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				<span class="title">Modeling Summary</span>
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					<li><a href="#First1">Hypothesis</a></li>
					<li><a href="#First2">Conclusion</a></li>

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					<div class="Text2" id="First1">Hypothesis</div>
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<ol class="part2">
        <li>Total oral ingestion of 10<sup>9</sup> <i>L. casei</i> on the first day.</li>
        <li>The varying ratio (%) of bacteria number to total ingested number attached on the intestine against time were according to the mouse experiment.</li>
        <li>Incorporate suicide mechanism: 4 days for bacteria survival.</li>
        <li>TAT penetrates through villi by an uncharacterized pinocytosis/endocytosis related mechanism, which is also receptor-independent.</li>
        <li>CPP-PYY complex production rate per <i>L. casei</i> : 10<sup>-10</sup> μg/min.</li>
        <li>One-fourth of the products secreted from <i>L. casei</i> penetrate through the small intestine epithelial cells, without being digested by the intestine fluid.</li>
        <li>Effective permeability of TAT-insulin conjugates from literature as reference for TAT-PYY complex : P<sub>eff</sub> = 1.62×10<sup>-5</sup> (cm/s).</li>
        <li>Mean total mucosal surface of the small intestine interior averages 32 m<sup>2</sup>.</li>
        <li><i>L. casei</i> cell size range = 0.7-1.1 x 2.0-4.0 μm. One-tenth of the bacteria height multiplied the mucosa surface area for the donor chamber volume.</li>
        <li>Fick’s Law of Binary Diffusion applied for CPP-PYY complex adsorption into bloodstream. Interstitial fluid diffusion coefficient of bovine serum albumin in tissues was taken for reference : D<sub>AB</sub> = 5.8 x 10<sup>-7</sup> cm<sup>2</sup>/s.</li>
        <li>The distance from epithelial cells to capillaries is 4 μm.</li>
        <li>The diffusion is rapid enough to adsorb all the products in every minute.</li>
        <li>All the calculation was based on reaching steady-state condition in the interval of every minute discretely.</li>
        <li>Thrombin cleavage efficiency of Arg-Ser(R-S) site in CPP-PYY complex was referred to Arg-Thr(R-T) site in salmon calcitonin.</li>
        <li>Nearly 100 % of the complexes would be cleaved during 30 minutes due to the fluid motion in circulation.</li>
        <li>PYY concentration of 100 pg/ml has the power of appetite suppression without drug resistance.</li>
        <li>Average total blood volume of 5 liter in human body.</li>


</ol>
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					<div class="Text2" id="First2">Conclusion</div>
						<div class="Text3">
Ideally, the optimal concentration of PYY is 0.1 μg/L for appetite suppression, giving little side effect. Here we performed the simulation with 10<sup>9</sup> of total <i>L. casei</i> intake, and 10<sup>-10</sup> μg/min of CPP-PYY complex production rate per <i>L. casei</i>. The results is shown below.
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								<img src="https://static.igem.org/mediawiki/2015/d/de/Pathway_Figure7.png" width="500px"/>
								<div class="Article_PictureText1"><div class="Text_Picture">[Fig.1-1] Final concentration of PYY (μg/L) in the blood vessel</div></div>
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						<div class="Text3">
By building the model for simulation step by step, we summarized the general formula with varies parameters to determine the dose response : 
						</div>
						<div class="Text3">
<b>[Final concentration of PYY in the blood (μg/L)] = 11745 × [Total <i>L. casei</i> intake] × [Distribution ratio of <i>L. casei</i>] × [CPP-PYY complex production rate per <i>L. casei</i> (μg/min)]</b>
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This general formula is based on one-dose response, and continuous drug intake should be further modified by successive accumulation for determining the appetite suppression effect.
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