Team:NJU China/Modeling

From 2013.igem.org

(Difference between revisions)
(Prototype team page)
 
(35 intermediate revisions not shown)
Line 1: Line 1:
-
<!-- *** What falls between these lines is the Alert Box!  You can remove it from your pages once you have read and understood the alert *** -->
+
<!DOCTYPE html>
 +
<html lang="en">
 +
    <head>
 +
<meta charset="UTF-8" />
 +
        <meta http-equiv="X-UA-Compatible" content="IE=edge,chrome=1">
 +
        <title>CSS-Only Responsive Layout with Smooth Transitions</title>
 +
        <meta name="viewport" content="width=defvice-width, initial-scale=1.0">
 +
        <meta name="description" content="CSS-only Responsive Layout with Smooth Transitions" />
 +
        <meta name="keywords" content="css3, transitions, animations, css-only, navigation, smooth scrolling, full width, full height, window width, window height" />
 +
        <meta name="author" content="Codrops" />
 +
<link href='http://fonts.googleapis.com/css?family=Tahoma:400,700' rel='stylesheet' type='text/css'>
 +
<style type="text/css">
 +
/* hiding the top section*/
 +
body{position:absolute; top:0px; width:100%; height:1480px;}
 +
#top-section{
 +
  height:0px;
 +
    border:none;
 +
    width:980px;
 +
    margin:0 auto;
 +
    padding:0 0 0 0;
 +
    background-color:transparent;
 +
    overflow:hide;
-
<html>
+
}
-
<div id="box" style="width: 700px; margin-left: 137px; padding: 5px; border: 3px solid #000; background-color: #fe2b33;">
+
#p-logo{display:none;}
-
<div id="template" style="text-align: center; font-weight: bold; font-size: large; color: #f6f6f6; padding: 5px;">
+
#search-controls{display:none;}
-
This is a template page. READ THESE INSTRUCTIONS.
+
#top{display:none;}
 +
.firstHeading{display:none;}
 +
/* end of hiding the top section*/
 +
 
 +
/* global setting*/
 +
#globalWrapper{position:absolute; top:0px;left:0px; width:100%; padding:0 0 0 0;margin:0 0 0 0;height:100%;font-family: Tahoma, sans-serif;}
 +
#content{
 +
    background-color:transparent;
 +
    border:none;
 +
    width:1360px;
 +
    height:700px;
 +
    marign:0 auto;
 +
    padding:0 0 0 0;
 +
    top:-40px;
 +
    }
 +
#bodyContent{
 +
    background-color:transparent;
 +
    border:none;
 +
   
 +
    }
 +
siteSub{
 +
    display:none;
 +
    border:none;
 +
    }
 +
contentSub{
 +
    display:none;
 +
    }
 +
/* end of global setting*/
 +
 
 +
/*hiding the footer-box*/
 +
#footer-box{display:none;}
 +
#catlinks{display:none;}
 +
/*end of hiding the footer book*/
 +
 
 +
/* menu (page, edit ...) */
 +
#menubar {
 +
    background-color:transparent;
 +
    position: relative;
 +
    float:left;
 +
    white-space: nowrap;
 +
    top:-6px;
 +
    width: 490px;
 +
    z-index: 5000;
 +
    font-family: sans-serif;
 +
    font-size: 55%;
 +
    line-height: 1em;
 +
    z-index:99;
 +
}
 +
/* MAIN STYLE DEFINITIONS */
 +
a{
 +
color:#870203;
 +
-webkit-transition-duration:0.3s;
 +
-moz-transition-duration:0.3s;
 +
-o-transition-duration:0.3s;
 +
}
 +
 
 +
a:hover {
 +
color:#3d3f3c;
 +
}
 +
 
 +
a:visited{
 +
color:#870203;
 +
}
 +
 
 +
td
 +
{
 +
font-family: Helvetica;
 +
font-size: 10pt;
 +
vertical-align: top;
 +
text-align: left;
 +
padding-right: 10px;
 +
}
 +
 
 +
tr
 +
{
 +
vertical-align: top;
 +
}
 +
 
 +
H1 {
 +
    font-family: Helvetica;
 +
    text-transform: uppercase;
 +
    color: #3d3f3c;
 +
    text-align: left;
 +
    }
 +
 
 +
 
 +
H4 {
 +
    font-family: Helvetica;
 +
    text-transform: uppercase;
 +
    color: #3d3f3c;
 +
    text-align: left;
 +
    }
 +
 
 +
/* CONTENT HEADING STYLES - overrides some main.css styling */
 +
 
 +
H6 {
 +
font-family:'Tahoma';
 +
font-size:30px;
 +
font-weight:100;
 +
text-align:left;
 +
text-transform:uppercase;
 +
color: #3d3f3c;
 +
border-bottom:1px solid orangered;
 +
padding-bottom:10px;
 +
margin:15px 0;
 +
}
 +
 
 +
H1, H3 {
 +
font-family:'Tahoma';
 +
font-weight:100;
 +
text-transform:uppercase;
 +
}
 +
 
 +
H1 {
 +
font-size:20px;
 +
border:none;
 +
}
 +
 
 +
img.headshot {
 +
width: 100px;
 +
height: auto;
 +
vertical-align: text-top;
 +
}
 +
 
 +
 
 +
 
 +
body {
 +
background:#fff;
 +
font-family: Helvetica;
 +
}
 +
 
 +
content {
 +
background: transparent;
 +
}
 +
 
 +
#tracking_nav
 +
{
 +
margin: 0px 0px 0px 950px;
 +
position: fixed;
 +
color:#bababa;
 +
border: 1px solid #3d3f3c;
 +
background:#3d3f3c;
 +
font-size: 16pt;
 +
padding: 5px;
 +
line-height: 120%;
 +
}
 +
 
 +
#tracking_nav a { color:#ffffff; text-transform: lowercase;font-size: 16pt;}
 +
#tracking_nav a:hover {background:#bababa;}
 +
 
 +
#parts_table
 +
{
 +
border: 1px solid #870203;
 +
border-collapse: collapse;
 +
width: 70%;
 +
margin: auto;
 +
}
 +
 
 +
#parts_table td
 +
{
 +
text-align: center;
 +
margin: 5px;
 +
border: 1px solid #870203;
 +
 +
}
 +
 
 +
#parts_table th
 +
{
 +
background-color: #bababa;
 +
border: 1px solid #870203;
 +
color: #ffffff;
 +
}
 +
 
 +
.table_part
 +
{
 +
vertical-align: middle;
 +
}
 +
 
 +
/* HEADER STYLES: banner, navbar, etc. */
 +
#banner { width:300px; display:block; float:left; }
 +
#banner img { width:100%; }
 +
 
 +
ul#nav {
 +
width:1800px;
 +
margin:47px 0 0 100px;
 +
position:relative;
 +
}
 +
 
 +
#nav li {
 +
color: #bbb;
 +
background-color:none;
 +
margin: 0 85px 0 0;
 +
float: left;
 +
position: relative;
 +
list-style: none;
 +
text-transform:uppercase;
 +
}
 +
#nav li:last-child { margin:0; }
 +
 
 +
/* main level link */
 +
#nav a {
 +
font-family:'Source Sans Pro', sans-serif;
 +
font-size:10pt;
 +
font-weight:100;
 +
line-height:110%;
 +
color: inherit;
 +
text-decoration: none;
 +
display: block;
 +
padding: 0 0 0 5px;
 +
margin: 0;
 +
}
 +
 
 +
ul#nav > li > a {
 +
line-height:12px;
 +
border-left:solid 2px #bbb;
 +
padding:0 0 0 3px;
 +
}
 +
 
