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At least 19 recordsLinked to original sources
PubMed2006

Source-filter comparison of measurements of fundamental frequency perturbation and amplitude perturbation for synthesized voice signals.

SUMMARY: An investigation of the effect of glottal source aperiodicities (jitter, shimmer, and aspiration noise) on the estimation of fundamental frequency (f0) perturbation and amplitude perturbation, of synthesized, glottal source and voiced speech waveforms, is considered. Firstly, 4, cycle-event f0 estimators are examined: (1) waveform matching of the low-pass filtered waveform, (2) positive peaks (PPs) from the speech waveform, (3) PPs from the low-pass filtered waveform, and (4) positive zero crossings from the low-pass filtered waveform. The analysis shows that f0 perturbation measures taken from the low-pass filtered waveform are affected by both amplitude perturbation and random glottal noise, whereas, f0 perturbation measures taken from the PPs of the original waveform are affected by noise but not by amplitude perturbation. It is shown for the low-pass filter methods that the effects of amplitude perturbation and noise lead to increased errors in the measurement of f0 perturbation for the synthesized speech waveforms when compared with the synthesized glottal waveforms. Shimmer of the synthesized speech waveform is approximately equal to shimmer of the synthesized glottal source. However, noise and jitter affect measures of amplitude perturbation. The estimation of f0 perturbation from the synthesized speech waveform is shown to be nonlinearly related to f0 perturbation estimation from the synthesized glottal waveform as a consequence of the filtering action of the vocal tract. Low-pass filtering the voiced speech waveform is shown to provide a partial solution to this problem.

Communication Devices for People with Disabilities↗
PubMed1982

Conformational changes induced by hapten in pig antibodies to the dinitrophenyl group. Analysis by temperature-perturbation and solvent-perturbation spectroscopy.

Pig antibodies to the dinitrophenyl group and fragments derived from them by limited proteolysis were studied by temperature-perturbation and solvent-perturbation spectroscopy with particular attention to differences between the number of perturbed chromophores in free antibodies and in antibody-hapten complexes. The position of the maxima in the difference spectra show that solvent-perturbed chromophores are exposed to water, but thermally perturbed chromophores are located in a microenvironment the polarity of which corresponds to 25-50% ethylene glycol. A significant fraction of tyrosine residues (65-90%) and tryptophan residues (20-45%) is perturbed by temperature. Much lower fractions, i.e. 35-45% of tyrosine residues and less than 15% of tryptophan residues, are perturbed by 20% glycerol. The numbers of perturbed chromophores in fragments constituting the molecule are lower than or equal to the numbers in the original molecule. The effect of hapten binding is significant only with one of the antibody types, the precipitating antibody. The number of thermally perturbed tyrosine residues is by about 17% lower in the liganded antibody. The absence of an analogous effect in the Fab fragment suggests that the fine conformational mechanism of signal transfer from the binding sites operates only in intact antibody molecules.

Animals↗
PubMed2024

Multiome Perturb-seq unlocks scalable discovery of integrated perturbation effects on the transcriptome and epigenome.

Single-cell CRISPR screens link genetic perturbations to transcriptional states, but high-throughput methods connecting these induced changes to their regulatory foundations are limited. Here, we introduce Multiome Perturb-seq, extending single-cell CRISPR screens to simultaneously measure perturbation-induced changes in gene expression and chromatin accessibility. We apply Multiome Perturb-seq in a CRISPRi screen of 13 chromatin remodelers in human RPE-1 cells, achieving efficient assignment of sgRNA identities to single nuclei via an improved method for capturing barcode transcripts from nuclear RNA. We organize expression and accessibility measurements into coherent programs describing the integrated effects of perturbations on cell state, finding that ARID1A and SUZ12 knockdowns induce programs enriched for developmental features. Modeling of perturbation-induced heterogeneity connects accessibility changes to changes in gene expression, highlighting the value of multimodal profiling. Overall, our method provides a scalable and simply implemented system to dissect the regulatory logic underpinning cell state. A record of this paper's transparent peer review process is included in the supplemental information.

Humans↗
PubMed1987

Thermal perturbation studies of membrane-bound acetylcholine receptor from Torpedo: effects of cholinergic ligands and membrane perturbants.

