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At least 1,315 records · Page 73Linked to original sources
PubMed1988

Open-state substructure of inwardly rectifying potassium channels revealed by magnesium block in guinea-pig heart cells.

1. Outward single-channel currents through inwardly rectifying K+ channels of cardiac myocytes were studied in the open cell-attached configuration to clarify the mechanism of the rectification. The outward currents, which were not recorded in the cell-attached configuration, appeared after the inner surface of the patch was exposed to low-Mg2+ solution by rupturing a part of the cell membrane. 2. The single-channel current-voltage (I-V) relation was linear in the absence of Mg2+ and crossed the voltage axis near the equilibrium potential for K+ (EK). The channel conductance was 22 and 16 pS (15-16 degrees C) at external K+ concentrations of 150 and 40 mM, respectively. 3. The channel rapidly closed on stepping the membrane potential of the patch to values more positive than EK. Decay of the average current during depolarization was fitted with a single-exponential function. The time constant appeared voltage dependent, but also tended to increase slowly with time after opening the cell to the bath solution. 4. Mg2+ on the cytoplasmic side blocked the outward currents without affecting the inward currents. The half-saturation concentration of the Mg2+ block was 1.7 microM as examined by measuring the mean patch current at +70 mV. 5. In the presence of internal Mg2+ at a micromolar level (2-10 microM), the outward single-channel current fluctuated between four levels including two intermediate levels (sublevels) in addition to the fully open channel current and the zero-current levels. The I-V relations of each sublevel were equally spaced with an interval of about 7 pS. Corresponding sublevels were found spontaneously in the inward direction. 6. Occupancy at each level was estimated from reconstructed traces at various Mg2+ concentrations and voltages, and compared with the value predicted from the binomial theorem. At different probabilities for the blocked state, the distribution of the current levels showed reasonable agreement with the binomial theorem. These findings suggest that the inwardly rectifying K+ channel of cardiac cells is composed of three identical conducting subunits and each subunit is blocked by Mg2+ independently. 7. Dwell times in each substate were distributed exponentially. On the assumption of the above model, the blocking (mu) and unblocking (lambda) rates were calculated. The value of mu increased with higher Mg2+ concentrations or larger depolarizations, while lambda ranged between 50 and 90 s-1 and seemed independent of Mg2+. 8. Owing to the voltage-dependent block by Mg2+, the average current decayed exponentially on depolarization beyond EK.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2002

A frequency distribution for the number of hematogenous organ metastases.

The number of metastases associated with a primary tumor can be a major determinant for the chance of cure. A model is proposed here where the frequency distribution of the number of experimental organ metastases is affected by Poisson statistics, and by stochastic variations in regional blood flow. The model predicts that the mean E (X) and variance var (X) of the number of metastases per organ should relate according to a power function,var (X)= E (X)(p)+E (X), where and p are the constants, and that the actual distribution has a Poisson-negative binomial form. This model was found consistent with the data derived from a meta-analysis of over 47 000 murine experimental metastases. This frequency distribution (together with knowledge of the size distribution for metastases and the fraction of clonogenic cells) could permit more accurate assessments for tumor control probabilities with adjuvant therapies.

Humans↗
PubMed2000

Flow and dispersion through a close-packed fixed bed of spheres

Fluid flow through a close-packed fixed bed of spheres in a face-centered cubic arrangement is investigated in numerical simulations using a lattice-Boltzmann formulation. The dispersion of a tracer gas is studied both experimentally and numerically. At low Reynolds numbers, Re</=14, the flow is steady with a distribution of normalized local kinetic energies that follows a power law over roughly three orders of magnitude. Consequently the "stagnant" zones play a significant role in determining transport through the packed bed in contrast with the dangling ends for the analogous electrical transport problem, where the distribution of local currents is log binomial. At higher Reynolds numbers transitions to time-oscillatory and chaotically (turbulently) varying flows are predicted to occur with a crossover to a log-normal distribution of local kinetic energies. At the onset of transverse velocity fluctuations the simulated trajectories of tracer particles can cross planes of symmetry, resulting in an abrupt enhancement of dispersion. The dispersion of tracer particles in the time-oscillatory and chaotic varying flows is predicted to be Fickian in the far field. Model predictions for dispersion in a chaotic flow with Re approximately 100 are shown to be in good agreement with experiment.

