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Targeted acquisition for real-time NMR spectroscopy.

A target-oriented approach for the acquisition of information in biomolecular NMR spectroscopy is being developed. This approach combines concurrent data accumulation, processing, and monitoring of spectral quality. Real-time estimation of parameters allows acquisition to be stopped when results are complete and have a specified precision. The technique is based on multidimensional decomposition, which can process incomplete data. An incremental nonuniform sampling scheme ensures the optimization of resolution sensitivity. To validate this method, 3D HNCO spectra of three biomolecular systems (8 kDa ubiquitin, 22 kDa barstar-barnase complex, and 82 kDa malate synthase G) are processed incrementally at small acquisition time steps. The range of molecular sizes illustrates applicability in both sample- and sensitivity-limited regimes. In each case, the target was to acquire all backbone resonances in the spectra. For the three systems, the targets are achieved after 4.5 min, 1.6 h, and 22 h of acquisition time, respectively. A number of other targets that can be similarly monitored as a function of time are discussed.

Bacterial Proteins↗

Photosynthesis research in India: transition from yield physiology into molecular biology.

Photosynthesis research in India can be traced back several thousand years, with the mention of the Sun energizing the plants, which form food for all living creatures on the earth (from the Mahabharata, the great epic, ca. 2600 B.C.) and the report of Sage Parasara (ca. 100 B.C.) on the ability of plants to make their own food, due to their pigments. With the pioneering studies by Sir Jagdish Chandra Bose, work on photosynthesis proceeded steadily during the first half of the 20th century. Some of the classic reports during this period are: malate metabolism in Hydrilla, spectrophotometric estimation of chlorophylls, importance of spectral quality for photosynthesis - an indication of two photosystems, photoinactivation of photosynthesis, and importance of flag leaf photosynthesis to grain yield. After the 1960s, there was a burst of research in the areas of physiology and biochemistry of carbon assimilation and photochemistry. A significant transition occurred, before the beginning of new millennium, into the area of molecular biology of chloroplasts, regulation of photosynthesis and stress tolerance. Future research work in India is geared to focus on the following aspects of photosynthesis: elucidation/analysis of genes, molecular biology/evolution of enzymes, development/use of transgenics and modeling.

Journal Article↗

Abnormalities in cardiac baroreceptor sensitivity in acute ischaemic stroke patients are related to aortic stiffness.

Cardiac BRS (baroreceptor reflex sensitivity) is impaired following ischaemic stroke and predicts the risk of subsequent long-term death and disability. Impaired cardiac BRS may be due to impaired central processing of baroreceptor information following stroke or reduced baroreceptor activity due to increased large artery stiffness. We evaluated the relationship between large (aortic) artery stiffness and cardiac BRS during the acute phase of ischaemic stroke and in comparison with a group of stroke-free control subjects. Thirty-one ischaemic stroke patients were studied within 48 h of onset and again on day 14, along with 26 control subjects free of cerebrovascular disease. Cardiac BRS (determined by spectral analyses) and arterial stiffness estimated by PWVcf (carotid-femoral pulse wave velocity) using applanation tonometry were obtained. At baseline, cardiac BRS was lower in the stroke compared with the control group (4.3+/-2.3 compared with 6.5+/-4.2 ms/mmHg; P < 0.05). Cardiac BRS values were correlated with PWVcf at < 48 h (r = -0.51, P < 0.01) and on day 14 (r = -0.54, P < 0.01), but not in the control group (r = -0.27, P = not significant). In quantile regression models, taking into account the effect of all cardiovascular variables, cardiac BRS was independently related to PWVcf at baseline and on day 14 in the stroke patients, but stroke was not related to cardiac BRS level when other cardiovascular variables were considered. Wall stiffness of the arterial vessels involved in the baroreflex arc may account for, at least in part, the reduced cardiac BRS observed in acute stroke patients.

Acute Disease↗

Short-term stability measures for the evaluation of vocal quality.