Thermal perturbation techniques have been used to probe structural features of the nicotinic acetylcholine receptor (AcChR). The information obtained from differential scanning calorimetry (DSC) of AcChR membranes (M.C. Farach and M. Martinez-Carrion (1983) J. Biol. Chem. 258, 4176) in the absence and in the presence of cholinergic ligands and local anesthetics, is comparable to that obtained from a simpler technique of heat inactivation of the alpha-bungarotoxin (alpha-Bgt) binding sites on the AcChR protein in similar samples. When AcChR membranes are heated at approximately 1 degree C/min, heat inactivation of toxin binding sites has a characteristic T50 value (temperature at which 50% of the initial capacity to bind alpha-Bgt remains) of approximately 60 degrees C. When heated at a constant temperature during increasing periods of time, the rate at which heat inactivation occurs is also characteristic of the temperature chosen for the experiment. The above thermal parameters are also sensitive to perturbation of the AcChR membrane matrix by the presence of subsolubilizing concentrations of detergents. Moreover, elimination of detergents by dialysis allows us to evaluate the reversibility or irreversibility of AcChR thermal destabilization induced by detergents or other membrane perturbants. Under the experimental conditions used, structural destabilization induced by octylglucoside or cholate can be fully reversed by detergent dialysis, while that exerted by deoxycholate cannot. "Thermal gel" analysis of the aggregation of AcChR subunits induced by heat (G. Soler, J. R. Mattingly, and M. Martinez-Carrion (1984) Biochemistry 23, 4630) has also been used to assess the effects of detergent presence on the AcChR protein. When deoxycholate is used as the perturbing agent, there is a particularly effective sulfhydryl-mediated aggregation of the gamma-delta subunit group, which appears to correlate with the irreversible destabilization of alpha-Bgt binding sites induced by that detergent.

Animals↗
PubMed2004

Is the trunk movement more perturbed after an asymmetric than after a symmetric perturbation during lifting?

Low back injury is associated with sudden movements and loading. Trunk motion after sudden loading depends on the stability of the spine prior to loading and on the trunk muscle activity in response to the loading. Both factors are not axis-symmetric. Therefore, it was hypothesized that the effects on trunk dynamics would be larger after an asymmetric than after a symmetric perturbation. Ten subjects lifted a crate in which, prior to lifting, a mass was displaced to the front or to the side without the subjects being aware of this. Crate and subject movements, crate reaction forces and muscle activity were recorded. From this, the stability prior to the perturbation was estimated, and the trunk angular kinematics and moments at the lumbo-sacral joint were calculated. Both perturbations only minimally affected the trunk kinematics, although the stability of the spine prior to the lifting movement was higher in the sagittal plane than in the frontal plane. In both conditions the stability appeared to be sufficient to absorb the applied perturbation.

Adult↗
PubMedDate not supplied

Perturbations due to the use of catheters with non-perturbing thermometry probes.

Perturbations due to the use of catheters with non-perturbing thermometry probes were investigated in static phantom at 915 MHz. Fibre optic probes for the Luxtron and Clini-Therm thermometry systems, and Vitek probes for the BSD hyperthermia systems, were inserted in closed-end catheters at depths up to 2 cm in the phantom and exposed parallel to the E-field. The probes alone produced 0-12 per cent changes in heating and catheters alone were 0-20 per cent. When the probes were inserted in catheters, perturbations were 0-12 per cent at the surface and 1 cm depth, and 5-15 per cent at 2 cm depth. Even with non-perturbing probes it is important to place catheters perpendicular to the E-field during microwave hyperthermia.

Electromagnetic Fields↗
PubMed2004

Dynamics of a single ion in a perturbed Penning trap: octupolar perturbation.

Imperfections in the design or implementation of Penning traps may give rise to electrostatic perturbations that introduce nonlinearities in the dynamics. In this paper we investigate, from the point of view of classical mechanics, the dynamics of a single ion trapped in a Penning trap perturbed by an octupolar perturbation. Because of the axial symmetry of the problem, the system has two degrees of freedom. Hence, this model is ideal to be managed by numerical techniques like continuation of families of periodic orbits and Poincaré surfaces of section. We find that, through the variation of the two parameters controlling the dynamics, several periodic orbits emanate from two fundamental periodic orbits. This process produces important changes (bifurcations) in the phase space structure leading to chaotic behavior.

Ions↗
PubMed2000

Resummation of QED perturbation series by sequence transformations and the prediction of perturbative coefficients

We propose a method for the resummation of divergent perturbative expansions in quantum electrodynamics and related field theories. The method is based on a nonlinear sequence transformation and uses as input data only the numerical values of a finite number of perturbative coefficients. The results obtained in this way are for alternating series superior to those obtained using Pade approximants. The nonlinear sequence transformation fulfills an accuracy-through-order relation and can be used to predict perturbative coefficients. In many cases, these predictions are closer to available analytic results than predictions obtained using the Pade method.

Journal Article↗
PubMed2001

Enhanced Access to the Dark Triplet States of (7)Li(2) through New Singlet-Triplet A(1)Sigma(+)(u) approximately b(3)Pi(u) Perturbation Window Levels: Perturbation-Facilitated Optical-Optical Double Resonance Study of the 2(3)Sigma(+)(g) State.

