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    <div id="MD-content-all" class="MD-content-container" style="margin-top:calc(25vh - 30px);">
        <div class="MD-title">
            <a style="border-bottom-style: solid;text-decoration: none;color:#131313;">H<sub>2</sub>O<sub>2</sub>
                Decomposition Model</a>
        </div>

        <div id="MD1" class="cd-section MD-margin-title1ToUp">
            <div class="MD-title-1" style="border-left-style:solid;padding-left:10px;">
                <a style="text-decoration:none;color:#131313;">Purpose</a>
            </div>

            <div class="MD-content MD-margin-toTitle1">
                <p class="MD-content-p">
                    In our experiment, we found it hard to measure the intracellular H<sub>2</sub>O<sub>2</sub>
                    concentration, so we
                    controlled the external H<sub>2</sub>O<sub>2</sub> concentration in culture to confirm our system'
                    function. Although the
                    H<sub>2</sub>O<sub>2</sub> can entry the cell quickly through simple diffusion, we needed to build
                    up a model to simulate
                    the intracellular H<sub>2</sub>O<sub>2</sub>. At the same time, this model will provide a base for
                    roGFP2-Orp1 Michealis
                    equation model.
                </p>
            </div>
        </div>

        <div id="MD2" class="cd-section">
            <div class="MD-title-1 MD-margin-title1ToUp" style="border-left-style:solid;padding-left:10px;">
                <a style="text-decoration:none;color:#131313;">Model simulation</a>
            </div>

            <div class="MD-content MD-margin-toTitle1">
                <p class="MD-content-p">
                    Firstly, in order to describe the process in cells more accurately, three reactions in this process
                    are considered: diffusion, fast degradation and slow degradation. The fast degradation is caused by
                    some natural reduction molecular (like Glutathione) directly react with H<sub>2</sub>O<sub>2</sub>.
                    And slow degradation
                    is led by enzymatic degradation.<sup onmouseover="tooltip.pop(this, '#tip-1', {position:1, offsetX:-20, effect:'slide',hideDelay: 10})"
                    style="color:#38679a;">[1]</sup>
                </p>

                <figure class="MD-Fig MD-margin-toContentP">
                    <img src="https://static.igem.org/mediawiki/2018/d/d3/T--BIT-China--iGEM2018-Modeling7.png">
                    <figcaption>Fig.1 The kinetic model for H2O2 degradation</figcaption>
                </figure>
            </div>
        </div>

        <div id="MD3" class="cd-section MD-margin-toP">
            <div class="MD-title-1 MD-margin-title1ToUp" style="border-left-style:solid;padding-left:10px;">
                <a style="text-decoration:none;color:#131313;">ODE model</a>
            </div>

            <div class="MD-content MD-margin-toTitle1">

                <p class="MD-formula">
                    $$\frac{\mathrm{d_{\mathit{p}_{e}}} }{\mathrm{d} t}=k_{1}(p_{i}-p_{e})v$$
                </p>
                <p class="MD-formula">
                    $$\frac{\mathrm{d_{\mathit{p}_{i}}}
                    }{\mathrm{d}t}=k_{1}(p_{e}-p_{i})-(k_{2}+k_{3}\frac{g}{k_{g}+g})p_{i}$$
                </p>
                <p class="MD-formula">
                    $$\frac{\mathrm{d_{\mathit{g}}} }{\mathrm{d} t}=-k_{3}(\frac{g}{k_{g}+g})p_{i}$$
                </p>

                <p class="MD-content-p">
                    The ODE model accounted for intracellular and extracellular H<sub>2</sub>O<sub>2</sub> levels, and the
                    consumption of a finite
                    antioxidant capacity using three rates:
                </p>