Journal Article↗
PubMed2005

A macroscopic kinetic model for DNA polymerase elongation and high-fidelity nucleotide selection.

The enzymatically catalyzed template-directed extension of ssDNA/primer complex is an important reaction of extraordinary complexity. The DNA polymerase does not merely facilitate the insertion of dNMP, but it also performs rapid screening of substrates to ensure a high degree of fidelity. Several kinetic studies have determined rate constants and equilibrium constants for the elementary steps that make up the overall pathway. The information is used to develop a macroscopic kinetic model, using an approach described by Ninio [Ninio J., 1987. Alternative to the steady-state method: derivation of reaction rates from first-passage times and pathway probabilities. Proc. Natl. Acad. Sci. U.S.A. 84, 663-667]. The principle idea of the Ninio approach is to track a single template/primer complex over time and to identify the expected behavior. The average time to insert a single nucleotide is a weighted sum of several terms, including the actual time to insert a nucleotide plus delays due to polymerase detachment from either the ternary (template-primer-polymerase) or quaternary (+nucleotide) complexes and time delays associated with the identification and ultimate rejection of an incorrect nucleotide from the binding site. The passage times of all events and their probability of occurrence are expressed in terms of the rate constants of the elementary steps of the reaction pathway. The model accounts for variations in the average insertion time with different nucleotides as well as the influence of G + C content of the sequence in the vicinity of the insertion site. Furthermore the model provides estimates of error frequencies. If nucleotide extension is recognized as a competition between successful insertions and time delaying events, it can be described as a binomial process with a probability distribution. The distribution gives the probability to extend a primer/template complex with a certain number of base pairs and in general it maps annealed complexes into extension products.

DNA-Directed DNA Polymerase↗
PubMed2002

Use of Akaike information criteria for model selection and inference. An application to assess prevention of gastrointestinal parasitism and respiratory mortality of Guinean goats in Kolda, Senegal.

A field experiment was carried out in Kolda (southern Senegal) from July 1986 to July 1988. Its goals were to: (1) describe the patterns of mortality of female Guinean goats by age, season and year; (2) assess preventive measures against respiratory diseases and gastrointestinal parasitism in reducing mortality; and (3) estimate the overall impact of these measures on survival to 1 year of age. Preventive measures for respiratory disease included vaccination against peste des petits ruminants (PPR) and pneumonic pasteurellosis (Pasteurella multocida types A and D). Control of gastrointestinal parasites was by deworming does with morantel (7.5mg kg(-1), three times during the rainy season). The effects of vaccines and deworming were tested in a randomised factorial field experiment with villages being the experimental units. A total of 19 villages, 113 goat herds and 1,458 goats were included in the study. Generalised linear models of survival for five cohorts of goats (defined by five different birth seasons) used a binomial assumption for the response distribution and a complementary log-log link. Explanatory variables included age, season, year, vaccination, deworming and their interactions. A complex a priori model was built on the basis of previous epidemiological knowledge; a purposely selected set of simpler models was compared to this full model by the Akaike information criterion (AIC) and derived statistics. Inference on 1-year survival and treatment effects accounted for model-selection uncertainty. It was carried out with a bootstrap procedure and used information from the whole set of selected models. Large variations in mortality by year and season were observed but no regular seasonal pattern was apparent. Mortality probabilities of kids in dewormed groups decreased quickly after birth, but remained elevated up to 9 months of age in the non-dewormed groups. Deworming lowered the risk of mortality. Vaccination alone was not protective (except during an observed outbreak of PPR).

Animals↗
PubMed2001

Counting statistics of photons produced by electronic shot noise.

