The efficiency of adapting aspiration levels

Win–stay, lose–shift strategies in repeated games are based on an aspiration level. A move is repeated if and only if the outcome, in the previous round, was satisficing in the sense that the pay-off was at least as high as the aspiration level. We investigate the conditions under which adaptive mechanisms acting on the aspiration level (selection, for instance, or learning) can lead to an efficient outcome; in other words, when can satisficing become optimizing? Analytical results for 2 times 2-games are presented. They suggest that in a large variety of social interactions, self-centred rules (based uniquely on one''s own pay-off) cannot suffice.     

Frequency responses of cat rapidly adapting mechanoreceptive fibers

The frequency responses of 11 rapidly adapting (RA) fibers in cat were studied by representing the average firing rate as a function of sinusoidal stimulus amplitude and stimulus frequency. Specifically, rate-intensity functions at different stimulation frequencies were fitted by four-parameter (a0, a1, a2, a3), piece-wise linear functions using nonlinear regression (n = 59; R2 > 0.877). Rate-intensity functions at intermediate frequencies were found by linear interpolation. The result of this analysis is rate-amplitude-frequency functions plotted as two-dimensional surfaces. The surfaces consist of five regions separated and sufficiently defined by four space curves. At 14 different frequencies, the statistical distribution of each rate-intensity-function parameter could be approximated by a particular lognormal distribution (n = 56; R2 > 0.796). The Kolmogorov-Smirnov test fails to reject this hypothesis for each combination of frequency and parameter (56 tests; p > 0.39). Therefore, at a given frequency, the variation of the parameters can be represented by lognormal distributions with specific means and standard deviations. Responses of six RA fibers, which are different from the data-set used for modeling, were compared with the stochastic model at different frequencies. The parameters of those fibers were tested against the null hypotheses that they were sampled from the particular parameter distributions dictated by the model. The Kolmogorov-Smirnov test fails to reject all the hypotheses at the alpha = 0.05 level (44 tests). At the alpha = 0.10 level, only a few test parameters were found to be departing from the model (a0 and a1 at 5 Hz; a2 at 20 Hz; a2 and a3 at 50 Hz). The remaining test parameters could be accurately described by the model. Having confirmed the validity of the model, the logarithmic means and the logarithmic standard deviations of the lognormally distributed rate-intensity-function parameters were estimated in the frequency range of 4-200 Hz. The rate-amplitude-frequency surfaces sampled from the established stochastic model completely characterize the rate responses of RA fibers to sinusoidal stimuli and are superior to tuning curves which require selecting criterion responses. The current rate-response model is promising for future computational work, especially on population modeling.     

Frequency responses of cat rapidly adapting mechanoreceptive fibers

The frequency responses of 11 rapidly adapting (RA) fibers in cat were studied by representing the average firing rate as a function of sinusoidal stimulus amplitude and stimulus frequency. Specifically, rate-intensity functions at different stimulation frequencies were fitted by four-parameter (a₀, a₁, a₂, a₃), piece-wise linear functions using nonlinear regression (n = 59; R² > 0.877). Rate-intensity functions at intermediate frequencies were found by linear interpolation. The result of this analysis is rate–amplitude–frequency functions plotted as two-dimensional surfaces. The surfaces consist of five regions separated and sufficiently defined by four space curves. At 14 different frequencies, the statistical distribution of each rate-intensity-function parameter could be approximated by a particular lognormal distribution (n = 56; R² > 0.796). The Kolmogorov–Smirnov test fails to reject this hypothesis for each combination of frequency and parameter (56 tests; p > 0.39). Therefore, at a given frequency, the variation of the parameters can be represented by lognormal distributions with specific means and standard deviations. Responses of six RA fibers, which are different from the data-set used for modeling, were compared with the stochastic model at different frequencies. The parameters of those fibers were tested against the null hypotheses that they were sampled from the particular parameter distributions dictated by the model. The Kolmogorov–Smirnov test fails to reject all the hypotheses at the α = 0.05 level (44 tests). At the α = 0.10 level, only a few test parameters were found to be departing from the model (a₀ and a₁ at 5?Hz; a₂ at 20?Hz; a₂ and a₃ at 50?Hz). The remaining test parameters could be accurately described by the model. Having confirmed the validity of the model, the logarithmic means and the logarithmic standard deviations of the lognormally distributed rate-intensity-function parameters were estimated in the frequency range of 4–200?Hz. The rate–amplitude–frequency surfaces sampled from the established stochastic model completely characterize the rate responses of RA fibers to sinusoidal stimuli and are superior to tuning curves which require selecting criterion responses. The current rate-response model is promising for future computational work, especially on population modeling.     