 +
#nav a:hover {
 +
/*background-color: #870203;
 +
color: #ffffff;*/
 +
}
 +
 
 +
/* main level link hover */
 +
#nav .current a, #nav li:hover > a {
 +
color: #000;
 +
border-color:orangered;
 +
}
 +
 
 +
/* sub levels link hover */
 +
#nav ul li:hover a, #nav li:hover li a {
 +
border: none;
 +
/*background-color: #FA9D1C;*/
 +
color:#000;
 +
}
 +
 
 +
#nav ul a:hover {
 +
color: orangered !important;
 +
/*background: #fff url(img/gradient.png) repeat-x 0 -100px !important;
 +
text-shadow: 0 1px 1px rgba(0,0,0, .1);*/
 +
}
 +
 
 +
 
 +
/* dropdown */
 +
#nav li:hover > ul {
 +
/*display: block;*/
 +
opacity:1;
 +
margin:0;
 +
background-color: none;
 +
z-index:0;
 +
}
 +
 
 +
/* level 2 list */
 +
#nav ul {
 +
/*display: none;*/
 +
opacity:0;
 +
margin: 20px 0 0 0;
 +
padding: 7px 0 0 0;
 +
width: 205px;
 +
position: absolute;
 +
left: 0;
 +
z-index:-1;
 +
-webkit-transition-duration:0.5s;
 +
-moz-transition-duration:0.5s;
 +
-o-transition-duration:0.5s;
 +
}
 +
#nav ul li {
 +
float: none;
 +
margin: 0;
 +
padding: 0;
 +
}
 +
 
 +
#nav ul a {
 +
font-weight: normal;
 +
/*text-shadow: 0 1px 0 #fff;*/
 +
}
 +
 
 +
/* clearfix */
 +
#nav:after {
 +
content: ".";
 +
display: block;
 +
clear: both;
 +
visibility: hidden;
 +
line-height: 0;
 +
height: 0;
 +
}
 +
#nav {
 +
display: inline-block;
 +
}
 +
html[xmlns] #nav {
 +
display: block;
 +
}
 +
 +
* html #nav {
 +
height: 1%;
 +
}
 +
 
 +
/* pinterest like photo grid for social page*/
 +
 
 +
/*
 +
body {
 +
background: url(http://subtlepatterns.com/patterns/scribble_light.png) ;
 +
}
 +
*/
 +
 
 +
#wrapper {
 +
width: 90%;
 +
max-width: 1100px;
 +
min-width: 800px;
 +
margin: 50px auto;
 +
}
 +
 
 +
#columns {
 +
-webkit-column-count: 3;
 +
-webkit-column-gap: 10px;
 +
-webkit-column-fill: auto;
 +
-moz-column-count: 3;
 +
-moz-column-gap: 10px;
 +
-moz-column-fill: auto;
 +
column-count: 3;
 +
column-gap: 15px;
 +
column-fill: auto;
 +
}
 +
 
 +
.pin {
 +
display: inline-block;
 +
background: #FEFEFE;
 +
border: 2px solid #FAFAFA;
 +
box-shadow: 0 1px 2px rgba(34, 25, 25, 0.4);
 +
margin: 0 2px 15px;
 +
-webkit-column-break-inside: avoid;
 +
-moz-column-break-inside: avoid;
 +
column-break-inside: avoid;
 +
padding: 15px;
 +
padding-bottom: 5px;
 +
background: -webkit-linear-gradient(45deg, #FFF, #F9F9F9);
 +
opacity: 1;
 +
 +
-webkit-transition: all .2s ease;
 +
-moz-transition: all .2s ease;
 +
-o-transition: all .2s ease;
 +
transition: all .2s ease;
 +
}
 +
 
 +
.pin img {
 +
width: 100%;
 +
border-bottom: 1px solid #ccc;
 +
padding-bottom: 15px;
 +
margin-bottom: 5px;
 +
}
 +
 
 +
.pin p {
 +
font: 12px/18px Arial, sans-serif;
 +
color: #333;
 +
margin: 0;
 +
}
 +
 
 +
@media (min-width: 960px) {
 +
#columns {
 +
-webkit-column-count: 4;
 +
-moz-column-count: 4;
 +
column-count: 4;
 +
}
 +
}
 +
 
 +
@media (min-width: 1100px) {
 +
#columns {
 +
-webkit-column-count: 5;
 +
-moz-column-count: 5;
 +
column-count: 5;
 +
}
 +
}
 +
 
 +
#columns:hover .pin:not(:hover) {
 +
opacity: 0.4;
 +
}
 +
 
 +
.left-menu, .left-menu a {
 +
    text-align: left;
 +
    color:#999999;
 +
    text-transform: lowercase;
 +
}
 +
 
 +
.left-menu:hover {
 +
    color: #D00000;
 +
    background-color: transparent;
 +
}
 +
 
 +
.right-menu{width:400px; float:right}
 +
.right-menu, .right-menu a {
 +
    right: 0px;
 +
    text-align: right;
 +
    color: #999999;
 +
}
 +
#menubar ul {
 +
    color: #999999;
 +
    list-style: none;
 +
}
 +
#menubar li {
 +
    display: inline;
 +
    position: relative;
 +
    cursor: pointer;
 +
    padding-left: 0px;
 +
    padding-right: 0px;
 +
}
 +
.left-menu li a {
 +
    padding: 0px 10px 0px 0px;
 +
}
 +
.left-menu .selected {
 +
#    color: #999999;
 +
}
 +
#.left-menu .selected:hover {
 +
#    color: #999999;
 +
#}
 +
 
 +
.left-menu:hover a {
 +
    color: #999999;;
 +
}
 +
 
 +
.left-menu li a:hover {
 +
    color: #D00000;
 +
    text-decoration: underline;
 +
}
 +
 
 +
 
 +
.right-menu li {
 +
#    background-color: transparent;
 +
}
 +
.right-menu li a {
 +
    padding: 0px 15px 0px 0px;
 +
    color: #999999;;
 +
    background-color: transparent;
 +
}
 +
.right-menu li a:hover {
 +
    color: #D00000;
 +
    text-decoration: underline;
 +
}
 +
/* end menu (edit, page ...) */
 +
 
 +
/*! normalize.css 2012-03-11T12:53 UTC - http://github.com/necolas/normalize.css */
 +
 
 +
/* =============================================================================
 +
  HTML5 display definitions
 +
  ========================================================================== */
 +
 
 +
/*
 +
* Corrects block display not defined in IE6/7/8/9 & FF3
 +
*/
 +
 
 +
article,
 +
aside,
 +
details,
 +
figcaption,
 +
figure,
 +
footer,
 +
header,
 +
hgroup,
 +
nav,
 +
section,
 +
summary {
 +
    display: block;
 +
}
 +
 
 +
/*
 +
* Corrects inline-block display not defined in IE6/7/8/9 & FF3
 +
*/
 +
 
 +
audio,
 +
canvas,
 +
video {
 +
    display: inline-block;
 +
    *display: inline;
 +
    *zoom: 1;
 +
}
 +
 
 +
/*
 +
* Prevents modern browsers from displaying 'audio' without controls
 +
* Remove excess height in iOS5 devices
 +
*/
 +
 
 +
audio:not([controls]) {
 +
    display: none;
 +
    height: 0;
 +
}
 +
 
 +
/*
 +
* Addresses styling for 'hidden' attribute not present in IE7/8/9, FF3, S4
 +
* Known issue: no IE6 support
 +
*/
 +
 