The vocal quality of 64 normal subjects and 57 subjects suffering various degrees of glottal cancer was investigated using acoustic measures of six different aspects of the voice signal: tone period perturbation, amplitude perturbation, waveform perturbation, vocal noise, spectral periodicity and spectral distortion. The measures were estimated taking the glottal cycle as temporal reference unit to make the influence of the differences in tone period from one person to another as low as possible. The measures were evaluated with regard to (a) their ability to discriminate between healthy and sick subjects, and (b) their correlation with the perceptual evaluation of four trained listeners. The results suggest that signal processing techniques are unsatisfactory for clinical diagnoses but useful for monitoring voice quality.

Aged↗

Naftidrofuryl in the treatment of mild senile dementia. A double-blind study.

After a wash-out period of four weeks 51 patients with mild to moderate senile dementia were treated with either 600 mg naftidrofuryl (n = 23) daily per os or placebo (n = 28) over an eight-week period. When classified according to Hachinski's score, 24 patients were found to be suffering from senile dementia of Alzheimer's type (SDAT), whereas 27 patients presented with vascular dementia (MID). During wash-out and the treatment period the somatic and social symptoms of the disease were assessed by the AGP score. Cerebral performance was evaluated by a battery of tests measuring memory, concentration, psychomotor coordination and degree of depression. Electrical activity of the brain was estimated by a power-spectral analysis of EEG. In the total study group, the naftidrofuryl group showed a significantly better improvement in the results of the psychometric test battery, which was the primary variable during treatment. A parallel development was to be found in the AGP score and electrical brain function. When results of subgroups were analyzed according to the etiopathogenetic background of patients with SDAT, it was possible to show that naftidrofuryl affected psychopathometry and EEG-parameters while patients with MID responded to naftidrofuryl with changes in AGP score and EEG variables. These findings indicate the importance of etiopathologic features in performing studies with nootropic drugs in obtaining information on possible different actions in patients with different kinds of senile dementia.

Age Factors↗

Baroreceptor sensitivity and haemodynamics in normal pregnancy.

The objective of the study was to determine baroreceptor sensitivity and haemodynamics during the third trimester in normal pregnancy. The study group consisted of 20 primigravidae. The measurements were made at 28, 30, 32, 34, 36 and 38 weeks. The haemodynamic measurements were made by Doppler echocardiography and parameters calculated with standard formulae. Power spectral analysis was used to estimate the baroreceptor sensitivity in mid-frequency (MF) and high-frequency (HF) bands in msec/mmHg. Statistical tests performed were paired t-test and correlation coefficient. The mean baroreceptor sensitivity (BRS) in the mid-frequency band at 28, 30, 32, 34, 36 and 38 weeks were 5.19; 5.03; 5.52; 6.00; 6.77 and 7.82 msec/mmHg. The respective values for the high-frequency band were 7.52; 5.71; 7.99; 8.15; 8.53 and 10.87 msec/mmHg. The BRS in mid-high-frequency and high-frequency bands, mean arterial pressure and peripheral vascular resistance at 38 weeks of pregnancy were significantly higher than at 28 weeks, but the cardiac output was lower. A significant positive correlation of BRS with peripheral vascular resistance was observed. There was a significant negative correlation with cardiac output. The beneficial effects of increase BRS may lead to haemodynamic stability and stronger autonomic control of circulation. This may assist in maintaining a stable normal maternal blood pressure and a satisfactory placental perfusion during pregnancy. The absence of changes in BRS may be associated with pregnancy-induced hypertension and intrauterine growth restriction.

Journal Article↗

The effect of covariance between the K alpha and the K beta lead peak concentrations on the uncertainty in the result of in vivo (109)Cd KXRF bone lead measurement.

The effect of covariance between the K alpha and K beta lead peak concentrations on the uncertainty in the (109)Cd K x-ray fluorescence measurement of lead in bone is addressed here. It is commonly believed that this covariance arises as a result of the mutual dependence of the ratios of x-ray to coherent amplitudes on the same coherent peak amplitude. Previous work assumes statistical independence between spectral quantities of interest, crudely estimates the uncertainties in the lead peak concentrations, and suggests that the effect of covariance on the measurement uncertainty is small and can be ignored. Consequently, the current method followed by most laboratories reports the measurement uncertainty as if the fluctuations in the measured peak concentrations were independent. The robustness of such assumption, however, is undermined by existing epidemiological data. This paper assesses the magnitude of the covariance effect, using a method based on the observed significant correlations between the ratios of x-ray to coherent peak amplitudes in series of repeat phantom measurements. The revised uncertainties following this approach can exceed the uncertainties estimated by the accepted method by as much as 40%, which suggests a much stronger effect of covariance on the measurement uncertainty than previously reported.

