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Time-based prediction in motor control: evidence from grip force response to external load perturbations.

An object held in precision grip creates predictable load forces on the hand during voluntary hand movement and these are associated with anticipatory modulation of grip force. Conflicting results have been obtained over whether predictable external load perturbations result in anticipatory grip force responses (e.g. Blakemore et al. in J Neurosci 18(18):7511-7518, 1998; Weeks et al. in Exp Brain Res 132:404-410, 2000). This paper investigated whether the discrepancies reflect differences in the methods used in estimating the time delay. Subjects held a manipulandum that delivered load force perturbations in the form of pulses of variable duration and interval or periodic 0.5 and 1 Hz square waves or sinusoids. The grip forces exerted by the subjects were measured. Two methods were used to assess the time delay of the grip force in relation to the load force: (1) cross-spectral analysis, (2) a single threshold method applied on time-locked averaged data. Despite a phase lag shown by the cross-spectral analysis, the threshold method revealed grip force increased 264.8+/-40.2 ms before the onset of the load force when 0.5 Hz square waves were used as the load force perturbation and 70.2+/-17.0 ms before the load force when 1 Hz square waves were used. Computer simulations indicated that the single threshold method gives a more sensitive estimate of the onset time than the cross-spectral analysis. We conclude that discrepancies in previous studies reflect differences in the methods used to assess the time-delay and that there is an anticipatory component in the grip force response to predictable external load perturbation.

Adult↗

Unsupervised analysis of polyphonic music by sparse coding.

We investigate a data-driven approach to the analysis and transcription of polyphonic music, using a probabilistic model which is able to find sparse linear decompositions of a sequence of short-term Fourier spectra. The resulting system represents each input spectrum as a weighted sum of a small number of "atomic" spectra chosen from a larger dictionary; this dictionary is, in turn, learned from the data in such a way as to represent the given training set in an (information theoretically) efficient way. When exposed to examples of polyphonic music, most of the dictionary elements take on the spectral characteristics of individual notes in the music, so that the sparse decomposition can be used to identify the notes in a polyphonic mixture. Our approach differs from other methods of polyphonic analysis based on spectral decomposition by combining all of the following: (a) a formulation in terms of an explicitly given probabilistic model, in which the process estimating which notes are present corresponds naturally with the inference of latent variables in the model; (b) a particularly simple generative model, motivated by very general considerations about efficient coding, that makes very few assumptions about the musical origins of the signals being processed; and (c) the ability to learn a dictionary of atomic spectra (most of which converge to harmonic spectral profiles associated with specific notes) from polyphonic examples alone-no separate training on monophonic examples is required.

Journal Article↗

Open channel noise. IV. Estimation of rapid kinetics of formamide block in gramicidin A channels.

Blocking events in currents through biological ion channels occur over a wide range of characteristic times. The interruptions in single-channel currents from blocking events may be characterized by the direct measurement of gap durations or by analyzing open-channel current histograms, provided that the events are not much shorter than the time resolution of single-channel recordings (approximately 10 microseconds). Here we present a method for the characterization of channel block on a much faster time scale by combining open-channel noise measurements with subsequent model fits according to a theoretical approach (Frehland, E. 1978. Biophysical Chemistry. 8:255-265). Although the bandwidth limitations in open-channel noise experiments are the same as in conventional single-channel experiments, from the dependence of the mean current and the spectral density of the noise on the concentration of the blocking agent, kinetics of very brief blocking events can be estimated. As an example we have analyzed the open-channel noise of K+ currents through the gramicidin A channel in the presence of various concentrations of formamide, a weak blocker, at neutral pH. We estimate the blocking and unblocking rates to be approximately 10(7)s-1 at 1 M formamide and discuss possible mechanisms for the blocking process.

Electric Conductivity↗

The design and testing of a noise reduction algorithm based on spectral subtraction.