 +
[hidden] {
 +
    display: none;
 +
}
 +
 
 +
 
 +
/* =============================================================================
 +
  Base
 +
  ========================================================================== */
 +
 
 +
/*
 +
* 1. Corrects text resizing oddly in IE6/7 when body font-size is set using em units
 +
*    http://clagnut.com/blog/348/#c790
 +
* 2. Prevents iOS text size adjust after orientation change, without disabling user zoom
 +
*    www.456bereastreet.com/archive/201012/controlling_text_size_in_safari_for_ios_without_disabling_user_zoom/
 +
*/
 +
 
 +
html {
 +
    font-size: 100%; /* 1 */
 +
    -webkit-text-size-adjust: 100%; /* 2 */
 +
    -ms-text-size-adjust: 100%; /* 2 */
 +
}
 +
 
 +
/*
 +
* Addresses font-family inconsistency between 'textarea' and other form elements.
 +
*/
 +
 
 +
html,
 +
button,
 +
input,
 +
select,
 +
textarea {
 +
    font-family: sans-serif;
 +
}
 +
 
 +
/*
 +
* Addresses margins handled incorrectly in IE6/7
 +
*/
 +
 
 +
body {
 +
    margin: 0;
 +
}
 +
 
 +
 
 +
/* =============================================================================
 +
  Links
 +
  ========================================================================== */
 +
 
 +
/*
 +
* Addresses outline displayed oddly in Chrome
 +
*/
 +
 
 +
a:focus {
 +
    outline: thin dotted;
 +
}
 +
 
 +
/*
 +
* Improves readability when focused and also mouse hovered in all browsers
 +
* people.opera.com/patrickl/experiments/keyboard/test
 +
*/
 +
 
 +
a:hover,
 +
a:active {
 +
    outline: 0;
 +
}
 +
 
 +
 
 +
/* =============================================================================
 +
  Typography
 +
  ========================================================================== */
 +
 
 +
/*
 +
* Addresses font sizes and margins set differently in IE6/7
 +
* Addresses font sizes within 'section' and 'article' in FF4+, Chrome, S5
 +
*/
 +
 
 +
h1 {
 +
    font-size: 2em;
 +
    margin: 0.67em 0;
 +
}
 +
 
 +
h2 {
 +
    font-size: 1.5em;
 +
    margin: 0.83em 0;
 +
}
 +
 
 +
h3 {
 +
    font-size: 1.17em;
 +
    margin: 1em 0;
 +
}
 +
 
 +
h4 {
 +
    font-size: 1em;
 +
    margin: 1.33em 0;
 +
}
 +
 
 +
h5 {
 +
    font-size: 0.83em;
 +
    margin: 1.67em 0;
 +
}
 +
 
 +
h6 {
 +
    font-size: 0.75em;
 +
    margin: 2.33em 0;
 +
}
 +
 
 +
/*
 +
* Addresses styling not present in IE7/8/9, S5, Chrome
 +
*/
 +
 
 +
abbr[title] {
 +
    border-bottom: 1px dotted;
 +
}
 +
 
 +
/*
 +
* Addresses style set to 'bolder' in FF3+, S4/5, Chrome
 +
*/
 +
 
 +
b,
 +
strong {
 +
    font-weight: normal;
 +
}
 +
 
 +
blockquote {
 +
    margin: 1em 40px;
 +
}
 +
 
 +
/*
 +
* Addresses styling not present in S5, Chrome
 +
*/
 +
 
 +
dfn {
 +
    font-style: italic;
 +
}
 +
 
 +
/*
 +
* Addresses styling not present in IE6/7/8/9
 +
*/
 +
 
 +
mark {
 +
    background: #ff0;
 +
    color: #000;
 +
}
 +
 
 +
/*
 +
* Addresses margins set differently in IE6/7
 +
*/
 +
 
 +
p,
 +
pre {
 +
    margin: 1em 0;
 +
}
 +
 
 +
/*
 +
* Corrects font family set oddly in IE6, S4/5, Chrome
 +
* en.wikipedia.org/wiki/User:Davidgothberg/Test59
 +
*/
 +
 
 +
pre,
 +
code,
 +
kbd,
 +
samp {
 +
    font-family: monospace, serif;
 +
    _font-family: 'Tahoma', monospace;
 +
    font-size: 1em;
 +
}
 +
 
 +
/*
 +
* Improves readability of pre-formatted text in all browsers
 +
*/
 +
 
 +
pre {
 +
    white-space: pre;
 +
    white-space: pre-wrap;
 +
    word-wrap: break-word;
 +
}
 +
 
 +
/*
 +
* 1. Addresses CSS quotes not supported in IE6/7
 +
* 2. Addresses quote property not supported in S4
 +
*/
 +
 
 +
/* 1 */
 +
 
 +
q {
 +
    quotes: none;
 +
}
 +
 
 +
/* 2 */
 +
 
 +
q:before,
 +
q:after {
 +
    content: '';
 +
    content: none;
 +
}
 +
 
 +
small {
 +
    font-size: 75%;
 +
}
 +
 
 +
/*
 +
* Prevents sub and sup affecting line-height in all browsers
 +
* gist.github.com/413930
 +
*/
 +
 
 +
sub,
 +
sup {
 +
    font-size: 75%;
 +
    line-height: 0;
 +
    position: relative;
 +
    vertical-align: baseline;
 +
}
 +
 
 +
sup {
 +
    top: -0.5em;
 +
}
 +
 
 +
sub {
 +
    bottom: -0.25em;
 +
}
 +
 
 +
 
 +
/* =============================================================================
 +
  Lists
 +
  ========================================================================== */
 +
 
 +
/*
 +
* Addresses margins set differently in IE6/7
 +
*/
 +
 
 +
dl,
 +
menu,
 +
ol,
 +
ul {
 +
    margin: 1em 0;
 +
}
 +
 
 +
dd {
 +
    margin: 0 0 0 40px;
 +
}
 +
 
 +
/*
 +
* Addresses paddings set differently in IE6/7
 +
*/
 +
 
 +
menu,
 +
ol,
 +
ul {
 +
    padding: 0 0 0 40px;
 +
}
 +
 
 +
/*
 +
* Corrects list images handled incorrectly in IE7
 +
*/
 +
 
 +
nav ul,
 +
nav ol {
 +
    list-style: none;
 +
    list-style-image: none;
 +
}
 +
 
 +
 
 +
/* =============================================================================
 +
  Embedded content
 +
  ========================================================================== */
 +
 
 +
/*
 +
* 1. Removes border when inside 'a' element in IE6/7/8/9, FF3
 +
* 2. Improves image quality when scaled in IE7
 +
*    code.flickr.com/blog/2008/11/12/on-ui-quality-the-little-things-client-side-image-resizing/
 +
*/
 +
 
 +
img {
 +
    border: 0; /* 1 */
 +
    -ms-interpolation-mode: bicubic; /* 2 */
 +
}
 +
 
 +
/*
 +
* Corrects overflow displayed oddly in IE9
 +
*/
 +
 
 +
svg:not(:root) {
 +
    overflow: hidden;
 +
}
 +
 
 +
 
 +
/* =============================================================================
 +
  Figures
 +
  ========================================================================== */
 +
 
 +
/*
 +
* Addresses margin not present in IE6/7/8/9, S5, O11
 +
*/
 +
 
 +
figure {
 +
    margin: 0;
 +
}
 +
 
 +
 
 +
/* =============================================================================
 +
  Forms
 +
  ========================================================================== */
 +
 
