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| − | {{Peking/Temp1}} | + | {{Peking/Temp1}} |
| | {{Peking/Temp2}} | | {{Peking/Temp2}} |
| | <html> | | <html> |
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| | <div id='write' class='is-mac'><h1><a name="modeling" | | <div id='write' class='is-mac'><h1><a name="modeling" |
| − | class="md-header-anchor"></a><span>Modeling</span> | + | class="md-header-anchor"></a><span style="text-align:center;font-size:40px;">Modeling</span> |
| | </h1> | | </h1> |
| | <p><span>Our team attach great importance to quantitative description of our biological systems and experimental phenomena. We applied modeling and quantitative methods in throughout our project, from macroscopic to microcosmic, from mechanics to applications. </span> | | <p><span>Our team attach great importance to quantitative description of our biological systems and experimental phenomena. We applied modeling and quantitative methods in throughout our project, from macroscopic to microcosmic, from mechanics to applications. </span> |
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| − | y="0"></use></g></g></g></g></g></g></svg></span></div>
| + | |
| − | <script type="math/tex; mode=display" id="MathJax-Element-25">\begin{cases}
| + | |
| − | \displaystyle \frac{\mathrm{d}}{\mathrm{d}t}n = -\frac{k_n n}{n+K_n}m\\
| + | |
| − | \displaystyle \frac{\mathrm{d}}{\mathrm{d}t}m = \frac{k_m n}{n+K_n}m\alpha\\
| + | |
| − | \displaystyle \frac{\mathrm{d}}{\mathrm{d}t}p = \frac{k_p n}{n+K_n}m(1-\alpha)\\
| + | |
| − | \end{cases}
| + | |
| − | </script>
| + | |
| − | </div>
| + | |
| − | </div>
| + | |
| − | <p><span>where </span><span class="MathJax_SVG" tabindex="-1"
| + | |
| − | style="font-size: 100%; display: inline-block;"><svg
| + | |
| − | xmlns:xlink=" " width="1.394ex" height="1.41ex" viewBox="0 -504.6 600 607.1"
| + | |
| − | role="img" focusable="false" style="vertical-align: -0.238ex;"><defs><path
| + | |
| − | stroke-width="0" id="E148-MJMATHI-6E"
| + | |
| − | d="M21 287Q22 293 24 303T36 341T56 388T89 425T135 442Q171 442 195 424T225 390T231 369Q231 367 232 367L243 378Q304 442 382 442Q436 442 469 415T503 336T465 179T427 52Q427 26 444 26Q450 26 453 27Q482 32 505 65T540 145Q542 153 560 153Q580 153 580 145Q580 144 576 130Q568 101 554 73T508 17T439 -10Q392 -10 371 17T350 73Q350 92 386 193T423 345Q423 404 379 404H374Q288 404 229 303L222 291L189 157Q156 26 151 16Q138 -11 108 -11Q95 -11 87 -5T76 7T74 17Q74 30 112 180T152 343Q153 348 153 366Q153 405 129 405Q91 405 66 305Q60 285 60 284Q58 278 41 278H27Q21 284 21 287Z"></path></defs><g
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| − | stroke="currentColor" fill="currentColor" stroke-width="0"
| + | |
| − | transform="matrix(1 0 0 -1 0 0)"><use xlink:href="#E148-MJMATHI-6E" x="0"
| + | |
| − | y="0"></use></g></svg></span>
| + | |
| − | <script type="math/tex">n</script>
| + | |
| − | <span> is the mass of nutrient, </span><span class="MathJax_SVG" tabindex="-1"
| + | |
| − | style="font-size: 100%; display: inline-block;"><svg
| + | |
| − | xmlns:xlink=" " width="2.039ex" height="1.41ex"
| + | |
| − | viewBox="0 -504.6 878 607.1" role="img" focusable="false"
| + | |
| − | style="vertical-align: -0.238ex;"><defs><path stroke-width="0"
| + | |
| − | id="E149-MJMATHI-6D"
| + | |
| − | d="M21 287Q22 293 24 303T36 341T56 388T88 425T132 442T175 435T205 417T221 395T229 376L231 369Q231 367 232 367L243 378Q303 442 384 442Q401 442 415 440T441 433T460 423T475 411T485 398T493 385T497 373T500 364T502 357L510 367Q573 442 659 442Q713 442 746 415T780 336Q780 285 742 178T704 50Q705 36 709 31T724 26Q752 26 776 56T815 138Q818 149 821 151T837 153Q857 153 857 145Q857 144 853 130Q845 101 831 73T785 17T716 -10Q669 -10 648 17T627 73Q627 92 663 193T700 345Q700 404 656 404H651Q565 404 506 303L499 291L466 157Q433 26 428 16Q415 -11 385 -11Q372 -11 364 -4T353 8T350 18Q350 29 384 161L420 307Q423 322 423 345Q423 404 379 404H374Q288 404 229 303L222 291L189 157Q156 26 151 16Q138 -11 108 -11Q95 -11 87 -5T76 7T74 17Q74 30 112 181Q151 335 151 342Q154 357 154 369Q154 405 129 405Q107 405 92 377T69 316T57 280Q55 278 41 278H27Q21 284 21 287Z"></path></defs><g
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| − | stroke="currentColor" fill="currentColor" stroke-width="0"
| + | |
| − | transform="matrix(1 0 0 -1 0 0)"><use xlink:href="#E149-MJMATHI-6D"
| + | |
| − | x="0"
| + | |
| − | y="0"></use></g></svg></span>
| + | |
| − | <script type="math/tex">m</script>
| + | |
| − | <span> is the biomass, </span><span class="MathJax_SVG" tabindex="-1"
| + | |
| − | style="font-size: 100%; display: inline-block;"><svg
| + | |
| − | xmlns:xlink=" " width="1.259ex" height="1.76ex"
| + | |
| − | viewBox="-39 -504.6 542 757.9" role="img" focusable="false"
| + | |
| − | style="vertical-align: -0.588ex; margin-left: -0.091ex;"><defs><path
| + | |
| − | stroke-width="0" id="E150-MJMATHI-70"
| + | |
