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At least 523 records · Page 29Linked to original sources
PubMed2005

Detection of high-frequency spectral notches as a function of level.

High-frequency spectral notches are important cues for sound localization. Our ability to detect them must depend on their representation as auditory nerve (AN) rate profiles. Because of the low threshold and the narrow dynamic range of most AN fibers, these rate profiles deteriorate at high levels. The system may compensate by using onset rate profiles whose dynamic range is wider, or by using low-spontaneous-rate fibers, whose threshold is higher. To test these hypotheses, the threshold notch depth necessary to discriminate between a flat spectrum broadband noise and a similar noise with a spectral notch centered at 8 kHz was measured at levels from 32 to 100 dB SPL. The importance of the onset rate-profile representation of the notch was estimated by varying the stimulus duration and its rise time. For a large proportion of listeners, threshold notch depth varied nonmonotonically with level, increasing for levels up to 70-80 dB SPL and decreasing thereafter. The nonmonotonic aspect of the function was independent of notch bandwidth and stimulus duration. Thresholds were independent of stimulus rise time but increased for the shorter noise bursts. Results are discussed in terms of the ability of the AN to convey spectral notch information at different levels.

Acoustic Stimulation↗
PubMed2005

Effects of waveform shape on human sensitivity to electrical stimulation of the inner ear.

Psychophysical measures of the electrically stimulated human auditory system were obtained for different types of symmetric and asymmetric charge-balanced waveforms. Absolute detection thresholds of biphasic, pseudomonophasic, and 'alternating monophasic' current waveforms delivered by a bipolar intra-cochlear electrode pair were determined for four subjects implanted with the LAURA device. Thresholds for alternating monophasic stimuli, in which anodic and cathodic phases alternated every 5 ms, were 5-8 dB lower than for the biphasic waveforms for all four subjects. For two of the four subjects, thresholds for the pseudomonophasic waveforms were also significantly lower than for the biphasic waveforms. These pseudomonophasic thresholds were greatly affected neither by a 500-micros gap inserted between the two phases, nor by whether the shorter phase preceded or followed the longer one. Loudness balancing measures performed at the most comfortable levels also showed that, for equal loudness, alternating monophasic stimuli required a lower level than biphasic and pseudomonophasic waveforms. For three of the four subjects, the dynamic ranges of the pseudomonophasic (but not alternating monophasic) waveforms were greater than those of the biphasic waveforms. The results demonstrate that thresholds and dynamic ranges of human cochlear implant users can be controlled by manipulating the way in which the charge produced by the initial phase of an electrical pulse is recovered.

Adult↗
PubMed2002

Separate, parallel sensory and hedonic pathways in the mammalian somatosensory system.

We propose that separate sensory and hedonic representations exist in each of the primary structures of the somatosensory system, including brainstem, thalamic and cortical components. In the dorsal horn of the spinal cord, the hedonic representation, which consists primarily of nociceptive-specific, wide dynamic range, and thermoreceptive neurons, is located in laminae I and II, while the sensory representation, composed primarily by low-threshold and wide dynamic range neurons, is found in laminae III through V. A similar arrangement is found in the caudal spinal trigeminal nucleus. Based on the available anatomical and electrophysiological data, we then determine the corresponding hedonic and sensory representations in the area of the dorsal column nuclei, ventrobasal and posterior thalamic complex, and cortex. In rodent primary somatosensory cortex, a hedonic representation can be found in laminae Vb and VI. In carnivore and primate primary and secondary somatosensory cortical areas no hedonic representation exists, and the activities of neurons in both areas represent the sensory aspect exclusively. However, there is a hedonic representation in the posterior part of insular cortex, bordering on retroinsular cortex, that receives projections from two thalamic areas in which hedonics are represented. The functions of the segregated components of the system are discussed, especially in relation to the subjective awareness of pain.

Afferent Pathways↗
PubMedDate not supplied

Protein identification in complex mixtures.

