1. We explore the roles of conductances in Hodgkin-Huxley (HH) models using a method that allows the explicit linking of HH model input-output behavior to parameter values for maximal conductances, voltage shifts, and time constants. The procedure can be used to identify not only the parameter values most critical to supporting a neuronal activity pattern of interest but also the relationships between parameters which may be required, e.g., limited ranges of relative magnitudes. 2. The method is the repeated use of stochastic search to find hundreds or even thousands of different sets of model parameter values that allow a HH model to produce a desired behavior, such as current-frequency transduction, to within a desired tolerance, e.g., frequency match to within 10 Hz. Graphical or other analysis may then be performed to reveal the shape and boundaries of the parameter solution regions that support the desired behavior. 3. The shape of these parameter regions can reveal parameter values and relationships essential to the behavior. For instance, graphical display may reveal covariances between maximal conductance values, or a much wider range of variation in some maximal conductance values than in others. 4. We demonstrate the use of these techniques with simple, representative HH models, primarily that of Connor et al. for crustacean walking leg axons, but also some extensions of the results are explored using the more complex model of McCormick and Huguenard for thalamocortical relay neurons. Both models are single compartment. Behaviors studied include current-to-frequency transduction, the time delay to first action potential in response to current steps, and the timing of action potential occurrences in response to both square-wave current injection and the injection of currents derived from in vitro records of excitatory postsynaptic currents. 5. Using these simple models, we find that relatively general behaviors such as current-frequency (I/F) curves may be supported by very broad, but bounded parameter solution regions, with the shape of the solution regions revealing the relative importance of the maximal conductances of a model in creating the behavior. Furthermore, we find that a focus on increasingly specific behaviors, such as I/F behavior, defined by tolerances of only a few hertz combined with strict requirements for action potential height, inevitably leads to increasingly narrow, and eventually nonphysiologically narrow, regions of acceptable parameter values. 6. We use the Connor et al. model to reproduce the in vitro action potential timing responses of a rat brain stem neuron to various stimuli.(ABSTRACT TRUNCATED AT 400 WORDS)

No abstract

Non-clinical drug safety profiles of the AR antagonist drug class create a significant barrier to the identification of next generation AR antagonists. GABA-A inhibition is a common off-target activity of approved and next generation AR antagonists potentially explaining some side effects and safety hazards of this class of drugs.

A field test to examine some aspects of surfactant behavior, and a later polymer injection study, led to the conclusion that a tertiary oil bank can polymer injection study, led to the conclusion that a tertiary oil bank can be formed in a reservoir using low-tension surfactants. Another conclusion is that it is essential to control the mobility immediately behind the bank to insure that a significant fraction of the mobilized oil will be driven to the producing wells. Introduction The work summarized here represents a part of the effort by Mobil Research and Development Corp. to develop an economic low-tension waterflooding process. Various aspects of displacement at low tension process. Various aspects of displacement at low tension are discussed in general terms. Details of the extensive background effort supporting the necessary laboratory and field experiments, an interpretation of results, and the development of an adequate transport theory are deferred to later publications. Not all aspects of this process have been field tested yet. However, Mobil has carried out a field test in South Texas to examine factors relating primarily to surfactant behavior. A polymer injection study was conducted at the same site some time later. As a result of these field studies and supporting theory we conducted that a tertiary oil bank can be fanned in a reservoir using low-tension surfactants and that mobility control immediately behind the bank is essential to insure that a significant fraction of the "mobilized oil" will be driven to producing wells. A surfactant waterflooding process capable of producing a tertiary oil bank has also been described by producing a tertiary oil bank has also been described by Gogarty and Tosch. One significant difference between their "Maraflood" process and the process described here is the manner in which the surfactant is used. Maraflood employs a surfactant slug that is miscible with the reservoir crude. Miscibility implies zero interfacial tension between this slug and the reservoir crude oil. Achieving and, particularly, maintaining this miscibility condition places rigorous requirements on the composition of the slug. Our process, on the other hand, does not depend upon process, on the other hand, does not depend upon miscibility between crude oil and water, but relies on very low interfacial tension between a water solution/ dispersion of a surfactant and the reservoir crude oil. Also, the compositional requirements that must be met in order to achieve and maintain a condition of very low tension are somewhat different from those needed in the Maraflood process. Description of the Process In what follows it is assumed that the process is started in a sandstone reservoir that is nearly or completely watered out. The water phase present in the reservoir at this stage is assumed to be a typical oilfield brine, high in total dissolved solids and in divalent cations, particularly calcium and magnesium. A regular pattern from the existing injectors and producers is chosen, with high areal sweep as an producers is chosen, with high areal sweep as an important design criterion. The process consists of injecting three slugs of water with different chemical compositions. These will be denoted as the protective slug, the surfactant slug, and the mobility-control slug, or as Slugs 1, 2, and 3, respectively. The protective slug is an aqueous solution of sodium chloride, Within limits, its volume is somewhat arbitrary, in the range of 0.1 of the pattern pore volume. JPT P. 205