Difference between revisions of "Team:UofC Calgary/Notebook"

 
(69 intermediate revisions by 4 users not shown)
Line 11: Line 11:
 
{{Team:UofC_Calgary/assets/plugins/owl-carousel/owl.theme.css}}
 
{{Team:UofC_Calgary/assets/plugins/owl-carousel/owl.theme.css}}
 
{{Team:UofC_Calgary/assets/plugins/owl-carousel/owl.transitions.css}}
 
{{Team:UofC_Calgary/assets/plugins/owl-carousel/owl.transitions.css}}
−
{{Team:UofC_Calgary/assets/plugins/jportilio.min.js}}
 
−
{{Team:UofC_Calgary/assets/plugins/prism.js}}
 
 
{{Team:UofC_Calgary/assets/plugins/fancybox/jquery.fancybox.css}}
 
{{Team:UofC_Calgary/assets/plugins/fancybox/jquery.fancybox.css}}
 
{{Team:UofC_Calgary/assets/base/css/themes/default.css}}
 
{{Team:UofC_Calgary/assets/base/css/themes/default.css}}
Line 27: Line 25:
 
{{Team:UofC_Calgary/assets/plugins/counterup/jquery.counterup.min.js}}
 
{{Team:UofC_Calgary/assets/plugins/counterup/jquery.counterup.min.js}}
 
{{Team:UofC_Calgary/assets/plugins/fancybox/jquery.fancybox.pack.js}}
 
{{Team:UofC_Calgary/assets/plugins/fancybox/jquery.fancybox.pack.js}}
−
{{Team:UofC_Calgary/assets/base/js/app.js}}
 
 
{{Team:UofC_Calgary/assets/base/js/components.js}}
 
{{Team:UofC_Calgary/assets/base/js/components.js}}
−
 
+
{{Team:UofC_Calgary/assets/base/js/app.js}}<html>
−
<html lang="en">
+
−
<!--<![endif]-->
+
−
<!-- BEGIN HEAD -->
+
 
<head>
 
<head>
−
+
    <title>iGEM Calgary 2016</title>
−
<meta charset="utf-8"/>
+
−
<title>iGEM Calgary 2016</title>
+
−
<meta http-equiv="X-UA-Compatible" content="IE=edge">
+
−
<meta content="width=device-width, initial-scale=1.0" name="viewport"/>
+
−
<meta http-equiv="Content-type" content="text/html; charset=utf-8">
+
−
<meta content="" name="description"/>
+
−
<meta content="" name="author"/>
+
−
 
+
−
<link rel="shortcut icon" href="favicon.ico"/>
+
 
</head>
 
</head>
−
<body class="c-layout-header-fixed">
+
<body>
−
<!-- BEGIN: LAYOUT/HEADERS/HEADER-1 -->
+
 
−
<!-- BEGIN: HEADER -->
+
    <!-- BEGIN HEAD -->
−
<header class="c-layout-header c-layout-header-3 c-layout-header-default-mobile c-header-seethrough" style="padding-top: 10px;
+
    <meta charset="utf-8">
−
    top: 0;
+
    <meta content="IE=edge" http-equiv="X-UA-Compatible">
−
    position: fixed;
+
    <meta content="width=device-width, initial-scale=1.0" name="viewport">
−
    z-index: 9995;
+
    <meta content="text/html; charset=utf-8" http-equiv="Content-type">
−
    width: 100%;
+
    <meta content="" name="description">
−
"><div class="c-navbar">
+
    <meta content="" name="author">
−
<div class="container-fluid" style="padding-left: 20px; padding-right: 20px;">
+
    <link href="favicon.ico" rel="shortcut icon">
−
<!-- BEGIN: BRAND -->
+
    <!-- BEGIN: LAYOUT/HEADERS/HEADER-1 -->
−
<div class="c-navbar-wrapper clearfix">
+
    <!-- BEGIN: HEADER -->
−
<div class="c-brand c-pull-left">
+
    <header class=
−
<a href="https://2016.igem.org/Team:UofC_Calgary/sandbox" class="c-logo">                                         
+
    "c-layout-header c-layout-header-3 c-layout-header-default-mobile c-header-seethrough"
−
<img src="https://static.igem.org/mediawiki/2016/9/9a/Logo-1.png" alt="iGEM" class="c-desktop-logo">
+
    style=
−
<img src="https://static.igem.org/mediawiki/2016/9/9a/Logo-1.png" alt="iGEM" class="c-desktop-logo-inverse">
+
    "padding-top: 10px; top: 0; position: fixed; z-index: 9995; width: 100%;">
−
<img src="https://static.igem.org/mediawiki/2016/9/9a/Logo-1.png" alt="iGEM" class="c-mobile-logo">
+
        <div class="c-navbar">
−
</a>
+
            <div class="container-fluid" style=
−
<button class="c-hor-nav-toggler" type="button" data-target=".c-mega-menu">
+
            "padding-left: 20px; padding-right: 20px;">
−
<span class="c-line"></span>
+
                <!-- BEGIN: BRAND -->
−
<span class="c-line"></span>
+
                <div class="c-navbar-wrapper clearfix">
−
<span class="c-line"></span>
+
                    <div class="c-brand c-pull-left">
−
</button>
+
                        <a class="c-logo" href=
−
</div>
+
                        "https://2016.igem.org/Team:UofC_Calgary"><img alt=
−
<!-- END: BRAND -->
+
                        "iGEM" class="c-desktop-logo" src=
−
<!-- BEGIN: HOR NAV -->
+
                        "https://static.igem.org/mediawiki/2016/9/9a/Logo-1.png">
−
<!-- BEGIN: MEGA MENU -->
+
                        <img alt="iGEM" class="c-desktop-logo-inverse" src=
−
<nav class="c-mega-menu c-pull-right c-mega-menu-dark c-mega-menu-dark-mobile c-fonts-uppercase c-fonts-bold">
+
                        "https://static.igem.org/mediawiki/2016/9/9a/Logo-1.png">
−
<!-- BEGIN: MEGA MENU -->
+
                        <img alt="iGEM" class="c-mobile-logo" src=
−
<ul class="nav navbar-nav c-theme-nav">
+
                        "https://static.igem.org/mediawiki/2016/9/9a/Logo-1.png"></a>
−
<li class="c-menu-type-classic">
+
                        <button class="c-hor-nav-toggler" data-target=
−
<a href="https://2016.igem.org/Team:UofC_Calgary/sandbox" class="c-link dropdown-toggle">Home</a>
+
                        ".c-mega-menu" type="button"><span class=
−
</li>
+
                        "c-line"></span> <span class="c-line"></span>
−
<li class="c-menu-type-classic">
+
                        <span class="c-line"></span></button>
−
<a href="https://2016.igem.org/Team:UofC_Calgary/project/sandbox" class="c-link dropdown-toggle">Project</a>
+
                    </div><!-- END: BRAND -->
−
<ul class="dropdown-menu c-menu-type-inline c-pull-left">
+
                    <!-- BEGIN: HOR NAV -->
−
<li>
+
                    <!-- BEGIN: LAYOUT/HEADERS/MEGA-MENU -->
−
<a href="https://2016.igem.org/Team:UofC_Calgary/project/problem/sandbox">Problem</a>
+
                    <!-- BEGIN: MEGA MENU -->
 +
                    <nav class=
 +
                    "c-mega-menu c-pull-right c-mega-menu-dark c-mega-menu-dark-mobile c-fonts-uppercase c-fonts-bold">
 +
                    <!-- BEGIN: MEGA MENU -->
 +
                        <!-- BEGIN: MEGA MENU -->
 +
                        <ul class="nav navbar-nav c-theme-nav">
 +
                            <li class="c-menu-type-classic">
 +
                                <a class="c-link dropdown-toggle" href=
 +
                                "https://2016.igem.org/Team:UofC_Calgary">Home</a>
 +
                            </li>
 +
                            <li class="c-menu-type-classic">
 +
                                <a class="c-link dropdown-toggle" href=
 +
                                "https://2016.igem.org/Team:UofC_Calgary/Description">
 +
                                Project</a>
 +
                                <ul class=
 +
                                "dropdown-menu c-menu-type-inline c-pull-left">
 +
                                    <li>
 +
                                        <a href=
 +
                                        "https://2016.igem.org/Team:UofC_Calgary/Description">
 +
                                        Problem</a>
 +
                                    </li>
 +
                                    <li>
 +
                                        <a href=
 +
                                        "https://2016.igem.org/Team:UofC_Calgary/Experiments">
 +
                                        Our Experiments</a>
 +
                                    </li>
 +
                                    <li>
 +
                                        <a href=
 +
                                        "https://2016.igem.org/Team:UofC_Calgary/Results">
 +
                                        Our Results</a>
 +
                                    </li>
 +
                                    <li>
 +
                                        <a href=
 +
                                        "https://2016.igem.org/Team:UofC_Calgary/Model">
 +
                                        Model</a>
 +
                                    </li><li>
 +
<a href="https://2016.igem.org/Team:UofC_Calgary/Design">Applied Design</a>
 
</li>
 
</li>
−
<li>
+
                                    <li>
−
<a href="https://2016.igem.org/Team:UofC_Calgary/project/solution/sandbox">Our Solution</a>
+
                                        <a href="https://2016.igem.org/Team:UofC_Calgary/Parts">Parts Registry</a>
 +
                                    </li>
 +
                                    <li>
 +
                                      <a href="https://2016.igem.org/Team:UofC_Calgary/Composite_Part">Composite Parts</a>
 
</li>
 
</li>
−
                                                                <li>
+
                                   
−
<a href="https://2016.igem.org/Team:UofC_Calgary/project/results/sandbox">Our Results</a>
+
                                </ul>
−
</li>
+
                            </li>
−
                                                                <li>
+
                            <li class="c-menu-type-classic">
−
<a href="https://2016.igem.org/Team:UofC_Calgary/project/model/sandbox">Model</a>
+
                                <a class="c-link" href=
−
</li>
+
                                "https://2016.igem.org/Team:UofC_Calgary/Judging">
−
<li>
+
                                Judging</a>
−
<a href="https://2016.igem.org/Team:UofC_Calgary/project/parts/sandbox">Parts Registry</a>
+
                            </li>
−
</li>
+
                            <li class="c-menu-type-classic">
−
</ul>
+
                                <a class="c-link dropdown-toggle" href=
−
</li>
+
                                "https://2016.igem.org/Team:UofC_Calgary/Human_Practices">
−
<li class="c-menu-type-classic">
+
                                Human Practices</a>
−
<a href="https://2016.igem.org/Team:UofC_Calgary/judging/sandbox" class="c-link">Judging</a>
+
                                <ul class=
−
</li>
+
                                "dropdown-menu c-menu-type-inline c-pull-left">
−
+
                                    <li>
−
<li class="c-menu-type-classic">
+
                                        <a href=
−
<a href="https://2016.igem.org/Team:UofC_Calgary/human-practices/sandbox" class="c-link dropdown-toggle">Human Practices</a>
+
                                        "https://2016.igem.org/Team:UofC_Calgary/Integrated_Practices">
−
<ul class="dropdown-menu c-menu-type-inline c-pull-left">
+
                                        Integrated Practices</a>
−
<li>
+
                                    </li>
−
<a href="https://2016.igem.org/Team:UofC_Calgary/Integrated_Practices/sandbox">Integrated Practices</a>
+
                                    <li>
−
</li>
+
                                        <a href=
−
<li>
+
                                        "https://2016.igem.org/Team:UofC_Calgary/Collaborations">
−
<a href="https://2016.igem.org/Team:UofC_Calgary/Collaborations/sandbox">Collaborations</a>
+
                                        Collaborations</a>
−
</li>
+
                                    </li>
−
<li>
+
                                    <li>
−
<a href="https://2016.igem.org/Team:UofC_Calgary/Engagement/sandbox">Engagement</a>
+
                                        <a href=
−
</li>
+
                                        "https://2016.igem.org/Team:UofC_Calgary/Engagement">
−
<li>
+
                                        Engagement</a>
−
<a href="https://2016.igem.org/Team:UofC_Calgary/Safety/sandbox">Safety</a>
+
                                    </li>
−
</li>
+
                                    <li>
−
<li>
+
                                        <a href=
−
<a href="https://2016.igem.org/Team:UofC_Calgary/HP/Silver/sandbox">Silver</a>
+
                                        "https://2016.igem.org/Team:UofC_Calgary/Safety">
−
</li>
+
                                        Safety</a>
−
<li>
+
                                    </li>
−
<a href="https://2016.igem.org/Team:UofC_Calgary/HP/Gold/sandbox">Gold</a>
+
                                    <li>
−
</li>
+
                                        <a href=
−
</ul>
+
                                        "https://2016.igem.org/Team:UofC_Calgary/HP/Silver">
−
</li>
+
                                        Silver</a>
−
                                <li class="c-active c-menu-type-classic">
+
                                    </li>
−
<a href="https://2016.igem.org/Team:UofC_Calgary/notebook/sandbox" class="c-link">Notebook</a>
+
                                    <li>
−
</li>
+
                                        <a href=
−
<li class="c-menu-type-classic">
+
                                        "https://2016.igem.org/Team:UofC_Calgary/HP/Gold">
−
<a href="https://2016.igem.org/Team:UofC_Calgary/team/sandbox" class="c-link dropdown-toggle">Team</a>
+
                                        Gold</a>
−
<ul class="dropdown-menu c-menu-type-inline c-pull-left">
+
                                    </li>
−
                                                                <li>
+
<li>
−
<a href="Team">Meet Our Team</a>
+
                                    <a href="https://2016.igem.org/Team:UofC_Calgary/Policy"> Policy Brief </a>
−
</li>
+
                                    </li>
−
<li>
+
                                </ul>
−
<a href="Attributions">Attributions</a>
+
                            </li>
−
</li>
+
                            <li class="c-active c-menu-type-classic">
−
<li>
+
                                <a class="c-link" href=
−
<a href="Sponsors">Sponsors</a>
+
                                "https://2016.igem.org/Team:UofC_Calgary/Notebook">
−
</li>
+
                                Notebook</a>
−
                             
+
                            </li>
−
</ul>
+
                            <li class="c-menu-type-classic">
−
</li>
+
                                <a class="c-link dropdown-toggle" href=
 +
                                "https://2016.igem.org/Team:UofC_Calgary/Team">Team</a>
 +
                                <ul class=
 +
                                "dropdown-menu c-menu-type-inline c-pull-left">
 +
                                    <li>
 +
                                        <a href=
 +
                                        "https://2016.igem.org/Team:UofC_Calgary/Team">
 +
                                        Meet Our Team</a>
 +
                                    </li>
 +
                                    <li>
 +
                                        <a href=
 +
                                        "https://2016.igem.org/Team:UofC_Calgary/Attributions">
 +
                                        Attributions</a>
 +
                                    </li>
 +
                                </ul>
 +
                            </li>
 +
                            <li>
 +
                                <a class=
 +
                                "c-btn-border-opacity-04 c-btn btn-no-focus c-btn-header btn btn-sm c-btn-border-1x c-btn-white c-btn-circle c-btn-sbold"
 +
                                data-target="#login-form" data-toggle="modal"
 +
                                href="https://2016.igem.org/Main_Page"><i class=
 +
                                "icon-chemistry"></i> iGEM</a>
 +
                            </li>
 +
                            <li class="c-quick-sidebar-toggler-wrapper">
 +
                                <a class="c-quick-sidebar-toggler" href=
 +
                                "#"><span class="c-line"></span> <span class=
 +
                                "c-line"></span> <span class=
 +
                                "c-line"></span></a>
 +
                            </li>
 +
                        </ul><!-- END MEGA MENU -->
 +
                        <!-- END MEGA MENU -->
 +
                    </nav><!-- END: MEGA MENU -->
 +
                    <!-- END: LAYOUT/HEADERS/MEGA-MENU -->
 +
                    <!-- END: HOR NAV -->
 +
                </div>
 +
            </div>
 +
        </div>
 +
    </header><!-- END: HEADER -->
 +
    <!-- END: LAYOUT/HEADERS/HEADER-1 -->
 +
    <!-- BEGIN: LAYOUT/SIDEBARS/QUICK-SIDEBAR -->
 +
    <nav class="c-layout-quick-sidebar">
 +
        <div class="c-header">
 +
            <button class="c-link c-close" type="button"><i class=
 +
            "icon-login"></i></button>
 +
        </div>
 +
        <div class="c-content">
 +
            <div class="c-section">
 +
                <h3>Theme Colors</h3>
 +
                <div class="c-settings">
 +
                    <span class="c-color c-default c-active" data-color=
 +
                    "default"></span> <span class="c-color c-green1"
 +
                    data-color="green1"></span> <span class="c-color c-green2"
 +
                    data-color="green2"></span> <span class="c-color c-green3"
 +
                    data-color="green3"></span> <span class="c-color c-yellow1"
 +
                    data-color="yellow1"></span> <span class=
 +
                    "c-color c-yellow2" data-color="yellow2"></span>
 +
                    <span class="c-color c-yellow3" data-color=
 +
                    "yellow3"></span> <span class="c-color c-red1" data-color=
 +
                    "red1"></span> <span class="c-color c-red2" data-color=
 +
                    "red2"></span> <span class="c-color c-red3" data-color=
 +
                    "red3"></span> <span class="c-color c-purple1" data-color=
 +
                    "purple1"></span> <span class="c-color c-purple2"
 +
                    data-color="purple2"></span> <span class=
 +
                    "c-color c-purple3" data-color="purple3"></span>
 +
                    <span class="c-color c-blue1" data-color="blue1"></span>
 +
                    <span class="c-color c-blue2" data-color="blue2"></span>
 +
                    <span class="c-color c-blue3" data-color="blue3"></span>
 +
                    <span class="c-color c-brown1" data-color="brown1"></span>
 +
                    <span class="c-color c-brown2" data-color="brown2"></span>
 +
                    <span class="c-color c-brown3" data-color="brown3"></span>
 +
                    <span class="c-color c-dark1" data-color="dark1"></span>
 +
                    <span class="c-color c-dark2" data-color="dark2"></span>
 +
                    <span class="c-color c-dark3" data-color="dark3"></span>
 +
                </div>
 +
            </div>
 +
            <div class="c-section">
 +
                <h3>Header Type</h3>
 +
                <div class="c-settings">
 +
                    <input class=
 +
                    "c-setting_header-type btn btn-sm c-btn-square c-btn-border-1x c-btn-white c-btn-sbold c-btn-uppercase active"
 +
                    data-value="boxed" type="button" value="boxed">
 +
                    <input class=
 +
                    "c-setting_header-type btn btn-sm c-btn-square c-btn-border-1x c-btn-white c-btn-sbold c-btn-uppercase"
 +
                    data-value="fluid" type="button" value="fluid">
 +
                </div>
 +
            </div>
 +
            <div class="c-section">
 +
                <h3>Header Mode</h3>
 +
                <div class="c-settings">
 +
                    <input class=
 +
                    "c-setting_header-mode btn btn-sm c-btn-square c-btn-border-1x c-btn-white c-btn-sbold c-btn-uppercase active"
 +
                    data-value="fixed" type="button" value="fixed">
 +
                    <input class=
 +
                    "c-setting_header-mode btn btn-sm c-btn-square c-btn-border-1x c-btn-white c-btn-sbold c-btn-uppercase"
 +
                    data-value="static" type="button" value="static">
 +
                </div>
 +
            </div>
 +
            <div class="c-section">
 +
                <h3>Mega Menu Style</h3>
 +
                <div class="c-settings">
 +
                    <input class=
 +
                    "c-setting_megamenu-style btn btn-sm c-btn-square c-btn-border-1x c-btn-white c-btn-sbold c-btn-uppercase active"
 +
                    data-value="dark" type="button" value="dark"> <input class=
 +
                    "c-setting_megamenu-style btn btn-sm c-btn-square c-btn-border-1x c-btn-white c-btn-sbold c-btn-uppercase"
 +
                    data-value="light" type="button" value="light">
 +
                </div>
 +
            </div>
 +
            <div class="c-section">
 +
                <h3>Font Style</h3>
 +
                <div class="c-settings">
 +
                    <input class=
 +
                    "c-setting_font-style btn btn-sm c-btn-square c-btn-border-1x c-btn-white c-btn-sbold c-btn-uppercase active"
 +
                    data-value="default" type="button" value="default">
 +
                    <input class=
 +
                    "c-setting_font-style btn btn-sm c-btn-square c-btn-border-1x c-btn-white c-btn-sbold c-btn-uppercase"
 +
                    data-value="light" type="button" value="light">
 +
                </div>
 +
            </div>
 +
        </div>
 +
    </nav><!-- END: LAYOUT/SIDEBARS/QUICK-SIDEBAR -->
 +
    <!-- BEGIN: PAGE CONTAINER  -->
 +
    <div class="c-layout-page" style="padding-top: 86px;">
 +
        <!-- BEGIN: PAGE CONTENT -->
 +
        <!--BEGIN: SLIDE #1 -->
 +
        <div class="row-fluid">
 +
          <div class="span12">
 +
            <div style="position: relative;">
  
−
<li>
+
<a id="img-scroll1">
−
<a href="https://2016.igem.org/Main_Page" data-toggle="modal" data-target="#login-form" class="c-btn-border-opacity-04 c-btn btn-no-focus c-btn-header btn btn-sm c-btn-border-1x c-btn-white c-btn-circle c-btn-uppercase c-btn-sbold"><i class="icon-chemistry"></i> iGEM </a>
+
               <img style="position:absolute;left:27%;top:80%;max-width: 15%;cursor: pointer;" src="https://static.igem.org/mediawiki/2016/a/a7/T--UofC_Calgary--biotarget-icon.jpg" alt="1" type="image" id="first">
−
</li>
+
−
<li class="c-quick-sidebar-toggler-wrapper">
+
−
<a href="#" class="c-quick-sidebar-toggler">
+
−
<span class="c-line"></span>
+
−
<span class="c-line"></span>
+
−
<span class="c-line"></span>
+
−
</a>
+
−
</li>
+
−
</ul>
+
−
<!-- END MEGA MENU -->
+
−
</nav>
+
−
<!-- END: MEGA MENU -->
+
−
<!-- END: LAYOUT/HEADERS/MEGA-MENU -->
+
−
<!-- END: HOR NAV -->
+
−
</div>
+
−
</div>
+
−
</div>
+
−
</header>
+
−
<!-- END: HEADER -->
+
−
<!-- END: LAYOUT/HEADERS/HEADER-1 -->
+
−
<!-- BEGIN: LAYOUT/SIDEBARS/QUICK-SIDEBAR -->
+
−
<nav class="c-layout-quick-sidebar">
+
−
<div class="c-header">
+
−
<button type="button" class="c-link c-close">
+
−
<i class="icon-login"></i>
+
−
</button>
+
−
</div>
+
−
<div class="c-content">
+
−
<div class="c-section">
+
−
<h3>Theme Colors</h3>
+
−
<div class="c-settings">
+
−
<span class="c-color c-default c-active" data-color="default"></span>
+
−
<span class="c-color c-green1" data-color="green1"></span>
+
−
<span class="c-color c-green2" data-color="green2"></span>
+
−
<span class="c-color c-green3" data-color="green3"></span>
+
−
<span class="c-color c-yellow1" data-color="yellow1"></span>
+
−
<span class="c-color c-yellow2" data-color="yellow2"></span>
+
−
<span class="c-color c-yellow3" data-color="yellow3"></span>
+
−
<span class="c-color c-red1" data-color="red1"></span>
+
−
<span class="c-color c-red2 " data-color="red2"></span>
+
−
<span class="c-color c-red3" data-color="red3"></span>
+
−
<span class="c-color c-purple1" data-color="purple1"></span>
+
−
<span class="c-color c-purple2" data-color="purple2"></span>
+
−
<span class="c-color c-purple3" data-color="purple3"></span>
+
−
<span class="c-color c-blue1" data-color="blue1"></span>
+
−
<span class="c-color c-blue2" data-color="blue2"></span>
+
−
<span class="c-color c-blue3" data-color="blue3"></span>
+
−
<span class="c-color c-brown1" data-color="brown1"></span>
+
−
<span class="c-color c-brown2" data-color="brown2"></span>
+
−
<span class="c-color c-brown3" data-color="brown3"></span>
+
−
<span class="c-color c-dark1" data-color="dark1"></span>
+
−
<span class="c-color c-dark2" data-color="dark2"></span>
+
−
<span class="c-color c-dark3" data-color="dark3"></span>
+
−
</div>
+
−
</div>
+
−
<div class="c-section">
+
−
<h3>Header Type</h3>
+
−
<div class="c-settings">
+
−
<input type="button" class="c-setting_header-type btn btn-sm c-btn-square c-btn-border-1x c-btn-white c-btn-sbold c-btn-uppercase active" data-value="boxed" value="boxed"/>
+
−
<input type="button" class="c-setting_header-type btn btn-sm c-btn-square c-btn-border-1x c-btn-white c-btn-sbold c-btn-uppercase" data-value="fluid" value="fluid"/>
+
−
</div>
+
−
</div>
+
−
<div class="c-section">
+
−
<h3>Header Mode</h3>
+
−
<div class="c-settings">
+
−
<input type="button" class="c-setting_header-mode btn btn-sm c-btn-square c-btn-border-1x c-btn-white c-btn-sbold c-btn-uppercase active" data-value="fixed" value="fixed"/>
+
−
<input type="button" class="c-setting_header-mode btn btn-sm c-btn-square c-btn-border-1x c-btn-white c-btn-sbold c-btn-uppercase" data-value="static" value="static"/>
+
−
</div>
+
−
</div>
+
−
<div class="c-section">
+
−
<h3>Mega Menu Style</h3>
+
−
<div class="c-settings">
+
−
<input type="button" class="c-setting_megamenu-style btn btn-sm c-btn-square c-btn-border-1x c-btn-white c-btn-sbold c-btn-uppercase active" data-value="dark" value="dark"/>
+
−
<input type="button" class="c-setting_megamenu-style btn btn-sm c-btn-square c-btn-border-1x c-btn-white c-btn-sbold c-btn-uppercase" data-value="light" value="light"/>
+
−
</div>
+
−
</div>
+
−
<div class="c-section">
+
−
<h3>Font Style</h3>
+
−
<div class="c-settings">
+
−
<input type="button" class="c-setting_font-style btn btn-sm c-btn-square c-btn-border-1x c-btn-white c-btn-sbold c-btn-uppercase active" data-value="default" value="default"/>
+
−
<input type="button" class="c-setting_font-style btn btn-sm c-btn-square c-btn-border-1x c-btn-white c-btn-sbold c-btn-uppercase" data-value="light" value="light"/>
+
−
</div>
+
−
</div>
+
−
</div>
+
−
</nav>
+
−
<!-- END: LAYOUT/SIDEBARS/QUICK-SIDEBAR -->
+
−
<!-- BEGIN: PAGE CONTAINER -->
+
−
<div class="c-layout-page" style="padding-top: 88px;"> <!-- BEGIN: PAGE CONTENT -->
+
−
<!--BEGIN: SLIDE #1 -->
+
−
<div class="row-fluid">   
+
−
        <div class="span12">
+
−
            <div style="position: relative;display: inline-block;">
+
−
                <a id="img-scroll">
+
−
               <img style="position:absolute;left:46%;top:87%;max-width: 10%;cursor: pointer;" src="https://static.igem.org/mediawiki/2016/0/0d/T--UofC_Calgary--scrollnotebook.jpg" alt="1" type="image" id="first"/>
+
 
               </a>
 
               </a>
−
               <img style="width:100%; height: 100%" src="https://static.igem.org/mediawiki/2016/f/f3/T--UofC_Calgary--notebook.jpg" alt="bg" />
+
 
 +
<a id="img-scroll2">
 +
              <img style="position:absolute;left:43%;top:80%;max-width: 15%;cursor: pointer;" src="https://static.igem.org/mediawiki/2016/9/95/T--UofC_Calgary--chassis-icon.jpg" alt="1" type="image">
 +
              </a>
 +
 
 +
<a id="img-scroll3">
 +
              <img style="position:absolute;left:58%;top:80%;max-width: 15%;cursor: pointer;" src="https://static.igem.org/mediawiki/2016/a/a5/T--UofC_Calgary--device-icon.jpg" alt="1" type="image">
 +
              </a>
 +
 
 +
               <img style="width:100%; height: 100%" src="https://static.igem.org/mediawiki/2016/f/f3/T--UofC_Calgary--notebook.jpg" alt="bg">
 
                  
 
                  
 
             </div>
 
             </div>
−
         </div>          
+
         </div>
−
</div>
+
        </div><!-- END: LAYOUT/SLIDERS/REVO-SLIDER-1 -->
−
  <!--        <img alt="" src="https://static.igem.org/mediawiki/2016/f/f3/T--UofC_Calgary--notebook.jpg" data-bgposition="center center" data-bgfit="cover" data-bgrepeat="no-repeat" style="width: 100%; height: 100%;"> -->
+
        <!-- BEGIN: CONTENT/MISC/ABOUT-1 -->
−
 
+
<div class="c-content-box c-size-md c-bg-white">
−
<!-- END: LAYOUT/SLIDERS/REVO-SLIDER-1 -->
+
−
+
−
<!-- BEGIN: CONTENT/MISC/ABOUT-1 -->
+
−
<div class="c-content-box c-size-md c-bg-white" >
+
 
<div class="container">
 
<div class="container">
−
<div class="row">
+
<div class="col-md-12">
−
<div class="col-sm-12">
+
 
<!-- Begin: Title 1 component -->
 
<!-- Begin: Title 1 component -->
 
<div class="c-content-title-1">
 
<div class="c-content-title-1">
−
<h3 class="c-font-uppercase c-font-bold">Device</h3>
+
<a href="https://static.igem.org/mediawiki/2016/2/21/T--UofC_Calgary--BioTJournalFreeze.pdf"><h3 class="c-font-uppercase c-font-bold">BioTarget Notebook</h3></a>
 
