Since Cannon, inspired by Bernard’s discussion of the conditions required for free and independent life, introduced the term homeostasis, many have embraced it as the main theoretical principle guiding physiology and medicine. Nonetheless, critics have argued that homeostasis is too limiting and have advanced a variety of alternative concepts such as heterostasis, rheostasis, and allostasis. We argue that the critics target a much narrower understanding of homeostasis put forward by the cyberneticists and that Bernard and Cannon embraced a far broader understanding that can accommodate the alternatives advanced by the critics and provide an integrated theoretical framework for physiology.

This paper is devoted to the study of a clearing queueing system with a special discipline. As soon as the server receives N negative feedbacks from customers, all present customers are forced to leave the system and the server undergoes a maintenance procedure. After an exponential maintenance time, the system resumes its service immediately. Using the matrix analytic method, we derive the steady-state distributions, which are then used for the computation of other performance measures. Furthermore, using first step analysis, we obtain the Laplace–Stieltjes transform of the sojourn time of an arbitrary customer. We also study the busy period of the system and derive the generating function of the total number of lost customers in a busy period. Finally, we investigate a long-run rate of cost and explore the optimal N value that minimizes the total cost per unit time. We also present some numerical examples to illustrate the impact of several model parameters to the performance measures.

In mammalian cells, the p53 pathway regulates the response to a variety of stresses, including oncogene activation, heat and cold shock, and DNA damage. Here we explore a mathematical model of this pathway, composed of a system of partial differential equations. In our model, the p53 pathway is activated by a DNA-compromising event of short duration. As is typical for mathematical models of the p53 pathway, our model contains a negative feedback loop representing interactions between the p53 and Mdm2 proteins. A novel feature of our model is that we combine a spatio-temporal approach with the appearance and repair of DNA damage. We investigate the behaviour of our model through numerical simulations. By ignoring the possibility of DNA repair, we first explore the scenario in which the cell has a very inefficient DNA repair mechanism. We find that spatio-temporal oscillations in p53 and Mdm2 may occur, consistent with experimental data. We then allow p53 to be directly involved in repairing DNA damage, since experimental evidence suggests this can happen. We find that oscillations in p53 and Mdm2 can still occur, but their amplitude damps down quickly as the DNA damage is repaired. Finally, we find that a minor change to the location of the DNA damage can notably change the spatial distribution of p53 within the nucleus. We discuss the biological implications of our results.

Drinking and thirst-motivated behaviour have traditionally been explained in terms of the rather simple concept of homeostasis. A homeostatic mechanism readily accounts for responses to acute changes in body-fluid levels. However, there are other factors regulating intake, for example, cues associated with eating, which interact with the time elapsed since last drinking and the availability of water. Future dehydration is avoided by behavioural hysteresis; a sudden reduction in fluid needs is not matched by an equivalent reduction in fluid intake. Another factor not explicable by traditional homeostasis is that, in general, drinking cannot be suppressed by water infusion. Nor are there rigid target values for body-fluid levels independent of the cost of obtaining water; when water is hard to get, a relatively low body fluid level is maintained, thus minimizing loss. On the basis of the results conflicting with traditional homeostatic theory, this paper tentatively suggests certain modifications toward a more realistic model of fluid ingestion.

The literature on path dependence has emphasized positive feedback effects that make it difficult to shift from a policy regime once it is in place. This article argues that policy regimes may also have strong negative feedback effects that undermine the political, fiscal or social sustainability of an existing policy regime. The prospects for a shift in policy regime depend largely on the balance between positive and negative feedback effects; the availability of incremental reform options that can be used to patch the status quo; and the availability of politically and fiscally attractive regime transition options. The paper argues that differential survival rates of different public pension regimes in western industrial countries can be understood by the interaction of these three factors.

The role of GABA in the outer plexiform layer of the turtle retina has been examined by intracellular recordings from L- and C-type horizontal cells in the isolated retina preparation.

GABA (1–5 mM) slightly depolarized the L-type horizontal cells, reduced the amplitude of their photoresponses, and slowed down the rate of hyperpolarization during the ON component of the photoresponse. These effects could not be replicated by either muscimol or baclofen. When synaptic transmission from the photoreceptors had been blocked by either kynurenic acid or cobalt ions, GABA depolarized L-type horizontal cells and augmented the remaining photoresponses. Neither muscimol nor baclofen exerted any effect on L-type horizontal cells under these conditions. Nipecotic acid, a competitive inhibitor of the GABA-uptake system, induced effects on turtle L-type horizontal cells which were similar to those exerted by GABA. Thus, the complex GABA effect on turtle L-type horizontal cells seems to represent the summation of at least two actions; an indirect one mediated by the red cones via GABAa-type receptors and a direct one which probably reflects the activation of an electrogenic GABA-uptake system.

GABA (1–5 mM) induced a transient depolarization in C-type horizontal cells but eliminated color opponency in only three cells out of seven studied. This observation is inconsistent with the notion that the only neural mechanism responsible for the chromatic properties of C-type horizontal cells in the turtle retina is a GABAergic negative feedback from the L-type horizontal cells onto the green ones.

In goldfish, negative feedback from horizontal cells to cones shifts the activation function of the Ca2+ current of the cones to more negative potentials. This shift increases the amount of Ca2+ flowing into the cones, resulting in an increase in glutamate release. The increased glutamate release forms the basis of the feedback-mediated responses in second-order neurons, such as the surround-induced responses of bipolar cells and the spectral coding of horizontal cells. Low concentrations of Co2+ block these feedback-mediated responses in turtle retina. The mechanism by which this is accomplished is unknown. We studied the effects of Co2+ on the cone/horizontal network of goldfish retina and found that Co2+ greatly reduced the feedback-mediated responses in both cones and horizontal cells in a GABA-independent way. The reduction of the feedback-mediated responses is accompanied by a small shift of the Ca2+ current of the cones to positive potentials. We have previously shown that hemichannels on the tips of the horizontal cell dendrites are involved in the modulation of the Ca2+ current in cones. Both the absence of this Co2+-induced shift of the Ca2+ current in the absence of a hemichannel conductance and the sensitivity of Cx26 hemichannels to low concentrations of Co2+ are consistent with a role for hemichannels in negative feedback from horizontal cells to cones.

Simple cells display a specific adaptation aftereffect when tested with drifting gratings. The onset of the response to each cycle of the grating is delayed after adapting, but the offset is unaffected. Testing with stationary bars whose luminance was modulated in time revealed that aftereffects occur only at certain points in both space and time. The aftereffects seen with moving stimuli were predicted from those seen with stationary stimuli. These adaptation experiments suggest a model that consists of mutually inhibitory simple cells that are in spatiotemporal quadrature. The inhibition is appropriately localized in space and time to create the observed aftereffects. In this model, inhibition onto direction-selective simple cells arises from simple cells with the same preferred direction.