Difference between revisions of "Team:Virginia/Team"

Line 1: Line 1:
 
{{Virginia}}
 
{{Virginia}}
−
 
−
<!--
 
−
JUNE 29TH
 
−
Page to do:
 
−
Individual descriptions
 
−
Team photo
 
−
-->
 
 
<html>
 
<html>
−
    <head>
+
<head>
−
        <!-- Bootstrap import -- Latest compiled and minified CSS -->
+
<!-- Bootstrap import -- Latest compiled and minified CSS -->
−
        <link rel="stylesheet" href="https://maxcdn.bootstrapcdn.com/bootstrap/3.3.4/css/bootstrap.min.css" type="text/css">
+
<link rel="stylesheet" href="https://maxcdn.bootstrapcdn.com/bootstrap/3.3.4/css/bootstrap.min.css" type="text/css">
−
        </head>
+
</head>
−
        <body>
+
<body>
−
            <div id="top-part">
+
<div class="popup">
−
                <p id="above-nav">University of Virginia iGEM 2015</p>
+
<h1>Welcome to the University of Virginia iGEM 2015 Wiki</h1>
−
                <div id="icon-box">
+
<p>Use the navigation bar at the top of every page to move between pages. Please let us know if you have any comments or questions about our project by visiting the “Contact Us” page.</p>
−
                    <a href="https://twitter.com/Virginia_iGEM">
+
<p>(click to close)</p>
−
                        <img id="twitter" src="/wiki/images/2/2c/Virginia_twitter_white.png"></img>
+
</div>
−
                    </a>
+
<div class="back">
−
                    <a href="https://www.facebook.com/uvaigem">
+
<div id="top-part">
−
                        <img id="facebook" src="/wiki/images/e/ed/Virginia_facebook.png"></img>
+
<p id="above-nav">University of Virginia iGEM 2015</p>
−
                    </a>
+
<div id="icon-box">
−
                </div>
+
<a href="https://twitter.com/Virginia_iGEM"><img id="twitter" src="/wiki/images/2/2c/Virginia_twitter_white.png"></img></a>
−
            </div>
+
<a href="https://www.facebook.com/uvaigem"><img id="facebook" src="/wiki/images/e/ed/Virginia_facebook.png"></img></a>
−
            <div class="nav">
+
</div>
−
                <div class="container">
+
</div>
−
                    <ul class="pull-left">
+
<div class="nav">
−
                        <li>
+
<div class="container">
−
                            <a href="/Team:Virginia">Home</a>
+
<ul class="pull-left">
−
                        </li>
+
<li><a href="/Team:Virginia">Home</a></li>
−
                    </ul>
+
</ul>
−
                    <ul class="pull-right">
+
<ul class="pull-right">
−
                        <li>
+
<li><a href="/Team:Virginia/Team">Team</a></li>
−
                            <a href="/Team:Virginia/Team">Team</a>
+
<li><a href="/Team:Virginia/Project">Project</a></li>
−
                        </li>
+
<li><a href="/Team:Virginia/Practices">Policy and Practices</a></li>
−
                        <li>
+
<li><a href="/Team:Virginia/Attributions">Attributions</a></li>
−
                            <a href="/Team:Virginia/Project">Project</a>
+
<li><a href="/Team:Virginia/Contact_us">Contact Us</a></li>
−
                        </li>
+
</ul>
−
                        <li>
+
</div>
−
                            <a href="/Team:Virginia/Practices">Policy and Practices</a>
+
</div>
−
                        </li>
+
<div class="jumbotron">
−
                        <li>
+
<h2>
−
                            <a href="/Team:Virginia/Attributions">Attributions</a>
+
House of Carbs
−
                        </li>
+
<p>A Novel Solution to Minimizing Postprandial Hyperglycemic Spikes</p>
−
                        <li>
+
</h2>
−
                            <a href="/Team:Virginia/Contact_us">Contact Us</a>
+
</div>
−
                        </li>
+
<div id="description-wrapper">
−
                    </ul>
+
<div id="description-text-wrapper">
−
                </div>
+
<h1>Project Overview</h1>
−
            </div>
+
<h3>The Problem: Diabetes Mellitus and Hyperglycemia</h3>
−
            <!-- POPUP SCRIPTS-->
+
< p >From diabetes mellitus a number of devastating complications, such as amputations, blindness, crippling neuropathies, and many others, can arise from increased blood sugar levels on a regular basis, but many of
−
            <script type="text/javascript">
+
the major complications of diabetes arise from drastic fluctuations in the blood glucose
−
jQuery(document).ready(function(){
+
level (Ceriello et al., 2012). Up to two-thirds of people with diabetes die of
−
$("#supraja-box").click(function(){
+
cardiovascular disease (CVD) brought about by diabetes-related macrovascular diseases
−
 
+
(Deshpande et al. 2008). In fact, the risk for cardiovascular disease mortality is 2 to 4
−
$("#popup-supraja").fadeIn("medium");
+
times higher in people with diabetes than in people who do not have diabetes.  
−
});
+
Additionally, diabetic retinopathy is the most common microvascular complication
−
$("#popup-supraja").click(function(){
+
among people with diabetes and results in more than 10,000 new cases of blindness per
−
$("#popup-supraja").fadeOut("medium");
+
year. Retinopathy is associated with prolonged hyperglycemia; it is slow to develop, and
−
});
+
there is some evidence that it can begin to develop as early as 7 years before clinical
−
$("#dominic-box").click(function(){
+
diagnosis of diabetes (Deshpande et al., 2008).</p>
−
$("#popup-dominic").fadeIn("medium");
+
<p>Postprandial (post-meal) blood sugar spikes specifically are one of the most
−
});
+
damaging complications of diabetes (Parkin et al., 2002). Many diabetics are able to
−
$("#popup-dominic").click(function(){
+
effectively manage post-meal glycemic spikes with self-administered doses of insulin,
−
$("#popup-dominic").fadeOut("medium");
+
but these hyperglycemic incidents still kill more Americans per year than any other
−
});
+
diabetes-related complications (Parkin et al., 2002). Arguably, the gravest consequence of
−
$("#jingyuan-box").click(function(){
+
glycemic spikes in diabetes patients is the development of progressive macrovascular
−
$("#popup-jingyuan").fadeIn("medium");
+
disease (MVD), which affects the large blood vessels of the body, hardening and
−
});
+
blocking these vessels (Ceriello et al., 2012). MVD is the leading cause of death among
−
$("#popup-jingyuan").click(function(){
+
T2DM patients in the United States, causing up to 65% of diabetes-related deaths, making it a huge target for diabetes treatments research (Deshpande et al., 2008). MVD
−
$("#popup-jingyuan").fadeOut("medium");
+
also frequently leads to other severe complications such as ischemia in the extremities
−
});
+
and blindness (Haffner et al., 1998).</p>
−
$("#liam-box").click(function(){
+
<h3>Controlling Hyperglycemic Spikes</h3>
−
$("#popup-liam").fadeIn("medium");
+
<p>For many T1DM and T2DM patients, it has been shown that the regular
−
$("#popup-liam").css("top","800px");
+
control and management of blood glucose levels prevents many of the vascular
−
});
+
complications of the disease, but most of the time control over glucose is difficult to
−
$("#popup-liam").click(function(){
+
attain because the self-dosing insulin treatment system that a lot of moderately to
−
$("#popup-liam").fadeOut("medium");
+
severely sick diabetes patients use is often hard to calibrate and use (Parkin et al., 2002).</p>
−
});
+
<p>Compared to sucrose-rich food, starch-rich food has been found to create less
−
$("#rena-box").click(function(){
+
fluctuation in blood glucose levels, and thus is beneficial to diabetes patients and
−
$("#popup-rena").fadeIn("medium");
+
hyperglycemia patients. There is evidence that this flatter response caused by a starch
−
$("#popup-rena").css("top","800px");
+
rich meal is associated with the slower rate of digestion of complex sugars versus simple
−
});
+
sugars (Jenkins, Wolever, & Jenkins, 1988). Thus, if some of the simple sugars are first
−
$("#popup-rena").click(function(){
+
converted into complex saccharides inside the E. coli and then released back into small
−
$("#popup-rena").fadeOut("medium");
+
intestine, a similar flatter glycemic response will take place, which will be beneficial to
−
});
+
the patients. </p>
−
$("#issac-box").click(function(){
+
<h3>Our Devices</h3>
−
$("#popup-issac").fadeIn("medium");
+
<p> We have assembled one plasmid with genes that dictate a controllable level of simple sugars uptake and one plasmid to produce glucan and fructan from simple sugars and then lyse to release the complex sugars back into the environment. In essence, this microbial device runs on two genetic devices -- an uptake circuit and a polymeriztion circuit. </p>
−
$("#popup-issac").css("top","800px");
+
<p style="font-style:italic"> In order to learn more details, please visit the <a href="/Team:Virginia/Project">Project page.</a> </p>
−
});
+
<div id="ref-button">
−
$("#popup-issac").click(function(){
+
<p>Show References</p>
−
$("#popup-issac").fadeOut("medium");
+
</div>
−
});
+
<div id="ref-button2">
−
$("#sean-box").click(function(){
+
<p>Hide References</p>
−
$("#popup-sean").fadeIn("medium");
+
</div>
−
$("#popup-sean").css("top","1100px");
+
<div id="ref-content">
−
});
+
<p>A. Ceriello, S. Colagiuri, (2011). Guideline for management of postmeal glucose in
−
$("#popup-sean").click(function(){
+
diabetes. International Diabetes Federation Guideline Development Group,
−
$("#popup-sean").fadeOut("medium");
+
http://www.idf.org/sites/default/files/postmeal%20glucose%20guidelines.pdf ,
−
});
+
Accessed May. 6th, 2015
−
$("#shiran-box").click(function(){
+
</p>
−
$("#popup-shiran").fadeIn("medium");
+
<p>American Diabetes Association (2014). National Diabetes Statistics Report.
−
$("#popup-shiran").css("top","1100px");
+
http://www.cdc.gov/diabetes/pubs/statsreport14/national-diabetes-report-web.pdf
−
});
+
Accessed May. 5th, 2015
−
$("#popup-shiran").click(function(){
+
</p>
−
$("#popup-shiran").fadeOut("medium");
+
<p>Anal, A. K., & Singh, H. (2007). Recent advances in microencapsulation of probiotics for
−
});
+
industrial applications and targeted delivery. Trends in Food Science &  
−
$("#connor-box").click(function(){
+
Technology, 18(5), 240–251. http://doi.org/10.1016/j.tifs.2007.01.004
−
$("#popup-connor").fadeIn("medium");
+
</p>
−
$("#popup-connor").css("top","1100px");
+
<p>Anan, F., Masaki, T., Eto, T., Fukunaga, N., Iwao, T., Kaneda, K., ... Yoshimatsu, H.
−
});
+
(2008). Postchallenge Plasma Glucose and Glycemic Spikes Are Associated with
−
$("#popup-connor").click(function(){
+
Pulse Pressure in Patients with Impaired Glucose Tolerance and Essential
−
$("#popup-connor").fadeOut("medium");
+
Hypertension. Hypertension Research, 31(8), 1565–1571.  
−
});
+
http://doi.org/10.1291/hypres.31.1565
−
});
+
</p>
−
 