 +
/*
 +
* Corrects margin displayed oddly in IE6/7
 +
*/
 +
 
 +
form {
 +
    margin: 0;
 +
}
 +
 
 +
/*
 +
* Define consistent border, margin, and padding
 +
*/
 +
 
 +
fieldset {
 +
    border: 1px solid #c0c0c0;
 +
    margin: 0 2px;
 +
    padding: 0.35em 0.625em 0.75em;
 +
}
 +
 
 +
/*
 +
* 1. Corrects color not being inherited in IE6/7/8/9
 +
* 2. Corrects text not wrapping in FF3
 +
* 3. Corrects alignment displayed oddly in IE6/7
 +
*/
 +
 
 +
legend {
 +
    border: 0; /* 1 */
 +
    padding: 0;
 +
    white-space: normal; /* 2 */
 +
    *margin-left: -7px; /* 3 */
 +
}
 +
 
 +
/*
 +
* 1. Corrects font size not being inherited in all browsers
 +
* 2. Addresses margins set differently in IE6/7, FF3+, S5, Chrome
 +
* 3. Improves appearance and consistency in all browsers
 +
*/
 +
 
 +
button,
 +
input,
 +
select,
 +
textarea {
 +
    font-size: 100%; /* 1 */
 +
    margin: 0; /* 2 */
 +
    vertical-align: baseline; /* 3 */
 +
    *vertical-align: middle; /* 3 */
 +
}
 +
 
 +
/*
 +
* Addresses FF3/4 setting line-height on 'input' using !important in the UA stylesheet
 +
*/
 +
 
 +
button,
 +
input {
 +
    line-height: normal; /* 1 */
 +
}
 +
 
 +
/*
 +
* 1. Improves usability and consistency of cursor style between image-type 'input' and others
 +
* 2. Corrects inability to style clickable 'input' types in iOS
 +
* 3. Removes inner spacing in IE7 without affecting normal text inputs
 +
*    Known issue: inner spacing remains in IE6
 +
*/
 +
 
 +
button,
 +
input[type="button"],
 +
input[type="reset"],
 +
input[type="submit"] {
 +
    cursor: pointer; /* 1 */
 +
    -webkit-appearance: button; /* 2 */
 +
    *overflow: visible;  /* 3 */
 +
}
 +
 
 +
/*
 +
* Re-set default cursor for disabled elements
 +
*/
 +
 
 +
button[disabled],
 +
input[disabled] {
 +
    cursor: default;
 +
}
 +
 
 +
/*
 +
* 1. Addresses box sizing set to content-box in IE8/9
 +
* 2. Removes excess padding in IE8/9
 +
* 3. Removes excess padding in IE7
 +
      Known issue: excess padding remains in IE6
 +
*/
 +
 
 +
input[type="checkbox"],
 +
input[type="radio"] {
 +
    box-sizing: border-box; /* 1 */
 +
    padding: 0; /* 2 */
 +
    *height: 13px; /* 3 */
 +
    *width: 13px; /* 3 */
 +
}
 +
 
 +
/*
 +
* 1. Addresses appearance set to searchfield in S5, Chrome
 +
* 2. Addresses box-sizing set to border-box in S5, Chrome (include -moz to future-proof)
 +
*/
 +
 
 +
input[type="search"] {
 +
    -webkit-appearance: textfield; /* 1 */
 +
    -moz-box-sizing: content-box;
 +
    -webkit-box-sizing: content-box; /* 2 */
 +
    box-sizing: content-box;
 +
}
 +
 
 +
/*
 +
* Removes inner padding and search cancel button in S5, Chrome on OS X
 +
*/
 +
 
 +
input[type="search"]::-webkit-search-decoration,
 +
input[type="search"]::-webkit-search-cancel-button {
 +
    -webkit-appearance: none;
 +
}
 +
 
 +
/*
 +
* Removes inner padding and border in FF3+
 +
* www.sitepen.com/blog/2008/05/14/the-devils-in-the-details-fixing-dojos-toolbar-buttons/
 +
*/
 +
 
 +
button::-moz-focus-inner,
 +
input::-moz-focus-inner {
 +
    border: 0;
 +
    padding: 0;
 +
}
 +
 
 +
/*
 +
* 1. Removes default vertical scrollbar in IE6/7/8/9
 +
* 2. Improves readability and alignment in all browsers
 +
*/
 +
 
 +
textarea {
 +
    overflow: auto; /* 1 */
 +
    vertical-align: top; /* 2 */
 +
}
 +
 
 +
 
 +
/* =============================================================================
 +
  Tables
 +
  ========================================================================== */
 +
 
 +
/*
 +
* Remove most spacing between table cells
 +
*/
 +
 
 +
table {
 +
    border-collapse: collapse;
 +
    border-spacing: 0;
 +
}
 +
/* Addition */
 +
/* apply a natural box layout model to all elements */
 +
/* By Paul Irish: http://paulirish.com/2012/box-sizing-border-box-ftw/ */
 +
* { -moz-box-sizing: border-box; -webkit-box-sizing: border-box; box-sizing: border-box; }
 +
@font-face {
 +
font-family:'Tahoma';
 +
    font-weight: normal;
 +
    font-style: normal;
 +
}
 +
/* General Demo Style */
 +
body{
 +
font-family: Tahoma, serif;
 +
background: #ddd;
 +
font-weight: 100;
 +
font-size: 15px;
 +
color: #333;
 +
overflow: hidden;
 +
-webkit-font-smoothing: antialiased;
 +
}
 +
a{
 +
color: #555;
 +
text-decoration: none;
 +
}
 +
.clr{
 +
clear: both;
 +
padding: 0;
 +
height: 0;
 +
margin: 0;
 +
}
 +
/* Header Style */
 +
.codrops-top{
 +
line-height: 24px;
 +
font-size: 9px;
 +
text-transform: uppercase;
 +
z-index: 9999;
 +
position: relative;
 +
font-family: Tahoma, serif;
 +
}
 +
.codrops-top a{
 +
padding: 0px 10px;
 +
letter-spacing: 1px;
 +
color: #888;
 +
display: inline-block;
 +
text-shadow: 0 1px 1px rgba(255,255,255,0.4);
 +
}
 +
.codrops-top span.right{
 +
float: right;
 +
}
 +
.codrops-top span.right a{
 +
float: left;
 +
display: block;
 +
}
 +
@media screen and (max-width: 520px) {
 +
.codrops-top { display: none; }
 +
}
 +
</style>
 +
<style type="text/css">
 +
.st-container {
 +
position: absolute;
 +
width: 100%;
 +
height: 100%;
 +
top: 0;
 +
left: 0;
 +
font-family: Tahoma, sans-serif;
 +
}
 +
 
 +
.st-container > input,
 +
.st-container > a {
 +
position: fixed;
 +
bottom: 0px;
 +
width: 20%;
 +
cursor: pointer;
 +
font-size: 16px;
 +
height: 34px;
 +
line-height: 34px;
 +
}
 +
 
 +
.st-container > input {
 +
opacity: 0;
 +
z-index: 1000;
 +
}
 +
 
 +
.st-container > a {
 +
z-index: 10;
 +
font-weight: 100;
 +
background: #46e23a;
 +
color: #fff;
 +
text-align: center;
 +
text-shadow: 1px 1px 1px rgba(151,24,64,0.2);
 +
}
 +
 
 +
/* "Fix" for percentage rounding: add a background bar pseudo element with the same color like the labels */
 +
.st-container:before {
 +
content: '';
 +
position: fixed;
 +
width: 100%;
 +
height: 34px;
 +
background: #46e23a;
 +
z-index: 9;
 +
bottom: 0;
 +
}
 +
 