                <ul class="MD-content-p">
                    <li>
                        1) The membrane permeability (k1).<sup onmouseover="tooltip.pop(this, '#tip-2', {position:1, offsetX:-20, effect:'slide',hideDelay: 10})"
                        style="color:#38679a;">[2]</sup><sup onmouseover="tooltip.pop(this, '#tip-3', {position:1, offsetX:-20, effect:'slide',hideDelay: 10})"
                        style="color:#38679a;">[3]</sup><sup onmouseover="tooltip.pop(this, '#tip-4', {position:1, offsetX:-20, effect:'slide',hideDelay: 10})"
                        style="color:#38679a;">[4]</sup>
                    </li>
                    <li>
                        2) Intracellular slow degradation rate (k2).<sup onmouseover="tooltip.pop(this, '#tip-5', {position:1, offsetX:-20, effect:'slide',hideDelay: 10})"
                        style="color:#38679a;">[5]</sup>
                    </li>
                    <li>
                        3) Intracellular fast degradation rate (k3) dependent upon a finite capacity (g), e.g. NADPH
                        levels in naive cells.<sup onmouseover="tooltip.pop(this, '#tip-6', {position:1, offsetX:-20, effect:'slide',hideDelay: 10})"
                        style="color:#38679a;">[6]</sup>
                    </li>
                </ul>

                <p class="MD-content-p">
                    We reviewed the above literature and combined the results of the wet experiment, as shown in Fig.3,
                    to determine the parameters required for the model simulation, listed in the table below.
                </p>

                <p class="MD-content-p MD-margin-toP">
                    Table 1. Description of Variables Used in The Kinetic Model.
                </p>
                <div class="table-head">
                    <table>
                        <colgroup>
                            <col style="width: 30%;" />
                            <col style="width: 30%;" />
                            <col style="width: 40%;" />
                        </colgroup>
                        <thead>
                            <tr style="font-size: 20px;">
                                <th>Variable</th>
                                <th>Explanation</th>
                                <th>Value</th>
                            </tr>
                        </thead>
                    </table>
                </div>
                <div class="table-body">
                    <table>
                        <colgroup>
                            <col style="width: 30%;" />
                            <col style="width: 30%;" />
                            <col style="width: 40%;" />
                        </colgroup>
                        <tbody style="font-size: 16px;">

                            <tr>
                                <td><b>k<sub>1</sub></b></td>
                                <td>Membrane Permeability</td>
                                <td>11</td>
                            </tr>

                            <tr>
                                <td><b>k<sub>2</sub></b></td>
                                <td>Slow Degradation Rate</td>
                                <td>8</td>
                            </tr>

                            <tr>
                                <td><b>k<sub>3</sub></b></td>
                                <td>Fast Degradation Rate</td>
                                <td>55</td>
                            </tr>

                            <tr>
                                <td><b>G</b></td>
                                <td>Finite Capacity Substance</td>
                                <td>60</td>
                            </tr>

                            <tr>
                                <td><b>p<sub>i</sub></b></td>
                                <td>Intracellular/Cytosolic [H<sub>2</sub>O<sub>2</sub>]</td>
                                <td>/</td>
                            </tr>


                            <tr>
                                <td><b>p<sub>e</sub></b></td>
                                <td>Extracellular [H<sub>2</sub>O<sub>2</sub>]</td>
                                <td>/</td>
                            </tr>

                            <tr>
                                <td><b>V</b></td>
                                <td>Ratio of Cell Volume to Media</td>
                                <td>0.005</td>
                            </tr>
                        </tbody>
                    </table>
                </div>

            </div>
        </div>

        <div id="MD4" class="cd-section MD-margin-toP">
            <div class="MD-title-1" style="border-left-style:solid;padding-left:10px;">
                <a style="text-decoration:none;color:#131313;"> Simulation result</a>
            </div>

            <div class="MD-content MD-margin-toTitle1">
                <p class="MD-content-p MD-margin-toP">
                    We used MATLAB to simulate the kinetics of extracellular and intracellular H<sub>2</sub>O<sub>2</sub>
                    changes over time.
                    (Fig. 2)
                </p>

                <figure class="MD-Fig MD-margin-toContentP">
                    <img src="https://static.igem.org/mediawiki/2018/4/41/T--BIT-China--iGEM2018-Modeling8.png">
                    <figcaption>Fig.2 Simulation result</figcaption>
                </figure>
            </div>
        </div>

        <div id="MD5" class="cd-section MD-margin-toP">
            <div class="MD-title-1" style="border-left-style:solid;padding-left:10px;">
                <a style="text-decoration:none;color:#131313;">Experimental result</a>
            </div>