A theory is presented for the photodetection statistics of radiation produced by current fluctuations in a phase-coherent conductor. Deviations are found from the Poisson statistics that would result from a classical current. For detection in a narrow frequency interval delta omega, the photocount distribution has the negative-binomial form of blackbody radiation if e delta omega is less than the mean current I in the conductor. When electronic localization sets in, I drops below e delta omega and a different type of super-Poissonian photon statistics results.

Journal Article↗
PubMed1975

Dissociation between nerve-muscle transmission and nerve trophic effects on rat diaphragm using type D botulinum toxin.

Small doses of botulinum toxin can produce partial blockage of transmitter release at the nerve--muscle junction. 2. Subthreshold e.p.p.s, 3--10 days after poisoning, show a distribution of amplitudes that is fitted by Poisson statistics. Successive e.p.p.s. in a short train show a marked facilitation. 3. Two weeks or more after poisoning with a dose of toxin that paralyses the whole muscle, when nerve--muscle transmission is in course of recovery, subthreshold e.p.p.s have an amplitude distribution that is fitted by binomial statistics. This property of transmission is similar to those described in newly formed nerve--muscle junctions, during embryogenesis or regeneration. 4. Muscle fibres with subthreshold transmission in the 5--10 day group of muscles were all supersensitive to ACh, as were a number of fibres in which nerve stimulation still produced an action potential. 5. Two weeks or more after poisoning, muscle fibres with subthreshold transmission had lost their extrajunctional ACh-sensitivity, as had many fibres with m.e.p.p.s of roughly normal frequency but no response to nerve stimulation. 6. In diaphragm muscles poisoned with botulinum toxin between 1 and 4 days previously, the rate of fast axonal transport of radioactively labelled proteins down the phrenic nerve is not greatly affected, but the amount of materials carried is reduced to about one quarter of normal. These labelled proteins accumulate in the intramuscular portion of the phrenic nerve, in or near the nerve terminals, to a much greater extent than in controls, showing that the normal release of some of these materials has been prevented by the toxin. 7. It is concluded that the blockage of the trophic effects of nerves by botulinum toxin is due to a blockage of release of trophic factors other than ACh. 8. The muscle nerve cannot maintain a muscle in its normal state simply by activation of contraction, and a regenerating nerve terminal can restore a muscle towards its normal state before it can release enough ACh to produce muscle contraction.

Acetylcholine↗
PubMed1983

Structural and functional analysis of synaptic transmission between identified leech neurones in culture.

The fine structure and physiological properties of chemical synapses that develop between identified leech neurones in culture have been studied by electron microscopy and by quantal analysis. Earlier work has shown that the transmitter liberated by isolated Retzius cells, serotonin, evokes chloride-dependent inhibitory post-synaptic potentials (i.p.s.p.s) in P sensory cells, and also in Retzius cells. When pairs of Retzius cells or Retzius and P sensory cells were placed in close apposition in culture for a few days, their somata extended numerous fine processes which came into contact and interdigitated. In the region of interdigitation, only narrow spaces, approximately 20-25 nm wide separated the membranes. The appearance of the cytoplasm of the two neurones was distinctive: in particular, Retzius cells contained agranular vesicles, as well as abundant dense core vesicles which were not as prevalent in P cells. Structures resembling synapses developed by 4 days, with characteristic vesicles clustered in terminals of the Retzius cell apposed to the post-synaptic membrane. In the presence of raised Mg or lowered Ca in the culture medium, the i.p.s.p. in the P cell evoked by an impulse in the Retzius cell became diminished in amplitude. The time-to-peak and half-time of decay were unchanged. Under these conditions, with repeated stimulation, quantal fluctuations of these post-synaptic potentials and failures were observed. In addition, there occurred spontaneous events which resembled miniature synaptic potentials and had amplitudes and time courses similar to those of the unitary events evoked by presynaptic impulses. The amplitudes of evoked synaptic potentials in raised Mg were distributed in accord with the Poisson equation. The agreement was good when either the spontaneous miniature potentials or the failures of evoked release were used to calculate m, the mean number of quanta per trial. With larger values of m the results were distributed as predicted by the binomial equation. These morphological and electrophysiological experiments together indicate that the inhibitory potentials observed in P cells result from quantal units of transmitter released by presynaptic terminals of the Retzius cell which are in close apposition to the post-synaptic membrane.

