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The results presented above suggest that application of artificial buffer systems to block pH changes in the synaptic cleft acts to inhibit feedback and decrease the intracellular pH.
We found that the pH buffers HEPES and Tris partially inhibit feedback responses in cones and horizontal cells and lead to intracellular acidification of neurons.
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Two of the seven missense mutations (c.154G>C (p.D52H) and c.385C>A (p.L129I)) causing PRS-I superactivity have been found to disrupt one of the two allosteric sites, therefore inhibiting feedback inhibition [ 1, 35].
HEPES maximally inhibits feedback by about 60% with a Kd of about 350 µM.
Thus, if the pH buffer component is the most prominent factor affecting feedback, acetate should be ineffective in inhibiting feedback.
Fig. 3C also gives data points for Tris. 4 mM Tris inhibits feedback by about half showing that this buffer is less effective than HEPES at blocking feedback.
This is in contrast to the effect of HEPES on feedback responses measured in cones, where 0.4 mM HEPES inhibits feedback half maximally and where 4 mM HEPES is a saturating concentration.
Interestingly, HEPES is more efficient in inhibiting feedback than Tris, whereas they have about equal pH buffer capacity in our experimental conditions (pH 7.8; 4 mM HEPES: 2.0 mM versus 4 mM Tris: 2.1 mM).
All the four methods effectively inhibit positive feedback, and BER continuously decreases with increasing iteration number (Fig. 3 b).
Comparison with the direct method shows that the two proposed algorithms can inhibit positive feedback and improve the power efficiency and reliability of the system we investigate.
All the other simulation parameters are similar to those in the settings in Fig. 2. Figure 3 a shows that the average and combined methods both inhibit positive feedback to some extent at E b /N 0=0.4 dB, avoid violent BER oscillation and maintain BER at a stable level with increasing iteration number.
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