Analysis of Variance↗

Time-varying analysis of heart rate variability signals with a Kalman smoother algorithm.

A time-varying parametric spectrum estimation method for analysing non-stationary heart rate variability signals is presented. As a case study, the dynamics of heart rate variability during an orthostatic test is examined. In this method, the non-stationary signal is first modelled with a time-varying autoregressive model and the model parameters are estimated recursively with a Kalman smoother algorithm. The benefit of using the Kalman smoother is that the lag error present in a Kalman filter, as well as in all other adaptive filters, can be avoided. The spectrum estimates for each time instant are then obtained from the estimated model parameters. Statistics of the obtained spectrum estimates are derived using the error propagation principle. The obtained spectrum estimates can further be decomposed into separate components and, thus, the time variation of low- and high-frequency components of heart rate variability can be examined separately. By using the presented method, high resolution time-varying spectrum estimates with no lag error can be produced. Other benefits of the method are the straightforward procedure for evaluating the statistics of the spectrum estimates and the option of spectral decomposition.

Adult↗

Resonance assignments, solution structure, and backbone dynamics of the DNA- and RPA-binding domain of human repair factor XPA.

XPA is involved in the damage recognition step of nucleotide excision repair (NER). XPA binds to other repair factors, and acts as a key element in NER complex formation. The central domain of human repair factor XPA (residues Met98 to Phe219) is responsible for the preferential binding to damaged DNA and to replication protein A (RPA). The domain consists of a zinc-containing subdomain with a compact globular structure and a C-terminal subdomain with a positively charged cleft in a novel alpha/beta structure. The resonance assignments and backbone dynamics of the central domain of human XPA were studied by multidimensional heteronuclear NMR methods. 15N relaxation data were obtained at two static magnetic fields, and analyzed by means of the model-free formalism under the assumption of isotropic or anisotropic rotational diffusion. In addition, exchange contributions were estimated by analysis of the spectral density function at zero frequency. The results show that the domain exhibits a rotational diffusion anisotropy (Dparallel/Dperpendicular) of 1.38, and that most of the flexible regions exist on the DNA binding surface in the cleft in the C-terminal subdomain. This flexibility may be involved in the interactions of XPA with various kinds of damaged DNA.

Binding Sites↗

The effect of increasing age on thiopental disposition and anesthetic requirement.

The dose of thiopental required to induce anesthesia in adults decreases with age. The pharmacokinetic and pharmacodynamic properties of thiopental were studied in two groups of surgical patients to determine the mechanism of this decrease. In one group (29 patients 19-88 yr of age), thiopental was infused at a rate of 75-150 mg/min until the electroencephalogram (EEG) demonstrated early burst suppression (phase III). Arterial blood samples were obtained frequently during and after the infusion to measure serum thiopental concentrations, and power spectral analysis was used to calculate the spectral edge (Hz), defined as the frequency below which 95% of the EEG power is located. Pharmacodynamic modeling was used to relate the serum thiopental concentrations to the spectral edge in order to estimate the individual patient's brain sensitivity to thiopental. In a second group (28 patients 24-88 yr of age), pharmacokinetics were determined after a bolus or rapid infusion of thiopental. Arterial blood samples were obtained frequently to characterize the initial distribution phases, sampling continued for 24-48 h to characterize elimination processes. The dose of thiopental required to achieve early burst suppression on the electroencephalogram (EEG) decreased linearly and significantly with age. Pharmacodynamic modeling also demonstrated that brain sensitivity to thiopental does not change with age. The age-related decrease of the thiopental dose requirement is due to a change in the initial distribution of the drug. That is, the initial distribution volume (central compartment, or V1) of thiopental decreases exponentially with age. This smaller initial distribution volume in the elderly results in higher serum levels after a given dose of thiopental.