+
<p>AHFS Consumer Medication Information [Internet]. Bethesda (MD): American Society
−
</script>
+
of Health-System Pharmacists, Inc.; ©2008. Acarbose; [revised 2015 Feb. 15;
−
            <!-- OTHER STRUCTURAL CODE GOES BELOW HERE -->
+
reviewed 2015 Apr. 28; cited 2015 May. 3]; Available from:
−
            <!-- Pop-ups structural code -->
+
http://www.nlm.nih.gov/medlineplus/druginfo/meds/ a696015.html
−
            <!-- Supraja’s popup structural code-->
+
</p>
−
            <div class="popup inactive" id="popup-supraja">
+
<p>AHFS Consumer Medication Information [Internet]. Bethesda (MD): American Society
−
                <div class="text-wrap">
+
of Health-System Pharmacists, Inc.; ©2008. Pramlintide; [revised 2015 Feb. 15;
−
                    <p>(click to close)</p>
+
reviewed 2015 Apr. 28; cited 2015 May. 3]; Available from:
−
                    <img src="/wiki/images/1/10/Virginia_supraja2.jpg"></img>
+
http://www.nlm.nih.gov/medlineplus/druginfo/meds/a605031.html
−
                    <h3>Supraja Chittari</h3>
+
</p>
−
                    <h5>Poster and Presentation Coordinator & Biological Research Team Member</h5>
+
<p>Banguela, A., Arrieta, J. G., Rodríguez, R., Trujillo, L. E., Menéndez, C., & Hernández,
−
                    <h4>Class of 2018 - College of Arts & Sciences, Undeclared</h4>
+
L. (2011). High levan accumulation in transgenic tobacco plants expressing the
−
                    <p>Supraja Chittari is a rising second-year at the University of Virginia from Vienna, Virginia. Supraja can’t quite make up her mind about what she’s studying, but we know it’ll be something that’s fairly science-heavy. A dedicated member of iGEM 2015’s so-called BioSquad, she can be seen in the lab at ungodly hours of the night screaming something about failed competent cells.</p>
+
Gluconacetobacter diazotrophicus levansucrase gene. Journal of Biotechnology,  
−
                </div>
+
154(1), 93–98. http://doi.org/10.1016/j.jbiotec.2011.04.007
−
            </div>
+
</p>
−
            <!-- Dominic’s popup structural code-->
+
<p>Barr EL, Zimmet PZ, Welborn TA et al. (2007). "Risk of cardiovascular and all-cause
−
            <div class="popup inactive" id="popup-dominic">
+
mortality in individuals with diabetes mellitus, impaired fasting glucose, and  
−
                <div class="text-wrap">
+
impaired glucose tolerance: the Australian Diabetes, Obesity, and Lifestyle Study
−
                    <p>(click to close)</p>
+
(AusDiab)". Circulation 116 (2): 151–7.
−
                    <img src="/wiki/images/6/6f/Virginia_dominic2.jpg"></img>
+
</p>
−
                    <h3>Dominic Ritchey</h3>
+
<p>Bernard, A. M., Anderson, L., Cook, C. B., & Phillips, L. S. (1999). What do internal
−
                    <h5>Chief Financial Officer and Wiki Programmer</h5>
+
medicine residents need to enhance their diabetes care? Diabetes Care, 22(5),
−
                    <h4>Class of 2018 - School of Engineering and Applied Sciences, Computer Science & Biology</h4>
+
661–666. http://doi.org/10.2337/diacare.22.5.661
−
                    <p> Dominic Ritchey is a rising second-year at the University of Virginia from Columbus, Ohio. Dominic is studying Computer Science and Biology because he has no idea yet what he wants to do with his life. Dominic is the Chief Financial Officer and Wiki Programmer for team, so he has not even touched a pipette in the lab as of yet. Dominic is a dedicated member of the so-called Ca$hCrew, and he can often be found camped-out in a U.Va. library coding for hours on end. </p>
+
</p>
−
                </div>
+
<p>Boada C, Martínez-Moreno J. Pathophysiology of diabetes mellitus type 2: beyond the
−
            </div>
+
duo "insulin resistance-secretion deficit.". Nutricion Hospitalaria [serial online].
−
            <!-- Jingyuan’s popup structural code-->
+
March 2, 2013;28:78-87. Available from: Fuente Académica, Ipswich, MA.
−
            <div class="popup inactive" id="popup-jingyuan">
+
Accessed April 16, 2015.
−
                <div class="text-wrap">
+
</p>
−
                    <p>(click to close)</p>
+
<p>B. Göke, H. F. (1995). Voglibose (AO128) Is an Efficient α-Glucosidase Inhibitor and
−
                    <img src="/wiki/images/a/ac/Virginia_jingyuan2.jpg"></img>
+
Mobilizes the Endogenous GLP-1 Reserve. Digestion, 56(6), 493–501.
−
                    <h3>Jingyuan Zhang</h3>
+
http://doi.org/10.1159/000201282
−
                    <h5>Laboratory Technician & Biological Research Team Member</h5>
+
</p>
−
                    <h4>Class of 2017 - School of Engineering and Applied Sciences, Biomedical Engineering</h4>
+
<p>Brown, J. B., Harris, S. B., Webster-Bogaert, S., Wetmore, S., Faulds, C., & Stewart, M.
−
                    <p>Jingyuan Zhang is a rising third-year at the University of Virginia from Beijing, China, and she studies Biomedical Engineering. Jingyuan is a dedicated member of the BioSquad, and officially she is one of the team laboratory technicians. Jingyuan can frequently be found running hastily around the lab with multiple timers going off. </p>
+
(2002). The role of patient, physician and systemic factors in the management of
−
                </div>
+
type 2 diabetes mellitus. Family Practice, 19(4), 344–349.
−
            </div>
+
http://doi.org/10.1093/fampra/19.4.344
−
            <!-- Liam’s popup structural code-->
+
</p>
−
            <div class="popup inactive" id="popup-liam">
+
<p>Butterworth, P. J., Warren, F. J., & Ellis, P. R. (2011). Human α-amylase and starch
−
                <div class="text-wrap">
+
digestion: An interesting marriage. Starch - Stärke, 63(7), 395–405.
−
                    <p>(click to close)</p>
+
http://doi.org/10.1002/star.201000150
−
                    <img src="/wiki/images/1/1e/Virginia_liam2.jpg"></img>
+
</p>
−
                    <h3>Liam Wolf</h3>
+
<p>Centers for Disease Control and Prevention. (2014). National Diabetes Statistics Report.</p>
−
                    <h5>Administrator, Policy and Practices, & Finance Team Member</h5>
+
<p>Chiasson, J.-L., Josse, R. G., Gomis, R., Hanefeld, M., Karasik, A., & Laakso, M. (2002).
−
                    <h4>Class of 2018 - School of Engineering and Applied Sciences, Systems Engineering</h4>
+
Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM
−
                    <p>Liam Wolf is a rising second-year at the University of Virginia from Pittsburgh, Pennsylvania. Liam is studying Systems Engineering, even though no one really knows what that is. Liam is involved in just about everything the team does, whether he is asked or not, and the team lovingly (and mostly jokingly) refers to him as the Overlord. Officially, Liam is the team Administrator, though he is also involved in every other part of the project. Liam claims that, one day, all 9 team members will get together for a team-building activity, but no one really believes it. </p>
+
randomised trial. The Lancet, 359(9323), 2072–2077.  
−
                </div>
+
http://doi.org/10.1016/S0140-6736(02)08905-5
−
            </div>
+
</p>
−
            <!-- Rena’s popup structural code-->
+
<p>Chiasson, J.-L., Josse, R. G., Hunt, J. A., Palmason, C., Rodger, N. W., Ross, S. A., ...
−
            <div class="popup inactive" id="popup-rena">
+
Wolever*, T. M. S. (1994). The Efficacy of Acarbose in the Treatment of Patients
−
                <div class="text-wrap">
+
with Non–Insulin-Dependent Diabetes Mellitus: A Multicenter, Controlled
−
                    <p>(click to close)</p>
+
Clinical Trial. Annals of Internal Medicine, 121(12), 928–935.
−
                    <img src="/wiki/images/9/9d/Virginia_rena2.jpg"></img>
+
http://doi.org/10.7326/0003-4819-121-12-199412150-00004
−
                    <h3>Rena Yuan</h3>
+
Crude and Age-Adjusted Rate per 100 of Civilian, Noninstitutionalized Population with
−
                    <h5>Policy & Practices and Biology Research Team Member</h5>
+
Diagnosed Diabetes, United States, 1980–2011. (2014, September 5). Retrieved
−
                    <h4>Class of 2018 - College of Arts and Sciences, Biology and Statistics</h4>
+
April 24, 2015, from
−
                    <p> Rena Yuan is a rising second-year at the University of Virginia studying biology and statistics. Rena is originally from Long Island, New York, but is now a NOVA (Northern Virginia) transplant. Rena is a dedicated member of the so-called BioSquad and though she works full-time in another position, she can frequently be seen coming into the lab at 4:00 am in order to get some of her work done, even when she knows that she’s not expected to do so.</p>
+
http://www.cdc.gov/diabetes/statistics/prev/national/figage.htm
−
                </div>
+
</p>
−
            </div>
+
<p>Dedonder, R. 1966. Levansucrase from Bacillus subtilis. Methods Enzymol. 8:500–505.</p>
−
            <!-- Issac’s popup structural code-->
+
<p>Deshpande, A. D., Harris-Hayes, M., & Schootman, M. (2008). Epidemiology of diabetes
−
            <div class="popup inactive" id="popup-issac">
+
and diabetes-related complications. Physical therapy, 88(11), 1254-1264.
−
                <div class="text-wrap">
+
</p>
−
                    <p>(click to close)</p>
+
<p>D.M. Nathan, P.A. Cleary, J.Y. Backlund, S.M. Genuth, J.M. Lachin, T.J. Orchard, et al.,
−
                    <img src="/wiki/images/3/38/Virginia_issac2.jpg"></img>
+
Intensive diabetes treatment and cardiovascular disease in patients with type 1
−
                    <h3>Issac Li</h3>
+
diabetes, N Engl J Med, 353 (2005), pp. 2643–2653
−
                    <h5>Head of Modelling, Policy & Practices Team Member and Biology Research Team Member</h5>
+
</p>
−
                    <h4>Class of 2016 - School of Engineering and Applied Sciences, Biomedical Engineering</h4>