 +
#st-control-1, #st-control-1 + a {
 +
left: 0;
 +
}
 +
 
 +
#st-control-2, #st-control-2 + a {
 +
left: 20%;
 +
}
 +
 
 +
#st-control-3, #st-control-3 + a {
 +
left: 40%;
 +
}
 +
 
 +
#st-control-4, #st-control-4 + a {
 +
left: 60%;
 +
}
 +
 
 +
#st-control-5, #st-control-5 + a {
 +
left: 80%;
 +
}
 +
 
 +
.st-container > input:checked + a,
 +
.st-container > input:checked:hover + a{
 +
background: #1c8211;
 +
}
 +
 
 +
.st-container > input:checked + a:after,
 +
.st-container > input:checked:hover + a:after{
 +
bottom: 100%;
 +
border: solid transparent;
 +
content: '';
 +
height: 0;
 +
width: 0;
 +
position: absolute;
 +
pointer-events: none;
 +
border-bottom-color: #1c8211;
 +
border-width: 20px;
 +
left: 50%;
 +
margin-left: -20px;
 +
}
 +
 
 +
.st-container > input:hover + a{
 +
background: #24ad3b;
 +
}
 +
 
 +
.st-container > input:hover + a:after {
 +
border-bottom-color: #24ad3b;
 +
}
 +
 
 +
.st-scroll,
 +
.st-panel {
 +
position: relative;
 +
width: 100%;
 +
height: 100%;
 +
}
 +
 
 +
.st-scroll {
 +
top: 0;
 +
left: 0;
 +
-webkit-transition: all 0.6s ease-in-out;
 +
-moz-transition: all 0.6s ease-in-out;
 +
-o-transition: all 0.6s ease-in-out;
 +
-ms-transition: all 0.6s ease-in-out;
 +
transition: all 0.6s ease-in-out;
 +
 +
/* Let's enforce some hardware acceleration */
 +
-webkit-transform: translate3d(0, 0, 0);
 +
-webkit-backface-visibility: hidden;
 +
}
 +
 
 +
.st-panel{
 +
background: #fff;
 +
overflow: hidden;
 +
}
 +
 
 +
#st-control-1:checked ~ .st-scroll {
 +
-webkit-transform: translateY(0%);
 +
-moz-transform: translateY(0%);
 +
-o-transform: translateY(0%);
 +
-ms-transform: translateY(0%);
 +
transform: translateY(0%);
 +
}
 +
#st-control-2:checked ~ .st-scroll {
 +
-webkit-transform: translateY(-100%);
 +
-moz-transform: translateY(-100%);
 +
-o-transform: translateY(-100%);
 +
-ms-transform: translateY(-100%);
 +
transform: translateY(-100%);
 +
}
 +
#st-control-3:checked ~ .st-scroll {
 +
-webkit-transform: translateY(-200%);
 +
-moz-transform: translateY(-200%);
 +
-o-transform: translateY(-200%);
 +
-ms-transform: translateY(-200%);
 +
transform: translateY(-200%);
 +
}
 +
#st-control-4:checked ~ .st-scroll {
 +
-webkit-transform: translateY(-300%);
 +
-moz-transform: translateY(-300%);
 +
-o-transform: translateY(-300%);
 +
-ms-transform: translateY(-300%);
 +
transform: translateY(-300%);
 +
}
 +
#st-control-5:checked ~ .st-scroll {
 +
-webkit-transform: translateY(-400%);
 +
-moz-transform: translateY(-400%);
 +
-o-transform: translateY(-400%);
 +
-ms-transform: translateY(-400%);
 +
transform: translateY(-400%);
 +
}
 +
 
 +
 
 +
/* Content elements */
 +
 
 +
.st-deco{
 +
width: 200px;
 +
height: 200px;
 +
position: absolute;
 +
top: 0px;
 +
left: 50%;
 +
margin-left: -100px;
 +
background: #96faa9;
 +
-webkit-transform: translateY(-50%) rotate(45deg);
 +
-moz-transform: translateY(-50%) rotate(45deg);
 +
-o-transform: translateY(-50%) rotate(45deg);
 +
-ms-transform: translateY(-50%) rotate(45deg);
 +
transform: translateY(-50%) rotate(45deg);
 +
}
 +
 
 +
[data-icon]:after {
 +
    content: attr(data-icon);
 +
    font-family: 'Tahoma';
 +
    color: #fff;
 +
text-shadow: 1px 1px 1px rgba(0,0,0,0.2);
 +
position: absolute;
 +
width: 200px;
 +
height: 200px;
 +
line-height: 200px;
 +
text-align: center;
 +
font-size: 60px;
 +
top: 50%;
 +
left: 50%;
 +
margin: -100px 0 0 -100px;
 +
-webkit-transform: rotate(-45deg) translateY(25%);
 +
-moz-transform: rotate(-45deg) translateY(25%);
 +
-o-transform: rotate(-45deg) translateY(25%);
 +
-ms-transform: rotate(-45deg) translateY(25%);
 +
transform: rotate(-45deg) translateY(25%);
 +
}
 +
 
 +
.st-panel h2 {
 +
color: #3ae24a;
 +
text-shadow: 2px 2px 2px rgba(0,0,0,0.5);
 +
position: absolute;
 +
font-size: 54px;
 +
font-weight: 100;
 +
width: 80%;
 +
left: 10%;
 +
text-align: center;
 +
line-height: 50px;
 +
margin: -70px 0 0 0;
 +
padding: 0;
 +
top: 23%;
 +
-webkit-backface-visibility: hidden;
 +
}
 +
 
 +
#st-control-1:checked ~ .st-scroll #st-panel-1 h2,
 +
#st-control-2:checked ~ .st-scroll #st-panel-2 h2,
 +
#st-control-3:checked ~ .st-scroll #st-panel-3 h2,
 +
#st-control-4:checked ~ .st-scroll #st-panel-4 h2,
 +
#st-control-5:checked ~ .st-scroll #st-panel-5 h2{
 +
-webkit-animation: moveDown 0.6s ease-in-out 0.2s backwards;
 +
-moz-animation: moveDown 0.6s ease-in-out 0.2s backwards;
 +
-o-animation: moveDown 0.6s ease-in-out 0.2s backwards;
 +
-ms-animation: moveDown 0.6s ease-in-out 0.2s backwards;
 +
animation: moveDown 0.6s ease-in-out 0.2s backwards;
 +
}
 +
@-webkit-keyframes moveDown{
 +
0% {
 +
-webkit-transform: translateY(-40px);
 +
opacity: 0;
 +
}
 +
100% {
 +
-webkit-transform: translateY(0px); 
 +
opacity: 1;
 +
}
 +
}
 +
 
 +
@-moz-keyframes moveDown{
 +
0% {
 +
-moz-transform: translateY(-40px);
 +
opacity: 0;
 +
}
 +
100% {
 +
-moz-transform: translateY(0px); 
 +
opacity: 1;
 +
}
 +
}
 +
 
 +
@-o-keyframes moveDown{
 +
0% {
 +
-o-transform: translateY(-40px);
 +
opacity: 0;
 +
}
 +
100% {
 +
-o-transform: translateY(0px); 
 +
opacity: 1;
 +
}
 +
}
 +
 
 +
@-ms-keyframes moveDown{
 +
0% {
 +
-ms-transform: translateY(-40px);
 +
opacity: 0;
 +
}
 +
100% {
 +
-ms-transform: translateY(0px); 
 +
opacity: 1;
 +
}
 +
}
 +
 
 +
@keyframes moveDown{
 +
0% {
 +
transform: translateY(-40px);
 +
opacity: 0;
 +
}
 +
100% {
 +
transform: translateY(0px); 
 +
opacity: 1;
 +
}
 +
}
 +
 