| − | d="M23 287Q24 290 25 295T30 317T40 348T55 381T75 411T101 433T134 442Q209 442 230 378L240 387Q302 442 358 442Q423 442 460 395T497 281Q497 173 421 82T249 -10Q227 -10 210 -4Q199 1 187 11T168 28L161 36Q160 35 139 -51T118 -138Q118 -144 126 -145T163 -148H188Q194 -155 194 -157T191 -175Q188 -187 185 -190T172 -194Q170 -194 161 -194T127 -193T65 -192Q-5 -192 -24 -194H-32Q-39 -187 -39 -183Q-37 -156 -26 -148H-6Q28 -147 33 -136Q36 -130 94 103T155 350Q156 355 156 364Q156 405 131 405Q109 405 94 377T71 316T59 280Q57 278 43 278H29Q23 284 23 287ZM178 102Q200 26 252 26Q282 26 310 49T356 107Q374 141 392 215T411 325V331Q411 405 350 405Q339 405 328 402T306 393T286 380T269 365T254 350T243 336T235 326L232 322Q232 321 229 308T218 264T204 212Q178 106 178 102Z"></path></defs><g
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| − | stroke="currentColor" fill="currentColor" stroke-width="0"
| + | |
| − | transform="matrix(1 0 0 -1 0 0)"><use xlink:href="#E150-MJMATHI-70"
| + | |
| − | x="0"
| + | |
| − | y="0"></use></g></svg></span>
| + | |
| − | <script type="math/tex">p</script>
| + | |
| − | <span> is the mass of the bioproduct, </span><span class="MathJax_SVG"
| + | |
| − | tabindex="-1"
| + | |
| − | style="font-size: 100%; display: inline-block;"><svg
| + | |
| − | xmlns:xlink=" " width="2.428ex" height="2.344ex"
| + | |
| − | viewBox="0 -755.9 1045.3 1009.2" role="img" focusable="false"
| + | |
| − | style="vertical-align: -0.588ex;"><defs><path stroke-width="0"
| + | |
| − | id="E159-MJMATHI-6B"
| + | |
| − | d="M121 647Q121 657 125 670T137 683Q138 683 209 688T282 694Q294 694 294 686Q294 679 244 477Q194 279 194 272Q213 282 223 291Q247 309 292 354T362 415Q402 442 438 442Q468 442 485 423T503 369Q503 344 496 327T477 302T456 291T438 288Q418 288 406 299T394 328Q394 353 410 369T442 390L458 393Q446 405 434 405H430Q398 402 367 380T294 316T228 255Q230 254 243 252T267 246T293 238T320 224T342 206T359 180T365 147Q365 130 360 106T354 66Q354 26 381 26Q429 26 459 145Q461 153 479 153H483Q499 153 499 144Q499 139 496 130Q455 -11 378 -11Q333 -11 305 15T277 90Q277 108 280 121T283 145Q283 167 269 183T234 206T200 217T182 220H180Q168 178 159 139T145 81T136 44T129 20T122 7T111 -2Q98 -11 83 -11Q66 -11 57 -1T48 16Q48 26 85 176T158 471L195 616Q196 629 188 632T149 637H144Q134 637 131 637T124 640T121 647Z"></path><path
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| + | |
| − | stroke="currentColor" fill="currentColor" stroke-width="0"
| + | |
| − | transform="matrix(1 0 0 -1 0 0)"><use xlink:href="#E159-MJMATHI-6B"
| + | |
| − | x="0" y="0"></use><use
| + | |
| − | transform="scale(0.707)" xlink:href="#E159-MJMATHI-6E" x="736"
| + | |
| − | y="-213"></use></g></svg></span>
| + | |
| − | <script type="math/tex">k_n</script>
| + | |
| − | <span> is the cell's nutrient uptake rate, </span><span class="MathJax_SVG"
| + | |
| − | tabindex="-1"
| + | |
| − | style="font-size: 100%; display: inline-block;"><svg
| + | |
| − | xmlns:xlink=" " width="2.884ex" height="2.344ex"
| + | |
| − | viewBox="0 -755.9 1241.8 1009.2" role="img" focusable="false"
| + | |
| − | style="vertical-align: -0.588ex;"><defs><path stroke-width="0"
| + | |
| − | id="E163-MJMATHI-6B"
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| − | d="M121 647Q121 657 125 670T137 683Q138 683 209 688T282 694Q294 694 294 686Q294 679 244 477Q194 279 194 272Q213 282 223 291Q247 309 292 354T362 415Q402 442 438 442Q468 442 485 423T503 369Q503 344 496 327T477 302T456 291T438 288Q418 288 406 299T394 328Q394 353 410 369T442 390L458 393Q446 405 434 405H430Q398 402 367 380T294 316T228 255Q230 254 243 252T267 246T293 238T320 224T342 206T359 180T365 147Q365 130 360 106T354 66Q354 26 381 26Q429 26 459 145Q461 153 479 153H483Q499 153 499 144Q499 139 496 130Q455 -11 378 -11Q333 -11 305 15T277 90Q277 108 280 121T283 145Q283 167 269 183T234 206T200 217T182 220H180Q168 178 159 139T145 81T136 44T129 20T122 7T111 -2Q98 -11 83 -11Q66 -11 57 -1T48 16Q48 26 85 176T158 471L195 616Q196 629 188 632T149 637H144Q134 637 131 637T124 640T121 647Z"></path><path
| + | |
| − | stroke-width="0" id="E163-MJMATHI-6D"
| + | |
| − | d="M21 287Q22 293 24 303T36 341T56 388T88 425T132 442T175 435T205 417T221 395T229 376L231 369Q231 367 232 367L243 378Q303 442 384 442Q401 442 415 440T441 433T460 423T475 411T485 398T493 385T497 373T500 364T502 357L510 367Q573 442 659 442Q713 442 746 415T780 336Q780 285 742 178T704 50Q705 36 709 31T724 26Q752 26 776 56T815 138Q818 149 821 151T837 153Q857 153 857 145Q857 144 853 130Q845 101 831 73T785 17T716 -10Q669 -10 648 17T627 73Q627 92 663 193T700 345Q700 404 656 404H651Q565 404 506 303L499 291L466 157Q433 26 428 16Q415 -11 385 -11Q372 -11 364 -4T353 8T350 18Q350 29 384 161L420 307Q423 322 423 345Q423 404 379 404H374Q288 404 229 303L222 291L189 157Q156 26 151 16Q138 -11 108 -11Q95 -11 87 -5T76 7T74 17Q74 30 112 181Q151 335 151 342Q154 357 154 369Q154 405 129 405Q107 405 92 377T69 316T57 280Q55 278 41 278H27Q21 284 21 287Z"></path></defs><g
| + | |
| − | stroke="currentColor" fill="currentColor" stroke-width="0"
| + | |
| − | transform="matrix(1 0 0 -1 0 0)"><use xlink:href="#E163-MJMATHI-6B"
| + | |
| − | x="0" y="0"></use><use
| + | |
| − | transform="scale(0.707)" xlink:href="#E163-MJMATHI-6D" x="736"
| + | |
| − | y="-213"></use></g></svg></span>
| + | |
| − | <script type="math/tex">k_m</script>
| + | |