Serum luteinizing hormone levels in Brangus cows following variable suckling intensity and administration of various levels of estrogen

Fifty Brangus cows were randomly allotted to suckled (S) or nonsuckled (NS) treatment groups on day 20 postpartum. Suckled cows were nursed at 6 hr intervals for 72 hours. Nonsuckled cows were separated from their calves for the entire 72 hours. At 24 hr after initial separation from calves, S and NS cows were given an I.M. challenge of 0, 0.5, 1.0, 2.0 or 4.0 mg estradiol-17beta (E2) to induce a luteinizing hormone (LH) surge (five cows per treatment group). Blood samples were taken at the time of E2 injection and at 2 hr intervals until hr 48 post-injection. Blood serum was analyzed for LH content via radioimmunoassay. Suckled and NS cows manifesting an LH surge after receiving less than 4 mg E2 were 2 of 15 vs 9 of 15 (P<.01), or 4 mg E2 dose were 5 of 5 vs 5 of 5, respectively. Greater serum LH concentrations in NS than S cows were found with dose levels of 0, 0.5 and 1.0 mg E2 (P<.005), but there was no difference by period. Differences by treatment (P<.05) and by period (P<.005) were found at the 2 mg E2 dose. Suckled and NS cows having an LH surge at less than a 4 mg E2 challenge had no differences in LH concentration or timing parameters. Four mg E2 hastened the time of onset of the LH surge (P<.025), time till peak height of the surge (P<.025) and completion of the surge (P<.10). No differences in postpartum interval or conception rate were found between S and nonsuckled. Suckling impairs hypothalamic/pituitary response to low E2 challenge dose and elicits changes in timing parameters in response to high E2 dosage.     

Functional modules with disease discrimination abilities for various cancers

Selecting differentially expressed genes (DEGs) is one of the most important tasks in microarray applications for studying multi-factor diseases including cancers. However, the small samples typically used in current microarray studies may only partially reflect the widely altered gene expressions in complex diseases, which would introduce low reproducibility of gene lists selected by statistical methods. Here, by analyzing seven cancer datasets, we showed that, in each cancer, a wide range of functional modules have altered gene expressions and thus have high disease classification abilities. The results also showed that seven modules are shared across diverse cancers, suggesting hints about the common mechanisms of cancers. Therefore, instead of relying on a few individual genes whose selection is hardly reproducible in current microarray experiments, we may use functional modules as functional signatures to study core mechanisms of cancers and build robust diagnostic classifiers.     

Frequency of chromosome aberrations induced by mutagens of various functions in cells of the first division at various times of fixation

The dynamics of chromosome aberrations in human lymphocyte culture cells of the 1-st division after exposure in the G0 phase for 1h to functionally different alkylating mutagens - ethyleneimine derivatives (bifunctional phosphamide, threefunctional thiophosphamide, tetrafunctional dipine and pentafunctional photrin) was analysed. The frequency of chromosome aberrations was constant after exposure to "dicentric" mutagens (dipine, photrin) at all times of fixation, while under the action of "monocentric" mutagens (phosphamide, thiophosphamide) this declined significantly with increasing the duration of cultivation. The portion of aberrations of the chromatid remains unaltered in time, in case of both "dicentric" and "monocentric" mutagens, reaching 75% for "monocentric" and 50% for "dicentric" of the total number of chromosome aberrations.     

Frequency discrimination in the central nerve cords of locusts

The auditory mechanism in locusts, especially the central mechanism of frequency analysis, was examined electrophysiologically. The central auditory response had a sharp rise of threshold at a certain frequency range, and it showed a remarkable change when all peripheral fibres except the tympanic nerve were cut off. The response pattern was also changed by this procedure. These results indicate the presence of an inhibitory interaction mechanism of various auditory inputs. It can be concluded that locusts are able to discriminate sound frequency to some degree by this interactive mechanism.     

Capability of intensity discrimination in multiple receptor model of insect taste

A simple model in which one CNS taste neuron integrates inputsfrom multiple peripheral receptors is introduced in order toinvestigate the mechanism of acute intensity taste discriminationin flies. Information theory is applied to evaluate the acuteability of discrimination provided by the model. The presentanalysis is carried out under two statistical conditions concerningthe uncertainty of receptor response. Based on experimentaldata obtained by Smith et al. (1983), we estimate the mutualinformation entropy of the model. The numerical results obtainedhere indicate that the uncertainty observed in a single receptorresponse is dramatically reduced by the central integration.Furthermore, each of the eleven stimulus intensity levels experimentallyapplied by Smith et al., can be discriminated completely byintegrating the responses of the realistic number of receptors(33–212). Such a great improvement of the differentialsensitivity in the model resolves the discrepancy between thelow differential sensitivity of single sugar receptors (Smithet al., 1983) and the high sensitivity obtained in the feedingbehavior (Dethier and Rhoades, 1954; Dethier and Bowdan, 1984)of the blowfly.     

