Latest revision as of 14:51, 6 October 2016

Modeling - TAS Taipei iGEM Wiki

PROJECT

Background

Achievements

Collaborations

Parts

Cataracts - the leading cause of blindness. Find out how we can noninvasively treat and prevent cataract formation.
EXPERIMENTAL

Lens Cataract Model

Prevention and Treatment Constructs

Delivery Prototype

Notebook

We don't just come up with great ideas. We show they work. Follow along our discovery of exciting science!
MODEL

Cataract Damage

GSR/25HC Pathway

Nanoparticle Degradation

Eyedrop Model

Computational Biology provides us models that we cannot easily test. Click to find out the results of our modeling, and if you want, the math behind it!
HUMAN PRACTICE

Research

Outreach

Impact

We don't just grow cool bacteria. We make a difference. Find out how we tackled social aspects of this project.
BIOSAFETY

Researcher Safety

Environmental Safety

Biobrick Safety

Local Safety

Safety first. Especially in a lab. Here's how we maintained and investigated the integrity and security of our work environment.
TEAM

Members

About

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Wiki Standard Pages

Behind every tough iGem project lies a hard-working yet cheerful group of students. Meet the team!

C◎UNTERACTS

Modeling

Abstract

We answer two questions: How much GSR to maintain in the lens, and how to maintain that amount? We find the amount of GSR needed in the lens (Model 2) to limit crystallin damage so the resulting cataract is less than LOCS 2.5 (Model 1). Then, we find the optimal design of eyedrops (Model 4) and nanoparticles that will maintain this amount of GSR in the lens (Model 3). These models allow our team to understand the impact of adding GSR-loaded nanoparticles into the lens, and to design a full treatment plan on how to prevent and treat cataracts.

Achievements

Designed a simple calculator to find amount of GSR or 25HC eyedrops needed for a patient's LOCS score.
Bridged the gap between the medical, biological, and chemical measurement of crystallin damage.
Predicted impact of adding GSR and 25HC on the amount of crystallin damage in the lens.
Created Nanoparticle Customizer for doctors to find a full treatment plan.
Generalized our Customizer to allow other iGEM teams who wish to use nanoparticle drug delivery
Analyzed sensitivity of prototype, and suggested insights into optimal manufacturing and clinical use of our prototype.
Used Experimental data to develop Models 1 and 3.

Outline

Introduction

Why Model?

In the lab, biologists are often unable to test everything experimentally. For example, in our cataracts project, cataract prevention occurs in the long-term, from 20-50 years. Obviously, although short experiments can provide us an idea of what prevention may look like, the power of computational biology allows us to model into the future. As a result, our modeling has been crucial in developing a prototype.

Focus

Most iGEM teams perform modeling on gene expression, which we accomplish in model 5. However, as our construct is not directly placed into the eyes, how our synthesized protein impacts the eyes after it is seperately transported is much more interesting. As a result, we spent the majority of our models on understanding the impacts on the eye.

Guiding Questions

How much GSR do we want inside the lens?
How do we use nanoparticles to control the amount of GSR in the lens?
How do we synthesize GSR, package into NP, and send it into the eye?

Model 1: Crystallin Damage

Abstract

In our experiments, absorbance measurements are meaningless without understanding how severe a cataract that absorbance measurement means. We use literature research to relate LOCS, the physician's scale of cataract severity) to absorbance, which is how we quantified crystallin damage in experiments. We use experimental data to understand how crystallin damage can be quantified by measuring absorbance. With this model, we can calculate how much crystallin damage we have to limit to reduce LOCS to an acceptable level.

Purpose

How much do we need to limit crystallin damage so surgery is not needed?

Measurement of Cataract Severity

There are four ways of measuring cataract severity, each used for a different purpose.

Lens Optical Cataract Scale (LOCS): Physicians use this scale, from 0 – 6, to grade the severity of cataracts.
Opacity (%): This is the physical, quantitative property of the LOC scale.
Absorbance at 397.5 nm: This is the experimental method, used by our team in the lab (c.d.).
Crystallin Damage: This is a chemical definition. We quantify cataract severity as a function of how much oxidizing agents there are, as well as how long crystalline is exposed to oxidizing agents. We define 1 crystallin damage unit as the damage done to human crystallin when exposed to 1 M hydrogen peroxide, the main oxidizing agent, for 1 hour.

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We use the unit of crystallin damage to connect cataract severity with the amount of GSR we add (in Model 2). We want to lower c.d. below so that the resulting cataract is of LOCS 2.5. For the rest of the model, our task is simple: relate each point of the LOCS scale to c.d., in order to connect to Model 2.

LOCS Equivalence to Absorbance: Literature Research

Past studies have done numerous studies on how absorbance measurements can be converted to the LOC scale that physicians end up using. With the results of ________ and ________, we construct the first three columns in Table 2.

Absorbance Equivalence to Crystallin Damage: Experimental Data

We use experimental data from our team’s Cataract Lens Model (link). In each trial, they added H2O2 to crystallin, and measured the resulting absorbance. The data used are shown in Table 1. We can calculate the theoretical c.d., and graph absorbance vs. crystallin damage in Figure 2.

With this relation in Figure 2, we calculate the equivalent crystallin damage to each LOCS rating and its equivalent absorbance.

Error Analysis

It may be surprising that only around 1 M-h is required to induce moderately severe cataracts. Remember that this is done in the absence of antioxidation systems (GSR) and at an extremely high oxidizing concentration of H2O2 (1M of H2O2). In the lens, H2O2 has a much lower concentration, so severe cataracts are induced over months to years.

There are some limitations of the model that arise from our assumptions. We assume that fish and human lens contain similar crystallin proteins that are degraded in the similar manner (Assumption 4). In addition, we made a rough adjustment of data based our diluting procedure. For better results to create a human cataract model, experiments will need to be done on human lens, even better if done in vitro, without any dilutions.

**Table 2: Results of Model 1 – Equivalent values for LOCS, Opacity, Absorbance, and Crystallin Damage.**
LOCS	Opacity (%)	Absorbance (@397.5 nm)	Crystallin Damage (M-h)
0.0	0.00	0.0000	0.0000
0.5	3.24	0.0143	0.1327
1.0	6.65	0.0299	0.2774
1.5	10.81	0.0497	0.4610
2.0	15.88	0.0751	0.6966
2.5	21.95	0.1076	0.9981
3.0	29.07	0.1492	1.3840
4.0	46.37	0.2706	2.5101
5.0	66.05	0.4691	4.3514

Background

There are four ways to measure cataract severity (how blurred the lens is):

Lens Optical Cataract Scale III (LOCS) - a scale from 0-6 used by physicians.
Opacity (%) - used to calculate the LOC scale
Absorbance at 397.5 nm - measurable in the lab.
Crystallin Damage - used to quantify how much crystallin has been reacted with hydrogen peroxide to create insoluble, damaged crystallin. The following definition of crystallin damage is used:

\[c.d.(t) = \int_{0}^{\infty} [H_2O_2]_t dt\]

In other words, 1 unit of crystallin damage, in M-h, is equal to the damage caused by 1 molar concentration of hydrogen peroxide reacting crystallin in the eyes for 1 hour.

LOCS Scale

Assumptions

Definition of crystallin damage: Crystallin damage is proportional to the concentration of hydrogen peroxide, and the time of exposure. This is a valid assumption, supported by the fact that the reaction between cysteine (molecules on crystallin) and hydrogen peroxide is linear.
We assume that the amount of crystallin is far greater than the amount oxidized. Our product is meant for long-term cataract prevention and minor treatment, and is not suggested for patients with extremely severe cataracts.
When the experiments diluted the cataract lens protein, the amount of crystallin is diluted. However, the final absorbance of degraded crystallin is also diluted, so we assume any errors in absorbance is canceled out.
We assume that fish and human lens contain similar crystallin proteins.

Procedure

In the first part, we find how the absorbance measurements in the lab are related to the severity of the cataracts. Through literature data, we can relate LOCS to the opacity of the lens. Then, via physical calculations, we can relate the opacity of the lens to the absorbance of the lens at 400 nm.
Then, we use our team’s experimental data in the cataract model. For each trial, the concentration of H2O2 and the length of exposure are given, so we can calculate the theoretical crystallin damage using the definition above and the assumptions we made. In each trial we also measured the absorbance, so we have a relation between crystallin damage and absorbance.
However, we need to make a minor adjustment, because absorbance is affected by dilution. When the fish lens was isolated, they were placed in Tris buffer and diluted. We calculate the ratio of volumes from diluted volume to the Tris buffer, and multiply each absorbance measurement by this value.

LOCS Scale

Results

**Table 1: Results of Model 1 - Equivalent values for LOCS, Opacity, Absorbance, and Crystallin Damage.**
LOCS	0.0	0.5	1.0	1.5	2.0	2.5	3.0	4.0	5.0
Degree	None	Trace		Mild			Moderate		Severe
Opacity (%)	0	3.24	6.65	10.81	15.88	21.95	29.07	46.37	66.05
Absorbance (a.u.)	0.0000	0.0143	0.0299	0.0497	0.0751	0.1076	0.1492	0.2706	0.4691
Crystallin Damage (c.d.)	0.0000	0.1327	0.2774	0.4610	0.6966	0.9981	1.3840	2.5101	4.3514

**Table 2: Experimental Data used for Model 1 from Cataract Lens Model (TAS) - Absorbance vs. Crystallin Damage**
Trial	H2O2 Concentration (M)	Exposure Time (h)	Crystallin Damage (c.d.)	Measured Absorbance (abs @400 nm)
1	0.100	24.0	2.40	0.105
2	0.100	46.5	4.65	0.451
3	0.100	72.0	7.20	0.0.695
4	0.100	20.0	2.00	0.089
5	0.100	42.0	4.20	0.392
6	0.100	15.0	1.50	0.093
7	0.100	42.0	0.340	0.340
8	0.100	67.0	6.70	0.563

Discussion

Model Result

The model successfully relates LOCS, opacity of lens, absorbance measurements, and the equivalent crystallin damage of the lens. The purpose of relating LOCS to crystallin damage, is that in Model 2, we will use chemical kinetics to determine how adding GSR to the lens will decrease the amount of crystallin damage. Exactly how much crystallin damage we need to decrease is determined by the desired LOCS. For example, if we want to have a LOCS rating of less than 2.5, then we must lower crystalline damage to only 0.9981 M-h.

Model Adjustment

When determining the relationship between absorbance and crystallin, in Figure 1 the best fit line has a x – intercept that is nonzero. However, when converting each absorbance rating to equivalent crystallin damage in Table 2, we ignore the constant term. When doing the experiments, the fish lens may have contained GSH that is still active, so the fact that the crystallin is exposed to H2O2, the degradation reaction does not happen until all GSH is depleted, and crystallin damage begins to form. We subtract around 1 unit of crystallin damage from all values.

Error Analysis

It may be surprising that only around 1 M-h is required to induce moderately severe cataracts. Remember that this is done in the absence of antioxidation systems (GSR) and at an extremely high oxidizing concentration of H2O2 (1M of H2O2). In the lens, H2O2 has a much lower concentration, so severe cataracts are induced over months to years.

There are some limitations of the model that arise from our assumptions. We assume that fish and human lens contain similar crystallin proteins that are degraded in the similar manner (Assumption 4). Also, to simplify the experiments, the lens were diluted in Tris buffer. Because of this dilution, the actual crystallin damage is much lower, but so is the actual absorbance. We assume that the decrease in crystallin damage and absorbance is the same, so no adjustments need to be made for the relation between crystallin damage and absorbance (Assumption 3). For better results to create a human cataract model, experiments will need to be done on human lens, even better if done in vitro, without any dilutions.

Conclusion

For surgery to not be needed, the LOCS value has to be below 2.5. This is equivalent to 21.95% in light opacity or 0.1076 abs units. Based on the results of our experiments, this is equivalent to 0.9981 units of crystallin damage, the damage done to crystallin if exposed to 0.9981 M of H2O2 for 1 hr. For future models, this value 0.9981 units of c.d. will be called the crystallin damage threshold for LOCS 2.5.