Three noise reduction algorithms based on amplitude subtraction were designed and used to process speech mixed with babble noise in two signal-to-noise ratios. The estimation of the noise-magnitude spectrum was performed with a novel synchro method, which exploits specific characteristics of the speech signal. The unprocessed and processed signals were evaluated psychoacoustically by means of a four-alternative-forced choice test with monosyllabic words (minimal pairs) in carrier phrases. The testing was carried out on groups of normally hearing and hearing-impaired subjects and the long-term power spectra of the processed signals were shaped to be essentially identical with those from the corresponding unprocessed signals. For the hearing-impaired subjects all signals were spectrally shaped according to the POGO-fitting rule. None of the algorithms improved speech intelligibility for any group of listeners and no change in the overall pattern of confusion was observed.

Acoustic Stimulation↗

Antenna size dependence of fluorescence decay in the core antenna of photosystem I: estimates of charge separation and energy transfer rates.

We have examined the photophysics of energy migration and trapping in photosystem I by investigating the spectral and temporal properties of the fluorescence from the core antenna chlorophylls as a function of the antenna size. Time-correlated single photon counting was used to determine the fluorescence lifetimes in the isolated P700 chlorophyll a-protein complex and in a mutant of Chlamydomonas reinhardtii that lacks the photosystem II reaction center complex. The fluorescence decay in both types of sample is dominated by a fast (15-45 psec) component that is attributed to the lifetime of excitations in the photosystem I core antenna. These excitations decay primarily by an efficient photochemical quenching on P700. The measured lifetimes show a linear relationship to the core antenna size. A linear dependence of the excitation lifetime on antenna size was predicted previously in a lattice model for excitation migration and trapping in arrays of photosynthetic pigments [Pearlstein, R.M. (1982) Photochem. Photobiol. 35, 835-844]. Based on this model, our data predict a time constant for photochemical charge separation in the photosystem I reaction center of 2.8 +/- 0.7 or 3.4 +/- 0.7 psec, assuming monomeric or dimeric P700, respectively. The predicted average single-step transfer time for excitation transfer between core antenna pigments is 0.21 +/- 0.04 psec. Under these conditions, excitation migration in photosystem I is near the diffusion limit, with each excitation making an average of 2.4 visits to the reaction center before photoconversion.

Chlorophyll↗

Influence of contralateral obstructions on Doppler-frequency spectral analysis of ipsilateral stenoses of the carotid arteries.

Contralateral obstructions have been suggested to be responsible for inaccuracy in Doppler sonographic diagnosis and estimation of severity of internal carotid artery stenoses. Therefore correlations of the systolic peak frequency of the internal carotid artery (Doppler-Frequency-Spectrum-Analysis) and severity of stenoses found by angiography have been compared in subgroups with (n = 36) and without (n = 48) additional contralateral obstructions. The linear regressions in both subgroups were found to be very similar (Y = 0.0098X - 12.4 and Y = 0.0099X - 14.0), the coefficients of correlation identical (r = 0.83). In 26 patients, the systolic peak frequency of the internal carotid artery did not demonstrate a significant change due to operation of the contralateral vascular lesion; thus indicating that contralateral obstructions do not influence CW-Doppler sonographic findings of an ipsilateral vessel wall lesion concerning diagnostic accuracy and non-invasive estimation of the severity of stenoses.

Arterial Occlusive Diseases↗

Assessment of postoperative sedation level with spectral EEG parameters.

OBJECTIVES: Several sedation scores have been developed, but still a need exists for an objective method to monitor sedation level during intensive care. Our study presents a procedure for finding a combination of electroencephalogram (EEG) characteristics, which could be used in estimating sedation level. METHODS: We measured EEG in 29 cardiac surgical patients prior to and after the cardiac bypass grafting operation at different sedation levels. The clinical assessment of sedation levels was evaluated with the Ramsay Score. Spectral EEG parameters were computed and a linear model to predict postoperative sedation level was constructed by using principal component analysis and regression analysis. RESULTS: Sedation levels modified all computed spectral EEG parameters. The model based on optimal combination of EEG parameters predicted the observed Ramsay Score value with a prediction probability of 88%. CONCLUSIONS: This study suggests that a combination of spectral EEG parameters may discriminate between 3 sedation levels: awake, moderate sedation and deep sedation.

