Difference between revisions of "Team:NTU-LIHPAO-Taiwan/Modeling/Conclusion"

 
(2 intermediate revisions by 2 users not shown)
Line 768: Line 768:
 
<div class="Slidemenu">
 
<div class="Slidemenu">
 
<ul>
 
<ul>
−
<li><div class=width_small><div id=Position_Now><a href="https://2015.igem.org/Team:NTU-LIHPAO-Taiwan">Home</a></div></div>
+
<li><div class=width_small><a href="https://2015.igem.org/Team:NTU-LIHPAO-Taiwan">Home</a></div>
 
</li>
 
</li>
  
Line 778: Line 778:
 
</li>
 
</li>
 
 
−
<li><div class=width_small span style="cursor:default"><a>Project</a></div>
+
<li><div class=width_small span style="cursor:default"><div id=Position_Now><a>Project</a></div></div>
 
<ul class="subs">
 
<ul class="subs">
 
<li><a href="https://2015.igem.org/Team:NTU-LIHPAO-Taiwan/Description">Description</a></li>
 
<li><a href="https://2015.igem.org/Team:NTU-LIHPAO-Taiwan/Description">Description</a></li>
Line 793: Line 793:
 
<li><a href="https://2015.igem.org/Team:NTU-LIHPAO-Taiwan/Basic_Part">Basic Parts</a></li>
 
<li><a href="https://2015.igem.org/Team:NTU-LIHPAO-Taiwan/Basic_Part">Basic Parts</a></li>
 
<li><a href="https://2015.igem.org/Team:NTU-LIHPAO-Taiwan/Composite_Part">Composite Parts</a></li>
 
<li><a href="https://2015.igem.org/Team:NTU-LIHPAO-Taiwan/Composite_Part">Composite Parts</a></li>
−
<li><a href="https://2015.igem.org/Team:NTU-LIHPAO-Taiwan/Part_Collection">Part Collection</a></li>
 
 
</ul>
 
</ul>
 
</li>
 
</li>
Line 902: Line 901:
 
<div class="Text3">
 
<div class="Text3">
 
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.
 
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.
 +
</div>
 +
<div class="Text3">
 +
<b>—></b>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;<a href="https://2015.igem.org/Team:NTU-LIHPAO-Taiwan/Modeling"><b>[Click on here back to Modeling Introduction]</b></a>
 +
</div>
 +
<div class="Text3">
 +
<b>—></b>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;<a href="https://2015.igem.org/Team:NTU-LIHPAO-Taiwan/Modeling/Conclusion"><b>[Click on here to see our Simulation Strategy and Results]</b></a>
 
</div>
 
</div>
  

Latest revision as of 13:17, 18 September 2015

NTU-LIHPAO-Taiwan

Modeling Summary
Hypothesis
  1. Total oral ingestion of 109 L. casei on the first day.
  2. The varying ratio (%) of bacteria number to total ingested number attached on the intestine against time were according to the mouse experiment.
  3. Incorporate suicide mechanism: 4 days for bacteria survival.
  4. TAT penetrates through villi by an uncharacterized pinocytosis/endocytosis related mechanism, which is also receptor-independent.
  5. CPP-PYY complex production rate per L. casei : 10-10 μg/min.
  6. One-fourth of the products secreted from L. casei penetrate through the small intestine epithelial cells, without being digested by the intestine fluid.
  7. Effective permeability of TAT-insulin conjugates from literature as reference for TAT-PYY complex : Peff = 1.62×10-5 (cm/s).
  8. Mean total mucosal surface of the small intestine interior averages 32 m2.
  9. L. casei 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.
  10. 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 : DAB = 5.8 x 10-7 cm2/s.
  11. The distance from epithelial cells to capillaries is 4 μm.
  12. The diffusion is rapid enough to adsorb all the products in every minute.
  13. All the calculation was based on reaching steady-state condition in the interval of every minute discretely.
  14. Thrombin cleavage efficiency of Arg-Ser(R-S) site in CPP-PYY complex was referred to Arg-Thr(R-T) site in salmon calcitonin.
  15. Nearly 100 % of the complexes would be cleaved during 30 minutes due to the fluid motion in circulation.
  16. PYY concentration of 100 pg/ml has the power of appetite suppression without drug resistance.
  17. Average total blood volume of 5 liter in human body.
Conclusion
Ideally, the optimal concentration of PYY is 0.1 μg/L for appetite suppression, giving little side effect. Here we performed the simulation with 109 of total L. casei intake, and 10-10 μg/min of CPP-PYY complex production rate per L. casei. The results is shown below.
[Fig.2-1] Final concentration of PYY (μg/L) in the blood vessel
By building the model for simulation step by step, we summarized the general formula with varies parameters to determine the dose response :
[Final concentration of PYY in the blood (μg/L)] = 11745 × [Total L. casei intake] × [Distribution ratio of L. casei] × [CPP-PYY complex production rate per L. casei (μg/min)]
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.
—>     [Click on here back to Modeling Introduction]
—>     [Click on here to see our Simulation Strategy and Results]
Maintained by the iGEM team NTU-LIHPAO-Taiwan    ©2015 NTU-LIHPAO-Taiwan