Patient-initiated transtelephone transmission of electrocardiographic signals in the diagnosis of arrhythmias.

Thirty-one patients who had complained of recurrent palpitations were given transtelephone transmitters of electrocardiographic signals and instructed to use the transmitters while they were having symptoms. From the transcribed electrocardiograms sinus tachycardia was documented in 12 patients, paroxysmal atrial tachycardia in 7, atrial fibrillation in 4, atrial flutter in 3, frequent ventricular premature beats in 4 and ventricular tachycardia in 1. Patient-initiated transtelephone transmission of electrocardiographic signals was found to be an effective means of documenting the nature of symptomatic paroxysmal tachycardia.     

Permanence of the cell-to-cell transmission of insulin induced hormonal imprinting

When insulin-treated (imprinted) Chang liver cell cultures were mixed with cultures which did not receive insulin treatment the information of imprinting was transmitted to the cultures which were not in direct contact with insulin. The ability of the cells to transmit imprinting was long lasting and could be detected even after four weeks, when it was nearly of the same degree as at the first measurement. Difference was found between the binding capacity of the receptors of the plasma membrane and those of the nuclear membrane.     

Peptidergic transmission in the brain. III. Hippocampal inhibition by the amygdala.

The mechanism of arginine vasopressin (AVP) action in the rat hippocampus has been determined. The peptide activates inhibitory interneurons and constricts cerebral microvessels. In the whole animal, each of these direct actions has secondary consequences for the excitability of pyramidal cells. Recent studies have shown that a peptide similar to AVP mediates endogenous neurotransmission in the hippocampus. Here we report experiments showing that the endogenous peptide activates the same mechanisms as exogenously applied AVP. The endogenous AVP-like peptide has no effect on the presynaptic fiber volley, or on pure somatic and dendritic postsynaptic potentials. These results are taken to exclude presynaptic mechanisms as explanations for the peptide's action. The endogenously released peptide inhibits individual pyramidal cells in single unit recording and excites presumed interneurons, just as AVP itself is known to act. The endogenous peptide is released only by stimuli applied to a nucleus that contains immunoreactive AVP and projects to the hippocampus.     

Basic models for differential inhibition of enzymes

The possible preferential action exerted by an inhibitor on the transformation of one of two agonist substrates catalyzed by the same enzyme has recently been reported in studies on aldose reductase inhibition. This event was defined as “intra-site differential inhibition” and the molecules able to exert this action as “differential inhibitors”. This work presents some basic kinetic models describing differential inhibition. Using a simple analytic approach, the results show that differential inhibition can occur through either competitive or mixed type inhibition in which the inhibitor prevalently targets the free enzyme. The results may help in selecting molecules whose differential inhibitory action could be advantageous in controlling the activity of enzymes acting on more than one substrate.     

Specificity of the cell-to-cell transmission of hormonal imprinting in cell cultures

Chang liver cells and Chinese hamster ovary (CHO) cells were imprinted either with insulin or with thyrotropin (TSH). Chang liver cells responded to insulin but not to TSH. As an effect of imprinting evoked by insulin administration the binding of insulin administered for the second time was enhanced. In the mixed culture of imprinted and intact cells the extent of the binding was similar to that seen in the cultures of the cells having received imprintatory treatment alone. CHO cells also responded to TSH, imprinting developed and was transmitted to the cells which were not in interaction with the hormone (intact cells). In CHO cells also insulin gave rise to imprinting for insulin, whereas TSH gave rise to moderate binding imprinting for insulin. On the other hand, insulin imprinting did not enhance the binding of TSH. The obtained results indicate that both the imprinting itself and the specificity of the transmission of imprinting depend on the characteristics of the cell-type in question. The extent of the transmission, however, is always proportional to the extent of imprinting.     

Transit of hormonal and EGF receptor-dependent signals through cholesterol-rich membranes

