Probability learning strategies of the retarded.
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Adolescent↗
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The application of network analysis to the study of branching patterns of large dendritic fields.
Network analysis of dendritic fields not only defines the topology and connectivity of segments of an arborescence, but offers a means of discovering how networks grow. An important theory has recently been formulated29 suggesting that dendritic branching patterns may be established by synaptogenic interaction of dendritic growth cones with growing axons. This thesis may be verified through network analysis since the theory predicts that growth at pendant vertices will predominate in dendritic networks, that dendritic growth will be directed into areas of maximal synaptogenic activity and that arc lengths will be inversely related, and the order of branching at vertices directly related, to the magnitude of the synaptogenic activity operating about growing dendritic terminals. The possibility of a preponderance of terminal growth may be detected by comparing the topologies in an observed dendritic network with those of a series of hypothetical growth models. This paper provides the frequency table for models grown by monochotomous, dichotomous and trichotomous branching on random pendant vertices and random arcs for large networks in which 'set theory' contingencies are included. The paper also describes a method of calculating branching probabilities from the measurement of segment lengths, which is a means of testing the last mentioned prediction of the synaptogenic theory of denddritic growth. The method of network analysis is then discussed in relation to probable dendritic growth patterns, the constancy of segment lengths and the interaction of extrinsic and intrinsic factors in determining branching probabilities.
Dendrites↗
Artificial intelligence and Bayesian decision theory in the prediction of chemical carcinogens.
Two procedures for predicting the carcinogenicity of chemicals are described. One of these (CASE) is a self-learning artificial intelligence system that automatically recognizes activating and/or deactivating structural subunits of candidate chemicals and uses this to determine the probability that the test chemical is or is not a carcinogen. If the chemical is predicted to be carcinogen, CASE also projects its probable potency. The second procedure (CPBS) uses Bayesian decision theory to predict the potential carcinogenicity of chemicals based upon the results of batteries of short-term assays. CPBS is useful even if the test results are mixed (i.e. both positive and negative responses are obtained in different genotoxic assays). CPBS can also be used to identify highly predictive as well as cost-effective batteries of assays. For illustrative purposes the ability of CASE and CPBS to predict the carcinogenicity of a carcinogenic and a non-carcinogenic polycyclic aromatic hydrocarbon is shown. The potential for using the two methods in tandem to increase reliability and decrease cost is presented.
Animals↗
Phonological priming in auditory word recognition.
Cohort theory, developed by Marslen-Wilson and Welsh (1978), proposes that a "cohort" of all the words beginning with a particular sound sequence will be activated during the initial stage of the word recognition process. We used a priming technique to test specific predictions regarding cohort activation in three experiments. In each experiment, subjects identified target words embedded in noise at different signal-to-noise ratios. The target words were either presented in isolation or preceded by a prime item that shared phonological information with the target. In Experiment 1, primes and targets were English words that shared zero, one, two, three, or all phonemes from the beginning of the word. In Experiment 2, nonword primes preceded word targets and shared initial phonemes. In Experiment 3, word primes and word targets shared phonemes from the end of a word. Evidence of reliable phonological priming was observed in all three experiments. The results of the first two experiments support the assumption of activation of lexical candidates based on word-initial information, as proposed in cohort theory. However, the results of the third experiment, which showed increased probability of correctly identifying targets that shared phonemes from the end of words, did not support the predictions derived from the theory. The findings are discussed in terms of current models of auditory word recognition and recent approaches to spoken-language understanding.
Cues↗
Defining treatment margins for six field conformal irradiation of localized prostate cancer.
