper && e._popper.destroy(), t && t() }; if (oe(this.element).trigger(i), !i.isDefaultPrevented()) { if (oe(n).removeClass(ye), "ontouchstart" in document.documentElement && oe(document.body).children().off("mouseover", null, oe.noop), this._activeTrigger[De] = !1, this._activeTrigger[Ae] = !1, this._activeTrigger[Ie] = !1, oe(this.tip).hasClass(Ee)) { var s = Cn.getTransitionDurationFromElement(n); oe(n).one(Cn.TRANSITION_END, r).emulateTransitionEnd(s) } else r(); this._hoverState = "" } }, t.update = function () { null !== this._popper && this._popper.scheduleUpdate() }, t.isWithContent = function () { return Boolean(this.getTitle()) }, t.addAttachmentClass = function (t) { oe(this.getTipElement()).addClass(ue + "-" + t) }, t.getTipElement = function () { return this.tip = this.tip || oe(this.config.template)[0], this.tip }, t.setContent = function () { var t = oe(this.getTipElement()); this.setElementContent(t.find(Te), this.getTitle()), t.removeClass(Ee + " " + ye) }, t.setElementContent = function (t, e) { var n = this.config.html; "object" == typeof e && (e.nodeType || e.jquery) ? n ? oe(e).parent().is(t) || t.empty().append(e) : t.text(oe(e).text()) : t[n ? "html" : "text"](e) }, t.getTitle = function () { var t = this.element.getAttribute("data-original-title"); return t || (t = "function" == typeof this.config.title ? this.config.title.call(this.element) : this.config.title), t }, t._getAttachment = function (t) { return _e[t.toUpperCase()] }, t._setListeners = function () { var i = this; this.config.trigger.split(" ").forEach(function (t) { if ("click" === t) oe(i.element).on(i.constructor.Event.CLICK, i.config.selector, function (t) { return i.toggle(t) }); else if (t !== be) { var e = t === Ie ? i.constructor.Event.MOUSEENTER : i.constructor.Event.FOCUSIN, n = t === Ie ? i.constructor.Event.MOUSELEAVE : i.constructor.Event.FOCUSOUT; oe(i.element).on(e, i.config.selector, function (t) { return i._enter(t) }).on(n, i.config.selector, function (t) { return i._leave(t) }) } oe(i.element).closest(".modal").on("hide.bs.modal", function () { return i.hide() }) }), this.config.selector ? this.config = h({}, this.config, { trigger: "manual", selector: "" }) : this._fixTitle() }, t._fixTitle = function () { var t = typeof this.element.getAttribute("data-original-title"); (this.element.getAttribute("title") || "string" !== t) && (this.element.setAttribute("data-original-title", this.element.getAttribute("title") || ""), this.element.setAttribute("title", "")) }, t._enter = function (t, e) { var n = this.constructor.DATA_KEY; (e = e || oe(t.currentTarget).data(n)) || (e = new this.constructor(t.currentTarget, this._getDelegateConfig()), oe(t.currentTarget).data(n, e)), t && (e._activeTrigger["focusin" === t.type ? Ae : Ie] = !0), oe(e.getTipElement()).hasClass(ye) || e._hoverState === me ? e._hoverState = me : (clearTimeout(e._timeout), e._hoverState = me, e.config.delay && e.config.delay.show ? e._timeout = setTimeout(function () { e._hoverState === me && e.show() }, e.config.delay.show) : e.show()) }, t._leave = function (t, e) { var n = this.constructor.DATA_KEY; (e = e || oe(t.currentTarget).data(n)) || (e = new this.constructor(t.currentTarget, this._getDelegateConfig()), oe(t.currentTarget).data(n, e)), t && (e._activeTrigger["focusout" === t.type ? Ae : Ie] = !1), e._isWithActiveTrigger() || (clearTimeout(e._timeout), e._hoverState = pe, e.config.delay && e.config.delay.hide ? e._timeout = setTimeout(function () { e._hoverState === pe && e.hide() }, e.config.delay.hide) : e.hide()) }, t._isWithActiveTrigger = function () { for (var t in this._activeTrigger) if (this._activeTrigger[t]) return !0; return !1 }, t._getConfig = function (t) { return "number" == typeof (t = h({}, this.constructor.Default, oe(this.element).data(), t)).delay && (t.delay = { show: t.delay, hide: t.delay }), "number" == typeof t.title && (t.title = t.title.toString()), "number" == typeof t.content && (t.content = t.content.toString()), Cn.typeCheckConfig(ae, t, this.constructor.DefaultType), t }, t._getDelegateConfig = function () { var t = {}; if (this.config) for (var e in this.config) this.constructor.Default[e] !