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PubMed1998

Patients with Cushing's disease secrete adrenocorticotropin and cortisol jointly more asynchronously than healthy subjects.

We examined serum concentration time-series for ACTH and cortisol in 20 patients with pituitary-dependent ACTH excess (Cushing's disease) and in 29 age- and gender-matched controls. For each subject, blood samples were obtained at 10-min intervals for 24 h. Joint ACTH-cortisol synchrony was quantified using the recently introduced cross-approximate entropy (cross-ApEn) statistic. In patients, cross-ApEn was greater than in controls (1.686 +/- 0.051 vs. 1.077 +/- 0.039, P = 3.45 x 10(-16), giving a sensitivity of 85%. In control subjects, but not in patients, cross-ApEn was correlated positively with age (r = 0.465, P = 0.011) There was no gender difference in cross-ApEn, nor a relationship between cross-ApEn and the 24-h ACTH and cortisol secretion, in patients or controls. In contrast, the maximal cross-correlation coefficient for the ACTH and cortisol series after detrending the series was 0.394 +/- 0.033 in controls and 0.297 +/- 0.034 in patients with considerable overlap of the subgroups, giving a sensitivity for this index of only 5%. In addition to previous findings of increased individual irregularity of ACTH and cortisol release in Cushing's disease, we can now also demonstrate greater joint asynchrony of the circulating concentrations of these hormones. Thus, Cushing's disease disrupts ensemble network secretory dynamics over individual hormone output. We conclude that, like GH-secreting pituitary and aldosterone-secreting adrenal tumors, ACTH-secreting pituitary tumors exhibit significant loss of orderly hormone release patterns. Moreover, Cushing's disease is marked further by deterioriation of bihormonal synchrony between ACTH and cortisol release, thus suggesting further erosion of within-axis feedback control.

Adolescent↗

PubMedDate not supplied

[Exposure levels of persons involved in cleaning-up after the Chernobyl AES accident and included in the Russian State Medical and Dosimetric Registry].

Theoretical and practical problems related to the dosimetric data verification for recovery workers at the Chernobyl NBB are considered. Approaches and conclusions presented in the paper of L.A. Ilyin at al, (1). By using probability theory it was clearly that the method of dose verification developed in the reviewed paper and based on delta-entropy of statistical distribution failed to be scientifically founded. It does not permit to prove the existence of non-random component in random sampling without additional assumptions. The main conclusion of the reviewed paper, that 60% of individual doses included in the all-russia state medical and dosimetric state registry (ARMDSR) differ from the real exposure doses, is analysed and quantitatively estimated for several group of recovery workers. Our results present evidence that ARMDSR data do not contain a considerable part of "distorted" values even if the above mentioned method to take as valid.

Humans↗

PubMed1999

Jointly amplified basal and pulsatile growth hormone (GH) secretion and increased process irregularity in women with anorexia nervosa: indirect evidence for disruption of feedback regulation within the GH-insulin-like growth factor I axis.

Anorexia nervosa (AN) is associated with multiple endocrine alterations. In the majority of AN patients, basal and GHRH-stimulated serum GH levels are increased. The metabolic effects of GH are known to be related to its pulsatile secretory pattern. The present study was performed to examine GH pulsatility in AN using the techniques of deconvolution analysis and approximate entropy, which quantify secretory activity and serial irregularity of underlying hormone release not reflected in peak occurrence or amplitudes. To this end, 24-h GH profiles were obtained by continuous blood sampling aliquoted at 20-min intervals in 8 nonfasting patients with AN [body mass index (BMI), 14.2 +/- 0.8 kg/m2; mean +/- SEM) and in 11 age-matched healthy women (BMI, 20.3 +/- 0.5 kg/m2). The deconvolution-estimated half-life of GH was not altered in the AN patients. The pituitary GH secretory burst frequency, burst mass, and burst duration were each significantly increased in women with AN compared to those in normal weight women. A 4-fold increase in daily pulsatile GH secretion was accompanied by a 20-fold increase in basal (nonpulsatile) GH secretion. There were significant negative correlations between BMI and the basal as well as pulsatile GH secretion rates. Moreover, AN patients exhibited significantly greater GH approximate entropy scores than the controls, denoting marked irregularity of the GH release process. In contrast to previous reports in healthy fasting subjects, cortisol levels in AN patients were positively correlated to GH secretion rates. Leptin levels were significantly inversely correlated to the pulsatile, but not the basal, GH secretion rate. The present data demonstrate augmented basal as well as pulsatile GH secretion with disruption of the orderliness of the GH release process in AN. Accordingly, GH secretion in AN probably reflects altered neuroendocrine feedback regulation, e.g. associated with increased hypothalamic GHRH discharge superimposed on reduced hypothalamic somatostatinergic tone.