PURPOSE: To define the "ideal margins" to be used for the delivery of six-field conformal radiotherapy for localized prostate cancer. METHODS AND MATERIALS: For a typical patient, 3-D based 6-field conformal treatment plans were generated using uniform margins ranging from 0.5-2.5 cm (in 0.25 cm increments). In a step-wise fashion the minimum margins required to encompass the gross tumor volume within the 90% isodose shell were identified. Additional margins were then added to account for extracapsular penetration, setup and patients movement error as well as for organ movement. Assumptions about the relative tolerance of surrounding normal tissues were also incorporated into the final decisions regarding margins. RESULTS: For the various areas of interface, between the prostate and surrounding normal tissues "ideal margins" varied from 0.75-2.25 cm. CONCLUSION: The use of nonuniform "ideal margins" appears to insure adequate coverage of the tumor, while minimizing the volume of surrounding dose limiting normal tissues irradiated. This approach should in theory improve the tumor control and complication probabilities compared to using conventional treatment techniques and to using a 6-field conformal technique with uniform margins.
Humans↗
Event-related potential evidence for multiple causes of the revelation effect.
Asking people to discover the identity of a recognition test probe immediately before making a recognition judgment increases the probability of an old judgment. To inform theories of this "revelation effect," event-related potentials (ERPs) were recorded for revealed and intact test items across two experiments. In Experiment 1, we used a revelation effect paradigm where half of the test probes were presented as anagrams (i.e., a related task) and the other items were presented intact. The pattern of ERP results from this experiment suggested that revealing an item decreases initial familiarity levels and caused the revealed items to elicit similar levels of activity. In Experiment 2, half of the probes were preceded by an addition task (i.e., an unrelated task). The pattern of ERP effects in this study were distinct from those observed in Experiment 1. More specifically, revealed item ERPs were more negative than intact ERPs at frontal electrodes and more positive at parietal electrodes early in the interval. Later in the epoch, revealed item ERPs were more negative than intact items. These data suggest that related tasks decrease familiarity and alter the signal-to-noise ratio of old and new items, whereas unrelated tasks affect processing in a different way (perhaps by changing decision processes) that also results in the revelation effect. The implications for current theories of the revelation effect are discussed.
Adolescent↗
Smoothing and cluster thresholding for cortical surface-based group analysis of fMRI data.
Cortical surface-based analysis of fMRI data has proven to be a useful method with several advantages over 3-dimensional volumetric analyses. Many of the statistical methods used in 3D analyses can be adapted for use with surface-based analyses. Operating within the framework of the FreeSurfer software package, we have implemented a surface-based version of the cluster size exclusion method used for multiple comparisons correction. Furthermore, we have a developed a new method for generating regions of interest on the cortical surface using a sliding threshold of cluster exclusion followed by cluster growth. Cluster size limits for multiple probability thresholds were estimated using random field theory and validated with Monte Carlo simulation. A prerequisite of RFT or cluster size simulation is an estimate of the smoothness of the data. In order to estimate the intrinsic smoothness of group analysis statistics, independent of true activations, we conducted a group analysis of simulated noise data sets. Because smoothing on a cortical surface mesh is typically implemented using an iterative method, rather than directly applying a Gaussian blurring kernel, it is also necessary to determine the width of the equivalent Gaussian blurring kernel as a function of smoothing steps. Iterative smoothing has previously been modeled as continuous heat diffusion, providing a theoretical basis for predicting the equivalent kernel width, but the predictions of the model were not empirically tested. We generated an empirical heat diffusion kernel width function by performing surface-based smoothing simulations and found a large disparity between the expected and actual kernel widths.
Cerebral Cortex↗
Feature detection and letter identification.