| − | <span> is the maximum growth rate when the nutrient is sufficient and all the uptaken nutrient are used for cell's own growth, and </span><span
| + | |
| − | class="MathJax_SVG" tabindex="-1"
| + | |
| − | style="font-size: 100%; display: inline-block;"><svg xmlns:xlink=" "
| + | |
| − | width="2.268ex"
| + | |
| − | height="2.577ex"
| + | |
| − | viewBox="0 -755.9 976.7 1109.7"
| + | |
| − | role="img"
| + | |
| − | focusable="false"
| + | |
| − | style="vertical-align: -0.822ex;"><defs><path
| + | |
| − | stroke-width="0" id="E160-MJMATHI-6B"
| + | |
| − | d="M121 647Q121 657 125 670T137 683Q138 683 209 688T282 694Q294 694 294 686Q294 679 244 477Q194 279 194 272Q213 282 223 291Q247 309 292 354T362 415Q402 442 438 442Q468 442 485 423T503 369Q503 344 496 327T477 302T456 291T438 288Q418 288 406 299T394 328Q394 353 410 369T442 390L458 393Q446 405 434 405H430Q398 402 367 380T294 316T228 255Q230 254 243 252T267 246T293 238T320 224T342 206T359 180T365 147Q365 130 360 106T354 66Q354 26 381 26Q429 26 459 145Q461 153 479 153H483Q499 153 499 144Q499 139 496 130Q455 -11 378 -11Q333 -11 305 15T277 90Q277 108 280 121T283 145Q283 167 269 183T234 206T200 217T182 220H180Q168 178 159 139T145 81T136 44T129 20T122 7T111 -2Q98 -11 83 -11Q66 -11 57 -1T48 16Q48 26 85 176T158 471L195 616Q196 629 188 632T149 637H144Q134 637 131 637T124 640T121 647Z"></path><path
| + | |
| − | stroke-width="0" id="E160-MJMATHI-70"
| + | |
| − | d="M23 287Q24 290 25 295T30 317T40 348T55 381T75 411T101 433T134 442Q209 442 230 378L240 387Q302 442 358 442Q423 442 460 395T497 281Q497 173 421 82T249 -10Q227 -10 210 -4Q199 1 187 11T168 28L161 36Q160 35 139 -51T118 -138Q118 -144 126 -145T163 -148H188Q194 -155 194 -157T191 -175Q188 -187 185 -190T172 -194Q170 -194 161 -194T127 -193T65 -192Q-5 -192 -24 -194H-32Q-39 -187 -39 -183Q-37 -156 -26 -148H-6Q28 -147 33 -136Q36 -130 94 103T155 350Q156 355 156 364Q156 405 131 405Q109 405 94 377T71 316T59 280Q57 278 43 278H29Q23 284 23 287ZM178 102Q200 26 252 26Q282 26 310 49T356 107Q374 141 392 215T411 325V331Q411 405 350 405Q339 405 328 402T306 393T286 380T269 365T254 350T243 336T235 326L232 322Q232 321 229 308T218 264T204 212Q178 106 178 102Z"></path></defs><g
| + | |
| − | stroke="currentColor" fill="currentColor" stroke-width="0"
| + | |
| − | transform="matrix(1 0 0 -1 0 0)"><use xlink:href="#E160-MJMATHI-6B"
| + | |
| − | x="0" y="0"></use><use
| + | |
| − | transform="scale(0.707)" xlink:href="#E160-MJMATHI-70" x="736"
| + | |
| − | y="-213"></use></g></svg></span>
| + | |
| − | <script type="math/tex">k_p</script>
| + | |
| − | <span> is maximum production rate when the nutrient is sufficient and all the uptaken nutrient are used for the bio-product's production, </span><span
| + | |
| − | class="MathJax_SVG" tabindex="-1"
| + | |
| − | style="font-size: 100%; display: inline-block;"><svg xmlns:xlink=" "
| + | |
| − | width="3.19ex"
| + | |
| − | height="2.344ex"
| + | |
| − | viewBox="0 -755.9 1373.3 1009.2"
| + | |
| − | role="img"
| + | |
| − | focusable="false"
| + | |
| − | style="vertical-align: -0.588ex;"><defs><path
| + | |
| − | stroke-width="0" id="E161-MJMATHI-4B"
| + | |
| − | d="M285 628Q285 635 228 637Q205 637 198 638T191 647Q191 649 193 661Q199 681 203 682Q205 683 214 683H219Q260 681 355 681Q389 681 418 681T463 682T483 682Q500 682 500 674Q500 669 497 660Q496 658 496 654T495 648T493 644T490 641T486 639T479 638T470 637T456 637Q416 636 405 634T387 623L306 305Q307 305 490 449T678 597Q692 611 692 620Q692 635 667 637Q651 637 651 648Q651 650 654 662T659 677Q662 682 676 682Q680 682 711 681T791 680Q814 680 839 681T869 682Q889 682 889 672Q889 650 881 642Q878 637 862 637Q787 632 726 586Q710 576 656 534T556 455L509 418L518 396Q527 374 546 329T581 244Q656 67 661 61Q663 59 666 57Q680 47 717 46H738Q744 38 744 37T741 19Q737 6 731 0H720Q680 3 625 3Q503 3 488 0H478Q472 6 472 9T474 27Q478 40 480 43T491 46H494Q544 46 544 71Q544 75 517 141T485 216L427 354L359 301L291 248L268 155Q245 63 245 58Q245 51 253 49T303 46H334Q340 37 340 35Q340 19 333 5Q328 0 317 0Q314 0 280 1T180 2Q118 2 85 2T49 1Q31 1 31 11Q31 13 34 25Q38 41 42 43T65 46Q92 46 125 49Q139 52 144 61Q147 65 216 339T285 628Z"></path><path
| + | |
| − | stroke-width="0" id="E161-MJMATHI-6E"
| + | |
| − | d="M21 287Q22 293 24 303T36 341T56 388T89 425T135 442Q171 442 195 424T225 390T231 369Q231 367 232 367L243 378Q304 442 382 442Q436 442 469 415T503 336T465 179T427 52Q427 26 444 26Q450 26 453 27Q482 32 505 65T540 145Q542 153 560 153Q580 153 580 145Q580 144 576 130Q568 101 554 73T508 17T439 -10Q392 -10 371 17T350 73Q350 92 386 193T423 345Q423 404 379 404H374Q288 404 229 303L222 291L189 157Q156 26 151 16Q138 -11 108 -11Q95 -11 87 -5T76 7T74 17Q74 30 112 180T152 343Q153 348 153 366Q153 405 129 405Q91 405 66 305Q60 285 60 284Q58 278 41 278H27Q21 284 21 287Z"></path></defs><g
| + | |
| − | stroke="currentColor" fill="currentColor" stroke-width="0"
| + | |
| − | transform="matrix(1 0 0 -1 0 0)"><use xlink:href="#E161-MJMATHI-4B"
| + | |
| − | x="0" y="0"></use><use
| + | |
| − | transform="scale(0.707)" xlink:href="#E161-MJMATHI-6E" x="1200"
| + | |
| − | y="-213"></use></g></svg></span>
| + | |
| − | <script type="math/tex">K_n</script>
| + | |