== this.config[e] && (t[e] = this.config[e]); return t }, t._cleanTipClass = function () { var t = oe(this.getTipElement()), e = t.attr("class").match(fe); null !== e && 0 < e.length && t.removeClass(e.join("")) }, t._handlePopperPlacementChange = function (t) { this._cleanTipClass(), this.addAttachmentClass(this._getAttachment(t.placement)) }, t._fixTransition = function () { var t = this.getTipElement(), e = this.config.animation; null === t.getAttribute("x-placement") && (oe(t).removeClass(Ee), this.config.animation = !1, this.hide(), this.show(), this.config.animation = e) }, i._jQueryInterface = function (n) { return this.each(function () { var t = oe(this).data(le), e = "object" == typeof n && n; if ((t || !/dispose|hide/.test(n)) && (t || (t = new i(this, e), oe(this).data(le, t)), "string" == typeof n)) { if ("undefined" == typeof t[n]) throw new TypeError('No method named "' + n + '"'); t[n]() } }) }, o(i, null, [{ key: "VERSION", get: function () { return "4.1.0" } }, { key: "Default", get: function () { return ge } }, { key: "NAME", get: function () { return ae } }, { key: "DATA_KEY", get: function () { return le } }, { key: "Event", get: function () { return ve } }, { key: "EVENT_KEY", get: function () { return he } }, { key: "DefaultType", get: function () { return de } }]), i }(), oe.fn[ae] = Se._jQueryInterface, oe.fn[ae].Constructor = Se, oe.fn[ae].noConflict = function () { return oe.fn[ae] = ce, Se._jQueryInterface }, Se), On = (Ne = "popover", ke = "." + (Oe = "bs.popover"), Pe = (we = e).fn[Ne], Le = "bs-popover", je = new RegExp("(^|\\s)" + Le + "\\S+", "g"), Re = h({}, Nn.Default, { placement: "right", trigger: "click", content: "",template: '
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n : null; if ((t || !/destroy|hide/.test(n)) && (t || (t = new i(this, e), we(this).data(Oe, t)), "string" == typeof n)) { if ("undefined" == typeof t[n]) throw new TypeError('No method named "' + n + '"'); t[n]() } }) }, o(i, null, [{ key: "VERSION", get: function () { return "4.1.0" } }, { key: "Default", get: function () { return Re } }, { key: "NAME", get: function () { return Ne } }, { key: "DATA_KEY", get: function () { return Oe } }, { key: "Event", get: function () { return Ke } }, { key: "EVENT_KEY", get: function () { return ke } }, { key: "DefaultType", get: function () { return He } }]), i }(Nn), we.fn[Ne] = Fe._jQueryInterface, we.fn[Ne].Constructor = Fe, we.fn[Ne].noConflict = function () { return we.fn[Ne] = Pe, Fe._jQueryInterface }, Fe), kn = (Qe = "scrollspy", Ye = "." + (Be = "bs.scrollspy"), Ge = (Ve = e).fn[Qe], qe = { offset: 10, method: "auto", target: "" }, ze = { offset: "number", method: "string", target: "(string|element)" }, Xe = { ACTIVATE: "activate" + Ye, SCROLL: "scroll" + Ye, LOAD_DATA_API: "load" + Ye + ".data-api" }, Je = "dropdown-item", Ze = "active", $e = { DATA_SPY: '[data-spy="scroll"]', ACTIVE: ".active", NAV_LIST_GROUP: ".nav, .list-group", NAV_LINKS: ".nav-link", NAV_ITEMS: ".nav-item", LIST_ITEMS: ".list-group-item", DROPDOWN: ".dropdown", DROPDOWN_ITEMS: ".dropdown-item", DROPDOWN_TOGGLE: ".dropdown-toggle" }, tn = "offset", en = "position", nn = function () { function n(t, e) { var n = this; this._element = t, this._scrollElement = "BODY" === t.tagName ? window : t, this._config = this._getConfig(e), this._selector = this._config.target + " " + $e.NAV_LINKS + "," + this._config.target + " " + $e.LIST_ITEMS + "," + this._config.target + " " + $e.DROPDOWN_ITEMS, this._offsets = [], this._targets = [], this._activeTarget = null, this._scrollHeight = 0, Ve(this._scrollElement).on(Xe.SCROLL, function (t) { return n._process(t) }), this.refresh(), this._process() } var t = n.prototype; return t.refresh = function () { var e = this, t = this._scrollElement === this._scrollElement.window ? tn : en, r = "auto" === this._config.method ? t : this._config.method, s = r === en ? this._getScrollTop() : 0; this._offsets = [], this._targets = [], this._scrollHeight = this._getScrollHeight(), Ve.makeArray(Ve(this._selector)).map(function (t) { var e, n = Cn.getSelectorFromElement(t); if (n && (e = Ve(n)[0]), e) { var i = e.getBoundingClientRect(); if (i.width || i.height) return [Ve(e)[r]().top + s, n] } return null }).filter(function (t) { return t }).sort(function (t, e) { return t[0] - e[0] }).forEach(function (t) { e._offsets.push(t[0]), e._targets.push(t[1]) }) }, t.dispose = function () { Ve.removeData(this._element, Be), Ve(this._scrollElement).off(Ye), this._element = null, this._scrollElement = null, this._config = null, this._selector = null, this._offsets = null, this._targets = null, this._activeTarget = null, this._scrollHeight = null }, t._getConfig = function (t) { if ("string" != typeof (t = h({}, qe, t)).target) { var e = Ve(t.target).attr("id"); e || (e = Cn.getUID(Qe), Ve(t.target).attr("id", e)), t.target = "#" + e } return Cn.typeCheckConfig(Qe, t, ze), t }, t._getScrollTop = function () { return this._scrollElement === window ? this._scrollElement.pageYOffset : this._scrollElement.scrollTop }, t._getScrollHeight = function () { return this._scrollElement.scrollHeight || Math.max(document.body.scrollHeight, document.documentElement.scrollHeight) }, t._getOffsetHeight = function () { return this._scrollElement === window ? window.innerHeight : this._scrollElement.getBoundingClientRect().height }, t._process = function () { var t = this._getScrollTop() + this._config.offset, e = this._getScrollHeight(), n = this._config.offset + e - this._getOffsetHeight(); if (this._scrollHeight !== e && this.refresh(), n <= t) { var i = this._targets[this._targets.length - 1]; this._activeTarget !== i && this._activate(i) } else { if (this._activeTarget && t < this._offsets[0] && 0 < this._offsets[0]) return this._activeTarget = null, void this._clear(); for (var r = this._offsets.length; r--;) { this._activeTarget !== this._targets[r] && t >= this._offsets[r] && ("undefined" == typeof this._offsets[r + 1] || t < this._offsets[r + 1]) && this._activate(this._targets[r]) } } }, t._activate = function (e) { this._activeTarget = e, this._clear(); var t = this._selector.split(","); t = t.map(function (t) { return t + '[data-target="' + e + '"],' + t + '[href="' + e + '"]' }); var n = Ve(t.join(",")); n.hasClass(Je) ? (n.closest($e.DROPDOWN).find($e.DROPDOWN_TOGGLE).addClass(Ze), n.addClass(Ze)) : (n.addClass(Ze), n.parents($e.NAV_LIST_GROUP).prev($e.NAV_LINKS + ", " + $e.LIST_ITEMS).addClass(Ze), n.parents($e.NAV_LIST_GROUP).prev($e.NAV_ITEMS).children($e.NAV_LINKS).addClass(Ze)), Ve(this._scrollElement).trigger(Xe.ACTIVATE, { relatedTarget: e }) }, t._clear = function () { Ve(this._selector).filter($e.ACTIVE).removeClass(Ze) }, n._jQueryInterface = function (e) { return this.each(function () { var t = Ve(this).data(Be); if (t || (t = new n(this, "object" == typeof e && e), Ve(this).data(Be, t)), "string" == typeof e) { if ("undefined" == typeof t[e]) throw new TypeError('No method named "' + e + '"'); t[e]() } }) }, o(n, null, [{ key: "VERSION", get: function () { return "4.1.0" } }, { key: "Default", get: function () { return qe } }]), n }(), Ve(window).on(Xe.LOAD_DATA_API, function () { for (var t = Ve.makeArray(Ve($e.DATA_SPY)), e = t.length; e--;) { var n = Ve(t[e]); nn._jQueryInterface.call(n, n.data()) } }), Ve.fn[Qe] = nn._jQueryInterface, Ve.fn[Qe].Constructor = nn, Ve.fn[Qe].noConflict = function () { return Ve.fn[Qe] = Ge, nn._jQueryInterface }, nn), Pn = (on = "." + (sn = "bs.tab"), an = (rn = e).fn.tab, ln = { HIDE: "hide" + on, HIDDEN: "hidden" + on, SHOW: "show" + on, SHOWN: "shown" + on, CLICK_DATA_API: "click" + on + ".data-api" }, hn = "dropdown-menu", cn = "active", un = "disabled", fn = "fade", dn = "show", _n = ".dropdown", gn = ".nav, .list-group", mn = ".active", pn = "> li > .active", vn = '[data-toggle="tab"], [data-toggle="pill"], [data-toggle="list"]', En = ".dropdown-toggle", yn = "> .dropdown-menu .active", Tn = function () { function i(t) { this._element = t } var t = i.prototype; return t.show = function () { var n = this; if (!(this._element.parentNode && this._element.parentNode.nodeType === Node.ELEMENT_NODE && rn(this._element).hasClass(cn) || rn(this._element).hasClass(un))) { var t, i, e = rn(this._element).closest(gn)[0], r = Cn.getSelectorFromElement(this._element); if (e) { var s = "UL" === e.nodeName ? pn : mn; i = (i = rn.makeArray(rn(e).find(s)))[i.length - 1] } var o = rn.Event(ln.HIDE, { relatedTarget: this._element }), a = rn.Event(ln.SHOW, { relatedTarget: i }); if (i && rn(i).trigger(o), rn(this._element).trigger(a), !a.isDefaultPrevented() && !o.isDefaultPrevented()) { r && (t = rn(r)[0]), this._activate(this._element, e); var l = function () { var t = rn.Event(ln.HIDDEN, { relatedTarget: n._element }), e = rn.Event(ln.SHOWN, { relatedTarget: i }); rn(i).trigger(t), rn(n._element).trigger(e) }; t ? this._activate(t, t.parentNode, l) : l() } } }, t.dispose = function () { rn.removeData(this._element, sn), this._element = null }, t._activate = function (t, e, n) { var i = this, r = ("UL" === e.nodeName ? rn(e).find(pn) : rn(e).children(mn))[0], s = n && r && rn(r).hasClass(fn), o = function () { return i._transitionComplete(t, r, n) }; if (r && s) { var a = Cn.getTransitionDurationFromElement(r); rn(r).one(Cn.TRANSITION_END, o).emulateTransitionEnd(a) } else o() }, t._transitionComplete = function (t, e, n) { if (e) { rn(e).removeClass(dn + " " + cn); var i = rn(e.parentNode).find(yn)[0]; i && rn(i).removeClass(cn), "tab" === e.getAttribute("role") && e.setAttribute("aria-selected", !1) } if (rn(t).addClass(cn), "tab" === t.getAttribute("role") && t.setAttribute("aria-selected", !0), Cn.reflow(t), rn(t).addClass(dn), t.parentNode && rn(t.parentNode).hasClass(hn)) { var r = rn(t).closest(_n)[0]; r && rn(r).find(En).addClass(cn), t.setAttribute("aria-expanded", !0) } n && n() }, i._jQueryInterface = function (n) { return this.each(function () { var t = rn(this), e = t.data(sn); if (e || (e = new i(this), t.data(sn, e)), "string" == typeof n) { if ("undefined" == typeof e[n]) throw new TypeError('No method named "' + n + '"'); e[n]() } }) }, o(i, null, [{ key: "VERSION", get: function () { return "4.1.0" } }]), i }(), rn(document).on(ln.CLICK_DATA_API, vn, function (t) { t.preventDefault(), Tn._jQueryInterface.call(rn(this), "show") }), rn.fn.tab = Tn._jQueryInterface, rn.fn.tab.Constructor = Tn, rn.fn.tab.noConflict = function () { return rn.fn.tab = an, Tn._jQueryInterface }, Tn); ! function (t) { if ("undefined" == typeof t) throw new TypeError("Bootstrap's JavaScript requires jQuery. jQuery must be included before Bootstrap's JavaScript."); var e = t.fn.jquery.split(" ")[0].split("."); if (e[0] < 2 && e[1] < 9 || 1 === e[0] && 9 === e[1] && e[2] < 1 || 4 <= e[0]) throw new Error("Bootstrap's JavaScript requires at least jQuery v1.9.1 but less than v4.0.0") }(e), t.Util = Cn, t.Alert = In, t.Button = An, t.Carousel = Dn, t.Collapse = bn, t.Dropdown = Sn, t.Modal = wn, t.Popover = On, t.Scrollspy = kn, t.Tab = Pn, t.Tooltip = Nn, Object.defineProperty(t, "__esModule", { value: !0 })
});