Activity Cycles↗

PubMed2005

Conformational transition free energy profiles of an adsorbed, lattice model protein by multicanonical Monte Carlo simulation.

Proteins often undergo changes in internal conformation upon interacting with a surface. We investigate the thermodynamics of surface induced conformational change in a lattice model protein using a multicanonical Monte Carlo method. The protein is a linear heteropolymer of 27 segments (of types A and B) confined to a cubic lattice. The segmental order and nearest neighbor contact energies are chosen to yield, in the absence of an adsorbing surface, a unique 3x3x3 folded structure. The surface is a plane of sites interacting either equally with A and B segments (equal affinity surface) or more strongly with the A segments (A affinity surface). We use a multicanonical Monte Carlo algorithm, with configuration bias and jump walking moves, featuring an iteratively updated sampling function that converges to the reciprocal of the density of states 1/Omega(E), E being the potential energy. We find inflection points in the configurational entropy, S(E)=k ln Omega(E), for all but a strongly adsorbing equal affinity surface, indicating the presence of free energy barriers to transition. When protein-surface interactions are weak, the free energy profiles F(E)=E-TS(E) qualitatively resemble those of a protein in the absence of a surface: a free energy barrier separates a folded, lowest energy state from globular, higher energy states. The surface acts in this case to stabilize the globular states relative to the folded state. When the protein surface interactions are stronger, the situation differs markedly: the folded state no longer occurs at the lowest energy and free energy barriers may be absent altogether.

Adsorption↗

PubMed1999

Photopolarimetric characterization of the transition between two turbulent states in a nematic liquid crystal film.

This work was aimed at the photopolarimetric characterization of the transition between two dynamic scattering modes that take place in a planarly aligned nematic liquid crystal sample, under the effect of an external low-frequency electric field. The time evolution of the degree of polarization and the behavior of the radiation entropy of the transmitted light allow us to interpret the transition between two turbulent states, or dynamic scattering modes, as a decay from a two-dimensional (2D) to a (3D) turbulence.

Journal Article↗

PubMed2004

Estimating mutual information.

We present two classes of improved estimators for mutual information M(X,Y), from samples of random points distributed according to some joint probability density mu(x,y). In contrast to conventional estimators based on binnings, they are based on entropy estimates from k -nearest neighbor distances. This means that they are data efficient (with k=1 we resolve structures down to the smallest possible scales), adaptive (the resolution is higher where data are more numerous), and have minimal bias. Indeed, the bias of the underlying entropy estimates is mainly due to nonuniformity of the density at the smallest resolved scale, giving typically systematic errors which scale as functions of k/N for N points. Numerically, we find that both families become exact for independent distributions, i.e. the estimator M(X,Y) vanishes (up to statistical fluctuations) if mu(x,y)=mu(x)mu(y). This holds for all tested marginal distributions and for all dimensions of x and y. In addition, we give estimators for redundancies between more than two random variables. We compare our algorithms in detail with existing algorithms. Finally, we demonstrate the usefulness of our estimators for assessing the actual independence of components obtained from independent component analysis (ICA), for improving ICA, and for estimating the reliability of blind source separation.

Journal Article↗

PubMed1997

An adaptive psychophysical method for subject classification.