This paper investigates the prospects of successful mass spectrometric protein identification based on mass data from proteolytic digests of complex protein mixtures. Sets of proteolytic peptide masses representing various numbers of digested proteins in a mixture were generated in silico. In each set, different proteins were selected from a protein sequence collection and for each protein the sequence coverage was randomly selected within a particular regime (15-30% or 30-60%). We demonstrate that the Probity algorithm, which is characterized by an optimal tolerance for random interference, employed in an iterative procedure can correctly identify >95% of proteins at a desired significance level in mixtures composed of hundreds of yeast proteins under realistic mass spectrometric experimental constraints. By using a model of the distribution of protein abundance, we demonstrate that the very high efficiency of identification of protein mixtures that can be achieved by appropriate choices of informatics procedures is hampered by limitations of the mass spectrometric dynamic range. The results stress the desire to choose carefully experimental protocols for comprehensive proteome analysis, focusing on truly critical issues such as the dynamic range, which potentially limits the possibilities of identifying low abundance proteins.

Fungal Proteins↗
PubMed2002

The human plasma proteome: history, character, and diagnostic prospects.

The human plasma proteome holds the promise of a revolution in disease diagnosis and therapeutic monitoring provided that major challenges in proteomics and related disciplines can be addressed. Plasma is not only the primary clinical specimen but also represents the largest and deepest version of the human proteome present in any sample: in addition to the classical "plasma proteins," it contains all tissue proteins (as leakage markers) plus very numerous distinct immunoglobulin sequences, and it has an extraordinary dynamic range in that more than 10 orders of magnitude in concentration separate albumin and the rarest proteins now measured clinically. Although the restricted dynamic range of conventional proteomic technology (two-dimensional gels and mass spectrometry) has limited its contribution to the list of 289 proteins (tabulated here) that have been reported in plasma to date, very recent advances in multidimensional survey techniques promise at least double this number in the near future. Abundant scientific evidence, from proteomics and other disciplines, suggests that among these are proteins whose abundances and structures change in ways indicative of many, if not most, human diseases. Nevertheless, only a handful of proteins are currently used in routine clinical diagnosis, and the rate of introduction of new protein tests approved by the United States Food and Drug Administration (FDA) has paradoxically declined over the last decade to less than one new protein diagnostic marker per year. We speculate on the reasons behind this large discrepancy between the expectations arising from proteomics and the realities of clinical diagnostics and suggest approaches by which protein-disease associations may be more effectively translated into diagnostic tools in the future.

Biological Assay↗
PubMed2002

Optimal source distribution for binaural synthesis over loudspeakers.

When binaural sound signals are presented with loudspeakers, the system inversion involved gives rise to a number of problems such as a loss of dynamic range and a lack of robustness to small errors and room reflections. The amplification required by the system inversion results in loss of dynamic range. The control performance of such a system deteriorates severely due to small errors resulting from, e.g., misalignment of the system and individual differences in the head related transfer functions at certain frequencies. The required large sound radiation results in severe reflection which also reduces the control performance. A method of overcoming these fundamental problems is proposed in this paper. A conceptual monopole transducer is introduced whose position varies continuously as frequency varies. This gives a minimum processing requirement of the binaural signals for the control to be achieved and all the above problems either disappear or are minimized. The inverse filters have flat amplitude response and the reproduced sound is not colored even outside the relatively large "sweet area." A number of practical solutions are suggested for the realization of such optimally distributed transducers. One of them is a discretization that enables the use of conventional transducer units.

Journal Article↗
PubMedDate not supplied

Determination of gibberellic acid residues on fruits by synchronous scanning derivative spectrofluorometry.

A synchronous derivative spectrofluorometric method is described for the determination of the plant growth regulator, gibberellic acid (GA3). The method is based on the formation of a fluorogen in concentrated sulfuric acid. The reaction is carried out at 85% sulfuric acid and in aqueous medium. The common fluorometric method with a linear dynamic range of 137-400 ppb, and a detection limit of 48 ppb is described. The synchronous first and second derivative method has linear dynamic ranges between 7.6-40 ppb and 12-40 ppb, with detection limits of 3.5 and 6.7 ppb, respectively. The influence of reaction variables and of other plant growth regulators present, and the application to residues on oranges, lemons, and grapes, are also described.

Fruit↗
PubMed1997

Substance P and enkephalin immunoreactivities in axonal boutons presynaptic to physiologically identified dorsal horn neurons. An ultrastructural multiple-labelling study in the cat.