Model 2: GSR/25HC Chemical Pathway

Abstract

The key question: How much GSR to add? Now that we know how much we need to limit crystallin damage, we use systems of ordinary differential equation to model the GSR Pathway. We calculate the necessary GSR concentration to be maintained over 50 years so that the resulting cataract is below LOCS 2.5./p>

Purpose

How much GSR do we need to maintain in the lens so that the crystallin damage recorded over 50 years is below the threshold for LOCS 2.5?

Chemical Kinetics Model: Differential Equations

By the Law of Mass Action, Michaelis-Menten Enzyme kinetics, Ping-pong mechanism, and the Law of Passive Diffusion, we build a system of 10 differential equations based on 6 chemical reactions. All parameters, constants, and initial conditions are based off literature data. Estimates made are also shown with assumptions and reasoning. The details are shown in the collapsible for interested readers.

Blackbox Approach: Testing GSR Impact

Image

We will vary the input, Initial GSR concentration, from 0 to 100 uM, holding all other variables constant, and numerically solve for the amount of hydrogen peroxide over time. With this graph, we can find the amount of crystallin damage accumulated over 20 to 50 years if different levels of GSR is maintained.

Background

The following 6 reactions describe the antioxidant system inside the cortex and nucleus.

$$GP_{xr}+[H_2O_2]_{in}+H^+ \xrightarrow[]{k_1} GP_{xo}+H_2O ...(1)$$ $$GP_{xo}+GSH+H^+ \xrightarrow[]{k_2} [GS-GP_x]+H_2O ...(2)$$ $$[GS-GP_x] + GSH \xrightarrow[]{k_3} GP_{xr}+GSSG+H^+ ...(3)$$ $$NADPH \xrightarrow[GSR]{k4, K_{4M}} NADP^+ ...(4)$$ $$GSSG \xrightarrow[GSR']{k_5, K_{5M}} 2GSH ...(5)$$ $$[H_2O_2]_{out} \xrightarrow[]{k_5} [H_2O_2]_{in} ...(6)$$

Each reaction will be discussed in detail, and we will derive rate equations.

Reaction 1:As hydrogen ions are numerous are negligible in the reaction, we will ignore it. By the law of mass action, the rate of this reaction is: $$r_1=k_1[GP_{xr}][H_2O_2]_{in}$$

Reaction 2: By the law of mass action, the rate of this reaction is: $$r_2=k_2[GP_{xo}][GSH]$$

Reaction 3: By the law of mass action, the rate of this reaction is: $$r_3=k_3[GS-GP_x][GSH]$$

Summary of Reaction 1-3:In these reactions, hydrogen peroxide is reduced to water. GSH is consumed to recycle the enzyme GPx back into reduced form, to neutralize more hydrogen peroxide.

Reaction 4: ByMichaelis-Menten kinetics and the Ping-Pong mechanism, the rate of this reaction, with rate constant k4, and Michaelis-Menten constant Km4, is: $$r_4=k_4\frac{[NADPH]}{K_{4M}+[NADPH]}$$

Reaction 5: ByMichaelis-Menten kinetics and the Ping-Pong mechanism, the rate of this reaction, with rate constant k5, and Michaelis-Menten constant Km5, is: $$r_5=k_5\frac{[GSSG]}{K_{4M}+[GSSG]}$$

Summary of Reaction 4-5: In these, GSSG is reduced back to form GSH, using the enzyme GSR. This is necessary for antioxidation to continue as reaction 1 is constantly using GSH, converting them to GSSG.

Reaction 6: By the Law of Passive Diffusion, the rate of diffusion into the cortex and lens is: is: $$r_6=k_6([H_2O_2]_{out}-[H_2O_2]_{in})$$

Differential Equations

We have six reaction rates derived from above. Now, we will form differential equations, where every time a species is used as a reactant, the reaction rate will be subtracted from the species’ derivative, while each time it is formed as a product, the reaction rate will be added to the species’ derivative. We will go through each species in detail:

Substituting the rate of each reaction, we get the following system of differential equations.

$$\frac{d[GP_{xr}]}{dt}=k_3[GS-GP_x][GSH]-k_1[GP_{xr}][H_2O_2]_{in}$$ $$\frac{d[H_2O_2]}{dt}=k_6[[H_2O_2]_{out}-{H_2O_2]_{in}]-k_1[GP_{xr}][H_2O_2]_{in}$$ $$\frac{d[H_2O_2]}{dt}=k_1([H_2O_2]_{out} - [H_2O_2]_{in})-k_1[GP_{xr}][H_2O_2]_{in}$$ $$\frac{d[GP_{x0}]}{dt}=k_1[GP_{xr}][H_2O_2]_{in}-k_2[GP_{xo}][GSH]$$ $$\frac{d[H_2O]}{dt}=k_1[GP_{xr}][H_2O_2]_{in}+k_2[GP_{xo}][GSH]$$ $$\frac{d[GSH]}{dt}=2k_5[GSR']\frac{[GSSG]}{K_{5M}+[GSSG]}-k_2[GP_{xo}][GSH]-k_3[GS-GP_x][GSH]$$ $$\frac{d[GS-GP_x]}{dt}=k_2[GP_{xo}][GSH]-k_3[GS-GP_x][GSH]$$ $$\frac{d[GSSG]}{dt}=k_3[GS-GP_x][GSH]-k_5[GSR']\frac{[GSSG]}{K_{5M}+[GSSG]}$$ $$\frac{d[NADPH]}{dt}=-k_4[GSR]\frac{[NADPH]}{K_{4M}+[NADPH]}$$ $$\frac{d[GSR]}{dt}=k_5[GSR']\frac{[GSSG]}{K_{5M}+[GSSG]}-k_4[GSR]\frac{[NADPH]}{K_{4M}+[NADPH]}$$ $$\frac{d[GSR']}{dt}=k_4[GSR]\frac{[NADPH]}{K_{4M}+[NADPH]}-k_5[GSR']\frac{[GSSG]}{K_{5M}+[GSSG]}$$

Part 1 Results

**Table 1: Data obtained from XXX relating each value of the LOCS scale, to opacity values.**
LOCS	0.0	0.5	1.0	2.0	3.0	4.0	5.0	6.0
Degree	None		Trace	Mild	Surgery Suggested	Moderate	Severe	Very Severe
Opacity (%)	0.34	4.24	5.80	18.88	23.60	49.14	65.61	90+
Absorbance (a.u.)	0.001	0.019	0.026	0.091	0.117	0.294	0.464	1.3+

We wish to remain below clinically significant levels, so we will reach attempt to lower the LOCS rating of a cataract to below grade 2.5, which means we want to control GSR such that the crystallin damage results in less than 0.108 a.u. at absorbance at 397.5 nm.

Menu 3

Eaque ipsa quae ab illo inventore veritatis et quasi architecto beatae vitae dicta sunt explicabo.

When determining the relationship between absorbance and crystallin, in Figure 1 the best fit line has a x – intercept that is nonzero. However, when converting each absorbance rating to equivalent crystallin damage in Table 2, we ignore the constant term. When doing the experiments, the fish lens may have contained GSH that is still active, so the fact that the crystallin is exposed to H2O2, the degradation reaction does not happen until all GSH is depleted, and crystallin damage begins to form. We subtract around 1 unit of crystallin damage from all values.

Conclusion

Model 3: Nanoparticles

Abstract

Purpose

Background

There are three quantifiers of how severe cataract formation is, two are measurable, one is not.

Absorbance @ 397.5 nm, which is measured with lab equipment.
LOCS scale, subjectively measured by physicians on a scale from 0 - 6.
Crystallin Damage, which we define as the following (for any time $t$)

\[c.d.(t) = \int_{0}^{\infty} [H_2O_2]_t dt\]

In other words, 1 unit of crystallin damage, in M-h, is equal to the damage caused by 1 molar concentration of hydrogen peroxide reacting crystallin in the eyes for 1 hour.

In making this definition, we assume that crystallin damage is directly proportional to the amount of time crystallin is exposed to hydrogen peroxide. Hydrogen peroxide causes damage by forming disulfide bridges within cysteine molecules on crystallin. This changes the structure of crystallin, causing misfolding and cataract damage. Our linear assumption is valid because the rate for this reaction is first order with respect to hydrogen peroxide concentration.

Method

We will relate the three by doing the following:

Relate LOCS scale to opacity via literature research.
Relate opacity to light transmittance via literature research.
Relate light transmittance to absorbance via physical calculations.
Relate absorbance to crystallin damage via experimental data.

Part 1 Results

**Table 1: Data obtained from XXX relating each value of the LOCS scale, to opacity values.**
LOCS	0.0	0.5	1.0	2.0	3.0	4.0	5.0	6.0
Degree	None		Trace	Mild	Surgery Suggested	Moderate	Severe	Very Severe
Opacity (%)	0.34	4.24	5.80	18.88	23.60	49.14	65.61	90+
Absorbance (a.u.)	0.001	0.019	0.026	0.091	0.117	0.294	0.464	1.3+

We wish to remain below clinically significant levels, so we will reach attempt to lower the LOCS rating of a cataract to below grade 2.5, which means we want to control GSR such that the crystallin damage results in less than 0.108 a.u. at absorbance at 397.5 nm.

Menu 3

Eaque ipsa quae ab illo inventore veritatis et quasi architecto beatae vitae dicta sunt explicabo.

Conclusion

Model 4: Eyedrops

Abstract

Purpose

Background

There are three quantifiers of how severe cataract formation is, two are measurable, one is not.

Absorbance @ 397.5 nm, which is measured with lab equipment.
LOCS scale, subjectively measured by physicians on a scale from 0 - 6.
Crystallin Damage, which we define as the following (for any time $t$)

\[c.d.(t) = \int_{0}^{\infty} [H_2O_2]_t dt\]

In other words, 1 unit of crystallin damage, in M-h, is equal to the damage caused by 1 molar concentration of hydrogen peroxide reacting crystallin in the eyes for 1 hour.

In making this definition, we assume that crystallin damage is directly proportional to the amount of time crystallin is exposed to hydrogen peroxide. Hydrogen peroxide causes damage by forming disulfide bridges within cysteine molecules on crystallin. This changes the structure of crystallin, causing misfolding and cataract damage. Our linear assumption is valid because the rate for this reaction is first order with respect to hydrogen peroxide concentration.

Method

We will relate the three by doing the following:

Relate LOCS scale to opacity via literature research.
Relate opacity to light transmittance via literature research.
Relate light transmittance to absorbance via physical calculations.
Relate absorbance to crystallin damage via experimental data.

Part 1 Results

**Table 1: Data obtained from XXX relating each value of the LOCS scale, to opacity values.**
LOCS	0.0	0.5	1.0	2.0	3.0	4.0	5.0	6.0
Degree	None		Trace	Mild	Surgery Suggested	Moderate	Severe	Very Severe
Opacity (%)	0.34	4.24	5.80	18.88	23.60	49.14	65.61	90+
Absorbance (a.u.)	0.001	0.019	0.026	0.091	0.117	0.294	0.464	1.3+

We wish to remain below clinically significant levels, so we will reach attempt to lower the LOCS rating of a cataract to below grade 2.5, which means we want to control GSR such that the crystallin damage results in less than 0.108 a.u. at absorbance at 397.5 nm.

Menu 3

Eaque ipsa quae ab illo inventore veritatis et quasi architecto beatae vitae dicta sunt explicabo.

