Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “modulators”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources
PubMed2000

Intensity modulation delivery techniques: "step & shoot" MLC auto-sequence versus the use of a modulator.

Two intensity modulation radiotherapy (IMRT) delivery systems, the "step & shoot" multileaf collimator (MLC) auto-sequence and the use of an intensity modulator, are compared with emphasis on the dose optimization quality and the treatment irradiation time. The intensity modulation (IM) was created by a dose gradient optimization algorithm which maximizes the target dose uniformity while maintaining dose to critical structures below a set tolerance defined by the user in terms of either a single dose value or a dose volume histogram curve for each critical structure. Two clinical cases were studied with and without dose optimization: a three-field sinus treatment and a six-field nasopharyngeal treatment. The optimization goal of the latter case included the sparing of several nearby normal structures in addition to the target dose uniformity. In both cases, the target dose uniformity initially improved quickly as the IM level increased to 5, then started to approach saturation when the MLC technique was used. In the absence of the both space and intensity discreteness intrinsic to the MLC technique, the modulator technique produced greater tumor dose uniformity and normal structure sparing. The latter showed no systematic improvement with increasing IM level using the MLC technique. For the sinus tumor treatment of 2 Gy the treatment irradiation time of the modulator technique is no more than that of the conventional treatment. For the MLC technique the irradiation time increased rapidly from 4.4 min to 12.4 min as the IM level increased from 2 to 10. Both clinical cases suggested that an IM level of 5 offered a good compromise between the dose optimization quality and treatment irradiation time. We showed that a realistic photon source model is necessary for dose computation accuracy in the MLC-IM treatments.

Algorithms↗
PubMed1997

Masking by modulated and unmodulated noise: effects of bandwidth, modulation rate, signal frequency, and masker level.

The threshold for a sinusoidal signal masked by a band of noise is often times lower when the masking noise is modulated than when it is unmodulated. The difference in masked thresholds is referred to as the modulated-unmodulated difference, or MUD. These present experiments examined the effects of masker bandwidth, masker rate, and masker level on the MUD at several different signal frequencies. The MUD generally increased with increasing masker bandwidth; for masker bandwidths wider than a critical band (or an equivalent rectangular bandwidth-ERB), the results may be influenced by across-channel processes underlying comodulation masking release. The MUD for an ERB masker (MUDERB) was influenced less by masker rate than was the MUD for a broadband (BB) masker (MUDBB). The MUDERB and especially the MUDBB increased significantly with increasing masker level when the modulated masker was modulated at a depth (m) of 1.0, but not when it was modulated at a depth of 0.75. These results have significant implications for extending the MUD paradigm to hearing-impaired subjects. Finally, the MUDERB and the MUDBB increased with increasing signal frequency. This effect for the ERB masker is largely (if not completely) due to the wider absolute bandwidths at higher frequencies. The effect with the BB masker may be influenced by differences in the magnitude of suppression across frequency.

Adult↗
PubMed1997

The modulated-unmodulated difference: effects of signal frequency and masker modulation depth.

The masked threshold for a signal is often times lower when the masker is modulated than when it is unmodulated. The difference in masked thresholds is referred to as the modulated-unmodulated difference, or MUD. The purpose of the present study was to follow up on the results of a previous study [Bacon et al., J. Acoust. Soc. Am. 101, 1600-1610 (1997)] which showed that the MUD is larger for high than for low signal frequencies, both when the masker is no wider than a critical band (and the processing is solely within channel) and when it is broadband (and the processing may be both within and across channel). The present results indicate that the effects of signal frequency primarily exist only when the modulated masker is modulated at a depth greater than about 0.75, and that at these large depths, thresholds in the presence of the modulated masker are governed largely by forward masking. By far, the effect of signal frequency is larger with the broadband masker than with the critical-band masker, suggesting that there may be an across-channel process whose contribution is greater at high than at low signal frequencies. It is argued here that this across-channel process may be related to psychophysical suppression.

Adult↗
PubMed2000

The effect of modulation rate on the detection of frequency modulation and mistuning of complex tones.