A combination of intracellular electrophysiological recording and injection of horseradish peroxidase with ultrastructural immunocytochemistry was used to investigate the synaptic interplay between substance P- and enkephalin-immunoreactive axonal boutons and three types of functionally characterized dorsal horn neurons in the cat spinal cord. The dorsal horn neurons were classified as nociceptive specific, wide dynamic range and non-nociceptive based on their responses to innocuous and noxious stimuli. Most of the nociceptive neurons (either nociceptive specific or wide dynamic range) contained enkephalin immunoreactivity, but none of the non-nociceptive neurons were positive for enkephalin. Three types of immunoreactive boutons were found in contact with the functionally characterized dorsal horn neurons. These boutons were positive for either substance P, enkephalin, or substance P+enkephalin. Quantitative analysis revealed that the percentages of substance P-immunoreactive boutons apposed to the cell bodies, proximal dendrites and distal dendrites of nociceptive neurons were significantly higher than those of non-nociceptive neurons. Furthermore, the percentages of substance P+enkephalin-immunoreactive axonal boutons apposed to the distal dendrites of nociceptive neurons were significantly higher than those of non-nociceptive neurons and the percentages of enkephalin-immunoreactive boutons apposed to the cell bodies and proximal dendrites of nociceptive neurons were significantly higher than in non-nociceptive neurons. Finally, neither enkephalin-immunoreactive nor substance P+enkephalin-immunoreactive boutons were ever seen presynaptic to substance P-immunoreactive boutons. These results provide evidence of an anatomical substrate within the dorsal horn for the interaction of substance P-mediated with enkephalin-mediated mechanisms. The data support the idea that the modulation of nociceptive input in the dorsal horn by enkephalinergic neurons occurs mainly via a postsynaptic mechanism, and thus suggest that dorsal horn enkephalinergic neurons participate in a local inhibitory feedback loop in a distinct pathway from the previously postulated opioid-mediated depression of substance P release from primary afferent terminals.

Animals↗
PubMed2000

Chronic microstimulation in the feline ventral cochlear nucleus: physiologic and histologic effects.

This study was conducted to help to establish the feasibility of a multi-channel auditory prosthesis based on microstimulation within the human ventral cochlear nucleus, and to define the range of stimulus parameters that can be used safely with such a device. We chronically implanted activated iridium microelectrodes into the feline ventral cochlear nucleus and, beginning 80-250 days after implantation, they were pulsed for 7 h/day, on up to 21 successive days. The stimulus was charge-balanced pulses whose amplitude was modulated by a simulated human voice. The pulse rate (250 Hz/electrode) and the maximum pulse amplitude were selected as those that are likely to provide a patient with useful auditory percepts. The changes in neuronal responses during the multi-day stimulation regimens were partitioned into long-lasting, stimulation-induced depression of neuronal excitability (SIDNE), and short-acting neuronal refractivity (SANR). Both SIDNE and SANR were quantified from the changes in the growth functions of the evoked potentials recorded in the inferior colliculus. All of the stimulation regimens that we tested induced measurable SIDNE and SANR. The combined effect of SIDNE and the superimposed SANR is to depress the neuronal response near threshold, and thereby, to depress the population response over the entire amplitude range of the stimulus pulses. SIDNE and SANR may cause the greatest degradation of the performance of a clinical device at the low end of the amplitude range, and this may represent an inherent limitation of this type of spatially localized, high-rate neuronal stimulation. We determined sets of stimulus parameters which preserved most of the dynamic range of the neuronal response, when using either long (150 micros/phase) or short (40 micros/phase) stimulus pulses. Increasing the amplitude of the stimulus was relatively ineffective as a means of increasing the dynamic range of neuronal response, since the greater stimulus amplitude induced more SIDNE. All of the pulsed and unpulsed electrode sites were examined histologically, and no neuronal changes attributable to the stimulation were detected. There was some aggregation of glial cells immediately adjacent to some of the electrodes that were pulsed with the short-duration pulses, and at the highest current densities.

Animals↗
PubMed2000

Effects of electrode configuration and stimulus level on rate and level discrimination with cochlear implants.