A neural coding model for sensory intensity discrimination,to be applied to gustation

Summary This paper presents a model of the neural coding and discrimination of sensory intensity. The model consists of five stages: (1) the coding of stimulus intensity in peripheral receptors or neurons by a rate code. The relevance of comparing different analysis intervals for the response is pointed out; (2) neural processing, according to either labeled-line or across-fiber pattern theory. In addition, two possible non-linearities in the processing are considered: a threshold mechanism, and contrast enhancement by reciprocal inhibition; (3) a neural discriminator, based on signal-detection theory; (4) a memory stage; (5) an effector organ providing a behavioral output. Emphasis is put on stages 2 and 3.The model produces predictions of the differential threshold, which should be directly testable in a behavioral two-alternative forced-choice paradigm. The model will be applied to gustatory intensity discrimination in rat in a subsequent study (Maes and Erickson 1984). The Discussion pays attention to the relative contributions of peripheral and central noise sources. It also compares the present model with Beidler's (1958) approach through just noticeable differences (JND's). The model presented here seems more adequate in providing an understanding of sensory information processing.Abbreviations AFP across fiber pattern - DA discrimination acuity - DT differential threshold - JND just noticeable difference - LL labeled line - NTS nucleus tractus solitarius     

SmpB functions in various steps of trans-translation

tmRNA has a dual function as a tRNA and an mRNA to facilitate trans-translation, in which a ribosome can switch between translation of a truncated mRNA and the tmRNA’s tag sequence. SmpB is a tmRNA binding protein that has been identified to be essential for trans-translation in vivo. To further study the function of SmpB, an S30 fraction from an Escherichia coli strain, in which the set of genes for SmpB and tmRNA has been deleted from the genome, and His-tagged SmpB active in trans-translation were prepared. The SmpB-depleted S30 fraction had an ability to facilitate poly(U)-dependent tag-peptide synthesis in vitro when purified His-tagged SmpB was exogenously added together with tmRNA, although SmpB was not required for in vitro poly(U)-dependent poly(Phe) synthesis. It was also found that depletion of SmpB leads to a decrease in the level of tmRNA in the cell. In addition, SmpB considerably enhanced the aminoacylation of tmRNA by alanyl-tRNA synthetase in vitro. The aminoacylation enhancement by SmpB, the binding of SmpB to tmRNA and the effect of depletion of SmpB on the expression level of tmRNA in the cell were all affected by some mutations in the tRNA-like domain which cause a defect in ribosome binding leading to a trans-translation deficiency. These results demonstrate that, via binding to the tRNA-like domain of tmRNA, SmpB plays various roles: rescuing the tmRNA molecule from degradation in the cell, enhancing the aminoacylation of tmRNA and mediating the binding of tmRNA to ribosome.     

Influence of intensity and duration of exposure to various stressors on serum TSH and GH levels in adult male rats

The effect of stressor intensity and duration of exposure to the stimuli on adrenocorticotropin (ACTH), somatotropin (GH) and thyrotropin (TSH) concentration in serum was studied in adult male Sprague-Dawley rats. The stressors used were noise, restraint in plastic tubes and immobilization on wood boards. The greatest ACTH release was found in immobilized rats and the smallest in noise-exposed animals. The inhibition of GH secretion was related to the intensity of ACTH release in that maximal GH inhibition was observed in immobilized rats and minimal in noise-exposed rats. The TSH response was more complex. Noise increased TSH release at all periods observed (10, 30 and 60 min); the stimulation of TSH release caused by restraint was significant at 30 and 60 min and was always of lesser magnitude than that in response to noise. Finally, immobilization significantly increased TSH levels at 10 min and decreased them at 30 and 60 min. These results suggest that, under appropriate conditions, all hormones studied discriminate between different stressor intensities. However, the complexity of the TSH response to stressors indicates that this hormone is not an adequate index of the stress experienced by the animals.     

Frequency response of the human controller for various processes and stochastic testsignals

The adaptive behaviour of the human controller in a closed loop system with stochastic testsignals is investigated. For several typical simulated processes functional models for the human controller are derived. These models describe the adaptability of the human controller to processes which are free of dead-time, assuming simple control tasks. Finally the results for processes with dead-time will be discussed.The investigations were done on a hybrid computer of the Deutsche Forschungsgemeinschaft     

Gustatory intensity discrimination in rat NTS: a tool for the evaluation of neural coding theories