Experiment 1 measured frequency modulation detection thresholds (FMTs) for harmonic complex tones as a function of modulation rate. Six complexes were used, with fundamental frequencies (F0s) of either 88 or 250 Hz, bandpass filtered into a LOW (125-625 Hz), MID (1375-1875 Hz) or HIGH (3900-5400 Hz) frequency region. The FMTs were about an order of magnitude greater for the three complexes whose harmonics were unresolved by the peripheral auditory system (F0 = 88 Hz in the MID region and both F0s in the HIGH region) than for the other three complexes, which contained some resolved harmonics. Thresholds increased with increases in FM rate above 2 Hz for all conditions. The increase was larger when the F0 was 88 Hz than when it was 250 Hz, and was also larger in the LOW than in the MID and HIGH regions. Experiment 2 measured thresholds for detecting mistuning produced by modulating the F0s of two simultaneously presented complexes out of phase by 180 degrees. The size of the resulting mistuning oscillates at a rate equal to the rate of FM applied to the two carriers. At low FM rates, thresholds were lowest when the harmonics were either resolved for both complexes or unresolved for both complexes, and highest when resolvability differed across complexes. For pairs of complexes with resolved harmonics, mistuning thresholds increased dramatically as the FM rate was increased above 2-5 Hz, in a way which could not be accounted for by the effect of modulation rate on the FMTs for the individual complexes. A third experiment, in which listeners detected constant ("static") mistuning between pairs of frequency-modulated complexes, provided evidence that this deterioration was due the harmonics in one of the two "resolved" complexes becoming unresolved at high FM rates, when analyzed over some finite time window. It is concluded that the detection of time-varying mistuning between groups of harmonics is limited by factors that are not apparent in FM detection data.

Adult↗
PubMed2000

An analysis of quasi-frequency-modulated noise and random-sideband noise as comparisons for amplitude-modulated noise.

Experiments were performed to determine under what conditions quasi-frequency-modulated (QFM) noise and random-sideband noise are suitable comparisons for AM noise in measuring a temporal modulation transfer function (TMTF). Thresholds were measured for discrimination of QFM from random-sideband noise and AM from QFM noise as a function of sideband separation. In the first experiment, the upper spectral edge of the noise stimuli was at 2400 Hz and the bandwidth was 1600 Hz. For sideband separations up to 256 Hz, at threshold sideband levels for discriminating AM from QFM noise, QFM was indiscriminable from random-sideband noise. For the largest sideband separation used (512 Hz), listeners may have used within-stimulus envelope correlation in the QFM noise to discriminate it from the random-sideband noise. Results when stimulus bandwidth was varied suggest that listeners were able to use this cue when the carrier was wider than a critical band, and the sideband separation approached the carrier bandwidth. Within-stimulus envelope correlation was also present in AM noise, and thus QFM noise was a suitable comparison because it made this cue unusable and forced listeners to use across-stimulus envelope differences. When the carrier bandwidth was less than a critical band or was wideband, QFM noise and random-sideband noise were equally suitable comparisons for AM noise. When discrimination thresholds for QFM and random-sideband noise were converted to modulation depth and modulation frequency, they were nearly identical to those for discrimination of AM from QFM noise, suggesting that listeners were using amplitude modulation cues in both cases.

Adult↗
PubMed2003

Neuromuscular modulation in Aplysia. II. Modulation of the neuromuscular transform in behavior.