Recent studies have demonstrated that speech perception with cochlear implants can be significantly affected by electrode configuration. Contrary to expectations, broader configurations (monopolar or broad bipolar) produced equal or better speech recognition compared with narrower configurations (narrow bipolar or common ground). One hypothesis that would account for these results is that broader configurations excite larger populations of neurons providing a more robust representation of information on each channel of the prosthesis. It is known that the number of neurons excited by an electrical stimulus increases considerably as the stimulus level increases. Furthermore, many types of discrimination improve as a function of stimulus level. If the discrimination improvements seen with increasing stimulus level are due to increasing the size of the neural population carrying the signal, and if broadening the electrode configuration also increases the size of the activated neural population, then one would expect level and electrode configuration to affect discrimination in similar ways. To test this hypothesis, we studied several types of discrimination as a function of level and electrode configuration in four nonhuman primates with cochlear implants. We tested electrode configurations that produced current fields ranging from very restricted (tripolar) to broad (parallel monopolar). For each configuration, pulse-rate discrimination, amplitude-modulation-frequency discrimination, and level discrimination were tested at current levels spanning much of the psychophysical dynamic range. Results showed large effects of current level on discrimination in many cases. However, effects of electrode configuration at comparable levels within the dynamic range were smaller or absent. Furthermore, the effect of level on discrimination was independent of electrode configuration in most cases even though the rate of spread of neural activation with level is expected to depend on electrode configuration. Possible interpretations of these results are that (1) the current level adjustments necessary to achieve comparable loudness for the various configurations significantly countered any effects of electrode configuration on the size of the activated neural population, or (2) the effects of level on discrimination do not result from its effects on the spatial extent of neural activation.

Animals↗
PubMed1992

Very high-frequency rhythmic activity during SEEG suppression in frontal lobe epilepsy.

Intracerebral EEG (SEEG) recordings showing the development of fast rhythmic activity at seizure onset provide important evidence for the localisation of an epileptic focus. However, very high-frequency activity (greater than 50 Hz) of low amplitude relative to the background may not be apparent on the paper record due to the limited bandwidth and dynamic range of conventional SEEG recording and display methods. The use of a digital telemetry system with a fast sampling rate (400 Hz) and a wide dynamic range (1 microV resolution, 4 mV range) has allowed us to utilize expanded time scale SEEG plots and autoregressive spectral estimation to identify this activity in chronic SEEG studies. This may be particularly useful in frontal lobe epilepsy, where rapid propagation often prevents adequate localization using conventional methods of analysis.

Adult↗
PubMed2006

Study of a toxin-alkaline phosphatase conjugate for the development of an immunosensor for tetrodotoxin determination.

This paper describes a direct competitive immunoenzymatic spectrophotometric assay (ELISA) for tetrodotoxin (TTX) determination and the adaptation of this method for use in an electrochemical assay format. The novelty of this work involves the use of the antigen labelled with alkaline phosphatase (AP); this conjugate was prepared in our laboratory as there is no commercially available conjugate of any kind for TTX. The new conjugate was characterized in terms of its affinity for the specific antibody as well as the residual concentration and the residual activity of the enzyme (AP) incorporated as label. The proposed method based on the new conjugate showed satisfactory results for TTX determination: for the spectrophotometric method the dynamic range was 4-15 ng mL(-1) with a limit of detection (LOD) of 2 ng mL(-1) (R=0.9247), whereas for the electrochemical protocol the dynamic range was 2-50 ng mL(-1) and the LOD was 1 ng mL(-1).

Alkaline Phosphatase↗
PubMed1997

Utilization of lipophilic ionic additives in liquid polymer film optodes for selective anion activity measurements.

Lipophilic anionic and cationic additives are investigated as components for use in liquid polymer film-based optodes. These ionic additives are known to strongly influence the selectivity behavior of anion-selective electrodes. They also make it possible to construct ion coextraction optodes that can measure anion activities. Theoretical, thermodynamic anion-optode equilibria formalisms were derived to help understand the influence these additives have on the overall optode response and on the selectivity behavior. Neutral and charged anion carrier film configurations are described and tested for two anion ionophores with known modes of action, ruthenium(II) octaethylporphyrin and a vitamin B12 derivative (cyanoaquacobyrinic acid heptakis(2-phenylethyl ester)). These film configurations were further tested using a less well-understood ionophore, indium(III) octaethylporphyrin. Notable is the indium(III) octaethylporphyrin optode, which has a dynamic range appropriate for physiological measurements of chloride at neutral pH values. Also of interest is the optode with the vitamin B12 derivative ionophore, which has a dynamic range appropriate for some physiological measurements of nitrite at neutral pH values.