<div class="c-line-left c-theme-bg">
 
<div class="c-line-left c-theme-bg">
 
</div>
 
</div>
 
</div>
 
</div>
−
<!-- End-->
+
<!-- End-->  
−
<head><meta content="text/html; charset=UTF-8" http-equiv="content-type"><style type="text/css">@import url('https://themes.googleusercontent.com/fonts/css?kit=M88JnubLobM--kNYN1H7JImz4LFx-WH96_kRiD6IAG4');.lst-kix_list_98-1>li:before{content:"o  "}.lst-kix_list_98-3>li:before{content:"\0025aa  "}.lst-kix_list_98-7>li:before{content:"\0025aa  "}.lst-kix_g5lskmm1i0dj-0>li{counter-increment:lst-ctn-kix_g5lskmm1i0dj-0}.lst-kix_list_60-0>li:before{content:"\0025cf  "}ol.lst-kix_list_118-8.start{counter-reset:lst-ctn-kix_list_118-8 0}.lst-kix_list_130-4>li:before{content:"\0025aa  "}.lst-kix_list_130-6>li:before{content:"\0025aa  "}.lst-kix_list_45-2>li{counter-increment:lst-ctn-kix_list_45-2}.lst-kix_list_98-5>li:before{content:"\0025aa  "}.lst-kix_list_119-7>li{counter-increment:lst-ctn-kix_list_119-7}.lst-kix_list_60-2>li:before{content:"\0025aa  "}ul.lst-kix_list_93-8{list-style-type:none}.lst-kix_list_42-1>li:before{content:"\0025cb  "}.lst-kix_list_112-3>li:before{content:"\0025cf  "}ul.lst-kix_list_93-7{list-style-type:none}ul.lst-kix_list_93-6{list-style-type:none}ul.lst-kix_list_105-3{list-style-type:none}ul.lst-kix_list_105-0{list-style-type:none}ul.lst-kix_list_93-1{list-style-type:none}ul.lst-kix_list_105-6{list-style-type:none}ul.lst-kix_list_93-0{list-style-type:none}ul.lst-kix_list_105-7{list-style-type:none}ul.lst-kix_list_105-4{list-style-type:none}ul.lst-kix_list_105-5{list-style-type:none}ul.lst-kix_list_93-5{list-style-type:none}ul.lst-kix_list_93-4{list-style-type:none}.lst-kix_list_42-7>li:before{content:"\0025cb  "}.lst-kix_list_112-5>li:before{content:"\0025aa  "}ul.lst-kix_list_93-3{list-style-type:none}ul.lst-kix_list_105-8{list-style-type:none}ul.lst-kix_list_93-2{list-style-type:none}.lst-kix_list_79-0>li:before{content:"\0025cf  "}.lst-kix_list_130-2>li:before{content:"\0025aa  "}.lst-kix_list_130-0>li:before{content:"\0025cf  "}.lst-kix_list_42-5>li:before{content:"\0025a0  "}.lst-kix_list_112-7>li:before{content:"\0025aa  "}.lst-kix_list_42-3>li:before{content:"\0025cf  "}.lst-kix_lvjn8glkfwf0-1>li:before{content:"\0025cb  "}ul.lst-kix_list_80-8{list-style-type:none}.lst-kix_list_79-6>li:before{content:"\0025cf  "}.lst-kix_list_79-8>li:before{content:"\0025a0  "}.lst-kix_lvjn8glkfwf0-3>li:before{content:"\0025cf  "}ul.lst-kix_list_27-0{list-style-type:none}.lst-kix_list_24-8>li:before{content:"\0025aa  "}ul.lst-kix_list_27-1{list-style-type:none}ul.lst-kix_list_27-2{list-style-type:none}ul.lst-kix_list_80-2{list-style-type:none}ul.lst-kix_list_80-3{list-style-type:none}ul.lst-kix_list_80-0{list-style-type:none}ul.lst-kix_list_80-1{list-style-type:none}.lst-kix_list_79-2>li:before{content:"\0025a0  "}ul.lst-kix_list_80-6{list-style-type:none}ul.lst-kix_list_80-7{list-style-type:none}ul.lst-kix_list_80-4{list-style-type:none}.lst-kix_list_24-2>li:before{content:"\0025aa  "}ul.lst-kix_list_80-5{list-style-type:none}.lst-kix_lvjn8glkfwf0-7>li:before{content:"\0025cb  "}.lst-kix_list_24-4>li:before{content:"\0025aa  "}.lst-kix_list_79-4>li:before{content:"\0025cb  "}ul.lst-kix_list_27-3{list-style-type:none}ol.lst-kix_list_118-3.start{counter-reset:lst-ctn-kix_list_118-3 0}.lst-kix_lvjn8glkfwf0-5>li:before{content:"\0025a0  "}ul.lst-kix_list_27-4{list-style-type:none}ul.lst-kix_list_27-5{list-style-type:none}ul.lst-kix_list_27-6{list-style-type:none}ul.lst-kix_list_27-7{list-style-type:none}ul.lst-kix_list_27-8{list-style-type:none}.lst-kix_list_24-6>li:before{content:"\0025aa  "}.lst-kix_list_23-6>li:before{content:"\0025aa  "}.lst-kix_list_23-2>li:before{content:"\0025aa  "}.lst-kix_list_23-0>li:before{content:"\0025cf  "}.lst-kix_list_23-8>li:before{content:"\0025aa  "}.lst-kix_1qgee6j7obt0-4>li:before{content:"\0025cb  "}.lst-kix_1qgee6j7obt0-2>li:before{content:"\0025a0  "}.lst-kix_list_24-0>li:before{content:"\0025cf  "}.lst-kix_1qgee6j7obt0-0>li:before{content:"\0025cf  "}.lst-kix_list_23-4>li:before{content:"\0025aa  "}.lst-kix_list_80-5>li:before{content:"\0025a0  "}.lst-kix_list_43-3>li:before{content:"\0025aa  "}.lst-kix_list_80-3>li:before{content:"\0025cf  "}.lst-kix_list_80-7>li:before{content:"\0025cb  "}.lst-kix_list_22-2>li:before{content:"\0025aa  "}.lst-kix_list_22-6>li:before{content:"\0025cf  "}.lst-kix_list_43-7>li:before{content:"\0025aa  "}.lst-kix_835ax5k7z1l9-7>li:before{content:"\0025cb  "}.lst-kix_list_43-1>li:before{content:"o  "}.lst-kix_list_22-0>li:before{content:"\0025cf  "}.lst-kix_list_22-8>li:before{content:"\0025aa  "}ol.lst-kix_list_102-1{list-style-type:none}ol.lst-kix_list_102-2{list-style-type:none}.lst-kix_1qgee6j7obt0-6>li:before{content:"\0025cf  "}ol.lst-kix_g5lskmm1i0dj-2.start{counter-reset:lst-ctn-kix_g5lskmm1i0dj-2 0}.lst-kix_1qgee6j7obt0-8>li:before{content:"\0025a0  "}.lst-kix_list_43-5>li:before{content:"\0025aa  "}.lst-kix_list_22-4>li:before{content:"o  "}.lst-kix_list_99-5>li:before{content:"\0025a0  "}.lst-kix_list_99-3>li:before{content:"\0025cf  "}.lst-kix_list_99-7>li:before{content:"\0025cb  "}.lst-kix_g5lskmm1i0dj-7>li{counter-increment:lst-ctn-kix_g5lskmm1i0dj-7}.lst-kix_list_78-2>li:before{content:"\0025a0  "}.lst-kix_list_78-6>li:before{content:"\0025cf  "}.lst-kix_list_99-1>li:before{content:"\0025cb  "}.lst-kix_835ax5k7z1l9-1>li:before{content:"\0025cb  "}.lst-kix_ee0fx9z4yp3a-1>li:before{content:"\0025cb  "}.lst-kix_list_62-8>li:before{content:"\0025aa  "}.lst-kix_list_41-7>li:before{content:"\0025cb  "}.lst-kix_list_78-0>li:before{content:"\0025cf  "}.lst-kix_list_78-8>li:before{content:"\0025a0  "}.lst-kix_61pipssxjd5z-8>li:before{content:"\0025a0  "}.lst-kix_835ax5k7z1l9-3>li:before{content:"\0025cf  "}.lst-kix_835ax5k7z1l9-5>li:before{content:"\0025a0  "}ul.lst-kix_6ppt4s25kk1y-0{list-style-type:none}.lst-kix_ee0fx9z4yp3a-5>li:before{content:"\0025a0  "}.lst-kix_ee0fx9z4yp3a-7>li:before{content:"\0025cb  "}.lst-kix_list_80-1>li:before{content:"\0025cb  "}ul.lst-kix_6ppt4s25kk1y-6{list-style-type:none}ul.lst-kix_6ppt4s25kk1y-5{list-style-type:none}ul.lst-kix_6ppt4s25kk1y-8{list-style-type:none}ul.lst-kix_6ppt4s25kk1y-7{list-style-type:none}.lst-kix_ee0fx9z4yp3a-3>li:before{content:"\0025cf  "}ol.lst-kix_list_120-7.start{counter-reset:lst-ctn-kix_list_120-7 0}ul.lst-kix_6ppt4s25kk1y-2{list-style-type:none}ul.lst-kix_6ppt4s25kk1y-1{list-style-type:none}.lst-kix_list_78-4>li:before{content:"\0025cb  "}ul.lst-kix_6ppt4s25kk1y-4{list-style-type:none}ul.lst-kix_6ppt4s25kk1y-3{list-style-type:none}.lst-kix_61pipssxjd5z-0>li:before{content:"\0025cf  "}.lst-kix_61pipssxjd5z-2>li:before{content:"\0025a0  "}.lst-kix_list_41-1>li:before{content:"\0025cb  "}.lst-kix_list_61-8>li:before{content:"\0025aa  "}.lst-kix_list_40-7>li:before{content:"\0025cb  "}.lst-kix_61pipssxjd5z-6>li:before{content:"\0025cf  "}.lst-kix_list_62-0>li:before{content:"\0025cf  "}.lst-kix_list_40-5>li:before{content:"\0025a0  "}.lst-kix_list_61-6>li:before{content:"\0025aa  "}.lst-kix_list_41-5>li:before{content:"\0025a0  "}.lst-kix_list_96-3>li:before{content:"\0025cf  "}.lst-kix_list_96-5>li:before{content:"\0025a0  "}.lst-kix_list_62-4>li:before{content:"\0025aa  "}.lst-kix_list_62-6>li:before{content:"\0025aa  "}.lst-kix_61pipssxjd5z-4>li:before{content:"\0025cb  "}.lst-kix_list_96-1>li:before{content:"\0025cb  "}.lst-kix_list_62-2>li:before{content:"\0025aa  "}.lst-kix_list_41-3>li:before{content:"\0025cf  "}ul.lst-kix_list_71-8{list-style-type:none}.lst-kix_list_60-8>li:before{content:"\0025aa  "}ul.lst-kix_list_71-6{list-style-type:none}.lst-kix_list_81-7>li:before{content:"\0025aa  "}ul.lst-kix_list_71-7{list-style-type:none}ul.lst-kix_list_127-3{list-style-type:none}ul.lst-kix_list_127-2{list-style-type:none}ul.lst-kix_list_127-1{list-style-type:none}.lst-kix_list_97-1>li:before{content:"\0025cb  "}ul.lst-kix_list_127-0{list-style-type:none}ul.lst-kix_list_71-0{list-style-type:none}ul.lst-kix_list_18-0{list-style-type:none}ul.lst-kix_list_127-7{list-style-type:none}.lst-kix_list_60-4>li:before{content:"\0025aa  "}ul.lst-kix_list_71-1{list-style-type:none}ul.lst-kix_list_127-6{list-style-type:none}.lst-kix_list_81-5>li:before{content:"\0025aa  "}ul.lst-kix_list_127-5{list-style-type:none}.lst-kix_list_96-7>li:before{content:"\0025cb  "}ul.lst-kix_list_127-4{list-style-type:none}ul.lst-kix_list_71-4{list-style-type:none}.lst-kix_list_60-6>li:before{content:"\0025aa  "}ul.lst-kix_list_71-5{list-style-type:none}ul.lst-kix_list_71-2{list-style-type:none}ul.lst-kix_list_71-3{list-style-type:none}.lst-kix_list_97-7>li:before{content:"\0025cb  "}ul.lst-kix_list_127-8{list-style-type:none}ul.lst-kix_list_18-8{list-style-type:none}.lst-kix_list_40-3>li:before{content:"\0025cf  "}ul.lst-kix_list_18-7{list-style-type:none}ul.lst-kix_list_18-6{list-style-type:none}ol.lst-kix_list_12-2.start{counter-reset:lst-ctn-kix_list_12-2 0}ul.lst-kix_list_18-5{list-style-type:none}ul.lst-kix_list_18-4{list-style-type:none}ul.lst-kix_list_18-3{list-style-type:none}ul.lst-kix_list_18-2{list-style-type:none}.lst-kix_list_61-0>li:before{content:"\0025cf  "}.lst-kix_list_61-4>li:before{content:"\0025aa  "}.lst-kix_list_97-5>li:before{content:"\0025a0  "}ul.lst-kix_list_18-1{list-style-type:none}.lst-kix_list_40-1>li:before{content:"\0025cb  "}.lst-kix_list_61-2>li:before{content:"\0025aa  "}.lst-kix_list_97-3>li:before{content:"\0025cf  "}.lst-kix_list_77-2>li:before{content:"\0025a0  "}ul.lst-kix_list_136-1{list-style-type:none}ul.lst-kix_list_136-0{list-style-type:none}ul.lst-kix_list_136-5{list-style-type:none}ul.lst-kix_list_136-4{list-style-type:none}ul.lst-kix_list_136-3{list-style-type:none}ul.lst-kix_list_136-2{list-style-type:none}.lst-kix_list_77-6>li:before{content:"\0025cf  "}ul.lst-kix_list_136-8{list-style-type:none}ul.lst-kix_list_136-7{list-style-type:none}ul.lst-kix_list_136-6{list-style-type:none}ol.lst-kix_list_107-4.start{counter-reset:lst-ctn-kix_list_107-4 0}.lst-kix_list_81-1>li:before{content:"o  "}ol.lst-kix_list_103-1.start{counter-reset:lst-ctn-kix_list_103-1 0}.lst-kix_list_21-8>li:before{content:"\0025aa  "}ol.lst-kix_list_133-0.start{counter-reset:lst-ctn-kix_list_133-0 0}.lst-kix_list_114-3>li:before{content:"\0025cf  "}.lst-kix_list_26-8>li:before{content:"\0025a0  "}ol.lst-kix_list_69-5.start{counter-reset:lst-ctn-kix_list_69-5 0}ul.lst-kix_list_101-2{list-style-type:none}ul.lst-kix_list_101-3{list-style-type:none}ul.lst-kix_list_101-0{list-style-type:none}.lst-kix_list_21-0>li:before{content:"\0025cf  "}ul.lst-kix_list_36-0{list-style-type:none}ul.lst-kix_list_101-1{list-style-type:none}ul.lst-kix_list_36-1{list-style-type:none}ul.lst-kix_list_101-6{list-style-type:none}ul.lst-kix_list_36-2{list-style-type:none}ul.lst-kix_list_101-7{list-style-type:none}ul.lst-kix_list_36-3{list-style-type:none}ul.lst-kix_list_101-4{list-style-type:none}ul.lst-kix_list_36-4{list-style-type:none}ul.lst-kix_list_101-5{list-style-type:none}.lst-kix_list_63-2>li:before{content:"\0025aa  "}ol.lst-kix_list_133-5.start{counter-reset:lst-ctn-kix_list_133-5 0}ul.lst-kix_list_101-8{list-style-type:none}.lst-kix_list_133-4>li:before{content:"" counter(lst-ctn-kix_list_133-4,decimal) ". "}.lst-kix_list_26-4>li:before{content:"\0025cb  "}.lst-kix_list_128-3>li:before{content:"\0025cf  "}.lst-kix_list_63-6>li:before{content:"\0025aa  "}ul.lst-kix_list_36-5{list-style-type:none}ul.lst-kix_list_36-6{list-style-type:none}ul.lst-kix_list_36-7{list-style-type:none}.lst-kix_list_21-4>li:before{content:"\0025aa  "}ul.lst-kix_list_36-8{list-style-type:none}.lst-kix_list_133-8>li:before{content:"" counter(lst-ctn-kix_list_133-8,decimal) ". "}.lst-kix_list_26-0>li:before{content:"\0025cf  "}.lst-kix_list_95-1>li:before{content:"\0025cb  "}ul.lst-kix_list_114-0{list-style-type:none}ul.lst-kix_list_23-0{list-style-type:none}ul.lst-kix_list_114-1{list-style-type:none}ul.lst-kix_list_23-1{list-style-type:none}ol.lst-kix_list_120-2.start{counter-reset:lst-ctn-kix_list_120-2 0}ul.lst-kix_list_23-2{list-style-type:none}ul.lst-kix_list_23-3{list-style-type:none}ul.lst-kix_list_114-4{list-style-type:none}ul.lst-kix_list_23-4{list-style-type:none}.lst-kix_list_128-7>li:before{content:"\0025cb  "}ul.lst-kix_list_114-5{list-style-type:none}ul.lst-kix_list_23-5{list-style-type:none}ul.lst-kix_list_114-2{list-style-type:none}ul.lst-kix_list_23-6{list-style-type:none}ul.lst-kix_list_114-3{list-style-type:none}ol.lst-kix_list_12-5{list-style-type:none}ul.lst-kix_list_114-8{list-style-type:none}ol.lst-kix_list_12-6{list-style-type:none}ol.lst-kix_list_12-7{list-style-type:none}ul.lst-kix_list_114-6{list-style-type:none}ol.lst-kix_list_12-8{list-style-type:none}ul.lst-kix_list_114-7{list-style-type:none}ol.lst-kix_list_12-1{list-style-type:none}ol.lst-kix_list_12-2{list-style-type:none}.lst-kix_list_59-1>li:before{content:"o  "}ol.lst-kix_list_12-3{list-style-type:none}.lst-kix_list_58-1>li:before{content:"o  "}ol.lst-kix_list_12-4{list-style-type:none}.lst-kix_list_115-7>li:before{content:"\0025aa  "}ol.lst-kix_list_45-6.start{counter-reset:lst-ctn-kix_list_45-6 0}ol.lst-kix_list_12-0{list-style-type:none}ul.lst-kix_list_23-7{list-style-type:none}.lst-kix_list_25-0>li:before{content:"\0025cf  "}.lst-kix_list_45-5>li:before{content:"" counter(lst-ctn-kix_list_45-5,decimal) ". "}ul.lst-kix_list_23-8{list-style-type:none}.lst-kix_list_129-3>li:before{content:"\0025cf  "}ol.lst-kix_g5lskmm1i0dj-7.start{counter-reset:lst-ctn-kix_g5lskmm1i0dj-7 0}.lst-kix_list_58-5>li:before{content:"\0025aa  "}.lst-kix_list_114-7>li:before{content:"\0025cb  "}ul.lst-kix_list_58-0{list-style-type:none}ul.lst-kix_list_58-2{list-style-type:none}ul.lst-kix_list_58-1{list-style-type:none}ul.lst-kix_list_58-4{list-style-type:none}ol.lst-kix_list_69-8{list-style-type:none}.lst-kix_list_39-0>li:before{content:"\0025cf  "}ul.lst-kix_list_58-3{list-style-type:none}ol.lst-kix_list_69-7{list-style-type:none}ol.lst-kix_list_69-6{list-style-type:none}ol.lst-kix_list_69-5{list-style-type:none}ol.lst-kix_list_69-4{list-style-type:none}ol.lst-kix_list_69-3{list-style-type:none}ol.lst-kix_list_69-2{list-style-type:none}.lst-kix_list_129-7>li:before{content:"\0025aa  "}ol.lst-kix_list_69-1{list-style-type:none}.lst-kix_list_44-1>li:before{content:"o  "}ol.lst-kix_list_69-0{list-style-type:none}.lst-kix_list_45-1>li:before{content:"o  "}.lst-kix_list_109-6>li:before{content:"\0025aa  "}ul.lst-kix_list_58-6{list-style-type:none}ul.lst-kix_list_58-5{list-style-type:none}ul.lst-kix_list_58-8{list-style-type:none}ul.lst-kix_list_58-7{list-style-type:none}.lst-kix_list_109-2>li:before{content:"" counter(lst-ctn-kix_list_109-2,lower-roman) ". "}.lst-kix_list_59-5>li:before{content:"\0025aa  "}.lst-kix_list_44-5>li:before{content:"\0025aa  "}.lst-kix_list_115-3>li:before{content:"\0025aa  "}.lst-kix_list_113-3>li:before{content:"\0025aa  "}.lst-kix_list_113-7>li:before{content:"\0025aa  "}ul.lst-kix_list_49-0{list-style-type:none}.lst-kix_list_134-4>li:before{content:"\0025aa  "}.lst-kix_list_134-8>li:before{content:"\0025aa  "}ul.lst-kix_list_49-2{list-style-type:none}ul.lst-kix_list_49-1{list-style-type:none}.lst-kix_list_27-4>li:before{content:"\0025aa  "}ul.lst-kix_list_7-5{list-style-type:none}ul.lst-kix_list_7-6{list-style-type:none}ul.lst-kix_list_7-3{list-style-type:none}ul.lst-kix_list_7-4{list-style-type:none}ul.lst-kix_list_7-7{list-style-type:none}ul.lst-kix_list_7-8{list-style-type:none}.lst-kix_list_39-4>li:before{content:"\0025cb  "}.lst-kix_list_39-8>li:before{content:"\0025a0  "}ul.lst-kix_list_49-4{list-style-type:none}ul.lst-kix_list_49-3{list-style-type:none}ul.lst-kix_list_49-6{list-style-type:none}ul.lst-kix_list_49-5{list-style-type:none}ul.lst-kix_list_7-1{list-style-type:none}ul.lst-kix_list_49-8{list-style-type:none}ul.lst-kix_list_7-2{list-style-type:none}.lst-kix_list_27-0>li:before{content:"\0025cf  "}ul.lst-kix_list_49-7{list-style-type:none}ul.lst-kix_list_7-0{list-style-type:none}.lst-kix_list_127-7>li:before{content:"\0025aa  "}.lst-kix_g5lskmm1i0dj-4>li:before{content:"" counter(lst-ctn-kix_g5lskmm1i0dj-4,lower-latin) ". "}.lst-kix_list_127-3>li:before{content:"\0025aa  "}ol.lst-kix_list_133-8{list-style-type:none}ol.lst-kix_list_133-7{list-style-type:none}.lst-kix_list_25-4>li:before{content:"\0025aa  "}ol.lst-kix_list_133-4{list-style-type:none}ol.lst-kix_list_133-3{list-style-type:none}ol.lst-kix_list_133-6{list-style-type:none}ol.lst-kix_list_133-5{list-style-type:none}.lst-kix_g5lskmm1i0dj-0>li:before{content:"" counter(lst-ctn-kix_g5lskmm1i0dj-0,decimal) ". "}ol.lst-kix_list_133-0{list-style-type:none}ol.lst-kix_list_133-2{list-style-type:none}.lst-kix_list_134-0>li:before{content:"\0025cf  "}.lst-kix_list_105-2>li{counter-increment:lst-ctn-kix_list_105-2}ol.lst-kix_list_133-1{list-style-type:none}.lst-kix_list_46-5>li:before{content:"\0025aa  "}.lst-kix_list_25-8>li:before{content:"\0025aa  "}.lst-kix_list_111-3>li:before{content:"\0025cf  "}.lst-kix_list_118-3>li{counter-increment:lst-ctn-kix_list_118-3}.lst-kix_list_132-4>li:before{content:"\0025cb  "}ol.lst-kix_list_120-6{list-style-type:none}ol.lst-kix_list_120-5{list-style-type:none}.lst-kix_list_111-7>li:before{content:"\0025cb  "}ol.lst-kix_list_120-8{list-style-type:none}ol.lst-kix_list_120-7{list-style-type:none}ol.lst-kix_list_120-2{list-style-type:none}ol.lst-kix_list_120-1{list-style-type:none}ol.lst-kix_list_120-4{list-style-type:none}ol.lst-kix_list_120-3{list-style-type:none}.lst-kix_list_28-8>li:before{content:"\0025aa  "}ol.lst-kix_list_120-0{list-style-type:none}.lst-kix_list_131-0>li:before{content:"\0025cf  "}.lst-kix_list_133-0>li:before{content:"" counter(lst-ctn-kix_list_133-0,decimal) ". "}.lst-kix_list_132-8>li:before{content:"\0025a0  "}.lst-kix_list_28-4>li:before{content:"\0025aa  "}ul.lst-kix_list_123-2{list-style-type:none}ul.lst-kix_list_123-3{list-style-type:none}ul.lst-kix_list_123-0{list-style-type:none}ul.lst-kix_list_123-1{list-style-type:none}.lst-kix_g5lskmm1i0dj-8>li:before{content:"" counter(lst-ctn-kix_g5lskmm1i0dj-8,lower-roman) ". "}.lst-kix_list_130-8>li:before{content:"\0025aa  "}ul.lst-kix_list_123-6{list-style-type:none}ul.lst-kix_list_123-7{list-style-type:none}ul.lst-kix_list_123-4{list-style-type:none}ul.lst-kix_list_123-5{list-style-type:none}ul.lst-kix_list_14-4{list-style-type:none}ul.lst-kix_list_14-3{list-style-type:none}ul.lst-kix_list_14-2{list-style-type:none}ul.lst-kix_list_123-8{list-style-type:none}ul.lst-kix_list_14-1{list-style-type:none}ul.lst-kix_list_14-0{list-style-type:none}.lst-kix_list_110-3>li:before{content:"\0025aa  "}.lst-kix_list_131-4>li:before{content:"\0025cb  "}.lst-kix_list_107-3>li{counter-increment:lst-ctn-kix_list_107-3}ul.lst-kix_list_14-8{list-style-type:none}ul.lst-kix_list_14-7{list-style-type:none}ul.lst-kix_list_14-6{list-style-type:none}ul.lst-kix_list_14-5{list-style-type:none}.lst-kix_list_28-0>li:before{content:"\0025cf  "}.lst-kix_list_131-8>li:before{content:"\0025a0  "}.lst-kix_list_27-8>li:before{content:"\0025aa  "}.lst-kix_list_110-7>li:before{content:"\0025aa  "}.lst-kix_list_132-0>li:before{content:"\0025cf  "}ul.lst-kix_list_89-2{list-style-type:none}ul.lst-kix_list_132-5{list-style-type:none}ul.lst-kix_list_89-1{list-style-type:none}.lst-kix_list_19-1>li:before{content:"\0025cb  "}ul.lst-kix_list_132-4{list-style-type:none}ol.lst-kix_list_107-7.start{counter-reset:lst-ctn-kix_list_107-7 0}ul.lst-kix_list_89-0{list-style-type:none}ul.lst-kix_list_132-3{list-style-type:none}.lst-kix_list_126-3>li:before{content:"\0025aa  "}.lst-kix_list_126-5>li:before{content:"\0025aa  "}ul.lst-kix_list_132-2{list-style-type:none}ul.lst-kix_list_89-6{list-style-type:none}ul.lst-kix_list_89-5{list-style-type:none}ul.lst-kix_list_132-8{list-style-type:none}ul.lst-kix_list_89-4{list-style-type:none}.lst-kix_list_93-5>li:before{content:"\0025a0  "}ul.lst-kix_list_132-7{list-style-type:none}ul.lst-kix_list_89-3{list-style-type:none}ul.lst-kix_list_132-6{list-style-type:none}.lst-kix_list_56-1>li:before{content:"o  "}.lst-kix_list_19-3>li:before{content:"\0025cf  "}.lst-kix_list_56-7>li:before{content:"\0025aa  "}.lst-kix_list_47-5>li:before{content:"\0025aa  "}.lst-kix_list_65-0>li:before{content:"\0025cf  "}.lst-kix_list_135-4>li:before{content:"\0025cb  "}ul.lst-kix_list_89-8{list-style-type:none}ul.lst-kix_list_89-7{list-style-type:none}ul.lst-kix_list_132-1{list-style-type:none}ul.lst-kix_list_132-0{list-style-type:none}.lst-kix_list_93-7>li:before{content:"\0025cb  "}ul.lst-kix_list_32-1{list-style-type:none}.lst-kix_list_84-1>li:before{content:"o  "}ul.lst-kix_list_32-2{list-style-type:none}ul.lst-kix_list_32-3{list-style-type:none}ul.lst-kix_list_32-4{list-style-type:none}ul.lst-kix_list_32-5{list-style-type:none}.lst-kix_list_120-3>li{counter-increment:lst-ctn-kix_list_120-3}.lst-kix_list_84-3>li:before{content:"\0025aa  "}ul.lst-kix_list_32-6{list-style-type:none}ul.lst-kix_list_32-7{list-style-type:none}ul.lst-kix_list_32-8{list-style-type:none}.lst-kix_list_47-3>li:before{content:"\0025aa  "}ul.lst-kix_list_32-0{list-style-type:none}.lst-kix_list_117-1>li:before{content:"" counter(lst-ctn-kix_list_117-1,decimal) ". "}.lst-kix_list_37-0>li:before{content:"\0025cf  "}.lst-kix_list_107-2>li:before{content:"" counter(lst-ctn-kix_list_107-2,lower-roman) ". "}.lst-kix_list_117-7>li:before{content:"" counter(lst-ctn-kix_list_117-7,decimal) ". "}.lst-kix_list_37-8>li:before{content:"\0025aa  "}ul.lst-kix_list_110-4{list-style-type:none}ul.lst-kix_list_110-5{list-style-type:none}ul.lst-kix_list_110-2{list-style-type:none}ul.lst-kix_list_110-3{list-style-type:none}.lst-kix_list_120-7>li{counter-increment:lst-ctn-kix_list_120-7}.lst-kix_list_37-6>li:before{content:"\0025aa  "}ul.lst-kix_list_110-8{list-style-type:none}ol.lst-kix_list_107-8{list-style-type:none}ul.lst-kix_list_110-6{list-style-type:none}ul.lst-kix_list_110-7{list-style-type:none}.lst-kix_list_108-0>li:before{content:"\0025cf  "}ol.lst-kix_list_107-4{list-style-type:none}.lst-kix_g5lskmm1i0dj-2>li{counter-increment:lst-ctn-kix_g5lskmm1i0dj-2}ol.lst-kix_list_133-2.start{counter-reset:lst-ctn-kix_list_133-2 0}ol.lst-kix_list_107-5{list-style-type:none}ol.lst-kix_list_107-6{list-style-type:none}.lst-kix_list_66-4>li:before{content:"\0025aa  "}.lst-kix_list_107-4>li:before{content:"" counter(lst-ctn-kix_list_107-4,lower-latin) ". "}ol.lst-kix_list_107-7{list-style-type:none}ol.lst-kix_list_107-0{list-style-type:none}.lst-kix_list_136-8>li:before{content:"\0025aa  "}ol.lst-kix_list_107-1{list-style-type:none}ol.lst-kix_list_107-2.start{counter-reset:lst-ctn-kix_list_107-2 0}ol.lst-kix_list_107-2{list-style-type:none}ol.lst-kix_list_107-3{list-style-type:none}.lst-kix_list_116-5>li:before{content:"\0025aa  "}.lst-kix_list_46-1>li:before{content:"o  "}.lst-kix_list_69-5>li{counter-increment:lst-ctn-kix_list_69-5}.lst-kix_list_66-6>li:before{content:"\0025aa  "}.lst-kix_list_116-3>li:before{content:"\0025aa  "}ul.lst-kix_list_110-0{list-style-type:none}ul.lst-kix_list_110-1{list-style-type:none}ul.lst-kix_list_54-2{list-style-type:none}.lst-kix_list_92-1>li:before{content:"\0025cb  "}ul.lst-kix_list_54-1{list-style-type:none}ul.lst-kix_list_54-4{list-style-type:none}ul.lst-kix_list_54-3{list-style-type:none}ul.lst-kix_list_54-6{list-style-type:none}.lst-kix_list_65-8>li:before{content:"\0025aa  "}ul.lst-kix_list_54-5{list-style-type:none}ul.lst-kix_list_54-8{list-style-type:none}ul.lst-kix_list_54-7{list-style-type:none}.lst-kix_list_65-2>li:before{content:"\0025aa  "}.lst-kix_list_135-6>li:before{content:"\0025cf  "}.lst-kix_list_92-3>li:before{content:"\0025cf  "}.lst-kix_list_136-0>li:before{content:"\0025cf  "}ul.lst-kix_list_54-0{list-style-type:none}.lst-kix_list_108-6>li:before{content:"\0025aa  "}.lst-kix_list_136-2>li:before{content:"\0025aa  "}.lst-kix_list_38-2>li:before{content:"\0025aa  "}.lst-kix_list_38-4>li:before{content:"\0025aa  "}.lst-kix_list_108-8>li:before{content:"\0025aa  "}.lst-kix_list_118-3>li:before{content:"" counter(lst-ctn-kix_list_118-3,decimal) ". "}.lst-kix_list_69-1>li{counter-increment:lst-ctn-kix_list_69-1}.lst-kix_list_64-4>li:before{content:"\0025aa  "}ul.lst-kix_list_45-1{list-style-type:none}.lst-kix_g5lskmm1i0dj-5>li{counter-increment:lst-ctn-kix_g5lskmm1i0dj-5}ul.lst-kix_list_3-7{list-style-type:none}ul.lst-kix_list_3-8{list-style-type:none}.lst-kix_list_73-2>li:before{content:"\0025a0  "}.lst-kix_list_85-7>li:before{content:"\0025aa  "}ul.lst-kix_list_3-1{list-style-type:none}ul.lst-kix_list_3-2{list-style-type:none}.lst-kix_list_64-6>li:before{content:"\0025aa  "}ul.lst-kix_list_3-0{list-style-type:none}.lst-kix_list_85-5>li:before{content:"\0025aa  "}.lst-kix_list_94-1>li:before{content:"\0025cb  "}ul.lst-kix_list_3-5{list-style-type:none}.lst-kix_list_118-5>li:before{content:"" counter(lst-ctn-kix_list_118-5,decimal) ". "}ul.lst-kix_list_3-6{list-style-type:none}.lst-kix_list_73-0>li:before{content:"\0025cf  "}ul.lst-kix_list_3-3{list-style-type:none}ul.lst-kix_list_3-4{list-style-type:none}.lst-kix_list_57-5>li:before{content:"\0025aa  "}.lst-kix_list_36-4>li:before{content:"\0025cb  "}.lst-kix_list_109-2>li{counter-increment:lst-ctn-kix_list_109-2}.lst-kix_list_94-3>li:before{content:"\0025cf  "}.lst-kix_list_107-5>li{counter-increment:lst-ctn-kix_list_107-5}.lst-kix_list_83-7>li:before{content:"\0025aa  "}.lst-kix_list_36-2>li:before{content:"\0025a0  "}.lst-kix_list_57-3>li:before{content:"\0025cf  "}.lst-kix_list_73-8>li:before{content:"\0025a0  "}ul.lst-kix_list_67-1{list-style-type:none}ul.lst-kix_list_67-2{list-style-type:none}ul.lst-kix_list_67-0{list-style-type:none}ul.lst-kix_list_67-5{list-style-type:none}ul.lst-kix_list_67-6{list-style-type:none}ul.lst-kix_list_67-3{list-style-type:none}.lst-kix_list_95-7>li:before{content:"\0025cb  "}ul.lst-kix_list_67-4{list-style-type:none}.lst-kix_list_74-6>li:before{content:"\0025aa  "}.lst-kix_list_74-4>li:before{content:"\0025aa  "}.lst-kix_list_95-5>li:before{content:"\0025a0  "}.lst-kix_list_83-5>li:before{content:"\0025aa  "}.lst-kix_list_20-4>li:before{content:"\0025aa  "}.lst-kix_list_20-2>li:before{content:"\0025aa  "}.lst-kix_list_75-0>li:before{content:"\0025cf  "}.lst-kix_list_104-1>li{counter-increment:lst-ctn-kix_list_104-1}ul.lst-kix_list_67-7{list-style-type:none}ul.lst-kix_list_67-8{list-style-type:none}.lst-kix_list_75-2>li:before{content:"\0025aa  "}.lst-kix_list_54-1>li:before{content:"o  "}ul.lst-kix_list_10-0{list-style-type:none}ul.lst-kix_list_10-8{list-style-type:none}ol.lst-kix_list_118-0.start{counter-reset:lst-ctn-kix_list_118-0 0}ul.lst-kix_list_10-7{list-style-type:none}ul.lst-kix_list_10-6{list-style-type:none}ul.lst-kix_list_10-5{list-style-type:none}.lst-kix_list_55-5>li:before{content:"\0025aa  "}ul.lst-kix_list_10-4{list-style-type:none}.lst-kix_list_76-6>li:before{content:"\0025aa  "}ul.lst-kix_list_10-3{list-style-type:none}ul.lst-kix_list_10-2{list-style-type:none}ul.lst-kix_list_10-1{list-style-type:none}.lst-kix_list_82-3>li:before{content:"\0025aa  "}.lst-kix_list_82-1>li:before{content:"o  "}.lst-kix_list_54-7>li:before{content:"\0025aa  "}.lst-kix_list_75-8>li:before{content:"\0025aa  "}.lst-kix_list_76-4>li:before{content:"\0025aa  "}.lst-kix_list_55-3>li:before{content:"\0025aa  "}.lst-kix_list_119-7>li:before{content:"" counter(lst-ctn-kix_list_119-7,decimal) ". "}ul.lst-kix_list_85-6{list-style-type:none}.lst-kix_list_105-4>li:before{content:"\0025aa  "}ul.lst-kix_list_85-5{list-style-type:none}ul.lst-kix_list_85-4{list-style-type:none}ul.lst-kix_list_85-3{list-style-type:none}ul.lst-kix_list_85-8{list-style-type:none}.lst-kix_list_100-5>li:before{content:"\0025a0  "}ul.lst-kix_list_85-7{list-style-type:none}.lst-kix_list_35-6>li:before{content:"\0025aa  "}.lst-kix_list_77-0>li:before{content:"\0025cf  "}.lst-kix_list_77-8>li:before{content:"\0025a0  "}ul.lst-kix_list_85-2{list-style-type:none}ul.lst-kix_list_85-1{list-style-type:none}ul.lst-kix_list_85-0{list-style-type:none}.lst-kix_list_3-2>li:before{content:"\0025a0  "}.lst-kix_list_8-1>li:before{content:"o  "}.lst-kix_list_119-1>li:before{content:"" counter(lst-ctn-kix_list_119-1,decimal) ". "}.lst-kix_list_30-7>li:before{content:"o  "}.lst-kix_list_72-6>li:before{content:"\0025aa  "}.lst-kix_list_69-8>li{counter-increment:lst-ctn-kix_list_69-8}ol.lst-kix_list_118-5.start{counter-reset:lst-ctn-kix_list_118-5 0}.lst-kix_list_133-6>li:before{content:"" counter(lst-ctn-kix_list_133-6,decimal) ". "}.lst-kix_list_26-2>li:before{content:"\0025a0  "}.lst-kix_list_21-6>li:before{content:"\0025aa  "}.lst-kix_list_68-4>li:before{content:"\0025aa  "}.lst-kix_list_123-1>li:before{content:"\0025cb  "}.lst-kix_list_63-0>li:before{content:"\0025cf  "}.lst-kix_list_63-8>li:before{content:"\0025aa  "}.lst-kix_list_90-3>li:before{content:"\0025cf  "}.lst-kix_6ppt4s25kk1y-3>li:before{content:"\0025cf  "}.lst-kix_list_106-1>li{counter-increment:lst-ctn-kix_list_106-1}.lst-kix_list_58-7>li:before{content:"o  "}.lst-kix_list_87-5>li:before{content:"\0025aa  "}.lst-kix_list_128-5>li:before{content:"\0025a0  "}.lst-kix_list_17-1>li:before{content:"\0025cb  "}.lst-kix_list_45-3>li:before{content:"" counter(lst-ctn-kix_list_45-3,decimal) ". "}.lst-kix_list_91-7>li:before{content:"\0025cb  "}ol.lst-kix_list_103-1{list-style-type:none}ol.lst-kix_list_103-2{list-style-type:none}.lst-kix_list_129-1>li:before{content:"o  "}.lst-kix_list_67-0>li:before{content:"\0025cf  "}.lst-kix_list_16-5>li:before{content:"\0025a0  "}.lst-kix_list_117-4>li{counter-increment:lst-ctn-kix_list_117-4}ul.lst-kix_list_50-6{list-style-type:none}ul.lst-kix_list_50-5{list-style-type:none}ul.lst-kix_list_50-8{list-style-type:none}ul.lst-kix_list_50-7{list-style-type:none}.lst-kix_list_44-7>li:before{content:"\0025aa  "}.lst-kix_list_86-1>li:before{content:"o  "}.lst-kix_list_114-5>li:before{content:"\0025a0  "}ul.lst-kix_list_50-0{list-style-type:none}ul.lst-kix_list_50-2{list-style-type:none}ul.lst-kix_list_50-1{list-style-type:none}ul.lst-kix_list_50-4{list-style-type:none}.lst-kix_list_71-2>li:before{content:"\0025a0  "}ul.lst-kix_list_50-3{list-style-type:none}.lst-kix_list_59-3>li:before{content:"\0025aa  "}.lst-kix_list_115-1>li:before{content:"o  "}.lst-kix_list_109-4>li:before{content:"\0025aa  "}ul.lst-kix_list_41-4{list-style-type:none}.lst-kix_list_2-6>li:before{content:"\0025cf  "}ul.lst-kix_list_41-3{list-style-type:none}ul.lst-kix_list_41-6{list-style-type:none}.lst-kix_list_69-0>li:before{content:"" counter(lst-ctn-kix_list_69-0,decimal) ". "}ul.lst-kix_list_41-5{list-style-type:none}ul.lst-kix_list_41-8{list-style-type:none}ul.lst-kix_list_41-7{list-style-type:none}.lst-kix_list_7-5>li:before{content:"\0025aa  "}.lst-kix_list_27-6>li:before{content:"\0025aa  "}ul.lst-kix_list_41-0{list-style-type:none}ul.lst-kix_list_41-2{list-style-type:none}ul.lst-kix_list_41-1{list-style-type:none}.lst-kix_list_133-6>li{counter-increment:lst-ctn-kix_list_133-6}.lst-kix_list_18-5>li:before{content:"\0025a0  "}.lst-kix_list_13-6>li:before{content:"\0025aa  "}.lst-kix_list_119-0>li{counter-increment:lst-ctn-kix_list_119-0}.lst-kix_list_122-5>li:before{content:"\0025a0  "}.lst-kix_list_127-1>li:before{content:"\0025cf  "}.lst-kix_list_106-0>li:before{content:"\0025cf  "}.lst-kix_list_39-6>li:before{content:"\0025cf  "}ul.lst-kix_list_76-3{list-style-type:none}ul.lst-kix_list_76-4{list-style-type:none}ul.lst-kix_list_76-1{list-style-type:none}ul.lst-kix_list_76-2{list-style-type:none}ul.lst-kix_list_76-7{list-style-type:none}ul.lst-kix_list_76-8{list-style-type:none}.lst-kix_list_120-0>li{counter-increment:lst-ctn-kix_list_120-0}ul.lst-kix_list_76-5{list-style-type:none}ul.lst-kix_list_76-6{list-style-type:none}.lst-kix_g5lskmm1i0dj-2>li:before{content:"" counter(lst-ctn-kix_g5lskmm1i0dj-2,lower-roman) ". "}.lst-kix_list_31-3>li:before{content:"\0025cf  "}ul.lst-kix_list_76-0{list-style-type:none}.lst-kix_list_10-2>li:before{content:"\0025aa  "}.lst-kix_list_4-6>li:before{content:"\0025cf  "}.lst-kix_list_113-1>li:before{content:"o  "}.lst-kix_list_67-8>li:before{content:"\0025aa  "}.lst-kix_list_25-6>li:before{content:"\0025aa  "}.lst-kix_list_134-2>li:before{content:"\0025aa  "}.lst-kix_list_106-8>li:before{content:"\0025aa  "}.lst-kix_list_46-7>li:before{content:"\0025aa  "}ul.lst-kix_list_63-5{list-style-type:none}ul.lst-kix_list_63-6{list-style-type:none}ul.lst-kix_list_63-3{list-style-type:none}ul.lst-kix_list_63-4{list-style-type:none}.lst-kix_list_111-1>li:before{content:"\0025cb  "}ol.lst-kix_list_105-2.start{counter-reset:lst-ctn-kix_list_105-2 0}ul.lst-kix_list_63-7{list-style-type:none}.lst-kix_list_132-2>li:before{content:"\0025a0  "}ul.lst-kix_list_63-8{list-style-type:none}.lst-kix_list_12-2>li{counter-increment:lst-ctn-kix_list_12-2}ul.lst-kix_list_63-1{list-style-type:none}ul.lst-kix_list_63-2{list-style-type:none}.lst-kix_list_9-5>li:before{content:"\0025aa  "}.lst-kix_list_29-6>li:before{content:"\0025aa  "}ul.lst-kix_list_63-0{list-style-type:none}.lst-kix_list_124-5>li:before{content:"\0025a0  "}.lst-kix_list_103-4>li:before{content:"\0025aa  "}.lst-kix_list_12-2>li:before{content:"" counter(lst-ctn-kix_list_12-2,decimal) ". "}.lst-kix_list_11-6>li:before{content:"\0025aa  "}ol.lst-kix_list_118-6.start{counter-reset:lst-ctn-kix_list_118-6 0}.lst-kix_list_32-7>li:before{content:"\0025cb  "}.lst-kix_list_1-2>li:before{content:"\0025a0  "}ul.lst-kix_list_98-4{list-style-type:none}ul.lst-kix_list_98-3{list-style-type:none}ul.lst-kix_list_98-2{list-style-type:none}.lst-kix_list_49-3>li:before{content:"\0025aa  "}ul.lst-kix_list_98-1{list-style-type:none}ul.lst-kix_list_98-8{list-style-type:none}ul.lst-kix_list_98-7{list-style-type:none}.lst-kix_list_104-0>li:before{content:"\0025cf  "}ul.lst-kix_list_98-6{list-style-type:none}ul.lst-kix_list_98-5{list-style-type:none}.lst-kix_list_125-1>li:before{content:"\0025cb  "}ul.lst-kix_list_98-0{list-style-type:none}.lst-kix_list_110-5>li:before{content:"\0025aa  "}.lst-kix_list_69-8>li:before{content:"" counter(lst-ctn-kix_list_69-8,decimal) ". "}.lst-kix_list_131-6>li:before{content:"\0025cf  "}.lst-kix_list_48-7>li:before{content:"\0025aa  "}.lst-kix_list_102-2>li{counter-increment:lst-ctn-kix_list_102-2}.lst-kix_list_104-8>li:before{content:"\0025aa  "}.lst-kix_list_28-2>li:before{content:"\0025aa  "}.lst-kix_list_51-4>li:before{content:"\0025cb  "}.lst-kix_list_14-1>li:before{content:"o  "}.lst-kix_list_121-5>li:before{content:"\0025aa  "}.lst-kix_list_14-4>li:before{content:"\0025aa  "}ol.lst-kix_list_120-0.start{counter-reset:lst-ctn-kix_list_120-0 0}.lst-kix_list_51-1>li:before{content:"\0025cb  "}.lst-kix_list_14-5>li:before{content:"\0025aa  "}.lst-kix_list_14-7>li:before{content:"\0025aa  "}ol.lst-kix_list_45-4.start{counter-reset:lst-ctn-kix_list_45-4 0}.lst-kix_list_121-8>li:before{content:"\0025aa  "}.lst-kix_list_118-6>li{counter-increment:lst-ctn-kix_list_118-6}.lst-kix_list_89-8>li:before{content:"\0025a0  "}.lst-kix_list_89-7>li:before{content:"\0025cb  "}.lst-kix_list_51-8>li:before{content:"\0025a0  "}.lst-kix_list_51-7>li:before{content:"\0025cb  "}ol.lst-kix_list_133-8.start{counter-reset:lst-ctn-kix_list_133-8 0}ul.lst-kix_list_70-7{list-style-type:none}ul.lst-kix_list_70-8{list-style-type:none}ul.lst-kix_list_128-2{list-style-type:none}ul.lst-kix_list_128-1{list-style-type:none}ul.lst-kix_list_128-0{list-style-type:none}ul.lst-kix_list_70-1{list-style-type:none}ul.lst-kix_list_17-1{list-style-type:none}ul.lst-kix_list_128-6{list-style-type:none}ul.lst-kix_list_70-2{list-style-type:none}ul.lst-kix_list_17-0{list-style-type:none}ul.lst-kix_list_128-5{list-style-type:none}.lst-kix_fahi2s4j7zmm-8>li:before{content:"\0025a0  "}ul.lst-kix_list_128-4{list-style-type:none}ul.lst-kix_list_70-0{list-style-type:none}.lst-kix_list_89-4>li:before{content:"\0025cb  "}ul.lst-kix_list_128-3{list-style-type:none}ul.lst-kix_list_70-5{list-style-type:none}ul.lst-kix_list_70-6{list-style-type:none}.lst-kix_fahi2s4j7zmm-6>li:before{content:"\0025cf  "}ul.lst-kix_list_70-3{list-style-type:none}ul.lst-kix_list_128-8{list-style-type:none}.lst-kix_list_102-1>li:before{content:"" counter(lst-ctn-kix_list_102-1,decimal) ". "}ul.lst-kix_list_70-4{list-style-type:none}.lst-kix_list_89-5>li:before{content:"\0025a0  "}ul.lst-kix_list_128-7{list-style-type:none}ul.lst-kix_list_17-8{list-style-type:none}.lst-kix_list_102-4>li:before{content:"\0025aa  "}ul.lst-kix_list_17-7{list-style-type:none}.lst-kix_list_32-3>li:before{content:"\0025cf  "}ul.lst-kix_list_17-6{list-style-type:none}ul.lst-kix_list_17-5{list-style-type:none}ul.lst-kix_list_17-4{list-style-type:none}ul.lst-kix_list_17-3{list-style-type:none}.lst-kix_list_14-8>li:before{content:"\0025aa  "}ul.lst-kix_list_17-2{list-style-type:none}.lst-kix_list_32-0>li:before{content:"\0025cf  "}.lst-kix_list_89-1>li:before{content:"\0025cb  "}ol.lst-kix_list_117-4.start{counter-reset:lst-ctn-kix_list_117-4 0}.lst-kix_list_70-2>li:before{content:"\0025aa  "}.lst-kix_list_5-1>li:before{content:"o  "}.lst-kix_list_5-7>li:before{content:"\0025aa  "}ul.lst-kix_list_8-4{list-style-type:none}ul.lst-kix_list_8-5{list-style-type:none}.lst-kix_list_5-8>li:before{content:"\0025aa  "}ul.lst-kix_list_8-2{list-style-type:none}.lst-kix_list_70-8>li:before{content:"\0025aa  "}ul.lst-kix_list_8-3{list-style-type:none}ul.lst-kix_list_8-8{list-style-type:none}.lst-kix_fahi2s4j7zmm-5>li:before{content:"\0025a0  "}ul.lst-kix_list_8-6{list-style-type:none}.lst-kix_list_88-2>li:before{content:"\0025aa  "}ul.lst-kix_list_8-7{list-style-type:none}.lst-kix_list_5-4>li:before{content:"\0025aa  "}ol.lst-kix_list_104-1.start{counter-reset:lst-ctn-kix_list_104-1 0}.lst-kix_list_5-5>li:before{content:"\0025aa  "}ul.lst-kix_list_8-0{list-style-type:none}ul.lst-kix_list_8-1{list-style-type:none}.lst-kix_list_120-2>li:before{content:"" counter(lst-ctn-kix_list_120-2,decimal) ". "}.lst-kix_fahi2s4j7zmm-2>li:before{content:"\0025a0  "}.lst-kix_list_70-5>li:before{content:"\0025aa  "}.lst-kix_list_120-3>li:before{content:"" counter(lst-ctn-kix_list_120-3,decimal) ". "}.lst-kix_list_50-1>li:before{content:"o  "}.lst-kix_list_50-2>li:before{content:"\0025aa  "}ul.lst-kix_list_92-8{list-style-type:none}ul.lst-kix_list_92-7{list-style-type:none}.lst-kix_list_6-1>li:before{content:"o  "}.lst-kix_list_6-3>li:before{content:"\0025aa  "}ul.lst-kix_list_39-0{list-style-type:none}.lst-kix_list_6-0>li:before{content:"\0025cf  "}.lst-kix_list_6-4>li:before{content:"\0025aa  "}ul.lst-kix_list_39-1{list-style-type:none}ul.lst-kix_list_106-0{list-style-type:none}ul.lst-kix_list_92-2{list-style-type:none}ul.lst-kix_list_106-5{list-style-type:none}ul.lst-kix_list_92-1{list-style-type:none}ul.lst-kix_list_106-6{list-style-type:none}ul.lst-kix_list_92-0{list-style-type:none}ul.lst-kix_list_106-3{list-style-type:none}ul.lst-kix_list_106-4{list-style-type:none}ul.lst-kix_list_92-6{list-style-type:none}ul.lst-kix_list_92-5{list-style-type:none}.lst-kix_list_120-6>li:before{content:"" counter(lst-ctn-kix_list_120-6,decimal) ". "}ul.lst-kix_list_92-4{list-style-type:none}ul.lst-kix_list_106-7{list-style-type:none}ul.lst-kix_list_92-3{list-style-type:none}ul.lst-kix_list_106-8{list-style-type:none}.lst-kix_list_50-8>li:before{content:"\0025aa  "}.lst-kix_list_121-2>li:before{content:"\0025aa  "}ul.lst-kix_list_39-2{list-style-type:none}ul.lst-kix_list_39-3{list-style-type:none}.lst-kix_list_50-5>li:before{content:"\0025aa  "}ul.lst-kix_list_39-4{list-style-type:none}.lst-kix_list_6-7>li:before{content:"\0025aa  "}ul.lst-kix_list_39-5{list-style-type:none}ul.lst-kix_list_39-6{list-style-type:none}ul.lst-kix_list_39-7{list-style-type:none}ul.lst-kix_list_39-8{list-style-type:none}.lst-kix_list_6-6>li:before{content:"\0025aa  "}ul.lst-kix_list_83-8{list-style-type:none}.lst-kix_list_69-1>li:before{content:"" counter(lst-ctn-kix_list_69-1,decimal) ". "}ul.lst-kix_list_83-7{list-style-type:none}ul.lst-kix_list_115-0{list-style-type:none}ul.lst-kix_list_83-6{list-style-type:none}ul.lst-kix_list_83-5{list-style-type:none}.lst-kix_list_7-6>li:before{content:"\0025aa  "}ul.lst-kix_list_115-3{list-style-type:none}ul.lst-kix_list_115-4{list-style-type:none}ul.lst-kix_list_115-1{list-style-type:none}ul.lst-kix_list_115-2{list-style-type:none}ul.lst-kix_list_83-0{list-style-type:none}ul.lst-kix_list_115-7{list-style-type:none}ul.lst-kix_list_115-8{list-style-type:none}ul.lst-kix_list_115-5{list-style-type:none}.lst-kix_list_7-2>li:before{content:"\0025aa  "}ul.lst-kix_list_115-6{list-style-type:none}ul.lst-kix_list_83-4{list-style-type:none}ul.lst-kix_list_83-3{list-style-type:none}ul.lst-kix_list_83-2{list-style-type:none}ul.lst-kix_list_83-1{list-style-type:none}.lst-kix_list_101-1>li:before{content:"o  "}.lst-kix_list_34-8>li:before{content:"\0025aa  "}.lst-kix_list_31-0>li:before{content:"\0025cf  "}.lst-kix_list_12-6>li{counter-increment:lst-ctn-kix_list_12-6}ol.lst-kix_list_118-1.start{counter-reset:lst-ctn-kix_list_118-1 0}.lst-kix_list_101-5>li:before{content:"\0025aa  "}.lst-kix_list_122-4>li:before{content:"\0025cb  "}.lst-kix_list_52-7>li:before{content:"\0025aa  "}.lst-kix_list_52-3>li:before{content:"\0025aa  "}.lst-kix_list_31-4>li:before{content:"\0025cb  "}.lst-kix_list_15-7>li:before{content:"\0025cb  "}.lst-kix_list_122-8>li:before{content:"\0025a0  "}.lst-kix_list_4-5>li:before{content:"\0025a0  "}.lst-kix_list_15-1>li:before{content:"\0025cb  "}.lst-kix_list_15-3>li:before{content:"\0025cf  "}.lst-kix_list_69-0>li{counter-increment:lst-ctn-kix_list_69-0}.lst-kix_list_88-8>li:before{content:"\0025aa  "}.lst-kix_tn8cl5j8lycz-7>li:before{content:"\0025cb  "}ol.lst-kix_g5lskmm1i0dj-4.start{counter-reset:lst-ctn-kix_g5lskmm1i0dj-4 0}.lst-kix_list_103-3>li:before{content:"\0025aa  "}.lst-kix_list_102-7>li:before{content:"\0025aa  "}.lst-kix_list_53-5>li:before{content:"\0025aa  "}.lst-kix_list_119-3>li{counter-increment:lst-ctn-kix_list_119-3}.lst-kix_list_103-7>li:before{content:"\0025aa  "}.lst-kix_list_133-3>li{counter-increment:lst-ctn-kix_list_133-3}.lst-kix_list_12-3>li:before{content:"" counter(lst-ctn-kix_list_12-3,decimal) ". "}.lst-kix_list_32-6>li:before{content:"\0025cf  "}.lst-kix_list_33-2>li:before{content:"\0025aa  "}.lst-kix_list_119-4>li{counter-increment:lst-ctn-kix_list_119-4}.lst-kix_tn8cl5j8lycz-1>li:before{content:"\0025cb  "}.lst-kix_list_117-8>li{counter-increment:lst-ctn-kix_list_117-8}.lst-kix_list_34-4>li:before{content:"\0025aa  "}.lst-kix_list_104-3>li:before{content:"\0025aa  "}.lst-kix_list_13-5>li:before{content:"\0025aa  "}ol.lst-kix_list_120-5.start{counter-reset:lst-ctn-kix_list_120-5 0}.lst-kix_list_69-7>li:before{content:"" counter(lst-ctn-kix_list_69-7,decimal) ". "}.lst-kix_list_33-6>li:before{content:"\0025aa  "}.lst-kix_list_120-8>li{counter-increment:lst-ctn-kix_list_120-8}.lst-kix_list_33-8>li:before{content:"\0025aa  "}.lst-kix_list_104-5>li:before{content:"\0025aa  "}.lst-kix_list_117-2>li{counter-increment:lst-ctn-kix_list_117-2}.lst-kix_list_34-2>li:before{content:"\0025aa  "}.lst-kix_list_120-2>li{counter-increment:lst-ctn-kix_list_120-2}.lst-kix_list_72-4>li:before{content:"\0025aa  "}.lst-kix_list_100-6>li:before{content:"\0025cf  "}.lst-kix_list_30-5>li:before{content:"\0025aa  "}.lst-kix_list_105-2>li:before{content:"" counter(lst-ctn-kix_list_105-2,lower-roman) ". "}.lst-kix_list_35-0>li:before{content:"\0025cf  "}.lst-kix_list_35-1>li:before{content:"o  "}.lst-kix_list_35-4>li:before{content:"\0025aa  "}.lst-kix_list_105-1>li:before{content:"" counter(lst-ctn-kix_list_105-1,lower-latin) ". "}.lst-kix_list_105-5>li:before{content:"\0025aa  "}.lst-kix_list_30-1>li:before{content:"o  "}.lst-kix_list_3-0>li:before{content:"\0025cf  "}.lst-kix_list_72-3>li:before{content:"\0025cf  "}.lst-kix_list_30-2>li:before{content:"\0025aa  "}.lst-kix_list_86-0>li:before{content:"\0025cf  "}ol.lst-kix_list_108-2.start{counter-reset:lst-ctn-kix_list_108-2 0}.lst-kix_list_3-3>li:before{content:"\0025cf  "}.lst-kix_list_72-7>li:before{content:"\0025aa  "}ul.lst-kix_list_124-1{list-style-type:none}ul.lst-kix_list_124-2{list-style-type:none}ul.lst-kix_list_124-0{list-style-type:none}ul.lst-kix_list_124-5{list-style-type:none}ul.lst-kix_list_124-6{list-style-type:none}ul.lst-kix_list_124-3{list-style-type:none}.lst-kix_list_118-5>li{counter-increment:lst-ctn-kix_list_118-5}ul.lst-kix_list_124-4{list-style-type:none}ul.lst-kix_list_13-5{list-style-type:none}ul.lst-kix_list_13-4{list-style-type:none}ul.lst-kix_list_13-3{list-style-type:none}ul.lst-kix_list_124-7{list-style-type:none}ul.lst-kix_list_13-2{list-style-type:none}ul.lst-kix_list_124-8{list-style-type:none}.lst-kix_list_123-0>li:before{content:"\0025cf  "}ul.lst-kix_list_13-1{list-style-type:none}ul.lst-kix_list_13-0{list-style-type:none}.lst-kix_list_53-2>li:before{content:"\0025aa  "}.lst-kix_list_53-3>li:before{content:"\0025aa  "}.lst-kix_list_123-4>li:before{content:"\0025cb  "}ul.lst-kix_list_13-8{list-style-type:none}.lst-kix_list_11-1>li:before{content:"o  "}ul.lst-kix_list_13-7{list-style-type:none}.lst-kix_list_69-6>li{counter-increment:lst-ctn-kix_list_69-6}ul.lst-kix_list_13-6{list-style-type:none}.lst-kix_list_123-3>li:before{content:"\0025cf  "}.lst-kix_list_123-7>li:before{content:"\0025cb  "}.lst-kix_list_68-2>li:before{content:"\0025aa  "}.lst-kix_6ppt4s25kk1y-4>li:before{content:"\0025cb  "}.lst-kix_list_11-0>li:before{content:"\0025cf  "}.lst-kix_list_90-5>li:before{content:"\0025a0  "}.lst-kix_list_8-8>li:before{content:"\0025aa  "}.lst-kix_6ppt4s25kk1y-0>li:before{content:"\0025cf  "}.lst-kix_6ppt4s25kk1y-1>li:before{content:"\0025cb  "}.lst-kix_list_4-8>li:before{content:"\0025a0  "}.lst-kix_list_90-8>li:before{content:"\0025a0  "}.lst-kix_list_87-3>li:before{content:"\0025aa  "}.lst-kix_list_91-1>li:before{content:"\0025cb  "}.lst-kix_list_16-0>li:before{content:"\0025cf  "}ul.lst-kix_list_4-8{list-style-type:none}.lst-kix_list_67-3>li:before{content:"\0025aa  "}ul.lst-kix_list_4-6{list-style-type:none}ul.lst-kix_list_4-7{list-style-type:none}ul.lst-kix_835ax5k7z1l9-6{list-style-type:none}.lst-kix_list_91-4>li:before{content:"\0025cb  "}.lst-kix_list_91-8>li:before{content:"\0025a0  "}ul.lst-kix_835ax5k7z1l9-5{list-style-type:none}.lst-kix_list_67-2>li:before{content:"\0025aa  "}ul.lst-kix_835ax5k7z1l9-8{list-style-type:none}ul.lst-kix_835ax5k7z1l9-7{list-style-type:none}ul.lst-kix_835ax5k7z1l9-2{list-style-type:none}ul.lst-kix_list_4-0{list-style-type:none}ul.lst-kix_835ax5k7z1l9-1{list-style-type:none}ul.lst-kix_list_4-1{list-style-type:none}ul.lst-kix_835ax5k7z1l9-4{list-style-type:none}.lst-kix_list_16-3>li:before{content:"\0025cf  "}ul.lst-kix_835ax5k7z1l9-3{list-style-type:none}ul.lst-kix_list_4-4{list-style-type:none}.lst-kix_list_91-5>li:before{content:"\0025a0  "}ul.lst-kix_list_4-5{list-style-type:none}ul.lst-kix_835ax5k7z1l9-0{list-style-type:none}ul.lst-kix_list_4-2{list-style-type:none}ul.lst-kix_list_4-3{list-style-type:none}.lst-kix_list_86-7>li:before{content:"\0025aa  "}ul.lst-kix_list_35-0{list-style-type:none}ul.lst-kix_list_35-1{list-style-type:none}ul.lst-kix_list_102-0{list-style-type:none}.lst-kix_list_86-4>li:before{content:"\0025aa  "}ul.lst-kix_list_35-2{list-style-type:none}ul.lst-kix_list_102-5{list-style-type:none}ul.lst-kix_list_35-3{list-style-type:none}ul.lst-kix_list_102-6{list-style-type:none}ul.lst-kix_list_35-4{list-style-type:none}ul.lst-kix_list_102-3{list-style-type:none}.lst-kix_list_71-4>li:before{content:"\0025cb  "}ul.lst-kix_list_35-5{list-style-type:none}ul.lst-kix_list_102-4{list-style-type:none}.lst-kix_list_86-3>li:before{content:"\0025aa  "}ul.lst-kix_list_102-7{list-style-type:none}ul.lst-kix_list_102-8{list-style-type:none}ul.lst-kix_1qgee6j7obt0-8{list-style-type:none}.lst-kix_list_17-8>li:before{content:"\0025a0  "}ul.lst-kix_1qgee6j7obt0-6{list-style-type:none}ul.lst-kix_1qgee6j7obt0-7{list-style-type:none}ul.lst-kix_1qgee6j7obt0-4{list-style-type:none}ul.lst-kix_1qgee6j7obt0-5{list-style-type:none}.lst-kix_list_87-0>li:before{content:"\0025cf  "}ul.lst-kix_1qgee6j7obt0-2{list-style-type:none}ul.lst-kix_1qgee6j7obt0-3{list-style-type:none}ul.lst-kix_1qgee6j7obt0-0{list-style-type:none}ul.lst-kix_1qgee6j7obt0-1{list-style-type:none}.lst-kix_list_71-8>li:before{content:"\0025a0  "}.lst-kix_list_133-2>li{counter-increment:lst-ctn-kix_list_133-2}ul.lst-kix_list_35-6{list-style-type:none}.lst-kix_list_100-2>li:before{content:"\0025a0  "}ul.lst-kix_list_35-7{list-style-type:none}ul.lst-kix_list_35-8{list-style-type:none}.lst-kix_list_71-7>li:before{content:"\0025cb  "}.lst-kix_list_72-0>li:before{content:"\0025cf  "}.lst-kix_list_7-0>li:before{content:"\0025cf  "}.lst-kix_list_100-3>li:before{content:"\0025cf  "}ul.lst-kix_list_111-3{list-style-type:none}ul.lst-kix_list_111-4{list-style-type:none}.lst-kix_list_85-4>li:before{content:"\0025aa  "}ul.lst-kix_list_111-1{list-style-type:none}ol.lst-kix_list_133-4.start{counter-reset:lst-ctn-kix_list_133-4 0}ul.lst-kix_list_111-2{list-style-type:none}ul.lst-kix_list_26-0{list-style-type:none}ul.lst-kix_list_111-7{list-style-type:none}.lst-kix_list_2-4>li:before{content:"\0025cb  "}ul.lst-kix_list_26-1{list-style-type:none}ul.lst-kix_list_111-8{list-style-type:none}ul.lst-kix_list_26-2{list-style-type:none}ul.lst-kix_list_111-5{list-style-type:none}ul.lst-kix_list_26-3{list-style-type:none}ul.lst-kix_list_111-6{list-style-type:none}.lst-kix_list_85-8>li:before{content:"\0025aa  "}.lst-kix_list_118-2>li:before{content:"" counter(lst-ctn-kix_list_118-2,decimal) ". "}.lst-kix_list_7-3>li:before{content:"\0025aa  "}.lst-kix_list_48-5>li:before{content:"\0025aa  "}.lst-kix_list_13-8>li:before{content:"\0025aa  "}.lst-kix_list_31-1>li:before{content:"\0025cb  "}.lst-kix_list_18-7>li:before{content:"\0025cb  "}.lst-kix_list_101-2>li:before{content:"\0025aa  "}ul.lst-kix_list_26-4{list-style-type:none}ul.lst-kix_list_26-5{list-style-type:none}ul.lst-kix_list_26-6{list-style-type:none}ul.lst-kix_list_26-7{list-style-type:none}ul.lst-kix_list_26-8{list-style-type:none}ul.lst-kix_list_111-0{list-style-type:none}.lst-kix_list_118-6>li:before{content:"" counter(lst-ctn-kix_list_118-6,decimal) ". "}.lst-kix_list_48-1>li:before{content:"o  "}.lst-kix_list_15-4>li:before{content:"\0025cb  "}.lst-kix_list_52-6>li:before{content:"\0025aa  "}.lst-kix_list_122-7>li:before{content:"\0025cb  "}ol.lst-kix_list_120-1.start{counter-reset:lst-ctn-kix_list_120-1 0}.lst-kix_list_10-4>li:before{content:"\0025aa  "}.lst-kix_list_10-8>li:before{content:"\0025aa  "}.lst-kix_list_73-3>li:before{content:"\0025cf  "}.lst-kix_list_120-0>li:before{content:"" counter(lst-ctn-kix_list_120-0,decimal) ". "}.lst-kix_list_15-0>li:before{content:"\0025cf  "}ol.lst-kix_g5lskmm1i0dj-8.start{counter-reset:lst-ctn-kix_g5lskmm1i0dj-8 0}.lst-kix_list_67-6>li:before{content:"\0025aa  "}.lst-kix_list_12-8>li{counter-increment:lst-ctn-kix_list_12-8}ul.lst-kix_list_48-1{list-style-type:none}ul.lst-kix_list_48-0{list-style-type:none}.lst-kix_list_9-7>li:before{content:"\0025aa  "}.lst-kix_list_29-4>li:before{content:"\0025aa  "}ul.lst-kix_list_48-3{list-style-type:none}ul.lst-kix_list_48-2{list-style-type:none}.lst-kix_list_53-6>li:before{content:"\0025aa  "}.lst-kix_list_124-3>li:before{content:"\0025cf  "}.lst-kix_list_11-4>li:before{content:"\0025aa  "}.lst-kix_list_103-6>li:before{content:"\0025aa  "}.lst-kix_list_29-0>li:before{content:"\0025cf  "}ul.lst-kix_list_48-5{list-style-type:none}ul.lst-kix_list_48-4{list-style-type:none}ul.lst-kix_list_48-7{list-style-type:none}.lst-kix_list_54-2>li:before{content:"\0025aa  "}ul.lst-kix_list_48-6{list-style-type:none}ol.lst-kix_list_133-3.start{counter-reset:lst-ctn-kix_list_133-3 0}ul.lst-kix_list_48-8{list-style-type:none}.lst-kix_list_12-0>li:before{content:"" counter(lst-ctn-kix_list_12-0,decimal) ". "}.lst-kix_list_1-4>li:before{content:"\0025cb  "}.lst-kix_list_104-2>li:before{content:"" counter(lst-ctn-kix_list_104-2,lower-roman) ". "}.lst-kix_list_119-2>li:before{content:"" counter(lst-ctn-kix_list_119-2,decimal) ". "}.lst-kix_list_34-5>li:before{content:"\0025aa  "}ol.lst-kix_list_45-8.start{counter-reset:lst-ctn-kix_list_45-8 0}.lst-kix_list_33-5>li:before{content:"\0025aa  "}.lst-kix_g5lskmm1i0dj-3>li{counter-increment:lst-ctn-kix_g5lskmm1i0dj-3}.lst-kix_list_2-0>li:before{content:"\0025cf  "}.lst-kix_list_1-8>li:before{content:"\0025a0  "}.lst-kix_list_104-6>li:before{content:"\0025aa  "}.lst-kix_list_49-1>li:before{content:"o  "}.lst-kix_list_34-1>li:before{content:"o  "}.lst-kix_list_126-4>li:before{content:"\0025aa  "}ul.lst-kix_list_66-2{list-style-type:none}.lst-kix_list_19-0>li:before{content:"\0025cf  "}ul.lst-kix_list_66-3{list-style-type:none}ul.lst-kix_list_66-0{list-style-type:none}ul.lst-kix_list_66-1{list-style-type:none}.lst-kix_list_93-6>li:before{content:"\0025cf  "}ul.lst-kix_list_66-6{list-style-type:none}ul.lst-kix_list_66-7{list-style-type:none}ul.lst-kix_list_66-4{list-style-type:none}ul.lst-kix_list_66-5{list-style-type:none}.lst-kix_list_56-6>li:before{content:"\0025aa  "}ul.lst-kix_61pipssxjd5z-1{list-style-type:none}ul.lst-kix_61pipssxjd5z-0{list-style-type:none}.lst-kix_list_56-0>li:before{content:"\0025cf  "}ul.lst-kix_61pipssxjd5z-3{list-style-type:none}ul.lst-kix_61pipssxjd5z-2{list-style-type:none}ul.lst-kix_61pipssxjd5z-5{list-style-type:none}.lst-kix_list_93-3>li:before{content:"\0025cf  "}ul.lst-kix_61pipssxjd5z-4{list-style-type:none}.lst-kix_list_126-7>li:before{content:"\0025aa  "}ul.lst-kix_list_66-8{list-style-type:none}.lst-kix_list_135-2>li:before{content:"\0025a0  "}.lst-kix_list_56-3>li:before{content:"\0025aa  "}.lst-kix_list_117-0>li:before{content:"" counter(lst-ctn-kix_list_117-0,upper-latin) ". "}.lst-kix_list_118-8>li{counter-increment:lst-ctn-kix_list_118-8}.lst-kix_list_84-2>li:before{content:"\0025aa  "}.lst-kix_list_47-2>li:before{content:"\0025aa  "}.lst-kix_list_117-3>li:before{content:"" counter(lst-ctn-kix_list_117-3,decimal) ". "}.lst-kix_list_74-2>li:before{content:"\0025aa  "}ul.lst-kix_61pipssxjd5z-7{list-style-type:none}.lst-kix_list_84-8>li:before{content:"\0025aa  "}ul.lst-kix_61pipssxjd5z-6{list-style-type:none}ul.lst-kix_61pipssxjd5z-8{list-style-type:none}.lst-kix_list_107-0>li:before{content:"" counter(lst-ctn-kix_list_107-0,decimal) ". "}.lst-kix_list_107-3>li:before{content:"" counter(lst-ctn-kix_list_107-3,decimal) ". "}.lst-kix_list_84-5>li:before{content:"\0025aa  "}.lst-kix_list_19-7>li:before{content:"\0025cb  "}ol.lst-kix_list_104-2.start{counter-reset:lst-ctn-kix_list_104-2 0}ul.lst-kix_list_88-3{list-style-type:none}ul.lst-kix_list_88-2{list-style-type:none}ul.lst-kix_list_88-1{list-style-type:none}ul.lst-kix_list_88-0{list-style-type:none}.lst-kix_list_107-1>li{counter-increment:lst-ctn-kix_list_107-1}ul.lst-kix_list_88-7{list-style-type:none}ul.lst-kix_list_88-6{list-style-type:none}ul.lst-kix_list_88-5{list-style-type:none}ul.lst-kix_list_88-4{list-style-type:none}.lst-kix_list_116-1>li:before{content:"o  "}.lst-kix_list_107-6>li:before{content:"" counter(lst-ctn-kix_list_107-6,decimal) ". "}.lst-kix_list_66-3>li:before{content:"\0025aa  "}.lst-kix_list_46-3>li:before{content:"\0025aa  "}.lst-kix_list_38-1>li:before{content:"o  "}.lst-kix_list_116-7>li:before{content:"\0025aa  "}.lst-kix_list_37-2>li:before{content:"\0025aa  "}.lst-kix_list_103-1>li{counter-increment:lst-ctn-kix_list_103-1}.lst-kix_list_37-5>li:before{content:"\0025aa  "}ul.lst-kix_list_88-8{list-style-type:none}.lst-kix_list_46-0>li:before{content:"\0025cf  "}.lst-kix_list_116-4>li:before{content:"\0025aa  "}.lst-kix_list_108-2>li:before{content:"" counter(lst-ctn-kix_list_108-2,lower-roman) ". "}.lst-kix_list_135-8>li:before{content:"\0025a0  "}ul.lst-kix_list_31-2{list-style-type:none}ul.lst-kix_list_31-3{list-style-type:none}ul.lst-kix_list_31-4{list-style-type:none}.lst-kix_list_65-7>li:before{content:"\0025aa  "}ul.lst-kix_list_31-5{list-style-type:none}ul.lst-kix_list_31-6{list-style-type:none}ol.lst-kix_list_119-7{list-style-type:none}.lst-kix_list_65-4>li:before{content:"\0025aa  "}.lst-kix_list_92-4>li:before{content:"\0025cb  "}ul.lst-kix_list_31-7{list-style-type:none}ol.lst-kix_list_119-8{list-style-type:none}.lst-kix_list_135-5>li:before{content:"\0025a0  "}ul.lst-kix_list_31-8{list-style-type:none}.lst-kix_list_108-2>li{counter-increment:lst-ctn-kix_list_108-2}ol.lst-kix_list_119-3{list-style-type:none}.lst-kix_list_18-1>li:before{content:"\0025cb  "}ol.lst-kix_list_119-4{list-style-type:none}ol.lst-kix_list_119-5{list-style-type:none}.lst-kix_list_65-1>li:before{content:"o  "}ol.lst-kix_list_119-6{list-style-type:none}.lst-kix_list_38-8>li:before{content:"\0025aa  "}ol.lst-kix_list_119-0{list-style-type:none}ul.lst-kix_list_31-0{list-style-type:none}ol.lst-kix_list_119-1{list-style-type:none}ul.lst-kix_list_31-1{list-style-type:none}ol.lst-kix_list_117-5.start{counter-reset:lst-ctn-kix_list_117-5 