+
<p>D.R. Whiting, L. Guariguata, C. Weil, J. Shaw, IDF diabetes atlas: global estimates of the  
−
                    <p> Issac Li is a rising fourth-year at the University of Virginia studying Biomedical Engineering from Shijiazhuang, China. Issac is the official Head of Modeling for the 2015 team. Issac is a de facto addition to the BioSquad and also aids in Policy and Practices. </p>
+
prevalence of diabetes for 2011 and 2030 Diabetes Res Clin Pract, 94 (2011), pp.  
−
                </div>
+
311–321
−
            </div>
+
</p>
−
            <!-- Sean’s popup structural code-->
+
<p>Duncan, A. E. (2012). Hyperglycemia and Perioperative Glucose Management.Current
−
            <div class="popup inactive" id="popup-sean">
+
Pharmaceutical Design, 18(38), 6195–6203.
−
                <div class="text-wrap">
+
</p>
−
                    <p>(click to close)</p>
+
<p>Edelman, P. S., Maier, H., & Wilhelm, K. (2012). Pramlintide in the Treatment of
−
                    <img src="/wiki/images/a/ad/Virginia_sean2.jpg"></img>
+
Diabetes Mellitus. BioDrugs, 22(6), 375–386. http://doi.org/10.2165/0063030-
−
                    <h3>Sean Sequeira</h3>
+
200822060-00004
−
                    <h5>Modelling Team Member, Policy and Practices Team Member, and Finance Team Member</h5>
+
</p>
−
                    <h4>Class of 2018 - School of Engineering and Applied Sciences, Biomedical Engineering</h4>
+
<p>Ferraris, R. P., Yasharpour, S. A. S. A. N., Lloyd, K. C., Mirzayan, R. A. F. F. Y., &
−
                    <p> Sean Sequeira is a rising second-year at the University of Virginia, from Richmond, Virginia. Sean is studying Biomedical Engineering and is a member of the BioSquad, the Ca$hCrew, and helps out in Policy and Practices. Sean can frequently either be found “working” in the second floor conference room with Connor or at his other lab. </p>
+
Diamond, J. M. (1990). Luminal glucose concentrations in the gut under normal
−
                </div>
+
conditions. American Journal of Physiology-Gastrointestinal and Liver
−
            </div>
+
Physiology, 259(5), G822-G837.
−
            <!-- Shiran’s popup structural code-->
+
</p>
−
            <div class="popup inactive" id="popup-shiran">
+
<p>Gay, P., Le Coq, D., Steinmetz, M., Ferrari, E., & Hoch, J. A. (1983). Cloning structural
−
                <div class="text-wrap">
+
gene sacB, which codes for exoenzyme levansucrase of Bacillus subtilis:
−
                    <p>(click to close)</p>
+
expression of the gene in Escherichia coli. Journal of bacteriology,153(3), 1424-
−
                    <img src="/wiki/images/0/0f/Virginia_shiran2.jpg"></img>
+
1431.
−
                    <h3>Shiran Su</h3>
+
</p>
−
                    <h5>Laboratory Technician and Biological Research Team Member</h5>
+
<p>Gray, G. M., & Ingelfinger, F. J. (1966). Intestinal absorption of sucrose in man:
−
                    <h4>Class of 2016 - School of Engineering and Applied Sciences, Biomedical Engineering</h4>
+
interrelation of hydrolysis and monosaccharide product absorption. Journal of
−
                    <p>Shiran Su is a rising fourth-year at the University of Virginia from Nanjing, China. Shiran is finishing up her degree in Biomedical Engineering this year. Shiran is a dedicated member of the so-called BioSquad. Without fail, one can either find Shiran somewhere in the building taking a quick daytime nap on a bench or lecturing another engineering teammate about the ease of the U.Va. engineering curriculum, especially after s/he has been complaining about a difficult class.</p>
+
Clinical Investigation, 45(3), 388.
−
                </div>
+
</p>
−
            </div>
+
<p>Grant, R. W., Buse, J. B., & Meigs, J. B. (2005). Quality of Diabetes Care in U.S.
−
            <!-- Connor’s popup structural code-->
+
Academic Medical Centers Low rates of medical regimen change. Diabetes Care,  
−
            <div class="popup inactive" id="popup-connor">
+
28(2), 337–442. http://doi.org/10.2337/diacare.28.2.337
−
                <div class="text-wrap">
+
</p>
−
                    <p>(click to close)</p>
+
<p>Grant, R. W., Pirraglia, P. A., Meigs, J. B., & Singer, D. E. (2004). Trends in complexity
−
                    <img src="/wiki/images/f/f3/Virginia_connor2.jpg"></img>
+
of diabetes care in the United States from 1991 to 2000. Archives of Internal
−
                    <h3>Connor Jahelka</h3>
+
Medicine, 164(10), 1134–1139. http://doi.org/10.1001/archinte.164.10.1134
−
                    <h5>Head of Policy & Practices</h5>
+
</p>
−
                    <h4>Class of 2017 - College of Arts and Sciences, Biology </h4>
+
<p>Halschou, K., Bukhave, K., & Rikardt, J. (2012). Intestinal Disaccharidase Activity and
−
                    <p> Connor Jahelka is a rising third-year at the University of Virginia from Fairfax, Virginia. Connor is studying biology and splits his time between a neuroscience lab and iGEM during the summer. Connor is the Head of Policy and Practices for this year’s team. Connor has a notoriously faulty alarm clock, on which he blames his persistent lateness, and he works most effectively when given very detailed, itemized to-do lists and constant negative reinforcement, mostly provided by Liam.</p>
+
Uptake of Glucose from Sucrose. In S. Chackrewarthy (Ed.), Glucose Tolerance.
−
                </div>
+
InTech. Retrieved from http://www.intechopen.com/books/glucose-
−
            </div>
+
tolerance/intestinal-disaccharidase-activity-and-uptake-of-glucose-from-sucrose
−
            <!-- END Pop-ups structural code -->
+
</p>
−
            <div class="wrapper1">
+
<p>Hanahan, D. (1983). Studies on transformation of Escherichia coli with plasmids. Journal
−
                <div class="team_profile_link">
+
of Molecular Biology, 166(4), 557–580.
−
                    <a href="https://igem.org/Team.cgi" >
+
</p>
−
                        <div>
+
<p>Hoffmann, J., & Spengler, M. (1997). Efficacy of 24-Week Monotherapy With Acarbose,
−
                            <img src="/wiki/images/1/10/Virginia_igem_logo.jpg"></img>
+
Metformin, or Placebo in Dietary-Treated NIDDM Patients: The Essen-II Study.
−
                        </div>
+
The American Journal of Medicine, 103(6), 483–490.
−
                        <div>
+
http://doi.org/10.1016/S0002-9343(97)00252-0
−
                            <p>Official iGEM Team Profile</p>
+
Intensive blood-glucose control with sulphonylureas or insulin compared with
−
                        </div>
+
conventional treatment and risk of complications in patients with type 2 diabetes
−
                    </a>
+
(UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group.
−
                </div>
+
</p>
−
                <div class="team_profile_link">
+
<p>Jenkins, D. J. A., Wolever, T. M. S., & Jenkins, A. L. (1988). Starchy Foods and  
−
                    <a href="http://seas.virginia.edu/students/igem/" >
+
Glycemic Index. Diabetes Care, 11(2), 149–159.
−
                        <div>
+
http://doi.org/10.2337/diacare.11.2.149
−
                            <img src="/wiki/images/a/a7/Virginia_rotunda.png"></img>
+
</p>
−
                        </div>
+
<p>Jones, M. C. (2007). Therapies for diabetes: pramlintide and exenatide. American Family
−
                        <div>
+
Physician, 75(12), 1831–1835.
−
                            <p>Official U.Va. iGEM Website</p>
+
</p>
−
                        </div>
+
<p>J Reizer, S. L. S. (1992). Functional interactions between proteins of the  
−
                    </a>
+
phosphoenolpyruvate:sugar phosphotransferase systems of Bacillus subtilis and
−
                </div>
+
Escherichia coli. The Journal of Biological Chemistry, 267(13), 9158–69.
−
            </div>
+
Jenkins, D. J., Wolever, T. M., & Jenkins, A. L. (1988). Starchy foods and glycemic
−
            <h1>University of Virginia 2015 iGEM Team Members</h1>
+
index. Diabetes care, 11(2), 149-159.
−
            <p id="parenth">(click an image to learn more about any team member)</p>
+
</p>
−
            <!-- BEGIN Team photos structural code -->
+
<p>Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Cotran, Ramzi S. ; Robbins, Stanley L.
−
            <div id="team-info">
+
(2005). Robbins and Cotran Pathologic Basis of Disease (7th ed.). Philadelphia,
−
                <div class="container">
+
Pa.: Saunders. pp. 1194–1195. ISBN 0-7216-0187-1. Lancet. 1998 Sep 12;
−
                    <!--Supraja Chittari-->
+
352(9131):837-53.
−
                    <div class="team-box" id="supraja-box">
+
</p>
−
                        <img src="/wiki/images/0/06/Virginia_supraja.jpg">
+
<p>Kundig, W., Ghosh, S., & Roseman, S. (1964). PHOSPHATE BOUND TO HISTIDINE
−
                            <p>Supraja Chittari</p>
+
IN A PROTEIN AS AN INTERMEDIATE IN A NOVEL PHOSPHO-
−
                        </img>
+
TRANSFERASE SYSTEM. Proceedings of the National Academy of Sciences of
−
                    </div>
+
the United States of America, 52, 1067–1074.
−
                    <!--Dominic Ritchey-->
+
</p>
−
                    <div class="team-box" id="dominic-box">
+
<p>Lebovitz, H. E. (1997). ALPHA-GLUCOSIDASE INHIBITORS. Endocrinology and
−
                        <img src="/wiki/images/a/af/Virginia_dominic.jpg">
+
Metabolism Clinics of North America, 26(3), 539–551.
−
                            <p>Dominic Ritchey</p>
+
http://doi.org/10.1016/S0889-8529(05)70266-8
−
                        </img>
+
</p>
−
                    </div>
+
<p>Lourens-Hattingh, A., & Viljoen, B. C. (2001). Yogurt as probiotic carrier food.
−
                    <!-- Jingyuan Zhang -->
+
International Dairy Journal, 11(1–2), 1–17. http://doi.org/10.1016/S0958-
−
                    <div class="team-box" id="jingyuan-box">
+
6946(01)00036-X