Adult↗

Non-linear changes of electrocortical activity after antenatal betamethasone treatment in fetal sheep.

We determined the effects of betamethasone on the fetal sheep electrocorticogram (ECoG) using linear (power spectral) and non-linear analysis. For non-linear analysis we used an algorithm based on the Wolf algorithm for the estimation of the leading Lyapunov exponent which calculates a prediction error based on the course of the time series in the phase space. A high prediction error stands for low predictibility or low regularity and vice versa. After 48 h of baseline recordings, vehicle (n = 6) or betamethasone (n = 7) at 10 microg h(-1) was infused over 48 h to the sheep fetus at 128 days gestational age (0.87 of gestation). ECoG spectral analysis revealed no difference in power spectrum between vehicle- and betamethasone-treated fetuses. The prediction error of the ECoG during REM sleep was higher than during non-REM or quiet sleep in both groups (P < 0.0001) revealing lower causality of brain activity during REM sleep. During REM sleep, prediction error significantly decreased 18-24 h after onset of betamethasone treatment (P < 0.05) and returned to baseline values within the following 24 h of continued betamethasone treatment. No ECoG changes were found during quiet sleep. Non-linear ECoG changes during metabolically active REM sleep accompanied the previously described decrease in cerebral blood flow. These results suggest that betamethasone in doses used in perinatal medicine acutely alters complex neuronal activity.

Algorithms↗

Instantaneous frequency decomposition: an application to spectrally sparse sounds with fast frequency modulations.

Classical time-frequency analysis is based on the amplitude responses of bandpass filters, discarding phase information. Instantaneous frequency analysis, in contrast, is based on the derivatives of these phases. This method of frequency calculation is of interest for its high precision and for reasons of similarity to cochlear encoding of sound. This article describes a methodology for high resolution analysis of sparse sounds, based on instantaneous frequencies. In this method, a comparison between tonotopic and instantaneous frequency information is introduced to select filter positions that are well matched to the signal. Second, a cross-check that compares frequency estimates from neighboring channels is used to optimize filter bandwidth, and to signal the quality of the analysis. These cross-checks lead to an optimal time-frequency representation without requiring any prior information about the signal. When applied to a signal that is sufficiently sparse, the method decomposes the signal into separate time-frequency contours that are tracked with high precision. Alternatively, if the signal is spectrally too dense, neighboring channels generate inconsistent estimates-a feature that allows the method to assess its own validity in particular contexts. Similar optimization principles may be present in cochlear encoding.

Acoustics↗

Magnetic circular dichroism analysis of the IHP effect on spin equilibria in human ferric hemoglobins.

Magnetic circular dichroism (MCD) spectroscopy has been to explore the connection between optical spectra and the high spin population of several hemoglobins under various conditions. It is found that the effectiveness of IHP in inducing spectral changes can be markedly affected by solvent. For example, the IHP-induced spectral changes in the visible region for nitritomethemoglobin-A in mixed buffer solvent systems (glycerol or polyethylene glycol (PEG), mw 190-210) are more than double those observed in aqueous buffers. We estimate that IHP induces a mix of R/T forms in bis-tris phosphate buffers, for NO-2metHb that is only about 50%. While PEG and glycerol both lead to enhanced IHP-induced spectral differences, they behave differently in two aspects. PEG shifts the visible MCD and absorption spectra of F-metHb-A, supposedly already biased towards the T form by ligand, in the same direction that IHP does. PEG also maximizes the spin state changes with IHP for three R from hemoglobins and N-3metHb-A, and so appears to stabilize the T form in all cases. Glycerol does not. In addition, the apparent binding constant for NO-2 to H2OmetHb-A differs between these two solvents. Comparison of the data from several hemoglobins leads to the conclusion that the changes in spin state distributions induced by IHP correlate well with quaternary structure for a given hemoglobin. An analogous correlation amongst various proteins between initial spin state distribution (IHP) absent) and quaternary structure is not found.