Conclusion

Yay

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-		        <span dir="auto">Team:TAS Taipei</span>
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-	<title>TAS Taipei iGEM Wiki</title>
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 });
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 		<ul style='margin-left:0px'>
 			<li class="dropdown">
-				<a href="https://2015.igem.org/Team:TAS_Taipei/project"><h4 class="dropdown-toggle disabled" data-toggle="dropdown"><b>PROJECT</b></h4></a>
+				<a href="https://2016.igem.org/Team:TAS_Taipei/project"><h4 class="dropdown-toggle disabled" data-toggle="dropdown"><b>PROJECT</b></h4></a>
 				<div class="dropdown-menu">
 					<div class='subcategories_container'>
 							<div>
-								<h5><a href="https://2015.igem.org/Team:TAS_Taipei/project#background">Background</a></h5>
+								<h5><a href="https://2016.igem.org/Team:TAS_Taipei/Description#background">Background</a></h5>
 							</div>
 							<div>
-								<h5><a href="https://2015.igem.org/Team:TAS_Taipei/project/achievements">Achievements</a></h5>
+								<h5><a href="https://2016.igem.org/Team:TAS_Taipei/Achievements">Achievements</a></h5>
 							</div>
 							<div>
-								<h5><a href="https://2015.igem.org/Team:TAS_Taipei/Collaborations">Collaborations</a></h5>
+								<h5><a href="https://2016.igem.org/Team:TAS_Taipei/Collaborations">Collaborations</a></h5>
 							</div>
 							<div>
-								<h5><a href="https://2015.igem.org/Team:TAS_Taipei/Parts">FUN!</a></h5>
+								<h5><a href="https://2016.igem.org/Team:TAS_Taipei/Parts">Parts</a></h5>
 							</div>
 						</div>
 					<div style='height:140px;'>
 						<img src="https://static.igem.org/mediawiki/2015/5/5b/Tas_icon_project.png">
-						<h4><b>GSH</b> - the solution to cataracts. How can we <b>increase</b> it in our eyes? </h4>
+						<h4><b>Cataracts</b> - the leading cause of blindness. Find out how we can noninvasively <b>treat</b> and <b>prevent</b> cataract formation.</b></h4>
 					</div>
@@ Line 117: / Line 91: @@
 					<div class='subcategories_container'>
 						<div>
-							<h5><a href="https://2015.igem.org/Team:TAS_Taipei/wetlab#construct">Granzyme Inhibitor Construct</a></h5>
+							<h5><a href="https://2016.igem.org/Team:TAS_Taipei/Experiments#lensmodel">Lens Cataract Model</a></h5>
 						</div>
 						<div>
-							<h5><a href="https://2015.igem.org/Team:TAS_Taipei/wetlab#prototype">Prototype Work</a></h5>
+							<h5><a href="https://2016.igem.org/Team:TAS_Taipei/Experiments#construct">Prevention and Treatment Constructs </a></h5>
 						</div>
 						<div>
-							<h5><a href="https://2015.igem.org/Team:TAS_Taipei/wetlab#safety">Safety Switch</a></h5>
+							<h5><a href="https://2016.igem.org/Team:TAS_Taipei/Experiments#prototype">Delivery Prototype</a></h5>
 						</div>
 						<div>
-							<h5><a href="https://2015.igem.org/Team:TAS_Taipei/Notebook">Notebook</a></h5>
+							<h5><a href="https://2016.igem.org/Team:TAS_Taipei/Notebook">Notebook</a></h5>
 						</div>
 					</div>
 					<div style='height:140px;'>
 						<img src="https://static.igem.org/mediawiki/2015/f/f8/Tas_icon_wetlab.png">
-						<h4>We conduct science - and we are proud to show it. Follow along with our journey of discovery in the lab.</h4>
+						<h4>We don't just come up with great ideas. We show they work. Follow along our discovery of exciting science!</h4>
 					</div>
 				</div>
 			</li>
 			<li class="dropdown">
-				<a href="https://2015.igem.org/Team:TAS_Taipei/Modeling"><h4 class='dropdown-toggle disabled' data-toggle="dropdown"><b>MODELING</b></h4></a>
+				<a href="https://2016.igem.org/Team:TAS_Taipei/Modeling"><h4 class='dropdown-toggle disabled' data-toggle="dropdown"><b>MODEL</b></h4></a>
 				<div class="dropdown-menu">
 					<div class='subcategories_container'>
 						<div>
-							<h5><a href="https://2015.igem.org/Team:TAS_Taipei/Modeling#serpin">SerpinA3N vs. GZMB</a></h5>
+							<h5><a href="https://2016.igem.org/Team:TAS_Taipei/Model#crystallin">Cataract Damage</a></h5>
 						</div>
 						<div>
-							<h5><a href="https://2015.igem.org/Team:TAS_Taipei/Modeling#act">ACT3m vs. GZMB</a></h5>
+							<h5><a href="https://2016.igem.org/Team:TAS_Taipei/Model#gsr25hc">GSR/25HC Pathway</a></h5>
 						</div>
 						<div>
-							<h5><a href="https://2015.igem.org/Team:TAS_Taipei/Modeling#analysis">Analysis</a></h5>
+							<h5><a href="https://2016.igem.org/Team:TAS_Taipei/Model#nanoparticle">Nanoparticle Degradation</a></h5>
 						</div>
 						<div>
-							<h5><a href="https://2015.igem.org/Team:TAS_Taipei/Modeling#calculator">Calculator</a></h5>
+							<h5><a href="https://2016.igem.org/Team:TAS_Taipei/Model#eyedrop">Eyedrop Model</a></h5>
-						</div>
-						<div>
-							<h5><a href="https://2015.igem.org/Team:TAS_Taipei/Modeling#flux">Flux Model</a></h5>
 						</div>
 					</div>
 					<div style='height:140px;'>
 						<img src="https://static.igem.org/mediawiki/2015/3/3e/Tas_icon_modeling.png">
-						<h4>The power of <b>Math and Computation</b> provides us with valuable models and information. Find out how.</h4>
+						<h4><b>Computational Biology</b> provides us models that we cannot easily test. Click to find out the results of our modeling, and if you want, the math behind it!</h4>
 					</div>
 				</div>
 			</li>
 			<li class="dropdown">
-				<a href="https://2015.igem.org/Team:TAS_Taipei/Practices"><h4 class='dropdown-toggle disabled' data-toggle="dropdown"><b>HUMAN PRACTICE</b></h4></a>
+				<a href="https://2016.igem.org/Team:TAS_Taipei/Practices"><h4 class='dropdown-toggle disabled' data-toggle="dropdown"><b>HUMAN PRACTICE</b></h4></a>
 				<div class="dropdown-menu">
 					<div class='subcategories_container'>
 						<div>
-							<h5><a href="https://2015.igem.org/Team:TAS_Taipei/Practices#research">Research</a></h5>
+							<h5><a href="https://2016.igem.org/Team:TAS_Taipei/Human_Practices#research">Research</a></h5>
-						</div>
-						<div>
-							<h5><a href="https://2015.igem.org/Team:TAS_Taipei/Practices#change">Change</a></h5>
 						</div>
 						<div>
-							<h5><a href="https://2015.igem.org/Team:TAS_Taipei/Practices#outreach">Outreach</a></h5>
+							<h5><a href="https://2016.igem.org/Team:TAS_Taipei/Human_Practices#outreach">Outreach</a></h5>
 						</div>
 						<div>
-							<h5><a href="https://2015.igem.org/Team:TAS_Taipei/Practices#entertainment">Entertainment</a></h5>
+							<h5><a href="https://2016.igem.org/Team:TAS_Taipei/Human_Practices#impact">Impact</a></h5>
 						</div>
 					</div>
 					<div style='height:140px;'>
 						<img src="https://static.igem.org/mediawiki/2015/0/0f/Tas_icon_hp.png">
-						<h4>We want to develop <b>socially concious solutions</b> - one that can be provided to all that need aid. Find out how we tackled <b>social aspects</b> of this project.</h4>
+						<h4>We don't just grow cool bacteria. We make a <b>difference</b>. Find out how we tackled <b>social aspects</b> of this project.</h4>
 					</div>
 				</div>
 			</li>
 			<li class="dropdown">
-				<a href="https://2015.igem.org/Team:TAS_Taipei/Safety"><h4 class='dropdown-toggle disabled' data-toggle="dropdown"><b>BIOSAFETY</b></h4></a>
+				<a href="https://2016.igem.org/Team:TAS_Taipei/Safety"><h4 class='dropdown-toggle disabled' data-toggle="dropdown"><b>BIOSAFETY</b></h4></a>
 				<div class="dropdown-menu">
 						<div style='height:100px;'>
 							<div class='subcategories_container'>
 								<div>
-									<h5><a href="https://2015.igem.org/Team:TAS_Taipei/Safety#researcher_safety">Researcher Safety</a></h5>
+									<h5><a href="https://2016.igem.org/Team:TAS_Taipei/Safety#researcher_safety">Researcher Safety</a></h5>
 								</div>
 								<div>
-									<h5><a href="https://2015.igem.org/Team:TAS_Taipei/Safety#environmental_safety">Environmental Safety</a></h5>
+									<h5><a href="https://2016.igem.org/Team:TAS_Taipei/Safety#environmental_safety">Environmental Safety</a></h5>
 								</div>
 								<div>
-									<h5><a href="https://2015.igem.org/Team:TAS_Taipei/Safety#biobrick_safety">Biobrick Safety</a></h5>
+									<h5><a href="https://2016.igem.org/Team:TAS_Taipei/Safety#biobrick_safety">Biobrick Safety</a></h5>
 								</div>
 								<div>
-									<h5><a href="https://2015.igem.org/Team:TAS_Taipei/Safety#local_safety">Local Safety</a></h5>
+									<h5><a href="https://2016.igem.org/Team:TAS_Taipei/Safety#local_safety">Local Safety</a></h5>
 								</div>
 							</div>
@@ Line 208: / Line 177: @@
 			</li>
 			<li class="dropdown">
-				<a href="https://2015.igem.org/Team:TAS_Taipei/team"><h4 class='dropdown-toggle disabled' data-toggle="dropdown"><b>TEAM</b></h4></a>
+				<a href="https://2016.igem.org/Team:TAS_Taipei/Team"><h4 class='dropdown-toggle disabled' data-toggle="dropdown"><b>TEAM</b></h4></a>
 				<div class="dropdown-menu">
 					<div class='subcategories_container'>
 						<div>
-							<h5><a href="https://2015.igem.org/Team:TAS_Taipei/team#members">Members</a></h5>
+							<h5><a href="https://2016.igem.org/Team:TAS_Taipei/Team#members">Members</a></h5>
 						</div>
 						<div>
-							<h5><a href="https://2015.igem.org/Team:TAS_Taipei/team#tas">About</a></h5>
+							<h5><a href="https://2016.igem.org/Team:TAS_Taipei/team#tas">About</a></h5>
 						</div>
 						<div>
-							<h5><a href="https://2015.igem.org/Team:TAS_Taipei/Attributions">Attributions</a></h5>
+							<h5><a href="https://2016.igem.org/Team:TAS_Taipei/Attributions">Attributions</a></h5>
+						</div>
+						<div>
+							<h5><a href="https://2016.igem.org/Team:TAS_Taipei/Standard_Pages">Wiki Standard Pages</a></h5>
 						</div>
 					</div>
 					<div style='height:140px;'>
 						<img src="https://static.igem.org/mediawiki/2015/3/34/Tas_icon_team.png">
-						<h4>Behind every tough iGem project lies a tough, hard-working yet cheerful group of students. <b>Meet the team!</b></h4>
+						<h4>Behind every tough iGem project lies a hard-working yet cheerful group of students. <b>Meet the team!</b></h4>
 					</div>
 				</div>
@@ Line 233: / Line 205: @@
 <br>
 <br>
-<div class="row center-block" style = "padding:10px;width:960px;background-color:#3321FB;box-shadow:0px 0px 5px black">
+<div class="row center-block" style = "padding:10px;width:960px;background-color:#07BEB8;box-shadow:0px 0px 5px black">
 		<div class="row" style = "text-align:center;">
 				<div class="col-sm-2">
-					<a href="https://2016.igem.org/Team:TAS_Taipei" style='text-decoration: none'><img src="https://static.igem.org/mediawiki/2015/2/2f/Tas_igemlogo.png
+					<a href="https://2015.igem.org/Team:TAS_Taipei" style='text-decoration: none'><img src="https://static.igem.org/mediawiki/2015/2/2f/Tas_igemlogo.png
 " alt="" style="width: 100px;"></a>
 				</div>
 				<div class="col-sm-8" style='text-align:center;'>
-					<a href="https://2016.igem.org/Team:TAS_Taipei" style='text-decoration: none;'>
+					<a href="https://2015.igem.org/Team:TAS_Taipei" style='text-decoration: none;'>
 						<h2 style="font-family:'Lato';letter-spacing:10px;color: white; font-size: 60px;  margin-top: 0;  margin-bottom: 0;"><b>
-						CATARACTS</b></h2>
+						C&#9678;UNTERACTS</b></h2>
 					</a>
 				</div>
@@ Line 250: / Line 222: @@
 			</div>
 </div>
+		<br>
+		<div class="row card" id='bodycontainer' class='row'>
+			<div class="col-sm-2" style='padding-left:8px;'>
+				<div id="category_navbar">
+					<ul class="nav nav-list" data-spy="affix" data-offset-top="160" style='-webkit-transform: translateZ(0);width:160px;margin-left:0' >
+						<li><a href="#overview">Overview</a></li>
+						<li><a href="#crystallin">Crystallin</a></li>
+						<li><a href="#gsr25hc">GSR/25HC</a></li>
+						<li><a href="#nanoparticle">Nanoparticles</a></li>
+						<li><a href="#eyedrop">Eyedrop</a></li>
+					</ul>
+				</div>
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+						<h1 id='overview'>Modeling</h1>
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+                                    <h3> Abstract </h4>
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+ 						                 <p>We answer two questions: How much GSR to maintain in the lens, and how to maintain that amount?  We find the amount of GSR needed in the lens (Model 2) to limit crystallin damage so the resulting cataract is less than LOCS 2.5 (Model 1). Then, we find the optimal design of eyedrops (Model 4) and nanoparticles that will maintain this amount of GSR in the lens (Model 3). These models allow our team to understand the impact of adding GSR-loaded nanoparticles into the lens, and to design a full treatment plan on how to prevent and treat cataracts. </p>