−
                        <img src="/wiki/images/3/37/Virginia_jingyuan.jpg">
+
</p>
−
                            <p>Jingyuan Zhang</p>
+
<p>Malagelada, J. R., Bazzoli, F., Elewaut, A., Fried, M., Krabshuis, J. H., Lindberg, G., ...
−
                        </img>
+
Vakil, N. (2007). World Gastroenterology Organisation Practice Guidelines.
−
                    </div>
+
Dysphagia. Retrieved from http://almacen-
−
                    <!-- Liam Wolf -->
+
gpc.dynalias.org/publico/Dysphagia%20WGO%202004%20Ingles.pdf
−
                    <div class="team-box" id="liam-box">
+
</p>
−
                        <img src="/wiki/images/e/ef/Virginia_liam.jpg">
+
<p>Man, C. D., Camilleri, M., & Cobelli, C. (2006). A System Model of Oral Glucose
−
                            <p>Liam Wolf</p>
+
Absorption: Validation on Gold Standard Data. IEEE Transactions on Biomedical  
−
                        </img>
+
Engineering, 53(12), 2472–2478. http://doi.org/10.1109/TBME.2006.883792
−
                    </div>
+
</p>
−
                    <!-- Rena Yuan -->
+
<p>Meigs, J. B., Nathan, D. M., Wilson, P. W., Cupples, L. A., & Singer, D. E. (1998).
−
                    <div class="team-box" id="rena-box">
+
Metabolic risk factors worsen continuously across the spectrum of nondiabetic
−
                        <img src="/wiki/images/b/bd/Virginia_rena.jpg">
+
glucose tolerance. The Framingham Offspring Study. Annals of Internal Medicine,  
−
                            <p>Rena Yuan</p>
+
128(7), 524–533.
−
                        </img>
+
</p>
−
                    </div>
+
<p>Narimasa, S., Tatsuo, H., Mitsutaka, Y., & Toshio, I. (1979). Action of human pancreatic
−
                    <!-- Issac Li -->
+
and salivary α-amylases on maltooligosaccharides: Evaluation of kinetic
−
                    <div class="team-box" id="issac-box">
+
parameters. Clinica Chimica Acta, 97(2–3), 253–260.
−
                        <img src="/wiki/images/3/3b/Virginia_issac.jpg">
+
http://doi.org/10.1016/0009-8981(79)90423-6
−
                            <p>Issac Li</p>
+
</p>
−
                        </img>
+
<p>National Diabetes Data Group. (1979). Classification and Diagnosis of Diabetes Mellitus
−
                    </div>
+
and Other Categories of Glucose Intolerance. Diabetes, 28(12), 1039–1057.
−
                    <!-- Sean Sequeira -->
+
http://doi.org/10.2337/diab.28.12.1039
−
                    <div class="team-box" id="sean-box">
+
</p>
−
                        <img src="/wiki/images/8/8e/Virginia_sean.jpg">
+
<p>Nissle, A. (1959). [Explanations of the significance of colonic dysbacteria & the
−
                            <p>Sean Sequeira</p>
+
mechanism of action of E. coli therapy (mutaflor)]. Die Medizinische, 4(21),
−
                        </img>
+
1017–1022.
−
                    </div>
+
</p>
−
                    <!-- Shiran Su -->
+
<p>Parkin, C. G., & Brooks, N. (2002). Is postprandial glucose control important? Is it
−
                    <div class="team-box" id="shiran-box">
+
practical in primary care settings?. Clinical Diabetes, 20(2), 71-76.
−
                        <img src="/wiki/images/8/8b/Virginia_shiran.jpg">
+
</p>
−
                            <p>Shiran Su</p>
+
<p>Patterson, Joan (2013). Many Schools Cutting Back on Physical Education. Las Vegas
−
                        </img>
+
Review - Journal.
−
                    </div>
+
Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S.
−
                    <!-- Connor Jahelka -->
+
adults. The Third National Health and Nutrition Examination Survey, 1988-1994.
−
                    <div class="team-box" id="connor-box">
+
</p>
−
                        <img src="/wiki/images/0/03/Virginia_connor.jpg">
+
<p>Peng, C.-K., Buldyrev, S. V., Havlin, S., Simons, M., Stanley, H. E., & Goldberger, A. L.
−
                            <p>Connor Jahelka</p>
+
(1994). Mosaic organization of DNA nucleotides. Physical Review E, 49(2),  
−
                        </img>
+
1685–1689. http://doi.org/10.1103/PhysRevE.49.1685
−
                    </div>
+
</p>
−
                </div>
+
<p>Rathmann, W., & Giani, G. (2004). Global Prevalence of Diabetes: Estimates for the
−
            </div>
+
Year 2000 and Projections for 2030: Response to Wild et al. Diabetes Care, 2568-
−
            <!-- SPECIFIC STRUCTURAL CODE ENDS HERE -->
+
2569.  
−
            <footer>
+
</p>
−
                <div id="foot-img">
+
<p>Recorbet, G. H. I. S. L. A. I. N. E., Robert, C., Givaudan, A., Kudla, B., Normand, P., &
−
                    <img src="https://static.igem.org/mediawiki/2015/d/d1/Virginia_logo4.png"></img>
+
Faurie, G. (1993). Conditional suicide system of Escherichia coli released into
−
                </div>
+
soil that uses the Bacillus subtilis sacB gene. Applied and environmental
−
                <div id="foot-text">
+
microbiology, 59(5), 1361-1366.
−
                    <p>University of Virginia iGEM</p>
+
</p>
−
                    <p>148 Gilmer Hall</p>
+
<p>Ried, J. L., and A. Collmer. 1987. An nptI-sacB-sacR cartridge for constructing directed,
−
                    <p>485 McCormick Road</p>
+
unmarked mutations in Gram-negative bacteria by marker exchange-eviction
−
                    <p>Charlottesville, Virginia 22904</p>
+
mutagenesis. Gene 57:239–246.
−
                    <p>United States of America</p>
+
</p>
−
                    <p>
+
<p>Riddle, M., Frias, J., Zhang, B., Maier, H., Brown, C., Lutz, K., & Kolterman, O. (2007).
−
                        <a href="mailto:virginia.igem@gmail.com">
+
Pramlintide Improved Glycemic Control and Reduced Weight in Patients With
 +
Type 2 Diabetes Using Basal Insulin. Diabetes Care, 30(11), 2794–2799.
 +
http://doi.org/10.2337/dc07-0589
 +
</p>
 +
<p>Saydah, S. H., Miret, M., Sung, J., Varas, C., Gause, D., & Brancati, F. L. (2001).
 +
Postchallenge Hyperglycemia and Mortality in a National Sample of U.S. Adults.
 +
Diabetes Care, 24(8), 1397–1402. http://doi.org/10.2337/diacare.24.8.1397
 +
</p>
 +
<p>Snelling, Anatasia; Korba, Casey; Burkey, Alyvia (2007). The National School Lunch
 +
and Competitive Food Offerings and Purchasing Behaviors of High School
 +
Students, 77(10), 701-705.
 +
</p>
 +
<p>Sonnenborn, Ulrich; Schulze, Jurgen. 2009. The Non-Pathogenic Escherichia coli strain
 +
Nissle 1917 - Features of a Versatile Probiotic. Microbial Ecology in Health and
 +
Disease, (21), 122-158.
 +
</p>
 +
<p>S.M. Haffner, S. Lehto, T. Ronnemaa, K. Pyorala, M. Laakso, Mortality from coronary
 +
heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and
 +
without prior myocardial infarction, N Engl J Med, 339 (1998), pp. 229–234
 +
</p>
 +
<p>Schultz, M. (2008). Clinical use of E. coli Nissle 1917 in inflammatory bowel disease.
 +
Inflammatory Bowel Diseases, 14(7), 1012–1018.
 +
http://doi.org/10.1002/ibd.20377
 +
</p>
 +
<p>Seifter, S., & Dayton, S. (1950). The estimation of glycogen with the anthrone reagent.
 +
Archives of Biochemistry, 25(1), 191–200.
 +
</p>
 +
<p>Shulman, N. B., Martinez, B., Brogan, D., Carr, A. A., & Miles, C. G. (1986). Financial
 +
cost as an obstacle to hypertension therapy. American Journal of Public Health,
 +
76(9), 1105–1108.
 +
</p>
 +
<p>Suwattee, P., Lynch, J. C., & Pendergrass, M. L. (2003). Quality of Care for Diabetic
 +
Patients in a Large Urban Public Hospital. Diabetes Care, 26(3), 563–568.
 +
http://doi.org/10.2337/diacare.26.3.563
 +
</p>
 +
<p>Temelkova-Kurktschiev, T. S., Koehler, C., Henkel, E., Leonhardt, W., Fuecker, K., &
 +
Hanefeld, M. (2000). Postchallenge plasma glucose and glycemic spikes are more
 +
strongly associated with atherosclerosis than fasting glucose or HbA1c level.
 +
</p>
 +
<p>Diabetes Care, 23(12), 1830–1834. http://doi.org/10.2337/diacare.23.12.1830
 +
What are normal blood glucose levels? Retrieved from Virginia Mason Medical Center
 +
website: https://www.virginiamason.org/whatarenormalbloodglucoselevels.
 +
Accessed: May. 5th ,2015
 +
</p>
 +
</div>
 +
</div>
 +
</div>
 +
<script type="text/javascript">
 +
jQuery(document).ready(function(){
 +
$("#ref-button").click(function(){
 +
$("#ref-button").fadeOut("fast");
 +
$("#ref-content").fadeIn("fast");
 +
$("#ref-button2").fadeIn("fast");
 +
});
 +
$("#ref-button2").click(function(){
 +
$("#ref-button2").fadeOut("fast");
 +
$("#ref-content").fadeOut("fast");
 +
$("#ref-button").fadeIn("fast");
 +
});
 +
});
 +
</script>
 +
<div class="learn-more">
 +
<div class="container">
 +
<div class="box" id="b1">
 +
<a href="/Team:Virginia/Team">
 +
<p>TEAM</p>
 +
<img src="/wiki/images/d/d1/Virginia_logo4.png"></img>
 +
</a>
 +
</div>
 +
<div class="box" id="b2">
 +
<a href="/Team:Virginia/Project">
 +
<p>PROJECT</p>
 +
<img src="/wiki/images/d/d1/Virginia_logo4.png"></img>
 +
</a>
 +
</div>
 +
<div class="box" id="b3">
 +
<a href="/Team:Virginia/Practices">
 +
<p>POLICY AND PRACTICES</p>
 +
<img src="/wiki/images/d/d1/Virginia_logo4.png"></img>
 +
</a>
 +
</div>
 +
<div class="box" id="b4">
 +
<a href="/Team:Virginia/Attributions">
 +
<p>ATTRIBUTIONS</p>
 +
<img src="/wiki/images/d/d1/Virginia_logo4.png"></img>
 +
</a>
 +
</div>
 +
<div class="box" id="b5">
 +
<a href="/Team:Virginia/Attributions">
 +
<p>CONTACT US</p>
 +
<img src="/wiki/images/d/d1/Virginia_logo4.png"></img>
 +
</a>
 +
</div>
 +
<div class="box" id="b6">
 +
<a href="#">
 +
<p>ABOUT</p>
 +
</a>
 +
</div>
 +
</div>
 +
</div>
 +
</div>
 +
</div>
 +
<footer>
 +
<div id="foot-img">
 +
<img src="https://static.igem.org/mediawiki/2015/d/d1/Virginia_logo4.png"></img>
 +
</div>
 +
<div id="foot-text">
 +
<p>University of Virginia iGEM</p>
 +
<p>148 Gilmer Hall</p>
 +
<p>485 McCormick Road</p>
 +
<p>Charlottesville, Virginia 22904</p>
 +
<p>United States of America</p>
 +
<p></p>
 +
<p><a href="mailto:virginia.igem@gmail.com">
 