0}ol.lst-kix_list_119-2{list-style-type:none}ol.lst-kix_list_133-7.start{counter-reset:lst-ctn-kix_list_133-7 0}.lst-kix_list_45-4>li{counter-increment:lst-ctn-kix_list_45-4}.lst-kix_list_66-0>li:before{content:"\0025cf  "}.lst-kix_list_136-1>li:before{content:"o  "}.lst-kix_list_93-0>li:before{content:"\0025cf  "}.lst-kix_list_133-5>li{counter-increment:lst-ctn-kix_list_133-5}ol.lst-kix_list_45-5.start{counter-reset:lst-ctn-kix_list_45-5 0}.lst-kix_list_92-7>li:before{content:"\0025cb  "}.lst-kix_list_136-4>li:before{content:"\0025aa  "}.lst-kix_list_133-8>li{counter-increment:lst-ctn-kix_list_133-8}ul.lst-kix_list_22-0{list-style-type:none}ul.lst-kix_list_22-1{list-style-type:none}.lst-kix_list_2-7>li:before{content:"\0025cb  "}ul.lst-kix_list_22-2{list-style-type:none}ul.lst-kix_list_22-3{list-style-type:none}.lst-kix_list_64-2>li:before{content:"\0025aa  "}ul.lst-kix_list_22-4{list-style-type:none}.lst-kix_list_134-3>li:before{content:"\0025aa  "}ul.lst-kix_list_22-5{list-style-type:none}ul.lst-kix_list_22-6{list-style-type:none}ul.lst-kix_list_22-7{list-style-type:none}.lst-kix_list_27-5>li:before{content:"\0025aa  "}.lst-kix_list_64-8>li:before{content:"\0025aa  "}.lst-kix_list_85-1>li:before{content:"o  "}.lst-kix_list_118-0>li{counter-increment:lst-ctn-kix_list_118-0}.lst-kix_list_127-0>li:before{content:"\0025cf  "}.lst-kix_list_109-8>li:before{content:"\0025aa  "}.lst-kix_list_39-7>li:before{content:"\0025cb  "}.lst-kix_list_55-7>li:before{content:"\0025aa  "}.lst-kix_list_10-1>li:before{content:"o  "}.lst-kix_list_18-4>li:before{content:"\0025cb  "}ul.lst-kix_list_22-8{list-style-type:none}.lst-kix_list_106-1>li:before{content:"" counter(lst-ctn-kix_list_106-1,lower-latin) ". "}ol.lst-kix_list_45-3.start{counter-reset:lst-ctn-kix_list_45-3 0}.lst-kix_list_106-7>li:before{content:"\0025aa  "}.lst-kix_list_36-6>li:before{content:"\0025cf  "}ul.lst-kix_list_57-1{list-style-type:none}ul.lst-kix_list_57-0{list-style-type:none}ul.lst-kix_list_57-3{list-style-type:none}ul.lst-kix_list_57-2{list-style-type:none}.lst-kix_list_73-6>li:before{content:"\0025cf  "}ul.lst-kix_list_57-5{list-style-type:none}ul.lst-kix_list_57-4{list-style-type:none}.lst-kix_list_36-0>li:before{content:"\0025cf  "}ol.lst-kix_g5lskmm1i0dj-5.start{counter-reset:lst-ctn-kix_g5lskmm1i0dj-5 0}.lst-kix_list_94-5>li:before{content:"\0025a0  "}.lst-kix_g5lskmm1i0dj-3>li:before{content:"" counter(lst-ctn-kix_g5lskmm1i0dj-3,decimal) ". "}ol.lst-kix_list_45-0.start{counter-reset:lst-ctn-kix_list_45-0 0}ol.lst-kix_g5lskmm1i0dj-0{list-style-type:none}ol.lst-kix_g5lskmm1i0dj-1{list-style-type:none}ol.lst-kix_g5lskmm1i0dj-2{list-style-type:none}ol.lst-kix_g5lskmm1i0dj-3{list-style-type:none}ol.lst-kix_list_120-4.start{counter-reset:lst-ctn-kix_list_120-4 0}ol.lst-kix_g5lskmm1i0dj-4{list-style-type:none}ol.lst-kix_g5lskmm1i0dj-5{list-style-type:none}ol.lst-kix_g5lskmm1i0dj-6{list-style-type:none}.lst-kix_list_20-8>li:before{content:"\0025aa  "}ol.lst-kix_g5lskmm1i0dj-7{list-style-type:none}ul.lst-kix_list_57-7{list-style-type:none}ol.lst-kix_g5lskmm1i0dj-8{list-style-type:none}ul.lst-kix_list_57-6{list-style-type:none}.lst-kix_list_46-6>li:before{content:"\0025aa  "}ul.lst-kix_list_57-8{list-style-type:none}.lst-kix_list_29-7>li:before{content:"\0025aa  "}ul.lst-kix_list_44-1{list-style-type:none}ul.lst-kix_list_44-0{list-style-type:none}ul.lst-kix_list_44-3{list-style-type:none}ul.lst-kix_list_44-2{list-style-type:none}ul.lst-kix_list_44-5{list-style-type:none}ul.lst-kix_list_44-4{list-style-type:none}ul.lst-kix_list_44-7{list-style-type:none}ul.lst-kix_list_44-6{list-style-type:none}.lst-kix_list_82-7>li:before{content:"\0025aa  "}.lst-kix_list_9-4>li:before{content:"\0025aa  "}.lst-kix_list_75-4>li:before{content:"\0025aa  "}ol.lst-kix_list_117-8.start{counter-reset:lst-ctn-kix_list_117-8 0}ol.lst-kix_list_120-6.start{counter-reset:lst-ctn-kix_list_120-6 0}ul.lst-kix_list_44-8{list-style-type:none}.lst-kix_list_74-8>li:before{content:"\0025aa  "}.lst-kix_list_83-3>li:before{content:"\0025aa  "}.lst-kix_list_1-1>li:before{content:"\0025cb  "}.lst-kix_list_11-7>li:before{content:"\0025aa  "}.lst-kix_list_124-6>li:before{content:"\0025cf  "}ul.lst-kix_list_79-0{list-style-type:none}.lst-kix_list_49-4>li:before{content:"\0025aa  "}.lst-kix_list_76-0>li:before{content:"\0025cf  "}ul.lst-kix_list_79-1{list-style-type:none}.lst-kix_list_125-2>li:before{content:"\0025a0  "}.lst-kix_list_55-1>li:before{content:"o  "}ul.lst-kix_list_79-4{list-style-type:none}ul.lst-kix_list_79-5{list-style-type:none}ul.lst-kix_list_79-2{list-style-type:none}.lst-kix_list_119-5>li:before{content:"" counter(lst-ctn-kix_list_119-5,decimal) ". "}ul.lst-kix_list_79-3{list-style-type:none}ol.lst-kix_list_109-1.start{counter-reset:lst-ctn-kix_list_109-1 0}.lst-kix_list_54-5>li:before{content:"\0025aa  "}ol.lst-kix_g5lskmm1i0dj-3.start{counter-reset:lst-ctn-kix_g5lskmm1i0dj-3 0}.lst-kix_list_125-8>li:before{content:"\0025a0  "}.lst-kix_list_48-8>li:before{content:"\0025aa  "}ul.lst-kix_list_79-8{list-style-type:none}ul.lst-kix_list_79-6{list-style-type:none}ul.lst-kix_list_79-7{list-style-type:none}.lst-kix_list_28-1>li:before{content:"o  "}ul.lst-kix_list_62-6{list-style-type:none}ul.lst-kix_list_62-7{list-style-type:none}ul.lst-kix_list_62-4{list-style-type:none}ul.lst-kix_list_62-5{list-style-type:none}ul.lst-kix_list_62-8{list-style-type:none}.lst-kix_list_30-8>li:before{content:"\0025aa  "}.lst-kix_list_35-7>li:before{content:"\0025aa  "}ul.lst-kix_list_62-2{list-style-type:none}ul.lst-kix_list_62-3{list-style-type:none}ul.lst-kix_list_62-0{list-style-type:none}ul.lst-kix_list_62-1{list-style-type:none}.lst-kix_list_26-6>li:before{content:"\0025cf  "}.lst-kix_list_8-2>li:before{content:"\0025aa  "}.lst-kix_list_105-8>li:before{content:"\0025aa  "}.lst-kix_list_12-0>li{counter-increment:lst-ctn-kix_list_12-0}.lst-kix_list_68-8>li:before{content:"\0025aa  "}ul.lst-kix_list_97-5{list-style-type:none}ul.lst-kix_list_97-4{list-style-type:none}ul.lst-kix_list_97-3{list-style-type:none}ul.lst-kix_list_97-2{list-style-type:none}.lst-kix_list_8-5>li:before{content:"\0025aa  "}ul.lst-kix_list_97-8{list-style-type:none}ul.lst-kix_list_97-7{list-style-type:none}ul.lst-kix_list_97-6{list-style-type:none}.lst-kix_list_26-3>li:before{content:"\0025cf  "}.lst-kix_list_3-6>li:before{content:"\0025cf  "}ul.lst-kix_list_97-1{list-style-type:none}ul.lst-kix_list_97-0{list-style-type:none}.lst-kix_list_68-5>li:before{content:"\0025aa  "}.lst-kix_list_21-7>li:before{content:"\0025aa  "}.lst-kix_6ppt4s25kk1y-7>li:before{content:"\0025cb  "}.lst-kix_list_90-2>li:before{content:"\0025a0  "}ol.lst-kix_list_117-7.start{counter-reset:lst-ctn-kix_list_117-7 0}ul.lst-kix_list_84-7{list-style-type:none}.lst-kix_list_58-8>li:before{content:"\0025aa  "}ul.lst-kix_list_84-6{list-style-type:none}ul.lst-kix_list_84-5{list-style-type:none}ul.lst-kix_list_84-4{list-style-type:none}.lst-kix_list_16-6>li:before{content:"\0025cf  "}.lst-kix_list_107-7>li{counter-increment:lst-ctn-kix_list_107-7}ul.lst-kix_list_84-8{list-style-type:none}ol.lst-kix_g5lskmm1i0dj-1.start{counter-reset:lst-ctn-kix_g5lskmm1i0dj-1 0}.lst-kix_list_115-8>li:before{content:"\0025aa  "}ul.lst-kix_list_84-3{list-style-type:none}ul.lst-kix_list_84-2{list-style-type:none}ul.lst-kix_list_84-1{list-style-type:none}ul.lst-kix_list_84-0{list-style-type:none}.lst-kix_list_129-5>li:before{content:"\0025aa  "}.lst-kix_list_45-4>li:before{content:"" counter(lst-ctn-kix_list_45-4,decimal) ". "}.lst-kix_list_87-6>li:before{content:"\0025aa  "}.lst-kix_list_45-7>li:before{content:"" counter(lst-ctn-kix_list_45-7,decimal) ". "}ol.lst-kix_g5lskmm1i0dj-0.start{counter-reset:lst-ctn-kix_g5lskmm1i0dj-0 0}.lst-kix_list_71-1>li:before{content:"\0025cb  "}.lst-kix_list_44-8>li:before{content:"\0025aa  "}ol.lst-kix_list_120-8.start{counter-reset:lst-ctn-kix_list_120-8 0}.lst-kix_list_129-8>li:before{content:"\0025aa  "}.lst-kix_list_17-2>li:before{content:"\0025a0  "}.lst-kix_list_59-4>li:before{content:"\0025aa  "}.lst-kix_list_115-5>li:before{content:"\0025aa  "}.lst-kix_list_59-7>li:before{content:"\0025aa  "}.lst-kix_list_17-5>li:before{content:"\0025a0  "}.lst-kix_list_45-7>li{counter-increment:lst-ctn-kix_list_45-7}.lst-kix_list_27-2>li:before{content:"\0025aa  "}.lst-kix_list_22-3>li:before{content:"\0025cf  "}.lst-kix_list_69-4>li:before{content:"" counter(lst-ctn-kix_list_69-4,decimal) ". "}ol.lst-kix_list_106-1{list-style-type:none}ol.lst-kix_list_106-2{list-style-type:none}.lst-kix_list_134-6>li:before{content:"\0025aa  "}.lst-kix_list_122-1>li:before{content:"\0025cb  "}.lst-kix_list_52-0>li:before{content:"\0025cf  "}.lst-kix_list_94-2>li:before{content:"\0025a0  "}.lst-kix_1qgee6j7obt0-7>li:before{content:"\0025cb  "}.lst-kix_list_64-5>li:before{content:"\0025aa  "}ol.lst-kix_list_117-3.start{counter-reset:lst-ctn-kix_list_117-3 0}.lst-kix_list_107-4>li{counter-increment:lst-ctn-kix_list_107-4}.lst-kix_list_78-5>li:before{content:"\0025a0  "}.lst-kix_g5lskmm1i0dj-6>li:before{content:"" counter(lst-ctn-kix_g5lskmm1i0dj-6,decimal) ". "}.lst-kix_list_31-7>li:before{content:"\0025cb  "}ul.lst-kix_list_53-3{list-style-type:none}ul.lst-kix_list_53-2{list-style-type:none}ul.lst-kix_list_53-5{list-style-type:none}ul.lst-kix_list_53-4{list-style-type:none}ul.lst-kix_list_53-7{list-style-type:none}ul.lst-kix_list_53-6{list-style-type:none}ul.lst-kix_list_53-8{list-style-type:none}ol.lst-kix_list_117-0.start{counter-reset:lst-ctn-kix_list_117-0 0}ul.lst-kix_list_53-1{list-style-type:none}.lst-kix_list_106-4>li:before{content:"\0025aa  "}.lst-kix_list_101-8>li:before{content:"\0025aa  "}ul.lst-kix_list_53-0{list-style-type:none}.lst-kix_list_88-5>li:before{content:"\0025aa  "}.lst-kix_list_4-2>li:before{content:"\0025a0  "}.lst-kix_list_80-2>li:before{content:"\0025a0  "}.lst-kix_list_36-3>li:before{content:"\0025cf  "}.lst-kix_list_69-3>li{counter-increment:lst-ctn-kix_list_69-3}.lst-kix_list_9-1>li:before{content:"o  "}ul.lst-kix_list_40-5{list-style-type:none}ul.lst-kix_list_40-4{list-style-type:none}.lst-kix_tn8cl5j8lycz-4>li:before{content:"\0025cb  "}ul.lst-kix_list_40-7{list-style-type:none}ul.lst-kix_list_40-6{list-style-type:none}ul.lst-kix_list_40-8{list-style-type:none}.lst-kix_list_103-0>li:before{content:"\0025cf  "}.lst-kix_list_40-8>li:before{content:"\0025a0  "}ol.lst-kix_list_117-1.start{counter-reset:lst-ctn-kix_list_117-1 0}.lst-kix_61pipssxjd5z-7>li:before{content:"\0025cb  "}ul.lst-kix_list_40-1{list-style-type:none}ul.lst-kix_list_40-0{list-style-type:none}.lst-kix_list_74-5>li:before{content:"\0025aa  "}ul.lst-kix_list_40-3{list-style-type:none}ul.lst-kix_list_40-2{list-style-type:none}.lst-kix_list_83-6>li:before{content:"\0025aa  "}.lst-kix_list_41-4>li:before{content:"\0025cb  "}.lst-kix_list_111-5>li:before{content:"\0025a0  "}.lst-kix_list_75-1>li:before{content:"o  "}.lst-kix_list_112-1>li:before{content:"o  "}ul.lst-kix_list_75-4{list-style-type:none}ul.lst-kix_list_75-5{list-style-type:none}ul.lst-kix_list_75-2{list-style-type:none}ul.lst-kix_list_75-3{list-style-type:none}ul.lst-kix_list_75-8{list-style-type:none}.lst-kix_list_119-8>li:before{content:"" counter(lst-ctn-kix_list_119-8,decimal) ". "}ul.lst-kix_list_75-6{list-style-type:none}ul.lst-kix_list_75-7{list-style-type:none}.lst-kix_list_49-7>li:before{content:"\0025aa  "}.lst-kix_list_131-2>li:before{content:"\0025a0  "}ul.lst-kix_list_75-0{list-style-type:none}ul.lst-kix_list_75-1{list-style-type:none}.lst-kix_list_60-5>li:before{content:"\0025aa  "}.lst-kix_list_120-5>li{counter-increment:lst-ctn-kix_list_120-5}ol.lst-kix_list_117-2.start{counter-reset:lst-ctn-kix_list_117-2 0}.lst-kix_list_97-6>li:before{content:"\0025cf  "}.lst-kix_list_61-1>li:before{content:"o  "}.lst-kix_list_12-6>li:before{content:"" counter(lst-ctn-kix_list_12-6,decimal) ". "}.lst-kix_list_55-4>li:before{content:"\0025aa  "}.lst-kix_list_125-5>li:before{content:"\0025a0  "}.lst-kix_list_126-1>li:before{content:"o  "}.lst-kix_list_13-2>li:before{content:"\0025aa  "}.lst-kix_list_54-8>li:before{content:"\0025aa  "}.lst-kix_list_98-2>li:before{content:"\0025aa  "}.lst-kix_list_98-6>li:before{content:"\0025aa  "}.lst-kix_list_98-0>li:before{content:"\0025cf  "}.lst-kix_list_98-8>li:before{content:"\0025aa  "}ul.lst-kix_list_9-3{list-style-type:none}ul.lst-kix_list_9-4{list-style-type:none}.lst-kix_list_42-8>li:before{content:"\0025a0  "}.lst-kix_list_130-3>li:before{content:"\0025aa  "}ul.lst-kix_list_9-1{list-style-type:none}ul.lst-kix_list_9-2{list-style-type:none}ul.lst-kix_list_9-7{list-style-type:none}ul.lst-kix_list_9-8{list-style-type:none}ul.lst-kix_list_9-5{list-style-type:none}.lst-kix_list_60-3>li:before{content:"\0025aa  "}ul.lst-kix_list_9-6{list-style-type:none}.lst-kix_list_130-5>li:before{content:"\0025aa  "}.lst-kix_list_130-7>li:before{content:"\0025aa  "}.lst-kix_list_98-4>li:before{content:"\0025aa  "}ul.lst-kix_list_9-0{list-style-type:none}.lst-kix_list_60-1>li:before{content:"o  "}.lst-kix_list_42-0>li:before{content:"\0025cf  "}.lst-kix_list_112-2>li:before{content:"\0025aa  "}.lst-kix_list_42-2>li:before{content:"\0025a0  "}.lst-kix_list_112-6>li:before{content:"\0025aa  "}.lst-kix_list_112-4>li:before{content:"\0025aa  "}.lst-kix_list_130-1>li:before{content:"o  "}ol.lst-kix_list_119-0.start{counter-reset:lst-ctn-kix_list_119-0 0}.lst-kix_list_42-6>li:before{content:"\0025cf  "}.lst-kix_list_42-4>li:before{content:"\0025cb  "}.lst-kix_list_112-8>li:before{content:"\0025aa  "}.lst-kix_lvjn8glkfwf0-0>li:before{content:"\0025cf  "}.lst-kix_list_24-7>li:before{content:"\0025aa  "}.lst-kix_lvjn8glkfwf0-2>li:before{content:"\0025a0  "}.lst-kix_list_79-7>li:before{content:"\0025cb  "}.lst-kix_list_79-1>li:before{content:"\0025cb  "}.lst-kix_lvjn8glkfwf0-8>li:before{content:"\0025a0  "}.lst-kix_list_24-3>li:before{content:"\0025aa  "}.lst-kix_lvjn8glkfwf0-6>li:before{content:"\0025cf  "}.lst-kix_list_79-3>li:before{content:"\0025cf  "}.lst-kix_list_24-5>li:before{content:"\0025aa  "}.lst-kix_lvjn8glkfwf0-4>li:before{content:"\0025cb  "}.lst-kix_list_79-5>li:before{content:"\0025a0  "}ul.lst-kix_list_129-1{list-style-type:none}ul.lst-kix_list_129-0{list-style-type:none}.lst-kix_list_23-3>li:before{content:"\0025aa  "}.lst-kix_list_23-7>li:before{content:"\0025aa  "}ul.lst-kix_list_16-2{list-style-type:none}ul.lst-kix_list_129-5{list-style-type:none}ul.lst-kix_list_16-1{list-style-type:none}ul.lst-kix_list_129-4{list-style-type:none}ul.lst-kix_list_16-0{list-style-type:none}ul.lst-kix_list_129-3{list-style-type:none}ul.lst-kix_list_129-2{list-style-type:none}ul.lst-kix_list_129-8{list-style-type:none}.lst-kix_list_23-1>li:before{content:"o  "}ul.lst-kix_list_129-7{list-style-type:none}ul.lst-kix_list_129-6{list-style-type:none}.lst-kix_list_24-1>li:before{content:"o  "}.lst-kix_1qgee6j7obt0-3>li:before{content:"\0025cf  "}ul.lst-kix_list_16-8{list-style-type:none}ul.lst-kix_list_16-7{list-style-type:none}ul.lst-kix_list_16-6{list-style-type:none}ul.lst-kix_list_16-5{list-style-type:none}ul.lst-kix_list_16-4{list-style-type:none}ul.lst-kix_list_16-3{list-style-type:none}.lst-kix_1qgee6j7obt0-1>li:before{content:"\0025cb  "}ol.lst-kix_list_107-8.start{counter-reset:lst-ctn-kix_list_107-8 0}.lst-kix_list_23-5>li:before{content:"\0025aa  "}ul.lst-kix_list_60-8{list-style-type:none}.lst-kix_list_113-4>li:before{content:"\0025aa  "}.lst-kix_list_113-6>li:before{content:"\0025aa  "}ol.lst-kix_list_106-2.start{counter-reset:lst-ctn-kix_list_106-2 0}ul.lst-kix_list_60-6{list-style-type:none}ul.lst-kix_list_60-7{list-style-type:none}ol.lst-kix_list_117-6.start{counter-reset:lst-ctn-kix_list_117-6 0}ul.lst-kix_list_60-0{list-style-type:none}ul.lst-kix_list_60-1{list-style-type:none}ul.lst-kix_list_60-4{list-style-type:none}ul.lst-kix_list_60-5{list-style-type:none}ul.lst-kix_list_60-2{list-style-type:none}ul.lst-kix_list_60-3{list-style-type:none}.lst-kix_list_113-8>li:before{content:"\0025aa  "}ul.lst-kix_list_95-7{list-style-type:none}ul.lst-kix_list_103-0{list-style-type:none}ul.lst-kix_list_95-6{list-style-type:none}ul.lst-kix_list_95-5{list-style-type:none}ul.lst-kix_list_95-4{list-style-type:none}ul.lst-kix_list_103-4{list-style-type:none}ul.lst-kix_list_103-5{list-style-type:none}ul.lst-kix_list_95-8{list-style-type:none}ul.lst-kix_list_103-3{list-style-type:none}ul.lst-kix_list_103-8{list-style-type:none}ul.lst-kix_list_103-6{list-style-type:none}ul.lst-kix_list_103-7{list-style-type:none}ul.lst-kix_list_95-3{list-style-type:none}ul.lst-kix_list_95-2{list-style-type:none}ul.lst-kix_list_95-1{list-style-type:none}ul.lst-kix_list_95-0{list-style-type:none}ul.lst-kix_fahi2s4j7zmm-4{list-style-type:none}ul.lst-kix_fahi2s4j7zmm-3{list-style-type:none}ul.lst-kix_fahi2s4j7zmm-6{list-style-type:none}ul.lst-kix_fahi2s4j7zmm-5{list-style-type:none}ul.lst-kix_fahi2s4j7zmm-8{list-style-type:none}.lst-kix_list_25-5>li:before{content:"\0025aa  "}ul.lst-kix_fahi2s4j7zmm-7{list-style-type:none}ol.lst-kix_list_107-3.start{counter-reset:lst-ctn-kix_list_107-3 0}ol.lst-kix_list_69-4.start{counter-reset:lst-ctn-kix_list_69-4 0}.lst-kix_list_25-7>li:before{content:"\0025aa  "}.lst-kix_list_113-0>li:before{content:"\0025cf  "}.lst-kix_list_113-2>li:before{content:"\0025aa  "}ul.lst-kix_fahi2s4j7zmm-0{list-style-type:none}ul.lst-kix_fahi2s4j7zmm-2{list-style-type:none}ul.lst-kix_fahi2s4j7zmm-1{list-style-type:none}ul.lst-kix_list_82-8{list-style-type:none}.lst-kix_list_111-0>li:before{content:"\0025cf  "}ul.lst-kix_list_82-7{list-style-type:none}ul.lst-kix_list_82-6{list-style-type:none}.lst-kix_list_132-1>li:before{content:"\0025cb  "}ul.lst-kix_list_116-2{list-style-type:none}ol.lst-kix_list_45-2.start{counter-reset:lst-ctn-kix_list_45-2 0}ul.lst-kix_list_116-3{list-style-type:none}.lst-kix_list_111-2>li:before{content:"\0025a0  "}ul.lst-kix_list_116-0{list-style-type:none}ul.lst-kix_list_29-0{list-style-type:none}ul.lst-kix_list_116-1{list-style-type:none}ul.lst-kix_list_82-1{list-style-type:none}ul.lst-kix_list_116-6{list-style-type:none}ul.lst-kix_list_82-0{list-style-type:none}ul.lst-kix_list_116-7{list-style-type:none}.lst-kix_list_111-4>li:before{content:"\0025cb  "}ul.lst-kix_list_116-4{list-style-type:none}.lst-kix_list_132-3>li:before{content:"\0025cf  "}.lst-kix_list_132-5>li:before{content:"\0025a0  "}ul.lst-kix_list_116-5{list-style-type:none}ul.lst-kix_list_82-5{list-style-type:none}ul.lst-kix_list_82-4{list-style-type:none}ul.lst-kix_list_82-3{list-style-type:none}ul.lst-kix_list_116-8{list-style-type:none}ul.lst-kix_list_82-2{list-style-type:none}.lst-kix_list_111-8>li:before{content:"\0025a0  "}.lst-kix_list_132-7>li:before{content:"\0025cb  "}.lst-kix_list_111-6>li:before{content:"\0025cf  "}.lst-kix_list_131-1>li:before{content:"\0025cb  "}ul.lst-kix_list_29-1{list-style-type:none}ul.lst-kix_list_29-2{list-style-type:none}ul.lst-kix_list_29-3{list-style-type:none}.lst-kix_list_110-0>li:before{content:"\0025cf  "}ul.lst-kix_list_29-4{list-style-type:none}ul.lst-kix_list_29-5{list-style-type:none}ol.lst-kix_list_109-2.start{counter-reset:lst-ctn-kix_list_109-2 0}ul.lst-kix_list_29-6{list-style-type:none}.lst-kix_list_112-0>li:before{content:"\0025cf  "}ul.lst-kix_list_29-7{list-style-type:none}ul.lst-kix_list_29-8{list-style-type:none}.lst-kix_list_110-2>li:before{content:"\0025aa  "}.lst-kix_list_131-3>li:before{content:"\0025cf  "}.lst-kix_list_110-4>li:before{content:"\0025aa  "}.lst-kix_list_131-5>li:before{content:"\0025a0  "}.lst-kix_list_110-8>li:before{content:"\0025aa  "}ol.lst-kix_list_119-5.start{counter-reset:lst-ctn-kix_list_119-5 0}.lst-kix_list_110-6>li:before{content:"\0025aa  "}.lst-kix_list_131-7>li:before{content:"\0025cb  "}ul.lst-kix_list_47-0{list-style-type:none}ul.lst-kix_list_47-2{list-style-type:none}ul.lst-kix_list_47-1{list-style-type:none}.lst-kix_list_120-4>li{counter-increment:lst-ctn-kix_list_120-4}ul.lst-kix_list_47-4{list-style-type:none}ol.lst-kix_g5lskmm1i0dj-6.start{counter-reset:lst-ctn-kix_g5lskmm1i0dj-6 0}ul.lst-kix_list_47-3{list-style-type:none}.lst-kix_list_119-6>li{counter-increment:lst-ctn-kix_list_119-6}.lst-kix_list_77-7>li:before{content:"\0025cb  "}.lst-kix_list_81-0>li:before{content:"\0025cf  "}ul.lst-kix_list_5-7{list-style-type:none}ul.lst-kix_list_5-8{list-style-type:none}ul.lst-kix_list_5-5{list-style-type:none}ul.lst-kix_list_5-6{list-style-type:none}.lst-kix_list_26-5>li:before{content:"\0025a0  "}ul.lst-kix_list_47-6{list-style-type:none}ul.lst-kix_list_5-0{list-style-type:none}ul.lst-kix_list_47-5{list-style-type:none}ul.lst-kix_list_47-8{list-style-type:none}ol.lst-kix_list_120-3.start{counter-reset:lst-ctn-kix_list_120-3 0}ul.lst-kix_list_47-7{list-style-type:none}ul.lst-kix_list_5-3{list-style-type:none}.lst-kix_list_114-2>li:before{content:"\0025a0  "}ul.lst-kix_list_5-4{list-style-type:none}.lst-kix_list_77-3>li:before{content:"\0025cf  "}ul.lst-kix_list_5-1{list-style-type:none}.lst-kix_list_133-0>li{counter-increment:lst-ctn-kix_list_133-0}ul.lst-kix_list_5-2{list-style-type:none}.lst-kix_list_26-1>li:before{content:"\0025cb  "}.lst-kix_list_133-3>li:before{content:"" counter(lst-ctn-kix_list_133-3,decimal) ". "}.lst-kix_list_21-1>li:before{content:"o  "}ol.lst-kix_list_45-7{list-style-type:none}ol.lst-kix_list_45-8{list-style-type:none}ol.lst-kix_list_45-5{list-style-type:none}ol.lst-kix_list_45-6{list-style-type:none}ol.lst-kix_list_45-3{list-style-type:none}.lst-kix_list_45-3>li{counter-increment:lst-ctn-kix_list_45-3}ol.lst-kix_list_45-4{list-style-type:none}.lst-kix_list_120-6>li{counter-increment:lst-ctn-kix_list_120-6}ol.lst-kix_list_45-2{list-style-type:none}.lst-kix_list_128-2>li:before{content:"\0025a0  "}ol.lst-kix_list_45-0{list-style-type:none}.lst-kix_list_63-7>li:before{content:"\0025aa  "}.lst-kix_list_95-0>li:before{content:"\0025cf  "}ol.lst-kix_list_45-7.start{counter-reset:lst-ctn-kix_list_45-7 0}.lst-kix_list_133-7>li:before{content:"" counter(lst-ctn-kix_list_133-7,decimal) ". "}.lst-kix_list_21-5>li:before{content:"\0025aa  "}.lst-kix_list_63-3>li:before{content:"\0025aa  "}.lst-kix_list_58-6>li:before{content:"\0025cf  "}.lst-kix_list_128-6>li:before{content:"\0025cf  "}.lst-kix_list_115-6>li:before{content:"\0025aa  "}ol.lst-kix_list_133-6.start{counter-reset:lst-ctn-kix_list_133-6 0}.lst-kix_g5lskmm1i0dj-8>li{counter-increment:lst-ctn-kix_g5lskmm1i0dj-8}.lst-kix_list_45-2>li:before{content:"" counter(lst-ctn-kix_list_45-2,decimal) ". "}.lst-kix_list_58-2>li:before{content:"\0025aa  "}.lst-kix_list_25-1>li:before{content:"o  "}.lst-kix_list_102-1>li{counter-increment:lst-ctn-kix_list_102-1}.lst-kix_list_129-2>li:before{content:"\0025aa  "}.lst-kix_list_45-6>li:before{content:"" counter(lst-ctn-kix_list_45-6,decimal) ". "}ul.lst-kix_list_125-1{list-style-type:none}.lst-kix_list_44-6>li:before{content:"\0025aa  "}ul.lst-kix_list_125-0{list-style-type:none}.lst-kix_g5lskmm1i0dj-1>li{counter-increment:lst-ctn-kix_g5lskmm1i0dj-1}.lst-kix_list_119-8>li{counter-increment:lst-ctn-kix_list_119-8}ul.lst-kix_list_125-5{list-style-type:none}ul.lst-kix_list_125-4{list-style-type:none}ul.lst-kix_list_125-3{list-style-type:none}ul.lst-kix_list_125-2{list-style-type:none}.lst-kix_list_109-1>li:before{content:"" counter(lst-ctn-kix_list_109-1,lower-latin) ". "}.lst-kix_list_44-2>li:before{content:"\0025aa  "}ul.lst-kix_list_125-8{list-style-type:none}ul.lst-kix_list_125-7{list-style-type:none}ul.lst-kix_list_125-6{list-style-type:none}.lst-kix_list_39-1>li:before{content:"\0025cb  "}.lst-kix_list_114-6>li:before{content:"\0025cf  "}.lst-kix_list_129-6>li:before{content:"\0025aa  "}ol.lst-kix_list_133-1.start{counter-reset:lst-ctn-kix_list_133-1 0}.lst-kix_list_59-2>li:before{content:"\0025aa  "}.lst-kix_list_115-2>li:before{content:"\0025aa  "}.lst-kix_list_109-5>li:before{content:"\0025aa  "}.lst-kix_list_59-6>li:before{content:"\0025aa  "}ol.lst-kix_list_103-2.start{counter-reset:lst-ctn-kix_list_103-2 0}ul.lst-kix_list_134-3{list-style-type:none}ul.lst-kix_ee0fx9z4yp3a-6{list-style-type:none}.lst-kix_list_64-3>li:before{content:"\0025aa  "}ul.lst-kix_list_134-2{list-style-type:none}ul.lst-kix_ee0fx9z4yp3a-5{list-style-type:none}.lst-kix_list_80-4>li:before{content:"\0025cb  "}ul.lst-kix_list_134-1{list-style-type:none}ul.lst-kix_ee0fx9z4yp3a-4{list-style-type:none}.lst-kix_list_22-5>li:before{content:"\0025aa  "}ul.lst-kix_list_134-0{list-style-type:none}ul.lst-kix_ee0fx9z4yp3a-3{list-style-type:none}ul.lst-kix_list_134-7{list-style-type:none}ul.lst-kix_list_134-6{list-style-type:none}.lst-kix_list_43-2>li:before{content:"\0025aa  "}.lst-kix_list_43-6>li:before{content:"\0025aa  "}ul.lst-kix_list_134-5{list-style-type:none}ul.lst-kix_ee0fx9z4yp3a-8{list-style-type:none}ul.lst-kix_list_134-4{list-style-type:none}ul.lst-kix_ee0fx9z4yp3a-7{list-style-type:none}.lst-kix_835ax5k7z1l9-8>li:before{content:"\0025a0  "}.lst-kix_list_64-7>li:before{content:"\0025aa  "}.lst-kix_list_119-1>li{counter-increment:lst-ctn-kix_list_119-1}.lst-kix_list_133-7>li{counter-increment:lst-ctn-kix_list_133-7}.lst-kix_list_45-8>li{counter-increment:lst-ctn-kix_list_45-8}.lst-kix_list_22-1>li:before{content:"o  "}ul.lst-kix_list_134-8{list-style-type:none}ul.lst-kix_ee0fx9z4yp3a-2{list-style-type:none}ul.lst-kix_ee0fx9z4yp3a-1{list-style-type:none}ul.lst-kix_ee0fx9z4yp3a-0{list-style-type:none}.lst-kix_ee0fx9z4yp3a-8>li:before{content:"\0025a0  "}.lst-kix_list_76-7>li:before{content:"\0025aa  "}.lst-kix_1qgee6j7obt0-5>li:before{content:"\0025a0  "}.lst-kix_list_97-8>li:before{content:"\0025a0  "}.lst-kix_list_80-8>li:before{content:"\0025a0  "}.lst-kix_list_94-0>li:before{content:"\0025cf  "}.lst-kix_list_99-4>li:before{content:"\0025cb  "}ul.lst-kix_list_91-8{list-style-type:none}.lst-kix_list_78-3>li:before{content:"\0025cf  "}.lst-kix_list_78-7>li:before{content:"\0025cb  "}ul.lst-kix_list_38-0{list-style-type:none}ul.lst-kix_list_38-1{list-style-type:none}.lst-kix_list_57-2>li:before{content:"\0025aa  "}.lst-kix_list_57-6>li:before{content:"\0025cf  "}ul.lst-kix_list_38-2{list-style-type:none}ul.lst-kix_list_91-3{list-style-type:none}.lst-kix_835ax5k7z1l9-0>li:before{content:"\0025cf  "}ul.lst-kix_list_91-2{list-style-type:none}.lst-kix_list_99-0>li:before{content:"\0025cf  "}.lst-kix_list_99-8>li:before{content:"\0025a0  "}ul.lst-kix_list_91-1{list-style-type:none}ul.lst-kix_list_91-0{list-style-type:none}ul.lst-kix_list_91-7{list-style-type:none}.lst-kix_list_83-8>li:before{content:"\0025aa  "}ul.lst-kix_list_91-6{list-style-type:none}ul.lst-kix_list_91-5{list-style-type:none}.lst-kix_list_94-4>li:before{content:"\0025cb  "}ul.lst-kix_list_91-4{list-style-type:none}.lst-kix_ee0fx9z4yp3a-0>li:before{content:"\0025cf  "}ol.lst-kix_list_108-1.start{counter-reset:lst-ctn-kix_list_108-1 0}.lst-kix_list_62-7>li:before{content:"\0025aa  "}.lst-kix_835ax5k7z1l9-4>li:before{content:"\0025cb  "}ul.lst-kix_list_38-3{list-style-type:none}ul.lst-kix_list_38-4{list-style-type:none}.lst-kix_list_80-0>li:before{content:"\0025cf  "}ul.lst-kix_list_38-5{list-style-type:none}ul.lst-kix_list_38-6{list-style-type:none}ul.lst-kix_list_38-7{list-style-type:none}ul.lst-kix_list_38-8{list-style-type:none}.lst-kix_list_94-8>li:before{content:"\0025a0  "}.lst-kix_ee0fx9z4yp3a-4>li:before{content:"\0025cb  "}.lst-kix_61pipssxjd5z-1>li:before{content:"\0025cb  "}ul.lst-kix_list_112-2{list-style-type:none}ul.lst-kix_list_112-3{list-style-type:none}ul.lst-kix_list_112-0{list-style-type:none}.lst-kix_list_95-8>li:before{content:"\0025a0  "}ul.lst-kix_list_25-0{list-style-type:none}ul.lst-kix_list_112-1{list-style-type:none}.lst-kix_list_108-1>li{counter-increment:lst-ctn-kix_list_108-1}ul.lst-kix_list_25-1{list-style-type:none}ul.lst-kix_list_112-6{list-style-type:none}.lst-kix_list_82-8>li:before{content:"\0025aa  "}ul.lst-kix_list_25-2{list-style-type:none}ul.lst-kix_list_112-7{list-style-type:none}ul.lst-kix_list_25-3{list-style-type:none}ul.lst-kix_list_112-4{list-style-type:none}.lst-kix_list_96-0>li:before{content:"\0025cf  "}ul.lst-kix_list_25-4{list-style-type:none}ul.lst-kix_list_112-5{list-style-type:none}.lst-kix_61pipssxjd5z-5>li:before{content:"\0025a0  "}.lst-kix_list_61-7>li:before{content:"\0025aa  "}ul.lst-kix_list_112-8{list-style-type:none}.lst-kix_list_95-4>li:before{content:"\0025cb  "}.lst-kix_list_83-0>li:before{content:"\0025cf  "}.lst-kix_list_40-6>li:before{content:"\0025cf  "}.lst-kix_list_69-4>li{counter-increment:lst-ctn-kix_list_69-4}ol.lst-kix_list_102-1.start{counter-reset:lst-ctn-kix_list_102-1 0}.lst-kix_list_41-6>li:before{content:"\0025cf  "}.lst-kix_list_20-5>li:before{content:"\0025aa  "}.lst-kix_list_75-3>li:before{content:"\0025aa  "}.lst-kix_list_96-4>li:before{content:"\0025cb  "}ul.lst-kix_list_25-5{list-style-type:none}ul.lst-kix_list_25-6{list-style-type:none}.lst-kix_list_41-2>li:before{content:"\0025a0  "}.lst-kix_list_20-1>li:before{content:"o  "}ul.lst-kix_list_25-7{list-style-type:none}ul.lst-kix_list_25-8{list-style-type:none}.lst-kix_list_12-3>li{counter-increment:lst-ctn-kix_list_12-3}.lst-kix_list_83-4>li:before{content:"\0025aa  "}.lst-kix_list_62-3>li:before{content:"\0025aa  "}.lst-kix_list_81-8>li:before{content:"\0025aa  "}.lst-kix_list_97-0>li:before{content:"\0025cf  "}.lst-kix_list_117-5>li{counter-increment:lst-ctn-kix_list_117-5}.lst-kix_list_60-7>li:before{content:"\0025aa  "}.lst-kix_list_81-4>li:before{content:"\0025aa  "}.lst-kix_list_82-0>li:before{content:"\0025cf  "}.lst-kix_list_61-3>li:before{content:"\0025aa  "}.lst-kix_list_82-4>li:before{content:"\0025aa  "}.lst-kix_list_75-7>li:before{content:"\0025aa  "}.lst-kix_list_96-8>li:before{content:"\0025a0  "}.lst-kix_list_76-3>li:before{content:"\0025aa  "}.lst-kix_list_97-4>li:before{content:"\0025cb  "}.lst-kix_list_40-2>li:before{content:"\0025a0  "}.lst-kix_list_93-4>li:before{content:"\0025cb  "}ul.lst-kix_list_43-2{list-style-type:none}ul.lst-kix_list_43-1{list-style-type:none}ul.lst-kix_list_43-4{list-style-type:none}ul.lst-kix_list_43-3{list-style-type:none}.lst-kix_list_56-2>li:before{content:"\0025aa  "}.lst-kix_list_93-2>li:before{content:"\0025a0  "}.lst-kix_list_126-2>li:before{content:"\0025aa  "}ul.lst-kix_list_43-6{list-style-type:none}.lst-kix_list_56-4>li:before{content:"\0025aa  "}ul.lst-kix_list_1-0{list-style-type:none}ul.lst-kix_list_43-5{list-style-type:none}ul.lst-kix_list_43-8{list-style-type:none}ul.lst-kix_list_43-7{list-style-type:none}.lst-kix_list_19-4>li:before{content:"\0025cb  "}ul.lst-kix_list_43-0{list-style-type:none}.lst-kix_list_135-1>li:before{content:"\0025cb  "}.lst-kix_list_47-6>li:before{content:"\0025aa  "}ul.lst-kix_list_1-3{list-style-type:none}.lst-kix_list_126-8>li:before{content:"\0025aa  "}ul.lst-kix_list_1-4{list-style-type:none}ul.lst-kix_list_1-1{list-style-type:none}ul.lst-kix_list_1-2{list-style-type:none}ul.lst-kix_list_1-7{list-style-type:none}ul.lst-kix_list_1-8{list-style-type:none}.lst-kix_list_135-3>li:before{content:"\0025cf  "}ul.lst-kix_list_1-5{list-style-type:none}ul.lst-kix_list_1-6{list-style-type:none}.lst-kix_list_47-8>li:before{content:"\0025aa  "}.lst-kix_list_117-7>li{counter-increment:lst-ctn-kix_list_117-7}ul.lst-kix_list_78-1{list-style-type:none}ul.lst-kix_list_78-2{list-style-type:none}ul.lst-kix_list_78-0{list-style-type:none}ul.lst-kix_list_78-5{list-style-type:none}ul.lst-kix_list_78-6{list-style-type:none}ul.lst-kix_list_78-3{list-style-type:none}ul.lst-kix_list_78-4{list-style-type:none}.lst-kix_list_117-6>li:before{content:"" counter(lst-ctn-kix_list_117-6,decimal) ". "}.lst-kix_list_84-6>li:before{content:"\0025aa  "}.lst-kix_list_74-3>li:before{content:"\0025aa  "}.lst-kix_list_84-4>li:before{content:"\0025aa  "}ul.lst-kix_list_78-7{list-style-type:none}ul.lst-kix_list_78-8{list-style-type:none}.lst-kix_list_117-4>li:before{content:"" counter(lst-ctn-kix_list_117-4,decimal) ". "}.lst-kix_list_19-6>li:before{content:"\0025cf  "}.lst-kix_list_74-1>li:before{content:"o  "}.lst-kix_list_47-0>li:before{content:"\0025cf  "}ol.lst-kix_list_118-2.start{counter-reset:lst-ctn-kix_list_118-2 0}.lst-kix_list_107-1>li:before{content:"" counter(lst-ctn-kix_list_107-1,lower-latin) ". "}ul.lst-kix_list_65-3{list-style-type:none}ul.lst-kix_list_65-4{list-style-type:none}ul.lst-kix_list_65-1{list-style-type:none}ul.lst-kix_list_65-2{list-style-type:none}ul.lst-kix_list_65-7{list-style-type:none}ul.lst-kix_list_65-8{list-style-type:none}ul.lst-kix_list_65-5{list-style-type:none}.lst-kix_list_107-7>li:before{content:"" counter(lst-ctn-kix_list_107-7,lower-latin) ". "}ul.lst-kix_list_65-6{list-style-type:none}.lst-kix_list_136-7>li:before{content:"\0025aa  "}ul.lst-kix_list_65-0{list-style-type:none}.lst-kix_list_116-0>li:before{content:"\0025cf  "}.lst-kix_list_37-1>li:before{content:"o  "}.lst-kix_list_46-2>li:before{content:"\0025aa  "}.lst-kix_list_108-3>li:before{content:"\0025aa  "}.lst-kix_list_108-5>li:before{content:"\0025aa  "}.lst-kix_list_116-2>li:before{content:"\0025aa  "}.lst-kix_list_37-3>li:before{content:"\0025aa  "}.lst-kix_list_66-7>li:before{content:"\0025aa  "}ul.lst-kix_list_121-4{list-style-type:none}ul.lst-kix_list_121-5{list-style-type:none}ul.lst-kix_list_121-2{list-style-type:none}.lst-kix_list_65-5>li:before{content:"\0025aa  "}ul.lst-kix_list_121-3{list-style-type:none}ul.lst-kix_list_121-8{list-style-type:none}.lst-kix_list_92-0>li:before{content:"\0025cf  "}.lst-kix_list_18-0>li:before{content:"\0025cf  "}ul.lst-kix_list_121-6{list-style-type:none}ul.lst-kix_list_121-7{list-style-type:none}.lst-kix_list_38-7>li:before{content:"\0025aa  "}.lst-kix_list_18-2>li:before{content:"\0025a0  "}.lst-kix_list_65-3>li:before{content:"\0025aa  "}.lst-kix_list_104-2>li{counter-increment:lst-ctn-kix_list_104-2}.lst-kix_list_66-1>li:before{content:"o  "}.lst-kix_list_92-8>li:before{content:"\0025a0  "}.lst-kix_list_136-5>li:before{content:"\0025aa  "}.lst-kix_list_92-6>li:before{content:"\0025cf  "}ul.lst-kix_list_121-0{list-style-type:none}ul.lst-kix_list_121-1{list-style-type:none}.lst-kix_list_38-5>li:before{content:"\0025aa  "}ul.lst-kix_list_130-7{list-style-type:none}.lst-kix_list_134-5>li:before{content:"\0025aa  "}ul.lst-kix_list_130-6{list-style-type:none}.lst-kix_list_27-1>li:before{content:"o  "}ul.lst-kix_list_130-5{list-style-type:none}ul.lst-kix_list_130-4{list-style-type:none}.lst-kix_list_48-2>li:before{content:"\0025aa  "}.lst-kix_list_134-7>li:before{content:"\0025aa  "}.lst-kix_list_27-3>li:before{content:"\0025aa  "}ul.lst-kix_list_130-8{list-style-type:none}.lst-kix_list_48-4>li:before{content:"\0025aa  "}.lst-kix_list_18-8>li:before{content:"\0025a0  "}.lst-kix_list_69-2>li{counter-increment:lst-ctn-kix_list_69-2}ul.lst-kix_list_130-3{list-style-type:none}ul.lst-kix_list_130-2{list-style-type:none}ul.lst-kix_list_130-1{list-style-type:none}ul.lst-kix_list_130-0{list-style-type:none}.lst-kix_list_10-7>li:before{content:"\0025aa  "}ul.lst-kix_list_34-0{list-style-type:none}ul.lst-kix_list_34-1{list-style-type:none}.lst-kix_list_127-6>li:before{content:"\0025aa  "}ul.lst-kix_list_34-2{list-style-type:none}.lst-kix_list_10-5>li:before{content:"\0025aa  "}ul.lst-kix_list_34-3{list-style-type:none}ul.lst-kix_list_34-4{list-style-type:none}.lst-kix_g5lskmm1i0dj-5>li:before{content:"" counter(lst-ctn-kix_g5lskmm1i0dj-5,lower-roman) ". "}ul.lst-kix_list_34-5{list-style-type:none}ul.lst-kix_list_34-6{list-style-type:none}.lst-kix_list_106-3>li:before{content:"\0025aa  "}.lst-kix_list_127-4>li:before{content:"\0025aa  "}.lst-kix_list_106-5>li:before{content:"\0025aa  "}.lst-kix_list_9-2>li:before{content:"\0025aa  "}.lst-kix_list_46-4>li:before{content:"\0025aa  "}.lst-kix_list_67-5>li:before{content:"\0025aa  "}.lst-kix_list_12-5>li{counter-increment:lst-ctn-kix_list_12-5}ul.lst-kix_list_34-7{list-style-type:none}ul.lst-kix_list_34-8{list-style-type:none}.lst-kix_list_9-0>li:before{content:"\0025cf  "}ul.lst-kix_list_21-1{list-style-type:none}ul.lst-kix_list_21-2{list-style-type:none}ul.lst-kix_list_21-3{list-style-type:none}ul.lst-kix_list_21-4{list-style-type:none}ul.lst-kix_list_21-5{list-style-type:none}ul.lst-kix_list_21-6{list-style-type:none}ul.lst-kix_list_21-7{list-style-type:none}ul.lst-kix_list_21-8{list-style-type:none}.lst-kix_list_124-0>li:before{content:"\0025cf  "}ol.lst-kix_list_109-2{list-style-type:none}.lst-kix_list_11-3>li:before{content:"\0025aa  "}ul.lst-kix_list_21-0{list-style-type:none}.lst-kix_list_124-2>li:before{content:"\0025a0  "}ol.lst-kix_list_109-1{list-style-type:none}.lst-kix_list_29-1>li:before{content:"o  "}.lst-kix_list_124-8>li:before{content:"\0025a0  "}.lst-kix_list_29-3>li:before{content:"\0025aa  "}.lst-kix_list_49-8>li:before{content:"\0025aa  "}.lst-kix_list_9-8>li:before{content:"\0025aa  "}.lst-kix_g5lskmm1i0dj-7>li:before{content:"" counter(lst-ctn-kix_g5lskmm1i0dj-7,lower-latin) ". "}.lst-kix_list_133-1>li:before{content:"" counter(lst-ctn-kix_list_133-1,decimal) ". "}ul.lst-kix_list_56-0{list-style-type:none}ul.lst-kix_list_56-2{list-style-type:none}ul.lst-kix_list_56-1{list-style-type:none}ul.lst-kix_list_56-4{list-style-type:none}ul.lst-kix_list_56-3{list-style-type:none}.lst-kix_list_28-7>li:before{content:"\0025aa  "}ul.lst-kix_list_56-6{list-style-type:none}ul.lst-kix_list_56-5{list-style-type:none}.lst-kix_list_1-7>li:before{content:"\0025cb  "}.lst-kix_list_125-4>li:before{content:"\0025cb  "}.lst-kix_list_49-6>li:before{content:"\0025aa  "}.lst-kix_list_1-5>li:before{content:"\0025a0  "}.lst-kix_list_28-5>li:before{content:"\0025aa  "}.lst-kix_g5lskmm1i0dj-6>li{counter-increment:lst-ctn-kix_g5lskmm1i0dj-6}.lst-kix_list_2-1>li:before{content:"\0025cb  "}ol.lst-kix_list_107-5.start{counter-reset:lst-ctn-kix_list_107-5 0}.lst-kix_list_126-0>li:before{content:"\0025cf  "}ul.lst-kix_list_56-8{list-style-type:none}.lst-kix_list_49-0>li:before{content:"\0025cf  "}.lst-kix_list_2-3>li:before{content:"\0025cf  "}ul.lst-kix_list_56-7{list-style-type:none}.lst-kix_list_125-6>li:before{content:"\0025cf  "}.lst-kix_list_35-3>li:before{content:"\0025aa  "}.lst-kix_list_100-8>li:before{content:"\0025a0  "}.lst-kix_list_77-5>li:before{content:"\0025a0  "}.lst-kix_list_72-1>li:before{content:"o  "}.lst-kix_list_30-4>li:before{content:"o  "}.lst-kix_list_114-0>li:before{content:"\0025cf  "}.lst-kix_list_26-7>li:before{content:"\0025cb  "}.lst-kix_list_3-5>li:before{content:"\0025a0  "}.lst-kix_list_81-2>li:before{content:"\0025aa  "}.lst-kix_list_105-7>li:before{content:"\0025aa  "}ul.lst-kix_list_74-5{list-style-type:none}ul.lst-kix_list_74-6{list-style-type:none}ul.lst-kix_list_74-3{list-style-type:none}ul.lst-kix_list_74-4{list-style-type:none}ul.lst-kix_list_74-7{list-style-type:none}.lst-kix_list_8-6>li:before{content:"\0025aa  "}ul.lst-kix_list_74-8{list-style-type:none}ul.lst-kix_list_74-1{list-style-type:none}ul.lst-kix_list_74-2{list-style-type:none}ul.lst-kix_list_74-0{list-style-type:none}.lst-kix_list_95-2>li:before{content:"\0025a0  "}.lst-kix_6ppt4s25kk1y-6>li:before{content:"\0025cf  "}.lst-kix_list_90-6>li:before{content:"\0025cf  "}.lst-kix_list_128-0>li:before{content:"\0025cf  "}.lst-kix_list_123-6>li:before{content:"\0025cf  "}.lst-kix_list_63-5>li:before{content:"\0025aa  "}.lst-kix_list_53-0>li:before{content:"\0025cf  "}.lst-kix_list_68-1>li:before{content:"o  "}.lst-kix_list_21-3>li:before{content:"\0025aa  "}ul.lst-kix_list_61-7{list-style-type:none}ul.lst-kix_list_61-8{list-style-type:none}ul.lst-kix_list_61-5{list-style-type:none}ul.lst-kix_list_61-6{list-style-type:none}.lst-kix_list_128-8>li:before{content:"\0025a0  "}.lst-kix_list_45-8>li:before{content:"" counter(lst-ctn-kix_list_45-8,decimal) ". "}.lst-kix_list_91-2>li:before{content:"\0025a0  "}ul.lst-kix_list_61-0{list-style-type:none}ul.lst-kix_list_61-3{list-style-type:none}ul.lst-kix_list_61-4{list-style-type:none}.lst-kix_list_25-3>li:before{content:"\0025aa  "}ul.lst-kix_list_61-1{list-style-type:none}ul.lst-kix_list_61-2{list-style-type:none}.lst-kix_list_129-4>li:before{content:"\0025aa  "}.lst-kix_list_16-2>li:before{content:"\0025a0  "}.lst-kix_list_59-0>li:before{content:"\0025cf  "}.lst-kix_list_58-4>li:before{content:"o  "}.lst-kix_list_86-6>li:before{content:"\0025aa  "}ul.lst-kix_list_96-6{list-style-type:none}.lst-kix_list_114-8>li:before{content:"\0025a0  "}ul.lst-kix_list_96-5{list-style-type:none}ul.lst-kix_list_96-4{list-style-type:none}ul.lst-kix_list_96-3{list-style-type:none}.lst-kix_list_44-4>li:before{content:"\0025aa  "}.lst-kix_list_59-8>li:before{content:"\0025aa  "}ul.lst-kix_list_96-8{list-style-type:none}ul.lst-kix_list_96-7{list-style-type:none}.lst-kix_list_39-3>li:before{content:"\0025cf  "}ul.lst-kix_list_96-2{list-style-type:none}ul.lst-kix_list_96-1{list-style-type:none}ul.lst-kix_list_96-0{list-style-type:none}.lst-kix_list_87-2>li:before{content:"\0025aa  "}.lst-kix_list_115-4>li:before{content:"\0025aa  "}.lst-kix_list_100-0>li:before{content:"\0025cf  "}.lst-kix_list_45-0>li:before{content:"" counter(lst-ctn-kix_list_45-0,decimal) ". "}.lst-kix_list_17-6>li:before{content:"\0025cf  "}.lst-kix_list_71-5>li:before{content:"\0025a0  "}ul.lst-kix_list_87-4{list-style-type:none}ul.lst-kix_list_87-3{list-style-type:none}.lst-kix_list_85-2>li:before{content:"\0025aa  "}ul.lst-kix_list_87-2{list-style-type:none}.lst-kix_list_80-6>li:before{content:"\0025cf  "}ul.lst-kix_list_87-1{list-style-type:none}ul.lst-kix_list_87-8{list-style-type:none}ul.lst-kix_list_87-7{list-style-type:none}ul.lst-kix_list_87-6{list-style-type:none}.lst-kix_list_118-0>li:before{content:"" counter(lst-ctn-kix_list_118-0,decimal) ". "}ul.lst-kix_list_87-5{list-style-type:none}.lst-kix_list_43-0>li:before{content:"\0025cf  "}.lst-kix_list_43-8>li:before{content:"\0025aa  "}.lst-kix_list_22-7>li:before{content:"o  "}ul.lst-kix_list_87-0{list-style-type:none}ol.lst-kix_list_118-4.start{counter-reset:lst-ctn-kix_list_118-4 0}.lst-kix_list_64-1>li:before{content:"o  "}ul.lst-kix_lvjn8glkfwf0-1{list-style-type:none}.lst-kix_list_109-7>li:before{content:"\0025aa  "}ul.lst-kix_lvjn8glkfwf0-0{list-style-type:none}.lst-kix_list_34-7>li:before{content:"\0025aa  "}.lst-kix_list_118-8>li:before{content:"" counter(lst-ctn-kix_list_118-8,decimal) ". "}.lst-kix_list_55-8>li:before{content:"\0025aa  "}ul.lst-kix_lvjn8glkfwf0-8{list-style-type:none}ul.lst-kix_lvjn8glkfwf0-7{list-style-type:none}ul.lst-kix_lvjn8glkfwf0-6{list-style-type:none}ul.lst-kix_lvjn8glkfwf0-5{list-style-type:none}ul.lst-kix_lvjn8glkfwf0-4{list-style-type:none}ul.lst-kix_lvjn8glkfwf0-3{list-style-type:none}.lst-kix_list_101-4>li:before{content:"\0025aa  "}ul.lst-kix_lvjn8glkfwf0-2{list-style-type:none}ol.lst-kix_list_105-1.start{counter-reset:lst-ctn-kix_list_105-1 0}ul.lst-kix_list_30-3{list-style-type:none}ul.lst-kix_list_30-4{list-style-type:none}.lst-kix_list_15-6>li:before{content:"\0025cf  "}ul.lst-kix_list_30-5{list-style-type:none}ul.lst-kix_list_30-6{list-style-type:none}.lst-kix_list_73-5>li:before{content:"\0025a0  "}ul.lst-kix_list_30-7{list-style-type:none}ol.lst-kix_list_118-8{list-style-type:none}ul.lst-kix_list_30-8{list-style-type:none}.lst-kix_list_94-6>li:before{content:"\0025cf  "}.lst-kix_ee0fx9z4yp3a-2>li:before{content:"\0025a0  "}.lst-kix_list_78-1>li:before{content:"\0025cb  "}ol.lst-kix_list_118-4{list-style-type:none}ol.lst-kix_list_118-5{list-style-type:none}.lst-kix_list_99-2>li:before{content:"\0025a0  "}ol.lst-kix_list_118-6{list-style-type:none}.lst-kix_list_52-4>li:before{content:"\0025aa  "}ol.lst-kix_list_118-7{list-style-type:none}.lst-kix_list_36-7>li:before{content:"\0025cb  "}ol.lst-kix_list_118-0{list-style-type:none}ul.lst-kix_list_30-0{list-style-type:none}ol.lst-kix_list_118-1{list-style-type:none}ul.lst-kix_list_30-1{list-style-type:none}ol.lst-kix_list_118-2{list-style-type:none}.lst-kix_list_57-0>li:before{content:"\0025cf  "}.lst-kix_list_57-8>li:before{content:"\0025aa  "}ul.lst-kix_list_30-2{list-style-type:none}.lst-kix_list_116-8>li:before{content:"\0025aa  "}ol.lst-kix_list_118-3{list-style-type:none}.lst-kix_list_20-7>li:before{content:"\0025aa  "}.lst-kix_835ax5k7z1l9-6>li:before{content:"\0025cf  "}.lst-kix_list_41-8>li:before{content:"\0025a0  "}.lst-kix_list_107-2>li{counter-increment:lst-ctn-kix_list_107-2}.lst-kix_tn8cl5j8lycz-8>li:before{content:"\0025a0  "}.lst-kix_list_118-2>li{counter-increment:lst-ctn-kix_list_118-2}.lst-kix_list_41-0>li:before{content:"\0025cf  "}.lst-kix_list_62-1>li:before{content:"o  "}.lst-kix_list_102-8>li:before{content:"\0025aa  "}.lst-kix_list_82-6>li:before{content:"\0025aa  "}ol.lst-kix_list_105-2{list-style-type:none}.lst-kix_list_75-5>li:before{content:"\0025aa  "}.lst-kix_list_54-4>li:before{content:"\0025aa  "}ol.lst-kix_list_105-1{list-style-type:none}.lst-kix_list_33-3>li:before{content:"\0025aa  "}.lst-kix_list_83-2>li:before{content:"\0025aa  "}.lst-kix_tn8cl5j8lycz-0>li:before{content:"\0025cf  "}.lst-kix_61pipssxjd5z-3>li:before{content:"\0025cf  "}.lst-kix_list_53-8>li:before{content:"\0025aa  "}ul.lst-kix_list_52-4{list-style-type:none}ul.lst-kix_list_52-3{list-style-type:none}ul.lst-kix_list_52-6{list-style-type:none}ul.lst-kix_list_52-5{list-style-type:none}.lst-kix_list_119-4>li:before{content:"" counter(lst-ctn-kix_list_119-4,decimal) ". "}ul.lst-kix_list_52-8{list-style-type:none}.lst-kix_list_76-1>li:before{content:"o  "}ul.lst-kix_list_52-7{list-style-type:none}ul.lst-kix_list_108-0{list-style-type:none}.lst-kix_list_55-0>li:before{content:"\0025cf  "}ul.lst-kix_list_108-3{list-style-type:none}ul.lst-kix_list_108-4{list-style-type:none}ul.lst-kix_list_52-0{list-style-type:none}ul.lst-kix_list_108-7{list-style-type:none}ul.lst-kix_list_108-8{list-style-type:none}ul.lst-kix_list_52-2{list-style-type:none}ul.lst-kix_list_108-5{list-style-type:none}.lst-kix_list_96-6>li:before{content:"\0025cf  "}ul.lst-kix_list_52-1{list-style-type:none}ul.lst-kix_list_108-6{list-style-type:none}ol.lst-kix_list_118-7.start{counter-reset:lst-ctn-kix_list_118-7 0}.lst-kix_list_61-5>li:before{content:"\0025aa  "}.lst-kix_list_40-4>li:before{content:"\0025cb  "}.lst-kix_list_97-2>li:before{content:"\0025a0  "}.lst-kix_list_121-6>li:before{content:"\0025aa  "}.lst-kix_list_51-5>li:before{content:"\0025a0  "}ul.lst-kix_list_81-8{list-style-type:none}ul.lst-kix_list_81-7{list-style-type:none}.lst-kix_list_14-3>li:before{content:"\0025aa  "}.lst-kix_list_69-7>li{counter-increment:lst-ctn-kix_list_69-7}ul.lst-kix_list_28-0{list-style-type:none}.lst-kix_list_14-0>li:before{content:"\0025cf  "}ul.lst-kix_list_28-1{list-style-type:none}ul.lst-kix_list_81-2{list-style-type:none}ul.lst-kix_list_81-1{list-style-type:none}ul.lst-kix_list_81-0{list-style-type:none}ul.lst-kix_list_81-6{list-style-type:none}.lst-kix_list_121-0>li:before{content:"\0025cf  "}ul.lst-kix_list_81-5{list-style-type:none}.lst-kix_list_51-2>li:before{content:"\0025a0  "}.lst-kix_list_51-3>li:before{content:"\0025cf  "}ul.lst-kix_list_81-4{list-style-type:none}.lst-kix_list_121-7>li:before{content:"\0025aa  "}ul.lst-kix_list_81-3{list-style-type:none}.lst-kix_list_14-6>li:before{content:"\0025aa  "}.lst-kix_list_89-6>li:before{content:"\0025cf  "}ul.lst-kix_tn8cl5j8lycz-6{list-style-type:none}ul.lst-kix_list_28-2{list-style-type:none}ul.lst-kix_tn8cl5j8lycz-5{list-style-type:none}ul.lst-kix_list_28-3{list-style-type:none}ul.lst-kix_tn8cl5j8lycz-8{list-style-type:none}ul.lst-kix_list_28-4{list-style-type:none}ul.lst-kix_tn8cl5j8lycz-7{list-style-type:none}ul.lst-kix_list_28-5{list-style-type:none}ul.lst-kix_tn8cl5j8lycz-2{list-style-type:none}ul.lst-kix_list_28-6{list-style-type:none}ul.lst-kix_tn8cl5j8lycz-1{list-style-type:none}ul.lst-kix_list_28-7{list-style-type:none}.lst-kix_list_51-6>li:before{content:"\0025cf  "}ul.lst-kix_tn8cl5j8lycz-4{list-style-type:none}ul.lst-kix_list_28-8{list-style-type:none}.lst-kix_list_14-2>li:before{content:"\0025aa  "}ul.lst-kix_tn8cl5j8lycz-3{list-style-type:none}ul.lst-kix_tn8cl5j8lycz-0{list-style-type:none}.lst-kix_list_89-0>li:before{content:"\0025cf  "}.lst-kix_list_102-0>li:before{content:"\0025cf  "}ol.lst-kix_list_12-0.start{counter-reset:lst-ctn-kix_list_12-0 0}.lst-kix_fahi2s4j7zmm-7>li:before{content:"\0025cb  "}.lst-kix_list_32-2>li:before{content:"\0025a0  "}.lst-kix_list_102-3>li:before{content:"\0025aa  "}.lst-kix_list_32-1>li:before{content:"\0025cb  "}.lst-kix_list_102-2>li:before{content:"" counter(lst-ctn-kix_list_102-2,decimal) ". "}.lst-kix_list_102-6>li:before{content:"\0025aa  "}.lst-kix_list_89-3>li:before{content:"\0025cf  "}.lst-kix_list_89-2>li:before{content:"\0025a0  "}.lst-kix_list_102-5>li:before{content:"\0025aa  "}.lst-kix_list_5-0>li:before{content:"\0025cf  "}.lst-kix_list_70-0>li:before{content:"\0025cf  "}.lst-kix_list_5-3>li:before{content:"\0025aa  "}.lst-kix_list_120-1>li{counter-increment:lst-ctn-kix_list_120-1}.lst-kix_fahi2s4j7zmm-0>li:before{content:"\0025cf  "}.lst-kix_list_5-2>li:before{content:"\0025aa  "}.lst-kix_list_70-1>li:before{content:"o  "}.lst-kix_fahi2s4j7zmm-3>li:before{content:"\0025cf  "}.lst-kix_fahi2s4j7zmm-4>li:before{content:"\0025cb  "}.lst-kix_list_5-6>li:before{content:"\0025aa  "}.lst-kix_list_70-6>li:before{content:"\0025aa  "}.lst-kix_list_88-3>li:before{content:"\0025aa  "}.lst-kix_fahi2s4j7zmm-1>li:before{content:"\0025cb  "}.lst-kix_list_70-3>li:before{content:"\0025aa  "}.lst-kix_list_70-7>li:before{content:"\0025aa  "}.lst-kix_list_70-4>li:before{content:"\0025aa  "}.lst-kix_list_88-1>li:before{content:"o  "}.lst-kix_list_88-0>li:before{content:"\0025cf  "}ol.lst-kix_list_107-1.start{counter-reset:lst-ctn-kix_list_107-1 0}ol.lst-kix_list_12-5.start{counter-reset:lst-ctn-kix_list_12-5 0}.lst-kix_list_120-4>li:before{content:"" counter(lst-ctn-kix_list_120-4,decimal) ". "}.lst-kix_list_120-5>li:before{content:"" counter(lst-ctn-kix_list_120-5,decimal) ". "}.lst-kix_list_50-0>li:before{content:"\0025cf  "}.lst-kix_list_50-3>li:before{content:"\0025aa  "}.lst-kix_list_50-4>li:before{content:"\0025aa  "}.lst-kix_list_120-7>li:before{content:"" counter(lst-ctn-kix_list_120-7,decimal) ". "}.lst-kix_list_6-2>li:before{content:"\0025aa  "}.lst-kix_list_50-7>li:before{content:"\0025aa  "}.lst-kix_list_120-8>li:before{content:"" counter(lst-ctn-kix_list_120-8,decimal) ". "}.lst-kix_list_121-1>li:before{content:"o  "}.lst-kix_list_6-8>li:before{content:"\0025aa  "}.lst-kix_list_51-0>li:before{content:"\0025cf  "}.lst-kix_list_50-6>li:before{content:"\0025aa  "}.lst-kix_list_6-5>li:before{content:"\0025aa  "}.lst-kix_list_121-4>li:before{content:"\0025aa  "}.lst-kix_list_121-3>li:before{content:"\0025aa  "}.lst-kix_list_7-4>li:before{content:"\0025aa  "}.lst-kix_list_117-1>li{counter-increment:lst-ctn-kix_list_117-1}.lst-kix_list_69-3>li:before{content:"" counter(lst-ctn-kix_list_69-3,decimal) ". "}.lst-kix_list_69-5>li:before{content:"" counter(lst-ctn-kix_list_69-5,decimal) ". "}.lst-kix_list_122-0>li:before{content:"\0025cf  "}.lst-kix_list_52-1>li:before{content:"o  "}.lst-kix_list_122-2>li:before{content:"\0025a0  "}.lst-kix_list_13-7>li:before{content:"\0025aa  "}.lst-kix_list_7-8>li:before{content:"\0025aa  "}.lst-kix_list_101-3>li:before{content:"\0025aa  "}ul.lst-kix_list_72-7{list-style-type:none}.lst-kix_list_15-5>li:before{content:"\0025a0  "}ul.lst-kix_list_126-0{list-style-type:none}ul.lst-kix_list_72-8{list-style-type:none}ul.lst-kix_list_72-5{list-style-type:none}.lst-kix_list_31-6>li:before{content:"\0025cf  "}.lst-kix_list_31-8>li:before{content:"\0025a0  "}.lst-kix_list_45-6>li{counter-increment:lst-ctn-kix_list_45-6}ul.lst-kix_list_72-6{list-style-type:none}ul.lst-kix_list_126-4{list-style-type:none}.lst-kix_list_52-5>li:before{content:"\0025aa  "}ul.lst-kix_list_126-3{list-style-type:none}.lst-kix_list_120-1>li:before{content:"" counter(lst-ctn-kix_list_120-1,decimal) ". "}ul.lst-kix_list_126-2{list-style-type:none}.lst-kix_list_122-6>li:before{content:"\0025cf  "}ul.lst-kix_list_126-1{list-style-type:none}ul.lst-kix_list_126-8{list-style-type:none}ul.lst-kix_list_72-0{list-style-type:none}ul.lst-kix_list_126-7{list-style-type:none}.lst-kix_list_4-1>li:before{content:"\0025cb  "}.lst-kix_list_31-2>li:before{content:"\0025a0  "}ul.lst-kix_list_126-6{list-style-type:none}ul.lst-kix_list_126-5{list-style-type:none}ul.lst-kix_list_72-3{list-style-type:none}.lst-kix_list_101-7>li:before{content:"\0025aa  "}ul.lst-kix_list_72-4{list-style-type:none}ul.lst-kix_list_72-1{list-style-type:none}ol.lst-kix_list_107-6.start{counter-reset:lst-ctn-kix_list_107-6 0}ul.lst-kix_list_72-2{list-style-type:none}.lst-kix_list_88-4>li:before{content:"\0025aa  "}ul.lst-kix_list_19-7{list-style-type:none}ul.lst-kix_list_19-6{list-style-type:none}ol.lst-kix_list_119-7.start{counter-reset:lst-ctn-kix_list_119-7 0}ul.lst-kix_list_19-5{list-style-type:none}.lst-kix_list_4-3>li:before{content:"\0025cf  "}ul.lst-kix_list_19-4{list-style-type:none}ul.lst-kix_list_19-3{list-style-type:none}ul.lst-kix_list_19-2{list-style-type:none}ul.lst-kix_list_19-1{list-style-type:none}.lst-kix_list_103-2>li{counter-increment:lst-ctn-kix_list_103-2}.lst-kix_list_88-6>li:before{content:"\0025aa  "}ul.lst-kix_list_19-0{list-style-type:none}ul.lst-kix_list_19-8{list-style-type:none}.lst-kix_tn8cl5j8lycz-3>li:before{content:"\0025cf  "}.lst-kix_list_123-8>li:before{content:"\0025a0  "}.lst-kix_tn8cl5j8lycz-5>li:before{content:"\0025a0  "}.lst-kix_list_32-4>li:before{content:"\0025cb  "}.lst-kix_list_103-1>li:before{content:"" counter(lst-ctn-kix_list_103-1,lower-latin) ". "}.lst-kix_list_33-4>li:before{content:"\0025aa  "}.lst-kix_list_12-1>li:before{content:"" counter(lst-ctn-kix_list_12-1,decimal) ". "}.lst-kix_list_45-5>li{counter-increment:lst-ctn-kix_list_45-5}.lst-kix_list_33-0>li:before{content:"\0025cf  "}.lst-kix_list_53-7>li:before{content:"\0025aa  "}.lst-kix_list_109-1>li{counter-increment:lst-ctn-kix_list_109-1}.lst-kix_list_32-8>li:before{content:"\0025a0  "}.lst-kix_list_103-5>li:before{content:"\0025aa  "}ul.lst-kix_list_94-8{list-style-type:none}ul.lst-kix_list_94-7{list-style-type:none}.lst-kix_list_34-0>li:before{content:"\0025cf  "}ul.lst-kix_list_104-0{list-style-type:none}.lst-kix_list_104-1>li:before{content:"" counter(lst-ctn-kix_list_104-1,lower-latin) ". "}ul.lst-kix_list_94-6{list-style-type:none}ol.lst-kix_list_69-2.start{counter-reset:lst-ctn-kix_list_69-2 0}ul.lst-kix_list_94-5{list-style-type:none}ul.lst-kix_list_104-3{list-style-type:none}ul.lst-kix_list_104-4{list-style-type:none}.lst-kix_list_13-3>li:before{content:"\0025aa  "}ul.lst-kix_list_94-0{list-style-type:none}ul.lst-kix_list_104-7{list-style-type:none}ul.lst-kix_list_104-8{list-style-type:none}ul.lst-kix_list_104-5{list-style-type:none}ul.lst-kix_list_104-6{list-style-type:none}ul.lst-kix_list_94-4{list-style-type:none}ul.lst-kix_list_94-3{list-style-type:none}.lst-kix_list_34-6>li:before{content:"\0025aa  "}ul.lst-kix_list_94-2{list-style-type:none}ul.lst-kix_list_94-1{list-style-type:none}.lst-kix_list_12-5>li:before{content:"" counter(lst-ctn-kix_list_12-5,decimal) ". "}.lst-kix_list_12-7>li:before{content:"" counter(lst-ctn-kix_list_12-7,decimal) ". "}.lst-kix_list_107-6>li{counter-increment:lst-ctn-kix_list_107-6}.lst-kix_list_106-2>li{counter-increment:lst-ctn-kix_list_106-2}.lst-kix_list_104-7>li:before{content:"\0025aa  "}.lst-kix_list_13-1>li:before{content:"o  "}ul.lst-kix_list_113-1{list-style-type:none}ul.lst-kix_list_113-2{list-style-type:none}ul.lst-kix_list_24-0{list-style-type:none}ul.lst-kix_list_24-1{list-style-type:none}ul.lst-kix_list_113-0{list-style-type:none}ul.lst-kix_list_24-2{list-style-type:none}ul.lst-kix_list_113-5{list-style-type:none}.lst-kix_list_105-6>li:before{content:"\0025aa  "}ul.lst-kix_list_24-3{list-style-type:none}.lst-kix_list_35-5>li:before{content:"\0025aa  "}ul.lst-kix_list_113-6{list-style-type:none}ul.lst-kix_list_24-4{list-style-type:none}ul.lst-kix_list_113-3{list-style-type:none}ul.lst-kix_list_24-5{list-style-type:none}ul.lst-kix_list_113-4{list-style-type:none}ul.lst-kix_list_113-7{list-style-type:none}ul.lst-kix_list_113-8{list-style-type:none}.lst-kix_list_100-7>li:before{content:"\0025cb  "}.lst-kix_list_68-6>li:before{content:"\0025aa  "}.lst-kix_list_68-7>li:before{content:"\0025aa  "}.lst-kix_list_72-8>li:before{content:"\0025aa  "}ul.lst-kix_list_24-6{list-style-type:none}ul.lst-kix_list_24-7{list-style-type:none}ul.lst-kix_list_24-8{list-style-type:none}.lst-kix_list_3-4>li:before{content:"\0025cb  "}.lst-kix_list_8-0>li:before{content:"\0025cf  "}.lst-kix_list_30-6>li:before{content:"\0025cf  "}.lst-kix_list_8-7>li:before{content:"\0025aa  "}.lst-kix_list_3-8>li:before{content:"\0025a0  "}ul.lst-kix_list_59-1{list-style-type:none}ul.lst-kix_list_59-0{list-style-type:none}ul.lst-kix_list_59-3{list-style-type:none}ul.lst-kix_list_59-2{list-style-type:none}.lst-kix_list_90-0>li:before{content:"\0025cf  "}.lst-kix_list_8-3>li:before{content:"\0025aa  "}.lst-kix_list_68-3>li:before{content:"\0025aa  "}.lst-kix_list_3-7>li:before{content:"\0025cb  "}ol.lst-kix_list_119-3.start{counter-reset:lst-ctn-kix_list_119-3 0}.lst-kix_list_90-1>li:before{content:"\0025cb  "}.lst-kix_list_8-4>li:before{content:"\0025aa  "}.lst-kix_list_90-4>li:before{content:"\0025cb  "}.lst-kix_list_35-8>li:before{content:"\0025aa  "}.lst-kix_6ppt4s25kk1y-5>li:before{content:"\0025a0  "}ul.lst-kix_list_59-5{list-style-type:none}ul.lst-kix_list_59-4{list-style-type:none}ul.lst-kix_list_59-7{list-style-type:none}ul.lst-kix_list_59-6{list-style-type:none}ul.lst-kix_list_59-8{list-style-type:none}.lst-kix_list_16-8>li:before{content:"\0025a0  "}.lst-kix_list_16-7>li:before{content:"\0025cb  "}ul.lst-kix_list_46-1{list-style-type:none}.lst-kix_list_87-8>li:before{content:"\0025aa  "}ul.lst-kix_list_46-0{list-style-type:none}ul.lst-kix_list_46-3{list-style-type:none}.lst-kix_list_91-0>li:before{content:"\0025cf  "}ul.lst-kix_list_46-2{list-style-type:none}ul.lst-kix_list_46-5{list-style-type:none}ul.lst-kix_list_46-4{list-style-type:none}.lst-kix_list_17-0>li:before{content:"\0025cf  "}.lst-kix_list_4-7>li:before{content:"\0025cb  "}.lst-kix_list_87-4>li:before{content:"\0025aa  "}.lst-kix_list_16-4>li:before{content:"\0025cb  "}ul.lst-kix_list_46-7{list-style-type:none}ul.lst-kix_list_46-6{list-style-type:none}ul.lst-kix_list_46-8{list-style-type:none}.lst-kix_list_87-7>li:before{content:"\0025aa  "}.lst-kix_list_71-3>li:before{content:"\0025cf  "}.lst-kix_list_86-8>li:before{content:"\0025aa  "}.lst-kix_list_71-0>li:before{content:"\0025cf  "}.lst-kix_list_17-7>li:before{content:"\0025cb  "}.lst-kix_list_17-3>li:before{content:"\0025cf  "}.lst-kix_list_17-4>li:before{content:"\0025cb  "}ol.lst-kix_list_69-6.start{counter-reset:lst-ctn-kix_list_69-6 0}ol.lst-kix_list_119-2.start{counter-reset:lst-ctn-kix_list_119-2 0}.lst-kix_list_69-2>li:before{content:"" counter(lst-ctn-kix_list_69-2,decimal) ". "}.lst-kix_list_2-8>li:before{content:"\0025a0  "}.lst-kix_list_85-0>li:before{content:"\0025cf  "}.lst-kix_list_69-6>li:before{content:"" counter(lst-ctn-kix_list_69-6,decimal) ". "}.lst-kix_list_10-0>li:before{content:"\0025cf  "}.lst-kix_list_117-0>li{counter-increment:lst-ctn-kix_list_117-0}ul.lst-kix_list_90-0{list-style-type:none}.lst-kix_list_122-3>li:before{content:"\0025cf  "}.lst-kix_list_18-3>li:before{content:"\0025cf  "}.lst-kix_list_106-2>li:before{content:"" counter(lst-ctn-kix_list_106-2,lower-roman) ". "}.lst-kix_list_7-7>li:before{content:"\0025aa  "}.lst-kix_list_73-7>li:before{content:"\0025cb  "}.lst-kix_list_36-5>li:before{content:"\0025a0  "}ul.lst-kix_list_122-3{list-style-type:none}ul.lst-kix_list_122-4{list-style-type:none}ul.lst-kix_list_122-1{list-style-type:none}ul.lst-kix_list_122-2{list-style-type:none}.lst-kix_list_31-5>li:before{content:"\0025a0  "}ul.lst-kix_list_122-7{list-style-type:none}ul.lst-kix_list_122-8{list-style-type:none}ul.lst-kix_list_122-5{list-style-type:none}.lst-kix_list_106-6>li:before{content:"\0025aa  "}.lst-kix_list_101-6>li:before{content:"\0025aa  "}ul.lst-kix_list_122-6{list-style-type:none}ul.lst-kix_list_15-3{list-style-type:none}.lst-kix_list_4-0>li:before{content:"\0025cf  "}.lst-kix_list_36-1>li:before{content:"\0025cb  "}ol.lst-kix_list_69-7.start{counter-reset:lst-ctn-kix_list_69-7 0}ul.lst-kix_list_15-2{list-style-type:none}ul.lst-kix_list_15-1{list-style-type:none}.lst-kix_list_15-8>li:before{content:"\0025a0  "}.lst-kix_list_52-2>li:before{content:"\0025aa  "}ul.lst-kix_list_15-0{list-style-type:none}.lst-kix_list_4-4>li:before{content:"\0025cb  "}ul.lst-kix_list_15-8{list-style-type:none}ul.lst-kix_list_15-7{list-style-type:none}ol.lst-kix_list_102-2.start{counter-reset:lst-ctn-kix_list_102-2 0}ul.lst-kix_list_15-6{list-style-type:none}ul.lst-kix_list_15-5{list-style-type:none}.lst-kix_list_9-3>li:before{content:"\0025aa  "}ul.lst-kix_list_15-4{list-style-type:none}.lst-kix_list_88-7>li:before{content:"\0025aa  "}ol.lst-kix_list_107-0.start{counter-reset:lst-ctn-kix_list_107-0 0}ul.lst-kix_list_122-0{list-style-type:none}ul.lst-kix_list_135-2{list-style-type:none}ul.lst-kix_list_135-1{list-style-type:none}ul.lst-kix_list_135-0{list-style-type:none}.lst-kix_tn8cl5j8lycz-2>li:before{content:"\0025a0  "}ul.lst-kix_list_135-6{list-style-type:none}ul.lst-kix_list_135-5{list-style-type:none}.lst-kix_list_74-7>li:before{content:"\0025aa  "}ul.lst-kix_list_135-4{list-style-type:none}.lst-kix_list_29-8>li:before{content:"\0025aa  "}ul.lst-kix_list_135-3{list-style-type:none}.lst-kix_list_103-2>li:before{content:"" counter(lst-ctn-kix_list_103-2,decimal) ". "}ul.lst-kix_list_135-8{list-style-type:none}.lst-kix_tn8cl5j8lycz-6>li:before{content:"\0025cf  "}.lst-kix_list_32-5>li:before{content:"\0025a0  "}ul.lst-kix_list_135-7{list-style-type:none}.lst-kix_list_12-4>li:before{content:"" counter(lst-ctn-kix_list_12-4,decimal) ". "}ul.lst-kix_list_6-6{list-style-type:none}ul.lst-kix_list_6-7{list-style-type:none}ul.lst-kix_list_6-4{list-style-type:none}ul.lst-kix_list_6-5{list-style-type:none}.lst-kix_list_124-7>li:before{content:"\0025cb  "}.lst-kix_6ppt4s25kk1y-8>li:before{content:"\0025a0  "}ul.lst-kix_list_6-8{list-style-type:none}.lst-kix_list_33-1>li:before{content:"o  "}.lst-kix_list_1-0>li:before{content:"\0025cf  "}.lst-kix_list_11-8>li:before{content:"\0025aa  "}ul.lst-kix_list_6-2{list-style-type:none}ul.lst-kix_list_6-3{list-style-type:none}ul.lst-kix_list_6-0{list-style-type:none}ul.lst-kix_list_6-1{list-style-type:none}.lst-kix_list_119-6>li:before{content:"" counter(lst-ctn-kix_list_119-6,decimal) ". "}ul.lst-kix_list_100-3{list-style-type:none}ul.lst-kix_list_100-4{list-style-type:none}.lst-kix_list_49-5>li:before{content:"\0025aa  "}ul.lst-kix_list_100-1{list-style-type:none}.lst-kix_list_13-0>li:before{content:"\0025cf  "}ul.lst-kix_list_100-2{list-style-type:none}ul.lst-kix_list_37-0{list-style-type:none}ul.lst-kix_list_100-7{list-style-type:none}ul.lst-kix_list_37-1{list-style-type:none}ul.lst-kix_list_100-8{list-style-type:none}ul.lst-kix_list_37-2{list-style-type:none}ul.lst-kix_list_100-5{list-style-type:none}ul.lst-kix_list_37-3{list-style-type:none}ul.lst-kix_list_100-6{list-style-type:none}ul.lst-kix_list_90-4{list-style-type:none}ul.lst-kix_list_90-3{list-style-type:none}ul.lst-kix_list_90-2{list-style-type:none}.lst-kix_list_13-4>li:before{content:"\0025aa  "}ul.lst-kix_list_90-1{list-style-type:none}ul.lst-kix_list_90-8{list-style-type:none}ul.lst-kix_list_90-7{list-style-type:none}ul.lst-kix_list_90-6{list-style-type:none}ul.lst-kix_list_90-5{list-style-type:none}.lst-kix_list_125-3>li:before{content:"\0025cf  "}.lst-kix_list_55-6>li:before{content:"\0025aa  "}.lst-kix_list_54-6>li:before{content:"\0025aa  "}ul.lst-kix_list_37-4{list-style-type:none}ul.lst-kix_list_37-5{list-style-type:none}ul.lst-kix_list_37-6{list-style-type:none}ul.lst-kix_list_37-7{list-style-type:none}.lst-kix_list_125-7>li:before{content:"\0025cb  "}ul.lst-kix_list_37-8{list-style-type:none}ul.lst-kix_list_100-0{list-style-type:none}.lst-kix_list_12-8>li:before{content:"" counter(lst-ctn-kix_list_12-8,decimal) ". "}.lst-kix_list_55-2>li:before{content:"\0025aa  "}ul.lst-kix_list_20-2{list-style-type:none}ul.lst-kix_list_20-3{list-style-type:none}ul.lst-kix_list_20-4{list-style-type:none}ul.lst-kix_list_20-5{list-style-type:none}.lst-kix_list_133-1>li{counter-increment:lst-ctn-kix_list_133-1}ul.lst-kix_list_20-6{list-style-type:none}.lst-kix_list_126-6>li:before{content:"\0025aa  "}ul.lst-kix_list_20-7{list-style-type:none}ol.lst-kix_list_12-6.start{counter-reset:lst-ctn-kix_list_12-6 0}.lst-kix_list_93-1>li:before{content:"\0025cb  "}ul.lst-kix_list_20-8{list-style-type:none}.lst-kix_list_56-5>li:before{content:"\0025aa  "}ol.lst-kix_list_69-8.start{counter-reset:lst-ctn-kix_list_69-8 0}.lst-kix_list_19-2>li:before{content:"\0025a0  "}ul.lst-kix_list_20-0{list-style-type:none}ol.lst-kix_list_108-1{list-style-type:none}ul.lst-kix_list_20-1{list-style-type:none}ol.lst-kix_list_108-2{list-style-type:none}.lst-kix_list_135-0>li:before{content:"\0025cf  "}.lst-kix_list_47-7>li:before{content:"\0025aa  "}.lst-kix_list_93-8>li:before{content:"\0025a0  "}ol.lst-kix_list_119-6.start{counter-reset:lst-ctn-kix_list_119-6 0}ul.lst-kix_list_55-1{list-style-type:none}.lst-kix_list_84-0>li:before{content:"\0025cf  "}ul.lst-kix_list_55-0{list-style-type:none}ul.lst-kix_list_55-3{list-style-type:none}.lst-kix_list_117-2>li:before{content:"" counter(lst-ctn-kix_list_117-2,decimal) ". "}ul.lst-kix_list_55-2{list-style-type:none}ul.lst-kix_list_55-5{list-style-type:none}.lst-kix_list_45-0>li{counter-increment:lst-ctn-kix_list_45-0}ul.lst-kix_list_55-4{list-style-type:none}ul.lst-kix_list_55-7{list-style-type:none}ul.lst-kix_list_55-6{list-style-type:none}.lst-kix_list_107-8>li{counter-increment:lst-ctn-kix_list_107-8}.lst-kix_list_47-4>li:before{content:"\0025aa  "}.lst-kix_list_117-8>li:before{content:"" counter(lst-ctn-kix_list_117-8,decimal) ". "}.lst-kix_list_19-8>li:before{content:"\0025a0  "}.lst-kix_list_56-8>li:before{content:"\0025aa  "}.lst-kix_list_84-7>li:before{content:"\0025aa  "}.lst-kix_list_19-5>li:before{content:"\0025a0  "}ul.lst-kix_list_55-8{list-style-type:none}.lst-kix_list_47-1>li:before{content:"o  "}.lst-kix_list_74-0>li:before{content:"\0025cf  "}.lst-kix_list_117-5>li:before{content:"" counter(lst-ctn-kix_list_117-5,decimal) ". "}ul.lst-kix_list_42-3{list-style-type:none}ul.lst-kix_list_42-2{list-style-type:none}ul.lst-kix_list_42-5{list-style-type:none}.lst-kix_list_37-7>li:before{content:"\0025aa  "}.lst-kix_list_66-8>li:before{content:"\0025aa  "}ul.lst-kix_list_42-4{list-style-type:none}.lst-kix_list_107-8>li:before{content:"" counter(lst-ctn-kix_list_107-8,lower-roman) ". "}ul.lst-kix_list_42-7{list-style-type:none}ul.lst-kix_list_42-6{list-style-type:none}ul.lst-kix_list_42-8{list-style-type:none}.lst-kix_list_136-6>li:before{content:"\0025aa  "}.lst-kix_list_38-0>li:before{content:"\0025cf  "}ul.lst-kix_list_42-1{list-style-type:none}ul.lst-kix_list_42-0{list-style-type:none}.lst-kix_list_107-5>li:before{content:"" counter(lst-ctn-kix_list_107-5,lower-roman) ". "}.lst-kix_list_117-3>li{counter-increment:lst-ctn-kix_list_117-3}ol.lst-kix_list_119-1.start{counter-reset:lst-ctn-kix_list_119-1 0}.lst-kix_list_116-6>li:before{content:"\0025aa  "}.lst-kix_list_108-4>li:before{content:"\0025aa  "}.lst-kix_list_118-4>li{counter-increment:lst-ctn-kix_list_118-4}.lst-kix_list_37-4>li:before{content:"\0025aa  "}.lst-kix_list_66-5>li:before{content:"\0025aa  "}.lst-kix_list_108-1>li:before{content:"" counter(lst-ctn-kix_list_108-1,lower-latin) ". "}ul.lst-kix_list_77-2{list-style-type:none}.lst-kix_list_12-1>li{counter-increment:lst-ctn-kix_list_12-1}.lst-kix_list_119-5>li{counter-increment:lst-ctn-kix_list_119-5}.lst-kix_list_65-6>li:before{content:"\0025aa  "}ul.lst-kix_list_77-3{list-style-type:none}.lst-kix_list_92-2>li:before{content:"\0025a0  "}ul.lst-kix_list_77-0{list-style-type:none}ul.lst-kix_list_77-1{list-style-type:none}ul.lst-kix_list_77-6{list-style-type:none}ul.lst-kix_list_77-7{list-style-type:none}ul.lst-kix_list_77-4{list-style-type:none}ul.lst-kix_list_77-5{list-style-type:none}.lst-kix_list_108-7>li:before{content:"\0025aa  "}.lst-kix_list_135-7>li:before{content:"\0025cb  "}.lst-kix_list_136-3>li:before{content:"\0025cf  "}.lst-kix_list_66-2>li:before{content:"\0025aa  "}.lst-kix_list_38-3>li:before{content:"\0025aa  "}.lst-kix_list_92-5>li:before{content:"\0025a0  "}ul.lst-kix_list_77-8{list-style-type:none}.lst-kix_list_38-6>li:before{content:"\0025aa  "}.lst-kix_list_85-3>li:before{content:"\0025aa  "}ul.lst-kix_list_68-0{list-style-type:none}ul.lst-kix_list_68-1{list-style-type:none}.lst-kix_list_48-0>li:before{content:"\0025cf  "}ul.lst-kix_list_68-4{list-style-type:none}.lst-kix_list_2-5>li:before{content:"\0025a0  "}ul.lst-kix_list_68-5{list-style-type:none}ul.lst-kix_list_68-2{list-style-type:none}ul.lst-kix_list_68-3{list-style-type:none}.lst-kix_list_118-1>li{counter-increment:lst-ctn-kix_list_118-1}.lst-kix_list_48-6>li:before{content:"\0025aa  "}.lst-kix_list_64-0>li:before{content:"\0025cf  "}.lst-kix_list_118-1>li:before{content:"" counter(lst-ctn-kix_list_118-1,decimal) ". "}.lst-kix_list_76-8>li:before{content:"\0025aa  "}.lst-kix_list_18-6>li:before{content:"\0025cf  "}.lst-kix_list_39-5>li:before{content:"\0025a0  "}.lst-kix_list_118-7>li:before{content:"" counter(lst-ctn-kix_list_118-7,decimal) ". "}ul.lst-kix_list_68-8{list-style-type:none}.lst-kix_list_127-2>li:before{content:"\0025aa  "}ul.lst-kix_list_68-6{list-style-type:none}ul.lst-kix_list_68-7{list-style-type:none}.lst-kix_list_94-7>li:before{content:"\0025cb  "}.lst-kix_list_127-8>li:before{content:"\0025aa  "}.lst-kix_list_10-3>li:before{content:"\0025aa  "}ul.lst-kix_list_11-7{list-style-type:none}.lst-kix_list_57-1>li:before{content:"o  "}ul.lst-kix_list_11-6{list-style-type:none}ul.lst-kix_list_11-5{list-style-type:none}.lst-kix_list_36-8>li:before{content:"\0025a0  "}ul.lst-kix_list_11-4{list-style-type:none}ul.lst-kix_list_11-3{list-style-type:none}.lst-kix_list_57-7>li:before{content:"o  "}ul.lst-kix_list_11-2{list-style-type:none}.lst-kix_list_73-4>li:before{content:"\0025cb  "}ul.lst-kix_list_11-1{list-style-type:none}ul.lst-kix_list_11-0{list-style-type:none}.lst-kix_g5lskmm1i0dj-1>li:before{content:"" counter(lst-ctn-kix_g5lskmm1i0dj-1,lower-latin) ". "}ul.lst-kix_list_11-8{list-style-type:none}.lst-kix_list_134-1>li:before{content:"o  "}ol.lst-kix_list_69-1.start{counter-reset:lst-ctn-kix_list_69-1 0}.lst-kix_list_67-7>li:before{content:"\0025aa  "}.lst-kix_list_46-8>li:before{content:"\0025aa  "}ul.lst-kix_list_131-6{list-style-type:none}ul.lst-kix_list_131-5{list-style-type:none}ul.lst-kix_list_131-4{list-style-type:none}ul.lst-kix_list_131-3{list-style-type:none}ol.lst-kix_list_119-4.start{counter-reset:lst-ctn-kix_list_119-4 0}ol.lst-kix_list_69-3.start{counter-reset:lst-ctn-kix_list_69-3 0}.lst-kix_list_20-0>li:before{content:"\0025cf  "}.lst-kix_list_29-5>li:before{content:"\0025aa  "}ul.lst-kix_list_131-8{list-style-type:none}ul.lst-kix_list_131-7{list-style-type:none}.lst-kix_list_9-6>li:before{content:"\0025aa  "}.lst-kix_list_83-1>li:before{content:"o  "}.lst-kix_list_133-4>li{counter-increment:lst-ctn-kix_list_133-4}.lst-kix_list_20-6>li:before{content:"\0025aa  "}ul.lst-kix_list_2-8{list-style-type:none}ol.lst-kix_list_12-1.start{counter-reset:lst-ctn-kix_list_12-1 0}.lst-kix_list_11-5>li:before{content:"\0025aa  "}.lst-kix_list_124-4>li:before{content:"\0025cb  "}.lst-kix_list_54-3>li:before{content:"\0025aa  "}ul.lst-kix_list_2-2{list-style-type:none}ul.lst-kix_list_2-3{list-style-type:none}ul.lst-kix_list_2-0{list-style-type:none}ul.lst-kix_list_2-1{list-style-type:none}ul.lst-kix_list_131-2{list-style-type:none}ul.lst-kix_list_2-6{list-style-type:none}ul.lst-kix_list_131-1{list-style-type:none}ul.lst-kix_list_2-7{list-style-type:none}ul.lst-kix_list_131-0{list-style-type:none}ul.lst-kix_list_2-4{list-style-type:none}ul.lst-kix_list_2-5{list-style-type:none}ul.lst-kix_list_33-0{list-style-type:none}ul.lst-kix_list_33-1{list-style-type:none}.lst-kix_list_1-3>li:before{content:"\0025cf  "}ul.lst-kix_list_33-2{list-style-type:none}ul.lst-kix_list_33-3{list-style-type:none}.lst-kix_list_125-0>li:before{content:"\0025cf  "}ul.lst-kix_list_33-4{list-style-type:none}ul.lst-kix_list_33-5{list-style-type:none}ul.lst-kix_list_33-6{list-style-type:none}.lst-kix_list_28-3>li:before{content:"\0025aa  "}ul.lst-kix_list_33-7{list-style-type:none}.lst-kix_list_75-6>li:before{content:"\0025aa  "}.lst-kix_list_119-3>li:before{content:"" counter(lst-ctn-kix_list_119-3,decimal) ". "}.lst-kix_list_107-0>li{counter-increment:lst-ctn-kix_list_107-0}.lst-kix_list_82-5>li:before{content:"\0025aa  "}.lst-kix_list_27-7>li:before{content:"\0025aa  "}ul.lst-kix_list_33-8{list-style-type:none}.lst-kix_list_49-2>li:before{content:"\0025aa  "}.lst-kix_list_76-2>li:before{content:"\0025aa  "}.lst-kix_list_35-2>li:before{content:"\0025aa  "}.lst-kix_list_30-3>li:before{content:"\0025cf  "}.lst-kix_list_100-4>li:before{content:"\0025cb  "}.lst-kix_list_77-1>li:before{content:"\0025cb  "}.lst-kix_list_72-5>li:before{content:"\0025aa  "}.lst-kix_list_72-2>li:before{content:"\0025aa  "}.lst-kix_list_105-3>li:before{content:"\0025aa  "}.lst-kix_list_3-1>li:before{content:"\0025cb  "}.lst-kix_list_114-1>li:before{content:"\0025cb  "}ol.lst-kix_list_104-1{list-style-type:none}ol.lst-kix_list_104-2{list-style-type:none}.lst-kix_list_44-0>li:before{content:"\0025cf  "}.lst-kix_list_119-0>li:before{content:"" counter(lst-ctn-kix_list_119-0,decimal) ". "}.lst-kix_list_114-4>li:before{content:"\0025cb  "}.lst-kix_list_81-3>li:before{content:"\0025aa  "}ol.lst-kix_list_12-3.start{counter-reset:lst-ctn-kix_list_12-3 0}.lst-kix_list_77-4>li:before{content:"\0025cb  "}.lst-kix_list_118-7>li{counter-increment:lst-ctn-kix_list_118-7}.lst-kix_list_133-2>li:before{content:"" counter(lst-ctn-kix_list_133-2,decimal) ". "}ul.lst-kix_list_51-5{list-style-type:none}ul.lst-kix_list_51-4{list-style-type:none}ul.lst-kix_list_51-7{list-style-type:none}.lst-kix_list_21-2>li:before{content:"\0025aa  "}ul.lst-kix_list_51-6{list-style-type:none}.lst-kix_list_63-1>li:before{content:"o  "}ol.lst-kix_list_106-1.start{counter-reset:lst-ctn-kix_list_106-1 0}ul.lst-kix_list_51-8{list-style-type:none}ul.lst-kix_list_109-3{list-style-type:none}ul.lst-kix_list_109-0{list-style-type:none}ul.lst-kix_list_51-1{list-style-type:none}ul.lst-kix_list_109-6{list-style-type:none}ul.lst-kix_list_51-0{list-style-type:none}ul.lst-kix_list_109-7{list-style-type:none}.lst-kix_list_133-5>li:before{content:"" counter(lst-ctn-kix_list_133-5,decimal) ". "}ul.lst-kix_list_51-3{list-style-type:none}ul.lst-kix_list_109-4{list-style-type:none}ul.lst-kix_list_51-2{list-style-type:none}ul.lst-kix_list_109-5{list-style-type:none}.lst-kix_list_11-2>li:before{content:"\0025aa  "}.lst-kix_list_58-0>li:before{content:"\0025cf  "}.lst-kix_list_128-1>li:before{content:"\0025cb  "}.lst-kix_list_117-6>li{counter-increment:lst-ctn-kix_list_117-6}.lst-kix_list_53-1>li:before{content:"o  "}.lst-kix_list_123-2>li:before{content:"\0025a0  "}.lst-kix_list_128-4>li:before{content:"\0025cb  "}.lst-kix_list_95-3>li:before{content:"\0025cf  "}.lst-kix_6ppt4s25kk1y-2>li:before{content:"\0025a0  "}.lst-kix_list_68-0>li:before{content:"\0025cf  "}.lst-kix_list_123-5>li:before{content:"\0025a0  "}.lst-kix_list_63-4>li:before{content:"\0025aa  "}ol.lst-kix_list_12-4.start{counter-reset:lst-ctn-kix_list_12-4 0}.lst-kix_list_90-7>li:before{content:"\0025cb  "}.lst-kix_list_91-3>li:before{content:"\0025cf  "}.lst-kix_list_129-0>li:before{content:"\0025cf  "}.lst-kix_list_25-2>li:before{content:"\0025aa  "}.lst-kix_list_91-6>li:before{content:"\0025cf  "}.lst-kix_list_16-1>li:before{content:"\0025cb  "}.lst-kix_list_67-1>li:before{content:"o  "}.lst-kix_list_58-3>li:before{content:"\0025cf  "}ol.lst-kix_list_69-0.start{counter-reset:lst-ctn-kix_list_69-0 0}ul.lst-kix_list_73-6{list-style-type:none}ul.lst-kix_list_73-7{list-style-type:none}.lst-kix_list_119-2>li{counter-increment:lst-ctn-kix_list_119-2}ul.lst-kix_list_73-4{list-style-type:none}.lst-kix_list_86-5>li:before{content:"\0025aa  "}ul.lst-kix_list_73-5{list-style-type:none}.lst-kix_list_12-4>li{counter-increment:lst-ctn-kix_list_12-4}.lst-kix_list_109-0>li:before{content:"\0025cf  "}ul.lst-kix_list_73-8{list-style-type:none}.lst-kix_list_44-3>li:before{content:"\0025aa  "}.lst-kix_list_86-2>li:before{content:"\0025aa  "}.lst-kix_list_115-0>li:before{content:"\0025cf  "}ul.lst-kix_list_73-2{list-style-type:none}ul.lst-kix_list_73-3{list-style-type:none}ul.lst-kix_list_73-0{list-style-type:none}ol.lst-kix_list_119-8.start{counter-reset:lst-ctn-kix_list_119-8 0}ul.lst-kix_list_73-1{list-style-type:none}.lst-kix_list_12-7>li{counter-increment:lst-ctn-kix_list_12-7}.lst-kix_list_39-2>li:before{content:"\0025a0  "}.lst-kix_list_87-1>li:before{content:"o  "}.lst-kix_list_100-1>li:before{content:"\0025cb  "}.lst-kix_list_30-0>li:before{content:"\0025cf  "}.lst-kix_list_71-6>li:before{content:"\0025cf  "}.lst-kix_list_109-3>li:before{content:"\0025aa  "}.lst-kix_list_113-5>li:before{content:"\0025aa  "}ul.lst-kix_list_64-4{list-style-type:none}.lst-kix_list_43-4>li:before{content:"\0025aa  "}ul.lst-kix_list_64-5{list-style-type:none}ul.lst-kix_list_64-2{list-style-type:none}ul.lst-kix_list_64-3{list-style-type:none}ul.lst-kix_list_64-8{list-style-type:none}.lst-kix_list_118-4>li:before{content:"" counter(lst-ctn-kix_list_118-4,decimal) ". "}ul.lst-kix_list_64-6{list-style-type:none}.lst-kix_list_7-1>li:before{content:"o  "}.lst-kix_list_48-3>li:before{content:"\0025aa  "}ul.lst-kix_list_64-7{list-style-type:none}ul.lst-kix_list_64-0{list-style-type:none}ul.lst-kix_list_64-1{list-style-type:none}.lst-kix_list_101-0>li:before{content:"\0025cf  "}.lst-kix_list_73-1>li:before{content:"\0025cb  "}.lst-kix_list_85-6>li:before{content:"\0025aa  "}.lst-kix_g5lskmm1i0dj-4>li{counter-increment:lst-ctn-kix_g5lskmm1i0dj-4}ul.lst-kix_list_99-3{list-style-type:none}ul.lst-kix_list_99-2{list-style-type:none}ul.lst-kix_list_99-1{list-style-type:none}.lst-kix_list_99-6>li:before{content:"\0025cf  "}.lst-kix_list_52-8>li:before{content:"\0025aa  "}ul.lst-kix_list_99-0{list-style-type:none}ul.lst-kix_list_99-7{list-style-type:none}ul.lst-kix_list_99-6{list-style-type:none}ul.lst-kix_list_99-5{list-style-type:none}ul.lst-kix_list_99-4{list-style-type:none}.lst-kix_list_127-5>li:before{content:"\0025aa  "}.lst-kix_list_67-4>li:before{content:"\0025aa  "}.lst-kix_835ax5k7z1l9-2>li:before{content:"\0025a0  "}.lst-kix_ee0fx9z4yp3a-6>li:before{content:"\0025cf  "}.lst-kix_list_15-2>li:before{content:"\0025a0  "}ul.lst-kix_list_99-8{list-style-type:none}.lst-kix_list_10-6>li:before{content:"\0025aa  "}.lst-kix_list_57-4>li:before{content:"o  "}ol.lst-kix_list_12-7.start{counter-reset:lst-ctn-kix_list_12-7 0}ul.lst-kix_list_86-5{list-style-type:none}ul.lst-kix_list_86-4{list-style-type:none}ul.lst-kix_list_86-3{list-style-type:none}ul.lst-kix_list_86-2{list-style-type:none}.lst-kix_list_105-1>li{counter-increment:lst-ctn-kix_list_105-1}ul.lst-kix_list_86-8{list-style-type:none}ul.lst-kix_list_86-7{list-style-type:none}ul.lst-kix_list_86-6{list-style-type:none}.lst-kix_list_95-6>li:before{content:"\0025cf  "}.lst-kix_list_124-1>li:before{content:"\0025cb  "}ul.lst-kix_list_86-1{list-style-type:none}.lst-kix_list_53-4>li:before{content:"\0025aa  "}ul.lst-kix_list_86-0{list-style-type:none}ul.lst-kix_list_109-8{list-style-type:none}.lst-kix_list_103-8>li:before{content:"\0025aa  "}ol.lst-kix_list_12-8.start{counter-reset:lst-ctn-kix_list_12-8 0}.lst-kix_list_132-6>li:before{content:"\0025cf  "}.lst-kix_list_62-5>li:before{content:"\0025aa  "}.lst-kix_list_20-3>li:before{content:"\0025aa  "}.lst-kix_list_54-0>li:before{content:"\0025cf  "}.lst-kix_list_29-2>li:before{content:"\0025aa  "}.lst-kix_list_96-2>li:before{content:"\0025a0  "}.lst-kix_list_104-4>li:before{content:"\0025aa  "}ol.lst-kix_list_117-5{list-style-type:none}.lst-kix_list_110-1>li:before{content:"o  "}ol.lst-kix_list_117-6{list-style-type:none}ol.lst-kix_list_117-7{list-style-type:none}ol.lst-kix_list_117-8{list-style-type:none}.lst-kix_list_81-6>li:before{content:"\0025aa  "}.lst-kix_list_28-6>li:before{content:"\0025aa  "}ol.lst-kix_list_117-1{list-style-type:none}.lst-kix_list_1-6>li:before{content:"\0025cf  "}ol.lst-kix_list_117-2{list-style-type:none}ol.lst-kix_list_117-3{list-style-type:none}ol.lst-kix_list_117-4{list-style-type:none}.lst-kix_list_82-2>li:before{content:"\0025aa  "}ol.lst-kix_list_117-0{list-style-type:none}.lst-kix_list_76-5>li:before{content:"\0025aa  "}.lst-kix_list_33-7>li:before{content:"\0025aa  "}.lst-kix_list_40-0>li:before{content:"\0025cf  "}.lst-kix_list_105-0>li:before{content:"\0025cf  "}.lst-kix_list_34-3>li:before{content:"\0025aa  "}.lst-kix_list_2-2>li:before{content:"\0025a0  "}ol{margin:0;padding:0}table td,table th{padding:0}.c98{border-right-style:solid;padding:3.8pt 3.8pt 3.8pt 3.8pt;border-bottom-color:#a3a3a3;border-top-width:1pt;border-right-width:1pt;border-left-color:#a3a3a3;vertical-align:top;border-right-color:#a3a3a3;border-left-width:1pt;border-top-style:solid;border-left-style:solid;border-bottom-width:1pt;width:243.3pt;border-top-color:#a3a3a3;border-bottom-style:solid}.c37{border-right-style:solid;padding:5.2pt 5.2pt 5.2pt 5.2pt;border-bottom-color:#000000;border-top-width:1pt;border-right-width:1pt;border-left-color:#000000;vertical-align:top;border-right-color:#000000;border-left-width:1pt;border-top-style:solid;border-left-style:solid;border-bottom-width:1pt;width:141.8pt;border-top-color:#000000;border-bottom-style:solid}.c60{border-right-style:solid;padding:5.2pt 5.2pt 5.2pt 5.2pt;border-bottom-color:#000000;border-top-width:1pt;border-right-width:1pt;border-left-color:#000000;vertical-align:top;border-right-color:#000000;border-left-width:1pt;border-top-style:solid;border-left-style:solid;border-bottom-width:1pt;width:105.8pt;border-top-color:#000000;border-bottom-style:solid}.c79{border-right-style:solid;padding:3.8pt 3.8pt 3.8pt 3.8pt;border-bottom-color:#a3a3a3;border-top-width:1pt;border-right-width:1pt;border-left-color:#a3a3a3;vertical-align:top;border-right-color:#a3a3a3;border-left-width:1pt;border-top-style:solid;border-left-style:solid;border-bottom-width:1pt;width:226.3pt;border-top-color:#a3a3a3;border-bottom-style:solid}.c107{border-right-style:solid;padding:3.8pt 3.8pt 3.8pt 3.8pt;border-bottom-color:#a3a3a3;border-top-width:1pt;border-right-width:1pt;border-left-color:#a3a3a3;vertical-align:top;border-right-color:#a3a3a3;border-left-width:1pt;border-top-style:solid;border-left-style:solid;border-bottom-width:1pt;width:276.2pt;border-top-color:#a3a3a3;border-bottom-style:solid}.c82{border-right-style:solid;padding:3.8pt 3.8pt 3.8pt 3.8pt;border-bottom-color:#a3a3a3;border-top-width:1pt;border-right-width:1pt;border-left-color:#a3a3a3;vertical-align:top;border-right-color:#a3a3a3;border-left-width:1pt;border-top-style:solid;border-left-style:solid;border-bottom-width:1pt;width:58.1pt;border-top-color:#a3a3a3;border-bottom-style:solid}.c91{border-right-style:solid;padding:3.8pt 3.8pt 3.8pt 3.8pt;border-bottom-color:#a3a3a3;border-top-width:1pt;border-right-width:1pt;border-left-color:#a3a3a3;vertical-align:top;border-right-color:#a3a3a3;border-left-width:1pt;border-top-style:solid;border-left-style:solid;border-bottom-width:1pt;width:162.8pt;border-top-color:#a3a3a3;border-bottom-style:solid}.c52{border-right-style:solid;padding:3.8pt 3.8pt 3.8pt 3.8pt;border-bottom-color:#a3a3a3;border-top-width:1pt;border-right-width:1pt;border-left-color:#a3a3a3;vertical-align:top;border-right-color:#a3a3a3;border-left-width:1pt;border-top-style:solid;border-left-style:solid;border-bottom-width:1pt;width:70.5pt;border-top-color:#a3a3a3;border-bottom-style:solid}.c85{border-right-style:solid;padding:3.8pt 3.8pt 3.8pt 3.8pt;border-bottom-color:#a3a3a3;border-top-width:1pt;border-right-width:1pt;border-left-color:#a3a3a3;vertical-align:top;border-right-color:#a3a3a3;border-left-width:1pt;border-top-style:solid;border-left-style:solid;border-bottom-width:1pt;width:223.8pt;border-top-color:#a3a3a3;border-bottom-style:solid}.c31{border-right-style:solid;padding:3.8pt 3.8pt 3.8pt 3.8pt;border-bottom-color:#a3a3a3;border-top-width:1pt;border-right-width:1pt;border-left-color:#a3a3a3;vertical-align:top;border-right-color:#a3a3a3;border-left-width:1pt;border-top-style:solid;border-left-style:solid;border-bottom-width:1pt;width:113.4pt;border-top-color:#a3a3a3;border-bottom-style:solid}.c32{border-right-style:solid;padding:3.8pt 3.8pt 3.8pt 3.8pt;border-bottom-color:#a3a3a3;border-top-width:1pt;border-right-width:1pt;border-left-color:#a3a3a3;vertical-align:top;border-right-color:#a3a3a3;border-left-width:1pt;border-top-style:solid;border-left-style:solid;border-bottom-width:1pt;width:120.5pt;border-top-color:#a3a3a3;border-bottom-style:solid}.c61{border-right-style:solid;padding:5.2pt 5.2pt 5.2pt 5.2pt;border-bottom-color:#000000;border-top-width:1pt;border-right-width:1pt;border-left-color:#000000;vertical-align:top;border-right-color:#000000;border-left-width:1pt;border-top-style:solid;border-left-style:solid;border-bottom-width:1pt;width:92.7pt;border-top-color:#000000;border-bottom-style:solid}.c10{border-right-style:solid;padding:5.2pt 5.2pt 5.2pt 5.2pt;border-bottom-color:#000000;border-top-width:1pt;border-right-width:1pt;border-left-color:#000000;vertical-align:top;border-right-color:#000000;border-left-width:1pt;border-top-style:solid;border-left-style:solid;border-bottom-width:1pt;width:106.5pt;border-top-color:#000000;border-bottom-style:solid}.c72{border-right-style:solid;padding:3.8pt 3.8pt 3.8pt 3.8pt;border-bottom-color:#a3a3a3;border-top-width:1pt;border-right-width:1pt;border-left-color:#a3a3a3;vertical-align:top;border-right-color:#a3a3a3;border-left-width:1pt;border-top-style:solid;border-left-style:solid;border-bottom-width:1pt;width:396.7pt;border-top-color:#a3a3a3;border-bottom-style:solid}.c56{border-right-style:solid;padding:3.8pt 3.8pt 3.8pt 3.8pt;border-bottom-color:#a3a3a3;border-top-width:1pt;border-right-width:1pt;border-left-color:#a3a3a3;vertical-align:top;border-right-color:#a3a3a3;border-left-width:1pt;border-top-style:solid;border-left-style:solid;border-bottom-width:1pt;width:168.2pt;border-top-color:#a3a3a3;border-bottom-style:solid}.c58{border-right-style:solid;padding:3.8pt 3.8pt 3.8pt 3.8pt;border-bottom-color:#a3a3a3;border-top-width:1pt;border-right-width:1pt;border-left-color:#a3a3a3;vertical-align:top;border-right-color:#a3a3a3;border-left-width:1pt;border-top-style:solid;border-left-style:solid;border-bottom-width:1pt;width:240.8pt;border-top-color:#a3a3a3;border-bottom-style:solid}.c18{margin-left:35.5pt;padding-top:0pt;list-style-position:inside;text-indent:45pt;padding-bottom:0pt;line-height:1.0;orphans:2;widows:2;text-align:justify}.c0{margin-left:36pt;padding-top:0pt;padding-left:0pt;padding-bottom:0pt;line-height:1.0;orphans:2;widows:2;text-align:justify}.c3{margin-left:108pt;padding-top:0pt;padding-left:0pt;padding-bottom:0pt;line-height:1.0;orphans:2;widows:2;text-align:justify}.c23{margin-left:0pt;padding-top:0pt;list-style-position:inside;text-indent:45pt;padding-bottom:0pt;orphans:2;widows:2;text-align:justify}.c9{margin-left:72pt;padding-top:0pt;padding-left:0pt;padding-bottom:0pt;line-height:1.0;orphans:2;widows:2;text-align:justify}.c1{color:#000000;font-weight:400;text-decoration:none;vertical-align:baseline;font-size:11pt;font-family:"Asap";font-style:normal}.c16{margin-left:72pt;padding-top:14pt;padding-left:0pt;padding-bottom:14pt;line-height:1.0;orphans:2;widows:2}.c12{padding-top:0pt;padding-bottom:0pt;line-height:1.0;orphans:2;widows:2;text-align:left}.c39{margin-left:108pt;padding-top:14pt;padding-left:0pt;padding-bottom:14pt;orphans:2;widows:2}.c14{margin-left:72pt;padding-left:0pt;padding-bottom:0pt;line-height:1.0;orphans:2;widows:2}.c21{color:#000000;text-decoration:none;vertical-align:baseline;font-size:10pt;font-style:normal}.c28{padding-top:0pt;padding-bottom:0pt;orphans:2;widows:2;text-align:center}.c30{padding-top:0pt;padding-bottom:0pt;orphans:2;widows:2;text-align:justify}.c15{margin-left:36pt;padding-bottom:0pt;orphans:2;widows:2;padding-left:0pt}.c38{margin-left:72pt;padding-bottom:0pt;orphans:2;widows:2;padding-left:0pt}.c4{vertical-align:sub;font-size:6.5pt;font-family:"Asap";color:#000000;font-weight:400}.c34{margin-left:36pt;orphans:2;widows:2;padding-left:0pt}.c17{background-color:#ffffff;font-size:11pt;font-family:"Asap";color:#1d2129}.c24{padding-top:0pt;padding-bottom:10pt;line-height:1.1500000000000001;text-align:justify}.c70{margin-left:-3.8pt;border-spacing:0;border-collapse:collapse;margin-right:auto}.c94{margin-left:-5.2pt;border-spacing:0;border-collapse:collapse;margin-right:auto}.c11{page-break-after:avoid;orphans:2;widows:2}.c57{padding-top:0pt;padding-bottom:6pt;text-align:justify}.c6{font-size:9pt;font-family:"Asap";font-weight:700}.c7{font-size:12pt;font-family:"Asap";font-weight:400}.c81{text-decoration:none;vertical-align:baseline;font-style:normal}.c5{font-size:11pt;font-family:"Asap";color:#000000}.c22{orphans:2;widows:2;height:10pt}.c53{color:#0000ff;text-decoration:underline}.c97{margin-left:72pt;padding-left:0pt}.c26{color:#1155cc;text-decoration:underline}.c44{orphans:2;widows:2}.c80{padding-top:5pt;text-align:justify}.c62{vertical-align:super;font-size:6.5pt}.c13{font-size:12pt;font-family:"Asap"}.c88{margin-left:108pt;padding-left:0pt}.c69{padding-top:14pt;padding-bottom:14pt}.c45{margin-left:36pt;padding-left:0pt}.c64{margin-left:144pt;padding-left:0pt}.c41{background-color:#ffffff;color:#212121}.c2{padding:0;margin:0}.c33{line-height:1.15;text-align:left}.c29{color:inherit;text-decoration:inherit}.c101{margin-left:34.5pt;padding-left:0pt}.c99{margin-left:72pt;text-indent:-18pt}.c103{max-width:468pt;padding:72pt 72pt 72pt 72pt}.c59{padding-top:18pt;padding-bottom:6pt}.c73{padding-bottom:10pt;line-height:1.1500000000000001}.c68{height:235pt}.c40{color:#000000}.c8{font-weight:400}.c35{font-size:16pt}.c90{color:#595959}.c50{font-size:9pt}.c83{margin-left:54pt}.c76{text-indent:36pt}.c104{margin-left:108pt}.c46{font-size:10pt}.c105{height:12pt}.c27{font-weight:700}.c95{font-size:8pt}.c47{text-align:center}.c63{color:#222222}.c48{background-color:#ffffff}.c84{text-decoration:underline}.c67{padding-top:0pt}.c25{font-size:11pt}.c71{text-align:left}.c43{color:#1d2129}.c66{padding-bottom:6pt}.c74{height:0pt}.c49{color:#70ad47}.c55{height:18pt}.c20{font-family:"Asap"}.c51{font-style:italic}.c93{padding-bottom:14pt}.c77{font-size:36pt}.c109{line-height:1.1500000000000001}.c65{height:16pt}.c19{line-height:1.0}.c87{margin-left:35.5pt}.c92{text-align:justify}.c86{color:#2e75b5}.c42{padding-bottom:0pt}.c89{margin-left:18pt}.c75{vertical-align:super}.c96{padding-bottom:12pt}.c100{font-size:18pt}.c54{margin-left:36pt}.c102{margin-left:72pt}.c106{text-align:right}.c36{height:10pt}.c108{padding-top:14pt}.c78{font-size:7pt}.c110{padding-bottom:19pt}.title{padding-top:0pt;color:#000000;font-size:26pt;padding-bottom:6pt;font-family:"Calibri";line-height:1.0;page-break-after:avoid;orphans:2;widows:2;text-align:right}.subtitle{padding-top:0pt;color:#666666;font-size:10pt;padding-bottom:36pt;font-family:"Calibri";line-height:1.0;page-break-after:avoid;font-style:italic;orphans:2;widows:2;text-align:right}li{color:#000000;font-size:10pt;font-family:"Calibri"}p{margin:0;color:#000000;font-size:10pt;font-family:"Calibri"}h1{padding-top:15pt;color:#000000;font-size:16pt;padding-bottom:2pt;font-family:"Calibri";line-height:1.1500000000000001;page-break-after:avoid;orphans:2;widows:2;text-align:left}h2{padding-top:0pt;color:#000000;font-size:14pt;padding-bottom:0pt;font-family:"Calibri";line-height:1.1500000000000001;page-break-after:avoid;orphans:2;widows:2;text-align:left}h3{padding-top:0pt;color:#000000;font-size:12pt;padding-bottom:0pt;font-family:"Calibri";line-height:1.1500000000000001;page-break-after:avoid;orphans:2;widows:2;text-align:left}h4{padding-top:0pt;color:#000000;font-size:11pt;padding-bottom:0pt;font-family:"Calibri";line-height:1.1500000000000001;page-break-after:avoid;font-style:italic;orphans:2;widows:2;text-align:left}h5{padding-top:0pt;color:#538135;font-size:14pt;padding-bottom:0pt;font-family:"Calibri";line-height:1.1500000000000001;page-break-after:avoid;orphans:2;widows:2;text-align:left}h6{padding-top:0pt;color:#70ad47;font-size:11pt;padding-bottom:0pt;font-family:"Calibri";line-height:1.1500000000000001;page-break-after:avoid;orphans:2;widows:2;text-align:left}</style></head><body class="c48 c103"><p class="c11 c36 title"><span class="c8 c20 c77"></span></p><p class="c11 c36 title"><span class="c8 c20 c77"></span></p><p class="c11 c36 title"><span class="c8 c20 c77"></span></p><p class="c11 c36 title"><span class="c8 c20 c77"></span></p><p class="c11 c36 title"><span class="c8 c20 c77"></span></p><p class="c11 c36 c92 title"><span class="c8 c20 c77"></span></p><p class="c11 title"><span class="c20 c77">Device&rsquo;s NOTEBOOK</span><hr style="page-break-before:always;display:none;"></p><h1 class="c11"><span class="c20">About Us</span></h1><h2 class="c11 c59"><span class="c13 c27 c49">Address: UOFC_CALGARY IGEM 2016</span></h2><p class="c30 c19"><span class="c5 c8">UNIVERSITY OF CALGARY</span></p><p class="c30 c19"><span class="c5 c8">HM393B - 3330 HOSPITAL DRIVE, NW</span></p><p class="c30 c19"><span class="c5 c8">CALGARY, AB T2N 4N1</span></p><p class="c30 c19"><span class="c5 c8">CANADA</span></p><p class="c30 c19 c36"><span class="c25 c20"></span></p><h2 class="c11 c59" id="h.17c9hp7vvxgk"><span class="c13 c27 c49">CONTRIBUTORS:</span></h2><p class="c22"><span class="c20"></span></p><h3 class="c11 c47 c42" id="h.i1jk585k7bns"><span class="c20">Mathematical Modelling/Academics</span></h3><p class="c44 c47 c42"><span class="c25 c20">Noshin Karim</span></p><p class="c44 c47 c42"><span class="c25 c20">Neliza Mendoza</span></p><p class="c44 c47 c42"><span class="c25 c20">David Nguyen</span></p><p class="c22 c47 c42"><span class="c25 c20"></span></p><h3 class="c11 c47 c42" id="h.lzv2lhy8cq9f"><span class="c20">Manufacturing/External affairs</span></h3><p class="c44 c47 c42"><span class="c25 c20">David Nguyen</span></p><p class="c44 c47 c42"><span class="c25 c20">Neliza Mendoza</span></p><p class="c22 c47 c42"><span class="c25 c20"></span></p><h3 class="c11 c47 c42" id="h.gmglmt8a3szt"><span class="c20">Visual Modelling/Graphic Designer</span></h3><p class="c44 c47 c42"><span class="c25 c20">Christine Phan</span></p><p class="c44 c47 c42"><span class="c25 c20">Tiffany Dang</span></p><p class="c22 c47 c42"><span class="c25 c20"></span></p><h3 class="c11 c47 c42" id="h.rb9ki0mzw88x"><span class="c20">Team Lead/Lab Technologist</span></h3><p class="c44 c47 c42"><span class="c25 c20">Tiffany Dang</span></p><p class="c22 c47 c42"><span class="c25 c20"></span></p><h3 class="c11 c19 c47" id="h.fiootgyqn60d"><span class="c20">Administrative</span></h3><p class="c44 c47 c19 c42"><span class="c25 c20">Tiffany Dang</span></p><p class="c44 c47 c19 c42"><span class="c25 c20">Noshin Karim</span></p><p class="c22 c47"><span class="c20"></span></p><p class="c22 c42"><span class="c25 c20"></span></p><p class="c22"><span class="c20"></span></p><p class="c30 c19 c36"><span class="c25 c20"></span></p><p class="c22"><span class="c20"></span></p><hr style="page-break-before:always;display:none;"><p class="c22"><span class="c35 c20 c86"></span></p><h1 class="c11"><span class="c20">Considerations</span></h1><p class="c22"><span class="c13 c27 c49"></span></p><p class="c44"><span class="c13 c27 c49">What we have to determine:</span></p><h3 class="c11"><span class="c20">Wednesday, May 4th</span></h3><ul class="c2 lst-kix_list_1-0 start"><li class="c15 c19"><span class="c5">How effectively diffusivity works</span></li><li class="c15 c19"><span class="c5">Scaling:</span></li></ul><ul class="c2 lst-kix_list_1-1 start"><li class="c14"><span class="c5">Model and prototype</span></li><li class="c14"><span class="c5">Measurements</span></li></ul><ul class="c2 lst-kix_list_1-0"><li class="c15 c19"><span class="c5">Layers:</span></li></ul><ul class="c2 lst-kix_list_1-1 start"><li class="c14"><span class="c5">Kill switch in backing layer and bottom layer </span></li><li class="c14"><span class="c5">Break controller</span></li></ul><ul class="c2 lst-kix_list_1-0"><li class="c15 c19"><span class="c5">Know how long proteins would stay in the body</span></li></ul><p class="c44 c19 c42 c89"><span class="c40 c20">&nbsp;</span></p><h3 class="c11"><span class="c20">Friday, May 6th </span></h3><ul class="c2 lst-kix_list_1-0"><li class="c15 c19"><span class="c40 c20">Habitation:</span></li></ul><ul class="c2 lst-kix_list_1-1 start"><li class="c9"><span class="c5 c8">Reservoir/chamber </span></li><li class="c9"><span class="c5 c8">Control temperature</span></li><li class="c9"><span class="c5 c8">Oxygen permeability </span></li><li class="c9"><span class="c5 c8">Specific parts of the body (heat, placement)</span></li><li class="c9"><span class="c5 c8">Delivery of nutrients - snapping mechanism?</span></li><li class="c9"><span class="c5 c8">Modelling - in different conditions, see the growth rate </span></li></ul><ul class="c2 lst-kix_list_1-0"><li class="c0"><span class="c5 c8">Entire Device:</span></li></ul><ul class="c2 lst-kix_list_1-1 start"><li class="c9"><span class="c5 c8">Design</span></li><li class="c9"><span class="c5 c8">Materials - contaminants</span></li><li class="c9"><span class="c5 c8">Eg) rate controlling membranes, diffusion of peptides </span></li></ul><ul class="c2 lst-kix_list_1-0"><li class="c0"><span class="c5 c8">Interface:</span></li></ul><ul class="c2 lst-kix_list_1-1 start"><li class="c9"><span class="c5 c8">Needle - size, density, material, design</span></li><li class="c9"><span class="c5 c8">Compatibility - initiation</span></li><li class="c9"><span class="c5 c8">Site of application </span></li><li class="c9"><span class="c5 c8">Disinfect prior to use, etc. </span></li></ul><p class="c30 c83 c19 c36"><span class="c5 c8"></span></p><h3 class="c11"><span class="c20">Friday, May 20th</span></h3><ul class="c2 lst-kix_list_25-0 start"><li class="c0"><span class="c5 c8">General</span></li></ul><ul class="c2 lst-kix_list_26-1 start"><li class="c9"><span class="c5 c8">How to apply to body?</span></li><li class="c9"><span class="c5 c8">How to discard after use (i.e. when we take it out, won&rsquo;t the media start to leak?)</span></li></ul><ul class="c2 lst-kix_list_26-0 start"><li class="c0"><span class="c5 c8">Microneedles/Drug Reservoir</span></li></ul><ul class="c2 lst-kix_list_26-1 start"><li class="c9"><span class="c5 c8">How to deliver drug through microneedle? (frozen, snap mechanism, isotonic?)</span></li><li class="c9"><span class="c5 c8">Hollow needle location &rarr; side or straight down?</span></li><li class="c9"><span class="c5 c8">What to test? (strain, stress, flow rate, diffusivity, etc.)</span></li><li class="c9"><span class="c5 c8">How to construct everything on a small scale? </span></li><li class="c9"><span class="c5 c8">Can we build a microneedle based on our own dimensions (i.e. can we customize the microneedle)? Or are the dimensions preset because we are ordering them in?</span></li><li class="c9"><span class="c5 c8">Backing layer &rarr; is that included in the microneedle or do we need to attach it on?</span></li><li class="c9"><span class="c5 c8">Actually getting microneedles</span></li><li class="c9"><span class="c5 c8">What is in the drug reservoir? (bacteria, nutrients (LB = nutrients))</span></li><li class="c9"><span class="c5 c8">Can we build on a microscopic scale? If so, how?</span></li><li class="c9"><span class="c5 c8">What is the media that is in the microneedle?</span></li><li class="c9"><span class="c5 c8">How do traditional microneedles work?</span></li><li class="c9"><span class="c5 c8">Snapping mechanism</span></li></ul><ul class="c2 lst-kix_list_26-0"><li class="c0"><span class="c5 c8">Size-controlling membrane</span></li></ul><ul class="c2 lst-kix_list_26-1 start"><li class="c9"><span class="c5 c8">How big should the pores be? (0.1 micrometer or smaller&hellip; 0.1 = size before bacteria can go through) &rarr; what else other than peptides will go into the body? Will they be harmful?</span></li><li class="c9"><span class="c5 c8">What material should it be made of? What else do we need to consider for the membrane (flexibility, etc.)?</span></li><li class="c9"><span class="c5 c8">How do we get it? (3M)?</span></li><li class="c9"><span class="c5 c8">Can we cut it to get it in a certain size?</span></li></ul><p class="c30 c19 c102 c36"><span class="c5 c8"></span></p><h3 class="c11"><span class="c20">Wednesday, May 25th</span></h3><p class="c30 c19"><span class="c17 c8">When researching materials, consider the following:</span></p><ul class="c2 lst-kix_list_29-0 start"><li class="c0"><span class="c17 c8">cost</span></li><li class="c0"><span class="c17 c8">environmentally friendly</span></li><li class="c0"><span class="c17 c8">the &ldquo;biological aspects&rdquo; (e.g. gas/oxygen permeability, elasticity permeable)</span></li><li class="c0"><span class="c17 c8">how can we get the material (local, international)</span></li><li class="c0"><span class="c17 c8">think about how can we use the material to assemble the device (e.g. if we need silicon for the device for example, is it easily machined?)</span></li></ul><p class="c30 c19 c36"><span class="c5 c8"></span></p><h3 class="c11"><span class="c20">Tuesday, May 31st</span></h3><p class="c30 c19"><span class="c5 c8">****The patch has to be</span><span class="c5 c27">&nbsp;transparent</span><span class="c5 c8">&nbsp;so that the indicator can be noticeable</span></p><p class="c30 c19 c36"><span class="c7"></span></p><h3 class="c11"><span class="c20">Monday, June 6th</span></h3><ul class="c2 lst-kix_list_51-0 start"><li class="c0"><span class="c5 c8">How to make the patch</span><span class="c5 c27">&nbsp;long term</span></li></ul><ul class="c2 lst-kix_list_51-1 start"><li class="c9"><span class="c5 c8">Look at disposable</span></li><li class="c9"><span class="c5 c8">Space the package would take</span></li><li class="c9"><span class="c5 c8">Shelf life, how long would it take for the patch contents to &quot;expire&rdquo;</span></li></ul><ul class="c2 lst-kix_list_51-0"><li class="c0"><span class="c5 c8">Think about the worse scenarios that we could get</span></li></ul><ul class="c2 lst-kix_list_51-1 start"><li class="c9"><span class="c5 c8">Then we can start thinking about alternatives</span></li><li class="c9"><span class="c5 c8">100 mL vs. 10 mL</span></li><li class="c9"><span class="c5 c8">Packets being unintentionally popped</span></li></ul><ul class="c2 lst-kix_list_51-0"><li class="c0"><span class="c5 c8">Actually have a plan, but it is also important to know how everything works out</span></li></ul><hr style="page-break-before:always;display:none;"><p class="c22"><span class="c35 c20 c86"></span></p><h1 class="c11"><span class="c20">Designs</span></h1><p class="c22"><span class="c20"></span></p><h3 class="c11"><span class="c20">Monday, May 9th </span></h3><h4 class="c11"><span class="c20">Design of Microneedles:</span></h4><ul class="c2 lst-kix_list_5-0 start"><li class="c0"><span class="c5 c8">Hollow cylindrical microneedle with conical tip </span></li><li class="c0"><span class="c5 c8">Enough strength to withstand bending and axial forces</span></li><li class="c0"><span class="c5 c8">Pressure uniform in main cavity of needle </span></li><li class="c0"><span class="c5 c8">Velocity constant in cavity; increase in outlet</span></li><li class="c0"><span class="c5 c8">Flow rate controlled by applied pressure and diameter of hole </span></li><li class="c0"><span class="c5 c8">For different materials - strength and deformation compared </span></li></ul><p class="c30 c19 c36 c89"><span class="c5 c8"></span></p><p class="c30 c19"><span class="c5 c8">Design 1:</span></p><ul class="c2 lst-kix_list_6-0 start"><li class="c0"><span class="c5 c8">The microneedle - from the machine shop</span></li><li class="c0"><span class="c5 c8">Semipermeable membrane - use a filter (different grades of filter paper)</span></li><li class="c0"><span class="c5 c8">Bacteria?</span></li><li class="c0"><span class="c5 c8">A top layer (to the bacteria)</span></li></ul><p class="c30 c19 c36"><span class="c5 c8"></span></p><p class="c30 c19"><span class="c5 c8">Design 2:</span></p><p class="c30 c19"><span class="c5 c8 c51">Part 1: MICRONEEDLE</span></p><ul class="c2 lst-kix_list_7-0 start"><li class="c0"><span class="c5 c8">The microneedle - from machine shop</span></li><li class="c0"><span class="c5 c8">Semipermeable membrane - use a filter (use different grades of filter paper)</span></li></ul><p class="c30 c19"><span class="c5 c8 c51">Part 2: CAPSULE WITH BACTERIA</span></p><ul class="c2 lst-kix_list_8-0 start"><li class="c0"><span class="c5 c8">Capsule with bacteria - the capsule can be put in the fridge; after, it would be inserted into the microneedle and then using a snapping mechanism/force to break the capsule which starts the process and peptides go through the semipermeable membrane</span></li></ul><p class="c30 c19 c36"><span class="c5 c8"></span></p><h3 class="c11"><span class="c20">Tuesday, May 17th</span></h3><p class="c30 c19"><span class="c5 c27">Device Prototypes:</span></p><ul class="c2 lst-kix_list_14-0 start"><li class="c0"><span class="c5 c8 c51">Major idea #1: Bacteria, rich media (LB), membrane all in top of drug reservoir&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;</span></li></ul><p class="c19 c28"><span style="overflow: hidden; display: inline-block; margin: 0.00px 0.00px; border: 0.00px solid #000000; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px); width: 174.53px; height: 130.93px;"><img alt="https://lh5.googleusercontent.com/hfUPu8YrWJxq--cd1ZWg0GVcXpfXV0UyK-sa5lZCxKPkEdYoHyadskkzR0jMyQ835cw1uHPwgyx-rgdCRuxbKWZIKvOv2bi_s_ygEMkt_H97Y3ZAYZb2eH2xlzsFY1QY3lGX0BKc" src="images/image14.png" style="width: 174.53px; height: 130.93px; margin-left: -0.00px; margin-top: -0.00px; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px);" title=""></span></p><ul class="c2 lst-kix_list_15-0 start"><li class="c0"><span class="c5 c8">Variations of Major idea #1</span></li></ul><ul class="c2 lst-kix_list_15-1 start"><li class="c9"><span class="c5 c8">Patch on top of microneedle array (patch is directly on top of patch)</span></li></ul><p class="c28 c19"><span style="overflow: hidden; display: inline-block; margin: 0.00px 0.00px; border: 0.00px solid #000000; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px); width: 183.27px; height: 111.02px;"><img alt="https://lh4.googleusercontent.com/lxSmEKFW3l2YMFL9-hmJQ281dsRzydFEJi19Jbsy2YIJxBMYiVY-A84XVB1hO1kLU-hHXro-NLL_pxI6hIXfnnnXv6c7bb_2DTqI3F-IoMVWzDpA1m9M-tZcM3eMD8cpuusz-24X" src="images/image16.png" style="width: 202.00px; height: 123.00px; margin-left: -6.24px; margin-top: -3.74px; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px);" title=""></span></p><ul class="c2 lst-kix_list_16-1 start"><li class="c9"><span class="c5 c8">Drug reservoir right on top of needles (i.e. no patch) and size controlling membrane </span></li></ul><ul class="c2 lst-kix_list_16-2 start"><li class="c3"><span class="c5 c8">Problems: How can we actually put in things in this small drug reservoir?</span></li></ul><p class="c22"><span class="c13"></span></p><p class="c28 c19"><span style="overflow: hidden; display: inline-block; margin: 0.00px 0.00px; border: 0.00px solid #000000; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px); width: 182.40px; height: 124.80px;"><img alt="https://lh3.googleusercontent.com/V7EYi-Ux8NAMnNr7EGec68yjSS9t7SF7U9IzDIMVkSXErxXzilEjzqeVHWWedbd6BRA7v2loqfoUIHlkMO45rFFvgn-JlPVv316AT-yvQgL8rwe_gIQ2O4Hl_IlAdi-m_rV8ClSP" src="images/image15.png" style="width: 182.40px; height: 124.80px; margin-left: -0.00px; margin-top: -0.00px; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px);" title=""></span></p><ul class="c2 lst-kix_list_17-1 start"><li class="c9"><span class="c5 c8">Drug reservoir right on top of needles &ndash; media is initially frozen and then melted after application to body due to body heat</span></li></ul><ul class="c2 lst-kix_list_17-2 start"><li class="c3"><span class="c5 c8">Problems: can&rsquo;t make the media frozen because expensive (buy refrigerator)</span></li><li class="c3"><span class="c5 c8">Frozen media will also expand like water, so when it melts it may not come into contact with spores</span></li></ul><p class="c28 c19 c54"><span style="overflow: hidden; display: inline-block; margin: 0.00px 0.00px; border: 0.00px solid #000000; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px); width: 182.40px; height: 163.20px;"><img alt="https://lh6.googleusercontent.com/WBWIoUltBy25UADG0T2fxz92aCI4N85sI1TAuM9jrzroWT9lFrPc64rGD5G0MBdU_PNRIgvYe2EYaQhhdxpPN2OYWWQkIn6d01SmRj0Hb3WAfmZxtsLLU7W2rX3w4O3fQ4rUrveI" src="images/image18.png" style="width: 182.40px; height: 163.20px; margin-left: -0.00px; margin-top: -0.00px; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px);" title=""></span></p><p class="c22"><span class="c20"></span></p><ul class="c2 lst-kix_list_18-1 start"><li class="c9"><span class="c5 c8">1 packet containing the bacteria in the drug reservoir &rarr; snap the packet to release bacteria spore </span></li></ul><ul class="c2 lst-kix_list_18-2 start"><li class="c3"><span class="c5 c8">Problems: How can we actually put spores in small packets and then put them in the small drug reservoir? How can we break those packets?</span></li></ul><p class="c28 c19"><span style="overflow: hidden; display: inline-block; margin: 0.00px 0.00px; border: 0.00px solid #000000; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px); width: 134.40px; height: 172.80px;"><img alt="https://lh3.googleusercontent.com/eA7WpsW7Sr6OUPl5cDPPpb9Z8edWt4im0f571AJiQlwwnf4FtgERUC8js-8tgMn8u9jtgXtYS0TLE1kLjRSZvFCisMDItPQpx_4F068rW3AQ38kA4kwi0vKpfxA7r37rAmRVuK1Z" src="images/image17.png" style="width: 134.40px; height: 172.80px; margin-left: -0.00px; margin-top: -0.00px; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px);" title=""></span></p><p class="c22"><span class="c20"></span></p><ul class="c2 lst-kix_list_19-1 start"><li class="c9"><span class="c5 c8">Introduction of a gel (on a &ldquo;lid&rdquo;/backing layer that is lowered onto the top of the microneedle array/drug reservoir) OR rate controlling membrane (hence we have a rate and size controlling membrane)</span></li></ul><ul class="c2 lst-kix_list_19-2 start"><li class="c3"><span class="c5 c8">Problems: How do we put a lid on the top of the microneedle array? How do we stick the gel on the lid? If the gel falls, won&rsquo;t it block the size controlling membrane? How do we put a rate controlling membrane in the small microneedle array?