Circular Dichroism↗

Probing the arterial baroreflex: is there a 'spontaneous' baroreflex?

The arterial baroreflex is important for beat-to-beat arterial pressure control and its sensitivity has predictive value for clinical outcomes in a myriad of cardiovascular conditions. Given this, researchers have sought approaches for baroreflex assessment that are not invasive and easily obtained. These techniques have exploited the beat-by-beat parallel changes in arterial pressure and heart period to produce estimates that have been termed 'spontaneous' baroreflex indices. The two most commonly used analyses--frequency domain or spectral analyses and sequence analysis have been evaluated in both animals and humans. The animal data suggests an important baroreflex role in linking spontaneous heart period and pressure variabilities, but do not resolve the extent to which these fluctuations reflect baroreflex gain. The human data suggest a high correlation between spontaneous indices and pharmacologically derived baroreflex gain, but also indicate a poor correspondence between them. This may be due to the fact that short-term fluctuations in RR interval are not intimately and always linked to those in pressure via the baroreflex and thus simple observation of arterial pressure and heart period alone may not reveal the extent of arterial baroreflex involvement. If baroreflex function is to be assessed with the fewest and safest assumptions, the input to the system should be driven externally to create large and apparent responses. Nonetheless, spontaneous baroreflex indices may have predictive power; although it remains unknown whether spontaneous indices provide predictive power beyond that provided by heart rate variability indices alone.

Animals↗

Effects of alcohol, at two times of day, on EEG-derived indices of physiological arousal.

Effects of alcohol consumption (0.8 ml/kg) on sleep propensity, spectral characteristics of the EEG and self-rated activation in 16 young male subjects, were investigated during sessions at each of two times of day (08.00 and 16.00). Within-session, time-related changes in the pattern of stage-1 sleep occurrence, and of spectral power in different EEG bands indicated that, irrespective of time of day, physiological arousal increased as estimated blood alcohol concentration (BAC) was rising, and decreased as BAC was falling. Subjective activation was reduced by alcohol during both phases of the BAC curve. A pattern of reduced stage-1 sleep occurrence, higher absolute high alpha power and higher ratings of activation suggested that, irrespective of alcohol condition, physiological and subjective arousal was higher during sessions starting at 16.00 than during those starting at 08.00. There were no significant interactions between alcohol and time of day in respect of any dependent variable. However, the degree to which effects reflecting circadian variation may have been masked by effects of limited sleep restriction prior to morning sessions remains unclear. Subjects reported having slept on only 23.5% of occasions when sleep was scored. Comparison of patterns of statistically significant changes in absolute and relative power in different bands indicated that the two indices do not provide exactly equivalent information about changes in the EEG.

Adult↗

Phrenic and recurrent laryngeal motoneuron activities during hyperoxia and hypoxia in piglets.

We hypothesized that synchronization of inspiratory motoneurons may involve inputs from two central pattern generators (CPG): one characterized by medium-frequency (< 50 Hz) and the other by high-frequency oscillations (> or = 50 Hz). We studied phrenic and recurrent laryngeal nerve activities recorded during hyperoxia and hypoxia in Saffan anesthetized, paralyzed, and artificially ventilated piglets. Spectral analyses, derived from the full as well as partitioned halves of inspiration, showed that phrenic and recurrent laryngeal discharges contained peaks in the medium-frequency band, which were indicative of common inputs. The phrenic spectra of many animals had peaks in the high-frequency band; such peaks were uncommon in recurrent laryngeal spectra; consequently, correlated activities corresponding to high-frequency oscillations were not usually observed. Thus, it is likely that acquisition of modulating inputs from a high-frequency CPG may emerge in an age-dependent manner in different motoneuron pools. During hypoxia, both phrenic and recurrent laryngeal discharges were facilitated as shown by increases in both the amplitudes of signal-averaged histograms and the magnitudes of their respective power spectral activities. Also, there was a significant increase in the values of phrenic-recurrent laryngeal coherence estimates in the medium-frequency region. Hence, medium-frequency oscillations are more apparent in early development, perhaps to facilitate synchronization of inspiratory motoneuron activities, especially under conditions of increased chemical drive.