 +
.pra{
 +
/*position: absolute;*/
 +
text-align: left;
 +
font-size: 16px;
 +
line-height: 18px;
 +
color: #000000;
 +
/*z-index: 2;*/
 +
padding: 0;
 +
width: 80%;
 +
        height:70%;
 +
margin-left: 10%;
 +
margin-top: 11%;
 +
        font-weight: normal;
 +
/*margin: 10px 0 0 0;*/
 +
-webkit-backface-visibility: hidden;
 +
}
 +
#st-control-1:checked ~ .st-scroll #st-panel-1 p,
 +
#st-control-2:checked ~ .st-scroll #st-panel-2 p,
 +
#st-control-3:checked ~ .st-scroll #st-panel-3 p,
 +
#st-control-4:checked ~ .st-scroll #st-panel-4 p,
 +
#st-control-5:checked ~ .st-scroll #st-panel-5 p{
 +
-webkit-animation: moveUp 0.6s ease-in-out 0.2s backwards;
 +
-moz-animation: moveUp 0.6s ease-in-out 0.2s backwards;
 +
-o-animation: moveUp 0.6s ease-in-out 0.2s backwards;
 +
-ms-animation: moveUp 0.6s ease-in-out 0.2s backwards;
 +
animation: moveUp 0.6s ease-in-out 0.2s backwards;
 +
}
 +
 
 +
@-webkit-keyframes moveUp{
 +
0% {
 +
-webkit-transform: translateY(40px);
 +
opacity: 0;
 +
}
 +
100% {
 +
-webkit-transform: translateY(0px); 
 +
opacity: 1;
 +
}
 +
}
 +
 
 +
@-moz-keyframes moveUp{
 +
0% {
 +
-moz-transform: translateY(40px);
 +
opacity: 0;
 +
}
 +
100% {
 +
-moz-transform: translateY(0px); 
 +
opacity: 1;
 +
}
 +
}
 +
 
 +
@-o-keyframes moveUp{
 +
0% {
 +
-o-transform: translateY(40px);
 +
opacity: 0;
 +
}
 +
100% {
 +
-o-transform: translateY(0px); 
 +
opacity: 1;
 +
}
 +
}
 +
 
 +
@-ms-keyframes moveUp{
 +
0% {
 +
-ms-transform: translateY(40px);
 +
opacity: 0;
 +
}
 +
100% {
 +
-ms-transform: translateY(0px); 
 +
opacity: 1;
 +
}
 +
}
 +
 
 +
@keyframes moveUp{
 +
0% {
 +
transform: translateY(40px);
 +
opacity: 0;
 +
}
 +
100% {
 +
transform: translateY(0px); 
 +
opacity: 1;
 +
}
 +
}
 +
 
 +
/* Colored sections */
 +
 
 +
.st-color,
 +
.st-deco{
 +
background: #96faa9;
 +
}
 +
.st-color [data-icon]:after {
 +
color: #96faa9;
 +
}
 +
.st-color .st-deco {
 +
background: #fff;
 +
}
 +
.st-color h2 {
 +
color: #fff;
 +
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    <body>
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<div style="float:left; position:absolute; margin-top:-50px;margin-left:70px; z-index:1; display:block; ">
 +
</br></br>
 +
<a href="https://2013.igem.org"><img src="https://static.igem.org/mediawiki/2013/8/80/NJU-Miniminiminilogocolored.png" ></a>
</div>
</div>
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<div id="instructions" style="text-align: center; font-weight: normal; font-size: small; color: #f6f6f6; padding: 5px;">
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        <div class="container">
-
You are provided with this team page template with which to start the iGEM season.  You may choose to personalize it to fit your team but keep the same "look." Or you may choose to take your team wiki to a different level and design your own wiki.  You can find some examples <a href="https://2008.igem.org/Help:Template/Examples">HERE</a>.
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<div class="st-container">
 +
 +
<input type="radio" name="radio-set" checked="checked" id="st-control-1"/>
 +
<a href="#st-panel-1">Introduction</a>
 +
<input type="radio" name="radio-set" id="st-control-2"/>
 +
<a href="#st-panel-2">Pharmacokinetic Modeling</a>
 +
<input type="radio" name="radio-set" id="st-control-3"/>
 +
<a href="#st-panel-3">Parameters</a>
 +
<input type="radio" name="radio-set" id="st-control-4"/>
 +
<a href="#st-panel-4">Mass balance equation of exosome</a>
 +
<input type="radio" name="radio-set" id="st-control-5"/>
 +
<a href="#st-panel-5">Results and conclusions</a>
 +
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<div class="st-scroll">
 +
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<section class="st-panel" id="st-panel-1">
 +
<div class="st-deco" data-icon="1"></div>
 +
<h2>Introduction</h2>
 +
<div class="pra">
 +
</br></br></br></br>
 +
Pharmacokinetics is the quantitative study of the drug absorption, distribution and metabolism within the body. It shows the fluctuation of the drug concentration within a certain part of the body along the time. For a new drug, we need to first experimentally obtain the pharmacokinetic parameters and then make the pharmacokinetic model to predict the concentration change after drug administration. Thus pharmacokinetic model plays a vital role in new drug development. Since our targeting-exosome is a brand new drug delivery system, we need to make a pharmacokinetic model to check if it can really target the specific site we want and predict the concentration change within that site.
</div>
</div>
-
<div id="warning" style="text-align: center; font-weight: bold; font-size: small; color: #f6f6f6; padding: 5px;">
+
</section>
-
You <strong>MUST</strong> have all of the pages listed in the menu below with the names specified. PLEASE keep all of your pages within your teams namespace.
+
 +
<section class="st-panel st-color" id="st-panel-2">
 +
<div class="st-deco" data-icon="2"></div>
 +
<h2>Pharmacokinetic Modeling</h2>
 +
 
 +
<div class="pra">
 +
<img width="500px"; height="400px"; src="https://static.igem.org/mediawiki/2013/5/54/NJU-Moduling-2-1.png" style="margin-right:10px; float:left;"/>
 +
</br></br></br>
 +
After drug administration, what happened within the body is quite complex and all the tissues are involved in the drug metabolism. In order to construct a pharmacokinetic model, we need to first make a few simplification of the body to make a pharmacokinetic model feasible.</br></br>
 +
Based on the multi-compartmental model, we divide the human body into central compartment (blood circulation) and peripheral compartment (body tissues). Since the exosome is administrated by intravenous injection, we assume that the concentration of exosome within the blood circulation reached its peak soon after injection and there is no variation within different parts of the blood circulation. Inspired by the pharmacokinetic model made by iGEM Slovenia 2012, we subdivide the peripheral compartment into liver (our target organ), kidney, lung, rapidly perfused tissues (such as skin, muscle) and slowly perfused tissues (such as spleen, heart). Each peripheral compartment has blood exchange with the central blood circulation, and during this process, certain percentage of exosome flow through a compartment will be absorbed. Apart from that, some of the exosome get into the kidney will be eliminated. Based on these simplifications, our multi-compartmental model is shown in the figure 1.</br>
 +
 