</span></li></ul><p class="c22"><span class="c13"></span></p><p class="c28 c19"><span style="overflow: hidden; display: inline-block; margin: 0.00px 0.00px; border: 0.00px solid #000000; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px); width: 202.00px; height: 160.80px;"><img alt="https://lh5.googleusercontent.com/3gKpz1cZJAeqnE-5NipZFMa4HOgtEktOPP_jn8kG7n2m42e9M7dlC6QNYx9pPEbMDQkuHO7EK3BUcaiyEyvDrASGPcNypYhPKx9Uxq5SJd7l1jzOSs1ismmrb4wHb_0sKMBQjL-l" src="images/image20.png" style="width: 202.00px; height: 160.80px; margin-left: -0.00px; margin-top: -0.00px; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px);" title=""></span></p><ul class="c2 lst-kix_list_20-0 start"><li class="c0"><span class="c5 c8 c51">Major idea #2: Leave microneedle as it is; have larger patch that contains 2 chambers to separate LB and spores</span></li></ul><p class="c28 c19"><span style="overflow: hidden; display: inline-block; margin: 0.00px 0.00px; border: 0.00px solid #000000; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px); width: 183.41px; height: 124.49px;"><img alt="https://lh5.googleusercontent.com/zzzX_cBjZ6DI91BcDIjbfGruvmtiGL2t5ZiwA6LRPWUS_W_edsVwKRPKS7nFuy_Y9SkofbSDaU03XE1NmiWriYu0wfNkdzDIz-eL3CRitLaVDUadgK4H1YZtLJFaW_uKqT-KvHaL" src="images/image19.png" style="width: 183.41px; height: 124.49px; margin-left: -0.00px; margin-top: -0.00px; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px);" title=""></span></p><ul class="c2 lst-kix_list_21-0 start"><li class="c0"><span class="c5 c8">backing material (what the block is made of)</span></li><li class="c0"><span class="c5 c8">&ldquo;valve&rdquo;</span></li><li class="c0"><span class="c5 c8">size controlling membrane</span></li><li class="c0"><span class="c5 c8">adhesive layer</span></li><li class="c0"><span class="c5 c8">microneedles</span></li></ul><p class="c30 c19 c36"><span class="c7"></span></p><p class="c30 c19"><span class="c5 c27">Constraints:</span></p><ul class="c2 lst-kix_list_22-0 start"><li class="c0"><span class="c5 c8">70 degrees C to activate spores</span></li><li class="c0"><span class="c5 c8">Oxygen transmission: available (80-100 cc/m2/24h)</span></li></ul><p class="c30 c19 c36"><span class="c5 c8"></span></p><h4 class="c11"><span class="c20">Dr. Dalton&rsquo;s Microneedles </span></h4><ul class="c2 lst-kix_list_31-0 start"><li class="c0"><span class="c5 c27">Problem 1</span><span class="c5 c8">: Geometry of microneedles</span></li></ul><ul class="c2 lst-kix_list_31-1 start"><li class="c9"><span class="c5 c8">TIP: </span></li></ul><ul class="c2 lst-kix_list_31-2 start"><li class="c3"><span class="c5 c8">Insertion force can be independent of the wall thickness</span></li><li class="c3"><span class="c5 c8">Fracture force increases with increasing wall thickness and increases with wall angle, also independent of tip radius</span></li><li class="c3"><span class="c5 c8">Side opened microneedles instead of standard tip microneedles &ndash; prevents tissue clog during insertion</span></li><li class="c3"><span class="c5 c8">High needle density can increase fluid flow rate </span></li><li class="c3"><span class="c5 c8">Sharper needles require less force for insertion, but has reduce needle tip strength </span></li><li class="c3"><span class="c5 c8">Microneedle needs to be 10-15 um but shorter than 50-100 um to avoid pain </span></li><li class="c3"><span class="c5 c8">Best option: small tip radius, large wall thickness</span></li></ul><ul class="c2 lst-kix_list_31-1"><li class="c9"><span class="c5 c8">BODY:</span></li></ul><ul class="c2 lst-kix_list_31-2 start"><li class="c3"><span class="c5 c8">Cylinder: eliminate stress concentrations, stronger needle structure, better self-adhesion</span></li></ul><ul class="c2 lst-kix_list_31-0"><li class="c0"><span class="c5 c27">Problem 2</span><span class="c5 c8">: Material for microneedles</span></li></ul><ul class="c2 lst-kix_list_31-1 start"><li class="c9"><span class="c5 c8">Single crystalline silicon: high resistance to bending, can be fragile</span></li><li class="c9"><span class="c5 c8">Metal &ndash; greater strength, but thin metals are soft </span></li></ul><ul class="c2 lst-kix_list_31-0"><li class="c0"><span class="c5 c27">Problem 3:</span><span class="c5 c8">&nbsp;Application/removal</span></li></ul><ul class="c2 lst-kix_list_31-1 start"><li class="c9"><span class="c5 c8">Application: Elastic nature of skin creates possibility of non-uniform contact of the array with the skin - an issue for correctly metering dosages</span></li></ul><ul class="c2 lst-kix_list_31-2 start"><li class="c3"><span class="c5 c8">Has to find out which area of the skin where the least strain happens</span></li></ul><ul class="c2 lst-kix_list_31-1"><li class="c9"><span class="c5 c8">Removal: Leakage when microneedle patch is removed</span></li></ul><ul class="c2 lst-kix_list_31-2 start"><li class="c3"><span class="c5 c8">Development of microvalves within microneedles = passive system</span></li></ul><p class="c22"><span class="c6"></span></p><p class="c44"><span class="c6">Reference: </span><span class="c50 c20">Ashraf, M., Tayyaba, S., Nisar, A., Afzulpurkar, N., Bodhale, D., &amp; Lomas, T. et al. (2010). Design, Fabrication and Analysis of Silicon Hollow Microneedles for Transdermal Drug Delivery System for Treatment of Hemodynamic Dysfunctions. </span><span class="c50 c20 c51">Cardiovascular Engineering</span><span class="c20 c50">, </span><span class="c50 c20 c51">10</span><span class="c50 c20">(3), 91-108. </span><span class="c26 c20 c95"><a class="c29" href="https://www.google.com/url?q=http://dx.doi.org/10.1007/s10558-010-9100-5&amp;sa=D&amp;ust=1475957476545000&amp;usg=AFQjCNE8go0KiowWQ9f7NkO0fS-WxaR9Qw">http://dx.doi.org/10.1007/s10558-010-9100-5</a></span></p><p class="c30 c19 c36"><span class="c5 c8"><a class="c29" href="https://www.google.com/url?q=http://dx.doi.org/10.1007/s10558-010-9100-5&amp;sa=D&amp;ust=1475957476546000&amp;usg=AFQjCNFHmX3CdV-OtCAebIpFS5CtYBliqA"></a></span></p><h3 class="c11"><span class="c20">Monday, May 9th </span></h3><h4 class="c11"><span class="c20">Future design testing:</span></h4><ul class="c2 lst-kix_list_9-0 start"><li class="c0"><span class="c5 c8">Test the proposed design with skin (animal skin?)</span></li><li class="c0"><span class="c5 c8">Change diameter of hole - how much more different is the flow </span></li><li class="c0"><span class="c5 c8">Heat of finger - enough to stimulate it?</span></li><li class="c0"><span class="c5 c8">Diffusion works?</span></li><li class="c0"><span class="c5 c8">Failure load (at what pressure does the needle break?)</span></li></ul><p class="c30 c19 c36"><span class="c5 c8"></span></p><h4 class="c11"><span class="c20">STORAGE IDEA 1: Freeze drying</span></h4><ul class="c2 lst-kix_list_1-0"><li class="c15 c19"><span class="c20">Order in microneedles &gt; put in freezer &gt; at temperature of freeze dry</span></li></ul><ul class="c2 lst-kix_list_1-1 start"><li class="c14"><span class="c20">If microneedles survive in the fridge, we should also test if diffusivity still works</span></li><li class="c14"><span class="c20">If diffusion did not work, we have to look at pumps</span></li></ul><ul class="c2 lst-kix_list_1-0"><li class="c15 c19"><span class="c20">Membrane/Filter test: does the drug reservoir/peptide actually go through the filter? Does it prevent the bacteria from going through? </span></li><li class="c15 c19"><span class="c20">Diffusion test: To test whether diffusion will actually work and what other problems we will face with diffusion (e.g. bacteria secretes peptides which go through the semipermeable membrane&hellip; but what about the media that goes through the membrane?</span></li><li class="c15 c19"><span class="c20">Making changes to the design</span></li></ul><ul class="c2 lst-kix_list_1-1 start"><li class="c14"><span class="c20">Is the drug reservoir actually contained properly in the microneedle?</span></li></ul><ul class="c2 lst-kix_list_1-0"><li class="c34 c69 c19"><span class="c20">Bacteria test</span></li></ul><p class="c30 c19 c36"><span class="c5 c8"></span></p><h3 class="c11"><span class="c20">Monday, May 16th</span></h3><h5 class="c11"><span class="c20">Experiment to somehow test the idea:</span></h5><p class="c30 c19"><span class="c5 c8 c51">Objective:</span></p><p class="c30 c19"><span class="c5 c8">Tested the level of frozen H2O in microneedle as it melts into a cup of H2O (l)</span></p><p class="c30 c19 c36"><span class="c7"></span></p><p class="c30 c19"><span class="c5 c8 c51">Materials:</span></p><ul class="c2 lst-kix_list_11-0 start"><li class="c0"><span class="c5 c8">200 uL pipet tip </span></li><li class="c0"><span class="c5 c8">Distilled H2O</span></li><li class="c0"><span class="c5 c8">200 uL pipetter</span></li><li class="c0"><span class="c5 c8">Freezer</span></li><li class="c0"><span class="c5 c8">300 uL H2O</span></li><li class="c0"><span class="c5 c8">Parafilm/tape</span></li><li class="c0"><span class="c5 c8">Black sharpie </span></li><li class="c0"><span class="c5 c8">Test tube rack </span></li></ul><p class="c30 c19 c36"><span class="c5 c8 c51"></span></p><p class="c30 c19"><span class="c5 c8 c51">Procedure:</span></p><ol class="c2 lst-kix_list_12-0 start" start="1"><li class="c0"><span class="c5 c8">We used a pipet to take in 150 uL of distilled water in a pipet tip and taped the bottom with parafilm/tape. We marked the water level with a black sharpie.</span></li><li class="c0"><span class="c5 c8">Put the pipet tip in freezer and let the H2O freeze (10:50 am - after lunch).</span></li><li class="c0"><span class="c5 c8">Put pipet tip (just the tip area) into test tube of 300 uL (2x the volume of water in the needle). Cap the top with parafilm. </span></li><li class="c0"><span class="c5 c8">Overtime, see whether amount of H2O (l) goes back to original height.</span></li></ol><p class="c30 c19 c54 c36"><span class="c5 c8"></span></p><p class="c30 c19"><span class="c5 c8 c51">Results/Observation:</span></p><p class="c30 c19"><span class="c5 c8">After putting the frozen water in the distilled H2O (l) test tube (at normal tap temperature), we put parafilm on top to mimic the microneedle being capped. </span></p><ul class="c2 lst-kix_list_13-0 start"><li class="c0"><span class="c5 c8">H2O melts extremely fast (this is without adding body heat) - melted within 1-2 minutes </span></li><li class="c0"><span class="c5 c8">In actual microneedle, H2O (s) will melt very fast due to body heat. Also, silicon vs. plastic tube</span></li><li class="c0"><span class="c5 c8">After melting we noticed H2O (l) level in needle is at a constant level (significantly lower than initial amount). Eg) doesn&rsquo;t go back to original level </span></li><li class="c0"><span class="c5 c8">H2O did expand, but not too significantly from initial observation, we think it won&rsquo;t affect/damage the needle tip </span></li></ul><p class="c30 c19 c36"><span class="c5 c8"></span></p><h3 class="c11"><span class="c20">Monday, May 9th </span></h3><h4 class="c11"><span class="c20">IDEA 2: Popping Idea</span></h4><ul class="c2 lst-kix_list_10-0 start"><li class="c0"><span class="c5 c8">Instead of pump, have a chamber with cells have a positive pressure already within it - have it sealed </span></li><li class="c0"><span class="c5 c8">Capsule - look into the 2014 team </span></li><li class="c0"><span class="c5 c8">Thinking about having water in the capsule, keep water in capsule, break it and everything gets hydrated </span></li><li class="c0"><span class="c5 c8">Coating the microneedles with palmitic acid, we don&rsquo;t need to create another compartment </span></li><li class="c0"><span class="c5 c8">For medical uses, need only single administration, would we need the bacteria there? Could dissolving microneedles work?</span></li></ul><p class="c30 c19 c36"><span class="c25 c20"></span></p><h3 class="c11"><span class="c20">Monday, June 6th </span></h3><p class="c44 c19 c42"><span class="c40 c27 c20 c84">Tentative Materials for Our Patch</span></p><a id="t.d7e873a4f0ebb5ffe45155d50d4634e2f95e223c"></a><a id="t.0"></a><table class="c94"><tbody><tr class="c74"><td class="c10" colspan="1" rowspan="1"><p class="c12"><span class="c40 c27 c20">Part of the patch</span></p></td><td class="c60" colspan="1" rowspan="1"><p class="c12"><span class="c40 c27 c20">Material</span></p></td><td class="c37" colspan="1" rowspan="1"><p class="c12"><span class="c40 c27 c20">Pros</span></p></td><td class="c61" colspan="1" rowspan="1"><p class="c12"><span class="c40 c27 c20">Cons</span></p></td></tr><tr class="c68"><td class="c10" colspan="1" rowspan="1"><p class="c12"><span class="c40 c20">Backing Layer</span></p><p class="c12 c36"><span class="c21 c8 c20"></span></p><p class="c12"><span class="c40 c20">Purpose: </span><span class="c48 c20 c63">&nbsp;</span></p><p class="c12 c36"><span class="c21 c8 c20"></span></p><p class="c12"><span class="c63 c48 c20">provides structural support and protects the middle adhesive layer from the environment</span></p></td><td class="c60" colspan="1" rowspan="1"><p class="c12"><span class="c40 c27 c20">3M CoTran&trade; 9722 Backing Polyethylene Monolayer Film<br><br></span></p><p class="c12"><span class="c40 c20">Alternative: (2nd best out of 3)</span></p><p class="c12 c36"><span class="c21 c8 c20"></span></p><p class="c12"><span class="c40 c20">3M CoTran&trade; 9719 Backing Polyethylene Monolayer Film<br></span></p></td><td class="c37" colspan="1" rowspan="1"><p class="c12"><span class="c40 c20">Out of the three films 3M offers, the qualities that we thought would be beneficial are:</span></p><ul class="c2 lst-kix_list_60-0 start"><li class="c12 c101"><span class="c21 c8 c20">Elongation = for movement of patient, has to 600% elongation, highest of the three</span></li><li class="c12 c101"><span class="c21 c8 c20">MVTR = this has the lowest amount out of all 3</span></li></ul><p class="c12"><span class="c40 c20">Translucent</span></p><p class="c12"><span class="c40 c20">Breathable</span></p><p class="c12"><span class="c40 c20">Printable</span></p><p class="c12"><span class="c40 c20">Can be directly laminated to adhesives</span></p><p class="c12"><span class="c40 c20">Heat Sealable (PE)</span></p><p class="c44 c67 c71 c19 c110"><span class="c40 c20">Designed to resist excipient and drug uptake</span></p></td><td class="c61" colspan="1" rowspan="1"><p class="c12"><span class="c40 c20">We are not sure how much oxygen the bacteria would be using. We are not sure if 6400 cc/m</span><span class="c40 c20 c75">2</span><span class="c40 c20">/day is enough for oxygen transmission.</span></p><p class="c12 c36"><span class="c21 c8 c20"></span></p><p class="c12"><span class="c40 c20">We do not know if this would turn cloudy after a period of time as currently existing patches with clear backing undergo the same issue.</span></p></td></tr><tr class="c74"><td class="c10" colspan="1" rowspan="1"><p class="c12"><span class="c40 c20">Adhesive Layer</span></p><p class="c12 c36"><span class="c21 c8 c20"></span></p><p class="c12"><span class="c40 c20">Also note that thicker adhesive layer also results in severe cold flow during storage in the pouch, and</span></p><p class="c12"><span class="c40 c20">higher affinity for lint and dirt to adhere to the edge of the</span></p><p class="c12"><span class="c40 c20">patch during wear.</span></p><p class="c12 c36"><span class="c21 c8 c20"></span></p></td><td class="c60" colspan="1" rowspan="1"><p class="c22 c67 c71 c19 c96"><span class="c21 c8 c20"><br><br></span></p><p class="c12"><span class="c26 c20"><a class="c29" href="https://www.google.com/url?q=http://na.henkel-adhesives.com/us/content_data/330922_11061_LT5343_Product_selector2_Web863600.pdf&amp;sa=D&amp;ust=1475957476586000&amp;usg=AFQjCNEFZFw8ge-ExoGl58r2mJtflo4ZKQ">pdf of Duro-Tak Transdermal Adhesives</a></span></p><p class="c12 c36"><span class="c21 c8 c20"><a class="c29" href="https://www.google.com/url?q=http://na.henkel-adhesives.com/us/content_data/330922_11061_LT5343_Product_selector2_Web863600.pdf&amp;sa=D&amp;ust=1475957476588000&amp;usg=AFQjCNGKXf9wgMR-qYgBSeIDbZ3ZwW57Pw"></a></span></p></td><td class="c37" colspan="1" rowspan="1"><p class="c12 c36"><span class="c21 c8 c20"><a class="c29" href="https://www.google.com/url?q=http://na.henkel-adhesives.com/us/content_data/330922_11061_LT5343_Product_selector2_Web863600.pdf&amp;sa=D&amp;ust=1475957476589000&amp;usg=AFQjCNE16Tb87yqzOEScghanD1ItfvJHRg"></a></span></p></td><td class="c61" colspan="1" rowspan="1"><p class="c12 c36"><span class="c21 c8 c20"><a class="c29" href="https://www.google.com/url?q=http://na.henkel-adhesives.com/us/content_data/330922_11061_LT5343_Product_selector2_Web863600.pdf&amp;sa=D&amp;ust=1475957476591000&amp;usg=AFQjCNH0rJYIEtTronG_8LNE6xh87VvQag"></a></span></p></td></tr><tr class="c74"><td class="c10" colspan="1" rowspan="1"><p class="c12"><span class="c40 c20">Release Liner</span></p></td><td class="c60" colspan="1" rowspan="1"><p class="c12"><span class="c40 c20">3M Scotchpak 1022</span></p><p class="c12"><span class="c40 c20">3M Scotchpak 9741</span></p><p class="c12"><span class="c40 c20">3M Scotchpak 9742</span></p><p class="c12"><span class="c40 c20">3M Scotchpak 9744</span></p><p class="c12"><span class="c40 c20">3M Scotchpak 9755</span></p><p class="c12 c36"><span class="c21 c8 c20"></span></p></td><td class="c37" colspan="1" rowspan="1"><ul class="c2 lst-kix_list_61-0 start"><li class="c12 c45"><span class="c21 c8 c20">Good for release with silicon skin contact adhesives, acrylate, PIB and rubber based PSA</span></li></ul><ul class="c2 lst-kix_list_62-0 start"><li class="c12 c45"><span class="c21 c8 c20">Excellent chemical stability</span></li></ul></td><td class="c61" colspan="1" rowspan="1"><p class="c12 c36"><span class="c21 c8 c20"></span></p></td></tr><tr class="c74"><td class="c10" colspan="1" rowspan="1"><p class="c12"><span class="c40 c20">Size-controlling membrane</span></p></td><td class="c60" colspan="1" rowspan="1"><p class="c12"><span class="c21 c8 c20">tentative</span></p></td><td class="c37" colspan="1" rowspan="1"><p class="c12 c36"><span class="c21 c8 c20"></span></p></td><td class="c61" colspan="1" rowspan="1"><p class="c12 c36"><span class="c21 c8 c20"></span></p></td></tr></tbody></table><h1 class="c11"><span class="c20">Important Notes</span></h1><p class="c22"><span class="c20"></span></p><h3 class="c11"><span class="c20">Monday, June 20th &nbsp;</span></h3><ul class="c2 lst-kix_list_75-0 start"><li class="c0"><span class="c5 c8">Emailed 3M for </span><span class="c25 c20">products</span><span class="c5 c8">, will </span><span class="c25 c20">talk</span><span class="c5 c8">&nbsp;</span><span class="c25 c20">to</span><span class="c5 c8">&nbsp;them tomorrow if they haven&rsquo;t replied.</span></li></ul><ul class="c2 lst-kix_list_75-1 start"><li class="c9"><span class="c5 c8">Got a reply from 3M. Will need to call them later to ask for</span><span class="c25 c20">&nbsp;products</span><span class="c5 c8">.</span></li></ul><ul class="c2 lst-kix_list_75-0"><li class="c0"><span class="c5 c8">Emailed Dow Corning for adhesives</span></li><li class="c0"><span class="c5 c8">Emailed Dr</span><span class="c25 c20">. </span><span class="c5 c8">Nezhad, an Electrical Engineering prof whose research is focused on microfluidics, for meeting</span></li><li class="c0"><span class="c5">Researched about different assays for material testing</span></li></ul><h3 class="c11"><span class="c20">Monday, June 27th</span></h3><ul class="c2 lst-kix_list_74-0 start"><li class="c0"><span class="c5 c8">Contacted 3M again, they are sending us the samples (YES). They should be here by the end of next week.</span></li><li class="c0"><span class="c5 c8">Dow Corning will send the adhesives on 29th of June</span></li><li class="c0"><span class="c5 c8">Today the device team focused on the math model for diffusion as weird numbers for the initial amount of peptides that needs to be produced have been calculated. Noshin found a paper with a MATLAB code that can be used to calculate the diffusion across a membrane using Fick&rsquo;s second law of diffusion. An email was sent out to Dr. Nygren to get his opinion on the code and see if we are heading in the right direction</span></li><li class="c0"><span class="c5 c8">UPDATE: We meet with Dr. Nygren Wednesday to go over the mathematical model developed. He suggested in his email that </span><span class="c41 c8 c25 c20">the equation is applicable in principle, but the situation is a little different because the membrane and skin surface are probably the main diffusion barriers and the diffusion constant is (very) different at those barriers compared to everywhere else. He also suggest we create a numerical method rather than doing it analytically. </span></li></ul><p class="c30 c19 c36"><span class="c5 c8"></span></p><h3 class="c11"><span class="c20">Tuesday, June 28th</span></h3><ul class="c2 lst-kix_list_76-0 start"><li class="c0"><span class="c5 c8">The device group continued to work on both learning Solidworks to build the graphical model as well as the mathematical model of the diffusion of BBI through the patch, skin and into the </span><span class="c25 c20">bloodstream</span><span class="c5 c8">.</span></li><li class="c34 c69 c19"><span class="c25 c20">From our results we calculated that we need 2 g of peptide being produced in the patch. This however is not feasible and needs to be reworked. </span></li></ul><h3 class="c11"><span class="c20">Wednesday, June 29th</span></h3><ul class="c2 lst-kix_list_78-0 start"><li class="c0"><span class="c5 c8">Protocols Tiff and Dave talked about with Dan</span></li></ul><ul class="c2 lst-kix_list_78-1 start"><li class="c9"><span class="c5 c8">Test how much media go through and if peptides go through; safety mechanism</span></li><li class="c9"><span class="c5 c8">Can we make dye as a qualitative or quantitative aspect of the assay?</span></li><li class="c9"><span class="c5 c8">How do we confirm peptides make it through?</span></li><li class="c9"><span class="c5 c8">Critical: make sure cells stay where they are, and peptides go through</span></li></ul><ul class="c2 lst-kix_list_77-1 start"><li class="c9"><span class="c5 c8">There may be a big difference in terms of the diffusion constants depending on the volume, barriers, material</span></li><li class="c9"><span class="c5 c8">Dr. Nygren&rsquo;s suggestions</span></li></ul><ul class="c2 lst-kix_list_77-2 start"><li class="c3"><span class="c5 c8">DRAW</span></li><li class="c3"><span class="c5 c8">Volumes separated by membranes</span></li><li class="c3"><span class="c5 c8">Faster production = would reach steady state at some point as too much BBI might stop bacteria from producing</span></li><li class="c3"><span class="c5 c8">Work equations out that he derived; make sure units are consistent</span></li><li class="c3"><span class="c5 c8">Degradation - might be in the bloodstream, not before the skin</span></li><li class="c3"><span class="c5 c8">Diffusion coefficients: testing would be necessary for peptide flow through membrane; for skin, could probably find from literature; or ask yourself, can we just find the diffusion coefficients rather than testing bunch of membranes?</span></li><li class="c3"><span class="c5 c8">In our case diffusion is too fast that equilibrium is achievable.</span></li><li class="c3"><span class="c5 c8">Make sure to state assumptions and a way to justify it.</span></li><li class="c39 c19"><span class="c40 c20">MATLAB: solving ODEs; recall ENGG 407 lecture</span></li></ul><h3 class="c11"><span class="c20">Tuesday, July 5th</span></h3><ul class="c2 lst-kix_list_79-0 start"><li class="c15 c19 c108"><span class="c5">The rest of the team continued to work on the diffusion model based on Dr. Nygren&rsquo;s suggestions. Based on Noshin&rsquo;s work, there were too many unknowns that we could solve for if we decided to solve the equation as a function of time. Therefore we went back to Fick&rsquo;s first law where the diffusion was a function of concentration over area. This however had unknowns such as protein solubility that we weren&rsquo;t sure of</span></li><li class="c15 c67 c19"><span class="c5">Adhesive? Gave the green light that the assays are doable</span></li></ul><ul class="c2 lst-kix_list_79-1 start"><li class="c14 c67"><span class="c5">Backing Layer? Gave a similar opinion that the assays are doable</span></li><li class="c14 c67"><span class="c5">Membrane? REASONABLE</span></li><li class="c14 c67"><span class="c5">Quantifying about how much peptide go through</span></li><li class="c14 c67"><span class="c5">Use of other peptides? (Since we want to quantify diffusion, maybe we could use something that is cheaper)</span></li><li class="c14 c67"><span class="c5">TRICKIEST: finding how much went through</span></li><li class="c44 c67 c93 c19 c97"><span class="c5">Glucagon, oxytocin (20 - 30 amino acids long)</span></li></ul><h3 class="c11"><span class="c20">Wednesday, July 13th</span></h3><ul class="c2 lst-kix_list_88-0 start"><li class="c0"><span class="c5 c8">Contacted Dr. Nezhad about manufacturing patches, asked for resources.</span></li><li class="c0"><span class="c5 c8">Contact Dr. Ingalls from Waterloo.</span></li><li class="c0"><span class="c5 c8">Update: Waterloo is open for collaboration.</span></li><li class="c0"><span class="c5 c8">In terms of modelling:</span></li></ul><ul class="c2 lst-kix_list_88-1 start"><li class="c9"><span class="c5 c8">Had our equations sent to Brian Ingalls for checking.</span></li></ul><ul class="c2 lst-kix_list_88-0"><li class="c0"><span class="c5 c8">Christine developed the patch using SolidWorks! See below:</span></li></ul><p class="c28 c19"><span style="overflow: hidden; display: inline-block; margin: 0.00px 0.00px; border: 0.00px solid #000000; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px); width: 240.74px; height: 218.59px;"><img alt="https://lh6.googleusercontent.com/95luN5VY1DQPEEZn6xdFivH9KrqA7sj3n81vc-wQQU5MMjOetj2M9ZvWvwGWyA4SzEA7nRSNAEH5oTWasxB2w0q4ZvqCLHbjPUblIF0iQ629ejJ2BVjple0vZJeL0K1pvXeV51Ku" src="images/image22.jpg" style="width: 240.74px; height: 218.59px; margin-left: -0.00px; margin-top: -0.00px; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px);" title=""></span></p><h3 class="c11"><span class="c20">Thursday, July 14th</span></h3><ul class="c2 lst-kix_list_89-0 start"><li class="c0"><span class="c5 c8">Meeting with Dr. Sundararaj (UT) next thursday the 21st at CCIT 320 at 1 pm for manufacturing.</span></li><li class="c0"><span class="c5 c8">Finished the analytical diffusion model across stratum corneum. See Device folder &gt;&gt; Patch Modelling &gt;&gt; open the only document there &gt;&gt; See Stratum corneum under Layer by Layer heading.</span></li><li class="c0"><span class="c5 c8">Tiffany finished her initial models for the bottom layer of the patch</span></li></ul><ul class="c2 lst-kix_list_89-1 start"><li class="c9"><span class="c5 c8">Optimized the dimensions to hold 10 mL in the main area, and either 0.5 and 1 mL of media in the pockets</span></li><li class="c9"><span class="c5 c8">Sent the models into 3D printing services at TFDL &lt;3</span></li><li class="c9"><span class="c5 c8">Will hear back in a couple of business days about the progress</span></li></ul><p class="c22 c19 c42"><span class="c40 c20"></span></p><h3 class="c11"><span class="c20">Friday, July 15th</span></h3><p class="c44 c19 c42"><span class="c40 c20">Team Meeting</span></p><ul class="c2 lst-kix_list_89-1"><li class="c14"><span class="c5">Nelly has finished the first part of the analytical model for the stratum corneum. She will continue working on the next two parts of the analytical model for the next week</span></li><li class="c14"><span class="c5">Dave has been researching ways to manufacture to create the patch. For most industries including 3M they will only manufacture for large scale industry</span></li><li class="c14"><span class="c5">As a result Dave is focussing on how to manufacture our patch ourselves or with some professors</span></li><li class="c14"><span class="c5">Nelly will help out with Dave with this by researching into the adhesive and how to attach it</span></li><li class="c14"><span class="c5">Both Nelly and David have contacted professors for help in manufacturing the patch. We have a meeting with Dr. UT next Thursday at 1:00 pm with David, Nelly and Tiff</span></li><li class="c14"><span class="c5">If worse comes to worse and no one can help us, we are visiting the machine shop to see if anyone can help us</span></li><li class="c14"><span class="c5">Christine and Tiff have finished their prototypes. Tiff has sent hers to get 3D printed and will hear back in a couple of business days about the progress</span></li><li class="c14"><span class="c5">Christine and Tiff will start David&rsquo;s assay next week and run triplicates throughout the week to see if the patch growth curves matches the ones under optimal conditions already done in the lab</span></li><li class="c14"><span class="c5">Discussed with Nishi what needs to be done for mouse trials</span></li></ul><ul class="c2 lst-kix_list_89-2 start"><li class="c44 c88 c19 c42"><span class="c5">There are three trials being run: 6 mice for a positive and negative control, 6 mice with patches with BBI dissolved in DMSO, and 6 mice with patches with cell culture</span></li><li class="c44 c88 c19 c42"><span class="c5">The patch is 1 cm X 1 cm X 0.2 cm</span></li><li class="c44 c88 c19 c42"><span class="c5">The patches need to be completed Monday prior the experiments begin the following Monday</span></li></ul><ul class="c2 lst-kix_list_89-1"><li class="c14"><span class="c5">Alina also messaged back Tiff to see how things were going</span></li></ul><ul class="c2 lst-kix_list_89-2 start"><li class="c44 c19 c42 c88"><span class="c5">She will be escorting an astronaut from the Apollo 11 mission during a science fair and so we can send her questions we can ask the astronauts that will be there</span></li><li class="c44 c88 c19 c42"><span class="c5">Tiff will create a document for questions to send to Alina. Focus the questions on either radiation in space or their lifestyles in space</span></li><li class="c44 c88 c19 c42"><span class="c5">As well she said she will try to help us with our model. She said to message her as a group if we have questions about the diffusion model. Currently she is working on her own MATLAB project and she said could help us with this aspect specifically </span></li></ul><p class="c44 c47 c19 c69"><span style="overflow: hidden; display: inline-block; margin: 0.00px 0.00px; border: 0.00px solid #000000; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px); width: 238.56px; height: 173.82px;"><img alt="Prototype_Christine.jpg" src="images/image21.jpg" style="width: 410.25px; height: 230.94px; margin-left: -93.47px; margin-top: -47.55px; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px);" title=""></span><span class="c40 c27 c20">&nbsp; </span><span style="overflow: hidden; display: inline-block; margin: 0.00px 0.00px; border: 0.00px solid #000000; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px); width: 273.91px; height: 174.47px;"><img alt="Prototype_Tiffany.jpg" src="images/image25.jpg" style="width: 340.97px; height: 196.71px; margin-left: -30.67px; margin-top: -20.44px; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px);" title=""></span></p><p class="c22 c47 c67 c19 c93"><span class="c40 c27 c20"></span></p><h3 class="c11"><span class="c20">Tuesday, July 19th</span></h3><ul class="c2 lst-kix_list_90-0 start"><li class="c0"><span class="c5 c8">This is what Nelly did for the whole day: </span><span class="c26 c8 c25 c20"><a class="c29" href="https://www.google.com/url?q=https://docs.google.com/document/d/1A2AMvbQ-WpV2omq_BrXjgnSq91J7drtvspDCaXYtqpc/edit?usp%3Dsharing&amp;sa=D&amp;ust=1475957476627000&amp;usg=AFQjCNGi4sd5yGp4ZFxkckvWYNn53QQKfw">Check this out</a></span><span class="c5 c8">. She tried to organize all the models she had on file into a document. Hopefully it is easier to navigate in this format. She also uploaded all the codes, functions, scripts etc. She uploaded it in a folder under Patch Modelling.</span></li><li class="c0"><span class="c5 c8">Followed up with Dr. Nezhad because he has not responded for 6 days.</span></li><li class="c0"><span class="c5 c8">Finished first draft of the powerpoint about our project. Check *presentation under *device for it.</span></li><li class="c0"><span class="c5 c8">Tiffany talked to Dr. Mayi concerning optimizing the diffusion assay</span></li></ul><ul class="c2 lst-kix_list_90-1 start"><li class="c9"><span class="c5 c8">Instead of an eight hour interval of taking the sample, we will run the project over a seven day period, taking samples at 24 hour period to mimic the patch.</span></li><li class="c9"><span class="c5">As well, we are now measuring the the optical densities over a spectrum as no literature points to a wavelength for saline solution/distilled water</span></li></ul><h3 class="c11"><span class="c20">Wednesday, July 20th</span></h3><ul class="c2 lst-kix_list_91-0 start"><li class="c15 c19"><span class="c5">Tiffany continued working on the diffusion assay and got initial results to determine the wavelength needed to determine the optical density of saline solution</span></li></ul><ul class="c2 lst-kix_list_91-1 start"><li class="c14"><span class="c5">The falcon tubes containing LB, </span><span class="c5 c51">B. subtiliis </span><span class="c5">and </span><span class="c5 c51">E.coli </span><span class="c5">were removed from the saline solution</span></li><li class="c14"><span class="c5">Saline solution was used as a blank</span></li><li class="c16"><span class="c5">Wavelengths of 260 nm, 300 nm, 600 nm, and 700 nm were used to measure the absorbance of the saline solutions contained in the erlenmeyer flask</span></li></ul><h3 class="c11"><span class="c20">Wednesday, July 27th</span></h3><ul class="c2 lst-kix_list_96-0 start"><li class="c0"><span class="c5 c8">Went to the machine shop to see if they can help us manufacture patches for prototype testing. </span></li></ul><ul class="c2 lst-kix_list_96-1 start"><li class="c9"><span class="c5 c8">Although they were not super clear about what we wanted initially they figured out the basics of what we needed from them</span></li><li class="c9"><span class="c5 c8">They took care of 3D printing for free for us as we are a student based project and they resolved the issues for us</span></li><li class="c9"><span class="c5 c8">Tiffany is in contact with them and will hear back from them in a couple of days</span></li><li class="c9"><span class="c5 c8">In addition, we learned that the machine shop cannot manufacture the patch. What they do recommend is the easiest way would be to proceed with something similar to the thermoforming method</span></li></ul><ul class="c2 lst-kix_list_96-0"><li class="c0"><span class="c5 c8">About the thermofolding method</span></li></ul><ul class="c2 lst-kix_list_96-1 start"><li class="c9"><span class="c5 c8">Suggested we cast a mold that they can help us design using metal. The mold would consist of two parts for the backing layer and the semipermeable membrane</span></li><li class="c9"><span class="c5 c8">We would then heat our materials and lay them onto the molds to conform to their shape. From there we place the molds together and inject our media into the mold and heat seal the entire patch together </span></li><li class="c9"><span class="c5 c8">Unfortunately they can only help us with the mold. They don&rsquo;t have equipment we could use </span></li></ul><ul class="c2 lst-kix_list_96-0"><li class="c0"><span class="c5 c8">We&rsquo;re gonna talk to Dr. Mayi/Nygren before we proceed to see if this is a good idea and how we can proceed about thermoforming. </span></li><li class="c0"><span class="c5 c8">We also need to determine experimentally at what temperature we get the two materials to seal together. This has to be determined ourselve</span><span class="c25 c20">s</span></li><li class="c0"><span class="c5">Tiff will bring hair iron + blow dryer tomorrow to test at what temperature we can heat seal our materials </span></li></ul><p class="c30 c19 c36"><span class="c25 c20"></span></p><h3 class="c11"><span class="c20">Thursday, July 28th</span></h3><ul class="c2 lst-kix_list_97-0 start"><li class="c0"><span class="c5 c8">The device team made prototypes today!</span></li></ul><ul class="c2 lst-kix_list_97-1 start"><li class="c9"><span class="c5 c8">We used the flat iron, iron, and blow dryer. Iron worked best. See pic below!</span></li></ul><p class="c28 c19 c54"><span style="overflow: hidden; display: inline-block; margin: 0.00px 0.00px; border: 0.00px solid #000000; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px); width: 225.00px; height: 155.34px;"><img alt="https://lh4.googleusercontent.com/83r22VBCFcCpmcATIgp2XtfMJeWXrfIsParzF8-_NDrXJ2vYyznjgSjS_KSxYprqehkaC7e4DiuwBWvwZ9t7RBklKE4bQipPKYPztWKjme-cF7dZiL4mZeVx7OcIa2j1fFGfKjbk" src="images/image23.jpg" style="width: 225.00px; height: 155.34px; margin-left: -0.00px; margin-top: -0.00px; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px);" title=""></span></p><ul class="c2 lst-kix_list_97-0"><li class="c0"><span class="c5 c8">Nelly worked on her adhesives. She tested BIO-PSA 7-4101 and 7-4301; however, both tests failed. What she did on her first test was she applied a thin film of adhesive on the release liner and let the heptane evaporate. She waited for 20 minutes, but the adhesive dried completely that it lost its adhesive properties. She tried the second time and she waited for heptane to evaporate for 5 minutes. The adhesives still contained heptane. She would run tests again tomorrow for 10 and 15 minutes.</span></li></ul><p class="c30 c19 c54 c36"><span class="c5 c8"></span></p><h3 class="c11"><span class="c20">Friday, July 29th</span></h3><ul class="c2 lst-kix_list_99-0 start"><li class="c0"><span class="c5 c8">Had our weekly meeting. See timeline for what we have to accomplish next week.</span></li><li class="c0"><span class="c5 c8">David contacted 3M to ask them to create a crude prototype so we have a better idea what the patch should look like.</span></li><li class="c0"><span class="c5 c8">Nelly did rounds of her adhesive testing assays. She found that the BIO-PSA 7-4201 will be the best adhesive for our current purposes. BIO PSA 7-4101 dries up quickly as when it was applied, it lost it adhesiveness. BIO PSA 7-4301, on the other hand, dries up very slowly, which also explained why it is less viscous than the other adhesives. This means it is dissolved in more heptane. In the pic below, Nelly was holding onto the release liner, the other layer was our membrane. The adhesive was successfully stuck to the membrane.</span></li></ul><ul class="c2 lst-kix_list_99-1 start"><li class="c9"><span class="c5 c8">Recommendations:</span></li></ul><ul class="c2 lst-kix_list_99-2 start"><li class="c3"><span class="c5 c8">Use of rolling pin for more uniform adhesive distribution.</span></li><li class="c3"><span class="c5 c8">Wait 1.5 minutes for the adhesive to dry up once spread as film before attaching the membrane.</span></li><li class="c3"><span class="c5 c8">Test on pork skin. Design assays for quantifying amounts of adhesive we need to apply, optimal temperature for drying, etc.</span></li><li class="c3"><span class="c5 c8">More prototypes next week!</span></li></ul><p class="c30 c19 c36"><span class="c5 c8"></span></p><p class="c28 c19"><span style="overflow: hidden; display: inline-block; margin: 0.00px 0.00px; border: 0.00px solid #000000; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px); width: 216.05px; height: 162.61px;"><img alt="https://lh3.googleusercontent.com/60Jbhx61W9q0phjrvzfOfPHuYXWcV4dxcV-1ZhghSo9bPKKQzQZjwUAVJ5GeYHpxOmKN1JS9LxEMwTYxKTr-33ZRf-_lZ0rRSxXVEikifCTDmZenrfT0Q3dw6KCg2YGAaAuMZJFo" src="images/image24.jpg" style="width: 218.82px; height: 297.61px; margin-left: -2.77px; margin-top: -79.98px; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px);" title=""></span></p><h3 class="c11"><span class="c20">Tuesday, August 2nd</span></h3><ul class="c2 lst-kix_list_100-0 start"><li class="c0"><span class="c5 c8">David finished a detailed word doc outline of the presentation (with some help from Nelly and Tiff &lt;3). Check under Presentation folder and edit anything you&rsquo;d like. Now pass on to Christine to create powerpoint. Christine started a rough draft of our presentation. </span></li><li class="c0"><span class="c5 c8">In the lab</span></li></ul><ul class="c2 lst-kix_list_100-1 start"><li class="c9"><span class="c5 c8">Tiff finished the last day of the diffusion assay</span></li><li class="c9"><span class="c5 c8">Nelly and David performed some adhesive experiments. They experienced problems and they are as follow:</span></li></ul><ul class="c2 lst-kix_list_100-2 start"><li class="c3"><span class="c5 c8">The adhesive did not stick to the liner completely</span></li><li class="c3"><span class="c5 c8">Uneven distribution of adhesive on liner</span></li></ul><p class="c30 c19 c36"><span class="c5 c8"></span></p><h3 class="c11"><span class="c20">Wednesday, August 3rd</span></h3><ul class="c2 lst-kix_list_101-0 start"><li class="c0"><span class="c5 c8">Christine did the data analysis for the diffusion assay</span></li></ul><p class="c28 c19"><span style="overflow: hidden; display: inline-block; margin: 0.00px 0.00px; border: 0.00px solid #000000; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px); width: 324.62px; height: 194.98px;"><img alt="https://lh6.googleusercontent.com/m3dDyIL1uE_GNFZynuFS_57Xnc1BJGEoSN5w7vITs-QOkYHEZy9837ILXqbXU_an8w16QSKXSrKa17pP6xI22sRsG2GASh13uxNLT-JUeHTGGK4mvKkIti_-aFy-TG4qdbwMaWqa" src="images/image26.png" style="width: 324.62px; height: 194.98px; margin-left: -0.00px; margin-top: -0.00px; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px);" title=""></span></p><p class="c28 c19"><span style="overflow: hidden; display: inline-block; margin: 0.00px 0.00px; border: 0.00px solid #000000; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px); width: 325.77px; height: 177.68px;"><img alt="https://lh5.googleusercontent.com/4gFPbGWT1reuLZK8HN57E-KCnMXxEjiWDldr7AmuH_yabV06PlLBESEDhZpxzoIdGfNYHL2PXv80iZWVNpO0ao6y_Cl_ooeJY_z-TKrPBusnURgjHufZRUy32x94SZHSJXHjgKwy" src="images/image27.png" style="width: 325.77px; height: 177.68px; margin-left: -0.00px; margin-top: -0.00px; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px);" title=""></span></p><p class="c28 c19"><span style="overflow: hidden; display: inline-block; margin: 0.00px 0.00px; border: 0.00px solid #000000; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px); width: 323.65px; height: 176.53px;"><img alt="https://lh3.googleusercontent.com/y5qddRKtejlpUm3AehyuaxwNgsffpGnkSMhYKr4qIGjb6CYz94Dokop_C7CsuXofbUlPUSiSE3sNBPcfsCGAXX7eXI70q8xlbP3LjY5wyaZ1qGcSf61Hu15Mv-67Jt_TcQEpryz3" src="images/image28.png" style="width: 323.65px; height: 176.53px; margin-left: -0.00px; margin-top: -0.00px; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px);" title=""></span></p><p class="c22"><span class="c20"></span></p><ul class="c2 lst-kix_list_102-0 start"><li class="c0"><span class="c5 c8">Nelly and David are testing adhesive. There were different methods used in doing these tests. They are as follow:</span></li></ul><ol class="c2 lst-kix_list_103-1 start" start="1"><li class="c23 c19"><span class="c5 c27">Rolling pin test</span></li></ol><ol class="c2 lst-kix_list_104-2 start" start="1"><li class="c18"><span class="c5 c8">An amount of adhesive was applied to the release liner.</span></li><li class="c18"><span class="c5 c8">A cut out of EVA membrane was placed onto the adhesive.</span></li><li class="c18"><span class="c5 c8">Place another layer of the release liner on the membrane to prevent the adhesives from sticking to the rolling pin.</span></li><li class="c18"><span class="c5 c8">Roll the pin on the layer to distribute adhesive.</span></li><li class="c18"><span class="c5 c8">Let it dry.</span></li></ol><ol class="c2 lst-kix_list_104-1 start" start="1"><li class="c23 c19"><span class="c5 c27">Film application test</span></li></ol><ol class="c2 lst-kix_list_104-2 start" start="1"><li class="c18"><span class="c5 c8">An amount of adhesive was applied to the release liner. The adhesive must be applied I a straight line.</span></li></ol><ol class="c2 lst-kix_list_105-2 start" start="1"><li class="c18"><span class="c5 c8">Spread the adhesive using a popsicle stick to form a thin film.</span></li><li class="c18"><span class="c5 c8">Wait for a minute before placing a cut out of EVA membrane onto the release liner to dry</span></li></ol><ol class="c2 lst-kix_list_105-1 start" start="1"><li class="c23 c19"><span class="c5 c27">Two - release - liner - sandwiched - together test</span></li></ol><p class="c30 c19 c87"><span class="c5 c8">An amount of adhesive was applied to the release liner. The adhesive must be applied in a spiral manner.</span></p><ol class="c2 lst-kix_list_106-2 start" start="1"><li class="c18"><span class="c5 c8">Place another layer of the release liner onto the initial liner.</span></li><li class="c18"><span class="c5 c8">Spread the adhesive using a rolling pin, by pressing, etc. until you see a clear film (meaning, no air bubbles, no accumulated glue anywhere, etc.)</span></li><li class="c18"><span class="c5 c8">Wait for 20 minutes to let the adhesives settle for a bit.</span></li><li class="c18"><span class="c5 c8">Peel the liners apart.</span></li><li class="c18"><span class="c5 c8">Place a cutout of the EVA membrane onto the liner. </span></li><li class="c18"><span class="c5 c8">Let it dry.</span></li></ol><p class="c30 c19 c36"><span class="c5 c27"></span></p><p class="c30 c19"><span class="c5 c27">Results from the adhesive tests:</span></p><ol class="c2 lst-kix_list_107-1 start" start="1"><li class="c23 c19"><span class="c5 c8">Rolling pin test: Opposite to what was expected, the adhesives were unevenly distributed. Air bubbles and bumps of glue were present. Some had not completely dried up, forming webs when peeled, some had.</span></li><li class="c23 c19"><span class="c5 c8">Film application test: The adhesives were unevenly distributed.</span></li><li class="c23 c19"><span class="c5 c8">Two - release - liner - sandwiched - together test: The adhesives were unevenly distributed, but this method was the most effective one. See pic below!</span></li></ol><p class="c28 c19"><span style="overflow: hidden; display: inline-block; margin: 0.00px 0.00px; border: 0.00px solid #000000; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px); width: 183.36px; height: 157.04px;"><img alt="https://lh6.googleusercontent.com/G1VGXsTZXwAzp2nytJ6fnDk7Mo8_dgi8mGyouQ_JWw6ABOBdlBOglKMJJ9j_D1g7lOnC6I_1WUFYWdx18F5Uaezw29ki4KDteUGihihwT8qZeE3WVdpTZSlqLlqcoJCWmiPKabre" src="images/image29.jpg" style="width: 183.36px; height: 157.04px; margin-left: -0.00px; margin-top: -0.00px; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px);" title=""></span></p><p class="c28 c19 c36"><span class="c7"></span></p><ul class="c2 lst-kix_list_110-0 start"><li class="c0"><span class="c5 c8">Tiffany also picked up the 3D printed models of our prototype from the machine shop </span></li></ul><p class="c28 c19 c89"><span style="overflow: hidden; display: inline-block; margin: 0.00px 0.00px; border: 0.00px solid #000000; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px); width: 174.68px; height: 174.68px;"><img alt="https://lh3.googleusercontent.com/Q6b-_3BxoTsmSJmaP0SfYbrbsnya6jmdGHCPQ37j7_P-rUjWzqHqTNrX3ttUboYEK8_ix3uFh94NshqsB20i_vxDMzTpOzwesveI4ZDZTykjT8xgh-vhwhANgUCg5_nim7Nh3fui" src="images/image30.jpg" style="width: 174.68px; height: 174.68px; margin-left: -0.00px; margin-top: -0.00px; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px);" title=""></span></p><h3 class="c11"><span class="c20">Thursday, August 4th</span></h3><p class="c19 c30"><span class="c5 c8">Team had a meeting with Dr. Nygren </span></p><ul class="c2 lst-kix_list_111-0 start"><li class="c0"><span class="c5 c8">Updates</span></li></ul><ul class="c2 lst-kix_list_111-1 start"><li class="c9"><span class="c5 c8">3D printing</span></li></ul><ul class="c2 lst-kix_list_111-2 start"><li class="c3"><span class="c5 c8">Patch seemed to be a reasonable size according to Dr. Nygren</span></li></ul><ul class="c2 lst-kix_list_111-1"><li class="c9"><span class="c5 c8">Diffusion assays</span></li></ul><ul class="c2 lst-kix_list_111-2 start"><li class="c3"><span class="c5 c8">There were bacteria leakage that happened</span></li><li class="c3"><span class="c5 c8">Back up plans, solving issues</span></li></ul><ul class="c2 lst-kix_list_111-1"><li class="c9"><span class="c5 c8">Meeting with Dr. UT</span></li></ul><ul class="c2 lst-kix_list_111-2 start"><li class="c3"><span class="c5 c8">Thermoforming</span></li></ul><ul class="c2 lst-kix_list_111-1"><li class="c9"><span class="c5 c8">Prototyping</span></li></ul><ul class="c2 lst-kix_list_111-2 start"><li class="c3"><span class="c5 c8">Maybe we could use wax paper or parchment paper. See what happens.</span></li><li class="c3"><span class="c5 c8">Machine shop may not be able to help us since they will be closing soon for renovations. They would require us to send the SolidWorks model asap. They can&rsquo;t do heat sealing for us, but they can make the mould.</span></li><li class="c3"><span class="c5 c8">For the mould: instead of making 18 patches at a time, make it simple by making 1 at a time. Easier to manufacture, cheaper</span></li><li class="c3"><span class="c5 c8">Adhesive: use of heat</span></li></ul><ul class="c2 lst-kix_list_111-0"><li class="c0"><span class="c5 c8">Manufacturing</span></li></ul><ul class="c2 lst-kix_list_111-1 start"><li class="c9"><span class="c5 c8">Materials for moulding</span></li></ul><ul class="c2 lst-kix_list_111-2 start"><li class="c3"><span class="c5 c8">Suggestions he could give us</span></li><li class="c3"><span class="c5 c8">Moulding design he could provide</span></li></ul><ul class="c2 lst-kix_list_111-3 start"><li class="c30 c64 c19"><span class="c5 c8">One at a time</span></li></ul><ul class="c2 lst-kix_list_111-1"><li class="c9"><span class="c5 c8">Contacts for manufacturing</span></li></ul><ul class="c2 lst-kix_list_111-2 start"><li class="c3"><span class="c5 c8">Companies: nope</span></li><li class="c3"><span class="c5 c8">Professors: nope</span></li></ul><ul class="c2 lst-kix_list_111-0"><li class="c0"><span class="c5 c8">Modelling</span></li></ul><ul class="c2 lst-kix_list_111-1 start"><li class="c9"><span class="c5 c8">Diffusion model Noshin prepared</span></li></ul><ul class="c2 lst-kix_list_111-2 start"><li class="c3"><span class="c5 c8">MATLAB code</span></li><li class="c3"><span class="c5 c8">ODE45 will help us get numerical values instead of having a function as a solution</span></li><li class="c3"><span class="c5 c8">C</span><span class="c4">2</span><span class="c5 c8">&nbsp;degradation</span></li><li class="c3"><span class="c5 c8">Flux = moles/(m</span><span class="c40 c8 c20 c62">2</span><span class="c5 c8">. s); production rate = moles/s</span></li><li class="c3"><span class="c5 c8">Start with assumed values for production rate and then move forward.</span></li></ul><ul class="c2 lst-kix_list_111-1"><li class="c9"><span class="c5 c8">Diffusion model Nelly prepared</span></li></ul><ul class="c2 lst-kix_list_111-2 start"><li class="c3"><span class="c5 c8">Will send the document to Dr. Nygren for checking </span></li></ul><p class="c22"><span class="c13"></span></p><h3 class="c11"><span class="c20">Friday, August 5th</span></h3><ul class="c2 lst-kix_list_113-0 start"><li class="c0"><span class="c5 c8">Mason completed a SolidWorks model of a previous microneedle prototype design </span></li><li class="c0"><span class="c5 c8">Noshin and David continued to manufacture patches in the lab. Following Nelly&rsquo;s procedure, the made patches that were 1 cm x 1 cm</span></li></ul><p class="c30 c19 c36"><span class="c5 c8"></span></p><p class="c28 c19"><span style="overflow: hidden; display: inline-block; margin: 0.00px 0.00px; border: 0.00px solid #000000; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px); width: 267.00px; height: 141.00px;"><img alt="https://lh5.googleusercontent.com/pfSoAS8wjfrF0sJF45faWbnPhemBGoxjt-oDBU5lyEd-DWZIPIpJ3T-JXC14ulvLhQjNIWKWU4OSf0Zj1NnYLGd8x--a8u5NBmnhj4GAq1GtO9DXrX8KzknhtyEXOlZAUfkIP-WO" src="images/image31.png" style="width: 317.93px; height: 190.73px; margin-left: -35.00px; margin-top: -24.00px; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px);" title=""></span><span style="overflow: hidden; display: inline-block; margin: 0.00px 0.00px; border: 0.00px solid #000000; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px); width: 154.84px; height: 136.20px;"><img alt="https://lh4.googleusercontent.com/REFz4eSdLc4kGa7rF-jSkvRmy655Lw7n9_fSH6lJoawV3EuvVj2oPCpiHRPC4V9BrYu9kjt4Vsb4njnq4L0VbpTYSUw6hEOyS7wsN9y-1VyKd5fxUqdLq9NaS-sl8ppyUowZQt2I" src="images/image32.png" style="width: 359.27px; height: 273.45px; margin-left: -110.39px; margin-top: -67.39px; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px);" title=""></span></p><p class="c30 c19"><span class="c7">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;</span></p><h3 class="c11"><span class="c20">Monday, August 8th</span></h3><ul class="c2 lst-kix_list_114-0 start"><li class="c0"><span class="c5 c8">Tiffany and Christine planned the week to perform the backing layer growth curves. These growth curves will be used to determine if cell growth is affected when gas exchange is limited</span></li></ul><ul class="c2 lst-kix_list_114-1 start"><li class="c9"><span class="c5 c8">The Plan</span></li></ul><ul class="c2 lst-kix_list_114-2 start"><li class="c3"><span class="c5 c8">Tuesday start the overnight cultures for the growth curves in the falcon tubes</span></li><li class="c3"><span class="c5 c8">Wednesday at 4:00 pm, 12:00 and Thursday at 8:00 am start inoculation for the tubes</span></li><li class="c3"><span class="c5 c8">Thursday start overnight cultures for the growth curves in the patch and perform growth curves for falcon tubes</span></li><li class="c3"><span class="c5 c8">Perform growth curves in the patch</span></li></ul><ul class="c2 lst-kix_list_114-1"><li class="c9"><span class="c5 c8">Before starting the growth curves in the patch, soak the 3D printed models in 70% ethanol overnight</span></li></ul><p class="c30 c19 c36 c102"><span class="c5 c8"></span></p><h3 class="c11"><span class="c20">Tuesday, August 9th</span></h3><ul class="c2 lst-kix_list_115-0 start"><li class="c0"><span class="c5 c8">Tiffany started the overnight cultures for the growth curves in the falcon tubes</span></li><li class="c0"><span class="c5 c8">Nelly and David made patch prototypes today. The procedures are as follows:</span></li></ul><p class="c30 c19"><span class="c5 c8 c51">Materials:</span></p><ul class="c2 lst-kix_list_116-0 start"><li class="c9"><span class="c5 c8">Strips of release liner ( 5cm x 13.2 cm )</span></li><li class="c9"><span class="c5 c8">Strips of EVA membrane ( 5cm x 13.2 cm )</span></li><li class="c9"><span class="c5 c8">Square cut outs of backing layer</span></li><li class="c9"><span class="c5 c8">BIO PSA adhesive</span></li><li class="c9"><span class="c5 c8">Cylindrical metal bar</span></li><li class="c9"><span class="c5 c8">Masking tape</span></li><li class="c9"><span class="c5 c8">Scissors, marker, ruler</span></li><li class="c9"><span class="c5 c8">Flat plastic surface </span></li><li class="c9"><span class="c5 c8">Iron </span></li><li class="c9"><span class="c5 c8">Syringe + needle</span></li></ul><p class="c30 c19"><span class="c5 c8 c51">Procedures:</span></p><ol class="c2 lst-kix_list_117-0 start" start="1"><li class="c19 c23"><span class="c5 c8 c51">Preparation of the adhesive layer</span></li></ol><ol class="c2 lst-kix_list_118-0 start" start="1"><li class="c9"><span class="c5 c8">Have the materials ready. Perform the process under the fume hood as the adhesives contain heptane. Heptane is flammable and create vapor trails that may cause fire.</span></li><li class="c9"><span class="c5 c8">Note that the coated side of the liner is where the adhesive will be applied. In case you cannot figure which one is the right side, grab a marker and try to write on both sides of the liner. If the ink stayed permanently on the liner, you wrote on the uncoated side. The side where the ink just slipped through would be the coated side. It would be recommended to write which side is which to avoid confusion.</span></li><li class="c9"><span class="c5 c8">Draw a horizontal line on one end of the release liners (1cm from the end) with a marker. This end will be taped to keep the liner in place when the adhesive is being applied.</span></li><li class="c9"><span class="c5 c8">Draw three 3cm x 3cm squares on the release liners. Make sure to leave ample amount of space between the squares. Draw 1cm x 1cm squares inside the initial squares. </span></li><li class="c9"><span class="c5 c8">Take all the materials under the fume hood. Tape the end release liner on the flat plastic surface. </span></li><li class="c9"><span class="c5 c8">Apply the adhesive on the line initially drawn. Apply a constant pea-size amount on the line.</span></li><li class="c9"><span class="c5 c8">Using the metal bar, spread the adhesive onto the liner. Spreading using a metal bar will form a thin film of adhesive on the liner.</span></li><li class="c9"><span class="c5 c8">Wait for about a minute before placing the EVA on the layer.</span></li><li class="c9"><span class="c5 c8">Carefully place the EVA membrane strip on the adhesive layer.</span></li><li class="c9"><span class="c5 c8">Lightly tap the membrane to stick. </span></li><li class="c9"><span class="c5 c8">Wait for the adhesive to completely dry (1 hr - 3 hrs).</span></li><li class="c9"><span class="c5 c8">Cut out the squares.</span></li></ol><p class="c30 c19"><span class="c5 c8 c51">B. Heat sealing the patch</span></p><ol class="c2 lst-kix_list_119-0 start" start="1"><li class="c9"><span class="c5 c8">Set the iron to the heat sealing temperature that was previously determined.</span></li><li class="c9"><span class="c5 c8">Place the backing layer on the prepared adhesive-membrane layer.</span></li><li class="c9"><span class="c5 c8">Carefully iron the sides of the layer. Avoid ironing parts of the 1cm x 1cm square &nbsp;centre drawn. This is where the nutrient rich media and bacteria will be stored.