Animals↗

Fluctuation and linear analysis of Na-current kinetics in squid axon.

The power spectrum of current fluctuations and the complex admittance of squid axon were determined in the frequency range 12.5 to 5,000 Hx during membrane voltage clamps to the same potentials in the same axon during internal perfusion with cesium. The complex admittance was determined rapidly and with high resolution by a fast Fourier transform computation of the current response, acquired after a steady state was attained, to a synthesized signal with predetermined spectral characteristics superposed as a continuous, repetitive, small perturbation on step voltage clamps. Linear conduction parameters were estimated directly from admittance data by fitting an admittance model, derived from the linearized Hodgkin-Huxley equations modified by replacing the membrane capacitance with a "constant-phase-angle" capacitance, to the data. The constant phase angle obtained was approximately 80 degrees. At depolarizations the phase of the admittance was 180 degrees, and the real part of the impedance locus was in the left-half complex plane for frequencies below 1 kHz, which indicates a steady-state negative Na conductance. The fits also yielded estimates of the natural frequencies of Na "activation" and "inactivation" processes. By fitting Na-current noise spectra with a double Lorentzian function, a lower and an upper corner frequency were obtained; these were compared with the two natural frequencies determined from admittance analysis at the corresponding potentials. The frequencies from fluctuation analyses ranged from 1.0 to 10.3 times higher than those from linear (admittance) analysis. This discrepancy is consistent with the concept that the fluctuations reflect a nonlinear rate process that cannot be fully characterized by linear perturbation analysis. Comparison of the real part of the admittance and the current noise spectrum shows that the Nyquist relation, which generally applies to equilibrium conductors, does not hold for the Na process in squid axon. The Na-channel conductance, gamma Na, was found to increase monotonically from 0.1 to 4.8 pS for depolarizations up to 50 mV from a holding potential of -60 mV, with no indication of a maximum value.

Animals↗

Pulse radiolysis studies indicate that electron transfer is involved in radioprotection by Hoechst 33342 and methylproamine.

PURPOSE: The aim of the study was to obtain evidence to support the hypothesis that the radioprotection by DNA-binding bibenzimidazoles is due to reduction by the DNA-bound ligand of transient radiation-induced oxidizing species on DNA, by following oxidation of the ligand after pulse radiolysis. A second aim was to compare the activities of methylproamine and Hoechst 33342 in the pulse radiolysis system, with the view to seeking a correlation with radioprotective activity. METHODS: Solutions of deoxyguanosine or DNA, with or without Hoechst 33342 or methylproamine, and containing sodium selenate and tert-butanol were subjected to pulse radiolysis, and the oxidation of the ligand followed by time-resolved spectrophotometry. RESULTS: The initial pulse radiolysis experiments using deoxyguanosine (dG) established that pulse radiolysis of sodium selenate produces a transient oxidant SeO3*-, which oxidizes dG to a species (presumably dG*+), with spectral characteristics indistinguishable from those described in previous pulse radiolysis studies using Br2*- as the oxidant. The estimate obtained for the bimolecular rate constant (k2) for the reaction of the selenite radical with dG, was 1.2 x 10(9) M(-1) s(-1). The corresponding reaction of SeO3*- with DNA is much slower (k2 3 x 10(7) M(-1) s(-1)). Although unbound Hoechst 33342 is oxidized directly by SeO3*- (k2 2.3 x 10(9) M(-1) s(-1)), experiments with mixtures of Hoechst 33342 with an excess of dG (or DNA) indicated that ligand oxidation was mediated by dG*+ (or DNAoxid). For example, successive dilution of a DNA-Hoechst solution had little impact on the rate of ligand oxidation, consistent with an intramolecular rate-determining step. When the concentration of DNA was maintained at 1.0 mM DNA bp, increasing the concentration of the ligand resulted in a linear increase in the rate of oxidation; the increase being steeper for methylproamine than for Hoechst 33342. Investigation of the dependence of yield of oxidized ligand on ligand occupancy also indicated that the methylproamine was more active than Hoechst 33342, with the estimates for the range of electron transfer from the ligand to DNAoxid being 14 and 31 bp for Hoechst 33342 and methylproamine, respectively. CONCLUSIONS: At this stage we conclude that radioprotection by these DNA-binding ligands is mediated by electron transfer, and that the improved radioprotective activity of methylproamine may be attributable to the observed kinetic differences. However, further studies are required to confirm the correlation, and if it is sustained, pulse radiolysis could be useful in evaluating new analogues in an attempt to further improve the radioprotective properties of methylproamine, which already has considerable clinical potential.