Action Potentials↗
PubMedDate not supplied

The robustness of the "binormal" assumptions used in fitting ROC curves.

The binormal form is the most common model used to formally fit ROC curves to the data from signal detection studies that employ the "rating" method. The author lists a number of justifications that have been offered for this choice, ranging from theoretical considerations of probability laws and signal detection theory, to mathematical tractability and convenience, to empirical results showing that "it fits!" To these justifications is added another, namely that even if an alternative formulation based on another underlying form (e.g., power law) or model (e.g., binomial, Poisson, or gamma type distributions) were in fact correct, the binormal fit differs so little from the true form as to be of no practical consequence. Moreover, the small lack of fit is unlikely to be demonstrated in practice: it is obscured by the much larger variation that can be attributed to sampling of cases. In addition, even if a very large sample of cases could be studied, the small number of rating categories used does not permit seemingly very different models to be distinguished from one another.

Mathematical Computing↗
PubMed2000

Sequential sampling plans for the hairy chinch bug (Hemiptera: Lygaeidae).

Two sequential sampling plans were developed to produce tools to reduce the use of pesticides for the control of the hairy chinch bug, Blissus leucopterus hirtus Montandon, on turfgrass lawns in the cool-humid region of Quebec, Canada. A first plan based on Wald's method was shown to be too conservative in a validation conducted on infested lawns. The second plan developed using Iwao's method yielded good results. The difference between the two plans may have occurred because no common k could be found for the negative binomial functions describing chinch bug distribution on lawns, thereby violating an essential assumption of Wald's approach. Application of the Iwao plan, which is based on visual sampling of 0.1-m2 quadrats, requires approximately 20 min when lawn evaluation is conducted by a single person. Estimation of the occurrence of chinch bug infestations (28% infested lawns in the regions of Montreal and Quebec cities), and results from validation of the Iwao plan on infested lawns, indicate that the error rates alpha and beta of the plan are lower than an upper limit of 0.05 and 0.14, respectively. The adequate precision and practicality of this plan suggest that it could become an essential tool for management of turfgrass lawns in regions where the hairy chinch bug completes less than two generations per growing season.

Animals↗
PubMed1979

[Quantum analysis of postsynaptic potentials].

Basic formulations of the quantum theory for synaptic transmission are listed. Methods for determining the mean quantum content, quantum value and binomial parameters describing the amplitude distributions of the unitary and "minimal" postsynaptic potentials are discussed. Literature and author's determinations of the quantum parameters for the synapses of the central nervous system are described. The comparison is made with similar determinations for more studied peripheral junctions. Some difficulties and perspective of the quantum theory are discussed.

Animals↗
PubMed1982

Analysis of proportions of affected foetuses in teratological experiments.

This paper is concerned with the analysis of proportions affected when an increasing dose of a compound is applied to a group of laboratory animals. Several sets of data, including a set from a teratological experiment at the Shell Toxicology Laboratory, Sittingbourne, are analysed and some simulations are performed. Among the distributional models, the beta-binomial model is, in general, found to be the most sensitive to departures from the binomial. For testing the equality of two proportions, a comparison is made between the pseudo-t test, based on the jackknife method, and the likelihood ratio test, based on the beta-binomial model. From the limited comparison, no definite advantage of one approach over the other has been found; at the 5% level of significance both approaches lead to similar conclusions.

Animals↗
PubMed1993

Technique for surveying larval populations of Coquillettidia perturbans.