Seeking to understand how people recognize objects, we have examined how they identify letters. We expected this 26-way classification of familiar forms to challenge the popular notion of independent feature detection ("probability summation"), but find instead that this theory parsimoniously accounts for our results. We measured the contrast required for identification of a letter briefly presented in visual noise. We tested a wide range of alphabets and scripts (English, Arabic, Armenian, Chinese, Devanagari, Hebrew, and several artificial ones), three- and five-letter words, and various type styles, sizes, contrasts, durations, and eccentricities, with observers ranging widely in age (3 to 68) and experience (none to fluent). Foreign alphabets are learned quickly. In just three thousand trials, new observers attain the same proficiency in letter identification as fluent readers. Surprisingly, despite this training, the observers-like clinical letter-by-letter readers-have the same meager memory span for random strings of these characters as observers seeing them for the first time. We compare performance across tasks and stimuli that vary in difficulty by pitting the human against the ideal observer, and expressing the results as efficiency. We find that efficiency for letter identification is independent of duration, overall contrast, and eccentricity, and only weakly dependent on size, suggesting that letters are identified by a similar computation across this wide range of viewing conditions. Efficiency is also independent of age and years of reading. However, efficiency does vary across alphabets and type styles, with more complex forms yielding lower efficiencies, as one might expect from Gestalt theories of perception. In fact, we find that efficiency is inversely proportional to perimetric complexity (perimeter squared over "ink" area) and nearly independent of everything else. This, and the surprisingly fixed ratio of detection and identification thresholds, indicate that identifying a letter is mediated by detection of about 7 visual features.
Adolescent↗
Indefinite self-association of a solute in linear and branched arrays.
Theory is formulated using reacted-site probability functions to relate the concentration of monomer to that of total solute for a multivalent monomer which undergoes indefinite self-association to form an equilibrium array of linear chains and branched networks governed by a single site-binding constant. In turn, this intrinsic constant is related to the stoichiometric equilibrium constants describing successive additions of monomer; and the characterization of the composition of the mixture at different total concentrations is discussed together with the onset of gelation, which occurs when each polymer (excluding the infinite network) attains a maximum concentration. Analogous expressions defining solution composition are presented for indefinitely self-associating systems involving non-identical sites when interactions occur in a head-to-tail fashion between dissimilar sites. Finally, a bivalent monomer is considered with head-to-head and tail-to-tail interactions forming an indefinite array of polymers with alternating bond types. It is shown that the latter description is quantitatively consistent with results obtained previously on the indefinitely self-associating zinc-free insulin system. The postulated self-association pattern involving two site-binding constants of magnitudes 5.75 X 10(4) M-1 and 0.85 X 10(4) M-1 is preferred to earlier suggested models on the basis of information available from X-ray crystallographic studies on insulin.
Animals↗
From local interactions to population dynamics in site-based models of ecology.
A central problem in ecology is relating the interactions of individuals-described in terms of competition, predation, interference, etc.-to the dynamics of the populations of these individuals-in terms of change in numbers of individuals over time. Here, we address this problem for a class of site-based ecological models, where local interactions between individuals take place at a finite number of discrete resource sites over non-overlapping generations and, between generations, individuals move randomly between sites over the entire system. Such site-based models have previously been applied to a wide range of ecological systems: from those involving contest or scramble competition for resources to host-parasite interactions and meta-populations. We show how the population dynamics of site-based models can be accurately approximated by and understood through deterministic and stochastic difference equations. Conversely, we use the inverse of this approximation to show what implicit assumptions are made about individual interactions by modelling of population dynamics in terms of difference equations. To this end, we prove a useful and general theorem: that any model in our class of site-based models has a corresponding stochastic difference equation population model, by which it can be approximated. This theorem allows us to calculate long-term population dynamics, evolutionary stable strategies and, by extending our theory to account for large deviations, extinction probabilities for a wide range of site-based systems. Our methodology is then illustrated to various examples of between species competition, predator-prey interactions and co-operation.
Competitive Behavior↗
Bayesian integration in sensorimotor learning.
When we learn a new motor skill, such as playing an approaching tennis ball, both our sensors and the task possess variability. Our sensors provide imperfect information about the ball's velocity, so we can only estimate it. Combining information from multiple modalities can reduce the error in this estimate. On a longer time scale, not all velocities are a priori equally probable, and over the course of a match there will be a probability distribution of velocities. According to bayesian theory, an optimal estimate results from combining information about the distribution of velocities-the prior-with evidence from sensory feedback. As uncertainty increases, when playing in fog or at dusk, the system should increasingly rely on prior knowledge. To use a bayesian strategy, the brain would need to represent the prior distribution and the level of uncertainty in the sensory feedback. Here we control the statistical variations of a new sensorimotor task and manipulate the uncertainty of the sensory feedback. We show that subjects internally represent both the statistical distribution of the task and their sensory uncertainty, combining them in a manner consistent with a performance-optimizing bayesian process. The central nervous system therefore employs probabilistic models during sensorimotor learning.