</div>
</div>
 +
 +
</section>
 +
 +
<section class="st-panel" id="st-panel-3">
 +
<div class="st-deco" data-icon="3"></div>
 +
<h2>Parameters</h2>
 +
<div class="pra" ><!--style="overflow-y:scroll;"-->
 +
 +
<img width="300px"; height="390px"; src="https://static.igem.org/mediawiki/2013/7/79/NJU-Module-3-1.png" style="margin-right:10px; float:right;"/ usemap="liver">
 +
<map name="liver">
 +
</br></br></br>
 +
For exosome is a brand new area of research, there are almost no papers have documentation of their pharmacokinetic figures. Since liposomes are also bilayer-membrane vesicles and the diameter of liposome is same as that of exosome, we used the figures from liposome study to predict some of figures we need to use[1][2][3][4]. Apart from that, we also obtain the figures concerning blood flow and organ volume from the documentation of iGEM Slovenia 2012.</br></br>
 +
&nbsp;&nbsp;&nbsp;&nbsp;Qi – blood flows to tissues </br>

 +
&nbsp;&nbsp;&nbsp;Pi-percentage of drug absorption in each compartment</br>
 +
&nbsp;&nbsp;&nbsp;&nbsp;Kmi – metabolism rate in each compartment</br>
</div>
</div>
-
</html>
+
</section>
 +
 +
<section class="st-panel st-color" id="st-panel-4">
 +
<div class="st-deco" data-icon="4"></div>
 +
<h2>Mass balance equation of Exosome</h2>
 +
<div class="pra" style="overflow-y:scroll;" >
 +
A. The concentration change of the exosome within each compartment over time</br></br>
 +
a .The central compartment-blood circulation</br>
 +
The exosomes are removed from the blood through two main ways: distribution to other compartments and metabolism in the blood. Based on that, the mass balance equation of exosomes goes like follows:</br></br></br>
-
<!-- *** End of the alert box *** -->
 
 +
b. The peripheral compartments</br>
 +
There are two main factors affect the concentration fluctuation in peripheral compartments: absorption from the blood and metabolism within the compartments.</br>
 +
For kidney, there is an additional factor, which is the elimination rate of the exosomes by kidney.</br>
 +
Thus the mass balance equations of the peripheral compartments are listed as below:</br></br></br>
 +
Liver:</br>
 +
<img width="453px"; height="81px"; src="https://static.igem.org/mediawiki/igem.org/7/79/M3-Model-%E5%BE%AE%E5%88%86liver.png"></br></br>
 +
Lung:</br>
 +
<img width="427px"; height="81px"; src="https://static.igem.org/mediawiki/igem.org/thumb/0/08/M3-Model-%E5%BE%AE%E5%88%86lung.png/800px-M3-Model-%E5%BE%AE%E5%88%86lung.png"></br></br>
 +
Kidney:</br>
 +
<img width="448px"; height="77px"; src="https://static.igem.org/mediawiki/igem.org/7/71/M3-Model-%E5%BE%AE%E5%88%86kidney.png"></br></br>
 +
Rapidly perfused tissues:</br>
 +
<img width="372px"; height="70px"; src="https://static.igem.org/mediawiki/igem.org/0/01/M3-Model-%E5%BE%AE%E5%88%86rpt.png"></br></br>
 +
Slowly perfused tissues:</br>
 +
<img width="363px"; height="70px"; src="https://static.igem.org/mediawiki/igem.org/6/63/M3-Model-%E5%BE%AE%E5%88%86spt.png"></br></br>
-
{| style="color:#1b2c8a;background-color:#0c6;" cellpadding="3" cellspacing="1" border="1" bordercolor="#fff" width="62%" align="center"
+
Solving all the mass equations above, we can get the function which show the concentration change within each compartment along the time:</br></br></br>
-
!align="center"|[[Team:NJU_China|Home]]
+
Blood circulation:</br>
-
!align="center"|[[Team:NJU_China/Team|Team]]
+
<img width="300px"; height="65px"; src="https://static.igem.org/mediawiki/igem.org/5/54/M3-Model-%E6%96%B9%E7%A8%8Bblood.png"></br></br>
-
!align="center"|[https://igem.org/Team.cgi?year=2013&team_name=NJU_China Official Team Profile]
+
Liver:</br>
-
!align="center"|[[Team:NJU_China/Project|Project]]
+
<img width="655px"; height="106px"; src="https://static.igem.org/mediawiki/igem.org/e/ec/M3-Model-%E6%96%B9%E7%A8%8Bliver.png"></br></br>
-
!align="center"|[[Team:NJU_China/Parts|Parts Submitted to the Registry]]
+
Lung:</br>
-
!align="center"|[[Team:NJU_China/Modeling|Modeling]]
+
<img width="652px"; height="106px"; src="https://static.igem.org/mediawiki/igem.org/8/8e/M3-Model-%E6%96%B9%E7%A8%8Blung.png"></br></br>
-
!align="center"|[[Team:NJU_China/Notebook|Notebook]]
+
Kidney:</br>
-
!align="center"|[[Team:NJU_China/Safety|Safety]]
+
<img width="637px"; height="107px"; src="https://static.igem.org/mediawiki/igem.org/4/40/M3-Model-%E6%96%B9%E7%A8%8Bkidney.png"></br></br>
-
!align="center"|[[Team:NJU_China/Attributions|Attributions]]
+
Rapidly perfused tissues:</br>
-
|}
+
<img width="642px"; height="102px"; src="https://static.igem.org/mediawiki/igem.org/0/0c/M3-Model-%E6%96%B9%E7%A8%8Brpt.png"></br></br>
 +
Slowly perfused tissues:</br>
 +
<img width="644px"; height="116px"; src="https://static.igem.org/mediawiki/igem.org/8/81/M3-Model-%E6%96%B9%E7%A8%8Bspt.png"></br></br>
 +
B. Examine the relationship between the exosome concentration change over time and absorption percentage within liver.
 +
</br></br>
 +
<img width="655px"; height="106px"; src="https://static.igem.org/mediawiki/igem.org/e/ec/M3-Model-%E6%96%B9%E7%A8%8Bliver.png"></br></br>
-
If you choose to include a '''Modeling''' page, please write about your modeling adventures here.  This is not necessary but it may be a nice list to include.
+
C. Examine the relationship between the exosme concentration change over time and drug half-life within liver.</br></br>
 +
<img width="655px"; height="106px"; src="https://static.igem.org/mediawiki/igem.org/e/ec/M3-Model-%E6%96%B9%E7%A8%8Bliver.png"></br></br>
 +
 
 +
<img width="125px"; height="71px"; src="https://static.igem.org/mediawiki/igem.org/a/a0/M3-model-kel.png"></br></br>
 +
 