In this work we use mathematical modeling and complementary experiments to study the dynamics of modulation in the accessory radula closer (ARC) neuromuscular system of Aplysia. Here we join a dynamic model of the modulation from the preceding paper to a model of the basal neuromuscular transform (NMT). The resulting complete model of the NMT allows us to predict, test, and analyze the actual modulated contraction shapes in different types of feeding behavior, through entire quasi-realistic meals. The model reproduces a variety of published and new experimental observations. We find that components of the modulatory network act in interdependency and mutual complementarity, one or another playing a key role depending on the behavior and its past history. The history is remembered by slow dynamical components whose persistence prepares the system for future behavior of the same kind. The persistence becomes counterproductive, however, when the behavior suddenly changes. Superposition of fast dynamical components alleviates the problem under most, but not all, circumstances. In the quasi-realistic meals, the modulation improves functional performance on average, but degrades it after certain behavioral switches, when the model predicts sharp contraction transients. These are indeed seen in the real muscle. We propose that the real system does not switch the underlying motor neuron firing patterns abruptly, but relaxes them gradually, matching the relaxation of the peripheral modulatory state, through such behavioral transitions. We model food-induced arousal, a known phenomenon of this kind. The peripheral dynamics of the modulated NMT thus constrain the motor commands of the CNS.

Animals↗
PubMed2003

Complex modulation with a twisted-nematic liquid-crystal spatial light modulator: double-pixel approach.

I modify the double-phase holographic code to implement complex modulation with a transmission twisted-nematic liquid-crystal display. This device is employed in the mostly phase configuration, for which the phase modulation is coupled with a nonconstant amplitude modulation. The modified double-phase code implements arbitrary complex modulation employing the constrained complex modulation of the display.

Journal Article↗
PubMed1993

Distinctness of perceived three-dimensional form induced by modulated illumination: effects of certain display and modulation conditions.

The present study concerns the distinctness of the 3-D shape induced on flat displays by space-modulated illumination ("shape from shading"). The displays that we used varied in structure, hue contrast, lightness contrast, and in the number of reflectance edges present. The modulations of the illumination were a square-wave grating, a gradual modulation (a blurred grating), and an "O'Brien modulation," which combines an edge and a gradient. The displays were compared, using the paired comparison method, as to the distinctness of the perceived 3-D form. The results showed that the structure and chromatic color of the display were important factors facilitating the distinctness of the induced 3-D shape under all the modulation conditions. The results are discussed in relation to the "vector model" for color constancy, proposed in earlier papers.

Adult↗
PubMed1978

The modulator-dependent protein kinase. A multifunctional protein kinase activatable by the Ca2+-dependent modulator protein of the cyclic nucleotide system.

A protein kinase which depends on the simultaneous presence of Ca2+ and the modulator protein for its histone phosphorylation activity has been demonstrated in rabbit skeletal muscle and partially purified. The purified enzyme was not activated by cAMP, cGMP, or incubation with trypsin. Nor was the enzyme inhibited by the protein inhibitor of cAMP-dependent protein kinase. In addition to histone, myosin light chains and phosphorylase kinase served as substrates for the protein kinase, and their phosphorylation also depended on the presence of Ca2+ and the modulator protein. The phosphorylation of phosphorylase kinase was accompanied with a marked activation of the enzyme. The results suggest that the protein kinase has multiple functions and may be involved in the mediation of Ca2+ effects in many biological processes. It is proposed that this enzyme be designated as the modulator-dependent protein kinase. The modulator-dependent protein kinase may be identical to the myosin light chain kinase; chicken gizzard light chain kinase has been shown activatable by the modulator protein (Dabrowska, R., Sherry, J. M. F., Aramatorio, D. K., and Hartshorne, D. J. (1978) Biochemistry 17, 253-258).

Animals↗
PubMed1996

Extending double modulation: combinatorial rules for identifying the modulations necessary for determining elasticities in metabolic pathways.

The double modulation method for determining the elasticities of pathway enzymes, originally devised by Kacser & Burns (Biochem. Soc. Trans. 7, 1149-1160, 1979), is extended to pathways of complex topological structure, including branching and feedback loops. An explicit system of linear equations for the unknown elasticities is derived. The constraints imposed on this linear system imply that modulations of more than one enzyme are not necessarily independent. Simple combinatorial rules are described for identifying without using any algebra the set of independent modulations that allow the determination of the elasticities of any enzyme. By repeated application, the minimum numbers of modulations required to determine the elasticities of all enzymes of a given pathway can be determined. The procedure is illustrated with numerous examples.

Animals↗
PubMed1995

Periodically modulated inhibition and its postsynaptic consequences--I. General features. Influence of modulation frequency.