In psychophysical experiments, one's goal is usually to measure some continuous parameter hypothesized to determine the statistical properties of a subject's responses. Methods are well developed that adaptively manipulate stimulus characteristics in such a way that the reliability of the parameter estimate is maximized. However, such methods are inapplicable in situations in which the goal is to assign subjects to discrete categories, rather than to measure a continuous parameter. This paper introduces a technique that is directly applicable to efficient categorization and that adaptively manipulates stimulus characteristics in such a way that the information obtained from each trial is maximized. This technique is based on the principle of minimum estimated expected entropy, whereby stimulus parameters on each trial are chosen in order to minimize the estimated expected entropy of the a posteriori probability distribution that expresses how likely a subject is to belong to each of a group of mutually exclusive categories. A sample implementation of the technique--the classification of infant subjects according to their audiograms--is then described and evaluated via computer simulation.

Auditory Perception↗

PubMedDate not supplied

[Thermodynamic studies of triple-helical structures of the collagen type in oligotripeptides during study of molecular chain elongation].

The conformational transition collagen-like triple helix in equilibrium with chains of oligotripeptides Z-(Gly-Pro-Pro)n-OMe with n = 6, 7, 8 in water by variation of solution temperature and sample concentration has been studied using IR-, CD-spectroscopy and microcalorimetry methods. The straight line correlation between the obtained value of the transition enthalpy and entropy and the number of the triplets (3n - 2), involved in the interpeptide set of hydrogen bonds was revealed. Evidently the effect of terminal groups is really weak in this case, and the interpeptide bonds of the triple helix may be regarded as equivalent one another. The estimated cooperative block of nucleation corresponds in length to the one full turn of the superhelix. The state diagrams of the oligotripeptides with n = 6, 7, 8 in aqueous solution are presented.

Collagen↗

PubMed2005

Cooling and clusters: when is heating needed?

There are (at least) two unsolved problems concerning the current state of the ther- mal gas in clusters of galaxies. The first is to identify the source of the heating which onsets cooling in the centres of clusters with short cooling times (the 'cooling-flow' problem). The second to understand the mechanism which boosts the entropy in cluster and group gas. Since both of these problems involve an unknown source of heating it is tempting to identify them with the same process, particularly since active galactic nuclei heating is observed to be operating at some level in a sample of well-observed 'cooling-flow' clusters. Here we show, using numerical simulations of cluster formation, that much of the gas ending up in clusters cools at high redshift and so the heating is also needed at high redshift, well before the cluster forms. This indicates that the same process operating to solve the cooling-flow problem may not also resolve the cluster-entropy problem.

Astronomy↗

PubMed2003

Extensions to minimum relative entropy inversion for noisy data.

Minimum relative entropy (MRE) and Tikhonov regularization (TR) were compared by Neupauer et al. [Water Resour. Res. 36 (2000) 2469] on the basis of an example plume source reconstruction problem originally proposed by Skaggs and Kabala [Water Resour. Res. 30 (1994) 71] and a boxcar-like function. Although Neupauer et al. [Water Resour. Res. 36 (2000) 2469] were careful in their conclusions to note the basis of these comparisons, we show that TR does not perform well on problems in which delta-like sources are convolved with diffuse-groundwater contamination response functions, particularly in the presence of noise. We also show that it is relatively easy to estimate an appropriate value for epsilon, the hyperparameter needed in the minimum relative entropy solution for the inverse problem in the presence of noise. This can be estimated in a variety of ways, including estimation from the data themselves, analysis of data residuals, and a rigorous approach using the real cepstrum and the Akaike Information Criterion (AIC). Regardless of the approach chosen, for the sample problem reported herein, excellent resolution of multiple delta-like spikes is produced from MRE from noisy, diffuse data. The usefulness of MRE for noisy inverse problems has been demonstrated.

Entropy↗

PubMed2000

Temporal coding of visual information in the thalamus.