 +
</div>
 +
</section>
 +
 +
<section class="st-panel" id="st-panel-5">
 +
<div class="st-deco" data-icon="5"></div>
 +
<h2>Results and Conclusions</h2>
 +
<div class="pra" style="overflow-y:scroll;" >
 +
A.Exosome concentration change over time within each compartment</br>
 +
<img width="620px"; height="400px"; src="https://static.igem.org/mediawiki/2013/6/60/Nju-Moduling-5-1.png" style="margin-right:10px;"/>
 +
</br>
 +
Figure.2 Exosome concentration change along the time in different compartments.
 +
</br></br></br>
 +
As we can see from the figure.2, the concentration of exosomes in the blood falls down along the time while the concentration of exosomes in the peripheral compartment goes up first then falls down. Comparing the concentration change of exosomes over time in the liver(our target organ) with other tissues, we can easily see that the peak concentration of exosomes in liver is much higher than that of non-target tissues. Thus we can assure that the after add the liver targeting protein to the exosome (the percentage of exosomes get into the liver increases), the concentration of exosomes in the liver greatly outnumber that in other tissues.
 +
</br></br>
 +
B.The relationship between the exosome concentration change over time and absorption percentage in liver.</br>
 +
<img width="750px"; height="600px"; src="https://static.igem.org/mediawiki/2013/0/06/Nju-Moduling-5-2.png" style="margin-right:10px;"/></br>
 +
Figure.3 exosome concentration change over time with different absorption percentage in liver
 +
</br></br></br>
 +
The difference of exosome distribution between liver and other tissues lie in that the absorption percentage of exosomes in liver is much higher than that in other tissues. After plot concentration change over time and absorption percentage in 3D(Figure.3),we can see that as the absorption percentage increases, the peak of drug concentration also goes up. To achieve higher concentration in liver, we can make outside modification to exosomes to direct more exosomes into the liver.
 +
</br></br>
 +
C.The relationship between the exosome concentration change over time and drug half-life.</br>
 +
<img width="850px"; height="500px"; src="https://static.igem.org/mediawiki/2013/2/2e/NJU-Moduling-5-3.png" style="margin-right:10px;"/></br>
 +
Figure.4 exosome concentration change over time with different exosome halflife in liver
 +
</br></br></br>
 +
Encapsulate the siRNA into exosomes can great increase the half-life of the siRNA, and via outside modification we can change the half-life of the exosome. As we can see from Figure.4 , after the drug half-life increases, the concentration falls more slowly so that the drug can function more time in the target tissue.
 +
</br></br></br>
 +
Reference:</br>
 +
1. Ishida T, Harashima H, Kiwada H. Liposome clearance[J]. Bioscience reports, 2002, 22: 197-224.
 +
</br></br>
 +
2. Dams ETM, Laverman P, Oyen W JG, et al. Accelerated blood clearance and altered biodistribution of repeated injections of sterically stabilized liposomes[J]. Journal of Pharmacology and Experimental Therapeutics, 2000, 292(3): 1071-1079.
 +
</br></br>
 +
3. Gao S, Dagnaes-Hansen F, Nielsen EJB, et al. The effect of chemical modification and nanoparticle formulation on stability and biodistribution of siRNA in mice[J]. Molecular Therapy, 2009, 17(7): 1225-1233.
 +
</br></br>
 +
4. Morrissey DV, Lockridge JA, Shaw L, et al. Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs[J]. Nature biotechnology, 2005, 23(8): 1002-1007.
 +
</div>
 +
</section>
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Introduction Pharmacokinetic Modeling Parameters Mass balance equation of exosome Results and conclusions

Introduction





Pharmacokinetics is the quantitative study of the drug absorption, distribution and metabolism within the body. It shows the fluctuation of the drug concentration within a certain part of the body along the time. For a new drug, we need to first experimentally obtain the pharmacokinetic parameters and then make the pharmacokinetic model to predict the concentration change after drug administration. Thus pharmacokinetic model plays a vital role in new drug development. Since our targeting-exosome is a brand new drug delivery system, we need to make a pharmacokinetic model to check if it can really target the specific site we want and predict the concentration change within that site.

Pharmacokinetic Modeling




After drug administration, what happened within the body is quite complex and all the tissues are involved in the drug metabolism. In order to construct a pharmacokinetic model, we need to first make a few simplification of the body to make a pharmacokinetic model feasible.

Based on the multi-compartmental model, we divide the human body into central compartment (blood circulation) and peripheral compartment (body tissues). Since the exosome is administrated by intravenous injection, we assume that the concentration of exosome within the blood circulation reached its peak soon after injection and there is no variation within different parts of the blood circulation. Inspired by the pharmacokinetic model made by iGEM Slovenia 2012, we subdivide the peripheral compartment into liver (our target organ), kidney, lung, rapidly perfused tissues (such as skin, muscle) and slowly perfused tissues (such as spleen, heart). Each peripheral compartment has blood exchange with the central blood circulation, and during this process, certain percentage of exosome flow through a compartment will be absorbed. Apart from that, some of the exosome get into the kidney will be eliminated. Based on these simplifications, our multi-compartmental model is shown in the figure 1.

Parameters




For exosome is a brand new area of research, there are almost no papers have documentation of their pharmacokinetic figures. Since liposomes are also bilayer-membrane vesicles and the diameter of liposome is same as that of exosome, we used the figures from liposome study to predict some of figures we need to use[1][2][3][4]. Apart from that, we also obtain the figures concerning blood flow and organ volume from the documentation of iGEM Slovenia 2012.

    Qi – blood flows to tissues

    Pi-percentage of drug absorption in each compartment
    Kmi – metabolism rate in each compartment

Mass balance equation of Exosome

A. The concentration change of the exosome within each compartment over time

a .The central compartment-blood circulation
The exosomes are removed from the blood through two main ways: distribution to other compartments and metabolism in the blood. Based on that, the mass balance equation of exosomes goes like follows:


b. The peripheral compartments
There are two main factors affect the concentration fluctuation in peripheral compartments: absorption from the blood and metabolism within the compartments.
For kidney, there is an additional factor, which is the elimination rate of the exosomes by kidney.
Thus the mass balance equations of the peripheral compartments are listed as below:


Liver:


Lung:


Kidney:


Rapidly perfused tissues:


Slowly perfused tissues:


Solving all the mass equations above, we can get the function which show the concentration change within each compartment along the time:


Blood circulation:


Liver:


Lung:


Kidney:


Rapidly perfused tissues:


Slowly perfused tissues:


B. Examine the relationship between the exosome concentration change over time and absorption percentage within liver.



C. Examine the relationship between the exosme concentration change over time and drug half-life within liver.





Results and Conclusions

A.Exosome concentration change over time within each compartment

Figure.2 Exosome concentration change along the time in different compartments.


As we can see from the figure.2, the concentration of exosomes in the blood falls down along the time while the concentration of exosomes in the peripheral compartment goes up first then falls down. Comparing the concentration change of exosomes over time in the liver(our target organ) with other tissues, we can easily see that the peak concentration of exosomes in liver is much higher than that of non-target tissues. Thus we can assure that the after add the liver targeting protein to the exosome (the percentage of exosomes get into the liver increases), the concentration of exosomes in the liver greatly outnumber that in other tissues.

B.The relationship between the exosome concentration change over time and absorption percentage in liver.

Figure.3 exosome concentration change over time with different absorption percentage in liver


The difference of exosome distribution between liver and other tissues lie in that the absorption percentage of exosomes in liver is much higher than that in other tissues. After plot concentration change over time and absorption percentage in 3D(Figure.3),we can see that as the absorption percentage increases, the peak of drug concentration also goes up. To achieve higher concentration in liver, we can make outside modification to exosomes to direct more exosomes into the liver.

C.The relationship between the exosome concentration change over time and drug half-life.

Figure.4 exosome concentration change over time with different exosome halflife in liver


Encapsulate the siRNA into exosomes can great increase the half-life of the siRNA, and via outside modification we can change the half-life of the exosome. As we can see from Figure.4 , after the drug half-life increases, the concentration falls more slowly so that the drug can function more time in the target tissue.


Reference:
1. Ishida T, Harashima H, Kiwada H. Liposome clearance[J]. Bioscience reports, 2002, 22: 197-224.

2. Dams ETM, Laverman P, Oyen W JG, et al. Accelerated blood clearance and altered biodistribution of repeated injections of sterically stabilized liposomes[J]. Journal of Pharmacology and Experimental Therapeutics, 2000, 292(3): 1071-1079.

3. Gao S, Dagnaes-Hansen F, Nielsen EJB, et al. The effect of chemical modification and nanoparticle formulation on stability and biodistribution of siRNA in mice[J]. Molecular Therapy, 2009, 17(7): 1225-1233.

4. Morrissey DV, Lockridge JA, Shaw L, et al. Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs[J]. Nature biotechnology, 2005, 23(8): 1002-1007.

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