| − | <span> is the nutrient corresponding to half-maximum nutrient uptaking rate, and </span><span
| + | |
| − | class="MathJax_SVG" tabindex="-1"
| + | |
| − | style="font-size: 100%; display: inline-block;"><svg xmlns:xlink=" "
| + | |
| − | width="1.486ex"
| + | |
| − | height="1.41ex"
| + | |
| − | viewBox="0 -504.6 640 607.1"
| + | |
| − | role="img"
| + | |
| − | focusable="false"
| + | |
| − | style="vertical-align: -0.238ex;"><defs><path
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| − | <script type="math/tex">\alpha</script>
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| − | <span> is the above-mentioned allocation ratio.</span></p>
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| − | <p><span>Noticing that for a given </span><span class="MathJax_SVG" tabindex="-1"
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| + | |
| − | <script type="math/tex">\alpha</script>
| + | |
| − | <span>, when the nutrient is sufficient, the second ODE can be re-written as </span>
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| − | <script type="math/tex; mode=display" id="MathJax-Element-26">
| + | |
| − | \frac{\mathrm{d}}{\mathrm{d}t}m = k_m\alpha\cdot m
| + | |
| − | </script>
| + | |
| − | </div>
| + | |
| − | </div>
| + | |
| − | <p><span>This corresponds to an exponential growth with a growth rate </span><span
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| − | <script type="math/tex">\lambda = k_m\alpha</script>
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| − | </div>
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| − | <script type="math/tex; mode=display" id="MathJax-Element-27">\begin{cases}
| + | |
| − | \displaystyle \frac{\mathrm{d}}{\mathrm{d}t}n = -\frac{k_n n}{n+K_n}m\\
| + | |
| − | \displaystyle \frac{\mathrm{d}}{\mathrm{d}t}m = \frac{n\lambda}{n+K_n}m\\
| + | |
| − | \displaystyle \frac{\mathrm{d}}{\mathrm{d}t}p = \frac{k_p n}{n+K_n}\left(1-\frac{\lambda}{k_m}\right)m\\
| + | |
| − | \end{cases}
| + | |
| − | </script>
| + | |
| − | </div>
| + | |
| − | </div>
| + | |
| − | <p><span>the equation explicitly includes the growth rate. The parameter values are given as follows</span>
| + | |
| − | </p>
| + | |
| − | <figure>
| + | |
| − | <table>
| + | |
| − | <thead>
| + | |
| − | <tr>
| + | |
| − | <th><span>parameter</span></th>
| + | |
| − | <th><span>description</span></th>
| + | |
| − | <th><span>value</span></th>
| + | |
| − | </tr>
| + | |
| − | </thead>
| + | |
| − | <tbody>
| + | |
| − | <tr>
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| + | |
| − | <script type="math/tex">k_m</script>
| + | |
| − | </td>
| + | |
| − | <td><span>the theoretical maximal growth rate of </span><em><span>E. coli</span></em><sup><span>[1]</span></sup>
| + | |
| − | </td>
| + | |
| − | <td><span>2.85 h</span><sup><span>-1</span></sup></td>
| + | |
| − | </tr>
| + | |
| − | <tr>
| + | |
| − | <td><span class="MathJax_SVG" tabindex="-1"
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| − | y="-213"></use></g></svg></span>
| + | |
| − | <script type="math/tex">k_n</script>
| + | |
| − | </td>
| + | |
| − | <td>
| + | |
| − | <span>the maximal nutrient uptake rate of </span><em><span>E. coli</span></em><span> </span><sup><span>[3]</span></sup>
| + | |
| − | </td>
| + | |
| − | <td><span>5.70 h</span><sup><span>-1</span></sup></td>
| + | |
| − | </tr>
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| − | <tr>
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| + | |
| − | <script type="math/tex">k_p</script>
| + | |
| − | </td>
| + | |
| − | <td><span>the maximal producting rate of the bio-product</span></td>
| + | |
| − | <td><span>0.1425 h</span><sup><span>-1</span></sup></td>
| + | |
| − | </tr>
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| − | <tr>
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| − | <td><span class="MathJax_SVG" tabindex="-1"
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| − | d="M285 628Q285 635 228 637Q205 637 198 638T191 647Q191 649 193 661Q199 681 203 682Q205 683 214 683H219Q260 681 355 681Q389 681 418 681T463 682T483 682Q500 682 500 674Q500 669 497 660Q496 658 496 654T495 648T493 644T490 641T486 639T479 638T470 637T456 637Q416 636 405 634T387 623L306 305Q307 305 490 449T678 597Q692 611 692 620Q692 635 667 637Q651 637 651 648Q651 650 654 662T659 677Q662 682 676 682Q680 682 711 681T791 680Q814 680 839 681T869 682Q889 682 889 672Q889 650 881 642Q878 637 862 637Q787 632 726 586Q710 576 656 534T556 455L509 418L518 396Q527 374 546 329T581 244Q656 67 661 61Q663 59 666 57Q680 47 717 46H738Q744 38 744 37T741 19Q737 6 731 0H720Q680 3 625 3Q503 3 488 0H478Q472 6 472 9T474 27Q478 40 480 43T491 46H494Q544 46 544 71Q544 75 517 141T485 216L427 354L359 301L291 248L268 155Q245 63 245 58Q245 51 253 49T303 46H334Q340 37 340 35Q340 19 333 5Q328 0 317 0Q314 0 280 1T180 2Q118 2 85 2T49 1Q31 1 31 11Q31 13 34 25Q38 41 42 43T65 46Q92 46 125 49Q139 52 144 61Q147 65 216 339T285 628Z"></path><path
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| − | y="-213"></use></g></svg></span>
| + | |
| − | <script type="math/tex">K_n</script>
| + | |
| − | </td>
| + | |