virginia.igem@gmail.com</a>
 
virginia.igem@gmail.com</a>
−
                    </p>
+
</p>
−
                </div>
+
</div>
−
            </footer>
+
</footer>
−
            <style type="text/css">
+
</div>
 +
<style type="text/css">
 +
#description-wrapper{
 +
width:100%;
 +
height:auto;
 +
padding: 50px;
 +
padding-bottom:200px;
 +
background:#000000;
 +
border-bottom: 3px dotted #fff;
 +
}
 +
#description-text-wrapper {
 +
width:85%;
 +
margin-left:7.5%;
 +
height:auto;
 +
}
 +
#description-wrapper p {
 +
font-size: 18px;
 +
font-family:Arial;
 +
color:#fff;
 +
}
 +
#description-text-wrapper p:last-child {
 +
font-style:italic;
 +
}
 +
#description-wrapper h1 {
 +
font-size: 26px;
 +
font-family:Arial;
 +
color:#fff;
 +
font-weight:bold;
 +
}
 
footer div img {
 
footer div img {
 
width:auto;
 
width:auto;
Line 330: Line 464:
 
}
 
}
 
footer div:first-child {  
 
footer div:first-child {  
−
background-image:url(‘https://encrypted-tbn3.gstatic.com/images?q=tbn:ANd9GcQUA5CF2C_kOVnWjyl62TA17VNs6RSsPIkrCejlLbtZ7rAVgzQxOQ’);
 
 
float:right;
 
float:right;
 
top:10px;
 
top:10px;
Line 338: Line 471:
 
display:inline;
 
display:inline;
 
overflow:hidden;
 
overflow:hidden;
 +
}
 +
.jumbotron {
 +
height: auto;
 +
background-size: 100%;
 +
background-image: url("https://static.igem.org/mediawiki/2015/b/b8/Virginia_cells.jpg");
 +
padding:60px;
 +
margin:0px 0px 0px 0px;
 +
color:white;
 +
opacity:0.9;
 +
}
 +
.jumbotron h2 {
 +
text-align:center;
 +
color:#ffffff;
 +
font-size:70px;
 +
font-weight:bold;
 +
padding-bottom:30px;
 +
margin-bottom:0px;
 +
width:50%;
 +
opacity:1;
 +
margin-left:25%;
 +
background-color:#007bb6;
 +
border-radius:30px;
 +
text-shadow:2px 2px 2px black;
 +
box-shadow: 5px 5px 10px #191919;
 +
}
 +
.jumbotron h1 {
 +
color: #fff;
 +
opacity:1;
 +
font-size: 48px; 
 +
font-weight: bold;
 +
text-align:center;
 +
padding-bottom:20px;
 +
}
 +
.learn-more {
 +
width:100%;
 +
background-color:#000000;
 +
text-align:center;
 +
}
 +
.learn-more .container .row {
 +
padding-bottom: 20px;
 +
padding-top:30px;
 +
}
 +
.learn-more h3 {
 +
font-family: 'Shift', sans-serif;
 +
font-size: 18px;
 +
font-weight: bold;
 +
text-align:center;
 +
}
 +
.learn-more a {
 +
color:#007bb6;
 +
}
 +
.learn-more img {
 +
width: 90%;
 +
height: auto;
 +
border-radius:20%;
 +
box-shadow: 5px 5px 2px #888888;
 