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+                                    <h3>Achievements</h4>
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+                                    <ul style="font-size:15px">
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+                                        <li>Designed a simple calculator to find amount of GSR or 25HC eyedrops needed for a patient's LOCS score.</li>
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+                                        <li>Bridged the gap between the medical, biological, and chemical measurement of crystallin damage.</li>
-                }
+                                        <li>Predicted impact of adding GSR and 25HC on the amount of crystallin damage in the lens.</li>
+                                        <li>Created Nanoparticle Customizer for doctors to find a full treatment plan.</li>
+                                        <li>Generalized our Customizer to allow other iGEM teams who wish to use nanoparticle drug delivery </li>
+                                        <li>Analyzed sensitivity of prototype, and suggested insights into optimal manufacturing and clinical use of our prototype.</li>
+                                        <li>Used Experimental data to develop Models 1 and 3.</li>
+                                    </ul>
+                                 </div>
+                            </div>
+                        </div>
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+						<h3> Outline </h3>
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-        <!-- Loading Screen -->
+						<h2>Introduction</h2>
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-        <!-- Slides Container -->
+  						<h3> Why Model? </h3>
-        <div u="slides" style="cursor: move; position: absolute; left: 0px; top: 0px; width: 1080px; height: 600px;
+						<p>In the lab, biologists are often unable to test everything experimentally. For example, in our cataracts project, cataract prevention occurs in the long-term, from 20-50 years. Obviously, although short experiments can provide us an idea of what prevention may look like, the power of computational biology allows us to model into the future. As a result, our modeling has been crucial in developing a prototype.</p>
-            overflow: hidden;">
-            <div><img u="image" src="https://static.igem.org/mediawiki/2015/0/00/Tas_frontpage_1.png"/></div>
+  						<h3> Focus </h3>
-            <div><div u="image" style = "lightgrey;text-align:center"><image src="https://static.igem.org/mediawiki/2015/d/df/Bg_fig6.gif"/></div>
+						<p>Most iGEM teams perform modeling on gene expression, which we accomplish in model 5. However, as our construct is not directly placed into the eyes, how our synthesized protein impacts the eyes after it is seperately transported is much more interesting. As a result, we spent the majority of our models on understanding the impacts on the eye.</p>
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-                    <p style = "color:white;font-size:32px;">
+						<h3>Guiding Questions </h3>
-                    INCREASING GSR/25HC
+						<ol>
-                    </p>
+						      <li>How much GSR do we want inside the lens?</li>
-                    <p style = "color:white;font-size: 20px">
+						      <li>How do we use nanoparticles to control the amount of GSR in the lens?</li>
-                    Our device produces GSR and 25HC
+						      <li>How do we synthesize GSR, package into NP, and send it into the eye?</li>
-                    </p>
+					        </ol>
+				</div>
                  </div>
-                </div>
-            <div><div u="image" style = "text-align:center"><image src="https://static.igem.org/mediawiki/2015/2/20/Exp_prototype.gif"/></div>
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-                    <p style = "color:white;font-size:32px;">
+<div class = "row">
-                    PROTOTYPE
+		<div class="col-sm-12">
-                    </p>
+				<h2 id = 'crystallin'>Model 1: Crystallin Damage</h2>
-                    <p style = "color:white;font-size: 20px">
+                        <h3>Abstract</h3>
-                    We designed and built a bandage with a semi-permeable membrane
+                        <p>In our experiments, absorbance measurements are meaningless without understanding how severe a cataract that absorbance measurement means. We use literature research to relate LOCS, the physician's scale of cataract severity) to absorbance, which is how we quantified crystallin damage in experiments. We use experimental data to understand how crystallin damage can be quantified by measuring absorbance. With this model, we can calculate how much crystallin damage we have to limit to reduce LOCS to an acceptable level.</p>
-                    </p>
-                </div>
+ 						<h3> Purpose </h3>
-            </div>
+ 						<p> How much do we need to limit crystallin damage so surgery is not needed? </p>
-            <div><div u="image" style = "text-align:center"><image src="https://static.igem.org/mediawiki/2015/6/6c/Tas_frontpage_2.jpeg"/></div>
-            <div u="caption" t="L" style="box-shadow: 0 0 10px 0;background-color:orange;padding:10px;position: absolute; top: 320px; left: 20px;">
+                        <h3>Measurement of Cataract Severity</h3>
-                    <p style = "width:350px; color:white;font-size:22px;">
+                        <div class="row">
-                    "iGEM is special. It creates a special place for me to practice my computational biology skills."
+                            <div class="col-sm-12">
-                    </p>
+                                    <p>
-                    <p style = "color:white;font-size: 16px">
+                                        There are four ways of measuring cataract severity, each used for a different purpose.
-                    - Avery Wang
+                                        <ol>
-                    </p>
+                                            <li><b>Lens Optical Cataract Scale (LOCS):</b> Physicians use this scale, from 0 – 6, to grade the severity of cataracts.</li>
-                </div>
+                                            <li><b>Opacity (%):</b> This is the physical, quantitative property of the LOC scale.</li>
-            </div>
+                                            <li><b>Absorbance at 397.5 nm:</b> This is the experimental method, used by our team in the lab (c.d.).</li>
-        </div>
+                                            <li><b>Crystallin Damage: </b>This is a chemical definition. We quantify cataract severity as a function of how much oxidizing agents there are, as well as how long crystalline is exposed to oxidizing agents. We define 1 crystallin damage unit as the damage done to human crystallin when exposed to 1 M hydrogen peroxide, the main oxidizing agent, for 1 hour.</li>
+                                        </ol>
+                                    </p>
+                            <</div>
+                        </div>
+                        <p>We use the unit of crystallin damage to connect cataract severity with the amount of GSR we add (in Model 2). We want to lower c.d. below so that the resulting cataract is of LOCS 2.5. For the rest of the model, our task is simple: relate each point of the LOCS scale to c.d., in order to connect to Model 2.</p>
+                        <h3>LOCS Equivalence to Absorbance: Literature Research</h3>
+                        <p>Past studies have done numerous studies on how absorbance measurements can be converted to the LOC scale that physicians end up using. With the results of ________ and ________, we construct the first three columns in Table 2.</p>
+                        <h3>Absorbance Equivalence to Crystallin Damage: Experimental Data</h3>
+                        <div class="row">
+                            <div class="col-sm-7">
+                                <div class="col-sm-12" >
+                                    <p>
+                                        We use experimental data from our team’s Cataract Lens Model (link).  In each trial, they added H2O2 to crystallin, and measured the resulting absorbance. The data used are shown in Table 1. We can calculate the theoretical c.d., and graph absorbance vs. crystallin damage in Figure 2.
+                                    </p>
+                                    <p>With this relation in Figure 2, we calculate the equivalent crystallin damage to each LOCS rating and its equivalent absorbance.</p>
+                                    <h3>Error Analysis</h3>
+                                    <p>It may be surprising that only around 1 M-h is required to induce moderately severe cataracts. Remember that this is done in the absence of antioxidation systems (GSR) and at an extremely high oxidizing concentration of H2O2 (1M of H2O2). In the lens, H2O2 has a much lower concentration, so severe cataracts are induced over months to years.</p>
+                                    <p>There are some limitations of the model that arise from our assumptions. We assume that fish and human lens contain similar crystallin proteins that are degraded in the similar manner (Assumption 4). In addition, we made a rough adjustment of data based our diluting procedure. For better results to create a human cataract model, experiments will need to be done on human lens, even better if done in vitro, without any dilutions.</p>
+                                </div>
+                            </div>
+                            <div class="col-sm-5" style="margin:0px">
+                                <div class="col-sm-12">
+                                    <p>
+                                        <table class="table table-bordered" style='width: 80%;margin-left:0%;'>
+							                 <caption style='caption-side:top;'><b>Table 2: Results of Model 1 – Equivalent values for LOCS, Opacity, Absorbance, and Crystallin Damage.</caption>
+							                 <thead>
+								                <tr>
+                                                    <th>LOCS</th>
+                                                    <th>Opacity (%)</th>
+                                                    <th>Absorbance (@397.5 nm)</th>
+                                                    <th>Crystallin Damage (M-h)</th>
+                                                </tr>
+                                            </thead>
+                                            <tr>
+                                                <th>0.0</th>
+                                                <th>0.00</th>
+                                                <th>0.0000</th>
+                                                <th>0.0000</th>
+                                            </tr>
+                                            <tr>
+                                                <th>0.5</th>
+                                                <th>3.24</th>
+                                                <th>0.0143</th>
+                                                <th>0.1327</th>
+                                            </tr>
+                                            <tr>
+                                                <th>1.0</th>
+                                                <th>6.65</th>
+                                                <th>0.0299</th>
+                                                <th>0.2774</th>
+                                            </tr>
+                                            <tr>
+                                                <th>1.5</th>
+                                                <th>10.81</th>
+                                                <th>0.0497</th>
+                                                <th>0.4610</th>
+                                            </tr>
+                                            <tr>
+                                                <th>2.0</th>
+                                                <th>15.88</th>
+                                                <th>0.0751</th>
