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At least 37 records · Page 2

Long-range correlation properties of coding and noncoding DNA sequences: GenBank analysis

An open question in computational molecular biology is whether long-range correlations are present in both coding and noncoding DNA or only in the latter. To answer this question, we consider all 33301 coding and all 29453 noncoding eukaryotic sequences--each of length larger than 512 base pairs (bp)--in the present release of the GenBank to dtermine whether there is any statistically significant distinction in their long-range correlation properties. Standard fast Fourier transform (FFT) analysis indicates that coding sequences have practically no correlations in the range from 10 bp to 100 bp (spectral exponent beta=0.00 +/- 0.04, where the uncertainty is two standard deviations). In contrast, for noncoding sequences, the average value of the spectral exponent beta is positive (0.16 +/- 0.05) which unambiguously shows the presence of long-range correlations. We also separately analyze the 874 coding and the 1157 noncoding sequences that have more than 4096 bp and find a larger region of power-law behavior. We calculate the probability that these two data sets (coding and noncoding) were drawn from the same distribution and we find that it is less than 10(-10). We obtain independent confirmation of these findings using the method of detrended fluctuation analysis (DFA), which is designed to treat sequences with statistical heterogeneity, such as DNA's known mosaic structure ("patchiness") arising from the nonstationarity of nucleotide concentration. The near-perfect agreement between the two independent analysis methods, FFT and DFA, increases the confidence in the reliability of our conclusion.

Non-NASA Center↗

Monitoring physical and chemical parameters of Delaware Bay waters with an ERTS-1 data collection platform

The author has identified the following significant results. Results of the analysis of data collected during the summer of 1974 demonstrate that the ERTS Data Collection Platform (DCP) is quite responsive to changing water parameters and that this information can be successfully transmitted under all weather conditions. The monitoring of on-site probe outputs reveals a rapid response to changing water temperature, salinity, and turbidity conditions on incoming tides as the tidal salt wedge passes the probe location. The changes in water properties were corroborated by simultaneously sampling the water for subsequent laboratory analysis. Fluctuations observed in the values of salinity, conductivity, temperature and water depth over short time intervals were extremely small. Due to the nature of the probe, 10% to 20% fluctuations were observed in the turbidity values. The use of the average of the values observed during an overpass provided acceptable results. Good quality data was obtained from the satellite on each overpass regardless of weather conditions. Continued use of the DCP will help provide an indication of the accuracy of the probes and transmission system during long term use.

Klemas, V.↗

The origin of the diffuse X-ray background

The Einstein Deep Survey fields are used to reexamine the problem of the origin of the extragalactic diffuse X-ray background. An approach based on fluctuation analysis is adopted, and a sophisticated Monte Carlo scheme is used to compare the X-ray images with a variety of models representing point and diffuse source contributions. Results are presented for two classes of models: those which determine the flux cutoff beyond which pointlike sources fail to contribute significantly if the log N-log S slope is fixed at the measured value of -1.5, and those which set limits on the slope of the log N-log S relation below its last measured point at the Deep Survey threshold. In both cases, it is found that the known population of X-ray-emitting quasars and any reasonable extrapolations therefrom do not comprise the entire X-ray background.

Hamilton, T. T.↗

Methylation of p16(INK4a) promoters occurs in vivo in histologically normal human mammary epithelia

Cultures of human mammary epithelial cells (HMECs) contain a subpopulation of variant cells with the capacity to propagate beyond an in vitro proliferation barrier. These variant HMECs, which contain hypermethylated and silenced p16(INK4a) (p16) promoters, eventually accumulate multiple chromosomal changes, many of which are similar to those detected in premalignant and malignant lesions of breast cancer. To determine the origin of these variant HMECs in culture, we used Luria-Delbruck fluctuation analysis and found that variant HMECs exist within the population before the proliferation barrier, thereby raising the possibility that variant HMECs exist in vivo before cultivation. To test this hypothesis, we examined mammary tissue from normal women for evidence of p16 promoter hypermethylation. Here we show that epithelial cells with methylation of p16 promoter sequences occur in focal patches of histologically normal mammary tissue of a substantial fraction of healthy, cancer-free women.

NASA Discipline Radiation Health↗

Statistical properties of DNA sequences

We review evidence supporting the idea that the DNA sequence in genes containing non-coding regions is correlated, and that the correlation is remarkably long range--indeed, nucleotides thousands of base pairs distant are correlated. We do not find such a long-range correlation in the coding regions of the gene. We resolve the problem of the "non-stationarity" feature of the sequence of base pairs by applying a new algorithm called detrended fluctuation analysis (DFA). We address the claim of Voss that there is no difference in the statistical properties of coding and non-coding regions of DNA by systematically applying the DFA algorithm, as well as standard FFT analysis, to every DNA sequence (33301 coding and 29453 non-coding) in the entire GenBank database. Finally, we describe briefly some recent work showing that the non-coding sequences have certain statistical features in common with natural and artificial languages. Specifically, we adapt to DNA the Zipf approach to analyzing linguistic texts. These statistical properties of non-coding sequences support the possibility that non-coding regions of DNA may carry biological information.