            <div class="MD-content MD-margin-toTitle1">
                <p class="MD-content-p MD-margin-toP">
                    To verify the feasibility of the model and to confirm this dynamic process, we did some experiments
                    using our system's output, roGFP2-Orp1. The results show that the fluorescence ratio value
                    I405/I488, an oxidant condition indicator, decreased by time when S. cerevisiae exposed to
                    different concentrations of H<sub>2</sub>O<sub>2</sub>. This ratio's decreasing stands for the
                    increasing of
                    intercellular H2O2 concentration. It also stopped at a stable concentration at last, which's
                    correspond to our model's result.
                </p>

                <figure class="MD-Fig MD-margin-toContentP">
                    <img src="https://static.igem.org/mediawiki/2018/7/78/T--BIT-China--iGEM2018-Modeling9.PNG">
                    <figcaption>Fig.3 Fluorescence ratio value changes with time</figcaption>
                </figure>
            </div>
        </div>

        <div id="MD6" class="cd-section MD-margin-toP">
            <div class="MD-title-1" style="border-left-style:solid;padding-left:10px;">
                <a style="text-decoration:none;color:#131313;">Summary</a>
            </div>

            <div class="MD-content MD-margin-toTitle1">
                <p class="MD-content-p MD-margin-toP">
                    In this model, we successfully simulated the kinetics of extracellular and intracellular H<sub>2</sub>O<sub>2</sub>
                    changes over time. Furthermore, the dynamic process of fluorescence ratio value by time was
                    detected by using roGFP2-Orp1 green fluorescent protein in wet experiment, and the feasibility of
                    the model was further verified.
                </p>
            </div>
        </div>
    </div>
    <div style="display:none;font-family: 'helveticaregular';">
        <div id="tip-1">
            <div class="column" style="width:230px;height: 100px;">
                <a>Altıntaş A, Davidsen K, Garde C, et al. High-resolution kinetics and modeling of hydrogen peroxide degradation in live cells.[J]. Free Radical Biology & Medicine, 2016, 101:143-153.
                </a>
            </div>
        </div>

        <div id="tip-2">
            <div class="column" style="width:230px;height: 100px;">
                <a>Branco M R, Marinho H S, Cyrne L, et al. Decrease of H<sub>2</sub>O<sub>2</sub> plasma membrane permeability during adaptation to H<sub>2</sub>O<sub>2</sub> in Saccharomyces cerevisiae.[J] . Journal of Biological Chemistry, 2004, 279(8):6501
                </a>
            </div>
        </div>

        <div id="tip-3">
            <div class="column" style="width:230px;height: 100px;">
                <a>Henzler T, Steudle E. Transport and metabolic degradation of hydrogen peroxide in Chara corallina: model calculations and measurements with the pressure probe suggest transport of H(2)O(2) across water channels.[J]. Journal of Experimental Botany, 2000, 51(353):2053-2066. 
                </a>
            </div>
        </div>
        <div id="tip-4">
            <div class="column" style="width:230px;height: 100px;">
                <a>Bienert G P, Schjoerring J K, Jahn T P. Membrane transport of hydrogen peroxide[J]. Biochimica Et Biophysica Acta, 2006, 1758(8):994-1003.
                </a>
            </div>
        </div>
        <div id="tip-5">
            <div class="column" style="width:230px;height: 100px;">
                <a>Branco M R, Marinho H S, Cyrne L, et al. Decrease of H<sub>2</sub>O<sub>2</sub> plasma membrane permeability during adaptation to H<sub>2</sub>O<sub>2</sub> in Saccharomyces cerevisiae.[J]. Journal of Biological Chemistry, 2004, 279(8):6501.
                </a>
            </div>
        </div>
        <div id="tip-6">
            <div class="column" style="width:230px;height: 100px;">
                <a>Altıntaş A, Davidsen K, Garde C, et al. High-resolution kinetics and modeling of hydrogen peroxide degradation in live cells.[J]. Free Radical Biology & Medicine, 2016, 101:143-153.
                </a>
            </div>
        </div>


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                Beijing Institute of Technology
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