Benzimidazoles↗

Field survey instrumentation and radioanalytical procedures for NORM.

The comprehensive monitoring and analysis of NORM is extremely difficult and involves a wide range of equipment and techniques. The instruments to be used can depend on both the national legislation of the country in which the measurements are being undertaken and the operational conditions under which they are carried out. These can dictate whether dose rate, alpha/beta contamination or gamma contamination measurements are taken. In some circumstances the total activity of the samples can be estimated using the gamma activities of the radionuclides present, while in others only full gamma and alpha spectral analysis will suffice.

Alpha Particles↗

Modeling through-space magnetic shielding over ethynyl, cyano, and nitro groups.

In a strong magnetic field, covalently bonded hydrogen nuclei located over a pi bonded functional group experience magnetic shielding (or deshielding) that results from the combined effect of the magnetic anisotropy of the pi bond and various other intramolecular shielding effects. Gauge including atomic orbital (GIAO)-HF in Gaussian 98 was employed to calculate isotropic shielding values and to predict the net through-space proton NMR shielding increment for a simple model system: the proximate proton of methane held in various positions over simple molecules that contain a carbon-carbon triple bond, a carbon-nitrogen triple bond, or a nitro group. These net shielding increments of the proximate proton of methane, plotted against their Cartesian coordinates, led to the development of a single empirical equation for predicting the NMR shielding experienced by a covalently bonded proton over each group. The predictive capability of each equation has been validated by calculating shielding increments of protons over the functional group in known structures. These shielding increments are then used to adjust predicted chemical shifts for through-space shielding effects, and the adjusted values are compared to experimentally observed chemical shifts. The algorithms for predicting the shielding increment for a proton over these functional groups can be used in a spreadsheet or incorporated into software that estimates chemical shifts using additive substituent constants or a database of structures. Their use can substantially improve the accuracy of the estimated chemical shift of a proton in the vicinity of these functional groups, and thus assist in spectral assignments and in correct structure determination.

Anisotropy↗

L and M cone proportions in polymorphic New World monkeys.

Platyrrhine monkeys typically have only a single X-chromosome opsin gene. Alleles of this gene code for multiple versions of middle- to long-wavelength cone photopigments. X-chromosome inactivation provides heterozygous females with a retinal mosaic of cones containing either of two types of M and L pigment, thus establishing the photopigment basis for trichromatic color vision. This study examined the proportions of L and M cones created by this process. For that purpose, electroretinogram flicker photometry was used to obtain complete spectral sensitivity functions from 60 heterozygous female monkeys drawn from seven genera of platyrrhine monkeys. To obtain estimates of cone proportions, these functions were subsequently fit with linear combinations of L and M cone fundamentals that were derived from similar recordings made on conspecific animals having only one type of M/L pigment. Consistent with a random X-chromosome inactivation process, the average L:M cone weighting across the sample was close to unity. At the same time, there were significant individual variations in L:M cone proportions. The genesis of this variation and its implications for seeing are discussed.

Animals↗