| − | <td><span>the nutrient concentration corresponding to half-maximal growth rate</span>
| + | |
| − | </td>
| + | |
| − | <td><span>4.0 kg/ml</span></td>
| + | |
| − | </tr>
| + | |
| − | <tr>
| + | |
| − | <td><span class="MathJax_SVG" tabindex="-1"
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| − | id="E162-MJMATHI-3BB"
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| − | d="M166 673Q166 685 183 694H202Q292 691 316 644Q322 629 373 486T474 207T524 67Q531 47 537 34T546 15T551 6T555 2T556 -2T550 -11H482Q457 3 450 18T399 152L354 277L340 262Q327 246 293 207T236 141Q211 112 174 69Q123 9 111 -1T83 -12Q47 -12 47 20Q47 37 61 52T199 187Q229 216 266 252T321 306L338 322Q338 323 288 462T234 612Q214 657 183 657Q166 657 166 673Z"></path></defs><g
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| − | y="0"></use></g></svg></span>
| + | |
| − | <script type="math/tex">\lambda</script>
| + | |
| − | </td>
| + | |
| − | <td><span>the growth rate</span></td>
| + | |
| − | <td><span>0~</span><span class="MathJax_SVG" tabindex="-1"
| + | |
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| − | xmlns:xlink=" " width="2.884ex" height="2.344ex"
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| − | d="M21 287Q22 293 24 303T36 341T56 388T88 425T132 442T175 435T205 417T221 395T229 376L231 369Q231 367 232 367L243 378Q303 442 384 442Q401 442 415 440T441 433T460 423T475 411T485 398T493 385T497 373T500 364T502 357L510 367Q573 442 659 442Q713 442 746 415T780 336Q780 285 742 178T704 50Q705 36 709 31T724 26Q752 26 776 56T815 138Q818 149 821 151T837 153Q857 153 857 145Q857 144 853 130Q845 101 831 73T785 17T716 -10Q669 -10 648 17T627 73Q627 92 663 193T700 345Q700 404 656 404H651Q565 404 506 303L499 291L466 157Q433 26 428 16Q415 -11 385 -11Q372 -11 364 -4T353 8T350 18Q350 29 384 161L420 307Q423 322 423 345Q423 404 379 404H374Q288 404 229 303L222 291L189 157Q156 26 151 16Q138 -11 108 -11Q95 -11 87 -5T76 7T74 17Q74 30 112 181Q151 335 151 342Q154 357 154 369Q154 405 129 405Q107 405 92 377T69 316T57 280Q55 278 41 278H27Q21 284 21 287Z"></path></defs><g
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| + | |
| − | <script type="math/tex">k_m</script>
| + | |
| − | </td>
| + | |
| − | </tr>
| + | |
| − | </tbody>
| + | |
| − | </table>
| + | |
| − | </figure>
| + | |
| − | <p style="text-align: center;">
| + | |
| − | <img src='https://2019.igem.org/wiki/images/3/35/T--Peking--prodictivity_odesolve.png'
| + | |
| − | alt='' referrerPolicy='no-referrer'/></p>
| + | |
| − | <p class='FigAnnotation' style="font-weight:bold;">Figure 19: The dynamic of the amount of bacteria, nutrient and product at different growth rate.</p>
| + | |
| − | <p>
| + | |
| − | <span>The ODE is difficult to solve but we can analyze the steady states of it.</span>
| + | |
| − | </p>
| + | |
| − | <p><span>suppose initially </span><span class="MathJax_SVG" tabindex="-1"
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| − | <script type="math/tex">m(0) = m_0, n(0) = n_0, p(0) = p_0</script>
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| − | <span>, noticing that </span></p>
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| − | <script type="math/tex; mode=display" id="MathJax-Element-28">
| + | |
| − | \frac{1}{k_n}\frac{\mathrm{d}}{\mathrm{d}t}n + \frac{1}{\lambda}\frac{\mathrm{d}}{\mathrm{d}t}m = \frac{1}{k_n}\frac{\mathrm{d}}{\mathrm{d}t}n + \frac{k_m}{k_p(k_m-\lambda)}\frac{\mathrm{d}}{\mathrm{d}t}p = 0
| + | |
| − | </script>
| + | |
| − | </div>
| + | |
| − | </div>
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| − | <p><span>thus we know that </span><span class="MathJax_SVG" tabindex="-1"
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| − | <script type="math/tex">\displaystyle \frac{n}{k_n} + \frac{m}{\lambda}</script>
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| − | <script type="math/tex">
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| − | \displaystyle \frac{n}{k_n} + \frac{k_m p}{k_p(k_m-\lambda)}
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| − | <span> remain constant in the entire dynamic process. Provided the initial condition, we can deduce</span>
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| − | <script type="math/tex; mode=display" id="MathJax-Element-29">\begin{cases}
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| − | \displaystyle \frac{n}{k_n} + \frac{m}{\lambda} = \frac{n_0}{k_n} + \frac{m_0}{\lambda} \\
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| − | \displaystyle \frac{n}{k_n} + \frac{k_m p}{k_p(k_m-\lambda)} = \frac{n_0}{k_n} + \frac{k_m p_0}{k_p(k_m-\lambda)}
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| − | \end{cases}
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| − | </script>
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| − | </div>
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| − | <p><span>holds throughout the growth-and-production process. Finally, the nutrients are exhausted and the microbiomes stop both growing and producing. Denoting the concentration of all the materials at the final state as </span><span
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| − | <script type="math/tex">n^{\mathrm{ss}}, m^{\mathrm{ss}}</script>