The amount of information a sensory neuron carries about a stimulus is directly related to response reliability. We recorded from individual neurons in the cat lateral geniculate nucleus (LGN) while presenting randomly modulated visual stimuli. The responses to repeated stimuli were reproducible, whereas the responses evoked by nonrepeated stimuli drawn from the same ensemble were variable. Stimulus-dependent information was quantified directly from the difference in entropy of these neural responses. We show that a single LGN cell can encode much more visual information than had been demonstrated previously, ranging from 15 to 102 bits/sec across our sample of cells. Information rate was correlated with the firing rate of the cell, for a consistent rate of 3.6 +/- 0.6 bits/spike (mean +/- SD). This information can primarily be attributed to the high temporal precision with which firing probability is modulated; many individual spikes were timed with better than 1 msec precision. We introduce a way to estimate the amount of information encoded in temporal patterns of firing, as distinct from the information in the time varying firing rate at any temporal resolution. Using this method, we find that temporal patterns sometimes introduce redundancy but often encode visual information. The contribution of temporal patterns ranged from -3.4 to +25.5 bits/sec or from -9.4 to +24.9% of the total information content of the responses.

Action Potentials↗

PubMed2005

Incorporating the effect of ionic strength in free energy calculations using explicit ions.

The incorporation of explicit ions to mimic the effect of ionic strength or to neutralize the overall charge on a system in free energy calculations using molecular dynamics simulations is investigated. The difference in the free energy of hydration between two triosephosphate isomerase inhibitors calculated at five different ion concentrations is used as an example. We show that the free energy difference can be highly sensitive to the presence of explicit ions even in cases where the mutation itself does not involve a change in the overall charge. The effect is most significant if the molecule carries a net charge close to the site mutated. Furthermore, it is shown that the introduction of a small number of ions can lead to very severe sampling problems suggesting that in practical calculations convergence can best be achieved by incorporating either no counterions or by simulating at high ionic strength to ensure sufficient sampling of the ion distribution.

Algorithms↗

PubMed2003

An intelligent system for diagnosis of the heart valve diseases with wavelet packet neural networks.

In this paper, an intelligent system is presented for interpretation of the Doppler signals of the heart valve diseases based on the pattern recognition. This paper especially deals with combination of the feature extraction and classification from measured Doppler signal waveforms at the heart valve using the Doppler Ultrasound. Because of this, a wavelet packet neural network model developed by us is used. The model consists of two layers: wavelet and multi-layer perceptron. The wavelet layer is used for adaptive feature extraction in the time-frequency domain and is composed of wavelet packet decomposition and wavelet packet entropy. The multi-layer perceptron used for classification is a feed-forward neural network. The performance of the developed system has been evaluated in 215 samples. The test results showed that this system was effective in detecting Doppler heart sounds. The correct classification rate was about 94% for abnormal and normal subjects.

Artificial Intelligence↗

PubMed2000

A novel phase locked cavity resonator for B/A measurements in fluids

A new technique for the measurement in fluids of the acoustic non-linearity parameter B/A is presented, together with measured B/A values for several fluids. The non-linearity parameter is measured by phase locking radial modes within a PZT cylinder. The system, which implements the isentropic phase technique, uses continuous wave phase locking to measure the change in sound velocity that is typically associated with a change in ambient pressure under constant entropy. The method provides a means of measuring B/A in vitro both accurately and simply without the typical problems involved in time-of-flight systems. Fluid samples can remain small due to the nature of the cavity resonator, so the system is well suited to small volume, biological samples.

Journal Article↗

PubMed1998

High frequency oscillations in early cortical somatosensory evoked potentials.

OBJECTIVE: To evaluate the characteristics of high frequency (HF) components of the early cortical somatosensory evoked potentials (SEPs). METHODS: We recorded 8-channel SEPs from the frontal and left centro-parietal scalp after right median nerve stimulation with a wide band-pass (0.5-2000 Hz) and digitized at 40 kHz sampling rate in 12 healthy subjects. HF components were analyzed after digital band-pass filtering (300-1000 Hz). The power spectrum was obtained by a maximum entropy method. RESULTS: HF oscillations (maximum power at 600-800 Hz) consisting of 5 to 8 peaks were discriminated from the preceding P14 far-field in all cases and their phases were reversed between the frontal and contralateral parietal regions. In addition, in subjects with a high amplitude central P22 potential in original wide-band recordings, a single HF oscillation with a maximum at the central region was present. Furthermore, this component showed no phase reversal over the centro-parietal area. CONCLUSION: We therefore conclude that HF oscillations are superimposed not only on the tangential N20-P20 but on the radial P22 potential, and are generated from both tangential (area 3b) and radial (area 1) current sources.