Two new pairs of singlet-triplet A(1)Sigma(+)(u) approximately b(3)Pi(u) mixed levels of (7)Li(2) have been observed and used here as "window" levels in cw perturbation-facilitated optical-optical double-resonance (PFOODR) experiments. Previously, only one b(3)Pi(u) vibrational level, v = 19, was known to mix with the singlet A(1)Sigma(+)(u) v = 13 level, resulting in three perturbed A approximately b pairs [L. Li, T. An, T.-J. Whang, A. M. Lyyra, W. C. Stwalley, R. W. Field, and R. A. Bernheim, J. Chem. Phys. 96, 3342 (1992)]. The scarcity of window levels and the resulting difficulty in accessing the dark triplet states of Li(2) is caused by the weak spin-orbit interaction of Li(2). The two new mixed b(3)Pi(u) v = 15 and 22 levels reported here enhance access to the dark triplet state manifold through expansion of the Franck-Condon overlap factor range. Furthermore, the earlier range of accessible rotational levels, N = 5, 7, and 10, is now expanded to include N = 8 and N = 16, thereby allowing for more reliable determination of the excited triplet states rotational structure. To demonstrate the importance of the new A(1)Sigma(+)(u) approximately b(3)Pi(u) mixed levels, we have studied the 2(3)Sigma(+)(g) state by cw PFOODR fluorescence excitation spectroscopy. New molecular constants and RKR potential curve have been determined. As previously reported [L. Li, G. Lazarov, and A. M. Lyyra, J. Mol. Spectrosc. 191, 387 (1998)], the 2(3)Sigma(+)(g) state interacts with the repulsive 1(3)Pi(g) state by L-uncoupling and predissociates. We show that some 2(3)Pi(g) levels predissociate accidentally by the 1(3)Pi(g) state via the 2(3)Sigma(+)(g) state through L-uncoupling. Copyright 2001 Academic Press.

Journal Article↗
PubMed2005

Improved perturbative treatment of electronic energies from a minimal-norm approach to many-body perturbation theory.

We propose a zeroth-order Hamiltonian for many-body perturbation theory based on the unitary decomposition of the two-particle reduced Hamiltonian. For the zeroth-order Hamiltonian constrained to be diagonal in the Hartree-Fock basis set, the two-particle reduced perturbation matrix is chosen to have a minimal Frobenius norm. When compared with the Møller-Plesset partitioning, the method yields more accurate second-order energies.

Journal Article↗
PubMed2006

Third-order multireference perturbation theory: the n-electron valence state perturbation-theory approach.

A formulation of the n-electron valence state perturbation theory (NEVPT) at the third order of perturbation is presented. The present implementation concerns the so-called strongly contracted variant of NEVPT, where only a subspace of the first-order interacting space is taken into account. The resulting strongly contracted NEVPT3 approach is discussed in three test cases: (a) the energy difference between the 3B1 and 1A1 states of the methylene molecule, (b) the potential-energy curve of the N2 molecule ground state, and (c) the chromium dimer (Cr2) ground-state potential-energy profile. Particular attention is devoted to the last case where large basis sets comprising also h orbitals are adopted and where remarkable differences between the second- and third-order results show up.

Journal Article↗
PubMed2000

Perturbation of EGF-activated MEK1 and PKB signal pathways by TGF-beta1 correlates with perturbation of EGF-induced cyclin D1 and DNA synthesis by TGF-beta1 in C3H 10T1/2 cells.

In mouse C3H 10T1/2 cells, we previously reported that TGF-beta1 first delays and later potentiates EGF-induced DNA synthesis corresponding to an inhibition of EGF-induced cyclin D1 expression at t = 13 h. We report here that in accord with DNA synthesis kinetics, TGF-beta1 initially suppresses EGF-induced cyclin D1 expression then later releases the inhibition. Furthermore, TGF-beta1 also first decreases and later potentiates the levels of EGF-activated MEK1/MAPK and PKB, indicating the existence of cross talk between TGF-beta 1- and EGF-activated signal transduction pathways. PD98059, the specific inhibitor of MEK1, significantly blocks EGF-induced DNA synthesis, whereas wortmannin, the PI3K inhibitor, exerts a modest inhibitory effect, which suggests that the activation of MEK1-MAPK pathway plays a major role in EGF-induced DNA synthesis and the activation of PI3K-PKB pathway plays a minor role. Upon examination of mechanisms underlying the cross talk, it was discovered that application of TGF-beta1 triggers a rapid association between Raf-1 and catalytic subunits of PKA, which are reported to be able to inactivate Raf-1 upon activation. Therefore, TGF-beta1 may activate PKA to inhibit the EGF-activated MEK1-MAPK pathway. The wortmannin-sensitive phosphorylation at the thr(389) site is necessary for activation of p70s6K, an important kinase involved in mitogen-stimulated protein synthesis. Although we found that EGF-stimulated p70s6K phosphorylates through a MAPK-dependent and a MAPK-independent (wortmannin-sensitive) pathway, TGF-beta1 failed to block EGF-triggered phosphorylation of p70s6K at thr(389) and thr(421)/ser(424) sites, implying that PKB inhibition by TGF-beta1 may result from inhibition of PDK1 activity instead of inhibition of PI3K activity. These data also suggest that TGF-beta1 may selectively perturb certain EGF-activated MAPK pools.