</span></li></ol><p class="c30 c19"><span class="c5 c8 c51">C. Adding the media in</span></p><ol class="c2 lst-kix_list_120-0 start" start="1"><li class="c9"><span class="c5 c8">Obtain the required amount/volume of media to be stored in the patch using a syringe.</span></li><li class="c9"><span class="c5 c8">Carefully inject the media into the middle compartments of the prepared patches by poking a hole on one of the corners of the drawn center squares.</span></li><li class="c9"><span class="c5 c8">Heat seal the holes created by the needles. &nbsp;</span></li></ol><p class="c30 c19 c36"><span class="c5 c8"></span></p><p class="c30 c19"><span class="c5 c8">***Check the whole document under </span><span class="c26 c25 c20"><a class="c29" href="https://www.google.com/url?q=https://docs.google.com/document/d/18uXLYuw3K3-0EAZaxPTyErA_iBWKPDveNloJpIzlsIU/edit&amp;sa=D&amp;ust=1475957476682000&amp;usg=AFQjCNGTw_WjDo2R5HiH7yt5D1XW2oJXhw">https://docs.google.com/document/d/18uXLYuw3K3-0EAZaxPTyErA_iBWKPDveNloJpIzlsIU/edit</a></span><span class="c25 c20">&nbsp;</span></p><p class="c30 c19 c36"><span class="c7"></span></p><h3 class="c11"><span class="c20">Wednesday, August 10th</span></h3><ul class="c2 lst-kix_list_121-0 start"><li class="c0"><span class="c5 c8">The team went to the Foothills machine shop yesterday at around 2pm to consult with Peter Byrne. He was the person Dr. Nygren had referred during our last meeting. We had set the mould specifications for him to follow. He had also given us suggestions to further improve our mould. The mould will be ready for about a week. ($50 per hour of labour by the way ladies and gentlemen).</span></li></ul><ul class="c2 lst-kix_list_121-1 start"><li class="c9"><span class="c5 c8">The mould will be made with aluminum and brass that may stick to our layers.He then recommended us to get a Teflon coating spray or something the same.</span></li></ul><ul class="c2 lst-kix_list_121-0"><li class="c0"><span class="c5 c8">Nelly finished adding her Powerpoint slides for the presentation on Monday. She also picked up a Dupont Non-stick Lubricant (with Teflon) from Canadian Tire.</span></li><li class="c0"><span class="c5 c8">David and Nelly made more adhesive layers before leaving the lab. Some had thicker adhesives applied, some had thinner layers. They will see how this quality would affect adhesion or if it has any effect at all.</span></li><li class="c0"><span class="c5 c8">Nelly tried one of the adhesive layer on her wrist. It took her a while to completely stick the layer on because it had thin adhesive coating. It also required applied pressure for it stick better. She had the layer on for 4 hours. </span></li></ul><ul class="c2 lst-kix_list_121-1 start"><li class="c9"><span class="c5 c8">Result: The layer was somehow painful to remove because some of her hair were stuck on the adhesive. She said the pain felt like a degree lower than a wax sheet slowly being peeled off your skin. There was no redness or irritation that happened on her skin, but itchiness was felt when the layer was on.</span></li><li class="c9"><span class="c5 c8">Recommendations: Disinfect the skin area before patch application.</span></li></ul><ul class="c2 lst-kix_list_121-0"><li class="c0"><span class="c5 c8">Christine continued working on the animation for Maya today and edited our presentation for August 15th.</span></li><li class="c0"><span class="c5 c8">Tiffany conducted assays in the laboratory today </span></li><li class="c0"><span class="c5 c8">Tiffany had also tested in the lab if the 3D models would hold the initially calculated volume of media.</span></li></ul><ul class="c2 lst-kix_list_121-1 start"><li class="c9"><span class="c5 c8">Results: The pockets exactly held 0.5 mL of liquid, while the content area held exactly 10 mL. Therefore, the 3D model is a good representation of our patch system in terms of holding capacity.</span></li></ul><p class="c30 c19 c36 c83"><span class="c5 c8"></span></p><h3 class="c11"><span class="c20">Thursday, August 11th</span></h3><ul class="c2 lst-kix_list_122-0 start"><li class="c0"><span class="c5 c8">Tiffany&rsquo;s focus today was to conduct the growth curve assays every 40 minutes.</span></li><li class="c0"><span class="c5 c8">Meeting with Dr, Nygren</span></li></ul><ul class="c2 lst-kix_list_122-1 start"><li class="c9"><span class="c5 c8">Potential questions here &rarr; </span><span class="c26 c8 c25 c20"><a class="c29" href="https://www.google.com/url?q=https://docs.google.com/document/d/1XVAW80zyGmWSUBj1KMXs12YQdXi7uQEtbdc4q-ZRPes/edit&amp;sa=D&amp;ust=1475957476690000&amp;usg=AFQjCNFUeArIbweNq1g2J-pFE1zcO1VfLQ">Questions for Dr. Nygren document</a></span></li></ul><ul class="c2 lst-kix_list_122-0"><li class="c0"><span class="c5 c8">Meeting minutes:</span></li></ul><ul class="c2 lst-kix_list_122-1 start"><li class="c9"><span class="c5 c8">Update: </span></li></ul><ul class="c2 lst-kix_list_122-2 start"><li class="c3"><span class="c5 c8">Showed Dr. Nygren the full system prototype Nelly and David made</span></li><li class="c3"><span class="c5 c8">Continuing assays by Tiffany and Christine</span></li><li class="c3"><span class="c5 c8">Christine is working on her video</span></li><li class="c3"><span class="c5 c8">Noshin is working on her math model</span></li><li class="c3"><span class="c5 c8">Went to machine shop to get the thermoforming mold done</span></li></ul><ul class="c2 lst-kix_list_122-1"><li class="c9"><span class="c5 c8">Modelling:</span></li></ul><ul class="c2 lst-kix_list_122-2 start"><li class="c3"><span class="c5 c8">Dr. Nygren said Noshin is on the right track. He will email her to clarify some details.</span></li></ul><ul class="c2 lst-kix_list_122-1"><li class="c9"><span class="c5 c8">Prototyping:</span></li></ul><ul class="c2 lst-kix_list_122-2 start"><li class="c3"><span class="c5 c8">Dr. Nygren suggested talking to Dr. Jenne about the prototype and alter it to better suit the mice.</span></li><li class="c3"><span class="c5 c8">Ask Dr. Mayi to buy the heat gun on our own</span></li></ul><ul class="c2 lst-kix_list_122-1"><li class="c9"><span class="c5 c8">Assays:</span></li></ul><ul class="c2 lst-kix_list_122-2 start"><li class="c3"><span class="c5 c8">Try to make a connection between the assays and math models. Answer the question of why we do the assay, why we have the models, what the connections are. Cohesion is key.</span></li></ul><h3 class="c11"><span class="c20">Friday, August 12th</span></h3><ul class="c2 lst-kix_list_123-0 start"><li class="c0"><span class="c5 c8">Christine and Tiffany worked on entering data values of their growth curve assays in a spreadsheet. They created time versus absorption plots.</span></li></ul><ul class="c2 lst-kix_list_123-1 start"><li class="c9"><span class="c5 c8">Results:</span></li></ul><p class="c30 c19 c54"><span class="c5 c8">Tube 1</span></p><p class="c30 c19 c54"><span style="overflow: hidden; display: inline-block; margin: 0.00px 0.00px; border: 0.00px solid #000000; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px); width: 380.27px; height: 240.60px;"><img alt="https://lh5.googleusercontent.com/h1dtXBI18oaz05qMdyqlZRzpa80B-MQI314SzStLNNLl4JdlN47qA3ZsiGrYS6tS2Iso4Gna9cmIDj69B8KNf4uRxSkPeH5lMbsxz101tWxSmekD9WFXqpCZ4RRaFPp6KQnuGhTA" src="images/image33.png" style="width: 380.27px; height: 240.60px; margin-left: -0.00px; margin-top: -0.00px; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px);" title=""></span></p><p class="c30 c19 c54"><span class="c5 c8">Tube 2</span></p><p class="c30 c19 c54"><span style="overflow: hidden; display: inline-block; margin: 0.00px 0.00px; border: 0.00px solid #000000; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px); width: 382.73px; height: 238.13px;"><img alt="https://lh3.googleusercontent.com/h3-QJBckEsZwi12oN8-fLjtVr55bvGLqTGj7LwpclwMSsnOQNP5gp5tV84nTpvdZUhcM6xhKhuEU4fPul68LzRDX5F6uqJBnLOZNSZF9se634trI24CRMvfp5hRS2Kkf1KhKrOjH" src="images/image04.png" style="width: 382.73px; height: 238.13px; margin-left: -0.00px; margin-top: -0.00px; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px);" title=""></span></p><p class="c30 c19 c54"><span class="c5 c8">Tube 3</span></p><p class="c30 c19 c54"><span style="overflow: hidden; display: inline-block; margin: 0.00px 0.00px; border: 0.00px solid #000000; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px); width: 384.00px; height: 235.67px;"><img alt="https://lh6.googleusercontent.com/zwfydSM_a0QzBxwecouoJMSiw6_7Y6Y_OupAraqEym9t6-cZgeXsHNr13cYJKbJCg9IUvVElYawVF034gVtdU4k81rsZk2BJoNRJvOdYK0xH06UneOW9Q04zQy4E9QmqspfHElx2" src="images/image05.png" style="width: 384.00px; height: 235.67px; margin-left: -0.00px; margin-top: -0.00px; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px);" title=""></span></p><p class="c30 c19 c54"><span class="c5 c8">Average of Tube 1, 2 &amp; 3</span></p><p class="c30 c19 c54"><span style="overflow: hidden; display: inline-block; margin: 0.00px 0.00px; border: 0.00px solid #000000; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px); width: 362.80px; height: 238.13px;"><img alt="https://lh4.googleusercontent.com/OB6hmeVcwG3v3YRqYT0un1gru7kET84YX1GrfYVWwHDyptqxwNs_oreDOeiCFBM_fnho4ZaHUgi__tpL1FP3BuexTMHLUA3aJJgPWQ1mbSvEf4lBUj1zdiSfnxTwtnIUDNpMSBlM" src="images/image06.png" style="width: 362.80px; height: 238.13px; margin-left: -0.00px; margin-top: -0.00px; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px);" title=""></span></p><p class="c22 c96"><span class="c20"></span></p><h3 class="c11"><span class="c20">Monday, August 15th</span></h3><ul class="c2 lst-kix_list_124-0 start"><li class="c0"><span class="c5 c8">Presentation day! What we basically did for today was preparing for our presentation and did run throughs.</span></li><li class="c0"><span class="c5 c8">After the presentation: dead. There were challenging questions thrown at us. This means we still have things to be solidified before we can say we&rsquo;re done.</span></li><li class="c0"><span class="c5 c8">We also asked our mentors for comments with regards to our presentation. They are as follows:</span></li></ul><ul class="c2 lst-kix_list_124-1 start"><li class="c9"><span class="c5 c8">Instead of having a slide with all equations on them, why not just use words that tells our audience what the terms represent.</span></li><li class="c9"><span class="c5 c8">Maya animation. Changes to be made could be:</span></li></ul><ul class="c2 lst-kix_list_124-2 start"><li class="c3"><span class="c5 c8">Making the adhesive liner take up the whole bottom area of the patch.</span></li><li class="c3"><span class="c5 c8">We&rsquo;re not using the indicator system to signal low media, but tells if the bacteria is activated.</span></li><li class="c3"><span class="c5 c8">After we have shown how the patch works, we can also extend the story by, say, an astronaut peels off the liner and apply patch, then wears this for this how many hours, and then through our modelling results we&rsquo;ll figure how long before we pop a packet and then what would happen next and, you know, the story goes on yadi yadi yada.</span></li></ul><ul class="c2 lst-kix_list_124-1"><li class="c9"><span class="c5 c8">Our graphs must be able to speak for themselves, meaning that by the time we look at them, we know right away what it is trying to tell us.</span></li><li class="c9"><span class="c5 c8">Explain all the terms that we are talking about.</span></li><li class="c9"><span class="c5 c8">CONNECT ALL THINGS TOGETHER.</span></li><li class="c9"><span class="c5 c8">Use constants that are from the other teams. The values we get from our model runs must correlate to the models and numbers Chassis and Biotarget get. Both Rai and Dr. Nygren brought this up.</span></li><li class="c9"><span class="c5 c8">Our model should also have a flow.</span></li></ul><p class="c30 c83 c19 c36"><span class="c5 c8"></span></p><h3 class="c11"><span class="c20">Friday, August 19th</span></h3><ul class="c2 lst-kix_list_130-0 start"><li class="c0"><span class="c5 c8">David and Nelly made more adhesive laminates, preparing for more prototypes</span></li></ul><p class="c30 c19 c89 c36"><span class="c5 c8"></span></p><h3 class="c11"><span class="c20">Tuesday, August 23rd</span></h3><ul class="c2 lst-kix_list_131-0 start"><li class="c0"><span class="c5 c8">Tiffany continued doing her diffusion assays. The dialysis membranes came today as well and treated for testing. There were two types of tubing membranes that were used: 20 kD and 628 kD pore size membranes. However, these membranes are not heat sealable which would be a problem in manufacturing. There were other &nbsp;limitations that were mentioned and these can be found in the email Nilesh sent/cc&rsquo;d us in. Tiffany will be performing diffusion assays for these membranes tomorrow.</span></li></ul><ul class="c2 lst-kix_list_131-1 start"><li class="c9"><span class="c5 c8">Must be soaked in room temperature distilled water for 30 minutes instead of being boiled</span></li><li class="c9"><span class="c5 c8">&ldquo;Just soak them- once you have figured out how to glue them together&rdquo; -- Dr. Volgo</span></li></ul><ul class="c2 lst-kix_list_131-0"><li class="c0"><span class="c5 c8">Nelly made around 80 adhesive laminates.</span></li></ul><p class="c30 c19 c54 c36"><span class="c5 c8"></span></p><h3 class="c11"><span class="c20">Wednesday, August 24th</span></h3><ul class="c2 lst-kix_list_132-0 start"><li class="c0"><span class="c5 c8">Tiffany performed her diffusion assays experiment using the dialysis tubing membranes.</span></li><li class="c0"><span class="c5 c8">Noshin worked on modelling and sent the codes to Dr. Nygren for checking. </span></li></ul><ul class="c2 lst-kix_list_132-1 start"><li class="c9"><span class="c5 c8">She also asked Dr. Nygren if he could give us a contact who could help us with cost analysis for our patch.</span></li></ul><p class="c30 c19 c54 c36"><span class="c25 c20"></span></p><h3 class="c11"><span class="c20">Friday, August 26th</span></h3><ul class="c2 lst-kix_list_134-0 start"><li class="c0"><span class="c5 c8">Tiffany and Christine picked up the moulds from the Foothills machine shop.</span></li><li class="c0"><span class="c5 c8">The results from dialysis membrane diffusion assays came out. There is still diffusion of bacteria through the membrane. </span></li><li class="c34 c69 c19"><span class="c5">The team also met with a PhD scholar, Xiaoan Li, whose research project focuses on water filtration using nanoporous membranes. Robert, a student who works in Li&rsquo;s lab, is also in the meeting.</span></li></ul><p class="c22 c67 c93 c19"><span class="c40 c20"></span></p><hr style="page-break-before:always;display:none;"><p class="c22"><span class="c35 c20 c86"></span></p><h1 class="c11"><span class="c20">Changing points in our Project</span></h1><p class="c22"><span class="c20"></span></p><h3 class="c11"><span class="c20">Monday, May 30</span><span class="c20 c75">th</span></h3><h3 class="c11"><span class="c5">Meeting with Dr. Dalton:</span></h3><ul class="c2 lst-kix_list_32-0 start"><li class="c0"><span class="c5 c8">Contact 3M for hollow microneedles, look at patents </span></li><li class="c0"><span class="c5 c8">If he can find his microneedles he will give it to us </span></li><li class="c0"><span class="c5 c8">Would have to consider shear stress, what if microneedles break off and go into the body</span></li><li class="c0"><span class="c5 c8">Utah array - solid microneedle </span></li><li class="c0"><span class="c5 c8">Lab on a chip - chips and tips </span></li><li class="c0"><span class="c5 c8">Perhaps make microneedle system separate with valve </span></li><li class="c0"><span class="c5 c8">Issues:</span></li></ul><ul class="c2 lst-kix_list_32-1 start"><li class="c9"><span class="c5 c8">In microfluidic systems are bubbles - bubble will block channels</span></li><li class="c9"><span class="c5 c8">LB chamber, what&rsquo;s stopping the fluid from flowing directly out the microneedles? Perhaps use a mechanical system to control pressure, could also suck the media back in </span></li><li class="c9"><span class="c5 c8">Diffusion would be way too slow or not even occur, would need an external syringe pump </span></li><li class="c9"><span class="c5 c8">Leaving microneedles in for too long will cause immune response from body, wound infections </span></li><li class="c9"><span class="c5 c8">Need to determine how much pressure the membrane can take </span></li><li class="c9"><span class="c5 c8">Consider stress on microneedles, fact that skin is very mobile </span></li><li class="c9"><span class="c5 c8">Skin elasticity, skin varies by thickness based on ethnicity and age, also have to consider the hairs on the skin </span></li></ul><p class="c30 c83 c19 c36"><span class="c5 c8"></span></p><h3 class="c11"><span class="c20">Wednesday, June 22nd</span></h3><ul class="c2 lst-kix_list_71-0 start"><li class="c0"><span class="c5 c8">Meeting with Dr. Amir Nezhad </span></li></ul><ul class="c2 lst-kix_list_71-1 start"><li class="c9"><span class="c5 c8">About Dr. Amir Nezhad&rsquo;s Research</span></li></ul><ul class="c2 lst-kix_list_71-2 start"><li class="c3"><span class="c5 c8 c48">Dr. Sanati-Nezhad&#39; primary research interest involves BioMEMS, Microfluidics, Tissue Engineering, Micro and Nano Technology, and Lab-on-Chip. </span></li><li class="c3"><span class="c5 c8 c48">His research group has focus on development of integrated bioinspired microdevices using microfluidics and tissue engineering approaches for disease modeling, biological systems modeling, and drug discovery. </span></li><li class="c3"><span class="c5 c8 c48">Another research interest of his group is to develop point-of-care devices for testing infectious diseases, and portable tools for detection of plant and food pathogens.</span></li></ul><ul class="c2 lst-kix_list_71-1"><li class="c9"><span class="c5 c8 c48">On meeting with him, we were invited to his lab where he showed us the process of micro fabricating the labs on the chips and how he uses microfluidics in order to do so</span></li><li class="c9"><span class="c5 c8 c48">The fabrication process is difficult. It requires a semi permeable membrane in the middle where the individual cells can be housed.</span></li><li class="c9"><span class="c5 c8 c48">Surrounding the permeable membrane is silicone mold to provide structure and handling.</span></li><li class="c9"><span class="c5 c8 c48">Although the chip looks simple, actual analysis requires a system of micropumps to transfer media, waste and byproducts across the system. This in turn is connected to a computer or microscope system for analysis.</span></li><li class="c9" id="h.gjdgxs"><span class="c5 c8 c48">In order to work for cells for 30 days, the first 6 - 15 days is incubating the cells and ensuring they are in a happy media. After that, you can start researching on the cells</span></li><li class="c9"><span class="c5 c8 c48">He mentioned the importance of finding the optimal flow rate in the chip because anything above or below they flow, will disrupt the cells and kill them</span></li><li class="c9"><span class="c5 c8 c48">In concerns with our project</span></li></ul><ul class="c2 lst-kix_list_71-2 start"><li class="c3"><span class="c5 c8 c48">He thinks the general idea of a patch system releasing various peptides into the body is very interesting and sees potential for collaboration with his lab</span></li><li class="c3"><span class="c5 c8 c48">When asked about companies to order from he suggested Dow Corning</span></li><li class="c3"><span class="c5 c8 c48">He stressed the importance of drafting up a prototype of our design in AutoCAD so he could better understand what our design will look like (not really? We asked him what he used for visual modelling and he said AutoCAD. However, he did stress making a powerpoint presentation to show people we consult to give them a better idea of what we are doing)</span></li></ul><ul class="c2 lst-kix_list_72-3 start"><li class="c30 c64 c19"><span class="c5 c8 c48">Gave us access from his lab to purchase AutoCAD</span></li></ul><ul class="c2 lst-kix_list_72-2 start"><li class="c3"><span class="c5 c8 c48">When asked about fabrication, he volunteered his services or that of the mechanical shop to create a prototype</span></li></ul><p class="c30 c19 c36"><span class="c5 c8"></span></p><h3 class="c11"><span class="c20">Thursday, June 23</span><span class="c20 c75">rd</span></h3><p class="c44"><span class="c20">Meeting with Dan and Dr. Mayi</span></p><ul class="c2 lst-kix_list_73-0 start"><li class="c0"><span class="c5 c8">Contacted Porex for EVA samples - waiting for response</span></li><li class="c0"><span class="c5 c8">Also discussed with Dan about assays we can perform for both the semi permeable membrane and backing layer</span></li></ul><ul class="c2 lst-kix_list_73-1 start"><li class="c9"><span class="c5 c8">For the semi permeable membrane&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;</span></li></ul><ul class="c2 lst-kix_list_73-2 start"><li class="c3"><span class="c5 c8">Using a 15 mL falcon tube, we can fill it with overnight cultures and wrap the semi permeable membrane underneath the lid. We then invert it in a larger 50 mL falcon tube with water, salts and at the same pH as the blood and leave it to sit. After hourly intervals, we would take samples of the water and take the OD readings.</span></li><li class="c3"><span class="c5 c8">Another assay that we can do is to use a brute force method and apply the same </span><span class="c25 c20">setup</span><span class="c5 c8">&nbsp;as the first assay. However we would centrifuge it down and see at the extremes how well our semi permeable membrane works.</span></li></ul><ul class="c2 lst-kix_list_73-1"><li class="c9"><span class="c5 c8">For the backing layer</span></li></ul><ul class="c2 lst-kix_list_73-2 start"><li class="c3"><span class="c5 c8">Dr. Mayi suggested creating a small patch with overnight cultures and leave it to sit in conditions similar to those found in the ISS. We take an OD reading initially and then let it sit for eight hours before taking another reading at the end and comparing the growth of our cells. We can also measure the amount of moisture vapour by measuring before and after the mass of the patch.</span></li><li class="c19 c39"><span class="c40 c20">Dan also suggested something similar to measure how well our cells grow. Using the small plates, we would aliquot some of our overnight cultures into two plates. We would then cover one with parafilm and the other with our backing layer. We then leave them to shake in the incubator. We take the initial OD and the final OD reading then of both to see how well our cells have grown</span></li></ul><h3 class="c11"><span class="c20">Thursday, July 21th</span></h3><ul class="c2 lst-kix_list_92-0 start"><li class="c0"><span class="c5 c8">David replied to 3M, they sent me back an email with useful info. I forwarded to everyone:</span></li></ul><ul class="c2 lst-kix_list_92-1 start"><li class="c9"><span class="c5 c8">Temperature and pressure depends on system: </span></li></ul><ul class="c2 lst-kix_list_92-2 start"><li class="c3"><span class="c5 c8">250F and 40 psi for their small single well sealer - 1 second so the liner doesn&rsquo;t warp.</span></li><li class="c3"><span class="c5 c8">However, multiple well sealer needs 300F, 50 psi</span></li><li class="c3"><span class="c5 c8">=&gt; May need a few trials to decide the parameters</span></li></ul><ul class="c2 lst-kix_list_92-1"><li class="c9"><span class="c5 c8">They can create a crude prototype to give us some idea of usability</span></li><li class="c9"><span class="c5 c8">If making it ourselves, they recommend a sequence of steps:</span></li></ul><ul class="c2 lst-kix_list_92-2 start"><li class="c3"><span class="c5 c8">coat adhesive onto the liner, laminate the membrane to the liner through a low pressure nip roller and lastly heat seal the backing to the lamination (on the membrane side) by placing the materials to be sealed onto a well type receiving fixture with silicone sealing gaskets and using a platen type seal plate above.</span></li></ul><ul class="c2 lst-kix_list_93-1 start"><li class="c9"><span class="c5 c8">Our membranes are the most permeable. The main difference is the thickness between the 2. The thicker one (9716) will have a slower transmission rate. If nothing works, they&rsquo;ll help us pick out another one.</span></li></ul><p class="c30 c19 c54 c36"><span class="c25 c20"></span></p><ul class="c2 lst-kix_list_94-0 start"><li class="c0"><span class="c5 c8">Meeting with Dr. UT Sundararaj about manufacturing:</span></li></ul><ul class="c2 lst-kix_list_94-1 start"><li class="c9"><span class="c5 c8">He went over the project with us and said gel media might be safer when being punctured but diffusion might be compromised. However, he said at equilibrium everything should be the same.</span></li><li class="c9"><span class="c5 c8">He approved our materials for the patch. He told us to consider the materials&rsquo; solubility parameters to make sure they are compatible and nothing will dissolve into each other when heated. EVA and polyethylene are fine. We might want to check hexane/heptane in the silicone adhesive and EVA though, but it should be fine.</span></li></ul><ul class="c2 lst-kix_list_94-2 start"><li class="c3"><span class="c26 c8 c25 c20"><a class="c29" href="https://www.google.com/url?q=http://cool.conservation-us.org/byauth/burke/solpar/solpar2.html&amp;sa=D&amp;ust=1475957476743000&amp;usg=AFQjCNGuEheOg58tIWDol6cZd1zb41qVTA">http://cool.conservation-us.org/byauth/burke/solpar/solpar2.html</a></span><span class="c5 c8">&nbsp;If delta is &gt;+-2 it should be okay.</span></li></ul><ul class="c2 lst-kix_list_94-1"><li class="c9"><span class="c5 c8">He recommended using thermoforming for our mouse patches. The general idea is to make a wood &ldquo;mold&rdquo;, heat our backing layer up, put it on, vacuum so it forms a reservoir, pour the media in, put the membrane on top, and then heat seal everything together. A flat iron for hair or something might work. It&rsquo;s also a good idea to apply heat on both sides.</span></li></ul><ul class="c2 lst-kix_list_94-2 start"><li class="c3"><span class="c5 c8">Thus, we need to get in touch with the machine shop ASAP</span></li></ul><p class="c44 c104"><span class="c26 c20"><a class="c29" href="https://www.google.com/url?q=http://www.plasticsmag.com/thermoforming.asp?fIssue%3DMar/Apr-03&amp;sa=D&amp;ust=1475957476745000&amp;usg=AFQjCNFTjtx3fu9TjL1MKCU3r15LqpOrhg">http://www.plasticsmag.com/thermoforming.asp?fIssue=Mar/Apr-03</a></span><span class="c40 c20">&nbsp;some reference we pulled out from google today about thermoforming.</span></p><h3 class="c11"><span class="c20">Friday, July 22nd</span></h3><ul class="c2 lst-kix_list_95-0 start"><li class="c0"><span class="c5 c8">Dow Corning (finally!) responded to Nelly about the preparation of adhesives.</span></li></ul><ul class="c2 lst-kix_list_95-1 start"><li class="c9"><span class="c5 c8">Basically, the actual adhesives are dissolved in heptane. This is the reason why handling it without precaution might cause irritation. The adhesive in its pure form is safe to use. </span></li><li class="c9"><span class="c5 c8">Easy enough, we just have to let the heptane evaporate so we can use the adhesives. The evaporation rate will depend on the temperature of the environment. In some patent documents she found online, companies dried the same type of adhesive in 100</span><span class="c62 c40 c8 c20">o </span><span class="c5 c8">C oven for 2-3 minutes.</span></li><li class="c16"><span class="c40 c20">Note, we must do any adhesive assays under the fume hood.</span></li></ul><h3 class="c11"><span class="c20">Wednesday, August 17th</span></h3><ul class="c2 lst-kix_list_125-0 start"><li class="c0"><span class="c5 c8">Meeting with Dr. Jenne (August 17, 2016)</span></li><li class="c9"><span class="c5 c8">Mouse orders done on W</span><span class="c5 c8">ed the 24th potentially</span></li><li class="c9"><span class="c5 c8">Might take some time to do training, he&rsquo;s concerned about the timeline since he technically can&rsquo;t order mice until he got ethics done</span></li><li class="c9"><span class="c5 c8">He thinks that the biggest thing for us is mass spectrometry</span></li><li class="c9"><span class="c5 c8">Problems we might encounter:</span></li></ul><ul class="c2 lst-kix_list_125-1 start"><li class="c3"><span class="c5 c8">Peptide not being found in the blood</span></li><li class="c3"><span class="c5 c8">If it&#39;s found in the blood, what if it&rsquo;s absorbed by other cells or organs</span></li></ul><ul class="c2 lst-kix_list_125-0"><li class="c9"><span class="c5 c8">The most important thing is what we get out of it, what the results tell us, and our future solutions for it. It&rsquo;s okay if it fails.</span></li><li class="c16"><span class="c5">We have to change the dimensions of our patch to make it narrower and longer.</span></li></ul><h3 class="c11"><span class="c20">Monday, August 22nd</span></h3><ul class="c2 lst-kix_list_128-0 start"><li class="c0"><span class="c5 c8">Modelling meeting with Dan</span></li></ul><ul class="c2 lst-kix_list_128-1 start"><li class="c9"><span class="c5 c8">In our modelling story, this experiment would be in the beginning of the story. This would be use which peptide we are going to use. Once our peptide has gone into the bloodstream, this model would help us determine how fast our peptides would diffuse through the cells to do its functions.</span></li><li class="c9"><span class="c5 c8">Different forms of our peptide</span></li></ul><ul class="c2 lst-kix_list_128-2 start"><li class="c3"><span class="c5 c8">How it would go through our membrane</span></li><li class="c3"><span class="c5 c8">Looking at the energy levels</span></li></ul><ul class="c2 lst-kix_list_128-3 start"><li class="c30 c64 c19"><span class="c5 c8">Applying force to membrane through a bilayer</span></li><li class="c30 c64 c19"><span class="c5 c8">Very hydrophobic = low energy in the middle</span></li><li class="c30 c64 c19"><span class="c5 c8">Calculate energy</span></li></ul><ul class="c2 lst-kix_list_128-1"><li class="c9"><span class="c5 c8">Size of the system</span></li></ul><ul class="c2 lst-kix_list_128-2 start"><li class="c3"><span class="c5 c8">Peptides: we want to model the different forms of our peptide and see which diffuse the fastest</span></li><li class="c3"><span class="c5 c8">9-residue monomer - linear (reduced form) and cyclic (oxidized form, ring, forming a disulfide bond = might affect diffusion, should it be reduced or not)</span></li><li class="c3"><span class="c5 c8">TD1 tag: compare that to BBI (combination of the 2 may have a better effect)</span></li><li class="c3"><span class="c5 c8">KSCI + monomer + F at the end</span></li></ul><ul class="c2 lst-kix_list_128-1"><li class="c9"><span class="c5 c8">Having a negative control </span></li></ul><ul class="c2 lst-kix_list_128-2 start"><li class="c3"><span class="c5 c8">Like a sodium ion (+ve)</span></li><li class="c3"><span class="c5 c8">Hormone that readily diffuses through</span></li></ul><ul class="c2 lst-kix_list_128-1"><li class="c9"><span class="c5 c8">Another important part: bilayer</span></li></ul><ul class="c2 lst-kix_list_128-2 start"><li class="c3"><span class="c5 c8">Simulate the actual membrane</span></li></ul><ul class="c2 lst-kix_list_128-3 start"><li class="c30 c64 c19"><span class="c5 c8">One type of human bilayer = have a smoother curve</span></li><li class="c30 c64 c19"><span class="c5 c8">Or a hydrocarbon bilayer/disc</span></li><li class="c30 c64 c19"><span class="c5 c8">Talk to them if we could have a simple bilayer with true phospholipid</span></li><li class="c30 c64 c19"><span class="c5 c8">Explicit water on the outside</span></li><li class="c30 c64 c19"><span class="c5 c8">Size of the environment (10nm cube, etc.)</span></li></ul><ul class="c2 lst-kix_list_128-1"><li class="c9"><span class="c5 c8">Ask if there is data already existing </span></li></ul><p class="c30 c19 c36"><span class="c5 c8"></span></p><h3 class="c11"><span class="c20">Friday, August 26th</span></h3><ul class="c2 lst-kix_list_135-0 start"><li class="c0"><span class="c5 c8">The team also met with a PhD scholar, Xiaoan Li, whose research project focuses on water filtration using nanoporous membranes. Robert, a student who works in Li&rsquo;s lab, is also in the meeting. He was a previous member of the winning iGEM team in 201_. Here&rsquo;s what we talked about:</span></li></ul><ul class="c2 lst-kix_list_135-1 start"><li class="c9"><span class="c5 c8">Ask Dr. Mayi or Deirdre about other membranes that we could test</span></li></ul><ul class="c2 lst-kix_list_135-2 start"><li class="c3"><span class="c5 c8">Examples </span></li></ul><ul class="c2 lst-kix_list_135-3 start"><li class="c30 c64 c19"><span class="c5 c8">centricon: small scale version, 5kD (ask Goodarzi&rsquo;s godmother): not as big, small scale purification, good for centrifuge works</span></li><li class="c30 c19 c64"><span class="c5 c8">filter sterilization membranes (0.22 micron)</span></li></ul><ul class="c2 lst-kix_list_135-1"><li class="c9"><span class="c5 c8">Watch 2011 NASA - video</span></li><li class="c9"><span class="c5 c8">figure out what carbon nanotubes we need, they got some. They have PPL, carbon nanotubes. Once we&rsquo;ve tried everything and still fail, then we should ask them.</span></li><li class="c9"><span class="c5 c8">Other ideas</span></li></ul><ul class="c2 lst-kix_list_135-2 start"><li class="c3"><span class="c5 c8">dissolving O</span><span class="c4">2 </span><span class="c5 c8">on the actual membrane</span></li><li class="c3"><span class="c5 c8">We need less than 200 nm of pore sizes</span></li><li class="c3"><span class="c5 c8">SEM, AFM: contact Matthias Amrein - does lung cells; Michael (runs SEM)</span></li></ul><ul class="c2 lst-kix_list_135-3 start"><li class="c30 c64 c19"><span class="c5 c8">use something conductive, Teflon is not conductive</span></li><li class="c30 c64 c19"><span class="c5 c8">thin sheet of gold</span></li></ul><ul class="c2 lst-kix_list_135-2"><li class="c3"><span class="c5 c8">figure out what materials we would need at the moment</span></li></ul><p class="c22 c69 c19"><span class="c40 c20"></span></p><hr style="page-break-before:always;display:none;"><p class="c22"><span class="c25 c20"></span></p><h1 class="c11"><span class="c20">Providers</span></h1><h3 class="c11" id="h.fdtmd7bfhu82"><span class="c20">Companies involved:</span></h3><p class="c22"><span class="c20"></span></p><h4 class="c11 c42" id="h.usxiqarmf0b2"><span class="c20">3M</span></h4><ul class="c2 lst-kix_lvjn8glkfwf0-0 start"><li class="c15"><span class="c25 c20">Provided us with all the sample materials used in the team&rsquo;s assays</span></li><li class="c15"><span class="c25 c20">The following materials are as follows:</span></li></ul><ul class="c2 lst-kix_lvjn8glkfwf0-1 start"><li class="c38"><span class="c25 c20">3M CoTran&trade; 9722 Backing Polyethylene Monolayer Film</span></li><li class="c38"><span class="c25 c20">3M CoTran&trade; 9719 Backing Polyethylene Monolayer Film</span></li><li class="c38"><span class="c25 c20">&nbsp;3M CoTran&trade; 9716 Ethylene Vinyl Acetate Membrane</span></li><li class="c38"><span class="c25 c20">3M CoTran&trade; 9728 Ethylene Vinyl Acetate Membrane</span></li><li class="c38"><span class="c25 c20">3M Scotchpak&trade; 1022 Release Liner Fluoropolymer Coated Polyester Film</span></li></ul><p class="c22 c42"><span class="c25 c20"></span></p><h4 class="c11 c42" id="h.ya27dyoiffqu"><span class="c20">Dow Corning</span></h4><ul class="c2 lst-kix_fahi2s4j7zmm-0 start"><li class="c15"><span class="c25 c20">Provides us with the adhesive samples used in our patches. </span></li><li class="c15"><span class="c25 c20">The following materials are as follows:</span></li></ul><ul class="c2 lst-kix_fahi2s4j7zmm-1 start"><li class="c38"><span class="c25 c20">Dow Corning BIO-PSA Silicone-based Adhesive 7-4101</span></li><li class="c38"><span class="c25 c20">Dow Corning BIO-PSA Silicone-based Adhesive 7-4201</span></li><li class="c38"><span class="c25 c20">Dow Corning BIO-PSA Silicone-based Adhesive 7-4301</span></li></ul><p class="c22 c42"><span class="c20"></span></p><p class="c22 c42"><span class="c20"></span></p><p class="c22"><span class="c20"></span></p><p class="c22"><span class="c20"></span></p><h1 class="c11 c65"><span class="c20"></span></h1><hr style="page-break-before:always;display:none;"><h1 class="c11 c65"><span class="c20"></span></h1><h1 class="c11"><span class="c20">Collaborations</span></h1><p class="c22"><span class="c20"></span></p><h3 class="c11"><span class="c20">Thursday, July 7th</span></h3><ul class="c2 lst-kix_list_80-0 start"><li class="c0"><span class="c5 c8">The team continued working on the diffusion model by either researching the equations further to see if there is another perspective we can take on the model or writing a code that can be used in MATLAB</span></li><li class="c0"><span class="c5 c8">Nelly was able to get a graph of the result of her MATLAB code [Insert image or comments here about the result Nelly!]</span></li><li class="c0"><span class="c5 c8">Meeting with Waterloo</span></li></ul><ul class="c2 lst-kix_list_80-1 start"><li class="c9"><span class="c5 c8">The modelling team met with the UWaterloo Modelling leads to discuss a possibility for collaboration</span></li><li class="c9"><span class="c5 c8">They are working on a project that uses yeast to take advantage of the higher readthrough rates during prion response</span></li><li class="c9"><span class="c5 c8">There is not very much commonality between the two projects but one potential would be a collaboration on their protein aggregation model as it would involve transcription rates</span></li><li class="c9"><span class="c5 c8">However after discussing, it may not be worth the collaboration between us and Waterloo</span></li></ul><p class="c30 c19 c36"><span class="c5 c8"></span></p><h4 class="c11"><span class="c20">iGEM Collaboration UCalgary &amp; UWaterloo MM</span></h4><p class="c44"><span class="c20">07 JULY 2016 / 4:00 PM</span></p><p class="c44 c66 c19"><span class="c27 c20">ATTENDEES</span></p><ul class="c2 lst-kix_list_81-0 start"><li class="c34 c57 c19"><span class="c8 c46 c20">Zo&euml; Humphries, Emily Watson, Tiffany Dang, Nelly Mendoza, David Nguyen, Sid Goutam and Nilesh Sharma</span></li></ul><p class="c44 c66 c19"><span class="c27 c20">BRIEF INTRO</span></p><p class="c44 c66 c19"><span class="c20 c51">UWaterloo Project Summary</span></p><ul class="c2 lst-kix_list_81-0"><li class="c0"><span class="c8 c46 c20">Creating a system that takes advantage of higher readthrough rates during [PSI+] state of prion response </span></li><li class="c0"><span class="c8 c46 c20">Model of iGEM collaboration network from 2015</span></li><li class="c0"><span class="c8 c20 c46">Model of plasmid retention - metabolic load of expressing our fusion protein</span></li><li class="c34 c57 c19"><span class="c8 c46 c20">Model of protein aggregation - how the prions are distributed through generations</span></li></ul><p class="c44 c66 c19"><span class="c20 c51">UCalgary Project Summary</span></p><ul class="c2 lst-kix_list_82-0 start"><li class="c0"><span class="c8 c46 c20">Working a transdermal delivery system to deliver peptides to the body</span></li><li class="c0"><span class="c8 c46 c20">Specifically working on the delivery of the Bowman Birk Inhibitor which as shown radioprotective effects </span></li><li class="c0"><span class="c8 c46 c20">Modelling the diffusion of BBI into the body to determine the initial concentration needed to be produced</span></li><li class="c34 c57 c19"><span class="c8 c46 c20">Model of the required transcription rates to produce the required amount of BBI or what a reasonable amount of BBI can be expected</span></li></ul><p class="c44 c66 c19"><span class="c20 c51">MORE DETAIL ABOUT WATERLOO MODEL</span></p><ul class="c2 lst-kix_list_83-0 start"><li class="c0"><span class="c8 c46 c20">Gene Retention Model</span></li><li class="c0"><span class="c8 c46 c20">Determine number of copies based on fluorescent protein in plasmids</span></li><li class="c0"><span class="c8 c46 c20">Retention is dependent on metabolic load, stability of plasmid, </span></li><li class="c0"><span class="c8 c46 c20">Quantify using fluorimetry</span></li><li class="c0"><span class="c8 c46 c20">Protein Aggregation Model</span></li><li class="c0"><span class="c8 c46 c20">Model how long it takes for aggregation to form (help lab subteam)</span></li><li class="c0"><span class="c8 c46 c20">No differential equations as of yet</span></li><li class="c0"><span class="c8 c46 c20">Probabilistics important for chance of inheritance in daughter cells</span></li><li class="c0"><span class="c8 c46 c20">Quantify aggregation via Western blots</span></li><li class="c0"><span class="c8 c46 c20">System should break down prions, will model this disassembly</span></li><li class="c34 c57 c19"><span class="c8 c46 c20">Quantify breakdown via GFP (sup35 prion protein begins functioning again)</span></li></ul><p class="c44 c66 c19"><span class="c20 c51">MORE DETAIL ABOUT CALGARY &nbsp;MODEL</span></p><ul class="c2 lst-kix_list_84-0 start"><li class="c0"><span class="c8 c46 c20">Diffusion Model </span></li><li class="c0"><span class="c8 c46 c20">Model how long it takes for the diffusion of BBI to reach steady state</span></li><li class="c0"><span class="c8 c46 c20">Compartmentalized the diffusion system into three components: the patch to the skin to the blood stream</span></li><li class="c0"><span class="c8 c46 c20">No differentials equations at this point but trying to use Fick&rsquo;s Law in MATLAB to see if we can analytically solve for the steady state</span></li><li class="c0"><span class="c8 c46 c20">Also using this model to determine the initial concentration needed in the patch for the desired amount of BBI to be found in the blood stream</span></li><li class="c0"><span class="c8 c46 c20">Transcription Rate Model </span></li><li class="c34 c19 c57"><span class="c8 c46 c20">Model to determine how fast the peptides are being produced inside the patch and how varying transcription rates will create the necessary concentration of peptide needed in the patch</span></li></ul><p class="c44 c19 c66"><span class="c20 c51">ACTUAL ITEMS FOR COLLABORATION</span></p><p class="c44 c66 c19"><span class="c20">UCalgary Assistance</span></p><ul class="c2 lst-kix_list_85-0 start"><li class="c0"><span class="c8 c46 c20">Help starting with the transcription rate models to determine how fast the peptides are being produced and what is a reasonable initial concentration based on these rates</span></li><li class="c0"><span class="c8 c46 c20">Mentoring for the diffusion model. This would be in the form of bouncing questions with Waterloo to see if we are on the right track and if there are any considerations we need to take</span></li><li class="c34 c57 c19"><span class="c8 c46 c20">With the gene retention model, UCalgary can help by collaborating on the transcription rates specifically</span></li></ul><p class="c44 c66 c19"><span class="c20">UWaterloo Assistance </span></p><ul class="c2 lst-kix_list_86-0 start"><li class="c0"><span class="c8 c46 c20">Gene retention subgroup most likely to benefit from assistance</span></li><li class="c0"><span class="c8 c46 c20">Optimising expression of plasmid number over gene copy number in plasmid</span></li><li class="c0"><span class="c8 c46 c20">Modelling expression of gene, how quickly the plasmid is lost during normal and prion states ([PSI+] condition)</span></li><li class="c0"><span class="c8 c46 c20">Dr. Brian Ingalls works on gene retention in bacteria, is a great resource</span></li><li class="c34 c57 c19"><span class="c8 c46 c20">Transcription rates would benefit gene retention and protein aggregation</span></li></ul><p class="c44 c66 c19"><span class="c20">ACTION ITEMS</span></p><ul class="c2 lst-kix_list_87-0 start"><li class="c0"><span class="c8 c46 c20">Use Google Drive to maintain collaboration docs</span></li><li class="c34 c57 c109"><span class="c8 c46 c20">UWaterloo will send update e-mail to math subteam &amp; CC UCalgary</span></li></ul><p class="c22"><span class="c20"></span></p><p class="c22"><span class="c13 c27 c49"></span></p><p class="c22"><span class="c20"></span></p><hr style="page-break-before:always;display:none;"><p class="c22"><span class="c35 c20 c86"></span></p><h1 class="c11"><span class="c20">Manufacturing</span></h1><h3 class="c11" id="h.oqjli87ma178"><span>Wednesday, August 24th</span></h3><ul class="c2 lst-kix_835ax5k7z1l9-0 start"><li class="c15 c33"><span class="c25 c20">Dave and Nel worked on manufacturing today. David had figure out a way to properly make our mice testing patches. The protocol is as follows:</span></li></ul><p class="c44 c33 c42"><span class="c27 c25 c20">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Procedure:</span></p><ol class="c2 lst-kix_g5lskmm1i0dj-0 start" start="1"><li class="c38 c33"><span class="c25 c20">Prepare the adhesive laminates following Nelly&rsquo;s procedure</span></li><li class="c38 c33"><span class="c25 c20">Plug the iron in to preheat.</span></li><li class="c38 c33"><span class="c25 c20">Look through the adhesive laminate under a light source and pick out and most even area. Sketch the 1 x 1 cm square on the liner at the center of the area</span></li><li class="c38 c33"><span class="c25 c20">Trim the laminate to roughly 1.5 x 1.5 cm</span></li><li class="c38 c33"><span class="c25 c20">Lay the laminate membrane-side up on the iron board, and the backing layer on top</span></li><li class="c38 c33"><span class="c25 c20">Iron 1 side of the patch up to the sketch. To make the seal even and bubble free, when sealing, apply more pressure on the side of the iron that&rsquo;s touching the line, then tilt the iron so that side of the iron lifts up slightly, then press it down again, after each time, move the iron away from the line to the edge of the patch. The seal should look clearer than the center. If not, then the iron is not hot enough, redo using a different side of the iron until it&rsquo;s clear</span></li><li class="c38 c33"><span class="c25 c20">Seal the other 3 edges. Now the patch should be stuck to the iron board, leave it there. Repeat the process for another 2 patches.</span></li><li class="c38 c33"><span class="c25 c20">Remove the first patch from the iron board. Prevent peeling the patch off the liner by sliding a finger under the patch after you peel off 1 corner when you reach the liner.</span></li><li class="c38 c33"><span class="c25 c20">Hold the patch diagonally, vertically, backing-side facing you. Bend it slightly so the backing folds towards you. The backing at the center (not sealed) should bend and separate from the membrane, creating a thin pocket running diagonally from the top corner to the bottom corner.</span></li><li class="c38 c33"><span class="c25 c20">Fill the syringe with water, use the needle to poke a hole at the top corner of the patch, make sure the needle did not poke anywhere else and the needle is in deeper than half of the patch.</span></li><li class="c38 c33"><span class="c25 c20">Inject the water slowly, keep a bend in the patch so we have a pocket, fill it from the bottom corner, tilt the needle and the patch to get the other 2 corners, then fill it nearly to the top corner. A good volume should be 0.06 - 0.08 mL</span></li><li class="c38 c33"><span class="c25 c20">Remove the needle straight out, a drop of water may leak out, dry it lightly with paper towel, don&rsquo;t push on it</span></li><li class="c38 c33"><span class="c25 c20">Lay it on the iron board. Make sure there&rsquo;s no water droplet visible. If there is, dry it gently with a paper towel, then iron on the hole for about 1-2 seconds</span></li><li class="c38 c33"><span class="c25 c20">Press on the patch slightly to see if there&rsquo;s still any leaks, if yes, dry the droplet of water with paper towel and re-iron the corner until there&rsquo;s no more leaks.</span></li><li class="c38 c33"><span class="c25 c20">Now the patch is done, trim the sealed sides with scissors to approximately half of the original side dimensions. Round off the sharp corners</span></li><li class="c38 c33"><span class="c25 c20">Cut a bandage in half, horizontally, then cut it vertically to create 2 small rectangles, with the sides approximately to be twice of the sealed sides of the patch </span></li><li class="c38 c33"><span class="c25 c20">To put the patch on a finger, remove the liner, put it on and press all edges lightly but firmly until all edges stay down</span></li><li class="c38 c33"><span class="c25 c20">To reinforce the patch, put the 2 bandage pieces on both sides that go down to the sides of the finger </span></li></ol><p class="c44 c33 c42"><span class="c27 c25 c20">*Note:</span><span class="c25 c20">&nbsp;A patch with &ldquo;YES&rdquo; written on it is on the iron board. It should show you the size of the patch, how clear the seals get, and how I seal the hole. You can ask Tiffany about the process of applying since she had 5 on her fingers today.</span></p><p class="c44 c33 c42"><span class="c27 c25 c20">*Note 2: </span><span class="c25 c20">This is a pretty reliable method. The seal works great most of the time. Poking more than 1 hole in the patch happens once in awhile. The patch stays on well most of the time. The water will leak when you put on if the seal is not good enough, or if there&rsquo;s another hole you accidentally poked.</span></p><h3 class="c11 c105" id="h.63wtgmetxp6p"><span></span></h3><h3 class="c11" id="h.h3fuz11zfuth"><span>Wednesday, August 31st</span></h3><ul class="c2 lst-kix_1qgee6j7obt0-0 start"><li class="c15 c33"><span class="c25 c20">David made some more mice patches for Thursday</span></li></ul><h3 class="c11" id="h.n0v42itdw701"><span>Thursday, September 1st</span></h3><ul class="c2 lst-kix_61pipssxjd5z-0 start"><li class="c15 c33"><span class="c25 c20">David put 3 patches of different shapes (square, rectangle, and triangle) on the mice in Dr. Jenne&rsquo;s lab and reinforced them with tissue glue.</span></li></ul><h3 class="c11" id="h.5doz1h9godgl"><span>Friday, September 2nd</span></h3><ul class="c2 lst-kix_6ppt4s25kk1y-0 start"><li class="c15 c33"><span class="c25 c20">All 3 patches from yesterday survived. The rectangle and triangle worked better than the square. Rachelle from Dr. Jenne&rsquo;s lab said the rectangle looked best.</span></li></ul><h3 class="c11" id="h.81lmk4oa5bpt"><span>Tuesday, September 5th</span></h3><ul class="c2 lst-kix_ee0fx9z4yp3a-0 start"><li class="c34"><span class="c25 c20">David created 28 patches for the mouse testing with 9 containing water, 9 containing bacteria and 10 containing pure BBI &nbsp;</span><hr style="page-break-before:always;display:none;"></li></ul><h1 class="c11"><span class="c20">Research</span></h1><p class="c22"><span class="c20"></span></p><p class="c30 c19"><span class="c5 c27">Papers:</span></p><p class="c30 c19"><span class="c26 c8 c25 c20"><a class="c29" href="https://www.google.com/url?q=http://www.ncbi.nlm.nih.gov/pubmed/21139238&amp;sa=D&amp;ust=1475957476814000&amp;usg=AFQjCNGnAEZv91aLCzjjaoDQo4_W4VpaDQ">http://www.ncbi.nlm.nih.gov/pubmed/21139238</a></span></p><ul class="c2 lst-kix_list_2-0 start"><li class="c0"><span class="c5 c8">Hydrophilic large molecular compounds</span></li><li class="c0"><span class="c5 c8">Via hollow microneedles </span></li></ul><ul class="c2 lst-kix_list_2-1 start"><li class="c9"><span class="c5 c8">Loaded into lower epidermis and superficial dermis</span></li></ul><ul class="c2 lst-kix_list_2-0"><li class="c0"><span class="c5 c8">Release rates (Fick&rsquo;s Law of Diffusion)</span></li></ul><ul class="c2 lst-kix_list_2-1 start"><li class="c9"><span class="c5 c8">Increase volume of FD-4 injected - faster the FD-4 release rate from skin</span></li><li class="c9"><span class="c5 c8">Release rate increases when FD-4 given in multiple injections</span></li><li class="c9"><span class="c5 c8">Large molecule = lower release rate from skin</span></li></ul><ul class="c2 lst-kix_list_2-0"><li class="c0"><span class="c5 c8">Silicon - useful material? </span></li><li class="c0"><span class="c5 c8">Questions:</span></li></ul><ul class="c2 lst-kix_list_2-1 start"><li class="c9"><span class="c5 c8">So is the drug being released secreted out of the skin after secretion?</span></li></ul><p class="c30 c19 c36"><span class="c5 c8"></span></p><p class="c30 c19"><span class="c26 c8 c25 c20"><a class="c29" href="https://www.google.com/url?q=http://www.ncbi.nlm.nih.gov/pubmed/22575858&amp;sa=D&amp;ust=1475957476819000&amp;usg=AFQjCNHZNxsPuut0irr_YvSYjBrI0p17CA">http://www.ncbi.nlm.nih.gov/pubmed/22575858</a></span></p><ul class="c2 lst-kix_list_3-0 start"><li class="c0"><span class="c5 c8">Sections 2.4, 3.1,2</span></li><li class="c0"><span class="c5 c8">Pressure gradient - greater pressure causes drug to flow through </span></li><li class="c0"><span class="c5 c8">Diffusion gradient </span></li><li class="c0"><span class="c5 c8">Questions:</span></li></ul><ul class="c2 lst-kix_list_3-1 start"><li class="c9"><span class="c5 c8">Based on methods of delivery - silicon; have to test and make sure peptide/fluid/bacteria doesn&rsquo;t react with silicon</span></li><li class="c9"><span class="c5 c8">Simulate a large scale prototype of design to test if we can use pressure/diffusion to get the peptide to flow through</span></li></ul><ul class="c2 lst-kix_list_3-0"><li class="c0"><span class="c5 c8">Problem:</span></li></ul><ul class="c2 lst-kix_list_3-1 start"><li class="c9"><span class="c5 c8">For microneedles that use multiple needles (our suggested form):</span></li></ul><ul class="c2 lst-kix_list_3-2 start"><li class="c3"><span class="c5 c8">1 microneedle leaks</span></li><li class="c3"><span class="c5 c8">Pressure can&rsquo;t be equally applied to all needles </span></li><li class="c3"><span class="c5 c8">Fluid won&rsquo;t flow through all microneedles equally</span></li></ul><ul class="c2 lst-kix_list_3-1"><li class="c9"><span class="c5 c8">The small size of microneedles - drugs given on/within microneedles limited to microgram dose </span></li></ul><ul class="c2 lst-kix_list_3-0"><li class="c0"><span class="c5 c8">Applications of microneedles </span></li></ul><ul class="c2 lst-kix_list_3-1 start"><li class="c9"><span class="c5 c8">Biotherapeutics, drugs (peptides, proteins, DNA,RNA)</span></li></ul><ul class="c2 lst-kix_list_3-0"><li class="c0"><span class="c5 c8">Hollow microneedles - used for insulin delivery in both rats and humans</span></li><li class="c0"><span class="c5 c8">Diffusion and active infusion worked, decreased blood-glucose levels after injection </span></li><li class="c0"><span class="c5 c8">Humans found it to be:</span></li></ul><ul class="c2 lst-kix_list_3-1 start"><li class="c9"><span class="c5 c8">Decreased pain</span></li><li class="c9"><span class="c5 c8">More preferred (compared to normal needles)</span></li><li class="c9"><span class="c5 c8">Increased insulin pharma</span><span class="c25 c20">c</span><span class="c5 c8">okinetics almost 2-fold - may cause better control over post plasma glucose levels </span></li><li class="c9"><span class="c5 c8">Had faster insulin absorption and enabled more rapid onset and offset metabolic effect on blood glucose levels than injection </span></li></ul><p class="c30 c19 c36"><span class="c5 c8"></span></p><p class="c30 c19"><span class="c26 c8 c25 c20"><a class="c29" href="https://www.google.com/url?q=https://www.researchgate.net/publication/228562173_Side-Opening_Hollow_Microneedles_for_Transdermal_Drug_Delivery&amp;sa=D&amp;ust=1475957476827000&amp;usg=AFQjCNFyycOUgFXczZghrV31m95lPrcZ7w">https://www.researchgate.net/publication/228562173_Side-Opening_Hollow_Microneedles_for_Transdermal_Drug_Delivery</a></span></p><ul class="c2 lst-kix_list_4-0 start"><li class="c0"><span class="c5 c8">Proposed design - measurements for diameter length of needle, etc. </span></li><li class="c0"><span class="c5 c8">pump/syringe for injection</span></li></ul><ul class="c2 lst-kix_list_4-1 start"><li class="c9"><span class="c5 c8">Need to test diffusion; if diffusion doesn&rsquo;t work, use hand to press </span></li></ul><ul class="c2 lst-kix_list_4-0"><li class="c15 c19"><span class="c40 c20">Overdose problem</span></li></ul><ul class="c2 lst-kix_list_4-1 start"><li class="c14"><span class="c40 c20">Reservoir patches give tighter control of delivery rates but can have an initial burst of drug release. If the membrane is damaged, there is also a risk of sudden release of drug into the skin and overdose as potentially a larger area of skin is exposed for drug absorption.