Adult↗

Adaptive denoising of event-related functional magnetic resonance imaging data using spectral subtraction.

A new adaptive signal-preserving technique for noise suppression in event-related functional magnetic resonance imaging (fMRI) data is proposed based on spectral subtraction. The proposed technique estimates a parametric model for the power spectrum of random noise from the acquired data based on the characteristics of the Rician statistical model. This model is subsequently used to estimate a noise-suppressed power spectrum for any given pixel time course by simple subtraction of power spectra. The new technique is tested using computer simulations and real data from event-related fMRI experiments. The results show the potential of the new technique in suppressing noise while preserving the other deterministic components in the signal. Moreover, we demonstrate that further analysis using principal component analysis and independent component analysis shows a significant improvement in both convergence and clarity of results when the new technique is used. Given its simple form, the new method does not change the statistical characteristics of the signal or cause correlated noise to be present in the processed signal. This suggests the value of the new technique as a useful preprocessing step for fMRI data analysis.

Algorithms↗

Recovery of spectral reflectances of objects being imaged without prior knowledge.

Prior knowledge of the noise present in a color image acquisition device is very important in estimating colorimetric values or in recovering the spectral reflectances of pixels of objects being imaged, since these values are greatly influenced by the noise. In this paper, a new model is proposed for the determination of the noise variance of a multispectral color image acquisition system and experimental results to demonstrate its accuracy are presented. It is demonstrated that the noise variance of an actual multispectral color image acquisition system computed by the proposal agrees fairly well with the variance which minimizes the mean-square error of the recovered reflectances by the Wiener filter. As an application of the proposal, it is shown that spectral reflectances of an art painting are recovered accurately by the use of sensor responses without prior knowledge of objects being imaged and noise present in an image acquisition system.

Algorithms↗

Improvement of color video demosaicking in temporal domain.

Color demosaicking is critical to the image quality of digital still and video cameras that use a single-sensor array. Limited by the mosaic sampling pattern of the color filter array (CFA), color artifacts may occur in a demosaicked image in areas of high-frequency and/or sharp color transition structures. However, a color digital video camera captures a sequence of mosaic images and the temporal dimension of the color signals provides a rich source of information about the scene via camera and object motions. This paper proposes an inter-frame demosaicking approach to take advantage of all three forms of pixel correlations: spatial, spectral, and temporal. By motion estimation and statistical data fusion between adjacent mosaic frames, the new approach can remove much of the color artifacts that survive intra-frame demosaicking and also improve tone reproduction accuracy. Empirical results show that the proposed inter-frame demosaicking approach consistently outperforms its intra-frame counterparts both in peak signal-to-noise measure and subjective visual quality.

Algorithms↗

Anxiety, antisocial behavior, and heart rate regulation in adolescent males.

We explored relationships between anxiety and antisocial behavior and autonomic heart rate regulation in a homogenous sample (N = 175) of 15-year-old males. Measures of anxiety and antisocial behavior were obtained at yearly intervals over a period of 4-6 years. Components of heart rate variability associated with postural (sympathetic) and respiratory (vagal) change and transfer of respiratory to heart rate variability were estimated at age 15 using spectral analytic techniques. Anxiety and antisocial behavior were predictably related to enhanced and diminished levels of mean heart rate, respectively. Anxiety was also predictably related to enhanced sympathetic mediation of phasic postural effects on heart rate. Antisocial behavior was unexpectedly related to disruption of vagally mediated, phasic respiratory effects on heart rate. Anxiety and antisocial behavior showed distinct relationships to heart rate, and to the autonomically mediated components of heart rate variability from postural and respiratory sources. Spectral analytic techniques helped elucidate these unique regulatory patterns, suggesting utility for future research in this area.

Adolescent↗

Foveal cone mosaic and visual pigment density in dichromats.