}
 
}
 
.nav {
 
.nav {
Line 377: Line 566:
 
.row {
 
.row {
 
width:100%;
 
width:100%;
−
}
 
−
h1 {
 
−
text-align:center;
 
−
color:white;
 
−
font-size:40px;
 
−
font-family:Arial;
 
−
padding-top:20px;
 
−
padding-bottom:20px;
 
−
font-weight:bold;
 
 
}
 
}
 
#content h1.firstHeading {
 
#content h1.firstHeading {
Line 424: Line 604:
 
background:#000000;
 
background:#000000;
 
clear:both;
 
clear:both;
−
border-top:5px solid #007bb6;
 
 
}
 
}
 
footer p:first-child {
 
footer p:first-child {
Line 434: Line 613:
 
footer a {
 
footer a {
 
color:#fff;
 
color:#fff;
−
text-decoration:underline;
 
 
}
 
}
 
footer p {
 
footer p {
 
width:auto;
 
width:auto;
−
font-size:10px;
 
 
}
 
}
 
p {  
 
p {  
Line 494: Line 671:
 
padding-top:15px;
 
padding-top:15px;
 
}
 
}
−
/* OTHER STYLE CODE GOES BELOW HERE */
+
.box{
−
.team-box{
+
width:60%;
−
width:30%;
+
height:100px;
−
height:400px;
+
 
display:inline-block;
 
display:inline-block;
−
margin-left:1.5%;
+
margin-left:20%;
 
margin-top:25px;
 
margin-top:25px;
 
margin-bottom:10px;
 
margin-bottom:10px;
Line 506: Line 682:
 
overflow:hidden;
 
overflow:hidden;
 
background-color:#003F87;
 
background-color:#003F87;
 +
float:left;
 
}
 
}
−
.team-box:hover{
+
.box:hover{
 
box-shadow: 5px 5px 10px #555555;
 
box-shadow: 5px 5px 10px #555555;
 
}
 
}
−
.team-box img {
+
.box img {
−
width:100%;
+
margin:50px;
 +
width:70%;
 
height:auto;
 
height:auto;
−
border-bottom: 5px solid #007bb6;
+
margin-left:15%;
 +
display:none;
 +
border-radius:10px;
 +
box-shadow:none;
 +
drop-shadow:none;
 
}
 
}
−
.team-box p {
+
.box p {
 
font-family:Arial;
 
font-family:Arial;
−
font-size:26px;
+
font-size:30px;
 
font-weight:bold;
 
font-weight:bold;
−
padding-top:10px;
+
padding-top:25px;
−
padding-bottom:10px;
+
 
text-align:center;
 
text-align:center;
 
}
 
}
−
/* Pop-ups style code */
 
 
.popup {
 
.popup {
−
width:80%;
+
background:#000000;
 +
width:60%;
 +
position:fixed;
 +
top:200px;
 +
margin-left:20%;
 
height:auto;
 
height:auto;
−
background-color:#191919;
+
border-radius:15px;
−
border-radius:30px;
+
border:5px solid #007bb6;
−
position:absolute;
+
box-shadow: 5px 5px 10px #191919;
−
top:500px;
+
−
left:10%;
+
−
z-index:5;
+
−
border: 10px solid #007bb6;
+
−
box-shadow: 10px 10px 20px black;
+
 
}
 
}
−
.text-wrap {
+
.popup h1 {
−
padding:20px 20px 20px 20px;
+
font-size:50px;
−
}
+
−
.text-wrap h3 {
+
−
text-align:center;
+
 
font-weight:bold;
 
font-weight:bold;
−
text-shadow:2px 2px 1px #007bb6;
+
width:90%;
−
color:white;
+
margin-left:5%;
−
margin-bottom:30px;
+
−
font-size:30px;
+
−
}
+
−
.text-wrap h5{
+
−
margin-bottom:10px;
+
−
font-weight:bold;
+
−
font-size:25px;
+
 
text-align:center;
 
text-align:center;
−
font-weight:bold;
+
font-family:Arial;
−
color:white;
+
color:#fff;
 +
padding:30px;
 +
background:#F59A2C;
 +
text-shadow: 2px 2px 4px #000000;
 +
border: none;
 +
border-radius:20px;
 
}
 
}
−
.text-wrap h4 {
+
.popup p{
−
text-align:center;
+
font-size:17px;
−
font-weight:bold;
+
 
color:#fff;
 
color:#fff;
−
padding-bottom:25px;
+
padding:10px;
 +
text-align:center;
 +
font-family:Arial;
 
}
 
}
−
.text-wrap img {
+
.popup p:last-child {
−
width:30%;
+
font-size:10px;
−
margin-left:35%;
+
color:#fff;
 +
width:80%;
 +
margin-left:10%;
 
height:auto;
 
height:auto;
−
border-radius:15px;
+
text-align:center;
−
border: 5px solid #fff;
+
 
}
 
}
−
.active {
+
.jumbotron p {
−
display:block;
+
font-family:Arial;
−
}
+
font-size:26px;
−
.inactive {
+
padding:5%;
−
display:none;
+
 
}
 
}
−
.team_profile_link{
+
#ref-button, #ref-button2 {
−
width:30%;
+
width:25%;
−
margin-left:15%;
+
padding:10px;
−
background-color:#007bb6;
+
−
border: 3px solid #fff;
+
−
border-radius: 10px;
+
−
            margin-top:25px;
+
−
    padding: 5px 5px 5px 5px;
+
−
display:inline-block;
+
−
}
+
−
.team_profile_link div {
+
−
display: inline;
+
−
}
+
−
.team_profile_link:hover {
+
−
background-color:#0276FD;
+
−
}
+
−
.team_profile_link img {
+
−
width:40%;
+
−
margin-left:30%;
+
 
height:auto;
 
height:auto;
−
border-radius:50%;
+
float:right;
−
border:3px solid #63D1F4;
+
border-radius:10px;
−
background:white;
+
margin-right:15%;
 +
background:#007bb6;
 +
border:5px solid white;
 +
margin-top:30px;
 +
margin-bottom:30px;
 
}
 
}
−
.team_profile_link p {
+
#ref-button a, #ref-button2 a {
−
font-family: Arial;
+
width:100%;
−
font-weight:bold;
+
height:100%;
−
font-size: 18px;
+
}
 +
#ref-button p, #ref-button2 p {
 +
font-size:20px;
 +
color:#fff;
 +
font-family:Arial;
 
text-align:center;
 
text-align:center;
 
}
 
}
−
.wrapper1 div:last-child{
+
#ref-button2{
−
margin-left:10%;
+
display:none;
 +
float:left;
 +
margin-left:15%;
 
}
 
}
−
#parenth{
+
.active {
−
font-size:12px;
+
//display:block;
−
text-align:center;
+
−
font-family:Arial;
+
 
}
 
}
−
            .text-wrap p{
+
#ref-content{
−
            font-size:20px;
+
display:none;
−
            font-family:Arial;
+
−
width:70%;
+
−
margin-left:15%;
+
−
border-top: 1px dotted white;
+
−
padding-top: 15px;
+
−
color:#87CEFA;
+
−
            }
+
−
.text-wrap p:first-child{
+
−
width:95%;
+
−
color:white;
+
−
margin-left:2.5%;
+
−
font-size:16px;
+
 
}
 
}
−
/* SPECIFIC STYLE CODE ENDS HERE */
 
 
</style>
 
</style>
−
        </body>
+
<script type="text/javascript">
−
    </html>
+
jQuery(document).ready(function(){
 +
$(".popup").css("z-index","11");
 +
$(".back").css("opacity",".3");
 +
$("#top_menu_14").css("opacity",".3");
 +
$(".popup").css("opacity","1");
 +
$(".popup").click(function(){
 +
$(".popup").fadeOut("slow");
 +
$("*").css("opacity","1");
 +
});
 +
$(".box").mouseenter(function(){
 +
$(this).css("width","80%");
 +
$(this).css("margin-left","10%");
 +
$("img", this).css("display","block");
 +
$(this).css("height","auto");
 +
});
 +
$(".box").mouseleave(function(){
 +
$(this).css("width","60%");
 +
$(this).css("margin-left","20%");
 +
$(this).css("height","100px");
 +
$("img", this).css("display","none");
 +
});
 +
});
 +
</script>
 +
</body>
 +
</html>

Revision as of 17:09, 14 July 2015

Welcome to the University of Virginia iGEM 2015 Wiki

Use the navigation bar at the top of every page to move between pages. Please let us know if you have any comments or questions about our project by visiting the “Contact Us” page.