Summary The neural coding of taste quality in vertebrates currently is addressed by the labeledline and the across-fiber pattern theory. Experimental tests that have tried to distinguish between these theories by manipulating taste quality have been problematic in that both are fairly successful. However, the two theories maintain that different numbers of neurons participate in coding the presence of a substance. In the labeled-line theory, only those neurons labeled by that substance are supposed to be involved, whereas in the across-fiber pattern theory, all neurons responding to the substance are taken into account. We therefore expected that the theories might predict different intensity discriminating abilities among the four classical taste stimuli, which could provide a less equivocal test between the theories.A previous paper (Maes 1984) described a model for the neural basis of intensity discrimination, based on signal-detection theory. In the present paper, experimental data obtained from single neurons in the nucleus of the solitary tract of rat are analyzed in terms of this model. Whole-mouth stimulation with the four classical taste substances was used. For both theories, predictions of the intensity discriminating acuity for the four substances were derived, using different response analysis intervals, and including two plausible non-linearities in neural processing.The acuity profile across the four stimuli (consisting of the reciprocals of the four differential thresholds) turned out to be sensitive to the choice of coding theory and non-linearity. The interval chosen for response analysis had a strong effect. The predicted profiles should be checked against behavioral data on intensity discrimination in rat, but since such data are not yet available, a comparison was made with human psychophysical data, for illustrative purposes. It appeared that a unique combination of variables (tonic part of the response, across-fiber pattern coding with a contrast enhancement type of non-linearity) could be selected to match the psychophysical profile.In the Discussion, special attention is paid to the fundamental differences between the two coding theories, to the relevance of whole-mouth stimulation, and to the informational significance of various parts of the phasic/tonic response.Abbreviations AFP across-fiber pattern - CT chorda tympani - DA discrimination acuity - DT differential threshold - H sour - LL labeled line - N salty - NTS nucleus tractus solitarius - PTA pontine taste area - Q bitter - S sweet     

Multiple levels of affinity-dependent DNA discrimination in Cre-LoxP recombination

Cre recombinase residue Arg259 mediates a canonical bidentate hydrogen-bonded contact with Gua27 of its LoxP DNA substrate. Substituting Cyt8-Gua27 with the three other basepairs, to give LoxAT, LoxTA, and LoxGC, reduced Cre-mediated recombination in vitro, with the preference order of Gua27 > Ade27 approximately Thy27 > Cyt27. While LoxAT and LoxTA exhibited 2.5-fold reduced affinity and 2.5-5-fold slower reaction rates, LoxGC was a barely functional substrate. Its maximum level of turnover was 6-fold reduced over other substrates, and it exhibited 8.5-fold reduced Cre binding and 6.3-fold slower turnover rate. With LoxP, the rate-limiting step for recombination occurs after protein-DNA complex assembly but before completion of the first strand exchange to form the Holliday junction (HJ) intermediate. With the mutant substrates, it occurs after HJ formation. Using an increased DNA-binding E262Q/E266Q "CreQQ" variant, all four substrates react more readily, but with much less difference between them, and maintained the earlier rate-limiting step. The data indicate that Cre discriminates substrates through differences in (i) concentration dependence of active complex assembly, (ii) turnover rate, and (iii) maximum yield of product at saturation, all of which are functions of the Cre-DNA binding interaction. CreQQ suppression of Lox mutant defects implies that coupling between binding and turnover involves a change in Cre subunit DNA affinities during the "conformational switch" that occurs prior to the second strand exchange. These results provide an example of how a DNA-binding enzyme can exert specificity via affinity modulation of conformational transitions that occur along its reaction pathway.     

Different Mi-2 complexes for various developmental functions in Caenorhabditis elegans

Biochemical purifications from mammalian cells and Xenopus oocytes revealed that vertebrate Mi-2 proteins reside in multisubunit NuRD (Nucleosome Remodeling and Deacetylase) complexes. Since all NuRD subunits are highly conserved in the genomes of C. elegans and Drosophila, it was suggested that NuRD complexes also exist in invertebrates. Recently, a novel dMec complex, composed of dMi-2 and dMEP-1 was identified in Drosophila. The genome of C. elegans encodes two highly homologous Mi-2 orthologues, LET-418 and CHD-3. Here we demonstrate that these proteins define at least three different protein complexes, two distinct NuRD complexes and one MEC complex. The two canonical NuRD complexes share the same core subunits HDA-1/HDAC, LIN-53/RbAp and LIN-40/MTA, but differ in their Mi-2 orthologues LET-418 or CHD-3. LET-418 but not CHD-3, interacts with the Krüppel-like protein MEP-1 in a distinct complex, the MEC complex. Based on microarrays analyses, we propose that MEC constitutes an important LET-418 containing regulatory complex during C. elegans embryonic and early larval development. It is required for the repression of germline potential in somatic cells and acts when blastomeres are still dividing and differentiating. The two NuRD complexes may not be important for the early development, but may act later during postembryonic development. Altogether, our data suggest a considerable complexity in the composition, the developmental function and the tissue-specificity of the different C. elegans Mi-2 complexes.