Non-NASA Center↗

Statistical and linguistic features of DNA sequences

We present evidence supporting the idea that the DNA sequence in genes containing noncoding regions is correlated, and that the correlation is remarkably long range--indeed, base pairs thousands of base pairs distant are correlated. We do not find such a long-range correlation in the coding regions of the gene. We resolve the problem of the "non-stationary" feature of the sequence of base pairs by applying a new algorithm called Detrended Fluctuation Analysis (DFA). We address the claim of Voss that there is no difference in the statistical properties of coding and noncoding regions of DNA by systematically applying the DFA algorithm, as well as standard FFT analysis, to all eukaryotic DNA sequences (33 301 coding and 29 453 noncoding) in the entire GenBank database. We describe a simple model to account for the presence of long-range power-law correlations which is based upon a generalization of the classic Levy walk. Finally, we describe briefly some recent work showing that the noncoding sequences have certain statistical features in common with natural languages. Specifically, we adapt to DNA the Zipf approach to analyzing linguistic texts, and the Shannon approach to quantifying the "redundancy" of a linguistic text in terms of a measurable entropy function. We suggest that noncoding regions in plants and invertebrates may display a smaller entropy and larger redundancy than coding regions, further supporting the possibility that noncoding regions of DNA may carry biological information.

Non-NASA Center↗

Quantification of scaling exponents and crossover phenomena in nonstationary heartbeat time series

The healthy heartbeat is traditionally thought to be regulated according to the classical principle of homeostasis whereby physiologic systems operate to reduce variability and achieve an equilibrium-like state [Physiol. Rev. 9, 399-431 (1929)]. However, recent studies [Phys. Rev. Lett. 70, 1343-1346 (1993); Fractals in Biology and Medicine (Birkhauser-Verlag, Basel, 1994), pp. 55-65] reveal that under normal conditions, beat-to-beat fluctuations in heart rate display the kind of long-range correlations typically exhibited by dynamical systems far from equilibrium [Phys. Rev. Lett. 59, 381-384 (1987)]. In contrast, heart rate time series from patients with severe congestive heart failure show a breakdown of this long-range correlation behavior. We describe a new method--detrended fluctuation analysis (DFA)--for quantifying this correlation property in non-stationary physiological time series. Application of this technique shows evidence for a crossover phenomenon associated with a change in short and long-range scaling exponents. This method may be of use in distinguishing healthy from pathologic data sets based on differences in these scaling properties.

NASA Discipline Number 14-10↗

Cardiac interbeat interval dynamics from childhood to senescence : comparison of conventional and new measures based on fractals and chaos theory

BACKGROUND: New methods of R-R interval variability based on fractal scaling and nonlinear dynamics ("chaos theory") may give new insights into heart rate dynamics. The aims of this study were to (1) systematically characterize and quantify the effects of aging from early childhood to advanced age on 24-hour heart rate dynamics in healthy subjects; (2) compare age-related changes in conventional time- and frequency-domain measures with changes in newly derived measures based on fractal scaling and complexity (chaos) theory; and (3) further test the hypothesis that there is loss of complexity and altered fractal scaling of heart rate dynamics with advanced age. METHODS AND RESULTS: The relationship between age and cardiac interbeat (R-R) interval dynamics from childhood to senescence was studied in 114 healthy subjects (age range, 1 to 82 years) by measurement of the slope, beta, of the power-law regression line (log power-log frequency) of R-R interval variability (10(-4) to 10(-2) Hz), approximate entropy (ApEn), short-term (alpha(1)) and intermediate-term (alpha(2)) fractal scaling exponents obtained by detrended fluctuation analysis, and traditional time- and frequency-domain measures from 24-hour ECG recordings. Compared with young adults (<40 years old, n=29), children (<15 years old, n=27) showed similar complexity (ApEn) and fractal correlation properties (alpha(1), alpha(2), beta) of R-R interval dynamics despite lower spectral and time-domain measures. Progressive loss of complexity (decreased ApEn, r=-0.69, P<0.001) and alterations of long-term fractal-like heart rate behavior (increased alpha(2), r=0.63, decreased beta, r=-0.60, P<0.001 for both) were observed thereafter from middle age (40 to 60 years, n=29) to old age (>60 years, n=29). CONCLUSIONS: Cardiac interbeat interval dynamics change markedly from childhood to old age in healthy subjects. Children show complexity and fractal correlation properties of R-R interval time series comparable to those of young adults, despite lower overall heart rate variability. Healthy aging is associated with R-R interval dynamics showing higher regularity and altered fractal scaling consistent with a loss of complex variability.