(click to close)

University of Virginia iGEM 2015

House of Carbs

A Novel Solution to Minimizing Postprandial Hyperglycemic Spikes

Project Overview

The Problem: Diabetes Mellitus and Hyperglycemia

< p >From diabetes mellitus a number of devastating complications, such as amputations, blindness, crippling neuropathies, and many others, can arise from increased blood sugar levels on a regular basis, but many of the major complications of diabetes arise from drastic fluctuations in the blood glucose level (Ceriello et al., 2012). Up to two-thirds of people with diabetes die of cardiovascular disease (CVD) brought about by diabetes-related macrovascular diseases (Deshpande et al. 2008). In fact, the risk for cardiovascular disease mortality is 2 to 4 times higher in people with diabetes than in people who do not have diabetes. Additionally, diabetic retinopathy is the most common microvascular complication among people with diabetes and results in more than 10,000 new cases of blindness per year. Retinopathy is associated with prolonged hyperglycemia; it is slow to develop, and there is some evidence that it can begin to develop as early as 7 years before clinical diagnosis of diabetes (Deshpande et al., 2008).

Postprandial (post-meal) blood sugar spikes specifically are one of the most damaging complications of diabetes (Parkin et al., 2002). Many diabetics are able to effectively manage post-meal glycemic spikes with self-administered doses of insulin, but these hyperglycemic incidents still kill more Americans per year than any other diabetes-related complications (Parkin et al., 2002). Arguably, the gravest consequence of glycemic spikes in diabetes patients is the development of progressive macrovascular disease (MVD), which affects the large blood vessels of the body, hardening and blocking these vessels (Ceriello et al., 2012). MVD is the leading cause of death among T2DM patients in the United States, causing up to 65% of diabetes-related deaths, making it a huge target for diabetes treatments research (Deshpande et al., 2008). MVD also frequently leads to other severe complications such as ischemia in the extremities and blindness (Haffner et al., 1998).

Controlling Hyperglycemic Spikes

For many T1DM and T2DM patients, it has been shown that the regular control and management of blood glucose levels prevents many of the vascular complications of the disease, but most of the time control over glucose is difficult to attain because the self-dosing insulin treatment system that a lot of moderately to severely sick diabetes patients use is often hard to calibrate and use (Parkin et al., 2002).

Compared to sucrose-rich food, starch-rich food has been found to create less fluctuation in blood glucose levels, and thus is beneficial to diabetes patients and hyperglycemia patients. There is evidence that this flatter response caused by a starch rich meal is associated with the slower rate of digestion of complex sugars versus simple sugars (Jenkins, Wolever, & Jenkins, 1988). Thus, if some of the simple sugars are first converted into complex saccharides inside the E. coli and then released back into small intestine, a similar flatter glycemic response will take place, which will be beneficial to the patients.

Our Devices

We have assembled one plasmid with genes that dictate a controllable level of simple sugars uptake and one plasmid to produce glucan and fructan from simple sugars and then lyse to release the complex sugars back into the environment. In essence, this microbial device runs on two genetic devices -- an uptake circuit and a polymeriztion circuit.

In order to learn more details, please visit the Project page.

Show References

Hide References

A. Ceriello, S. Colagiuri, (2011). Guideline for management of postmeal glucose in diabetes. International Diabetes Federation Guideline Development Group, http://www.idf.org/sites/default/files/postmeal%20glucose%20guidelines.pdf , Accessed May. 6th, 2015

American Diabetes Association (2014). National Diabetes Statistics Report. http://www.cdc.gov/diabetes/pubs/statsreport14/national-diabetes-report-web.pdf Accessed May. 5th, 2015

Anal, A. K., & Singh, H. (2007). Recent advances in microencapsulation of probiotics for industrial applications and targeted delivery. Trends in Food Science & Technology, 18(5), 240–251. http://doi.org/10.1016/j.tifs.2007.01.004

Anan, F., Masaki, T., Eto, T., Fukunaga, N., Iwao, T., Kaneda, K., ... Yoshimatsu, H. (2008). Postchallenge Plasma Glucose and Glycemic Spikes Are Associated with Pulse Pressure in Patients with Impaired Glucose Tolerance and Essential Hypertension. Hypertension Research, 31(8), 1565–1571. http://doi.org/10.1291/hypres.31.1565

AHFS Consumer Medication Information [Internet]. Bethesda (MD): American Society of Health-System Pharmacists, Inc.; ©2008. Acarbose; [revised 2015 Feb. 15; reviewed 2015 Apr. 28; cited 2015 May. 3]; Available from: http://www.nlm.nih.gov/medlineplus/druginfo/meds/ a696015.html

AHFS Consumer Medication Information [Internet]. Bethesda (MD): American Society of Health-System Pharmacists, Inc.; ©2008. Pramlintide; [revised 2015 Feb. 15; reviewed 2015 Apr. 28; cited 2015 May. 3]; Available from: http://www.nlm.nih.gov/medlineplus/druginfo/meds/a605031.html

Banguela, A., Arrieta, J. G., Rodríguez, R., Trujillo, L. E., Menéndez, C., & Hernández, L. (2011). High levan accumulation in transgenic tobacco plants expressing the Gluconacetobacter diazotrophicus levansucrase gene. Journal of Biotechnology, 154(1), 93–98. http://doi.org/10.1016/j.jbiotec.2011.04.007

Barr EL, Zimmet PZ, Welborn TA et al. (2007). "Risk of cardiovascular and all-cause mortality in individuals with diabetes mellitus, impaired fasting glucose, and impaired glucose tolerance: the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab)". Circulation 116 (2): 151–7.

Bernard, A. M., Anderson, L., Cook, C. B., & Phillips, L. S. (1999). What do internal medicine residents need to enhance their diabetes care? Diabetes Care, 22(5), 661–666. http://doi.org/10.2337/diacare.22.5.661

Boada C, Martínez-Moreno J. Pathophysiology of diabetes mellitus type 2: beyond the duo "insulin resistance-secretion deficit.". Nutricion Hospitalaria [serial online]. March 2, 2013;28:78-87. Available from: Fuente Académica, Ipswich, MA. Accessed April 16, 2015.

B. Göke, H. F. (1995). Voglibose (AO128) Is an Efficient α-Glucosidase Inhibitor and Mobilizes the Endogenous GLP-1 Reserve. Digestion, 56(6), 493–501. http://doi.org/10.1159/000201282

Brown, J. B., Harris, S. B., Webster-Bogaert, S., Wetmore, S., Faulds, C., & Stewart, M. (2002). The role of patient, physician and systemic factors in the management of type 2 diabetes mellitus. Family Practice, 19(4), 344–349. http://doi.org/10.1093/fampra/19.4.344

Butterworth, P. J., Warren, F. J., & Ellis, P. R. (2011). Human α-amylase and starch digestion: An interesting marriage. Starch - Stärke, 63(7), 395–405. http://doi.org/10.1002/star.201000150

Centers for Disease Control and Prevention. (2014). National Diabetes Statistics Report.

Chiasson, J.-L., Josse, R. G., Gomis, R., Hanefeld, M., Karasik, A., & Laakso, M. (2002). Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial. The Lancet, 359(9323), 2072–2077. http://doi.org/10.1016/S0140-6736(02)08905-5

Chiasson, J.-L., Josse, R. G., Hunt, J. A., Palmason, C., Rodger, N. W., Ross, S. A., ... Wolever*, T. M. S. (1994). The Efficacy of Acarbose in the Treatment of Patients with Non–Insulin-Dependent Diabetes Mellitus: A Multicenter, Controlled Clinical Trial. Annals of Internal Medicine, 121(12), 928–935. http://doi.org/10.7326/0003-4819-121-12-199412150-00004 Crude and Age-Adjusted Rate per 100 of Civilian, Noninstitutionalized Population with Diagnosed Diabetes, United States, 1980–2011. (2014, September 5). Retrieved April 24, 2015, from http://www.cdc.gov/diabetes/statistics/prev/national/figage.htm

Dedonder, R. 1966. Levansucrase from Bacillus subtilis. Methods Enzymol. 8:500–505.

Deshpande, A. D., Harris-Hayes, M., & Schootman, M. (2008). Epidemiology of diabetes and diabetes-related complications. Physical therapy, 88(11), 1254-1264.

D.M. Nathan, P.A. Cleary, J.Y. Backlund, S.M. Genuth, J.M. Lachin, T.J. Orchard, et al., Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes, N Engl J Med, 353 (2005), pp. 2643–2653

D.R. Whiting, L. Guariguata, C. Weil, J. Shaw, IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030 Diabetes Res Clin Pract, 94 (2011), pp. 311–321

Duncan, A. E. (2012). Hyperglycemia and Perioperative Glucose Management.Current Pharmaceutical Design, 18(38), 6195–6203.

Edelman, P. S., Maier, H., & Wilhelm, K. (2012). Pramlintide in the Treatment of Diabetes Mellitus. BioDrugs, 22(6), 375–386. http://doi.org/10.2165/0063030- 200822060-00004

Ferraris, R. P., Yasharpour, S. A. S. A. N., Lloyd, K. C., Mirzayan, R. A. F. F. Y., & Diamond, J. M. (1990). Luminal glucose concentrations in the gut under normal conditions. American Journal of Physiology-Gastrointestinal and Liver Physiology, 259(5), G822-G837.

Gay, P., Le Coq, D., Steinmetz, M., Ferrari, E., & Hoch, J. A. (1983). Cloning structural gene sacB, which codes for exoenzyme levansucrase of Bacillus subtilis: expression of the gene in Escherichia coli. Journal of bacteriology,153(3), 1424- 1431.