Anions↗
PubMed2004

Correlation between ligand-receptor affinity and the transcription readout in a yeast three-hybrid system.

The yeast two-hybrid assay has proven to be a powerful method to detect protein-protein interactions as well as to derive genome-wide protein interaction maps. More recently, three-hybrid assays have emerged as a means to detect both protein-RNA and protein-small molecule interactions. Despite the routine use of the two-hybrid assay and the potential of three-hybrid systems, there has been little quantitative characterization to understand how the strength of the protein interaction correlates with transcription activation. It is not known if the additional interaction in three-hybrid systems compromises the sensitivity of the system. Thus, here, we set out to determine the K(D) cutoff of a small molecule three-hybrid system and to determine if there is a correlation between the K(D) and the levels of transcription activation. A series of mutations to FK506-binding protein 12 (FKBP12) were designed to vary the affinity of this protein for the small molecule synthetic ligand for FK506-binding protein 12 (SLF). These FKBP12 variants were overexpressed and purified, and their K(D)'s for SLF were measured using a fluorescence polarization assay. Then the levels of transcription activation in a Mtx-DHFR yeast three-hybrid system were determined for these variants using a lacZ reporter gene. The K(D) cutoff of the Mtx yeast three-hybrid system is found to be ca. 50 nM. Further, the levels of transcription activation correlate with the strength of the binding interaction, though the dynamic range is only 1 order of magnitude. These results establish that the three-hybrid assay has the requisite sensitivity for drug discovery. However, the small dynamic range highlights a limitation to equilibrium-based assays for discriminating interactions based on affinity.

Escherichia coli↗
PubMed1989

The role of sensory adaptation in the retina.

Adaptation, a change in response to a sustained stimulus, is a widespread property of sensory systems, occurring at many stages, from the most peripheral energy-gathering structures to neural networks. Adaptation is also implemented at many levels of biological organization, from the molecule to the organ. Despite adaptation's diversity, it is fruitful to extract some unifying principles by considering well-characterized components of the insect visual system. A major function of adaptation is to increase the amount of sensory information an organism uses. The amount of information available to an organism is ultimately defined by its environment and its size. The amount of information collected depends upon the ways in which an organism samples and transduces signals. The amount of information that is used is further limited by internal losses during transmission and processing. Adaptation can increase information capture and reduce internal losses by minimizing the effects of physical and biophysical constraints. Optical adaptation mechanisms in compound eyes illustrate a common trade-off between energy (quantum catch) and acuity (sensitivity to changes in the distribution of energy). This trade-off can be carefully regulated to maximize the information gathered (i.e. the number of pictures an eye can reconstruct). Similar trade-offs can be performed neurally by area summation mechanisms. Light adaptation in photoreceptors introduces the roles played by cellular constraints in limiting the available information. Adaptation mechanisms prevent saturation and, by trading gain for temporal acuity, increase the rate of information uptake. By minimizing the constraint of nonlinear summation (imposed by membrane conductance mechanisms) a cell's sensitivity follows the Weber-Fechner law. Thus, a computationally advantageous transformation is generated in response to a cellular constraint. The synaptic transfer of signals from photoreceptors to second-order neurones emphasizes that the cellular constraints of nonlinearity, noise and dynamic range limit the transmission of information from cell to cell. Synaptic amplification is increased to reduce the effects of noise but this resurrects the constraint of dynamic range. Adaptation mechanisms, both confined to single synapses and distributed in networks, remove spatially and temporally redundant signal components to help accommodate more information within a single cell. The net effect is a computationally advantageous removal of the background signal. Again, the cellular constraints on information transfer have dictated a computationally advantageous operation.

Adaptation, Physiological↗
PubMed1993

Advanced multiple beam equalization radiography (AMBER) combined with computed radiography. Preliminary evaluation.