Animals↗
PubMed1988

In Vivo Perturbation of Membrane-Associated Calcium by Freeze-Thaw Stress in Onion Bulb Cells : Simulation of This Perturbation in Extracellular KCl and Alleviation by Calcium.

Incipient freeze-thaw stress in onion bulb scale tissue is known to cause enhanced efflux of K(+), along with small but significant loss of cellular Ca(2+). During the post-thaw period, irreversibly injured cells undergo a cytological aberration, namely, ;protoplasmic swelling.' This cellular symptom is thought to be caused by replacement of Ca(2+) from membrane by extracellular K(+) and subsequent perturbation of K(+) transport properties of plasma membrane. In the present study, onion (Allium cepa L. cv Sweet Sandwich) bulbs were slowly frozen to either -8.5 degrees C or -11.5 degrees C and thawed over ice. Inner epidermal peels from bulb scales were treated with fluorescein diacetate for assessing viability. In these cells, membrane-associated calcium was determined using chlorotetracycline fluorescence microscopy combined with image analysis. Increased freezing stress and tissue infiltration (visual water-soaking) were paralleled by increased ion leakage. Freezing injury (-11.5 degrees C; irreversible) caused a specific and substantial loss of membrane-associated Ca(2+) compared to control. Loss of membrane-associated Ca(2+) caused by moderate stress (-8.5 degrees C; reversible) was much less relative to -11.5 degrees C treatment. Ion efflux and Ca(2+)-chlorotetracycline fluorescence showed a negative relationship. Extracellular KCl treatment simulated freeze-thaw stress by causing a similar loss of membrane-associated calcium. This loss was dramatically reduced by presence of extracellular CaCl(2). Our results suggest that the loss of membrane-associated Ca(2+), in part, plays a role in initiation and progression of freezing injury.

Journal Article↗
PubMed1995

Probing protein structure by solvent perturbation of NMR spectra. Photochemically induced dynamic nuclear polarization and paramagnetic perturbation techniques applied to the study of the molten globule state of alpha-lactalbumin.

We have characterized the high-temperature molten globule state of bovine alpha-lactalbumin by a combined use of photochemically induced dynamic nuclear polarization and nitroxide surface perturbation. Both techniques are extremely well suited to follow the progressive increase of exposed surfaces in the native state and the appearance of partially or completely unfolded species. Our results suggest that the molten globule state obtained at high temperature and pH 7, and the state obtained at pH 2 are not only thermodynamically but also structurally very similar.

Animals↗
PubMed2006

Perturbation of auditory feedback causes systematic perturbation in vocal structure in adult cotton-top tamarins.

Auditory feedback is critical for the development and maintenance of speech in humans. In contrast, studies of nonhuman primate vocal production generally report that subjects show little reliance on auditory input. We examined the extent to which cotton-top tamarin (Saguinus oedipus) vocal production is sensitive to perturbation of auditory feedback by manipulating the predictability of presentation of a 1 s burst of white noise during the production of the species-specific contact call, the combination long call (CLC). We used three experimental conditions: the Begin condition, in which white noise was presented only during the first half of a recording session, the End condition, in which white noise was presented only in the last half, and the Random condition, in which each call had a 50% probability of receiving white noise playback throughout the recording session, making the auditory feedback unpredictable. In addition we recorded calls before and after the experimental series (Baseline condition) to determine whether any changes induced by modification of auditory feedback persisted. Results showed that playback of white noise during the production of the CLC produced changes in the temporal structure of the CLC: calls were shorter and had fewer pulses, indicating that modification of auditory feedback can interrupt vocal production. In addition, calls that received modified feedback were louder and had longer inter-pulse intervals than those that did not, consistent with an adaptive response to the masking effect of white noise playback. The magnitude of this compensatory effect and the interruption rate were both sensitive to whether the feedback modification occurred at the beginning or end of the experimental session: early feedback produced less interruption and more compensation. Finally, when auditory feedback modification was unpredictable, adaptive changes were observed in both calls that received modified feedback and those that received normal feedback, suggesting that tamarins can generate an expectation of noise playback and increase vocal amplitude in anticipation of masking.

Acoustic Stimulation↗