Bayes Theorem↗
Permian tetrapods from the Sahara show climate-controlled endemism in Pangaea.
New fossils from the Upper Permian Moradi Formation of northern Niger provide an insight into the faunas that inhabited low-latitude, xeric environments near the end of the Palaeozoic era (approximately 251 million years ago). We describe here two new temnospondyl amphibians, the cochleosaurid Nigerpeton ricqlesi gen. et sp. nov. and the stem edopoid Saharastega moradiensis gen. et sp. nov., as relicts of Carboniferous lineages that diverged 40-90 million years earlier. Coupled with a scarcity of therapsids, the new finds suggest that faunas from the poorly sampled xeric belt that straddled the Equator during the Permian period differed markedly from well-sampled faunas that dominated tropical-to-temperate zones to the north and south. Our results show that long-standing theories of Late Permian faunal homogeneity are probably oversimplified as the result of uneven latitudinal sampling.
Amphibians↗
First principles resonance widths for Li near an Al(001) surface: predictions of scattered ion neutralization probabilities.
By combining a first-principles periodic density functional theory calculation of adsorbate resonance widths with a many-body dynamical theory of charge transfer, we assess charge-transfer rates for ions scattering off metal surfaces. This goes beyond previous approaches, which have been limited to modeling the surfaces with either static potentials or finite clusters. Here we consider Li(+) scattering from an Al(001) surface. We show how the Li 2s orbital hybridizes with metal valence bands, near the surface, increasing the width of the 2s energy level. This in turn affects the charge-transfer rates between the ion and the metal surface. Our predictions for Li(+)-Al(001) scattering yield the correct angular dependence of the fraction of neutral Li atoms formed when compared to experiment.
Aluminum↗
Occurrence of cell division is not exponentially distributed: differences in the generation times of sister cells can be derived from the theory of survival of populations.
The Eyring-Stover survival theory has been applied to the kinetics of the distribution of intermitotic intervals of mammalian cells and by inference to the transition from the G1 phase into DNA synthesis (S phase). The theory faithfully fits experimental data acquired by time-lapse cinemicrography of cloned HeLa cells in tissue culture and also suggests the existence of a labile initiator substance which mediates the G1-S phase transition. This theory provides an alternative to the transition probability model proposed by Smith and Martin [Smith J. A. & Martin, L. (1973) Proc. Natl. Acad. Sci. USA 70, 1263-1267; see also Shields, R. & Smith, J. A. (1977) J. Cell Physiol. 91, 345-355 and Brooks, R. F., Bennett, D. C. & Smith, J. A. (1980) Cell 19, 493-504].
Cell Division↗
Phenomenological theory of mortality evolution: its singularities, universality, and superuniversality.
The probability to survive to the age x universally increases with the mean lifespan x(bar). For species as remote as humans and flies, for a given x the rate of its evolution with x is constant, except for the narrow vicinity of a certain x(bar) = x* (which equals 75 years for humans and 32 days for flies and which is independent of age, population, and living conditions). At x(bar) approximately x* the evolution rate jumps to a different value. Its next jump is predicted at x(bar) approximately 87 years for humans and approximately 59 days for flies. Such singularities are well known in physics and mathematics as phase transitions. In the considered case different population "phases" have significantly different survival evolution rates. The evolution is rapid-life expectancy may double within a lifespan of a single generation. Survival probability depends on age x and mean longevity x(bar) only (for instance, survival curves of 1896 Swedes and 1947 Japanese with approximately equal x(bar) are very close, although they are related to different races in different countries at different periods in their different history.) With no adjustable parameters, its presented universal law quantitatively agrees with all lifetable data. According to this law, the impact of all factors but age reduces to the mean lifespan only. In advanced and old age, this law is superuniversal--it is approximately the same for species as remote as humans and flies. It yields survival probability that linearly depends on the mean lifespan x(bar). As a result, when human x(bar) almost doubles (from 35.5 to 69.3 years), life expectancy at 70 years increases from 8 to 9.5 years only. Other implications of the universal law are also considered.