The combined use of AMBER (Advanced Multiple Beam Equalization Radiography) and a digital storage phosphor (SP) radiography system was evaluated for chest radiography in a pilot study with 4 patients. Four image modes with different dose levels were compared: the SP in combination with an AMBER equalized exposure (SP/AMBER) and 3 nonequalized exposures with dose levels corresponding to the respective calculated AMBER lung dose (SP/lung field dose), the calculated AMBER mediastinal dose (SP/mediastinal dose) and the calculated AMBER average dose (SP/average dose). All image modes were matched for Hurter and Driffield characteristics and subjectively rated according to visibility of details. The improved signal-to-noise (S/N) ratio of SP/AMBER resulted in a better visualization of structures in the mediastinum and the basal lung where SP/lung field dose scored lowest. For the central lung no quality differences were seen between techniques. The compressed dynamic range of the SP/AMBER images was more easily displayed on the hard-copy film. The combination of AMBER with SP radiography promises to overcome the dynamic range limitations of digital displays while, at moderate doses, giving better S/N and image quality than standard SP technique.

Adult↗
PubMed2001

Fever-range hyperthermia dynamically regulates lymphocyte delivery to high endothelial venules.

Fever is associated with increased survival during acute infection, although its mechanism of action is largely unknown. This study found evidence of an unexpectedly integrated mechanism by which fever-range temperatures stimulate lymphocyte homing to secondary lymphoid tissues by increasing L-selectin and alpha4beta7 integrin-dependent adhesive interactions between circulating lymphocytes and specialized high endothelial venules (HEV). Exposure of splenic lymphocytes in vivo to fever-like whole-body hyperthermia (WBH; 39.8 +/- 0.2 degrees C for 6 hours) stimulated both L-selectin and alpha4beta7 integrin-dependent adhesion of lymphocytes to HEV under shear conditions in lymph nodes and Peyer patches. The adhesiveness of HEV ligands for L-selectin and alpha4beta7 integrin (ie, peripheral lymph node addressin and mucosal addressin cell adhesion molecule-1) also increased during WBH or febrile responses associated with lipopolysaccharide-induced or turpentine-induced inflammation. Similar increases in HEV adhesion occurred during hyperthermia treatment of lymph node and Peyer patch organ cultures in vitro, indicating that the local lymphoid tissue microenvironment is sufficient for the hyperthermia response. In contrast, WBH did not augment adhesion in squamous endothelium of nonlymphoid tissues. Analysis of homing of alpha4beta7(hi) L-selectin(lo) murine TK1 cells and L-selectin(hi) alpha4beta7 integrin-negative 300.19/L-selectin transfectant cells showed that fever-range temperatures caused a 3- to 4-fold increase in L-selectin and alpha4beta7 integrin-dependent trafficking to secondary lymphoid tissues. Thus, enhanced lymphocyte delivery to HEV by febrile temperatures through bimodal regulation of lymphocyte and endothelial adhesion provides a novel mechanism to promote immune surveillance.

Animals↗
PubMed1987

Effects of excitatory and non-excitatory suppressor tones on two-tone rate suppression in auditory nerve fibers.

Recordings were obtained from individual auditory nerve fibers in anesthetized chinchillas. Rate versus level functions were obtained for best frequency (BF) tones alone and for simultaneously-gated tone pairs comprising a BF tone and a second tone at a fixed intensity that produced evidence of two-tone rate suppression. Care was taken in selecting a range of suppressor tone levels that included excitatory (i.e., the suppressor tone evoked a rate change by itself) and non-excitatory (i.e., no suppressor tone-evoked rate increase) suppressor tone levels. Addition of a suppressor tone produced a shift of the dynamic range portion of the BF rate versus level function to higher test intensities. A parallel shift of the dynamic range portion of the rate versus level function was associated with a non-excitatory suppressor tone. The shift produced by an excitatory suppressor tone was characterized by a decrease in slope. Results indicated that the magnitude of shift increased monotonically as suppressor tone intensity was raised and that there was a gradual transition from a non-excitatory response to an excitatory response. The rate of shift (i.e., dB of shift per dB change in suppressor tone intensity) did not differ for non-excitatory versus excitatory responses, but was substantially greater for below-BF suppressor tones (1.38 dB/dB) than for above-BF suppressor tones (0.54 dB/dB). The rate of shift did not, however, appear to be related systematically to suppressor tone frequency separation from BF. Above- and below-BF suppression was noted for fibers over the range of best frequencies tested (110 Hz to 16.4 kHz).

Acoustic Stimulation↗