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| − | <span> and </span><span class="MathJax_SVG" tabindex="-1"
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| − | <script type="math/tex">p^{\mathrm{ss}}</script>
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| − | <span>, the above-mentioned equation still holds:</span></p>
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| − | <script type="math/tex; mode=display" id="MathJax-Element-30">\begin{cases}
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| − | \displaystyle \frac{n^{\mathrm{ss}}}{k_n} + \frac{m^{\mathrm{ss}}}{\lambda} = \frac{n_0}{k_n} + \frac{m_0}{\lambda} \\
| + | |
| − | \displaystyle \frac{n^{\mathrm{ss}}}{k_n} + \frac{k_m p^{\mathrm{ss}}}{k_p(k_m-\lambda)} = \frac{n_0}{k_n} + \frac{k_m p_0}{k_p(k_m-\lambda)}
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| − | \end{cases}
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| − | </script>
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| − | </div>
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| − | </div>
| + | |
| − | <p><span>moreover, at the final stage, the nutrients are exhausted so </span><span
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| − | <script type="math/tex">n^{\mathrm{ss}}=0</script>
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| − | <span>. Then we can solve</span></p>
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| − | </div>
| + | |
| − | <script type="math/tex; mode=display" id="MathJax-Element-31">\begin{cases}
| + | |
| − | \displaystyle m^{\mathrm{ss}} = m_0 + \frac{\lambda n_0}{k_n} \\
| + | |
| − | \displaystyle p^{\mathrm{ss}} = p_0 + \frac{n_0k_p}{k_n}(1 - \frac{\lambda}{k_m})
| + | |
| − | \end{cases}
| + | |
| − | </script>
| + | |
| − | </div>
| + | |
| − | </div>
| + | |
| − | <p><span>It's worth noting that </span><span class="MathJax_SVG" tabindex="-1"
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| − | <script type="math/tex">p^{\mathrm{ss}}</script>
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| − | <span> is negatively and linearly related to the growth rate. This result is in accordance with the empirical formula provided in [1].</span>
| + | |
| − | </p>
| + | |
| − | <p><span>In this section, we discussed the possibility of our system being used to increase production of biological products. Our experiments also confirmed that in our system, the yield of GFP and indigo would increase with the increase of the concentration of inducer. It is consistent with the prediction of our model. In general, we can control the growth rate of bacteria by reducing nutrition, and our system has successfully controlled the growth rate of bacteria under the condition of sufficient nutrition. At this time, the energy of bacteria will be allocated to more other metabolic activities, specifically, those metabolic activities that are not so closely related to their core life activities. This is the core mechanism that our model will explain.</span>
| + | |
| − | </p>
| + | |
| − | <h3><a name="references" class="md-header-anchor"></a><span>References</span></h3>
| + | |
| − | <ol start=''>
| + | |
| − | <li><span>Matthew Scott, Carl W. Gunderson, Eduard M. Mateescu, Zhongge Zhang, Terence Hwa. Interdependence of Cell Growth and Gene Expression: Origins and Consequences. Science 330, 1099 (2010)</span>
| + | |
| − | </li>
| + | |
| − | <li><span>Chen Liao, Andrew E. Blanchard and Ting Lu. An integrative circuit–host modelling framework for predicting synthetic gene network behaviours. Nature Microbiology volume 2, pages1658–1666 (2017)</span>
| + | |
| − | </li>
| + | |
| − | <li><span>Smil, 1998, Energies: An illustrated guide to the biosphere and civilization, MIT Press</span>
| + | |
| − | </li>
| + | |
| − | </ol>
| + | |
| − | | + | |
| − | <div class="clear extra_space" id="Quorum Sensing"></div>
| + | |
| − | <div class="clear extra_space"></div>
| + | |
| − | <div class="clear extra_space"></div>
| + | |
| − | <h2><a name="quorum-sensing"
| + | |
| − | class="md-header-anchor"></a><span>Quorum Sensing</span></h2>
| + | |
| − | <p><span>In this section we model to illustrate how our system works coupling with a quorum sensing system. We want out system to realize the population's auto-regulation - the cells stop growing fast when they sense a lot of other cells crowding around it. We realize this by applying LuxI-LuxR system, in which a kind of small molecule call AHL. This system was firstly discovered in </span><em><span>V. fischeri</span></em><span> as a means of intercellular communication. The cells produce exceeding amount of AHL which can move either into or out of the cells. When the population is large or dense in a region, the local AHL concentration increases and the cells sense this high concentration and respond to this by up- or down-regulating some genes' expression. In our system, the sensing of AHL results in an increment of dCas9, and consequently a down regulation in growth or replication rate (see </span><a
| + | |