Our aim was to examine the relation, or "synaptic coding", between spike trains across a synapse with inhibitory postsynaptic potentials when the presynaptic rate is modulated periodically and the postsynaptic cell is a pacemaker. Experiments were on the synapse in crayfish stretch receptor organs. Spike trains were considered point processes along time; the time series of corresponding pre- and postsynaptic intervals were extracted. Analyses used displays of intervals along time and order ("basic graphs", and "rasters", respectively), displays of differences between intervals along order ("recurrence plots"), cycle histograms (as such and as Lissajous diagrams with presynaptic and postsynaptic on the abscissae and ordinate, respectively), and correlation histograms. Cycle histograms and correlation histograms demonstrated that all presynaptic modulation frequencies (1/60-10 Hz) are reflected postsynaptically; novel frequencies may arise, not always relating simply to the pre- or postsynaptic ones. The transferred frequency domain is broad and physiologically meaningful. Indeed, vitally important functions have strong periodicities in all portions of the explored domain, and so do the discharges of participating neurons. Overall, pre- and postsynaptic discharges change oppositely, one accelerating while the other slows. Locally, however, pre- and postsynaptic discharges contrast clearly in other ways. The presynaptic evolution is everywhere smooth and orderly, half-cycles usually are symmetric, and there is a single kind of discharge, as expected because the presynaptic axon follows well the controlling stimuli. The postsynaptic cycle shows marked local distortions. These involve presynaptic domains called "congruent portions" where changes are in the same sense (e.g., joint accelerations), "saturated" domains where postsynaptic discharges are arrested, and asymmetric sensitivities to presynaptic change with hysteretic loops in the Lissajous diagrams; the postsynaptic discharge is heterogeneous showing dissimilar forms in succession. Congruent portions are either "positive segments" with pre- to postsynaptic rate ratios practically 1:1, 2:1, 1:1, or parts of Lissajous loops. Different modulation frequencies have different postsynaptic consequences. Differences involve the width and number of positive segments, the proportion of the cycle with saturation, the sense, magnitude and lead-lag characteristics of the hysteretic loops, etc. Because their consequences are separable, frequencies are classified within categories labelled "low" (under 0.5 Hz), "high" (between 0.5 and 5.0 Hz) and "very high" (over 5.0 Hz). Categories arise widely but each prevails in different biological functions (e.g., low or high in, respectively, respiration or vibratory sensitivity). The refactoriness of the inhibitory fibre affects how it can be modulated: consequently, the very high category resembles pacemaker discharges and was not analysed.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed2001

Binding of a peptide from a Streptococcus dysgalactiae MSCRAMM to the N-terminal F1 module pair of human fibronectin involves both modules.

Host invasion by a number of pathogenic bacteria such as staphylococci and streptococci involves binding to fibronectin, a ubiquitous extracellular matrix protein. On the bacterial side, host extracellular matrix adherence is mediated by MSCRAMMs (microbial surface components recognizing adhesive matrix molecules) which, in some cases, have been identified to be important virulence factors. In this study we used nuclear magnetic resonance spectroscopy to characterize the interaction of B3, a synthetic peptide derived from an adhesin of Streptococcus dysgalactiae, with the N-terminal module pair 1F12F1 of human fibronectin. 1F12F1 chemical shift changes occurring on formation of the 1F12F1/B3 complex indicate that both modules bind to the peptide and that a similar region of each module is involved. A similar surface of the 4F15F1 module pair had previously been identified as the binding site for a fibronectin-binding peptide from Staphylococcus aureus.

Adhesins, Bacterial↗
PubMed2003

Comparative analysis of intensity modulation inverse planning modules of three commercial treatment planning systems applied to head and neck tumour model.