The functional consequences of changes in membrane lipid composition that coincide with malignant growth are poorly understood. Sufficient data have been acquired from studies of lipid binding proteins, post-translational modifications of signaling proteins, and biochemical inhibition of lipidogenic pathways to indicate that growth and survival pathways might be substantially re-directed by alterations in the lipid content of membranes. Cholesterol and glycosphingolipids segregate into membrane patches that exhibit a liquid-ordered state in comparison to membrane domains containing relatively lower amounts of these classes of lipids. These "lipid raft" structures, which may vary in size and stability in different cell types, both accumulate and exclude signaling proteins and have been implicated in signal transduction through a number of cancer-relevant pathways. In prostate cancer cells, signaling from epidermal growth factor receptor (EGFR) to the serine-threonine kinase Akt1, as well as from IL-6 to STAT3, have been demonstrated to be influenced by experimental interventions that target cholesterol homeostasis. The recent finding that classical steroid hormone receptors also reside in these microdomains, and thus may function within these structures in a signaling capacity independent of their role as nuclear factors, suggests a novel means of cross-talk between receptor tyrosine kinase-derived and steroidogenic signals. Potential points of intersection between components of the EGFR family of receptor tyrosine kinases and androgen receptor signaling pathways, which may be sensitive to disruptions in cholesterol metabolism, are discussed. Understanding the manner in which these pathways converge within cholesterol-rich membranes may present new avenues for therapeutic intervention in hormone-dependent cancers.     

Statistical models of synaptic transmission evaluated using the expectation-maximization algorithm.

Amplitude fluctuations of evoked synaptic responses can be used to extract information on the probabilities of release at the active sites, and on the amplitudes of the synaptic responses generated by transmission at each active site. The parameters that describe this process must be obtained from an incomplete data set represented by the probability density of the evoked synaptic response. In this paper, the equations required to calculate these parameters using the Expectation-Maximization algorithm and the maximum likelihood criterion have been derived for a variety of statistical models of synaptic transmission. These models are ones where the probabilities associated with the different discrete amplitudes in the evoked responses are a) unconstrained, b) binomial, and c) compound binomial. The discrete amplitudes may be separated by equal (quantal) or unequal amounts, with or without quantal variance. Alternative models have been considered where the variance associated with the discrete amplitudes is sufficiently large such that no quantal amplitudes can be detected. These models involve the sum of a normal distribution (to represent failures) and a unimodal distribution (to represent the evoked responses). The implementation of the algorithm is described in each case, and its accuracy and convergence have been demonstrated.     

Optimizing agent-based transmission models for infectious diseases

Background

Infectious disease modeling and computational power have evolved such that large-scale agent-based models (ABMs) have become feasible. However, the increasing hardware complexity requires adapted software designs to achieve the full potential of current high-performance workstations.

Results

We have found large performance differences with a discrete-time ABM for close-contact disease transmission due to data locality. Sorting the population according to the social contact clusters reduced simulation time by a factor of two. Data locality and model performance can also be improved by storing person attributes separately instead of using person objects. Next, decreasing the number of operations by sorting people by health status before processing disease transmission has also a large impact on model performance. Depending of the clinical attack rate, target population and computer hardware, the introduction of the sort phase decreased the run time from 26 % up to more than 70 %. We have investigated the application of parallel programming techniques and found that the speedup is significant but it drops quickly with the number of cores. We observed that the effect of scheduling and workload chunk size is model specific and can make a large difference.

Conclusions

Investment in performance optimization of ABM simulator code can lead to significant run time reductions. The key steps are straightforward: the data structure for the population and sorting people on health status before effecting disease propagation. We believe these conclusions to be valid for a wide range of infectious disease ABMs. We recommend that future studies evaluate the impact of data management, algorithmic procedures and parallelization on model performance.

Electronic supplementary material

The online version of this article (doi:10.1186/s12859-015-0612-2) contains supplementary material, which is available to authorized users.     

Proportionate mixing models for age-dependent infection transmission

We present explicit formulas for the transmission potential of an immunizing infection where the contact rates and the vaccination rates depend on the chronological age of an individual, and the infectivity and the recovery rate depend on the duration of an infection.     

Long-distance of transmission of facial affect signals

This study examined the distance at which certain facial expression can transmit affect messages. A man and a woman assumed—facial expressions that were selected carefully to represent six affects. These expressions were shown in still photographs and in live portrayals to 49 observers who composed four groups which were 30, 35, 40, and 45 meters away from the stimuli. Photographs and live portrayals produced comparable results. Every observer was able to label the expressions accurately although accuracy declined as distance increased. Extrapolation from the data suggested that some messages may be sent far beyond the distances used in this study. These results raise important issues about the transmission of facial signals over distance and suggest that the face is a long-distance transmitter of affect signals.     

