Table A1.
Effect | Parameter | Est’d Value | LHS Rangea | References |
---|---|---|---|---|
NF-κB turnover | a1 | 2.4 h−1 | [0.01, 50] | (Hoffmann et al., 2002) |
Stat1 turnover | a2 | 2.77 h−1 | [0.01, 50] | (Haspel et al., 1996) |
iNOS mRNA turnover | a3 | 0.173 h−1 | [0.116, 0.347] | (Ray & Kirschner, 2006) |
INOS turnover | a4 | 0.0693 h−1 | [0.0365, 0.693] | (Ray & Kirschner, 2006) |
NHA turnover | a5 | 5.545 µmol/h | [5.454, 332.711] | (Ray & Kirschner, 2006) |
NO turnover | a6 | 2.773 h−1 | [2.727, 166.355] | (Ray & Kirschner, 2006) |
LIP turnover | a7 | 32.201 µmol/h | [2.565, 61.820] | (Ray & Kirschner, 2006) |
Ferritin turnover | a8 | 40.0 µmol/h | [4, 89] | (Ray & Kirschner, 2006) |
IRP turnover | a9 | 35.0 µmol−1 h−1 | [29.17, 44.06] | (Ray & Kirschner, 2006) |
NF-κB reg. by TNF | g111 | 1.18 | Not Varied | (Harant et al., 1996) |
TNF conc. scaling | dTNF | 117.4 | Not Varied | (Harant et al., 1996) |
Stat1 reg. by IFN-γ | g212 | cf. Table A2 | Not Varied | cf. Table A2 |
IFN-γ conc. scaling | dIFN-γ | 20 | Not Varied | cf. Table A2 |
NF-κB txn reg. | g31 | cf. Table A2 | [0.1, 1.5] | cf. Table A2 |
Stat1 txn reg. | g32 | 0.26 | [0.1, 1] | cf. Table A2 |
LIP txn reg. | g37 | −0.177 | [−0.1, −2] | (Ray & Kirschner, 2006) |
NO feedback to NF-κB | g16 | cf. Table A2 | [−0.3, −1.5] | (Hattori et al., 2004); cf. Table A2 |
NO feedback to Stat1 | g26 | −0.5 | [−0.3, −1.5] | (Ray & Kirschner, 2006) |
Translation | g43 | 1 | Not Varied | (Ray & Kirschner, 2006) |
Arg NHA reg. | g54 | 1 | Not Varied | (Ray & Kirschner, 2006) |
NHA NO reg. | h54 | 1 | Not Varied | (Ray & Kirschner, 2006) |
reg. Of iron influx | g79 | 0.5 | [0.1, 1.5] | (Ray & Kirschner, 2006) |
LIP sequestration | h78 | 0.74 | Not Varied | (Kakhlon et al., 2001) |
IRP reg. of ferritin | g89 | −0.645 | [−0.1, −2] | (Ray & Kirschner, 2006) |
LIP Ferritin | h87 | 1 | Not Varied | (Ray & Kirschner, 2006) |
NO reg. of IRP | h96 | −0.5 | [−0.1, −1] | (Ray & Kirschner, 2006) |
LIP reg. of IRP | h97 | 0.5 | [0.4, 2] | (Ray & Kirschner, 2006) |
Mtb growth rate | αb | 0.0250 Mtb/h | [0.0191, 0.0385] | Avg. of (Graham & Clark-Curtiss, 1999; Manca et al., 1999; Silver et al., 1998; Zhang et al., 1998) |
NO reg. of Mtb growth | gbNO | −0.5 | [−0.3, −1.5] | Initial guess |
Iron enhancement of Mtb growth | gbLIP | 1 | [0.3, 1.0] | Initial guess |
Iron effect saturation | kbLIP | 1 | [0.1, 2] | Initial guess |
Intrinsic Mtb death rate | βb | 2.5×10−4 Mtb/h | [2.5 × 10−5, 2.5 × 10−4] | 1 % of αb |
Killing by NO | hbNO | 0.75 | [0.1, 2] | Initial guessb |
NF-κB reg. by LAM | gκB | 0.2 | Not Varied | cf. Table A2 |
Sloughed LAM | σ | 120 Mtb−1 | [10, 10000] | (Nigou et al., 2000) |
Scaling of Mtb on LIP | kLIPb | 106 Mtb−1 | Not Varied | Initial guess |
Effect of Mtb on LIP | hLIPb | 0.05 | [0.1, 0.001] | Initial guess |
Maximum Mtb per Mϕ | bmax | 50 Mtb/Mϕ | Not Varied | Guess from (Paul et al., 1996; Zhang et al., 1998) |
LHS: Latin hypercube sampling.
Calibrated to achieve approximately 50% killing at the default cytokine dose for default parameter values.