</span></li><li class="c14"><span class="c40 c20">In a matrix patch, the active ingredient is distributed evenly throughout the patch. One-half of a patch will have half the original surface area and deliver half the original dose per hour. The matrix patch carries less risk of accidental overdose and offers less potential for abuse than the reservoir system.</span></li></ul><p class="c30 c19 c36"><span class="c17 c8"></span></p><p class="c30 c19"><span class="c5 c8 c48 c84"><a class="c29" href="https://www.google.com/url?q=http://ieeexplore.ieee.org/stamp/stamp.jsp?tp%3D%26arnumber%3D659727&amp;sa=D&amp;ust=1475957476830000&amp;usg=AFQjCNGu57kWJcT_VdYBemUiA3zwu_u-_w">http://ieeexplore.ieee.org/stamp/stamp.jsp?tp=&amp;arnumber=659727</a></span></p><ul class="c2 lst-kix_list_30-0 start"><li class="c0"><span class="c17 c8">The principle of operation is based on the pressure barrier that develops when cross section of capillaries change abruptly in neck and expansion regions. This type of gating device in its normal state can only stop flow, but it can be electrically triggered to re-establish flow when used in combination with two electrodes.</span></li><li class="c0"><span class="c8 c17">Mechanics: The capillary stop consists of a region of the tube that is necked down followed by a sharp enlargement. When the liquid as first introduce in the reservoir, it wicks in the necked region and abruptly stops at the neck of the outer edge preventing any outer flow. The pressure barrier provided by the stop can be overcome by external pressure to re-establish a flow.</span></li></ul><p class="c28 c19 c36"><span class="c7"></span></p><p class="c30 c19 c36"><span class="c5 c8"></span></p><p class="c30 c19 c36"><span class="c5 c8"></span></p><hr style="page-break-before:always;display:none;"><p class="c22"><span class="c35 c20"></span></p><h1 class="c11"><span class="c20">Material Research</span></h1><p class="c22"><span class="c20"></span></p><h3 class="c11"><span class="c20">Tuesday, May 31st</span></h3><p class="c44 c19 c42"><span class="c26 c20"><a class="c29" href="https://www.google.com/url?q=http://images.alfresco.advanstar.com/alfresco_images/pharma/2014/08/22/ba2e9668-a586-4daf-9179-70f220be6e56/article-18600.pdf&amp;sa=D&amp;ust=1475957476836000&amp;usg=AFQjCNERbTjXLTj8M9afTq86__oduerDpg">http://images.alfresco.advanstar.com/alfresco_images/pharma/2014/08/22/ba2e9668-a586-4daf-9179-70f220be6e56/article-18600.pdf</a></span></p><p class="c44 c19 c42"><span class="c40 c27 c20">PSA = Pressure Sensitive Adhesives</span></p><ul class="c2 lst-kix_list_33-0 start"><li class="c15 c19"><span class="c40 c20">Materials that adhere to skin with application of light pressure and do not leave residue upon removal</span></li><li class="c15 c19"><span class="c40 c20">See paper for materials used</span></li></ul><ul class="c2 lst-kix_list_33-1 start"><li class="c14"><span class="c40 c20">Acrylic-, polyisobutylene- &amp; silicone based adhesives commonly used in transdermal patches </span></li></ul><ul class="c2 lst-kix_list_33-0"><li class="c15 c19"><span class="c40 c20">Increasing the polymer content provides a softer and tackier adhesive, whereas higher resin levels result in lower tack but higher adhesion and resistance to cold flow.</span></li><li class="c15 c19"><span class="c40 c20">Release liner is peeled off = also has the adhesive properties</span></li></ul><p class="c44 c19 c42"><span class="c40 c27 c20">Idea to prevent water from leaking out:</span></p><ul class="c2 lst-kix_list_34-0 start"><li class="c15 c19"><span class="c40 c20">Adding some sort of liquid in pores that will let peptide through and not let media mix with it</span></li><li class="c15 c19"><span class="c40 c20">Gel-like fluid for media</span></li></ul><p class="c44 c19 c42"><span class="c40 c27 c20">Design of patches:</span></p><ul class="c2 lst-kix_list_36-0 start"><li class="c15 c19"><span class="c40 c20">Polymer membrane partition-controlled TDD systems</span></li></ul><ul class="c2 lst-kix_list_36-1 start"><li class="c14"><span class="c40 c20">There is a constant release as long as concentration is maintained, but release rapidly decline when device approaches exhaustion</span></li><li class="c14 c47"><span style="overflow: hidden; display: inline-block; margin: 0.00px 0.00px; border: 0.00px solid #000000; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px); width: 381.53px; height: 189.53px;"><img alt="https://lh5.googleusercontent.com/JCscMWwIIWCZyQmhyo_RWNyF40eYT0ch-4-EVTEAFEFeC1shib1cXuxpdL8CGpVBTrZ4_cB0vFXafs0tE2v1AeEOYY4S-t0v-z77Vf4dG_JOsxlvmhMicI0lsgwBWDmczCc6iVBt" src="images/image07.png" style="width: 381.53px; height: 189.53px; margin-left: -0.00px; margin-top: -0.00px; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px);" title=""></span></li></ul><ul class="c2 lst-kix_list_36-0"><li class="c15 c19"><span class="c40 c20">Reservoir system</span></li></ul><ul class="c2 lst-kix_list_36-1 start"><li class="c14"><span class="c40 c20">Same concept</span></li></ul><ul class="c2 lst-kix_list_36-0"><li class="c15 c19"><span class="c20 c40">Drug in adhesives</span></li></ul><ul class="c2 lst-kix_list_36-1 start"><li class="c14"><span class="c40 c20">I don&rsquo;t think this is applicable for us, but would put it here just for reference</span></li></ul><p class="c44 c47 c19 c42 c54"><span style="overflow: hidden; display: inline-block; margin: 0.00px 0.00px; border: 0.00px solid #000000; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px); width: 426.40px; height: 158.33px;"><img alt="https://lh4.googleusercontent.com/h7rTSADFOw6X9T3I3CBLc5iCg8a4Dtr9oximAGA7e0HLF11-_Bx7wPfhAYrjvE9E3NH6rJhW2pasWWxZWKU2yKe4O7JrVG7iwReQJ-kGD1Wt0A97VItuJNCRFiUuoqV25KTvCoil" src="images/image08.png" style="width: 426.40px; height: 158.33px; margin-left: -0.00px; margin-top: -0.00px; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px);" title=""></span></p><ul class="c2 lst-kix_list_39-0 start"><li class="c15 c19"><span class="c40 c20">Micro reservoir type</span></li></ul><ul class="c2 lst-kix_list_39-1 start"><li class="c14"><span class="c40 c20">Suspension of drug with aqueous solution of water-soluble liquid soluble polymer</span></li><li class="c14"><span class="c40 c20">Homogenous dispersion of drug suspension in a lipophilic polymer (silicone elastomer)</span></li><li class="c16"><span class="c40 c20">Example: nitroglycerin patches</span></li></ul><p class="c30 c19"><span class="c5 c27">Competitors:</span></p><ul class="c2 lst-kix_list_40-0 start"><li class="c0"><span class="c5 c8">TEPI Patch </span></li></ul><ul class="c2 lst-kix_list_40-1 start"><li class="c9"><span class="c5 c8">Articles:</span></li></ul><ul class="c2 lst-kix_list_40-2 start"><li class="c3"><span class="c26 c8 c25 c20"><a class="c29" href="https://www.google.com/url?q=http://futurerxdream.com.ng/ibuprofen-patch-heralds-side-effect-free-drug-future/&amp;sa=D&amp;ust=1475957476847000&amp;usg=AFQjCNHIdvqfFZE3z16Ot72Wompo-NrO3g">http://futurerxdream.com.ng/ibuprofen-patch-heralds-side-effect-free-drug-future/</a></span></li><li class="c3"><span class="c26 c8 c25 c20"><a class="c29" href="https://www.google.com/url?q=http://www.painnewsnetwork.org/stories/2015/12/9/new-skin-patch-delivers-pain-relief-with-ibuprofen&amp;sa=D&amp;ust=1475957476849000&amp;usg=AFQjCNEv2XIwS9wJj1S_O_QE7zt5HLU0uQ">http://www.painnewsnetwork.org/stories/2015/12/9/new-skin-patch-delivers-pain-relief-with-ibuprofen</a></span></li></ul><ul class="c2 lst-kix_list_40-1"><li class="c9"><span class="c5 c8">24 hour medication</span></li><li class="c9"><span class="c5 c8">Constant drug delivery for 24 hours</span></li><li class="c9"><span class="c5 c8">The drug is dissolved into the adhesive layer which helped it to release the drug in a steady rate and to take up more drug</span></li><li class="c9"><span class="c5 c8">Will be used for pain medication, so this will be applied to the </span><span class="c5 c27">SPECIFIC </span><span class="c5 c8">area where pain is felt</span></li><li class="c9"><span class="c5 c8">Will be out in the market for 3 years</span></li></ul><p class="c30 c19 c36"><span class="c5 c8"></span></p><h3 class="c11"><span class="c20">Wednesday, June 1st</span></h3><p class="c30 c19"><span class="c5 c27">Adhesive layer research:</span></p><ul class="c2 lst-kix_list_41-0 start"><li class="c0"><span class="c26 c8 c25 c20"><a class="c29" href="https://www.google.com/url?q=https://geckskin.umass.edu/&amp;sa=D&amp;ust=1475957476854000&amp;usg=AFQjCNHJyezq0oM5ItSa860-zjKsKBDxrg">https://geckskin.umass.edu/</a></span></li></ul><ul class="c2 lst-kix_list_41-1 start"><li class="c9"><span class="c5 c8">Super-adhesive based on mechanics of gecko feet </span></li><li class="c9"><span class="c5 c8">Leaves no residue </span></li><li class="c9"><span class="c5 c8">Not sure if we can get our hands on this though&hellip; </span></li></ul><p class="c30 c19 c36"><span class="c5 c8"></span></p><h3 class="c11"><span class="c20">Friday, June 3rd</span></h3><p class="c30 c19"><span class="c26 c8 c25 c20"><a class="c29" href="https://www.google.com/url?q=http://www.tandfonline.com/doi/pdf/10.1517/17425247.2012.637107&amp;sa=D&amp;ust=1475957476857000&amp;usg=AFQjCNHYlcWkMVwuxkQyoC7VFwKUt7k3Mw">http://www.tandfonline.com/doi/pdf/10.1517/17425247.2012.637107</a></span></p><ul class="c2 lst-kix_list_42-0 start"><li class="c0"><span class="c5 c8">PSA&rsquo;s fall into three categories: solvent based, water based and hot-melt</span></li></ul><ul class="c2 lst-kix_list_42-1 start"><li class="c9"><span class="c5 c8">Solvent based are traditionally used in patch production</span></li></ul><ul class="c2 lst-kix_list_42-0"><li class="c0"><span class="c5 c8">o</span><span class="c40 c8 c20 c78">&nbsp;&nbsp;&nbsp;</span><span class="c5 c8">Water based and hot-melt are more beneficial for skin irritation, sensitization and environmental contamination risks</span></li><li class="c0"><span class="c5 c8">o</span><span class="c40 c8 c20 c78">&nbsp;&nbsp;&nbsp;</span><span class="c5 c8">Polyisobutylenes are better for allergenicity compared to acrylics and silicone-based</span></li><li class="c0"><span class="c5 c8">Patch failures:</span></li><li class="c0"><span class="c5 c8">o</span><span class="c40 c8 c20 c78">&nbsp;&nbsp;&nbsp;</span><span class="c5 c8">Case I: Adhesive failure</span></li><li class="c0"><span class="c5 c8">o</span><span class="c40 c8 c20 c78">&nbsp;&nbsp;&nbsp;</span><span class="c5 c8">Case II: PSA doesn&rsquo;t adhere to backing layer</span></li></ul><p class="c30 c19 c99"><span class="c5 c8">o</span><span class="c40 c8 c20 c78">&nbsp;&nbsp;&nbsp;</span><span class="c5 c8">Case III: matrix has good adhesive strength, poor cohesive strength</span></p><p class="c30 c99 c19"><span class="c5 c8">o</span><span class="c40 c8 c20 c78">&nbsp;&nbsp;&nbsp;</span><span class="c5 c8">Case IV: adhesive and cohesive failure</span></p><p class="c22"><span class="c20"></span></p><p class="c28 c19"><span style="overflow: hidden; display: inline-block; margin: 0.00px 0.00px; border: 0.00px solid #000000; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px); width: 376.53px; height: 210.73px;"><img alt="https://lh6.googleusercontent.com/VAm_47mD-Nusi9DxE923OGCPLdhmls7Pi50h3QlVLzndcmqNLNr8CWACw3GfsvQ_76KJRYJl7sso9jhDhszTO5dsP3gEbRrYme2JSRFGV_4GlY48fh00QcHPvsidcthgGxuFMb_m" src="images/image09.png" style="width: 376.53px; height: 210.73px; margin-left: -0.00px; margin-top: -0.00px; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px);" title=""></span></p><ul class="c2 lst-kix_list_44-0 start"><li class="c0"><span class="c5 c8">PIB-based adhesives:</span></li></ul><ul class="c2 lst-kix_list_44-1 start"><li class="c9"><span class="c5 c8">Disadvantage: easy oxidation and low air and water vapour permeability</span></li></ul><ul class="c2 lst-kix_list_44-0"><li class="c0"><span class="c5 c8">Acrylic-based adhesives:</span></li></ul><ul class="c2 lst-kix_list_44-1 start"><li class="c9"><span class="c5 c8">Colorless and transparent</span></li><li class="c9"><span class="c5 c8">More resistant to oxidation</span></li></ul><ul class="c2 lst-kix_list_44-0"><li class="c0"><span class="c5 c8">Silicon-based adhesives</span></li><li class="c0"><span class="c5 c8">When testing in vivo performance:</span></li></ul><ul class="c2 lst-kix_list_44-1 start"><li class="c9"><span class="c5 c8">Need to find an artificial material that is able to simulate continuous variations of skin humidity - related to critical surface tension, surface roughness and deformability</span></li><li class="c9"><span class="c5 c8">Skin deformability is most critical to consider </span></li><li class="c9"><span class="c5 c8">Effects of relative adherend humidity on peel adhesion performances can be studied using collagen-coated plates</span></li><li class="c9"><span class="c5 c8">When peeling off a patch, need to consider tensile deformation, bending stiffness and substrate deformation</span></li><li class="c9"><span class="c5 c8">Stress distribution on skin deformation was measured in vivo by tension, torsion, suction and indentation tests</span></li></ul><p class="c30 c19 c36"><span class="c5 c8"></span></p><p class="c44 c19 c42"><span class="c5 c27">Some Market Research:</span></p><p class="c44 c19 c42"><span class="c5">Paper: &nbsp;</span><span class="c5 c27 c48">Challenges and opportunities in dermal/transdermal delivery</span></p><p class="c44 c19 c42"><span class="c90 c25 c20">From &lt;</span><span class="c25 c20 c26"><a class="c29" href="https://www.google.com/url?q=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2995530/&amp;sa=D&amp;ust=1475957476873000&amp;usg=AFQjCNHtSzC8v_OEfmcQ81GqqzzHJnRakw">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2995530/</a></span><span class="c90 c25 c20">&gt;</span></p><p class="c19 c42 c44"><span class="c5">PATCHES that is applicable in our subgroup:</span></p><ul class="c2 lst-kix_list_58-0 start"><li class="c0"><span class="c5 c8">Clonidine patches</span></li></ul><ul class="c2 lst-kix_list_45-1 start"><li class="c14"><span class="c5">Catapres TTS</span><span class="c5 c48">&reg;</span><span class="c5">&nbsp;was introduced in </span><span class="c5 c27">1984</span><span class="c5">&nbsp;for high blood pressure as the first 7-day patch system</span></li><li class="c14"><span class="c5">&quot;The patch should stay in place during showering, bathing, or swimming for </span><span class="c5 c27">a full 7 days</span><span class="c5">.&quot; From &lt;</span><span class="c26 c25 c20"><a class="c29" href="https://www.google.com/url?q=http://www.mayoclinic.org/drugs-supplements/clonidine-transdermal-route/proper-use/drg-20073656&amp;sa=D&amp;ust=1475957476877000&amp;usg=AFQjCNEMYXr3aQZlBIipBxUhMXgo4n0frQ">http://www.mayoclinic.org/drugs-supplements/clonidine-transdermal-route/proper-use/drg-20073656</a></span><span class="c5">&gt;</span></li><li class="c14"><span class="c5">Clonidine is in a class of medications called centrally acting alpha-agonist hypotensive agents. It works by decreasing your heart rate and relaxing the blood vessels so that blood can flow more easily through the body. From &lt;</span><span class="c26 c25 c20"><a class="c29" href="https://www.google.com/url?q=https://www.nlm.nih.gov/medlineplus/druginfo/meds/a608049.html%23precautions&amp;sa=D&amp;ust=1475957476878000&amp;usg=AFQjCNFoZliKdjDN0kKy3fG7NGzwsgHdPQ">https://www.nlm.nih.gov/medlineplus/druginfo/meds/a608049.html#precautions</a></span><span class="c5">&gt;</span></li><li class="c14"><span class="c5">How did they solve the problem with loss of adhesion? &quot;If the clonidine patch loosens while wearing it, apply the adhesive cover that comes with the patch. The adhesive cover will help to keep the clonidine patch on until it is time for the patch to be replaced. If the clonidine patch significantly loosens or falls off, replace it with a new one in a different area. Replace the new patch on your next scheduled patch change day.&quot;</span></li></ul><p class="c44 c76 c19 c42 c54"><span class="c90 c25 c20">From &lt;</span><span class="c26 c25 c20"><a class="c29" href="https://www.google.com/url?q=https://www.nlm.nih.gov/medlineplus/druginfo/meds/a608049.html%23precautions&amp;sa=D&amp;ust=1475957476879000&amp;usg=AFQjCNH1OfBBiuVjnRnb1gYda-ZzleZZ1Q">https://www.nlm.nih.gov/medlineplus/druginfo/meds/a608049.html#precautions</a></span><span class="c90 c25 c20">&gt;</span></p><p class="c22 c19 c42"><span class="c25 c20"></span></p><ul class="c2 lst-kix_list_57-0 start"><li class="c0"><span class="c5 c8">Climara patches</span></li></ul><ul class="c2 lst-kix_list_46-1 start"><li class="c14"><span class="c5">Treating conditions due to menopause (eg, hot flashes; vaginal itching, burning, or dryness), treating vulvar and vaginal atrophy, and preventing osteoporosis. It is also used for estrogen replacement therapy after failure of the ovaries and to relieve symptoms of breast cancer. </span><span class="c25 c20 c90">From &lt;</span><span class="c26 c25 c20"><a class="c29" href="https://www.google.com/url?q=http://www.drugs.com/cdi/climara-weekly-patch.html&amp;sa=D&amp;ust=1475957476881000&amp;usg=AFQjCNF08DbnodFxgNIyqdZXwxgbm95k3A">http://www.drugs.com/cdi/climara-weekly-patch.html</a></span><span class="c90 c25 c20">&gt;</span></li><li class="c14"><span class="c5">Method of application: &nbsp;A new patch should be applied to your skin on the same day once a week (i.e., the patch should be changed once every 7 days)</span></li></ul><p class="c44 c19 c42 c54 c76"><span class="c5">From &lt;</span><span class="c26 c25 c20"><a class="c29" href="https://www.google.com/url?q=http://chealth.canoe.com/Drug/GetDrug/Climara&amp;sa=D&amp;ust=1475957476883000&amp;usg=AFQjCNF275JGhfDoHJyae6KZxSnOA1LZYA">http://chealth.canoe.com/Drug/GetDrug/Climara</a></span><span class="c5">&gt;</span></p><p class="c22"><span class="c25 c20"></span></p><h3 class="c11"><span class="c25 c20">Tuesday, June 7th</span></h3><p class="c30 c19"><span class="c5 c27">isosorbide dinitrate (ISDN) Patch</span></p><p class="c30 c19"><span class="c26 c8 c25 c20"><a class="c29" href="https://www.google.com/url?q=http://www.scielo.br/pdf/bjps/v51n2/1984-8250-bjps-51-02-00373.pdf&amp;sa=D&amp;ust=1475957476885000&amp;usg=AFQjCNHhdvGnJ0ZhnJ4R9T4NPYrAxuzMyA">http://www.scielo.br/pdf/bjps/v51n2/1984-8250-bjps-51-02-00373.pdf</a></span></p><p class="c30 c19"><span class="c5 c8">***They are dealing with a drug called isosorbide dinitrate (ISDN) &nbsp;which is used as &nbsp;vasodilator for angina, congestive heart failure, and esophageal spasms.</span></p><p class="c22"><span class="c25 c20"></span></p><p class="c30 c19"><span class="c5 c8">What they are trying to create:</span></p><ul class="c2 lst-kix_list_52-0 start"><li class="c0"><span class="c5 c27">Acrylate polymers</span><span class="c5 c8">&nbsp;= they used this as the rate controlling membrane, as this polymer has not been extensively used in patches before</span></li></ul><ul class="c2 lst-kix_list_52-1 start"><li class="c9"><span class="c5 c27">Why use this</span><span class="c5 c8">? keep drug release for at least 48 hours at constant rate</span></li></ul><p class="c22"><span class="c25 c20"></span></p><p class="c30 c19"><span class="c5 c8">Here&#39;s how their patch looks like: poor mouse :&rsquo;(</span></p><p class="c30 c19"><span style="overflow: hidden; display: inline-block; margin: 0.00px 0.00px; border: 0.00px solid #000000; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px); width: 294.27px; height: 128.40px;"><img alt="https://lh5.googleusercontent.com/47sngBiSR3vPe3giXNgKjP3ylwNrvQL1Amvl4vEuLd0eugXTpuh13FyF1Ki0nYflGSlUy7z09lwk1I1WE5hxpc4ytZirOVC1bqK-pei8f6_Cfy2dpaSu3d7Je7Jfg0AavL7cJ85P" src="images/image10.png" style="width: 294.27px; height: 128.40px; margin-left: -0.00px; margin-top: -0.00px; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px);" title=""></span><span style="overflow: hidden; display: inline-block; margin: 0.00px 0.00px; border: 0.00px solid #000000; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px); width: 224.40px; height: 132.13px;"><img alt="https://lh4.googleusercontent.com/I8kkgP-xA8u6Or1qC14qMm9IQxNIM7PMH6jIQ0UCQtWlHZsXHMVw91Qjat0GK39QycyMAAaji__lwVzzvyxZMIkR99BJmAgyCAfNKrPNUfICJgCPcsLn5oiDJd_k_Ug8FI88uRch" src="images/image11.png" style="width: 224.40px; height: 132.13px; margin-left: -0.00px; margin-top: -0.00px; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px);" title=""></span></p><ul class="c2 lst-kix_list_53-0 start"><li class="c0"><span class="c5 c8">Patch was stored in a sealed aluminium pouch = &nbsp;minimise the loss of solvent</span></li></ul><a id="t.0b40ba80bb9ce74fb647b95ebd6c46a1b2bd1647"></a><a id="t.1"></a><table class="c70"><tbody><tr class="c74"><td class="c52" colspan="1" rowspan="1"><p class="c12"><span class="c5 c27">Part of the Patch</span></p></td><td class="c32" colspan="1" rowspan="1"><p class="c12"><span class="c5 c27">Brand or what material was used</span></p></td><td class="c31" colspan="1" rowspan="1"><p class="c12"><span class="c5 c27">Why was it chosen</span></p></td></tr><tr class="c74"><td class="c52" colspan="1" rowspan="1"><p class="c12"><span class="c5 c8">Backing layer</span></p></td><td class="c32" colspan="1" rowspan="1"><p class="c22 c73 c67 c71"><span class="c1"></span></p></td><td class="c31" colspan="1" rowspan="1"><p class="c12"><span class="c5 c8">Same material as what is existing</span></p></td><td class="c91" colspan="1" rowspan="1"><p class="c12"><span class="c5 c8">Temporary liner and the backing layer were then </span><span class="c5 c27">heat-sealed</span><span class="c5 c8">&nbsp;and cut to the appropriate sizes</span></p></td></tr><tr class="c74"><td class="c52" colspan="1" rowspan="1"><p class="c12"><span class="c5 c8">Temporary Liner</span></p></td><td class="c32" colspan="1" rowspan="1"><p class="c12"><span class="c5 c27">3M, Scotchpak 1022</span></p></td><td class="c31" colspan="1" rowspan="1"><p class="c12"><span class="c5 c8">Packaging purposes, protects adhesive</span></p></td><td class="c91" colspan="1" rowspan="1"><p class="c12"><span class="c5 c8">Adhesive solution was coated onto the temporary liner (</span><span class="c5 c27">3M, Scotchpak 1022</span><span class="c5 c8">), allowed to dry completely</span></p></td></tr><tr class="c74"><td class="c52" colspan="1" rowspan="1"><p class="c12"><span class="c5 c8">Rate controlling membrane</span></p></td><td class="c32" colspan="1" rowspan="1"><p class="c12"><span class="c5 c8">Polyacrylate membrane (made from scratch),</span></p><p class="c12"><span class="c5 c8">synthesised</span></p><p class="c12"><span class="c5 c8">by 2-hydroxy-3-phenoxypropylacrylate, 4-hydroxybutyl</span></p><p class="c12"><span class="c5 c8">acrylate and diethyl maleate</span></p></td><td class="c31" colspan="1" rowspan="1"><p class="c12"><span class="c5 c8">To keep drug release for at least 48 hours at constant rate</span></p><p class="c12"><span class="c5 c8">Better permeation, does not involve degradation, erosion or dissolution of the polymer</span></p></td><td class="c91" colspan="1" rowspan="1"><p class="c12"><span class="c5 c8">These are non-degradable polymers</span></p><p class="c12"><span class="c5 c8">Thickness: 14 microns</span></p><p class="c22 c67 c71 c73"><span class="c1"></span></p><p class="c12"><span class="c5 c8">Pore sizes are fabricated randomly by polymer chains</span></p></td></tr><tr class="c74"><td class="c52" colspan="1" rowspan="1"><p class="c12"><span class="c5 c8">Reservoir layer</span></p></td><td class="c32" colspan="1" rowspan="1"><p class="c12"><span class="c5 c8">75% PVA, 10% ISDN and 5% urea</span></p></td><td class="c31" colspan="1" rowspan="1"><p class="c12"><span class="c5 c8">Showed better permeation</span></p><p class="c12"><span class="c5 c8">Permeation rate is increased by 25.4 fold, a 31.1-fold cumulative release after 24 h, and a 30.8-fold cumulative ratio of release at 24 h compared to EC</span></p></td><td class="c91" colspan="1" rowspan="1"><p class="c12"><span class="c5 c8">Also has the penetration enhancers</span></p></td></tr><tr class="c55"><td class="c52" colspan="1" rowspan="1"><p class="c12"><span class="c5 c8">Adhesive layer</span></p></td><td class="c32" colspan="1" rowspan="1"><p class="c12"><span class="c5 c8">PSA (pressure sensitive adhesives): 5%</span></p><p class="c12"><span class="c5 c8">ISDN dispersed in the mixture of PVP K90, PEG400</span></p><p class="c12"><span class="c5 c8">and gelatine</span></p></td><td class="c107" colspan="2" rowspan="1"><p class="c12"><span class="c5 c8">This whole combination helps enhance drug permeation</span></p></td></tr><tr class="c55"><td class="c52" colspan="1" rowspan="1"><p class="c12"><span class="c5 c8">THEIR CONCLUSION</span></p></td><td class="c72" colspan="3" rowspan="1"><p class="c12"><span class="c5 c8">This presented a longer release time at a sustained release rate</span></p><p class="c12"><span class="c5 c8">Would promote patient satisfaction</span></p><p class="c12"><span class="c5 c8">Sustained release rate, owing to the rate-controlling membrane,</span></p><p class="c12"><span class="c5 c8">A higher loading-drug amount, owing to the separated drug reservoir layer</span></p><p class="c12"><span class="c5 c8">Easier to tune release rate and release time to achieve the prediction</span></p></td></tr></tbody></table><p class="c30 c19"><span class="c6 c40">Patch 2:</span></p><p class="c30 c19"><span class="c6 c40">Contraceptive patch </span><span class="c26 c8 c50 c20"><a class="c29" href="https://www.google.com/url?q=http://www.google.com/patents/WO2013112806A2?cl%3Den&amp;sa=D&amp;ust=1475957476934000&amp;usg=AFQjCNGgVAAxUSi9iJhybB9Y6oPJx7n1dQ">http://www.google.com/patents/WO2013112806A2?cl=en</a></span></p><p class="c30 c19"><span class="c40 c8 c50 c20">Dosage: 20 mg per day, $14 for a full month of medication</span></p><p class="c30 c19 c36"><span class="c7"></span></p><p class="c28 c19"><span style="overflow: hidden; display: inline-block; margin: 0.00px 0.00px; border: 0.00px solid #000000; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px); width: 124.68px; height: 125.49px;"><img alt="https://lh6.googleusercontent.com/sgR4esDJ0XHS6590Z3-2ad_wzcevNi5PjaQwUf4Ubjh0PxmRo3kEK44zV3DSBUrqbpLCLnz9MjDbkhbVVFy32Vn8NCzpge31YV3wXv0yVZwhSZwMR1AasITuja6luUL4iQh8VmmZ" src="images/image12.png" style="width: 124.68px; height: 125.49px; margin-left: -0.00px; margin-top: -0.00px; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px);" title=""></span></p><p class="c28 c19 c36"><span class="c7"></span></p><a id="t.add5caefb492a4ca578bc357ef4eb52214d17aea"></a><a id="t.2"></a><table class="c70"><tbody><tr class="c74"><td class="c79" colspan="2" rowspan="1"><p class="c30 c19"><span class="c5 c27">Pros about this patch</span></p></td><td class="c58" colspan="1" rowspan="1"><p class="c30 c19"><span class="c5 c27">Cons about this patch</span></p></td></tr><tr class="c74"><td class="c79" colspan="2" rowspan="1"><p class="c30 c19"><span class="c5 c8">Entire patch is flexible enough to effectively and comfortably adhere to contoured sites of the body</span></p><p class="c30 c19"><span class="c5 c8">Used destrogel mixed with carriers</span></p></td><td class="c58" colspan="1" rowspan="1"><p class="c24 c22"><span class="c1"></span></p></td></tr><tr class="c74"><td class="c82" colspan="1" rowspan="1"><p class="c30 c19"><span class="c5 c27">Part of the patch</span></p></td><td class="c56" colspan="1" rowspan="1"><p class="c30 c19"><span class="c5 c27">Material used</span></p></td><td class="c58" colspan="1" rowspan="1"><p class="c30 c19"><span class="c5 c27">Why did they use it</span></p></td></tr><tr class="c74"><td class="c82" colspan="1" rowspan="1"><p class="c30 c19"><span class="c5 c8">Backing layer</span></p></td><td class="c56" colspan="1" rowspan="1"><p class="c24 c22"><span class="c1"></span></p></td><td class="c58" colspan="1" rowspan="1"><p class="c24 c22"><span class="c1"></span></p></td></tr><tr class="c74"><td class="c82" colspan="1" rowspan="1"><p class="c30 c19"><span class="c5 c8">Release liner</span></p></td><td class="c56" colspan="1" rowspan="1"><p class="c22 c24"><span class="c1"></span></p></td><td class="c58" colspan="1" rowspan="1"><p class="c24 c22"><span class="c1"></span></p></td></tr><tr class="c74"><td class="c82" colspan="1" rowspan="1"><p class="c30 c19"><span class="c5 c8">Adhesives</span></p></td><td class="c56" colspan="1" rowspan="1"><p class="c30 c19"><span class="c5 c8">Duro Tak&reg; 87-4098 by Henkel Corporation., Bridgewater, N.J.</span></p><p class="c30 c19"><span class="c5 c8">Comprises a certain percentage of vinyl acetate co-monomer</span></p><p class="c30 c19"><span class="c5 c8">PIB adhesives such as 0.1 to 30 wt% PVP (i.e., povidone) or a PVP co-polymer such as PVP/VA (i.e., copovidone) as a humectant and plasticizer</span></p></td><td class="c58" colspan="1" rowspan="1"><p class="c30 c19"><span class="c5 c8">PVPs are very hydrophilic as compared to PIBs, which are hydrophobic, has an ability to absorb moisture. The use of PVP copolymers, such as PVP/VA, can improve compatibility with other polymers and modulate the water absorption.</span></p></td></tr></tbody></table><p class="c33 c67 c42 c36"><span class="c8 c25 c20"></span></p><a id="t.a985f5d339ab19b7faff4a7c094ef00960f87cfa"></a><a id="t.3"></a><table class="c70"><tbody><tr class="c74"><td class="c85" colspan="1" rowspan="1"><p class="c30 c19"><span class="c5 c27 c81">Recommendations:</span></p></td><td class="c98" colspan="1" rowspan="1"><p class="c30 c19"><span class="c5 c27">WHY</span></p></td></tr><tr class="c74"><td class="c85" colspan="1" rowspan="1"><p class="c30 c19"><span class="c5 c8">use of water soluble polymers is generally </span><span class="c5 c27">less preferred</span></p></td><td class="c98" colspan="1" rowspan="1"><p class="c30 c19"><span class="c5 c8">Would cause dissolution or erosion of the matrix</span></p><p class="c30 c19"><span class="c5 c8">Would affect the release rate of the desogestrel</span></p><p class="c30 c19"><span class="c5 c8">Would affect capability of the dosage unit to remain in place on the skin</span></p></td></tr><tr class="c74"><td class="c85" colspan="1" rowspan="1"><p class="c30 c19"><span class="c5 c8">Incorporate cross-linking monomeric units or sites</span></p></td><td class="c98" colspan="1" rowspan="1"><p class="c30 c19"><span class="c5 c8">Would solve problems with polymers having </span><span class="c5 c27">glass transition</span><span class="c5 c8">&nbsp;temperatures below room temperature which are used to form a polymer matrix as the transdermal desogestrel-containing composition</span></p></td></tr><tr class="c74"><td class="c85" colspan="1" rowspan="1"><p class="c30 c19"><span class="c5 c8">In development of suitable polyisobutylene PSAs, one consideration is that PIBs are not crosslinked so they flow slightly.</span></p></td><td class="c98" colspan="1" rowspan="1"><p class="c30 c19"><span class="c5 c8">Within a patch, that slight flow can cause an unsightly ring around the patch when it is worn for several days.</span></p></td></tr><tr class="c74"><td class="c85" colspan="1" rowspan="1"><p class="c30 c19"><span class="c5 c8">A higher content of high molecular weight PIB in the PSA formulation. </span></p><p class="c30 c19"><span class="c5 c8">**Polybutene in certain PIB formulations, such as the Oppanol B-12 functions as a plasticizer to allow for incorporation of more high molecular weight PIB.</span></p><p class="c30 c19"><span class="c5 c8">Mineral oil can be used as a plasticizer for the same purpose.</span></p></td><td class="c98" colspan="1" rowspan="1"><p class="c22 c67 c109 c92 c96"><span class="c1"></span></p></td></tr></tbody></table><p class="c22"><span class="c20"></span></p><h3 class="c11"><span class="c20">Wednesday, June 8th</span></h3><p class="c30 c19"><span class="c26 c8 c25 c20"><a class="c29" href="https://www.google.com/url?q=http://www.technicaljournalsonline.com/ijpsr/VOL%2520II/IJPSR%2520VOL%2520II%2520ISSUE%2520I%2520JANUARY%2520MARCH%25202011/IJPSR%2520VOL%2520II%2520ISSUE%2520I%2520Article%252019.pdf&amp;sa=D&amp;ust=1475957476976000&amp;usg=AFQjCNHdyW0_l5XtT33n92qUaRvUk5DD7w">http://www.technicaljournalsonline.com/ijpsr/VOL%20II/IJPSR%20VOL%20II%20ISSUE%20I%20JANUARY%20MARCH%202011/IJPSR%20VOL%20II%20ISSUE%20I%20Article%2019.pdf</a></span></p><p class="c30 c19"><span class="c5 c8">Polymer requirements:</span></p><ul class="c2 lst-kix_list_54-0 start"><li class="c0"><span class="c5 c8">Biocompatible + Chemically compatible -&gt; with both drug and body</span></li></ul><p class="c30 c19"><span class="c5 c8">Different companies use different polymer systems:</span></p><ul class="c2 lst-kix_list_55-0 start"><li class="c0"><span class="c5 c8">Alza Corporation: EVA (Ethylene Vinyl Acetate) or microporous polypropylene</span></li><li class="c0"><span class="c5 c8">Searle Pharmacia: Silicone rubber</span></li></ul><p class="c30 c76 c19"><span class="c5 c27">Backing Layer: </span><span class="c5 c8">Most common is Polyester-polyethylene composite</span></p><p class="c30 c76 c19"><span class="c5 c27">Rate controlling membrane:</span><span class="c5 c8">&nbsp;</span></p><ul class="c2 lst-kix_list_56-0 start"><li class="c3"><span class="c5 c8">EVA: The percentage of VA can be manipulated. Higher VA -&gt; higher permeability and higher polarity. Maximum VA is 60% by weight (or else glass transition temperature will increase)</span></li><li class="c3"><span class="c5 c8">&nbsp;Silicone rubber: Biocompatible, ease of fabrication, high permeability (especially steroids), free rotation around silicone rubber backbone -&gt; Low microscopic viscosity within polymer</span></li></ul><p class="c30 c19"><span class="c5 c8">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;</span><span class="c5 c27">Adhesive:</span><span class="c5 c8">&nbsp;(also referred to as PSA) We talked about PIB today</span></p><p class="c30 c19"><span class="c5 c27">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Release liners:</span><span class="c5 c8">&nbsp;Fluoropolymers</span></p><p class="c22"><span class="c20"></span></p><h3 class="c11"><span class="c20">Monday, June 13th &nbsp;</span></h3><p class="c30 c19"><span class="c5 c27">Media Release Material</span></p><p class="c30 c19"><span class="c5 c8">Water Soluble Materials</span></p><ul class="c2 lst-kix_list_64-0 start"><li class="c0"><span class="c5 c8">Aquasol uses a mixture of sodium carboxy cellulose and wooden pulp to create the water soluble material</span></li><li class="c0"><span class="c5 c8">Aquasol specifically designs their packaging to biodegrade over time or with the introduction of water at any various temperature</span></li><li class="c0"><span class="c5 c8">Monosol is another company which specializes in the use of water soluble packaging and dispersible materials. The water soluble film is made from PVOH (Poly Vinyl Alcohol)</span></li><li class="c0"><span class="c5 c8">Like Aquasol, the material is water soluble at all temperatures. At higher temperatures, the material is more soluble. That is why they suggest moderate temperatures of 10-20 degrees celsius with relative humidity of 30-60%</span></li><li class="c0"><span class="c5 c8">With the material being quickly degraded, water soluble materials are not the best materials to use for the media release. The material however does not harm the environment as the bacteria naturally found in wastewater can break it down into harmless components </span></li><li class="c0"><span class="c5 c8">As well, there are no specifics about their material as you have to customize it to your needs</span></li></ul><p class="c30 c19"><span class="c5 c8">Polyethylene and Bubble Wrap</span></p><ul class="c2 lst-kix_list_65-0 start"><li class="c0"><span class="c5 c8">An alternative would be to use a single layer of polyethylene used for bubble wrap. By filling the media bubble with media and air, it&rsquo;ll form a pouch that can be popped. </span></li><li class="c0"><span class="c5 c8">Polycell makes a bubble wrap called Oxo-B Eco Bubble which incorporates their Reverte Oxo Biodegradable into their polyethylene resins. After discard, through the use of substantial UV light, oxygen and/or heat it will break down in smaller pieces. These smaller pieces are then broken down further by the ingestion of bacteria and through respiration will degrade the plastic into carbon dioxide and water. &nbsp;</span></li><li class="c0"><span class="c5 c8">Will look into plastics that degrade over time</span></li></ul><p class="c30 c19 c36"><span class="c5 c8"></span></p><p class="c30 c19"><span class="c5 c27">Membrane:</span><span class="c5 c8">&nbsp;</span></p><ul class="c2 lst-kix_list_66-0 start"><li class="c0"><span class="c5 c8">Contacted Dr. Mintchev for a meeting about transdermal patch + materials. </span></li><li class="c0"><span class="c5 c8">Reading this paper: page 13</span></li></ul><p class="c30 c19"><span class="c26 c8 c25 c20"><a class="c29" href="https://www.google.com/url?q=https://www.ualberta.ca/~csps/JPPS8(1)/N.Udupa/glibenclamide.htm&amp;sa=D&amp;ust=1475957476990000&amp;usg=AFQjCNGcjnuhEY_n8Ya1oumMelXSNPqL1A">https://www.ualberta.ca/~csps/JPPS8(1)/N.Udupa/glibenclamide.htm</a></span></p><ul class="c2 lst-kix_list_67-0 start"><li class="c9"><span class="c5 c8">This paper tested EVA 2%, 9% and 19% both </span><span class="c5 c8 c51">in vitro</span><span class="c5 c8">&nbsp;and </span><span class="c5 c8 c51">in vivo</span><span class="c5 c8">. The trend held true that the higher the % of EVA, the more drug diffuses.</span></li><li class="c9"><span class="c5 c8">They also tested ethyl cellulose, Eudragit RS-100 and Eudragit RL-100 but only </span><span class="c5 c8 c51">in vitro.</span></li><li class="c9"><span class="c5 c8">The drug was glibenclamide to treat diabetes.</span></li></ul><p class="c30 c83 c19"><span class="c5 c8">Reading this atm:</span></p><p class="c30 c83 c19"><span class="c26 c8 c25 c20"><a class="c29" href="https://www.google.com/url?q=http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2014/12/WC500179071.pdf&amp;sa=D&amp;ust=1475957476994000&amp;usg=AFQjCNHiBkvzFop4RdEW7dmHAba1GqJyog">http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2014/12/WC500179071.pdf</a></span></p><p class="c30 c19 c36"><span class="c5 c27"><a class="c29" href="https://www.google.com/url?q=http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2014/12/WC500179071.pdf&amp;sa=D&amp;ust=1475957476996000&amp;usg=AFQjCNEyqMe3wpUtzkiLcAcHfKjqrEJUAg"></a></span></p><p class="c30 c19"><span class="c5 c27">Release Liner:</span></p><ul class="c2 lst-kix_list_68-0 start"><li class="c0"><span class="c5 c8">Needs to be chemically inert with drug penetration, penetration enhancer and water</span></li><li class="c0"><span class="c5 c8">3M Scotchpak 1022</span></li><li class="c0"><span class="c5 c8">3M Scotchpak 9741</span></li><li class="c0"><span class="c5 c8">3M Scotchpak 9742</span></li><li class="c0"><span class="c5 c8">3M Scotchpak 9744</span></li><li class="c0"><span class="c5 c8">3M Scotchpak 9755</span></li></ul><ul class="c2 lst-kix_list_68-1 start"><li class="c9"><span class="c5 c8">Fluoropolymer Coated Polyester Film</span></li><li class="c9"><span class="c5 c8">Good for release with silicon skin contact adhesives, acrylate, PIB and rubber based PSA</span></li><li class="c9"><span class="c5 c8">Excellent chemical stability</span></li></ul><p class="c30 c19 c36"><span class="c5 c27"></span></p><p class="c30 c19"><span class="c5 c27">Adhesives:</span></p><p class="c30 c19"><span class="c5 c8">Links:</span></p><ol class="c2 lst-kix_list_69-0 start" start="1"><li class="c0"><span class="c26 c8 c25 c20"><a class="c29" href="https://www.google.com/url?q=https://label.averydennison.co.za/content/dam/averydennison/lpm/na/en/doc/home/resource%2520center/Adhesive%2520Overview(1).pdf&amp;sa=D&amp;ust=1475957477001000&amp;usg=AFQjCNESPmAYb6BtxwDAqm97VbRC4_Z0BQ">https://label.averydennison.co.za/content/dam/averydennison/lpm/na/en/doc/home/resource%20center/Adhesive%20Overview(1).pdf</a></span></li><li class="c0"><span class="c53 c8 c25 c20"><a class="c29" href="https://www.google.com/url?q=https://www.researchgate.net/publication/51881833_Adhesive_properties_a_critical_issue_in_transdermal_patch_development_Expert_Opin_Drug_Deliv_933-45&amp;sa=D&amp;ust=1475957477003000&amp;usg=AFQjCNH_TmpX-NglP7VCDEphhfHuMwxDfg">https://www.researchgate.net/publication/51881833_Adhesive_properties_a_critical_issue_in_transdermal_patch_development_Expert_Opin_Drug_Deliv_933-45</a></span></li></ol><p class="c22 c19 c42"><span class="c5"><a class="c29" href="https://www.google.com/url?q=https://www.researchgate.net/publication/51881833_Adhesive_properties_a_critical_issue_in_transdermal_patch_development_Expert_Opin_Drug_Deliv_933-45&amp;sa=D&amp;ust=1475957477004000&amp;usg=AFQjCNF-616lUFKFtOyMXLjDnHJ9W-JaBg"></a></span></p><p class="c44 c19 c42"><span class="c5">The typical adhesive properties include:</span></p><ul class="c2 lst-kix_list_70-0 start"><li class="c15 c19"><span class="c5 c27">Initial Tack</span><span class="c5">&nbsp;- The immediate holding power of the label upon contact with the substrate. A label with high initial tack will grab the substrate quickly. A label with low initial tack will exhibit a low level of adhesion when first applied and may remove cleanly.</span></li><li class="c15 c19"><span class="c5 c27">Ultimate Adhesion</span><span class="c5">&nbsp;- The ultimate or maximum holding power that the label will achieve as the adhesive penetrates into the substrate. The time required to obtain ultimate adhesion may depend on the stiffness (shear) of the adhesive, the roughness of the substrate and the temperature of the environment.</span></li><li class="c15 c19"><span class="c5 c27">Shear Resistance</span><span class="c5">&nbsp;- A measure of the internal cohesive strength of the adhesive. The shear of the adhesive is an indication of how soft an adhesive is. A low-shear adhesive (soft) has more of a tendency to flow (resulting in higher initial tack), and has a higher chance that the adhesive will split apart if put under stress. A high-shear adhesive (firm) is less likely to split under stress because of its good internal cohesive strength, and will be less likely to flow (possibly lower initial tack).</span></li></ul><p class="c22"><span class="c25 c20"></span></p><ul class="c2 lst-kix_list_57-0"><li class="c0"><span class="c5 c8">Solvent-based</span></li></ul><ul class="c2 lst-kix_list_68-1 start"><li class="c9"><span class="c5 c8">Traditionally used in patch production</span></li><li class="c9"><span class="c5 c8">Good for extended wear</span></li><li class="c9"><span class="c5 c8">Provide tighter hold</span></li><li class="c9"><span class="c5 c8">Stingy</span></li></ul><ul class="c2 lst-kix_list_68-0"><li class="c15 c80 c19"><span class="c5 c8">Silicone-based</span></li></ul><ul class="c2 lst-kix_list_68-1 start"><li class="c14 c80"><span class="c5 c8">High oxygen/gas permeability</span></li><li class="c14 c80"><span class="c5 c8">Low pain upon removal to sensitive skin</span></li><li class="c14 c80"><span class="c5 c8">Can be customized to improve chemical compatibility and stability with cationic drugs</span></li><li class="c14 c80"><span class="c5 c8">Increased diffusivity</span></li><li class="c9"><span class="c5 c8">Tendency to cause drug crystallization</span></li></ul><ul class="c2 lst-kix_list_68-0"><li class="c15 c19"><span class="c20 c41">DOW CORNING&reg; BIO-PSA 7-4101 SILICONE ADHESIVE, DOW CORNING&reg; BIO-PSA 7-4201 SILICONE ADHESIVE and DOW CORNING&reg; BIO-PSA 7-4301 SILICONE ADHESIVE that way you can compare the different levels of tack. They are all amine compatible with heptane as the carrier solvent.&rdquo;</span></li></ul><p class="c28 c19"><span style="overflow: hidden; display: inline-block; margin: 0.00px 0.00px; border: 0.00px solid #000000; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px); width: 391.47px; height: 331.67px;"><img alt="https://lh4.googleusercontent.com/xdtfxPnOp3r5KjOANmMQD20Z_XWvdMr8UqGb2Zv4_gMrNVxhmWd1hD0RryzWOttItduILIEiVqfnaF_ahu0eg443nizevRAyQ0xBeCXRd1Kc3nv-u_Mfeoi3H7M-UDzTGqFnQJDn" src="images/image13.png" style="width: 391.47px; height: 331.67px; margin-left: -0.00px; margin-top: -0.00px; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px);" title=""></span></p><hr style="page-break-before:always;display:none;"><p class="c22"><span class="c35 c20"></span></p><h1 class="c11"><span class="c20">Math Research</span></h1><p class="c22"><span class="c20"></span></p><h5 class="c11"><span class="c20">Diffusion:</span></h5><p class="c30 c19"><span class="c5 c8 c84">Factors affecting diffusivity:</span></p><p class="c30 c19"><span class="c5 c8">Search up: Chapter 2: Overview of Controlled Release Mechanisms by Ronald A. Siegel and Michael J. Rathbone</span></p><ul class="c2 lst-kix_list_47-0 start"><li class="c0"><span class="c5 c8">Depends on </span><span class="c5 c27">size of molecule</span><span class="c5 c8">&nbsp;and </span><span class="c5 c27">medium</span><span class="c5 c8">, as well as the membrane that we&rsquo;re using</span></li><li class="c0"><span class="c5 c8">For a hard spherical molecule diffusing through:</span></li></ul><p class="c30 c19 c54"><span class="c5 c8">Equation: D = kT/(6*pi*a*n)</span></p><ul class="c2 lst-kix_list_48-1 start"><li class="c9"><span class="c5 c8">a = molecule&#39;s radius</span></li><li class="c9"><span class="c5 c8">T = absolute temperature (K)</span></li><li class="c9"><span class="c5 c8">n = solvent viscosity</span></li><li class="c9"><span class="c5 c8">k = Boltzmann&#39;s constant &nbsp;(this accounts for intensity of thermal agitation)</span></li></ul><ul class="c2 lst-kix_list_48-0 start"><li class="c0"><span class="c5 c8">In terms of the medium: in</span><span class="c5 c8 c51">&nbsp;free volume theory</span><span class="c5 c8">, each drug, solvent, and polymer molecule contains an impenetrable core that is surrounded by nanovoids, called free volume</span></li></ul><ul class="c2 lst-kix_list_48-1 start"><li class="c9"><span class="c5 c8">Thermal motions cause the size of voids to fluctuate. Occasionally, a void becomes large enough for a diffusing molecule to move into or through it</span></li></ul><ul class="c2 lst-kix_list_49-0 start"><li class="c9"><span class="c5 c8">Free volume of a matrix depends on the its composition</span></li><li class="c9"><span class="c5 c8">Free volume can also be increased substantially by sorption of small molecules, such as water. (sorption is the physical and chemical process by which one substance becomes attached to another)</span></li></ul><ul class="c2 lst-kix_list_50-0 start"><li class="c9"><span class="c5 c8">For a molecule diffusing through a water-swollen hydrogel, diffusivity of drug is affected by the viscosity of the water space and also by obstructions placed in the drug molecule&rsquo;s path by the hydrogel chains</span></li></ul><p class="c30 c19 c36"><span class="c5 c8"></span></p><h3 class="c11"><span class="c25 c20">Monday, June 6th</span></h3><p class="c30 c19"><span class="c5 c27">What we need to model:</span></p><ul class="c2 lst-kix_list_59-0 start"><li class="c0"><span class="c5 c8">Oxygen diffusion through the backing layer (outside to inside and vice versa)</span></li><li class="c0"><span class="c5 c8">The amount of peptides that go through the rate membrane </span></li><li class="c0"><span class="c5 c8">How much force would we apply to the pouches for them to break </span></li><li class="c0"><span class="c5 c8">Mixing of media in patch and in pouches </span></li><li class="c15 c19"><span class="c5">Start modelling the system</span></li></ul><ul class="c2 lst-kix_list_59-1 start"><li class="c14"><span class="c5">Play around with the sizes of the packets</span></li><li class="c14"><span class="c5">Do math around, having some idea about how something works would be necessary, at least we have an idea how it works </span></li><li class="c14"><span class="c5">Determine what we&rsquo;re actually trying to solve</span></li><li class="c16"><span class="c5">MATLAB = useful way we could deal with our model - trying different values for a parameter we don&rsquo;t know about and see how it changed, identify what it represents, it&rsquo;s a framework of understanding which parameters are important</span></li></ul><h3 class="c11"><span class="c25 c20">Friday, June 10th</span></h3><p class="c44 c19 c42"><span class="c5 c51">Rate of release of therapeutic agents from reservoir transdermal systems:</span></p><ul class="c2 lst-kix_list_63-0 start"><li class="c15 c19"><span class="c26 c25 c20"><a class="c29" href="https://www.google.com/url?q=https://www.researchgate.net/file.PostFileLoader.html?id%3D55f196f8614325b8798b456f%26assetKey%3DAS%253A272146475778050%25401441896184273&amp;sa=D&amp;ust=1475957477026000&amp;usg=AFQjCNERQOZapz9xOiox4nMMVWsMBJHU4g">https://www.researchgate.net/file.PostFileLoader.html?id=55f196f8614325b8798b456f&amp;assetKey=AS%3A272146475778050%401441896184273</a></span><span class="c5">&nbsp;</span></li><li class="c15 c19"><span class="c5">Assuming mechanism of drug delivery involves these steps:</span></li></ul><ul class="c2 lst-kix_list_63-1 start"><li class="c14"><span class="c5">Drug dissolution within the reservoir matrix</span></li><li class="c14"><span class="c5">Drug diffusion and partitioning into the membrane</span></li><li class="c14"><span class="c5">Drug diffusion within the membrane and partitioning into the adhesive layer</span></li><li class="c14"><span class="c5">Drug diffusion within the adhesive and partitioning into the stratum corneum</span></li></ul><ul class="c2 lst-kix_list_63-0"><li class="c15 c19"><span class="c5">Rate controlling membrane controls drug diffusion into the adjacent adhesive layer and therefore is the rate-limiting step in the diffusion process</span></li></ul><p class="c22 c19 c42"><span class="c25 c20"></span></p><p class="c44 c19 c42"><span style="overflow: hidden; display: inline-block; margin: 0.00px 0.00px; border: 0.00px solid #000000; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px); width: 315.40px; height: 79.80px;"><img alt="https://lh4.googleusercontent.com/MF7-NyDC-3v5_Boz8mE8geWeR9JYnhRww_Exief1GZdWQnovYTQtdzgj6BBQAYv6ZHCqG9F4z-e4tboQt-_aLjiVSuR90QM59rbR7qAmdXZyrdYXpixfGGhu8Dcpwc8v29hHsdkT" src="images/image00.png" style="width: 315.40px; height: 79.80px; margin-left: -0.00px; margin-top: -0.00px; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px);" title=""></span></p><p class="c44 c19 c42"><span style="overflow: hidden; display: inline-block; margin: 0.00px 0.00px; border: 0.00px solid #000000; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px); width: 376.53px; height: 259.33px;"><img alt="https://lh3.googleusercontent.com/VCCXVGBqw0a8nNzCSHjMg9nqvy5RPNbr_B_I5xOnOPgyB2aWJhYIoO7X-o-NYPz5rys6CyeMSTCo4nORL2tUzrzcSxBLVuNzz1EWrPKaoccO8er04jPKUz_jP6MXZAEd68NJzbog" src="images/image01.png" style="width: 376.53px; height: 259.33px; margin-left: -0.00px; margin-top: -0.00px; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px);" title=""></span></p><p class="c44 c19 c42"><span class="c53 c25 c20"><a class="c29" href="https://www.google.com/url?q=https://www.quora.com/Why-arent-patches-used-as-drug-delivery-systems-more-often&amp;sa=D&amp;ust=1475957477030000&amp;usg=AFQjCNEYdagB67Y5hlNepkLbuWfak9IyzQ">https://www.quora.com/Why-arent-patches-used-as-drug-delivery-systems-more-often</a></span></p><p class="c44 c19 c42"><span class="c25 c20 c53"><a class="c29" href="https://www.google.com/url?q=http://ceaccp.oxfordjournals.org/content/7/5/171.full&amp;sa=D&amp;ust=1475957477031000&amp;usg=AFQjCNHiPRo8Df0RvwPLLNYUXIpF7PMgZQ">http://ceaccp.oxfordjournals.org/content/7/5/171.full</a></span></p><ul class="c2 lst-kix_list_23-0 start"><li class="c15 c19"><span class="c5">Reservoir = drug concentration is established, drug moves further into the skin, into the capillaries, and then into the circulation</span></li><li class="c15 c71 c19"><span class="c5">There is a time to reach steady state of plasma concentration</span></li></ul><p class="c44 c19 c42 c54 c71"><span style="overflow: hidden; display: inline-block; margin: 0.00px 0.00px; border: 0.00px solid #000000; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px); width: 491.20px; height: 410.20px;"><img alt="https://lh3.googleusercontent.com/6sT4lf9ZHcREJ5bYiPkbMnT6yn05ekmrOC6UH5fWPHfnqWDBenOxMBSHYbJIo1QL9hk9_Ood8DylxURog4Fx9qX1ks4ri-gdlMz1AKUamEEqmZx7Wv-dTGIV2hVJ7inBHkE1agPs" src="images/image02.png" style="width: 491.20px; height: 410.20px; margin-left: -0.00px; margin-top: -0.00px; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px);" title=""></span></p><p class="c22 c19 c42"><span class="c5 c27"></span></p><p class="c44 c19 c42"><span class="c5 c27">Parameters that we have to consider</span><span class="c5">:</span></p><ul class="c2 lst-kix_list_35-0 start"><li class="c15 c19"><span class="c5">Diffusing peptide must not affect the adhesive and vice versa</span></li><li class="c15 c19"><span class="c5">Skin compatibility, chemical compatibility</span></li><li class="c15 c19"><span class="c5">Tack, peel adhesion, skin adhesion and cohesive strength </span></li><li class="c15 c19"><span class="c5">Hydration of skin</span></li></ul><ul class="c2 lst-kix_list_35-1 start"><li class="c14"><span class="c5">Tissue swells when skin is saturated with water and its permeability increases = this would be an important factor to increase penetration</span></li></ul><ul class="c2 lst-kix_list_35-0"><li class="c15 c19"><span class="c5">Temperature</span></li><li class="c15 c19"><span class="c5">Diffusion coefficient</span></li></ul><ul class="c2 lst-kix_list_35-1 start"><li class="c14"><span class="c5">Diffusion speed of molecules depend on the state of matter in the medium</span></li></ul><ul class="c2 lst-kix_list_35-0"><li class="c15 c19"><span class="c5">Drug concentration</span></li></ul><ul class="c2 lst-kix_list_35-1 start"><li class="c14"><span class="c5">Drug permeation usually follows the </span><span class="c25 c20">F</span><span class="c5">ick</span><span class="c25 c20">&rsquo;</span><span class="c5">s law. The flux of solute is proportional to the concentration gradient across the entire barrier phase</span></li></ul><ul class="c2 lst-kix_list_35-0"><li class="c15 c19"><span class="c5">Partition coefficient</span></li></ul><ul class="c2 lst-kix_list_35-1 start"><li class="c14"><span class="c5">Important in establishing flux of drug through stratum corneum</span></li></ul><ul class="c2 lst-kix_list_35-0"><li class="c15 c19"><span class="c5">Molecular size</span></li></ul><p class="c44 c47 c19 c42 c89"><span style="overflow: hidden; display: inline-block; margin: 0.00px 0.00px; border: 0.00px solid #000000; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px); width: 372.80px; height: 269.27px;"><img alt="https://lh6.googleusercontent.com/9UOC_nSDXCR05YIycG4_u8L51N6410loSabIjbS5AeXKiMrH_9vrpJRydb_Z80nacIiPJ-rdaV8BTQ0r-CwtZlnC41m0rYxJEdivjhkbXrCzaWMvmYBtkD1uqbjp8Iil5G4xLqZh" src="images/image03.png" style="width: 372.80px; height: 269.27px; margin-left: -0.00px; margin-top: -0.00px; transform: rotate(0.00rad) translateZ(0px); -webkit-transform: rotate(0.00rad) translateZ(0px);" title=""></span></p><p class="c22 c19 c42"><span class="c5"></span></p><p class="c22 c19 c42"><span class="c20 c25"></span></p><p class="c22 c69 c19"><span class="c5"></span></p><p class="c22"><span class="c25 c20"></span></p><div><p class="c22 c106"><span></span></p></div></body></html>
+
<center><object data="https://static.igem.org/mediawiki/2016/2/21/T--UofC_Calgary--BioTJournalFreeze.pdf" type="application/pdf" width="100%" height="600px">
 +
Your device does not support embed PDFs. Please click the following link to open up the PDF. <a href="https://static.igem.org/mediawiki/2016/2/21/T--UofC_Calgary--BioTJournalFreeze.pdf">Biotarget_Journal.pdf</a>
 +
</object> </center>
 +
 