NASA Discipline Cardiopulmonary↗

Mosaic organization of DNA nucleotides

Long-range power-law correlations have been reported recently for DNA sequences containing noncoding regions. We address the question of whether such correlations may be a trivial consequence of the known mosaic structure ("patchiness") of DNA. We analyze two classes of controls consisting of patchy nucleotide sequences generated by different algorithms--one without and one with long-range power-law correlations. Although both types of sequences are highly heterogenous, they are quantitatively distinguishable by an alternative fluctuation analysis method that differentiates local patchiness from long-range correlations. Application of this analysis to selected DNA sequences demonstrates that patchiness is not sufficient to account for long-range correlation properties.

NASA Discipline Number 14-10↗

Predicting survival in heart failure case and control subjects by use of fully automated methods for deriving nonlinear and conventional indices of heart rate dynamics

BACKGROUND: Despite much recent interest in quantification of heart rate variability (HRV), the prognostic value of conventional measures of HRV and of newer indices based on nonlinear dynamics is not universally accepted. METHODS AND RESULTS: We have designed algorithms for analyzing ambulatory ECG recordings and measuring HRV without human intervention, using robust methods for obtaining time-domain measures (mean and SD of heart rate), frequency-domain measures (power in the bands of 0.001 to 0.01 Hz [VLF], 0.01 to 0.15 Hz [LF], and 0.15 to 0.5 Hz [HF] and total spectral power [TP] over all three of these bands), and measures based on nonlinear dynamics (approximate entropy [ApEn], a measure of complexity, and detrended fluctuation analysis [DFA], a measure of long-term correlations). The study population consisted of chronic congestive heart failure (CHF) case patients and sex- and age-matched control subjects in the Framingham Heart Study. After exclusion of technically inadequate studies and those with atrial fibrillation, we used these algorithms to study HRV in 2-hour ambulatory ECG recordings of 69 participants (mean age, 71.7+/-8.1 years). By use of separate Cox proportional-hazards models, the conventional measures SD (P<.01), LF (P<.01), VLF (P<.05), and TP (P<.01) and the nonlinear measure DFA (P<.05) were predictors of survival over a mean follow-up period of 1.9 years; other measures, including ApEn (P>.3), were not. In multivariable models, DFA was of borderline predictive significance (P=.06) after adjustment for the diagnosis of CHF and SD. CONCLUSIONS: These results demonstrate that HRV analysis of ambulatory ECG recordings based on fully automated methods can have prognostic value in a population-based study and that nonlinear HRV indices may contribute prognostic value to complement traditional HRV measures.

Non-NASA Center↗

Degree Of Diminution In Vagal-Cardiac Activity Predicts Sudden Death In Familial Dysautonomia When Resting Tachycardia Is Absent

Patients with familial dysautonomia (FD) have an increased risk of sudden death, but sensitive and specific predictors of sudden death in FD are lacking. Methods. We recorded 10-min resting high-fidelity 12-lead ECGs in 14 FD patients and in 14 age/gender-matched healthy subjects and studied 25+ different heart rate variability (HRV) indices for their ability to predict sudden death in the FD patients. Indices studied included those from 4 "nonlinear" HRV techniques (detrended fluctuation analysis, approximate entropy, correlation dimension, and PoincarC analyses). The predictive value of PR, QRS, QTc and JTc intervals, QT dispersion (QTd), beat-to-beat QT and PR interval variability indices (QTVI and PRVI) and 12- lead high frequency QRS ECG (150-250 Hz) were also studied. FD patients and controls (C) differed (Pless than 0.0l) with respect to 20+ of the HRV indices (FD less than C) and with respect to QTVI and PRVI (FDBC) and HF QRS- related root mean squared voltages (FDBC) and reduced amplitude zone counts (FD less than C). They differed less with respect to PR intervals (FD less than C) and JTc intervals (FD greater than C) (P less than 0.05 for both) and did not differ at all with respect to QRS and QTc intervals and to QTd. Within 12 months after study, 2 of the 14 patients succumbed to sudden cardiac arrest. The best predictor of sudden death was the degree of diminution in HRV vagal-cardiac (parasympathetic) parameters such as RMSSD, the SDl of Poincare plots, and HF spectral power. Excluding the two FD patients who had resting tachycardia (HR greater than 100, which confounds traditional HRV analyses), the following criteria were independently 100% sensitive and 100% specific for predicting sudden death in the remaining 12 FD patients during spontaneous breathing: RMSSD less than 13 ms and/or PoincarC SD1 less than 9 ms. In FD patients without supine tachycardia, the degree of diminution in parasympathetic HRV parameters (by high-fidelity ECG) predicts incipient death.

