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Positive feedback closes a causal loop whose net effect reinforces an initiating change. A loop with two inhibitory links can therefore have positive feedback. In signal transduction, a product that increases the activity of the enzyme making it illustrates reinforcement; the consequences depend on the full mathematical model, not just the loop sign. See signaling feedback.

A biological example is cell-cycle activation feedback. Cyclin B binds Cdc2, whose activity promotes activation of Cdc25; Cdc25 removes inhibitory phosphorylation from Cdc2, permitting further activation. Cdc2 also inhibits Wee1, an enzyme that inhibits Cdc2 through phosphorylation. That second return contains two inhibitions and therefore also has positive feedback. These are regulatory paths, not a claim that every connection is a single direct molecular encounter. ^[ref]

Reinforcement can preserve a decision after its initiating stimulus weakens: returning from the high state may require a lower input than entering it. The cell-cycle hysteresis experiment below tests this history dependence at matched cyclin B concentrations. A steep response alone is insufficient evidence of bistability, and finite observation times can make slow relaxation look like memory. A proposed switch must specify its input, readout and observation interval.

Saturating positive feedback limits the reinforcing rate as activity increases. Here is an explicitly synthetic ordinary differential equation for normalized nonnegative input $u$, response $x$, and return strength $\beta$:The return is an increasing, nonproportional function of $x$, while removal is proportional to $x$. Time and activities are dimensionless variables. At $x=0$ the vector field points into the nonnegative domain, and $dx/dt\le u+\beta -x$ prevents unbounded growth there. This makes the toy useful for asking about a bounded switch; it supplies no molecular mechanism for the chosen rate law.

At an equilibrium point, $f=0$. For a simple equilibrium point, the sign of the derivativedetermines local asymptotic stability. If $\beta =1$, the maximum reinforcing slope is $3\sqrt{3}/8<1$, so $f$ decreases strictly: every $u\ge 0$ has one asymptotically stable equilibrium point despite positive feedback.

Three equilibrium points become possible only if the reinforcing slope exceeds removal's slope somewhere. Its maximum is $3\sqrt{3}\beta /8$, at $x=1/\sqrt{3}$. Consequently this toy requiresfor two distinct folds. This is a necessary threshold for a bistability interval in this toy, not a universal biochemical number. At a fold, both $f=0$ and $f_x=0$, givingFor $\beta =1.8$, the folds are at $(x,u)\simeq (0.350003,0.153563)$ and $(0.887240,0.094405)$. Between these input values there are two asymptotically stable equilibrium points separated by an unstable one. At $u=0.12$, the three activities are approximately $0.171331$, $0.621230$ and $1.127439$; the low and high ones are stable.

A sufficiently slow increasing sweep follows the low branch to $u_{\mathrm{on}}\simeq 0.153563$ and then jumps upward. A decreasing sweep follows the high branch to $u_{\mathrm{off}}\simeq 0.094405$ and then jumps downward: hysteresis. These are limiting quasistatic thresholds, with relaxation between input changes and negligible perturbations that could cause earlier switching. Finite sweep rates and fluctuations can alter observed thresholds. A switchlike response with only one stable equilibrium point does not have this equilibrium hysteresis mechanism.

Signaling feedback returns the effect of a downstream event to an earlier stage of signal transduction, closing a loop analogous to feedback control. Trace the causal arrows: if an earlier relay activates a later relay and the later relay changes the earlier relay's activity, the return path closes the loop. Negative feedback opposes the initiating change; positive feedback reinforces it. Signaling feedback is a possible property of signal transduction, not a requirement of every pathway.

For a schematic example, let relay $A$ activate relay $B$. If $B$ inhibits $A$, increased $A$ eventually produces an opposing influence: negative feedback. If $B$ activates $A$, increased $A$ produces a reinforcing influence: positive feedback. These signs describe effects on activity, rather than the direction in which molecules travel. A closed loop containing two inhibitions can have positive feedback, because inhibiting an inhibitor reinforces the original change. The sign belongs to the whole loop.

Negative feedback can restrain excessive activation and help preserve a usable range of responses. Positive feedback can support a decisive transition: Alberts and colleagues describe an enzyme whose product increases its own activity. Such reinforcement can contribute to switchlike behavior, but a positive feedback arrow alone does not prove bistability. A different structure, an incoherent feedforward loop, sends opposing influences forward from the same input; inhibition there is not a downstream return. ^{[ref] [ref]}

A worked mathematical model shows why negative feedback does not automatically produce complete signaling adaptation. Let $s$ be a fixed normalized input, $r$ a normalized response, $g\ge 0$ a dimensionless feedback gain, and $\tau >0$ a time constant. Suppose response removal contributes $-r$ and a return proportional to the response contributes $-gr$. The ordinary differential equation isSetting the derivative to zero gives the equilibrium point $r_{\ast }=s/(1+g)$. A displacement $\delta r=r-r_{\ast }$ obeys $\tau d(\delta r)/dt=-(1+g)\delta r$, so its decaying exponential function establishes asymptotic stability. For a unit input switched on at $t=0$, initial condition $r(0)=0$, $g=2$ and $\tau =1$ second,The negative feedback reduces the eventual response from $1$ to $1/3$, but this response rises monotonically and never returns to its zero baseline. Attenuation and complete signaling adaptation are different properties. This deliberately simple mathematical model specifies no molecular pathway; integral action provides a contrasting way to remove a lasting offset in a stable feedback control system. ^[ref]