+                                                <th>0.6966</th>
+                                            </tr>
+                                            <tr>
+                                                <th>2.5</th>
+                                                <th>21.95</th>
+                                                <th>0.1076</th>
+                                                <th>0.9981</th>
+                                            </tr>
+                                            <tr>
+                                                <th>3.0</th>
+                                                <th>29.07</th>
+                                                <th>0.1492</th>
+                                                <th>1.3840</th>
+                                            </tr>
+                                            <tr>
+                                                <th>4.0</th>
+                                                <th>46.37</th>
+                                                <th>0.2706</th>
+                                                <th>2.5101</th>
+                                            </tr>
+                                            <tr>
+                                                <th>5.0</th>
+                                                <th>66.05</th>
+                                                <th>0.4691</th>
+                                                <th>4.3514</th>
+                                            </tr>
+                                        </table>
+                                    </p>
+                                </div>
+                            </div>
+                        </div>
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-        <!--#endregion Bullet Navigator Skin End -->
-        <a style="display: none" href="http://www.jssor.com">Image Slider</a>
-    </div>
-<br>
-<br>
-<div class = "card" id = "bodycontainer" style = "overflow:hidden;font-family:Lato; text-align:left;">
+	<div class="accordionmenu1" class ="col-sm-12" >
-	<div class = "col-sm-12">
+  		<ul class="nav nav-tabs">
-		<h1 style = "padding:10px;background-color: rgb(33,50,250);color:white">
+   			 <li class="active"><a data-toggle="tab" href="#cryshome">Background</a></li>
-			ABSTRACT
+   			 <li><a data-toggle="tab" href="#crysmenu1">Assumptions</a></li>
-		</h1>
+   			 <li><a data-toggle="tab" href="#crysmenu2">Procedure</a></li>
-		<div style = "font-size:20px; line-height:40px">
+   			 <li><a data-toggle="tab" href="#crysmenu3">Results</a></li>
-            <div class = "col-sm-1"></div>
+   			 <li><a data-toggle="tab" href="#crysmenu4">Discussion</a></li>
-            <div class = "col-sm-10"><br>
+ 		 </ul>
+  		<div class="tab-content">
+   			 <div id="cryshome" class="tab-pane fade in active">
+      			<h3>Background</h3>
+                <div class="row">
+                    <div class="col-sm-8">
+                        <div class="col-sm-12" style="border:1px solid black">
+                            <p>There are four ways to measure cataract severity (how blurred the lens is):
+					           <ol>
+						          <li>Lens Optical Cataract Scale III (LOCS) - a scale from 0-6 used by physicians.</li>
+						          <li>Opacity (%) - used to calculate the LOC scale</li>
+						          <li>Absorbance at 397.5 nm - measurable in the lab.	</li>
+                                    <li>Crystallin Damage - used to quantify how much crystallin has been reacted with hydrogen peroxide to create insoluble, damaged crystallin. The following definition of crystallin damage is used:</li>
+					           </ol>
+                                \[c.d.(t) = \int_{0}^{\infty} [H_2O_2]_t dt\]
+				            </p>
+				            <p> In other words, 1 unit of crystallin damage, in M-h,  is equal to the damage caused by 1 molar concentration of hydrogen peroxide reacting crystallin in the eyes for 1 hour.</p>
+                        </div>
+                    </div>
+                    <div class="col-sm-4" style="background-color:lightpink;margin:0px">
+                        <div class="col-sm-12" style="border:1px solid black">
+                            <h3>LOCS Scale</h3><br> <br> <br><br> <br> <br> <br><br><br><br>
+                        </div>
+                    </div>
+                </div>
+   			 </div>
+    		<div id="crysmenu1" class="tab-pane fade">
+     			 <h3>Assumptions</h3>
+                <div class="row">
+                    <div class="col-sm-12">
+                        <div class="col-sm-12">
+                            <p>
+                                <ol>
+                                       <li>Definition of crystallin damage: Crystallin damage is proportional to the concentration of hydrogen peroxide, and the time of exposure. This is a valid assumption, supported by the fact that the reaction between cysteine (molecules on crystallin) and hydrogen peroxide is linear. </li>
+                                       <li>We assume that the amount of crystallin is far greater than the amount oxidized. Our product is meant for long-term cataract prevention and minor treatment, and is not suggested for patients with extremely severe cataracts. </li>
+                                       <li>When the experiments diluted the cataract lens protein, the amount of crystallin is diluted. However, the final absorbance of degraded crystallin is also diluted, so we assume any errors in absorbance is canceled out.</li>
+                                       <li>We assume that fish and human lens contain similar crystallin proteins.</li>
+                                </ol>
+      			           </p>
+                        </div>
+                    </div>
+                </div>
-                 <b>Cataracts</b> is the leading cause of blindness in the world. Oxidation of the lens crystallin protein, which leads to its misfolding and aggregation, is the main cause of cataracts. Among the 20 million people affected annually, over 50% are caused by old age. Currently, eye surgery is the only effective method for treatment. This method, however, is expensive and invasive. Therefore, our goal is to prevent and treat age related cataracts non-invasively by producing an eyedrop that includes <b>GSR</b> for prevention and <b>CH25H</b> for treatment. GSR catalyzes the conversion from GSSG to GSH in order to prevent crystallin oxidation. CH25H converts cholesterol into 25-hydroxycholesterol, which is a molecule that can reverse aggregation and restore solubility of the crystallin protein. To deliver proteins into the lens more efficiently, we engineered an <b>eyedrop containing biodegradable Chitosan nanoparticles</b> that encapsulate the proteins.
-			</div>
-            <br>
-			<div class = "col-sm-12">
+   			 </div>
-				<img class = "col-sm-12" src = "https://static.igem.org/mediawiki/2015/1/15/Tas_home_1.png">
+   			 <div id="crysmenu2" class="tab-pane fade">
+      			<h3>Procedure</h3>
+                 <div class="row">
+                    <div class="col-sm-8">
+                        <div class="col-sm-12" style="border:1px solid black">
+                            <p>
+                                <ol>
+                                    <li>In the first part, we find how the absorbance measurements in the lab are related to the severity of the cataracts. Through literature data, we can relate LOCS to the opacity of the lens. Then, via physical calculations, we can relate the opacity of the lens to the absorbance of the lens at 400 nm.</li>
+                                    <li>Then, we use our team’s experimental data in the cataract model. For each trial, the concentration of H2O2 and the length of exposure are given, so we can calculate the theoretical crystallin damage using the definition above and the assumptions we made. In each trial we also measured the absorbance, so we have a relation between crystallin damage and absorbance. </li>
+                                    <li>However, we need to make a minor adjustment, because absorbance is affected by dilution. When the fish lens was isolated, they were placed in Tris buffer and diluted. We calculate the ratio of volumes from diluted volume to the Tris buffer, and multiply each absorbance measurement by this value.</li>
+                                </ol>
+      			           </p>
+                        </div>
+                    </div>
+                    <div class="col-sm-4" style="background-color:lightpink;margin:0px">
+                        <div class="col-sm-12" style="border:1px solid black">
+                            <h3>LOCS Scale</h3><br> <br> <br><br> <br> <br> <br><br><br><br>
+                        </div>
+                    </div>
+                </div>
+   			 </div>
+   			 <div id="crysmenu3" class="tab-pane fade">
+                <h3>Results</h3>
+      			<table class="table table-bordered" style='width: 70%;margin-left:15%;'>
+                    <caption style='caption-side:top;'><b>Table 1: Results of Model 1 - Equivalent values for LOCS, Opacity, Absorbance, and Crystallin Damage. </b> </caption>
+							<tbody>
+								<tr>
+									<td>LOCS</td>
+									<td>0.0</td>
+									<td>0.5</td>
+									<td>1.0</td>
+                                    <td>1.5</td>
+									<td>2.0</td>
+                                    <td>2.5</td>
+									<td>3.0</td>
+									<td>4.0</td>
+									<td>5.0</td>
+								</tr>
+								<tr>
+									<td>Degree</td>
+									<td>None</td>
+									<td colspan="2">Trace</td>
+									<td colspan="3">Mild</td>
+									<td colspan="2">Moderate</td>
+									<td>Severe</td>
+								</tr>
+								<tr>
+									<td>Opacity (%)</td>
+									<td>0</td>
+                                    <td>3.24</td>
+									<td>6.65</td>
+									<td>10.81</td>
+									<td>15.88</td>
+									<td>21.95</td>
+									<td>29.07</td>
+									<td>46.37</td>
+									<td>66.05</td>
+								</tr>
+								<tr>
+									<td>Absorbance (a.u.)</td>
+									<td>0.0000</td>
+									<td>0.0143</td>
+									<td>0.0299</td>
+									<td>0.0497</td>
+									<td>0.0751</td>
+									<td>0.1076</td>
+									<td>0.1492</td>
+									<td>0.2706</td>
+                                    <td>0.4691</td>
+								</tr>
+                                <tr>
+									<td>Crystallin Damage (c.d.)</td>
+									<td>0.0000</td>
+									<td>0.1327</td>
+                                    <td>0.2774</td>
+									<td>0.4610</td>
+									<td>0.6966</td>
+									<td>0.9981</td>
+									<td>1.3840</td>
+									<td>2.5101</td>
+									<td>4.3514</td>
+								</tr>
+							</tbody>
+				</table>
+                 <br><br><br>
+                <table class="table table-bordered" style='width: 70%;margin-left:15%;'>
+                    <caption style='caption-side:top;'><b>Table 2: Experimental Data used for Model 1 from Cataract Lens Model (TAS) - Absorbance vs. Crystallin Damage </b></caption>
+							<tbody>
+                                <thead>
+                                    <td>Trial</td>
+									<td>H2O2 Concentration (M)</td>
+									<td>Exposure Time (h)</td>
+									<td>Crystallin Damage (c.d.)</td>
+                                    <td>Measured Absorbance (abs @400 nm)</td>
+                                </thead>
+								<tr>
+                                    <td>1</td>
+                                    <td>0.100</td>
+                                    <td>24.0</td>
+                                    <td>2.40</td>
+                                    <td>0.105</td>
+								</tr>
+                                <tr>
+                                    <td>2</td>
+                                    <td>0.100</td>
+                                    <td>46.5</td>
+                                    <td>4.65</td>
+                                    <td>0.451</td>
+								</tr>
+                                <tr>
+                                    <td>3</td>
+                                    <td>0.100</td>
+                                    <td>72.0</td>
+                                    <td>7.20</td>
+                                    <td>0.0.695</td>
+								</tr>
+                                <tr>
+                                    <td>4</td>
+                                    <td>0.100</td>