Schlegel, T. T.↗

Spectral analysis of magnetohydrodynamic fluctuations near interplanetary shocks

Preliminary results of an investigation of magnetic fluctuations seen upstream of two interplanetary shocks are presented. The spectral analysis includes calculation of the normalized reduced magnetic helicity spectrum, the normalized reduced cross-helicity spectrum, and the Alfven ratio as discussed by Matthaeus and Goldstein (1982). Minimum variance methods are used to compute wave polarization as a function of frequency. The Taylor 'frozen in flow' hypothesis is assumed to convert frequencies to wave vectors. Some of the basic properties of the waves, including the probable mode of propagation in association with both quasi-parallel forward and reverse shocks, are described. A comparison with previous results on the generation of waves at interplanetary and planetary shocks is presented.

Vinas, A. F.↗

Spectral analysis of magnetohydrodynamic fluctuations near interplanetary schocks

Evidence for two types of relatively large amplitude MHD waves upstream and downstream of quasi-parallel forward and reverse interplanetary shocks is presented. The first mode is an Alfven wave with frequencies (in the spacecraft frame) in the range of 0.025 to 0.07 Hz. This is a left-hand polarized mode and propagates within a few degrees of the ambient magnetic field. The second is a fast MHD mode with frequencies in the range of 0.025 to 0.17 Hz, right-hand polarization and propagating along the magnetic field. These waves are detected principally in association with quasi-parallel shock. The Alfven waves are found to have plasma rest frame frequencies in the range of 1.1 to 6.3 mHz with wavelengths in the order of 4.8 x 10 to the 8th power to 2.7 x 10 to the 9th power cm. Similarly, the fast MHD modes have rest frame frequencies in the range 1.6 to 26 mHz with typical wavelengths about 2.19 x 10 to the 8th power cm. The magnetic field power spectrum in the vicinity of these interplanetary shocks is much steeper than f to the -s/3 at high frequencies. The observed spectra have a high frequency dependence of f to the -2/5 to f to the -4.

Vinas, A. F.↗

Termination shock response to large-scale solar wind fluctuations

The analysis of data recorded by the Voyager 2 spacecraft indicates the presence of large-scale fluctuations in the solar wind ram pressure on the time scale of tens of days. The amplitude of the fluctuations is highly variable but often lies within a factor of 5 to 10 change from an average or mean value of the ram pressure. Since the spacecraft has presumably not encountered the termination shock yet, these fluctuations should eventually interact with the shock and thereby play a role in determining the shock location. Numerical solutions of the time-dependent gasdynamic equations are used to simulate the response of the termination shock to fluctuations in the solar wind ram pressure comparable to those observed. The primary result of this study is that the maximum shock excursion due to the fluctuations is of the order of 1 AU, which is much smaller than that predicted by other studies. Additional simulations show that the limited movement is due to the fact that the time scale for the termination shock response is substantially larger than the time scale of the fluctuations. It is also shown that the heliopause acts as a barrier for the fluctuations and confines them to the heliosphere.

Steinolfson, R. S.↗

Termination shock response to large-scale solar wind fluctuations

The analysis of data recorded by the Voyager 2 spacecraft indicates the presence of large-scale fluctuations in the solar wind ram pressure on the time scale of tens of days. The amplitude of the fluctuations is highly variable but often lies within a factor of 5 to 10 change from an average or mean value of the ram pressure. Since the spacecraft has presumably not encountered the termination shock yet, these fluctuations should eventually interact with the shock and thereby play a role in determining the shock location. Numerical solutions of the time-dependent gas dynamic equations are used to simulate the response of the termination shock to fluctuations in the solar wind ram pressure comparable to those observed. The primary result of this study is that the maximum shock excursion due to the fluctuations is of the order of 1 AU, which is much smaller than that predicted by other studies. Additional simulations show that the limited movement is due to the fact that the time scale for the termination shock response is substantially larger than the time scale of the fluctuations. It is also shown that the heliopause acts as a barrier for the fluctuations and confines them to the heliosphere.

Steinolfson, R. S.↗

An analysis of solar wind fluctuations between 1 and 10 AU

A cross-correlation analysis between different parameters of the solar wind plasma based on Voyager 1 and 2 data from 1 to 9.5 AU evidences a persistent presence of time periods characterized by high anitcorrelation between the magnetic field magnitude and the proton density. These events are present at least 25 percent of the total time, and their frequency of occurrence progressively increases with increasing heliocentric distance. These results have been satisfactorily interpreted as being due to the presence of nonpropagating structures with internal pressure balance and characteristic time scale of less than about 10 hours. Alfvenic fluctuations are confirmed to dominate the microscale at 1-2 AU, but they seem to become less important at larger heliocentric distances.

Vellante, M.↗