| − | href='http://2019.igem.org/Team:Peking/Results'><span>design</span></a><span> for the design and experiments)</span>
| + | |
| − | </p>
| + | |
| − | <h3><a name="a-simulation-of-donor-receptor-experiment"
| + | |
| − | class="md-header-anchor"></a><span>A Simulation of Donor-Receptor Experiment</span>
| + | |
| − | </h3>
| + | |
| − | <p><span>Our first series of experiments involve the testing of our fore-mentioned logic. We separately introduced the AHL producing parts and the AHL sensing parts to two strains of </span><em><span>E. coli</span></em><span>. The former is called "donor" and the latter is called "recipient". The recipient cells are evenly coated onto the solid medium and the donor cells were dropped at the center of the medium. It is expected that the donors AHL, the AHL difusses around and inhibits the growth of the receptors around it (see </span><a
| + | |
| − | href='http://2019.igem.org/Team:Peking/Results'><span>design</span></a><span>)</span>
| + | |
| − | </p>
| + | |
| − | <p><span>Here we use a simple diffusion model and visualized simulation to describe this process. We suppose that the solid media is a 2D plane, the recipients are uniformly distributed on the plane, and the donor is dense at the center </span><span
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| − | y="408"></use></g></g></g></g><use xlink:href="#E33-MJMAIN-29"
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| − | x="9104" y="0"></use><use
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| − | xlink:href="#E33-MJMATHI-75" x="9493" y="0"></use><use
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| − | x="0" y="0"></use><use
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| − | transform="translate(975,0)"><use transform="scale(0.5)"
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| − | xlink:href="#E33-MJMATHI-79" x="0"
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| − | y="0"></use><use
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| − | y="362"></use></g></g><g transform="translate(529,-455)"><use
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| − | transform="scale(0.5)" xlink:href="#E33-MJMATHI-3C3" x="0"
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| − | y="0"></use><use transform="scale(0.5)" xlink:href="#E33-MJMAIN-32"
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| − | x="572" y="288"></use></g></g></g></g></g></g></g></g></g></svg></span>
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| − | </div>
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| − | <script type="math/tex; mode=display" id="MathJax-Element-32">
| + | |
| − | \frac{\partial u}{\partial t} = D(\frac{\partial^2}{\partial x^2} + \frac{\partial^2}{\partial y^2})u + C\mathrm{e}^{-\frac{x^2 + y^2}{\sigma^2}}
| + | |
| − | </script>
| + | |
| − | </div>
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| − | </div>
| + | |
| − | <p><span>where </span><span class="MathJax_SVG" tabindex="-1"
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| − | style="font-size: 100%; display: inline-block;"><svg
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| − | xmlns:xlink=" " width="3.516ex" height="1.877ex"
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| − | style="vertical-align: -0.705ex;"><defs><path stroke-width="0"
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| − | id="E173-MJMATHI-78"
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| − | d="M52 289Q59 331 106 386T222 442Q257 442 286 424T329 379Q371 442 430 442Q467 442 494 420T522 361Q522 332 508 314T481 292T458 288Q439 288 427 299T415 328Q415 374 465 391Q454 404 425 404Q412 404 406 402Q368 386 350 336Q290 115 290 78Q290 50 306 38T341 26Q378 26 414 59T463 140Q466 150 469 151T485 153H489Q504 153 504 145Q504 144 502 134Q486 77 440 33T333 -11Q263 -11 227 52Q186 -10 133 -10H127Q78 -10 57 16T35 71Q35 103 54 123T99 143Q142 143 142 101Q142 81 130 66T107 46T94 41L91 40Q91 39 97 36T113 29T132 26Q168 26 194 71Q203 87 217 139T245 247T261 313Q266 340 266 352Q266 380 251 392T217 404Q177 404 142 372T93 290Q91 281 88 280T72 278H58Q52 284 52 289Z"></path><path
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| − | stroke-width="0" id="E173-MJMAIN-2C"
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| − | d="M78 35T78 60T94 103T137 121Q165 121 187 96T210 8Q210 -27 201 -60T180 -117T154 -158T130 -185T117 -194Q113 -194 104 -185T95 -172Q95 -168 106 -156T131 -126T157 -76T173 -3V9L172 8Q170 7 167 6T161 3T152 1T140 0Q113 0 96 17Z"></path><path
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| − | d="M21 287Q21 301 36 335T84 406T158 442Q199 442 224 419T250 355Q248 336 247 334Q247 331 231 288T198 191T182 105Q182 62 196 45T238 27Q261 27 281 38T312 61T339 94Q339 95 344 114T358 173T377 247Q415 397 419 404Q432 431 462 431Q475 431 483 424T494 412T496 403Q496 390 447 193T391 -23Q363 -106 294 -155T156 -205Q111 -205 77 -183T43 -117Q43 -95 50 -80T69 -58T89 -48T106 -45Q150 -45 150 -87Q150 -107 138 -122T115 -142T102 -147L99 -148Q101 -153 118 -160T152 -167H160Q177 -167 186 -165Q219 -156 247 -127T290 -65T313 -9T321 21L315 17Q309 13 296 6T270 -6Q250 -11 231 -11Q185 -11 150 11T104 82Q103 89 103 113Q103 170 138 262T173 379Q173 380 173 381Q173 390 173 393T169 400T158 404H154Q131 404 112 385T82 344T65 302T57 280Q55 278 41 278H27Q21 284 21 287Z"></path></defs><g