+                                    <td>20.0</td>
+                                    <td>2.00</td>
+                                    <td>0.089</td>
+								</tr>
+                                <tr>
+                                    <td>5</td>
+                                    <td>0.100</td>
+                                    <td>42.0</td>
+                                    <td>4.20</td>
+                                    <td>0.392</td>
+								</tr>
+                                <tr>
+                                    <td>6</td>
+                                    <td>0.100</td>
+                                    <td>15.0</td>
+                                    <td>1.50</td>
+                                    <td>0.093</td>
+								</tr>
+                                <tr>
+                                    <td>7</td>
+                                    <td>0.100</td>
+                                    <td>42.0</td>
+                                    <td>0.340</td>
+                                    <td>0.340</td>
+								</tr>
+                                <tr>
+                                    <td>8</td>
+                                    <td>0.100</td>
+                                    <td>67.0</td>
+                                    <td>6.70</td>
+                                    <td>0.563</td>
+								</tr>
+							</tbody>
+				</table>
+   			 </div>
+   			 <div id="crysmenu4" class="tab-pane fade">
+     			 <h3>Discussion</h3>
+                 <h4>Model Result</h4>
+      			    <div class="row">
+                        <div class="col-sm-6">
+                            <div class="col-sm-12" >
+                                <p>
+                                    The model successfully relates LOCS, opacity of lens, absorbance measurements, and the equivalent crystallin damage of the lens. The purpose of relating LOCS to crystallin damage, is that in Model 2, we will use chemical kinetics to determine how adding GSR to the lens will decrease the amount of crystallin damage. Exactly how much crystallin damage we need to decrease is determined by the desired LOCS. For example, if we want to have a LOCS rating of less than 2.5, then we must lower crystalline damage to only 0.9981 M-h.
+                                </p>
+                            </div>
+                        </div>
+                        <div class="col-sm-6" style="background-color:lightpink;margin:0px">
+                            <div class="col-sm-12">
+                                <p>
+                                    <br><br><br><br><br>
+                                </p>
+                            </div>
+                        </div>
+                    </div>
+                 <h4>Model Adjustment</h4>
+                    <div class="row">
+                        <div class="col-sm-6" style="background-color:lightpink;margin:0px">
+                            <div class="col-sm-12" >
+                                <p>
+                                    <br><br><br><br><br>
+                                </p>
+                            </div>
+                        </div>
+                        <div class="col-sm-6" >
+                            <div class="col-sm-12">
+                                <p>
+                                    When determining the relationship between absorbance and crystallin, in Figure 1 the best fit line has a x – intercept that is nonzero. However, when converting each absorbance rating to equivalent crystallin damage in Table 2, we ignore the constant term. When doing the experiments, the fish lens may have contained GSH that is still active, so the fact that the crystallin is exposed to H2O2, the degradation reaction does not happen until all GSH is depleted, and crystallin damage begins to form. We subtract around 1 unit of crystallin damage from all values.
+                                </p>
+                            </div>
+                        </div>
+                    </div>
+                 <h4>Error Analysis</h4>
+                 <div class="row">
+                        <div class="col-sm-12">
+                            <div class="col-sm-12" >
+                                <p>
+                                    It may be surprising that only around 1 M-h is required to induce moderately severe cataracts. Remember that this is done in the absence of antioxidation systems (GSR) and at an extremely high oxidizing concentration of H2O2 (1M of H2O2). In the lens, H2O2 has a much lower concentration, so severe cataracts are induced over months to years.
+                                </p>
+                            </div>
+                        </div>
+                    </div>
+                 <div class="row">
+                        <div class="col-sm-12">
+                            <div class="col-sm-12" >
+                                <p>
+                                    There are some limitations of the model that arise from our assumptions. We assume that fish and human lens contain similar crystallin proteins that are degraded in the similar manner (Assumption 4). Also, to simplify the experiments, the lens were diluted in Tris buffer. Because of this dilution, the actual crystallin damage is much lower, but so is the actual absorbance. We assume that the decrease in crystallin damage and absorbance is the same, so no adjustments need to be made for the relation between crystallin damage and absorbance (Assumption 3). For better results to create a human cataract model, experiments will need to be done on human lens, even better if done in vitro, without any dilutions.
+                                </p>
+                            </div>
+                        </div>
+                    </div>
+    			</div>
+ 		 </div>
+	</div>
+</div>  <!-- End Menu -->
+ 			    <h3> Conclusion</h3>
+ 						<div class="row">
+                        <div class="col-sm-6" style="background-color:lightpink;margin:0px">
+                            <div class="col-sm-12" >
+                                <p>
+                                    <br><br><br><br><br>
+                                </p>
+                            </div>
+                        </div>
+                        <div class="col-sm-6">
+                            <div class="col-sm-12">
+                                <p>
+                                    For surgery to not be needed, the LOCS value has to be below 2.5. This is equivalent to 21.95% in light opacity or 0.1076 abs units. Based on the results of our experiments, this is equivalent to 0.9981 units of crystallin damage, the damage done to crystallin if exposed to 0.9981 M of H2O2 for 1 hr.
+                                    For future models, this value 0.9981 units of c.d. will be called the crystallin damage threshold for LOCS 2.5.
+                                </p>
+                            </div>
+                        </div>
+                    </div>
+	</div> <!-- Container -->
+</div> <!-- Container -->
+<div class = "row">
+		<div class="col-sm-12">
+						<h2 id = 'gsr25hc'>Model 2: GSR/25HC Chemical Pathway</h2>
+                        <div class="row">
+                                <div class="col-sm-6" >
+                                        <h3> Abstract </h3>
+                                        <p> The key question: <b>How much GSR to add?</b> Now that we know how much we need to limit crystallin damage, we use systems of ordinary differential equation to model the GSR Pathway. We calculate the necessary GSR concentration to be maintained over 50 years so that the resulting cataract is below LOCS 2.5./p>
+                                        </p>
+                                </div>
+                                <div class="col-sm-6" >
+                                        <h3> Purpose </h3>
+                                        <p> How much GSR do we need to maintain in the lens so that the crystallin damage recorded over 50 years is below the threshold for LOCS 2.5? </p>
+                                </div>
+                        </div>
+                        <h3> Chemical Kinetics Model: Differential Equations </h3>
+                        <div class="row">
+                                <div class="col-sm-12" >
+                                        <p> By the Law of Mass Action, Michaelis-Menten Enzyme kinetics, Ping-pong mechanism, and the Law of Passive Diffusion, we build a system of 10 differential equations based on 6 chemical reactions. All parameters, constants, and initial conditions are based off literature data. Estimates made are also shown with assumptions and reasoning. The details are shown in the collapsible for interested readers. </p>
+                                </div>
+                        </div>
+                        <div class="row">
+                                <div class="col-sm-6" >
+                                        <h3>Blackbox Approach: Testing GSR Impact </h3>
+                                        <p> Image</p>
+                                </div>
+                                <div class="col-sm-6" >
+                                        <h3>  </h3>
+                                        <p> We will vary the input, Initial GSR concentration, from 0 to 100 uM, holding all other variables constant, and numerically solve for the amount of hydrogen peroxide over time. With this graph, we can find the amount of crystallin damage accumulated over 20 to 50 years if different levels of GSR is maintained.  </p>
+                                </div>
+                        </div>
+    </div>
+<button class="accordion">Background, Method, Results, Discussion</button>
+<div class="panel">
+	<div class="accordionmenu1" class ="col-sm-12" >
+  		<ul class="nav nav-tabs">
+   			 <li class="active"><a data-toggle="tab" href="#gsrhome">Background</a></li>
+   			 <li><a data-toggle="tab" href="#gsrmenu1">Method</a></li>
+   			 <li><a data-toggle="tab" href="#gsrmenu2">Results Part 1</a></li>
+   			 <li><a data-toggle="tab" href="#gsrmenu2">Results Part 2</a></li>
+   			 <li><a data-toggle="tab" href="#gsrmenu3">Discussion</a></li>
+ 		 </ul>
+  		<div class="tab-content">
+   			 <div id="gsrhome" class="tab-pane fade in active">
+      			<h4>Background</h4>
+				<p> The following 6 reactions describe the antioxidant system inside the cortex and nucleus.</p>
+$$GP_{xr}+[H_2O_2]_{in}+H^+ \xrightarrow[]{k_1} GP_{xo}+H_2O ...(1)$$
+$$GP_{xo}+GSH+H^+ \xrightarrow[]{k_2} [GS-GP_x]+H_2O ...(2)$$
+$$[GS-GP_x] + GSH \xrightarrow[]{k_3} GP_{xr}+GSSG+H^+ ...(3)$$
+$$NADPH \xrightarrow[GSR]{k4, K_{4M}} NADP^+ ...(4)$$
+$$GSSG \xrightarrow[GSR']{k_5, K_{5M}} 2GSH ...(5)$$
+$$[H_2O_2]_{out} \xrightarrow[]{k_5} [H_2O_2]_{in} ...(6)$$
+				<p> Each reaction will be discussed in detail, and we will derive rate equations.</p>
+                 <p><b>Reaction 1:</b>As hydrogen ions are numerous are negligible in the reaction, we will ignore it. By the <b>law of mass</b> action, the rate of this reaction is: $$r_1=k_1[GP_{xr}][H_2O_2]_{in}$$</p>
+                 <p><b>Reaction 2:</b> By the <b>law of mass</b> action, the rate of this reaction is: $$r_2=k_2[GP_{xo}][GSH]$$</p>
+                 <p><b>Reaction 3:</b> By the <b>law of mass</b> action, the rate of this reaction is: $$r_3=k_3[GS-GP_x][GSH]$$</p>
+                 <p><b>Summary of Reaction 1-3:</b>In these reactions, hydrogen peroxide is reduced to water. GSH is consumed to recycle the enzyme GPx back into reduced form, to neutralize more hydrogen peroxide.</p>
+                 <br>
+                 <p><b>Reaction 4:</b> By<b>Michaelis-Menten kinetics </b>and the <b>Ping-Pong mechanism</b>, the rate of this reaction, with rate constant k4, and Michaelis-Menten constant Km4, is: $$r_4=k_4\frac{[NADPH]}{K_{4M}+[NADPH]}$$</p>
+                 <p><b>Reaction 5:</b> By<b>Michaelis-Menten kinetics </b>and the <b>Ping-Pong mechanism</b>, the rate of this reaction, with rate constant k5, and Michaelis-Menten constant Km5, is: $$r_5=k_5\frac{[GSSG]}{K_{4M}+[GSSG]}$$</p>
+                 <p><b>Summary of Reaction 4-5</b>: In these, GSSG is reduced back to form GSH, using the enzyme GSR. This is necessary for antioxidation to continue as reaction 1 is constantly using GSH, converting them to GSSG.</p>
+                 <br>