Temporal patterns in the acoustic signals of beaked whales at Cross Seamount

Seamounts may influence the distribution of marine mammals through a combination of increased ocean mixing, enhanced local productivity and greater prey availability. To study the effects of seamounts on the presence and acoustic behaviour of cetaceans, we deployed a high-frequency acoustic recording package on the summit of Cross Seamount during April through October 2005. The most frequently detected cetacean vocalizations were echolocation sounds similar to those produced by ziphiid and mesoplodont beaked whales together with buzz-type signals consistent with prey-capture attempts. Beaked whale signals occurred almost entirely at night throughout the six-month deployment. Measurements of prey presence with a Simrad EK-60 fisheries acoustics echo sounder indicate that Cross Seamount may enhance local productivity in near-surface waters. Concentrations of micronekton were aggregated over the seamount in near-surface waters at night, and dense concentrations of nekton were detected across the surface of the summit. Our results suggest that seamounts may provide enhanced foraging opportunities for beaked whales during the night through a combination of increased productivity, vertical migrations by micronekton and local retention of prey. Furthermore, the summit of the seamount may act as a barrier against which whales concentrate prey.     

Biokinetic models for representing the complete inhibition of microbial activity at high substrate concentrations.

This paper reintroduces the Wayman and Tseng model for representing substrate inhibition effects on specific growth rate by further documenting its potential predictive capabilities. It also introduces a modification to this model in which an Andrews inhibition function is used in place of the Monod noninhibitory substrate function. This modification better represents the relationship between specific growth rate and substrate concentration for those substrates that show Andrews type inhibition at lower substrate concentrations, rather than the Monod type noninhibitory behavior described in the model of Wayman and Tseng. Results from nonlinear, least squares regression analysis are used to evaluate the ability of these models to empirically represent experimental data (both new and from the literature). The statistical goodness of fit is evaluated by comparing the regression results against those obtained using other empirical models. Finally, possible mechanisms of toxicity responsible for the observed inhibition trends are used to further justify use of these empirical models. The dominant mechanism considered to be relevant for conceptually explaining complete inhibition at high concentrations of solvents is the deterioration of cell membrane integrity. Literature citations are used to support this argument. This work should lead to improvements in the mathematical modeling of contaminant fate and transport in the environment and in the simulation of microbial growth and organic compound biodegradation in engineered systems.     

Phorbol ester inhibition of hormonal induction of tyrosine aminotransferase

The liver specific enzyme, tyrosine aminotransferase, can be induced by glucocorticoids, cAMP analogs, or insulin. Each of these different inducing agents is believed to act through a separate pathway. The tumor promoting phorbol esters have been reported to stimulate phosphorylation of the insulin receptor and thereby decrease the ability of insulin to induce tyrosine aminotransferase. Our results demonstrate that TPA will not only inhibit the insulin stimulated increase in tyrosine aminotransferase, but will also inhibit induction of the enzyme by glucocorticoids or by cAMP.     

Contribution to the probabilistic theory of neural nets: IV. Various models for inhibition

Input-output formulas are derived for a neuron upon which converge single axones of two other neurons, which are subjected to a Poisson shower, where a number of different assumptions are made concerning the mechanism of inhibition. In one assumption so-called “bilateral pre-inhibition” is considered. That is to say, both neuronsN ₁ andN ₂ may exciteN ₃, but if the stimulus of one of them follows within a certain interval σ of the other, the second stimulus is not effective. This model is essentially no different from that involving two excitatory neurons acting upon a neuron having a refractory period. Another mechanism considered involves so-called “pre-and-post” inhibition, in which if two stimuli fromN ₁ andN ₂ fall within σ,both are ineffective. This case being mathematically much more involved than the preceding, an approximation method is used for deriving the input-output formula. Previous papers of this series are denoted by I, II, and III in this paper.     

Discriminating among complex signals: the roles of inhibition for creating response selectivities

The review deals largely with studies from my laboratory that were prompted by conversations I had with Gerhard Neuweiler more than 15 years ago. The studies were conducted on bats and dealt with mechanisms that enable the population of neurons in the inferior colliculus (IC) to respond selectively to the variety of signals bats emit for both communication and echolocation. The first section is concerned with how neurons in the dorsal nucleus of the lateral lemniscus (DNLL), the nucleus ventral to the IC, respond to species-specific signals and how they compare to responses of IC neurons evoked by the same signals. Those studies showed that DNLL neurons have no sideband inhibition and their responses are determined by excitation. In contrast, inhibition dominates in the IC where it carves out highly selective discharge properties. Those studies, in turn, raised questions about the quantitative features of inhibition that could only be answered with more sophisticated techniques. In the second section, results from analyses with spectrotemporal receptive fields (STRFs) are presented, and in the final section I show data derived from in vivo whole cell recordings that illustrate how features of inhibition interact with excitation to generate directionality selective responses in the IC.