Adult↗

PubMed1993

Direct phase determination by entropy maximization and likelihood ranking: status report and perspectives.

A new multisolution phasing method based on entropy maximization and likelihood ranking, proposed for the specific purpose of extending probabilistic direct methods to the field of macromolecules, has been implemented in two different computer programs and applied to a wide variety of problems. The latter comprise the determination of small crystal structures from X-ray diffraction data obtained from single crystals or from powders, and from electron diffraction data partially phased by image processing of electron micrographs, the ab initio generation and ranking of phase sets for small proteins; and the improvement of poor quality phases for a larger protein at medium resolution under constraint of solvent flatness. These applications show that the primary goal of this new method - namely increasing the accuracy and sensitivity of probabilistic phase indications compared with conventional direct methods - has been achieved. The main components of the method are (1) a tree-directed search through a space of trial phase sets; (2) the saddle-point method for calculating joint probabilities of structure factors, using entropy maximization; (3) likelihood-based scores to rank trial phase sets and prune the search tree; (4) efficient schemes, based on error-correcting codes, for sampling trial phase sets; (5) a statistical analysis of the scores for automatically selecting reliable phase indications. They have been implemented to varying degrees of completeness in a computer program (BUSTER) and tested on two small structures as well as on the small protein crambin. The main obstructions to successful ab initio phasing in the latter case seem to reside in the accumulation of phase sampling errors and in the lack of a properly defined molecular envelope, both of which can be remedied within the methods proposed. A review of the Bayesian statistical theory encompassing all phasing procedures, proposed earlier as an extension of the initial theory, shows that the techniques now available in BUSTER bring closer a number of major enhancements of standard macromolecular phasing techniques, namely isomorphous replacement, molecular replacement, solvent flattening and non-crystallographic symmetry averaging. The gradual implementation of the successive stages of this 'Bayesian programme' should lead to an increasingly integrated, effective and dependable phasing procedure for macromolecular structure determination.

Journal Article↗

PubMed1998

Augmented frequency and mass of LH discharged per burst are accompanied by marked disorderliness of LH secretion in adolescents with polycystic ovary syndrome.

The aim of this study was to quantify pulsatile LH secretion, burst frequency and mass, LH half-life, and the approximate entropy (ApEn) or (dis-) orderliness of LH release in adolescents with polycystic ovary syndrome (PCOS), combining a high-precision immunofluorimetric LH assay with deconvolution techniques. We sampled LH concentration profiles every 20 min overnight in 12 girls with PCOS (mean +/- S.E.M. age 16.4+/-0.57 years, body mass index (BMI) 24.4+/-1.6 kg/m2) and 11 eumenorrheic early-follicular-phase controls (mean +/- S.E.M. age 16.5+/-0.47 years, BMI 22.2+/-1.0 kg/m2). Fasting serum levels of androstenedione, testosterone, 17-hydroxyprogesterone (17-OHP), estrone, estradiol, FSH and sex hormone-binding globulin (SHBG) were determined. Compared with euandrogenic girls, PCOS adolescents had significantly (P<0.005) elevated serum LH/FSH ratios, 17-OHP, androstenedione, esterone and testosterone levels, decreased SHBG, and similar estradiol. PCOS subjects exhibited a 3-fold higher mean serum LH concentration with almost no overlap with controls (8.8+/-1.2 and 2.8+/-0.3 IU/l respectively, P<0.001). We initially used a conventional serum hormone concentration peak analysis method (Cluster) to evaluate the characteristics of pulsatile LH release. Cluster analysis disclosed a significant increase in serum LH concentration maximal peak height, a higher LH peak frequency and a higher mean serum LH concentration in interpulse nadirs in the PCOS group. Deconvolution analysis of mechanisms underlying the foregoing showed higher frequency in the PCOS group than the controls (7.9+/-0.4 and 5.7+/-0.6 pulses/12 h respectively, P<0.05). The mass of LH released per secretory event was also significantly higher in PCOS subjects than controls (5.4+/-0.57 and 3.4+/-0.56 IU/l respectively, P<0.05). Since the pulsatile production rate is the product of the mean mass of hormone secreted per pulse and the number of pulses per day, we estimated a significantly higher mean pulsatile production rate of (endogenous) LH in the PCOS group (41+/-4.2 IU/l per day in the PCOS group vs 18+/-2.3 IU/l per day in the controls, P<0.01). The mean estimated half-life of endogenous LH disappearance was also significantly higher in patients with PCOS than in controls (110+/-8.5 and 77+/-3.7 min respectively, P<0.01). To quantify the orderliness of LH release, we used ApEn. PCOS patients had remarkably increased disorderliness (higher ApEn) of LH release (1.09+/-0.04 vs 0.77+/-0.08 in controls, P = 0.002). Mean serum LH concentration, mass of LH secreted per burst, and LH production rate in PCOS, but not in normal adolescents, correlated positively with androstenedione (P<0.02, 0.02 and 0.05 respectively). The same parameters also correlated positively with 17-OHP (P<0.05, 0.02 and 0.05 respectively). Stepwise regression analysis unmasked a negative influence of BMI in PCOS on both mass of LH secreted per burst (r = -0.77, P<0.005) and LH production rate (r = -0.70, P<+/0.01). We conclude that PCOS adolescents secrete LH molecules with amplified frequency and burst mass and with markedly disrupted orderliness. A rise in basal (non-pulsatile) LH release, more basic LH isoforms, and/or a prolongation or asymmetry of the LH secretory burst could account for the apparently prolonged LH half-life. Determining whether disorderliness of the amplified pituitary LH release process is an intrinsic abnormality in PCOS. or reflects androgen excess, may help to clarify the pathophysiology of this oligo-ovulatory syndrome in young women.