+                 <p><b>Reaction 6:</b> By the <b>Law of Passive Diffusion</b>, the rate of diffusion into the cortex and lens is: is: $$r_6=k_6([H_2O_2]_{out}-[H_2O_2]_{in})$$</p>
+   			 </div>
+    		<div id="gsrmenu1" class="tab-pane fade">
+     			 <h4>Differential Equations</h4>
+      			<p>We have six reaction rates derived from above. Now, we will form differential equations, where every time a species is used as a reactant, the reaction rate will be subtracted from the species’ derivative, while each time it is formed as a product, the reaction rate will be added to the species’ derivative. We will go through each species in detail:</p>
+                <p>Substituting the rate of each reaction, we get the following system of differential equations. </p>
+     			<p>
+                    $$\frac{d[GP_{xr}]}{dt}=k_3[GS-GP_x][GSH]-k_1[GP_{xr}][H_2O_2]_{in}$$
+                    $$\frac{d[H_2O_2]}{dt}=k_6[[H_2O_2]_{out}-{H_2O_2]_{in}]-k_1[GP_{xr}][H_2O_2]_{in}$$
+                    $$\frac{d[H_2O_2]}{dt}=k_1([H_2O_2]_{out} - [H_2O_2]_{in})-k_1[GP_{xr}][H_2O_2]_{in}$$
+                    $$\frac{d[GP_{x0}]}{dt}=k_1[GP_{xr}][H_2O_2]_{in}-k_2[GP_{xo}][GSH]$$
+                    $$\frac{d[H_2O]}{dt}=k_1[GP_{xr}][H_2O_2]_{in}+k_2[GP_{xo}][GSH]$$
+                    $$\frac{d[GSH]}{dt}=2k_5[GSR']\frac{[GSSG]}{K_{5M}+[GSSG]}-k_2[GP_{xo}][GSH]-k_3[GS-GP_x][GSH]$$
+                    $$\frac{d[GS-GP_x]}{dt}=k_2[GP_{xo}][GSH]-k_3[GS-GP_x][GSH]$$
+                    $$\frac{d[GSSG]}{dt}=k_3[GS-GP_x][GSH]-k_5[GSR']\frac{[GSSG]}{K_{5M}+[GSSG]}$$
+                    $$\frac{d[NADPH]}{dt}=-k_4[GSR]\frac{[NADPH]}{K_{4M}+[NADPH]}$$
+                    $$\frac{d[GSR]}{dt}=k_5[GSR']\frac{[GSSG]}{K_{5M}+[GSSG]}-k_4[GSR]\frac{[NADPH]}{K_{4M}+[NADPH]}$$
+                    $$\frac{d[GSR']}{dt}=k_4[GSR]\frac{[NADPH]}{K_{4M}+[NADPH]}-k_5[GSR']\frac{[GSSG]}{K_{5M}+[GSSG]}$$
+      			</p>
+   			 </div>
+   			 <div id="gsrmenu2" class="tab-pane fade">
+      			<h4>Part 1 Results</h4>
+      			<table class="table table-bordered" style='width: 70%;margin-left:15%;'>
+							<caption style='caption-side:top;'><b>Table 1: Data obtained from XXX<b> relating each value of the LOCS scale, to opacity values. </caption>
+							<tbody>
+								<tr>
+									<td>LOCS</td>
+									<td>0.0</td>
+									<td>0.5</td>
+									<td>1.0</td>
+									<td>2.0</td>
+									<td>3.0</td>
+									<td>4.0</td>
+									<td>5.0</td>
+									<td>6.0</td>
+								</tr>
+								<tr>
+									<td>Degree</td>
+									<td>None</td>
+									<td></td>
+									<td>Trace</td>
+									<td>Mild</td>
+									<td>Surgery Suggested</td>
+									<td>Moderate</td>
+									<td>Severe</td>
+									<td>Very Severe</td>
+								</tr>
+								<tr>
+									<td>Opacity (%)</td>
+									<td>0.34</td>
+									<td>4.24</td>
+									<td>5.80</td>
+									<td>18.88</td>
+									<td>23.60</td>
+									<td>49.14</td>
+									<td>65.61</td>
+									<td>90+</td>
+								</tr>
+								<tr>
+									<td>Absorbance (a.u.)</td>
+									<td>0.001</td>
+									<td>0.019</td>
+									<td>0.026</td>
+									<td>0.091</td>
+									<td>0.117</td>
+									<td>0.294</td>
+									<td>0.464</td>
+									<td>1.3+</td>
+								</tr>
+							</tbody>
+						</table>
+<p> We wish to remain below clinically significant levels, so we will reach attempt to lower the  LOCS rating of a cataract to below grade 2.5, which means we want to control GSR such that the crystallin damage results in less than 0.108 a.u. at absorbance at 397.5 nm. </p>
+   			 </div>
+   			 <div id="gsrmenu3" class="tab-pane fade">
+   			 </div>
+   			 <div id="gsrmenu4" class="tab-pane fade">
+     			 <h4>Menu 3</h4>
+      			<p>Eaque ipsa quae ab illo inventore veritatis et quasi architecto beatae vitae dicta sunt explicabo.</p>
+    			</div>
+ 		 </div>
+	</div>
+</div>  <!-- End Menu -->
+                        <h3></h3>
+                        <div class="row">
+                            <div class="col-sm-6">
+                                <div class="col-sm-12" >
+                                    <p>
+                                        <br><br><br><br><br>
+                                    </p>
+                                </div>
+                            </div>
+                            <div class="col-sm-6" >
+                                <div class="col-sm-12">
+                                    <p>
+                                        When determining the relationship between absorbance and crystallin, in Figure 1 the best fit line has a x – intercept that is nonzero. However, when converting each absorbance rating to equivalent crystallin damage in Table 2, we ignore the constant term. When doing the experiments, the fish lens may have contained GSH that is still active, so the fact that the crystallin is exposed to H2O2, the degradation reaction does not happen until all GSH is depleted, and crystallin damage begins to form. We subtract around 1 unit of crystallin damage from all values.
+                                    </p>
+                                </div>
+                            </div>
+ 						<h4> Conclusion</h4>
+ 						<p> Conclusion</p>
+	</div> <!-- Container -->
+</div> <!-- Container -->
+<div class = "row">
+		<div class="col-sm-12">
+						<h2 id = 'nanoparticle'>Model 3: Nanoparticles</h2>
+ 						<h4> Abstract </h4>
+ 						<p> Abstract </p>
+ 						<h4> Purpose </h4>
+ 						<p> Purpose </p>
+<button class="accordion">Background, Method, Results, Discussion</button>
+<div class="panel">
+	<div class="accordionmenu1" class ="col-sm-12" >
+  		<ul class="nav nav-tabs">
+   			 <li class="active"><a data-toggle="tab" href="#nphome">Background</a></li>
+   			 <li><a data-toggle="tab" href="#npmenu1">Method</a></li>
+   			 <li><a data-toggle="tab" href="#npmenu2">Results Part 1</a></li>
+   			 <li><a data-toggle="tab" href="#npmenu2">Results Part 2</a></li>
+   			 <li><a data-toggle="tab" href="#npmenu3">Discussion</a></li>
+ 		 </ul>
+  		<div class="tab-content">
+   			 <div id="home" class="tab-pane fade in active">
+      			<h4>Background</h4>
+				<p>There are three quantifiers of how severe cataract formation is, two are measurable, one is not.
+					<ol>
+						<li>Absorbance @ 397.5 nm, which is measured with lab equipment.</li>
+						<li>LOCS scale, subjectively measured by physicians on a scale from 0 - 6.
+</li>
+						<li>Crystallin Damage, which we define as the following (for any time $t$)																														    </li>
+					</ol>
+				</p>
+\[c.d.(t) = \int_{0}^{\infty} [H_2O_2]_t dt\]
+				<p> In other words, 1 unit of crystallin damage, in M-h,  is equal to the damage caused by 1 molar concentration of hydrogen peroxide reacting crystallin in the eyes for 1 hour.</p>
+                               <p> In making this definition, we assume that crystallin damage is directly proportional to the amount of time crystallin is exposed to hydrogen peroxide. Hydrogen peroxide causes damage by forming disulfide bridges within cysteine molecules on crystallin. This changes the structure of crystallin, causing misfolding and cataract damage. Our linear assumption is valid because the rate for this reaction is first order with respect to hydrogen peroxide concentration. </p>
+   			 </div>
+    		<div id="npmenu1" class="tab-pane fade">
+     			 <h4>Method</h4>
+      			<p>We will relate the three by doing the following:
+     				 <ol>
+                                       <li>Relate LOCS scale to opacity via literature research. </li>
+                                       <li>Relate opacity to light transmittance via literature research. </li>
+                                       <li>Relate light transmittance to absorbance via physical calculations. </li>
+                                       <li>Relate absorbance to crystallin damage via experimental data. </li>
+     				 </ol>
+      			</p>
+   			 </div>
+   			 <div id="npmenu2" class="tab-pane fade">
+      			<h4>Part 1 Results</h4>
+      			<table class="table table-bordered" style='width: 70%;margin-left:15%;'>
+							<caption style='caption-side:top;'><b>Table 1: Data obtained from XXX<b> relating each value of the LOCS scale, to opacity values. </caption>
+							<tbody>
+								<tr>
+									<td>LOCS</td>
+									<td>0.0</td>
+									<td>0.5</td>
+									<td>1.0</td>
+									<td>2.0</td>
+									<td>3.0</td>
+									<td>4.0</td>
+									<td>5.0</td>
+									<td>6.0</td>
+								</tr>
+								<tr>
+									<td>Degree</td>
+									<td>None</td>
+									<td></td>
+									<td>Trace</td>
+									<td>Mild</td>
+									<td>Surgery Suggested</td>
+									<td>Moderate</td>
+									<td>Severe</td>
+									<td>Very Severe</td>
+								</tr>
+								<tr>
+									<td>Opacity (%)</td>
+									<td>0.34</td>
+									<td>4.24</td>
+									<td>5.80</td>
+									<td>18.88</td>
+									<td>23.60</td>
+									<td>49.14</td>
+									<td>65.61</td>
+									<td>90+</td>
+								</tr>
+								<tr>
+									<td>Absorbance (a.u.)</td>
+									<td>0.001</td>
+									<td>0.019</td>
+									<td>0.026</td>
+									<td>0.091</td>
+									<td>0.117</td>
+									<td>0.294</td>
+									<td>0.464</td>
+									<td>1.3+</td>
+								</tr>
+							</tbody>
+						</table>
+<p> We wish to remain below clinically significant levels, so we will reach attempt to lower the  LOCS rating of a cataract to below grade 2.5, which means we want to control GSR such that the crystallin damage results in less than 0.108 a.u. at absorbance at 397.5 nm. </p>
+   			 </div>
+   			 <div id="npmenu3" class="tab-pane fade">
+   			 </div>
+   			 <div id="npmenu4" class="tab-pane fade">
+     			 <h4>Menu 3</h4>
+      			<p>Eaque ipsa quae ab illo inventore veritatis et quasi architecto beatae vitae dicta sunt explicabo.</p>
+    			</div>
+ 		 </div>
+	</div>
+</div>  <!-- End Menu -->
+ 						<h4> Conclusion</h4>
+ 						<p> Conclusion </p>
+	</div> <!-- Container -->
+</div> <!-- Container -->
+<div class = "row">
+		<div class="col-sm-12">
+						<h2 id = 'eyedrop'>Model 4: Eyedrops</h2>
+ 						<h4> Abstract </h4>
+ 						<p> Abstract </p>
+ 						<h4> Purpose </h4>
+ 						<p> Purpose </p>
+<button class="accordion">Background, Method, Results, Discussion</button>
+<div class="panel">
+	<div class="accordionmenu1" class ="col-sm-12" >
+  		<ul class="nav nav-tabs">
+   			 <li class="active"><a data-toggle="tab" href="#eyehome">Background</a></li>
+   			 <li><a data-toggle="tab" href="#eyemenu1">Method</a></li>
+   			 <li><a data-toggle="tab" href="#eyemenu2">Results Part 1</a></li>
+   			 <li><a data-toggle="tab" href="#eyemenu2">Results Part 2</a></li>
+   			 <li><a data-toggle="tab" href="#eyemenu3">Discussion</a></li>
+ 		 </ul>
+  		<div class="tab-content">
+   			 <div id="eyehome" class="tab-pane fade in active">
+      			<h4>Background</h4>
+				<p>There are three quantifiers of how severe cataract formation is, two are measurable, one is not.
+					<ol>
+						<li>Absorbance @ 397.5 nm, which is measured with lab equipment.</li>
+						<li>LOCS scale, subjectively measured by physicians on a scale from 0 - 6.
+</li>
+						<li>Crystallin Damage, which we define as the following (for any time $t$)																														    </li>
+					</ol>
+				</p>
+\[c.d.(t) = \int_{0}^{\infty} [H_2O_2]_t dt\]
+				<p> In other words, 1 unit of crystallin damage, in M-h,  is equal to the damage caused by 1 molar concentration of hydrogen peroxide reacting crystallin in the eyes for 1 hour.</p>
+                               <p> In making this definition, we assume that crystallin damage is directly proportional to the amount of time crystallin is exposed to hydrogen peroxide. Hydrogen peroxide causes damage by forming disulfide bridges within cysteine molecules on crystallin. This changes the structure of crystallin, causing misfolding and cataract damage. Our linear assumption is valid because the rate for this reaction is first order with respect to hydrogen peroxide concentration. </p>
+   			 </div>
+    		<div id="eyemenu1" class="tab-pane fade">
+     			 <h4>Method</h4>
+      			<p>We will relate the three by doing the following:
+     				 <ol>
+                                       <li>Relate LOCS scale to opacity via literature research. </li>
