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J A Rice

Publications and source records attributed to J A Rice.

13 recordsLinked to original sources

Maximum likelihood estimation and identification directly from single-channel recordings.

We present a method for analysis of noisy sampled data from a single-channel patch clamp which bypasses restoration of an idealized quantal signal. We show that, even in the absence of a specific model, the conductance levels and mean dwell times within those levels can be estimated. Estimation of the rate constants of a hypothesized kinetic scheme is more difficult. We present examples in which the rate constants can be effectively estimated and examples in which they cannot.

Animals

Bayesian restoration of single-channel patch clamp recordings.

The technique of patch clamp recording makes possible the measurement of current flowing through a single ion channel in a cell membrane. Examination of such recordings suggests that the current is quantal in nature, alternating in a seemingly random manner between "on" and "off," but the recordings are corrupted by noise from a variety of sources. In this paper we propose and illustrate methods for restoring the underlying quantal signal from such noisy measurements. The methods use a Markov chain prior distribution for the underlying quantal process and base the restoration on the resulting posterior distribution.

Algorithms

On the superposition of currents from ion channels.

We derive a number of statistical properties of the superposition of several independent channels contributing to a patch-clamp recording. Failure of these properties indicates dependence of the channels and may suggest the nature of interactions. We show how properties such as dwell-time distributions of the individual channels may be determined from those of the superposition in the case that the channels are independent.

Animals

Water analysis.

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Water Pollutants

Determination of the extent of DNA bending by an adenine-thymine tract.

We determined the magnitude of the bend induced in DNA by an adenine-thymine tract by measuring the rate of cyclization of DNA oligonucleotides containing phased A tracts. A series of linear multimers with 2-bp single-stranded ends, in which the (A.T)6 tracts are separated by CG2-3C sequences and are positioned 10 and 11 bp apart alternately, were prepared from 21 bp long synthetic duplexed deoxyoligonucleotides. The cyclization rates of the multimers (105-210 bp) and the bimolecular association rate of the 84 bp long multimer were measured in the presence of DNA ligase. From the rate constants of the cyclization and bimolecular association reactions, ring closure probabilities were obtained for the multimers. The systematically bent molecules were simulated by Monte Carlo methods, and the ring closure probabilities were calculated for a given set of junction bend angles. By comparing the calculated values of ring closure probabilities to experimental values and adjusting the junction bend angles to fit experimental values, the extent of bending at the junctions (or the extent of bending for an adenine tract) was determined. We conclude that an A6 tract bends the DNA helix by 17-21 degrees.

Adenine

A note on single-channel autocorrelation functions.

It is shown for time-reversible ion channel gating mechanisms that the sojourn time autocorrelation functions are necessarily nonnegative, decreasing, and convex. It is also shown, again for time-reversible mechanisms, that the lagged moments of all orders are determined by the first three moments. The application of these results to the statistical analysis of single-channel kinetics is briefly discussed.

Ion Channel Gating

Kinetic analysis of channel gating. Application to the cholinergic receptor channel and the chloride channel from Torpedo californica.

Identification of the minimum number of ways in which open and closed states communicate is a crucial step in defining the gating kinetics of multistate channels. We used certain correlation functions to extract information about the pathways connecting the open and closed states of the cation channel of the purified nicotinic acetylcholine receptor and of the chloride channel of Torpedo californica electroplax membranes. Single channel currents were recorded from planar lipid bilayers containing the membrane channel proteins under investigation. The correlation functions are conveniently computed from single channel current records and yield information on E, the minimum number of entry/exit states into the open or closed aggregates. E gives a lower limit on the numbers of transition pathways between open and closed states. For the acetylcholine receptor, the autocorrelation analysis shows that there are at least two entry/exit states through which the open and closed aggregates communicate. The chloride channel fluctuates between three conductance substates, here indentified as C, M, and H for closed, intermediate, and high conductance, respectively. Correlation analysis shows that E is greater than or equal to 2 for the M aggregate, indicating that there are at least two distinct entry/exit states in the M aggregate. In contrast, there is no evidence for the existence of more than one entry/exit state in the C or H aggregates. Thus, these correlation functions provide a simple and general strategy to extract information on channel gating kinetics.

Animals

Hospitals must follow strategy to lead regional sharing efforts.

A hospital that wants to initiate or expand service sharing with other institutions in its service area must analyze and act on many considerations that affect the success of such relationships. For example, the hospital must identify its resources and goals for sharing as well as those of the other participants, eliminate personal and institutional 'ego needs' from the relationship, and promote effective interpersonal relationships among the key individuals from the participating institutions.

Goals

Effect of probenecid on cerebrospinal fluid methotrexate kinetics.

The effect of probenecid (PBC) on methotrexate (MTX) kinetics in the cerebrospinal fluid (CSF) and serum was studied in 4 patients on high-dose MTX with leucovorin rescue to determine whether addition of PBC could prolong effective CSF MTX levels. Each patient received 2 courses of MTX, 1 with and 1 without PBC. PBC caused a 2.8 to 4.2-fold increase in CSF MTX concentrations but failed to prolong the CSF half-life (1 1/2). PBC prolonged the initial MTX elimination t 1/2 in the blood from 2.7 to 4.1 hr, but had little effect on subsequent t 1/2s. No effect of MTX on PBC clearance was detected. Our data suggest that in man PBC in concentrations that were high enough to inhibit the renal clearance of MTX failed to alter the clearance of MTX from the CSF when both drugs were administered systemically.

Adult