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| − | stroke="currentColor" fill="currentColor" stroke-width="0"
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| − | transform="matrix(1 0 0 -1 0 0)"><use xlink:href="#E173-MJMATHI-78" x="0"
| + | |
| − | y="0"></use><use
| + | |
| − | xlink:href="#E173-MJMAIN-2C" x="572" y="0"></use><use
| + | |
| − | xlink:href="#E173-MJMATHI-79" x="1016" y="0"></use></g></svg></span>
| + | |
| − | <script type="math/tex">x, y</script>
| + | |
| − | <span> are coordinates, </span><span class="MathJax_SVG" tabindex="-1"
| + | |
| − | style="font-size: 100%; display: inline-block;"><svg
| + | |
| − | xmlns:xlink=" " width="1.329ex" height="1.41ex"
| + | |
| − | viewBox="0 -504.6 572 607.1" role="img" focusable="false"
| + | |
| − | style="vertical-align: -0.238ex;"><defs><path stroke-width="0"
| + | |
| − | id="E174-MJMATHI-3C3"
| + | |
| − | d="M184 -11Q116 -11 74 34T31 147Q31 247 104 333T274 430Q275 431 414 431H552Q553 430 555 429T559 427T562 425T565 422T567 420T569 416T570 412T571 407T572 401Q572 357 507 357Q500 357 490 357T476 358H416L421 348Q439 310 439 263Q439 153 359 71T184 -11ZM361 278Q361 358 276 358Q152 358 115 184Q114 180 114 178Q106 141 106 117Q106 67 131 47T188 26Q242 26 287 73Q316 103 334 153T356 233T361 278Z"></path></defs><g
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| − | stroke="currentColor" fill="currentColor" stroke-width="0"
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| + | |
| − | x="0"
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| − | y="0"></use></g></svg></span>
| + | |
| − | <script type="math/tex">\sigma</script>
| + | |
| − | <span> represents the radius of the donor colony, </span><span
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| − | class="MathJax_SVG" tabindex="-1"
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| + | |
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| + | |
| − | x="0"
| + | |
| − | y="0"></use></g></svg></span>
| + | |
| − | <script type="math/tex">C</script>
| + | |
| − | <span> and </span><span class="MathJax_SVG" tabindex="-1"
| + | |
| − | style="font-size: 100%; display: inline-block;"><svg
| + | |
| − | xmlns:xlink=" " width="1.923ex" height="1.877ex"
| + | |
| − | viewBox="0 -755.9 828 808.1" role="img" focusable="false"
| + | |
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| − | id="E176-MJMATHI-44"
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| − | d="M287 628Q287 635 230 637Q207 637 200 638T193 647Q193 655 197 667T204 682Q206 683 403 683Q570 682 590 682T630 676Q702 659 752 597T803 431Q803 275 696 151T444 3L430 1L236 0H125H72Q48 0 41 2T33 11Q33 13 36 25Q40 41 44 43T67 46Q94 46 127 49Q141 52 146 61Q149 65 218 339T287 628ZM703 469Q703 507 692 537T666 584T629 613T590 629T555 636Q553 636 541 636T512 636T479 637H436Q392 637 386 627Q384 623 313 339T242 52Q242 48 253 48T330 47Q335 47 349 47T373 46Q499 46 581 128Q617 164 640 212T683 339T703 469Z"></path></defs><g
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| − | stroke="currentColor" fill="currentColor" stroke-width="0"
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| − | x="0"
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| − | y="0"></use></g></svg></span>
| + | |
| − | <script type="math/tex">D</script>
| + | |
| − | <span> denotes the diffusion constant. The randomly distributed recipients stop growing when the local concentration reach 10</span><sup><span>-6</span></sup><span>μM/L.</span>
| + | |
| − | </p>
| + | |
| − | <p><span>Here we numerically solve the equation with finite difference method. We draw an animation visualize this dynamic process. Furthermore, we randomly place 400 receptors on the plane to show their colony formation. It can be seen that the receptors distant from the center grow into colonies, while most of the receptors nearby the center grow into relatively small colonies or cannot grow into colonies. </span>
| + | |
| − | </p>
| + | |
| − | <p style="text-align: center;"><img src='https://2019.igem.org/wiki/images/7/79/T--Peking--im.png' alt=''
| + | |
| − | referrerPolicy='no-referrer' style="width: 70%"></p>
| + | |
| − | <p class='FigAnnotation' style="font-weight:bold;">Figure 20: The simulation result.</p>
| + | |
| − | <h3><a name="reference" class="md-header-anchor"></a><span>Reference</span></h3>
| + | |
| − | <ol start=''>
| + | |
| − | <li><span>Lupp C1, Ruby EG. Vibrio fischeri uses two quorum-sensing systems for the regulation of early and late colonization factors. J Bacteriol. 2005 Jun;187(11):3620-9.</span>
| + | |
| − | </li>
| + | |
| − | </ol>
| + | |
| − | <p> </p></div>
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| − | </div>
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| − | </body>
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| − | <div class="column full_size" id="footer_locate"></div>
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| − | </html>
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