+                                       <li>Relate opacity to light transmittance via literature research. </li>
+                                       <li>Relate light transmittance to absorbance via physical calculations. </li>
+                                       <li>Relate absorbance to crystallin damage via experimental data. </li>
+     				 </ol>
+      			</p>
+   			 </div>
+   			 <div id="eyemenu2" class="tab-pane fade">
+      			<h4>Part 1 Results</h4>
+      			<table class="table table-bordered" style='width: 70%;margin-left:15%;'>
+							<caption style='caption-side:top;'><b>Table 1: Data obtained from XXX<b> relating each value of the LOCS scale, to opacity values. </caption>
+							<tbody>
+								<tr>
+									<td>LOCS</td>
+									<td>0.0</td>
+									<td>0.5</td>
+									<td>1.0</td>
+									<td>2.0</td>
+									<td>3.0</td>
+									<td>4.0</td>
+									<td>5.0</td>
+									<td>6.0</td>
+								</tr>
+								<tr>
+									<td>Degree</td>
+									<td>None</td>
+									<td></td>
+									<td>Trace</td>
+									<td>Mild</td>
+									<td>Surgery Suggested</td>
+									<td>Moderate</td>
+									<td>Severe</td>
+									<td>Very Severe</td>
+								</tr>
+								<tr>
+									<td>Opacity (%)</td>
+									<td>0.34</td>
+									<td>4.24</td>
+									<td>5.80</td>
+									<td>18.88</td>
+									<td>23.60</td>
+									<td>49.14</td>
+									<td>65.61</td>
+									<td>90+</td>
+								</tr>
+								<tr>
+									<td>Absorbance (a.u.)</td>
+									<td>0.001</td>
+									<td>0.019</td>
+									<td>0.026</td>
+									<td>0.091</td>
+									<td>0.117</td>
+									<td>0.294</td>
+									<td>0.464</td>
+									<td>1.3+</td>
+								</tr>
+							</tbody>
+						</table>
+<p> We wish to remain below clinically significant levels, so we will reach attempt to lower the  LOCS rating of a cataract to below grade 2.5, which means we want to control GSR such that the crystallin damage results in less than 0.108 a.u. at absorbance at 397.5 nm. </p>
+   			 </div>
+   			 <div id="eyemenu3" class="tab-pane fade">
+   			 </div>
+   			 <div id="eyemenu4" class="tab-pane fade">
+     			 <h4>Menu 3</h4>
+      			<p>Eaque ipsa quae ab illo inventore veritatis et quasi architecto beatae vitae dicta sunt explicabo.</p>
+    			</div>
+ 		 </div>
+	</div>
+</div>  <!-- End Menu -->
+ 						<h4> Conclusion</h4>
+ 						<p> Conclusion</p>
+	</div> <!-- Container -->
+</div> <!-- Container -->
+				<div class = "row">
+					<div class="col-sm-12">
+						<h2 id ="X">Conclusion</h2>
+						<p class="col-sm-12">Yay</p>
+					</div>
+				</div>
+				<div class = "row">
+					<div class="col-sm-12">
+						<h3>Citations</h3>
+					        <br> <br>  <br>  <br>  <br>  <br>  <br>  <br>
+					</div>
+				</div>
 			</div>
-		</div>
+		</div>
 	</div>
+	<br>
+<br><br>
+<style type='text/css'>
+     #bg { position: fixed; top: 0; left: 0; }
+     .bgwidth { width: 100%; }
+     .bgheight { height: 100%; }
+</style>
-</div>
+<div class="backgroundpic">
+<img src="https://static.igem.org/mediawiki/2016/d/dd/T--TAS_Taipei--TaipeiBackground-reflected3.png" style="z-index:0" width="100%" height="100%" id="bg" alt="" >
 </div>
-<br>
+<script>
-<br><br>
+var nowRadius = 0
+$(function() {
+    $({blurRadius: 0}).animate({blurRadius: 10}, {
+        duration: 20000,
+        easing:'swing', // or "linear"
+                         // use jQuery UI or Easing plugin for more options
+        step: function() {
+            console.log(this.blurRadius);
+            if ($("#bluebutton").hasClass("isOn") ) {return;};
+            if($('#redbutton').hasClass("isOn") ) {return;}
+            $('.backgroundpic').css({
+                "-webkit-filter": "blur("+this.blurRadius+"px)",
+                "filter": "blur("+this.blurRadius+"px)"
-<canvas id="canvas-container" style = "z-index:-1"></canvas>
+            });
-<script type="text/javascript" src='https://2015.igem.org/Template:TAS_Taipei/js/field?action=raw&amp;ctype=text/javascript'></script>
+            nowRadius = this.blurRadius;
-</body>
+         var LOCSnum = Math.round(nowRadius*6/9);
+         if (LOCSnum > 6) LOCSnum = "6+";
+         $('#LOCS').text(LOCSnum+"");
+         if (LOCSnum ==0) document.getElementById('bluebutton').click();
+        }
+    });
-<!--?action=raw&amp;ctype=text/javascript-->
+});
+startBlur= function(speed) {
-</p>
+     $({blurRadius: nowRadius}).animate({blurRadius: 10}, {
-<!--
+        duration: speed,
-NewPP limit report
+        easing: 'swing', // or "linear"
-CPU time usage: 0.004 seconds
+                         // use jQuery UI or Easing plugin for more options
-Real time usage: 0.004 seconds
+        step: function() {
-Preprocessor visited node count: 4/1000000
+            console.log(this.blurRadius);
-Preprocessor generated node count: 24/1000000
+            if ($("#bluebutton").hasClass("isOn") ) {return;};
-Post‐expand include size: 0/2097152 bytes
+            if($('#redbutton').hasClass("isOn") ) {return;}
-Template argument size: 0/2097152 bytes
-Highest expansion depth: 2/40
+            $('.backgroundpic').css({
-Expensive parser function count: 0/100
+                "-webkit-filter": "blur("+this.blurRadius+"px)",
--->
+                "filter": "blur("+this.blurRadius+"px)"
+            });
+         nowRadius = this.blurRadius;
+         var LOCSnum = Math.round(nowRadius*6/9);
+         if (LOCSnum > 6) LOCSnum = "6+";
+         $('#LOCS').text(LOCSnum+"");
+        }
+    });
+};
+stopBlur= function(speed) {
+     $({blurRadius: nowRadius}).animate({blurRadius: 0}, {
+        duration: speed,
+        easing: 'swing', // or "linear"
+                         // use jQuery UI or Easing plugin for more options
+        step: function() {
+            console.log(this.blurRadius);
+         if ($("#redbutton").hasClass("isOn") ) {} else{return;};
+            $('.backgroundpic').css({
+                "-webkit-filter": "blur("+this.blurRadius+"px)",
+                "filter": "blur("+this.blurRadius+"px)"
+            });
+          nowRadius = this.blurRadius;
+         var LOCSnum = Math.round(nowRadius*6/9);
+         if (LOCSnum > 6) LOCSnum = "6+";
+         $('#LOCS').text(LOCSnum+"");
+        }
+    });
+};
+function chooseBlur() {
+   if ($("#redbutton").hasClass("isOn") )
+       {
+       stopBlur(3500);
+            }
+     else {
+             if($("#bluebutton").hasClass("isOn") ) {}
+             else {startBlur(12000);}
+           }
+};
+</script>
+<script>
+function switchToggleB() {
+    if ( $("#bluebutton").hasClass("isOn") ) {
+         $("#bluebutton").removeClass("isOn"); }
+   else { $("#bluebutton").addClass("isOn"); }
+};
+function switchToggleR() {
+    if ( $("#redbutton").hasClass("isOn") ) {
+         $("#redbutton").removeClass("isOn"); }
+   else { $("#redbutton").addClass("isOn"); }
+};
+</script>
+<canvas id="canvas-container" style = "z-index:-1" hidden></canvas>
+<script type="text/javascript" src='https://2015.igem.org/Template:TAS_Taipei/js/field?action=raw&ctype=text/javascript' hidden></script/>
+<script type="text/javascript">
+/* Toggle between adding and removing the "active" and "show" classes when the user clicks on one of the "Section" buttons. The "active" class is used to add a background color to the current button when its belonging panel is open. The "show" class is used to open the specific accordion panel */
+var acc = document.getElementsByClassName("accordion");
+var i;
+for (i = 0; i < acc.length; i++) {
+    acc[i].onclick = function(){
+        this.classList.toggle("active");
+        this.nextElementSibling.classList.toggle("show");
+    }
+}
+</script>
+<script type="text/javascript">
+$("#category_navbar a").on('click', function(event) {
+    // Make sure this.hash has a value before overriding default behavior
+    if (this.hash !== "") {
+      // Prevent default anchor click behavior
+      event.preventDefault();
+      // Store hash0
+      var hash = this.hash;
+      // Using jQuery's animate() method to add smooth page scroll
+      // The optional number (800) specifies the number of milliseconds it takes to scroll to the specified area
+      $('html, body').animate({
+        scrollTop: $(hash).offset().top
+      }, 800, function(){
+        // Add hash (#) to URL when done scrolling (default click behavior)
+        window.location.hash = hash;
+      });
+    }  // End if
+  });
+</script>
+<div id="slideout">
+    <div id="slidecontent">
+        <h3>Prevention</h3>
+        <h5>GSR Eyedrop</h5>
+        <label class="switch">
+             <input id="bluebutton" onClick="switchToggleB(); chooseBlur()" type="checkbox">
+             <div class="slider round bluecolorbutton"></div>
+        </label>
+<br>
+        <h3>Treatment</h3>
+        <h5>25HC Eyedrop</h5>
+        <label class="switch">
+             <input id="redbutton" onClick="switchToggleR(); chooseBlur()" type="checkbox">
+             <div class="slider round redcolorbutton"></div>
+        </label>
+        <h4><b> LOCS: <span id="LOCS">0</span> </b></h4>
-<!-- Saved in parser cache with key 2015_igem_org:pcache:idhash:1828-0!*!*!*!*!*!* and timestamp 20151029153229 and revision id 399114
- -->
-</div>			<div class="visualClear"></div>
-		    </div>
-		</div>
      </div>
-	</body>
+    <div id="clickme">
+    <h2 class="vertical-text" style="Serif" >
+             Eyedrops
+    </h2>
+    </div>
+</div>
+<style type='text/css'>
+#slideout {
+    background: #FFD700;
+    position: fixed;
+    height: 300px;
+    width: 200px;
+    top: 30%;
+    right:-150px;
+    padding-left: 60px;
+    z-index:30;
+    border-radius: 25px;
+}
+#clickme {
+    position: absolute;
+    top: 0; left: 0;
+    height: 300px;
+    width: 50px;
+    background: #C0FF3E;
+    z-index:30;
+    border-radius: 25px 5px 5px 25px;
+}
+#slidecontent {
+    float:left;
+}
+.vertical-text {
+	transform: rotate(90deg);
+	transform-origin: left bottom 0;
+  float: left;
+}
+/* The switch - the box around the slider */
+.switch {
+  position: relative;
+  display: inline-block;
+  width: 60px;
+  height: 34px;
+}
+/* Hide default HTML checkbox */
+.switch input {display:none;}
+/* The slider */
+.slider {
+  position: absolute;
+  cursor: pointer;
+  top: 0;
+  left: 0;
+  right: 0;
+  bottom: 0;
+  background-color: #ccc;
+  -webkit-transition: .4s;
+  transition: .4s;
+}
+.slider:before {
+  position: absolute;
+  content: "";
+  height: 26px;
+  width: 26px;
+  left: 4px;
+  bottom: 4px;
+  background-color: white;
+  -webkit-transition: .4s;
+  transition: .4s;
+}
+input:checked + .slider.bluecolorbutton {
+  background-color: #2196F3;
+}
+input:focus + .slider.bluecolorbutton {
+  box-shadow: 0 0 1px #2196F3;
+}
+input:checked + .slider.redcolorbutton {
+  background-color: #FF0000;
+}
+input:focus + .slider.redcolorbutton {
+  box-shadow: 0 0 1px #FF0000;
+}
+input:checked + .slider:before {
+  -webkit-transform: translateX(26px);
+  -ms-transform: translateX(26px);
+  transform: translateX(26px);
+}
+/* Rounded sliders */
+.slider.round {
+  border-radius: 34px;
+}
+.slider.round:before {
+  border-radius: 50%;
+}
+</style>
+<script>
+$(function () {
+    var rightVal = -150;
+    $("#clickme").click(function () {
+        rightVal = (rightVal * -1) - 150;
+        $(this).parent().animate({right: rightVal + 'px'}, {queue: false, duration: 500});
+    });
+});
+</script>
+</body>
 </html>

Difference between revisions of "Team:TAS Taipei/Modeling"

Latest revision as of 14:51, 6 October 2016

C◎UNTERACTS

Modeling

Abstract

Achievements

Outline

Introduction

Why Model?

Focus

Guiding Questions

Model 1: Crystallin Damage

Abstract

Purpose

Measurement of Cataract Severity

LOCS Equivalence to Absorbance: Literature Research

Absorbance Equivalence to Crystallin Damage: Experimental Data

Error Analysis

Background

LOCS Scale

Assumptions

Procedure

LOCS Scale

Results

Discussion

Model Result

Model Adjustment

Error Analysis

Conclusion

Model 2: GSR/25HC Chemical Pathway

Abstract

Purpose

Chemical Kinetics Model: Differential Equations

Blackbox Approach: Testing GSR Impact

Background

Differential Equations

Part 1 Results

Menu 3

Conclusion

Model 3: Nanoparticles

Abstract

Purpose

Background

Method

Part 1 Results

Menu 3

Conclusion

Model 4: Eyedrops

Abstract

Purpose

Background

Method

Part 1 Results

Menu 3

Conclusion

Conclusion

Citations

Prevention

GSR Eyedrop

Treatment

25HC Eyedrop

LOCS: 0

Eyedrops