A dipper with a 1-mm mesh screen bottom was used to sample larval populations of Coquillettidia perturbans from plant roots in Minnesota wetlands. This sampling technique was especially useful for large-scale larval surveys because the sampler was portable, individual sample collection and processing could be completed in < 10 min and data collected were appropriate for statistical analyses. Sampling indicated that larval populations were clumped, with a negative binomial model closely describing larval distributions.

Animals↗
PubMed1999

Modelling MRI enhancing lesion counts in multiple sclerosis using a negative binomial model: implications for clinical trials.

In multiple sclerosis (MS) the number of new enhancing lesions seen on monthly magnetic resonance imaging (MRI) scans is the most widely used response variable in MRI-monitored studies of experimental treatments. However, no statistical model has been proposed to describe the distribution of the number of such lesions across MS patients. This article briefly summarizes the statistical models for counted data. The negative binomial (NB) model is proposed to fit the number of new enhancing lesions counted in a set of 56 untreated MS patients followed for 9 months. It is shown that the large variability present in this data set is better addressed by the NB model (residual deviance=66.6, 54 degrees of freedom) than by the Poisson model (residual deviance=1830.1, 55 degrees of freedom). Applications of the parametrization of lesion counts are discussed, and an example related to computer simulations for the sample size estimation is presented.

Adolescent↗
PubMed1992

Simple SAS macros for the calculation of exact binomial and Poisson confidence limits.

Statistical analysis using confidence intervals is now a preferred approach in the medical literature, and confidence limits for binomial proportions and Poisson counts are commonly required. Normal approximations of varying accuracy are often used in such situations and it is not generally realised that non-iterative exact solutions are available. This paper shows that the exact binomial and Poisson confidence limits can be expressed very simply in terms of the inverse beta and inverse gamma distributions, and describes two macros in the SAS programming language to perform the computations. The exact solutions are compared with some approximations and further applications of the techniques are described.

Binomial Distribution↗
PubMed2002

Unconditional small-sample confidence intervals for the odds ratio.

The traditional approach to 'exact' small-sample interval estimation of the odds ratio for binomial, Poisson, or multinomial samples uses the conditional distribution to eliminate nuisance parameters. This approach can be very conservative. For two independent binomial samples, we study an unconditional approach with overall confidence level guaranteed to equal at least the nominal level. With small samples this interval tends to be shorter and have coverage probabilities nearer the nominal level.

Journal Article↗
PubMed1995

Frequency distribution of Wuchereria bancrofti infection in the vector host in relation to human host: evidence for density dependence.

This paper uses detailed entomological data from Pondicherry to compare the microfilaria distribution in vector with that of human and also to examine the evidence for the operation of density dependence on parasite transmission. Analysis showed that the distribution in vector is similar to that in human. The expected distribution derived from the fit of a zero-truncated negative binomial to the human data, closely reflected the observed microfilaria distribution in the vector. This implies that a relatively large proportion of observed microfilaria negatives in the vector population may be true zeros, as observed in human, arising from the biting on true negatives (as yet uninfected, with unmated female worms or immune) in humans, rather than attributable to the blood sampling process. Further it was found that both the prevalence of infection and the degree of parasite aggregation in the vector population falls significantly with parasite stage, implying the operation of density dependence, perhaps via parasite-induced vector mortality.

Animals↗
PubMed1996

A study on the distribution of Bothriocephalus andresi (Cestoda, Pseudophyllidea) in Citharus linguatula.

The distribution of Bothriocephalus andresi (Porta, 1911) in a population of Citharus linguatula (L.) caught off the Tuscan coasts was studied for one year. The negative binomial model proved useful for analysing the distribution of the parasite (B. andresi) in the host population. The ability of the parasite to adjust not only to its own environment but also to that of its host was clear, as it may be evinced from the greater amount of eggs and, hence, of larvae noticed in the period when there was abundance of plankton (high number of intermediate hosts). The balance achieved between host and parasite populations was also evident, and the modulation of the intensity of the infestation was such that it may be imputed to a greater immune response in the host.

Animals↗