Gray, G. M., & Ingelfinger, F. J. (1966). Intestinal absorption of sucrose in man: interrelation of hydrolysis and monosaccharide product absorption. Journal of Clinical Investigation, 45(3), 388.

Grant, R. W., Buse, J. B., & Meigs, J. B. (2005). Quality of Diabetes Care in U.S. Academic Medical Centers Low rates of medical regimen change. Diabetes Care, 28(2), 337–442. http://doi.org/10.2337/diacare.28.2.337

Grant, R. W., Pirraglia, P. A., Meigs, J. B., & Singer, D. E. (2004). Trends in complexity of diabetes care in the United States from 1991 to 2000. Archives of Internal Medicine, 164(10), 1134–1139. http://doi.org/10.1001/archinte.164.10.1134

Halschou, K., Bukhave, K., & Rikardt, J. (2012). Intestinal Disaccharidase Activity and Uptake of Glucose from Sucrose. In S. Chackrewarthy (Ed.), Glucose Tolerance. InTech. Retrieved from http://www.intechopen.com/books/glucose- tolerance/intestinal-disaccharidase-activity-and-uptake-of-glucose-from-sucrose

Hanahan, D. (1983). Studies on transformation of Escherichia coli with plasmids. Journal of Molecular Biology, 166(4), 557–580.

Hoffmann, J., & Spengler, M. (1997). Efficacy of 24-Week Monotherapy With Acarbose, Metformin, or Placebo in Dietary-Treated NIDDM Patients: The Essen-II Study. The American Journal of Medicine, 103(6), 483–490. http://doi.org/10.1016/S0002-9343(97)00252-0 Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group.

Jenkins, D. J. A., Wolever, T. M. S., & Jenkins, A. L. (1988). Starchy Foods and Glycemic Index. Diabetes Care, 11(2), 149–159. http://doi.org/10.2337/diacare.11.2.149

Jones, M. C. (2007). Therapies for diabetes: pramlintide and exenatide. American Family Physician, 75(12), 1831–1835.

J Reizer, S. L. S. (1992). Functional interactions between proteins of the phosphoenolpyruvate:sugar phosphotransferase systems of Bacillus subtilis and Escherichia coli. The Journal of Biological Chemistry, 267(13), 9158–69. Jenkins, D. J., Wolever, T. M., & Jenkins, A. L. (1988). Starchy foods and glycemic index. Diabetes care, 11(2), 149-159.

Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Cotran, Ramzi S. ; Robbins, Stanley L. (2005). Robbins and Cotran Pathologic Basis of Disease (7th ed.). Philadelphia, Pa.: Saunders. pp. 1194–1195. ISBN 0-7216-0187-1. Lancet. 1998 Sep 12; 352(9131):837-53.

Kundig, W., Ghosh, S., & Roseman, S. (1964). PHOSPHATE BOUND TO HISTIDINE IN A PROTEIN AS AN INTERMEDIATE IN A NOVEL PHOSPHO- TRANSFERASE SYSTEM. Proceedings of the National Academy of Sciences of the United States of America, 52, 1067–1074.

Lebovitz, H. E. (1997). ALPHA-GLUCOSIDASE INHIBITORS. Endocrinology and Metabolism Clinics of North America, 26(3), 539–551. http://doi.org/10.1016/S0889-8529(05)70266-8

Lourens-Hattingh, A., & Viljoen, B. C. (2001). Yogurt as probiotic carrier food. International Dairy Journal, 11(1–2), 1–17. http://doi.org/10.1016/S0958- 6946(01)00036-X

Malagelada, J. R., Bazzoli, F., Elewaut, A., Fried, M., Krabshuis, J. H., Lindberg, G., ... Vakil, N. (2007). World Gastroenterology Organisation Practice Guidelines. Dysphagia. Retrieved from http://almacen- gpc.dynalias.org/publico/Dysphagia%20WGO%202004%20Ingles.pdf

Man, C. D., Camilleri, M., & Cobelli, C. (2006). A System Model of Oral Glucose Absorption: Validation on Gold Standard Data. IEEE Transactions on Biomedical Engineering, 53(12), 2472–2478. http://doi.org/10.1109/TBME.2006.883792

Meigs, J. B., Nathan, D. M., Wilson, P. W., Cupples, L. A., & Singer, D. E. (1998). Metabolic risk factors worsen continuously across the spectrum of nondiabetic glucose tolerance. The Framingham Offspring Study. Annals of Internal Medicine, 128(7), 524–533.

Narimasa, S., Tatsuo, H., Mitsutaka, Y., & Toshio, I. (1979). Action of human pancreatic and salivary α-amylases on maltooligosaccharides: Evaluation of kinetic parameters. Clinica Chimica Acta, 97(2–3), 253–260. http://doi.org/10.1016/0009-8981(79)90423-6

National Diabetes Data Group. (1979). Classification and Diagnosis of Diabetes Mellitus and Other Categories of Glucose Intolerance. Diabetes, 28(12), 1039–1057. http://doi.org/10.2337/diab.28.12.1039

Nissle, A. (1959). [Explanations of the significance of colonic dysbacteria & the mechanism of action of E. coli therapy (mutaflor)]. Die Medizinische, 4(21), 1017–1022.

Parkin, C. G., & Brooks, N. (2002). Is postprandial glucose control important? Is it practical in primary care settings?. Clinical Diabetes, 20(2), 71-76.

Patterson, Joan (2013). Many Schools Cutting Back on Physical Education. Las Vegas Review - Journal. Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults. The Third National Health and Nutrition Examination Survey, 1988-1994.

Peng, C.-K., Buldyrev, S. V., Havlin, S., Simons, M., Stanley, H. E., & Goldberger, A. L. (1994). Mosaic organization of DNA nucleotides. Physical Review E, 49(2), 1685–1689. http://doi.org/10.1103/PhysRevE.49.1685

Rathmann, W., & Giani, G. (2004). Global Prevalence of Diabetes: Estimates for the Year 2000 and Projections for 2030: Response to Wild et al. Diabetes Care, 2568- 2569.

Recorbet, G. H. I. S. L. A. I. N. E., Robert, C., Givaudan, A., Kudla, B., Normand, P., & Faurie, G. (1993). Conditional suicide system of Escherichia coli released into soil that uses the Bacillus subtilis sacB gene. Applied and environmental microbiology, 59(5), 1361-1366.

Ried, J. L., and A. Collmer. 1987. An nptI-sacB-sacR cartridge for constructing directed, unmarked mutations in Gram-negative bacteria by marker exchange-eviction mutagenesis. Gene 57:239–246.

Riddle, M., Frias, J., Zhang, B., Maier, H., Brown, C., Lutz, K., & Kolterman, O. (2007). Pramlintide Improved Glycemic Control and Reduced Weight in Patients With Type 2 Diabetes Using Basal Insulin. Diabetes Care, 30(11), 2794–2799. http://doi.org/10.2337/dc07-0589

Saydah, S. H., Miret, M., Sung, J., Varas, C., Gause, D., & Brancati, F. L. (2001). Postchallenge Hyperglycemia and Mortality in a National Sample of U.S. Adults. Diabetes Care, 24(8), 1397–1402. http://doi.org/10.2337/diacare.24.8.1397

Snelling, Anatasia; Korba, Casey; Burkey, Alyvia (2007). The National School Lunch and Competitive Food Offerings and Purchasing Behaviors of High School Students, 77(10), 701-705.

Sonnenborn, Ulrich; Schulze, Jurgen. 2009. The Non-Pathogenic Escherichia coli strain Nissle 1917 - Features of a Versatile Probiotic. Microbial Ecology in Health and Disease, (21), 122-158.

S.M. Haffner, S. Lehto, T. Ronnemaa, K. Pyorala, M. Laakso, Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction, N Engl J Med, 339 (1998), pp. 229–234

Schultz, M. (2008). Clinical use of E. coli Nissle 1917 in inflammatory bowel disease. Inflammatory Bowel Diseases, 14(7), 1012–1018. http://doi.org/10.1002/ibd.20377

Seifter, S., & Dayton, S. (1950). The estimation of glycogen with the anthrone reagent. Archives of Biochemistry, 25(1), 191–200.

Shulman, N. B., Martinez, B., Brogan, D., Carr, A. A., & Miles, C. G. (1986). Financial cost as an obstacle to hypertension therapy. American Journal of Public Health, 76(9), 1105–1108.

Suwattee, P., Lynch, J. C., & Pendergrass, M. L. (2003). Quality of Care for Diabetic Patients in a Large Urban Public Hospital. Diabetes Care, 26(3), 563–568. http://doi.org/10.2337/diacare.26.3.563

Temelkova-Kurktschiev, T. S., Koehler, C., Henkel, E., Leonhardt, W., Fuecker, K., & Hanefeld, M. (2000). Postchallenge plasma glucose and glycemic spikes are more strongly associated with atherosclerosis than fasting glucose or HbA1c level.

Diabetes Care, 23(12), 1830–1834. http://doi.org/10.2337/diacare.23.12.1830 What are normal blood glucose levels? Retrieved from Virginia Mason Medical Center website: https://www.virginiamason.org/whatarenormalbloodglucoselevels. Accessed: May. 5th ,2015

University of Virginia iGEM

148 Gilmer Hall

485 McCormick Road

Charlottesville, Virginia 22904

United States of America

virginia.igem@gmail.com