BACKGROUND AND PURPOSE: Three commercial treatment planning modules for intensity modulated radiation therapy (IMRT) Inverse Planning, MDS-Nordion Helax-TMS, Varian Cadplan-Helios, and CMS Focus, were compared in an attempt to determine potential application limits or dosimetric differences among various optimisation algorithms. MATERIALS AND METHODS: A comparative analysis of intensity modulated dose distributions was conducted at planning level on a group of four patients presenting advanced head and neck cancers. In the study, we analysed primarily the static 'step and shoot' multileaf implementation of modulation realisation with some investigation, on the Cadplan-Helios implementation of the 'sliding window', the Varian dynamic approach to IMRT delivery. The whole study was carried out using the inverse planning tools implemented by vendors fully optimising each plan to obtain the best dosimetry given some general plan objectives. To achieve adequate target coverage, optimisation was carried out on Helax-TMS and CMS Focus adding extra margins of 5 or 6mm to the planning target volume (PTV). Beam arrangements were set with five and nine equally spaced fields. The study was conducted with two complexity levels. At the first level, dose-volume constraints were applied only to the target volume and to the spinal cord, while parotid glands were added at the second level. The relative values of dose distributions and dose-volume histograms were compared, together with an estimate of the biological implications in terms of Equivalent Uniform Dose to the target. In the Cadplan-Helios system also the dosimetric implications of the number of intensity levels selected for the discretisation of the fluence matrix were investigated. RESULTS: With the application of common planning strategies and the proper consideration of treatment planning system (TPS) specific features (e.g. the PTV margin problem), no substantial differences among the three algorithms were demonstrated at the first level for PTV and spinal cord. At the second level of the study differences were outlined for Helax-TMS, where sub-optimal results were obtained with the 5-field geometry. Mainly due to the differences in optimisation volumes, Cadplan-Helios presented significant better sparing of healthy tissue around the PTV, in terms of mean dose to healthy tissue and Irradiated Volume at 50% dose level. Finally, to achieve dosimetrically acceptable and stable results on target, a minimum of eight intensity levels should be applied for the multileaf collimator (MLC) segmentation, giving an average of 1.5 segments per field and per intensity level. CONCLUSIONS: Results obtained for the three IMRT TPS show in first instance that the optimisation algorithms analysed, as well as the conversion from computed fluences to multileaf sequences implemented in the planning systems can produce substantially equivalent dose plans (for target coverage and organs at risk sparing) if planning is performed with common strategies and once a strong understanding of each system feature is achieved. Secondly, a limited number of dose levels (about eight) is adequate at planning level.

Brachytherapy↗
PubMed1992

Signal transduction by phytochrome: phytochromes have a module related to the transmitter modules of bacterial sensor proteins.

A C-terminal section of phytochromes turned out to share sequence homologies with the full length of the transmitter modules (about 250 amino acids) of bacterial sensor proteins. Coinciding hydrophobic clusters within the homologous domains imply that the overall folding of the two different types of peptides is similar. Hence, phytochromes appear to possess the structural prerequisites to transmit signals in a way bacterial sensor proteins do. The bacterial sensor proteins are known to be environmental stimuli-regulated kinases belonging to two-component systems. After sensing a stimulus by the N-terminal part of the sensor protein, conformational alterations confer the signal to its (mostly) C-terminal transmitter module which in turn is transitionally autophosphorylated at a conserved histidine. From the histidine the phosphate is transferred to the receiver module of a system-specific regulator protein which eventually acts on transcription or enzyme activity. The histidine is not conserved in phytochromes. Instead, a conserved tyrosine is found spatially very close to the histidine position. This tyrosine might play the role of histidine, and kinase function might be associated with this part of phytochrome. In spite of this divergence, the structural similarities point to a common evolutionary origin of the phytochrome and bacterial modules.

Amino Acid Sequence↗
PubMed1980

Theory of frequency modulation detection for low modulation frequencies.

There is general agreement that the frequency difference limen measured in a two-sine-tone frequency discrimination experiment is smaller than that measured in a frequency modulation (FM) experiment. We present a model of frequency modulation detection for low modulation frequencies, within the framework of signal detection theory, which accounts well for the observed difference between frequency discrimination experiments and FM detection experiments. The FM detection model also predicts psychometric functions for detection of FM with different modulation waveforms. FM detection experiments with square, sine, trapezoid, and triangle FM are in reasonable agreement with the model predictions.