 
</div>
 
</div>
−
+
 
−
</div>
+
 
</div>
 
</div>
 +
<br><br>
 +
<a href="https://static.igem.org/mediawiki/2016/f/f1/T--UofC_Calgary--biotargetjournal.pdf"<center><p style="text-align: center"><font-size="4"> Click here to view the above PDF</p></font></center></a>
 
</div>
 
</div>
−
<!-- END: CONTENT/MISC/ABOUT-1 -->
+
<!-- END: CONTENT/MISC/ABOUT-1 -->
−
<!-- END: PAGE CONTENT -->
+
<!-- BEGIN: CONTENT/MISC/ABOUT-1 -->
−
</div>
+
<div class="c-content-box c-size-md c-bg-white" id="second">
−
<!-- END: PAGE CONTAINER -->
+
<div class="container">
−
<!-- Split start -->
+
<div class="col-md-12">
−
<!--Split-->
+
<!-- Begin: Title 1 component -->
−
 
+
−
<head>
+
−
 
+
−
</head>
+
−
<!-- BEGIN: LAYOUT/FOOTERS/FOOTER-5 -->
+
−
<a name="footer"></a>
+
−
<footer class="c-layout-footer c-layout-footer-3 c-bg-dark">
+
−
<div class="c-prefooter">
+
−
<div class="container">
+
−
<div class="row">
+
−
<div class="col-md-3">
+
−
<div class="c-container c-first">
+
 
<div class="c-content-title-1">
 
<div class="c-content-title-1">
−
<h3 class="c-font-uppercase c-font-bold c-font-white">i<span class="c-theme-font">GEM</span></h3>
+
<a href="https://static.igem.org/mediawiki/2016/3/30/T--UofC_Calgary--chassisjournal.pdf"><h3 class="c-font-uppercase c-font-bold">Chassis Notebook</h3></a>
−
<div class="c-line-left hide">
+
<div class="c-line-left c-theme-bg"></a>
 
</div>
 
</div>
−
<p class="c-text">
 
−
Lorem ipsum dolor sit amet, consectetuer adipiscing elit, s ed elit diam nonummy ad minim veniam quis nostrud exerci et tation diam.
 
−
</p>
 
 
</div>
 
</div>
−
<ul class="c-links">
+
<!-- End--> <center><object data="https://static.igem.org/mediawiki/2016/3/30/T--UofC_Calgary--chassisjournal.pdf" type="application/pdf" width="100%" height="600px">
−
<li>
+
Your device does not support embed PDFs. Please click the following link to open up the PDF. <a href="https://static.igem.org/mediawiki/2016/9/9d/T--UofC_Calgary--ChassisJournalFreeze.pdf">Chassis_Journal.pdf</a>
−
<a href="#">Home</a>
+
</object> </center>
−
</li>
+
 
−
<li>
+
−
<a href="#">About</a>
+
−
</li>
+
−
<li>
+
−
<a href="#">Terms</a>
+
−
</li>
+
−
<li>
+
−
<a href="#">Contact</a>
+
−
</li>
+
−
</ul>
+
 
</div>
 
</div>
−
</div>
+
 
−
<div class="col-md-3">
+
</div>
−
<div class="c-container">
+
<br><br>
 +
<a href="https://static.igem.org/mediawiki/2016/3/30/T--UofC_Calgary--chassisjournal.pdf"<center><p style="text-align: center"><font-size="4"> Click here to view the above PDF</p></font></center></a>
 +
</div>
 +
<!-- END: CONTENT/MISC/ABOUT-1 -->
 +
<!-- BEGIN: CONTENT/MISC/ABOUT-1 -->
 +
<div class="c-content-box c-size-md c-bg-white" id="third">
 +
<div class="container">
 +
<div class="col-md-12">
 +
<!-- Begin: Title 1 component -->
 
<div class="c-content-title-1">
 
<div class="c-content-title-1">
−
<h3 class="c-font-uppercase c-font-bold c-font-white">Latest Entries</h3>
+
<a href="https://static.igem.org/mediawiki/2016/3/35/T--UofC_Calgary--Devicejournal.pdf"><h3 class="c-font-uppercase c-font-bold">Device Notebook</h3></a>
−
<div class="c-line-left hide">
+
<div class="c-line-left c-theme-bg">
 
</div>
 
</div>
 
</div>
 
</div>
−
<div class="c-blog">
+
<!-- End--> <center><object data="https://static.igem.org/mediawiki/2016/3/35/T--UofC_Calgary--Devicejournal.pdf" type="application/pdf" width="100%" height="600px">
−
<div class="c-post">
+
Your device does not support embed PDFs. Please click the following link to open up the PDF. <a href="https://static.igem.org/mediawiki/2016/3/35/T--UofC_Calgary--Devicejournal.pdf">Device_Journal.pdf</a>
−
<div class="c-post-img">
+
</object> </center>
−
<img src="assets/base/img/content/stock/9.jpg" alt="" class="img-responsive"/>
+
 
−
</div>
+
−
<div class="c-post-content">
+
−
<h4 class="c-post-title"><a href="#">BBI & KTI Have Arrived!</a></h4>
+
−
<p class="c-text">
+
−
Lorem ipsum dolor sit amet ipsum sit, consectetuer adipiscing elit sit amet
+
−
</p>
+
−
</div>
+
−
</div>
+
−
<div class="c-post c-last">
+
−
<div class="c-post-img">
+
−
<img src="assets/base/img/content/stock/14.jpg" alt="" class="img-responsive"/>
+
−
</div>
+
−
<div class="c-post-content">
+
−
<h4 class="c-post-title"><a href="#">Fully Trained!</a></h4>
+
−
<p class="c-text">
+
−
Lorem ipsum dolor ipsum sit ipsum amet, consectetuer sit adipiscing elit ipsum elit elit ipsum elit
+
−
</p>
+
−
</div>
+
−
</div>
+
−
<a href="#" class="btn btn-md c-btn-border-1x c-theme-btn c-btn-uppercase c-btn-square c-btn-bold c-read-more hide">Read More</a>
+
−
</div>
+
 
</div>
 
</div>
−
</div>
+
 
−
<div class="col-md-3">
+
−
<div class="c-container">
+
−
<div class="c-content-title-1">
+
−
<h3 class="c-font-uppercase c-font-bold c-font-white">Latest Pictures</h3>
+
−
<div class="c-line-left hide">
+
−
</div>
+
−
</div>
+
−
<ul class="c-works">
+
−
<li class="c-first">
+
−
<a href="https://www.instagram.com/igemcalgary/"><img src="https://static.igem.org/mediawiki/2016/8/8a/T--UofC_Calgary--wikiinsat8-1.jpg"" class="img-responsive"/></a>
+
−
</li>
+
−
<li>
+
−
<a href="https://www.instagram.com/igemcalgary/"><img src="https://static.igem.org/mediawiki/2016/b/b8/T--UofC_Calgary--wikiinsat9.jpg" class="img-responsive"/></a>
+
−
</li>
+
−
<li class="c-last">
+
−
<a href="https://www.instagram.com/igemcalgary/"><img src="https://static.igem.org/mediawiki/2016/c/c5/T--UofC_Calgary--wikiinsat7.jpg"" class="img-responsive"/></a>
+
−
</li>
+
−
</ul>
+
−
<ul class="c-works">
+
−
<li class="c-first">
+
−
<a href="https://www.instagram.com/igemcalgary/"><img src="https://static.igem.org/mediawiki/2016/a/a5/T--UofC_Calgary--wikiinsat6.jpg" class="img-responsive" /></a>
+
−
</li>
+
−
<li>
+
−
<a href="https://www.instagram.com/igemcalgary/"><img src="https://static.igem.org/mediawiki/2016/9/94/T--UofC_Calgary--wikiinsat5.jpg" class="img-responsive" /></a>
+
−
</li>
+
−
<li class="c-last">
+
−
<a href="https://www.instagram.com/igemcalgary"><img src="https://static.igem.org/mediawiki/2016/f/f3/T--UofC_Calgary--wikiinsat4.jpg" class="img-responsive" /></a>
+
−
</li>
+
−
</ul>
+
−
<ul class="c-works">
+
−
<li class="c-first">
+
−
<a href="https://www.instagram.com/igemcalgary/"><img src="https://static.igem.org/mediawiki/2016/5/5e/T--UofC_Calgary--wikiinsat3.jpg" class="img-responsive" alt=""/></a>
+
−
</li>
+
−
<li>
+
−
<a href="https://www.instagram.com/igemcalgary/"><img src="https://static.igem.org/mediawiki/2016/2/2a/T--UofC_Calgary--wikiinsat2.jpg" class="img-responsive" alt=""/></a>
+
−
</li>
+
−
<li class="c-last">
+
−
<a href="https://www.instagram.com/igemcalgary/"><img src="https://static.igem.org/mediawiki/2016/b/b1/T--UofC_Calgary--wikiinsat1.jpg" class="img-responsive" alt=""/></a>
+
−
</li>
+
−
</ul>
+
−
<a href="#" class="btn btn-md c-btn-border-1x c-theme-btn c-btn-uppercase c-btn-square c-btn-bold c-read-more hide">View More</a>
+
−
</div>
+
−
</div>
+
−
<div class="col-md-3">
+
−
<div class="c-container c-last">
+
−
<div class="c-content-title-1">
+
−
<h3 class="c-font-uppercase c-font-bold c-font-white">Find us</h3>
+
−
<div class="c-line-left hide">
+
−
</div>
+
−
<p>
+
−
Located in Calgary, Alberta, Canada.
+
−
</p>
+
−
</div>
+
−
<ul class="c-socials">
+
−
<li style="width: 43px;">
+
−
<a href="https://www.facebook.com/igemcalgary/"><i class="icon-social-facebook"></i></a>
+
−
</li>
+
−
<li style="width: 48px;">
+
−
<a href="https://twitter.com/igemcalgary"><i class="icon-social-twitter"></i></a>
+
−
</li>
+
−
<li>
+
−
<a href="#"><i class="icon-social-youtube"></i></a>
+
−
</li>
+
−
<li>
+
−
<a href="http://www.instagram.com/igemcalgary"><i class="icon-social-instagram"></i></a>
+
−
</li>
+
−
</ul>
+
−
<ul class="c-address">
+
−
<li>
+
−
<i class="icon-pointer c-theme-font"></i> University of Calgary
+
−
</li>
+
−
<li>
+
−
<i class="icon-call-end c-theme-font"></i> +587 717 7233
+
−
</li>
+
−
<li>
+
−
<i class="icon-envelope c-theme-font"></i> syed.jafri2@ucalgary.ca
+
−
</li>
+
−
</ul>
+
−
</div>
+
−
</div>
+
 
</div>
 
</div>
 +
<br><br>
 +
<a href="https://static.igem.org/mediawiki/2016/3/35/T--UofC_Calgary--Devicejournal.pdf"<center><p style="text-align: center"><font-size="4"> Click here to view the above PDF</p></font></a>
 
</div>
 
</div>
−
</div>
+
<!-- END: CONTENT/MISC/ABOUT-1 -->
−
<div class="c-postfooter">
+
                <!-- END: PAGE CONTENT -->
−
<div class="container">
+
            </div><!-- END: PAGE CONTAINER -->
−
<p class="c-font-oswald c-font-14">
+
            <!-- BEGIN: LAYOUT/FOOTERS/FOOTER-5 -->
−
Copyright &copy; University of Calgary 2016.
+
            <a id="footer" name="footer"></a>
−
</p>
+
            <footer class="c-layout-footer c-layout-footer-3 c-bg-dark">
−
</div>
+
                <div class="c-prefooter">
−
</div>
+
                    <div class="container">
−
</footer>
+
                        <div class="row">
−
<!-- END: LAYOUT/FOOTERS/FOOTER-5 -->
+
                            <div class="col-md-3">
−
<!-- BEGIN: LAYOUT/FOOTERS/GO2TOP -->
+
                                <div class="c-container c-first">
−
<div class="c-layout-go2top">
+
                                    <div class="c-content-title-1">
−
<i class="icon-arrow-up"></i>
+
                                        <h3 class="c-font-bold c-font-white">
−
</div>
+
                                        i<span class=
−
<!-- END: LAYOUT/FOOTERS/GO2TOP -->
+
                                        "c-theme-font">GEM</span></h3>
−
<!-- BEGIN: LAYOUT/BASE/BOTTOM -->
+
                                        <div class="c-line-left hide"></div>
−
<!-- BEGIN: CORE PLUGINS -->
+
                                        <p class="c-text">iGEM is an
−
 
+
                                        international competition promoting
−
<!--[if lt IE 9]>
+
                                        synthetic biology as a means to solve
−
<script src="../assets/global/plugins/excanvas.min.js"></script>  
+
                                        social, economic and humanitarian
−
<![endif]-->
+
                                        problems around the globe. The iGEM
−
<!-- END: CORE PLUGINS -->
+
                                        Jamboree is held in Boston annually. In
−
<!-- BEGIN: LAYOUT PLUGINS -->
+
                                        2016, over 300 teams are competing
−
<script>
+
                                        against each other.</p>
−
$("#img-scroll").click(function() {
+
                                    </div>
−
    $('html,body').animate({
+
                                    <ul class="c-links"></ul>
−
    scrollTop: $("#first").offset().top},
+
                                </div>
−
    'slow');
+
                            </div>
−
});
+
                            <div class="col-md-3">
−
</script>
+
                                <div class="c-container">
−
<script>
+
                                    <div class="c-content-title-1">
−
$(document).ready(function() {  
+
                                        <h3 class=
−
App.init(); // init core   
+
                                        "c-font-uppercase c-font-bold c-font-white">
 +
                                        Latest Entries</h3>
 +
                                        <div class="c-line-left hide"></div>
 +
                                    </div>
 +
                                    <div class="c-blog">
 +
                                        <div class="c-post"></div>
 +
                                        <div class="c-post c-last">
 +
                                            <div class="c-post-img"><img alt=""
 +
                                            class="img-responsive" src=
 +
                                            "https://static.igem.org/mediawiki/2016/d/dc/T--UofC_Calgary--WHMIS.jpg"></div>
 +
                                            <div class="c-post-content">
 +
                                                <h4 class="c-post-title">
 +
                                                <a href="#">Fully
 +
                                                Trained!</a></h4>
 +
                                                <p class="c-text">Our entire
 +
                                                team received a full BioSafety
 +
                                                education from the University
 +
                                                of Calgary! This entailed going
 +
                                                to classes to prepare for a
 +
                                                final quiz that tested our
 +
                                                ability to be safe in the lab.
 +
                                                Several of our members also had
 +
                                                radiation training and
 +
                                                clearance to ensure that work
 +
                                                done with radiation was
 +
                                                safe!</p>
 +
                                            </div>
 +
                                        </div><a class=
 +
                                        "btn btn-md c-btn-border-1x c-theme-btn c-btn-uppercase c-btn-square c-btn-bold c-read-more hide"
 +
                                        href="#">Read More</a>
 +
                                    </div>
 +
                                </div>
 +
                            </div>
 +
                            <div class="col-md-3">
 +
                                <div class="c-container">
 +
                                    <div class="c-content-title-1">
 +
                                        <h3 class=
 +
                                        "c-font-uppercase c-font-bold c-font-white">
 +
                                        Latest Pictures</h3>
 +
                                        <div class="c-line-left hide"></div>
 +
                                    </div>
 +
                                    <ul class="c-works">
 +
                                        <li class="c-first">
 +
                                            <a href=
 +
                                            "https://www.instagram.com/igemcalgary/">
 +
                                            <img class="img-responsive" src=
 +
                                            "https://static.igem.org/mediawiki/2016/8/8a/T--UofC_Calgary--wikiinsat8-1.jpg"></a>
 +
                                        </li>
 +
                                        <li>
 +
                                            <a href=
 +
                                            "https://www.instagram.com/igemcalgary/">
 +
                                            <img class="img-responsive" src=
 +
                                            "https://static.igem.org/mediawiki/2016/b/b8/T--UofC_Calgary--wikiinsat9.jpg"></a>
 +
                                        </li>
 +
                                        <li class="c-last">
 +
                                            <a href=
 +
                                            "https://www.instagram.com/igemcalgary/">
 +
                                            <img class="img-responsive" src=
 +
                                            "https://static.igem.org/mediawiki/2016/c/c5/T--UofC_Calgary--wikiinsat7.jpg"></a>
 +
                                        </li>
 +
                                    </ul>
 +
                                    <ul class="c-works">
 +
                                        <li class="c-
 +
">
 +
                                            <a href=
 +
                                            "https://www.instagram.com/igemcalgary/">
 +
                                            <img class="img-responsive" src=
 +
                                            "https://static.igem.org/mediawiki/2016/a/a5/T--UofC_Calgary--wikiinsat6.jpg"></a>
 +
                                        </li>
 +
                                        <li>
 +
                                            <a href=
 +
                                            "https://www.instagram.com/igemcalgary/">
 +
                                            <img class="img-responsive" src=
 +
                                            "https://static.igem.org/mediawiki/2016/9/94/T--UofC_Calgary--wikiinsat5.jpg"></a>
 +
                                        </li>
 +
                                        <li class="c-last">
 +
                                            <a href=
 +
                                            "https://www.instagram.com/igemcalgary">
 +
                                            <img class="img-responsive" src=
 +
                                            "https://static.igem.org/mediawiki/2016/f/f3/T--UofC_Calgary--wikiinsat4.jpg"></a>
 +
                                        </li>
 +
                                    </ul>
 +
                                    <ul class="c-works">
 +
                                        <li class="c-first">
 +
                                            <a href=
 +
                                            "https://www.instagram.com/igemcalgary/">
 +
                                            <img alt="" class="img-responsive"
 +
                                            src=
 +
                                            "https://static.igem.org/mediawiki/2016/5/5e/T--UofC_Calgary--wikiinsat3.jpg"></a>
 +
                                        </li>
 +
                                        <li>
 +
                                            <a href=
 +
                                            "https://www.instagram.com/igemcalgary/">
 +
                                            <img alt="" class="img-responsive"
 +
                                            src=
 +
                                            "https://static.igem.org/mediawiki/2016/2/2a/T--UofC_Calgary--wikiinsat2.jpg"></a>
 +
                                        </li>
 +
                                        <li class="c-last">
 +
                                            <a href=
 +
                                            "https://www.instagram.com/igemcalgary/">
 +
                                            <img alt="" class="img-responsive"
 +
                                            src=
 +
                                            "https://static.igem.org/mediawiki/2016/b/b1/T--UofC_Calgary--wikiinsat1.jpg"></a>
 +
                                        </li>
 +
                                    </ul><a class=
 +
                                    "btn btn-md c-btn-border-1x c-theme-btn c-btn-uppercase c-btn-square c-btn-bold c-read-more hide"
 +
                                    href="#">View More</a>
 +
                                </div>
 +
                            </div>
 +
                            <div class="col-md-3">
 +
                                <div class="c-container c-last">
 +
                                    <div class="c-content-title-1">
 +
                                        <h3 class=
 +
                                        "c-font-uppercase c-font-bold c-font-white">
 +
                                        Find us</h3>
 +
                                        <div class="c-line-left hide"></div>
 +
                                        <p>Located in Calgary, Alberta,
 +
                                        Canada.</p>
 +
                                    </div>
 +
                                    <ul class="c-socials">
 +
                                        <li style="width: 43px;">
 +
                                            <a href=
 +
                                            "https://www.facebook.com/igemcalgary/">
 +
                                            <i class=
 +
                                            "icon-social-facebook"></i></a>
 +
                                        </li>
 +
                                        <li style="width: 48px;">
 +
                                            <a href=
 +
                                            "https://twitter.com/igemcalgary"><i class="icon-social-twitter">
 +
                                            </i></a>
 +
                                        </li>
 +
                                        <li>
 +
                                            <a href=
 +
                                            "http://www.instagram.com/igemcalgary">
 +
                                            <i class="icon-camera"></i></a>
 +
                                        </li>
 +
                                    </ul>
 +
                                    <ul class="c-address">
 +
                                        <li><i class=
 +
                                        "icon-pointer c-theme-font"></i>
 +
                                        University of Calgary</li>
 +
                                        <li><i class=
 +
                                        "icon-envelope c-theme-font"></i>
 +
                                        igem.calgary@gmail.com</li>
 +
                                    </ul>
 +
                                </div>
 +
                            </div>
 +
                        </div>
 +
                    </div>
 +
                </div>
 +
                <div class="c-postfooter">
 +
                    <div class="container">
 +
                        <p class="c-font-oswald c-font-14">Copyright &copy;
 +
                        University of Calgary 2016.</p>
 +
                    </div>
 +
                </div>
 +
            </footer><!-- END: LAYOUT/FOOTERS/FOOTER-5 -->
 +
            <!-- BEGIN: LAYOUT/FOOTERS/GO2TOP -->
 +
            <div class="c-layout-go2top">
 +
                <i class="icon-arrow-up"></i>
 +
            </div><!-- END: LAYOUT/FOOTERS/GO2TOP -->
 +
            <!-- BEGIN: LAYOUT/BASE/BOTTOM -->
 +
            <!-- BEGIN: CORE PLUGINS -->
 +
            <!--[if lt IE 9]>
 +
    <script src="../assets/global/plugins/excanvas.min.js"></script>  
 +
    <![endif]-->
 +
            <!-- END: CORE PLUGINS -->
 +
            <!-- BEGIN: LAYOUT PLUGINS -->
 +
            <script>
 +
            $("#img-scroll1").click(function() {
 +
            $('html,body').animate({
 +
                    scrollTop: $("#first").offset().top
 +
                },
 +
                'slow');
 +
            });
 +
            $("#img-scroll2").click(function() {
 +
            $('html,body').animate({
 +
                    scrollTop: $("#second").offset().top
 +
                },
 +
                'slow');
 +
            });
 +
            $("#img-scroll3").click(function() {
 +
            $('html,body').animate({
 +
                    scrollTop: $("#third").offset().top
 +
                },
 +
                'slow');
 +
            });
 +
            $("#img-scroll4").click(function() {
 +
            $('html,body').animate({
 +
                    scrollTop: $("#fourth").offset().top
 +
                },
 +
                'slow');
 +
            });
 +
            </script>  
 +
            <script>
 +
            $(document).ready(function() {
 +
            App.init(); // init core   
  
−
// init main slider  
+
            // init main slider  
−
var slider = $('.c-layout-revo-slider .tp-banner');
+
            var slider = $('.c-layout-revo-slider .tp-banner');
−
    var cont = $('.c-layout-revo-slider .tp-banner-container');
+
            var cont = $('.c-layout-revo-slider .tp-banner-container');
−
    var api = slider.show().revolution({
+
            var api = slider.show().revolution({
−
        delay: 15000,  
+
                delay: 15000,
−
        startwidth:1170,
+
                startwidth: 1170,
−
        startheight: 620,
+
                startheight: 620,
−
        navigationType: "hide",
+
                navigationType: "hide",
−
        navigationArrows: "solo",
+
                navigationArrows: "solo",
−
        touchenabled: "on",
+
                touchenabled: "on",
−
        onHoverStop: "on",
+
                onHoverStop: "on",
−
        keyboardNavigation: "off",
+
                keyboardNavigation: "off",
−
        navigationStyle: "circle",
+
                navigationStyle: "circle",
−
        navigationHAlign: "center",
+
                navigationHAlign: "center",
−
        navigationVAlign: "bottom",
+
                navigationVAlign: "bottom",
−
        spinner: "spinner2",
+
                spinner: "spinner2",
−
        fullScreen: "on",  
+
                fullScreen: "on",
−
        fullScreenAlignForce:"on",
+
                fullScreenAlignForce: "on",
−
        fullScreenOffsetContainer: (App.getViewPort().width < App.getBreakpoint('md') ? '.c-layout-header' : ''),
+
                fullScreenOffsetContainer: (App.getViewPort().width < App.getBreakpoint('md') ? '.c-layout-header' : ''),
−
        shadow: 0,
+
                shadow: 0,
−
        fullWidth: "off",
+
                fullWidth: "off",
−
        forceFullWidth: "off",
+
                forceFullWidth: "off",
−
        hideTimerBar:"on",
+
                hideTimerBar: "on",
−
        hideThumbsOnMobile: "on",
+
                hideThumbsOnMobile: "on",
−
        hideNavDelayOnMobile: 1500,
+
                hideNavDelayOnMobile: 1500,
−
        hideBulletsOnMobile: "on",
+
                hideBulletsOnMobile: "on",
−
        hideArrowsOnMobile: "on",
+
                hideArrowsOnMobile: "on",
−
        hideThumbsUnderResolution: 0
+
                hideThumbsUnderResolution: 0
−
    });
+
            });
−
});
+
            });
−
</script>
+
            </script>
 +
        </div>
 +
    </div>
 
</body>
 
</body>
 
</html>
 
</html>

Latest revision as of 02:08, 20 October 2016

iGEM Calgary 2016

BioTarget Notebook
Your device does not support embed PDFs. Please click the following link to open up the PDF. Biotarget_Journal.pdf


Click here to view the above PDF

Chassis Notebook
Your device does not support embed PDFs. Please click the following link to open up the PDF. Chassis_Journal.pdf


Click here to view the above PDF

Device Notebook
Your device does not support embed PDFs. Please click the following link to open up the PDF. Device_Journal.pdf


Click here to view the above PDF

iGEM

iGEM is an international competition promoting synthetic biology as a means to solve social, economic and humanitarian problems around the globe. The iGEM Jamboree is held in Boston annually. In 2016, over 300 teams are competing against each other.

    Latest Entries

    Fully Trained!

    Our entire team received a full BioSafety education from the University of Calgary! This entailed going to classes to prepare for a final quiz that tested our ability to be safe in the lab. Several of our members also had radiation training and clearance to ensure that work done with radiation was safe!

    Read More

    Latest Pictures

    View More

    Find us

    Located in Calgary, Alberta, Canada.

    • University of Calgary
    • igem.calgary@gmail.com

    Copyright © University of Calgary 2016.