1. Optical reflectance spectra of the fovea were measured in ten subjects with normal colour vision, ten protanopes and seven deuteranopes. Four conditions were used: perpendicular and oblique angle of incident and reflected light on the retina, both in a dark-adapted and a fully bleached state. 2. The spectra were analysed to assess the effects of dichromacy on the cone mosaic. A replacement model, i.e. one where the total number of cones remains unchanged and all cones are filled with a single type of pigment, was found to fit our data best. 3. The analysis of the spectral fundus reflectance also provided estimates for densities of photo-labile and photo-stable retinal pigments and fraction of long wavelength-sensitive (LWS) cones. Visual pigment density was 0.39 for protanopes and 0.42 for deuteranopes, significantly lower than the 0.57 found for colour normals. Macular pigment density was 0.54 for colour normals, 0.46 for protanopes and 0.42 for deuteranopes. 4. For colour normals the LWS cone fraction was 0.56, in agreement with psychophysical literature. The LWS cone fraction for protanopes was -0.04, and for deuteranopes 0.96, consistent with their Rayleigh matches.

Color Vision Defects↗

Dynamics of frequency and amplitude modulations in vocalizations produced by eastern towhees, Pipilo erythrophthalmus.

Eastern towhees, Pipilo erythrophthalmus (Emberizidae, Passeriformes), appear to estimate source-SPL using spectral or temporal variables. Nevertheless, vocalizations are dynamic by nature and it remains unclear whether subjects pay attention to correlations between discrete variables or pay attention to the dynamics that these variables summarize. Sine functions are used to describe coarse (slow, < 10 Hz) frequency and amplitude modulations in towhee calls and correlations between variables are identified. Towhee calls are also finely (rapidly, > 400 Hz) modulated in both amplitude and frequency. Fine amplitude and frequency modulations correlate well (occur in phase) over relatively low fundamental frequencies (< approximately 3.5 kHz) and tend to have greater amplitudes and frequencies over these same frequencies. Modulations and correlations between modulations might exist due to stable dynamic interactions that occur within and between the physical forces that function to produce modulations in vocalizations. Results support the hypothesis that towhees communicate within separate sound frequency channels defined to each side of approximately 3.5 kHz.

Animals↗

Blood flow in deep abdominal and pelvic vessels: ultrasonic pulsed-Doppler analysis.

Ultrasonic pulsed-Doppler signals from deep-lying vessels in the normal abdomen and pelvis are described. The signal characteristics combine to produce a Doppler "signature" that is specific for each vessel. The clinical potential of this method of deep flow detection is considered in relation to three areas of Doppler signal analysis: first, qualitative indication of the presence, direction, or absence of flow in a structure; second, more quantitative description of time velocity waveforms and Doppler spectral content; and third, the estimation of absolute volume flow. Limitations of these methods for the abdominal signals obtained are discussed.

Abdomen↗

Transfer function analysis of vagal control of heart rate during synchronized vagal stimulation.

Synchronized electrical stimulation was used to study the heart rate (HR) response to fluctuations in parasympathetic input to the sinus node in anesthetized dogs. This was obtained by varying the time interval (interpulse interval) between stimulatory vagal pulses. Spectral methods were used to estimate transfer functions between the excitatory signal and the resulting HR response for different intensities of vagal stimulation. The intensity of vagal stimulation was proportional to the number of pulses delivered in each cardiac cycle. From the estimated transfer functions, and based on a mathematical model of the time course of ACh concentration at the sinus node, filter models were derived by using a system identification approach. HR response was characterized by a combination of two different filter behaviors: a low-pass filter behavior of mean cut-off frequency of 0.065 Hz and an all-pass filter behavior. The magnitude of the low-pass filter gain decreased with increasing intensity of vagal stimulation. The magnitude of the all-pass filter gain increased and then decreased with increasing intensity of vagal stimulation. The all-pass filter characteristics of HR response during synchronized stimulation of the vagus nerves are specific to this mode of stimulation, because they were not observed in nonsynchronized modes of vagal stimulation. We can conclude that, during synchronized vagal stimulation, the HR response exhibits both a slow dynamic component and a fast component related to beat-to-beat variations.

Animals↗