Acoustic Stimulation↗
PubMed1995

Interference in detection of interaural delay in a sinusoidally amplitude-modulated tone produced by a second, spectrally remote sinusoidally amplitude-modulated tone.

Sensitivity to interaural time delays (ITDs) within high-frequency sinusoidally amplitude-modulated (SAM) target tones was measured in the presence of a second, spectrally remote diotic SAM tone (termed an interferer). Targets and interferers were 100% modulated at 250 Hz and each was presented at 77 dB SPL for a duration of 250 ms. The modulations of targets and interferers were either in-phase or out-of-phase. In the first experiment, when the target SAM tone was centered at 4 kHz, interferers were centered at either 500 Hz, 1 kHz, or 2 kHz. Threshold ITDs were substantially increased in the presence of the interferers as compared to when the targets were presented in isolation. The greatest effects were observed with interferers centered at 500 Hz and 1 kHz. In the second experiment, when the target SAM tone was centered at 2 kHz, interferers were centered at either 500 Hz or 4 kHz. Threshold ITDs increased in the presence of either interferer, but the greatest increase occurred in the presence of the 500-Hz SAM tone. In the third experiment, it was found that presenting the low-frequency SAM tones continuously resulted in less interference than did presenting the interferers and targets coincidently. In all three experiments, the effects produced by the interferers did not depend upon whether they were modulated in-phase or out-of-phase with the target. Taken together, the data argue against the notion that the interference could result from a peripheral, monaural interaction between target and interferer waveforms.

Auditory Perception↗
PubMed1999

Modulation gap detection: effects of modulation rate, carrier separation, and mode of presentation.

Modulation gap detection (MGD) is a procedure that measures the sensitivity to an interruption in the modulation pattern imposed upon one or more carrier frequencies. The MGD task was developed to test conditions where a temporal event traverses frequency, but without a concomitant interruption in the spectral continuity of the stimulus. This contrasts with across-frequency gap detection where there is an inherent spectral discontinuity associated with the temporal gap, and where there is a marked decline in performance when the markers of the temporal gap are widely separated in frequency. The purpose of this study was to test the hypothesis that a wideband temporal analysis will be facilitated if there exists a spectral continuity throughout the temporal event. Experiment 1 established the procedure of MGD and indicated that a modulation rate of 8 Hz was optimal for the task. Experiment 2 showed that performance declined markedly when the carrier frequencies of the modulation markers were widely separated in frequency. This finding indicates that spectral continuity across the temporal event is not a sufficient prerequisite for the auditory system to undertake a wideband temporal analysis. Experiment 3 revealed that dichotic MGD also results in poor performance, similar to that seen for widely separated carrier frequencies in the monaural case. This supports the hypothesis that the "channels" across which temporal events are poorly processed do not necessarily correspond to peripheral frequency channels.

Audiometry, Pure-Tone↗
PubMed2001

Modulation of P-glycoprotein (PGP) mediated multidrug resistance (MDR) using chemosensitizers: recent advances in the design of selective MDR modulators.

Over the past two decades, a number of chemical entities have been investigated in the continuing quest to reverse P-glycoprotein (PGP) mediated multidrug resistance (MDR) in cancer. The complexity of interactions between these agents and the proteins responsible for MDR in conjunction with the challenges associated with developing SAR/QSAR relationships for MDR modulators has hampered our ability to develop agents that modulate MDR with enhanced specificity of target, increased efficacy, and minimized toxicity when coadministered with anticancer drugs. With an increased understanding of the molecular interaction, target-mediated SAR and combinatorial chemistry approaches, newer more selective inhibitors have been recently reported. These agents have shown remarkable promise in preclinical trials; although their ultimate clinical therapeutic utility remains to be established. The emphasis of this review is placed on the current understanding of modulator-drug transport protein interactions and to review the advances in the structure-based design, synthetic efforts and the cellular pharmacology of MDR modulating activity of a number of known PGP inhibitors.

ATP Binding Cassette Transporter, Subfamily B, Mem↗