Biological Evolution↗
MEDock: a web server for efficient prediction of ligand binding sites based on a novel optimization algorithm.
The prediction of ligand binding sites is an essential part of the drug discovery process. Knowing the location of binding sites greatly facilitates the search for hits, the lead optimization process, the design of site-directed mutagenesis experiments and the hunt for structural features that influence the selectivity of binding in order to minimize the drug's adverse effects. However, docking is still the rate-limiting step for such predictions; consequently, much more efficient algorithms are required. In this article, the design of the MEDock web server is described. The goal of this sever is to provide an efficient utility for predicting ligand binding sites. The MEDock web server incorporates a global search strategy that exploits the maximum entropy property of the Gaussian probability distribution in the context of information theory. As a result of the global search strategy, the optimization algorithm incorporated in MEDock is significantly superior when dealing with very rugged energy landscapes, which usually have insurmountable barriers. This article describes four different benchmark cases that span a diverse set of different types of ligand binding interactions. These benchmarks were compared with the use of the Lamarckian genetic algorithm (LGA), which is the major workhorse of the well-known AutoDock program. These results demonstrate that MEDock consistently converged to the correct binding modes with significantly smaller numbers of energy evaluations than the LGA required. When judged by a threshold of the number of energy evaluations consumed in the docking simulation, MEDock also greatly elevates the rate of accurate predictions for all benchmark cases. MEDock is available at http://medock.csie.ntu.edu.tw/ and http://bioinfo.mc.ntu.edu.tw/medock/.
Algorithms↗
The effect of adrenergic blockade on potassium concentrations in different conditions.
A moderate increase in serum potassium concentrations has been observed in several controlled clinical trials with beta-blockers. This increase cannot be explained by the retention of potassium in the organism, and is probably caused by the redistribution of potassium from intracellular to extracellular compartments. beta-adrenergic mechanisms seem to be concerned in the extrarenal handling of the potassium-load in man, presumably by inducing an increased uptake of potassium in muscular cells and liver cells. These beta-adrenergic mechanisms are probably of the beta 2-type. In theory there are several conditions in which it is important to have a defence against hyperkalaemia from exogenous or endogenous sources for example, during heavy physical exercise, after a potassium-rich meal, or after traumatic tissue damage. Available data indicate that non-selective beta-blockade increases serum potassium concentrations during and after heavy exercise and during coronary bypass. The clinical implications of these findings are unknown.
Adrenergic beta-Antagonists↗
Error patterns on the continuous performance test in non-medicated and medicated samples of children with and without ADHD: a meta-analytic review.
We systematically reviewed the patterns of Continuous Performance Test (CPT) errors of omission and commission exhibited by normal children and children with Attention Deficit and Hyperactivity Disorder (ADHD) under no drug, placebo and methylphenidate drug conditions. Findings from 26 studies were submitted to a meta-analytic procedure. In contrast to the contradictory findings of individual reports, our results revealed that children with ADHD made significantly more errors of omission and commission than normal children. As well, in children with ADHD and treated with methylphenidate, statistically significant reductions in the rate of both error types were noted. The effects of methylphenidate on the percentage of hits (i.e. 1 - omissions) were greater in experiments using shorter stimulus duration, smaller number of trials and higher probability of a target. Using Signal Detection Theory (SDT) parameters, we found that children with ADHD were less sensitive to the difference between targets and non-targets than their normal counterparts, while showing a comparable response bias. Similarly, the effects of methylphenidate were restricted to improving the sensitivity, while not affecting response bias, in both normal children and those with ADHD.
Attention↗