Adolescent↗

PubMed2006

A novel technique to evaluate fluctuations of mood: implications for evaluating course and treatment effects in bipolar/affective disorders.

OBJECTIVES: Several psychiatric conditions are associated with frequent fluctuations of affect. In this study, we propose a new technique to uniformly score depression and mania objectively and use a new mathematical technique to model the frequent fluctuations in mood using simulated data. Our main aim is to examine the usefulness of this measure for evaluating treatment effects or course of illness, especially in bipolar or unipolar affective illness to quantify mood fluctuations. METHODS: We use a prototypical model, which takes into account the mean, the standard deviation (SD) and the coefficient of variation (CV = SD*100/mean) of the mood scores of the subjects over a user-defined period. We utilize simulated data of subjects for euthymia, minor depression, minor mania, severe depression, severe mania and cyclic bipolar illness (manic depression, MDP). We propose an objective method to quantify the mood of the subjects at weekly intervals (the interval can be user-defined) using a scale of 1-9 (1-4 = degrees of depression, 5 = euthymia, 6-9 = degrees of mania). These scores can be sampled according to the convenience and feasibility of the measurements, which can be derived from various clinical scales or by observation of the subjects in hospitals or other environments. We derive a new mathematical technique to arrive at a normalized measure for each of these conditions of simulated data in addition to the mean, SD and approximate entropy (ApEn). RESULTS: We utilize three sets of data, one to train the model to classify the condition of the subjects and the other two to test the reliability of the technique. We are able to successfully classify the condition of the subjects over a 52-timepoint period (length can be days or weeks depending upon the sampling rate). The New Index (NI) correlates significantly only with the mean (r(2) = 0.78), but not with the SD or ApEn score. CONCLUSIONS: These results indicate that it may be beneficial to reduce data according to the techniques we propose so that there is greater uniformity within which to compare future studies to evaluate treatment effects, not only in rapid-cycling MDP but also in other affective disorders. This method may be suitable for the meta-analysis of several studies, although different scales have been used in each of those studies. Our measure derived from simulated data has shown sufficient deviation of all the abnormal states from the euthymic state. The advantages and pitfalls of these techniques are further discussed to evaluate affect in various disorders. However, future prospective studies must address the importance of this measure in comparison with mean, SD and ApEn scores or other nonlinear measures of these time series. We are evaluating other nonlinear dynamic models, which may provide a continuous measure with which to identify different degrees of fluctuation of mood.

Affect↗