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PubMed1991

Space charge effects in a kinestatic charge detector.

The effects of space charge in a kinestatic charge detector (KCD) were examined using computer solutions to Poisson's equation. The KCD is a strip-beam parallel-plate drift chamber used for digital radiography. It was assumed that there is negligible electron attachment, i.e. there are no negative ions formed. The ionization rate per mA as a function of x-ray interaction depth was calculated for a detector filled with xenon at 25.3 x 10(5) Pa. Solution of Thomson's equations gave the positive ion density at the cathode, also as a function of depth. Water filtration values ranging from 0 to 30 cm were used in order to estimate the range of ion density values expected in a clinical KCD. The case of steady-state x-ray illumination was simulated for ionization rates less than the zero field limit (above which space charge changes the polarity of the electric field). Line spread responses were found for varying ionization rates to show the effect of space charge due to electric field distortion on the spatial resolution performance in the drift direction. The effect of imaging ideal edges with a KCD was calculated and the expected output signal was plotted for densities up to the zero field limit. Space charge dependence on the selection of KCD design and operating parameters is discussed. Because of the dependence of the KCD drift-direction spatial resolution on the uniformity of the electric field, space charge effects impose an upper limit on the detector entrance exposure and define the dynamic range of the device.

Humans↗
PubMed1997

Quantitative measurements of linear birefringence during heating of native collagen.

BACKGROUND AND OBJECTIVE: Linear birefringence is an anisotropic property of rat tail tendon, which is largely composed of collagen. Our goal is to show that the dynamic range and sensitivity of the linear birefringence loss of collagen during heating are sufficient for kinetic modeling of the reaction. STUDY DESIGN, MATERIALS AND METHODS: The linear birefringence loss was quantified for tendon denatured via both a heated-isotonic-saline bath and a heated stage. All measurements were made with a polarizing transmission microscope equipped with a Berek compensator. RESULTS: The data show that the loss of linear birefringence is a first-order kinetic reaction. The native rat tail tendon birefringence, delta n = 3.0 +/- 0.6 x 10(-3) (mean +/- std. err.), is lost after denaturation occurs (delta n = 0). Application of the Arrhenius equation to the linear birefringence data yields the activation energy (Ea = 89 +/- 1 kcal/mole), pre-exponential coefficient (A = e130 +/- 1 s-1), enthalpy (delta H = 88 +/- 1 kcal/mole) and entropy (delta S = 197 +/- 2 cal/degree K.mole). CONCLUSION: This study shows that dynamic changes in linear birefringence can be used to monitor thermally induced changes in collagen.

Animals↗
PubMed2006

Theodor Bücher Lecture. Metabolomics, modelling and machine learning in systems biology - towards an understanding of the languages of cells. Delivered on 3 July 2005 at the 30th FEBS Congress and the 9th IUBMB conference in Budapest.

The newly emerging field of systems biology involves a judicious interplay between high-throughput 'wet' experimentation, computational modelling and technology development, coupled to the world of ideas and theory. This interplay involves iterative cycles, such that systems biology is not at all confined to hypothesis-dependent studies, with intelligent, principled, hypothesis-generating studies being of high importance and consequently very far from aimless fishing expeditions. I seek to illustrate each of these facets. Novel technology development in metabolomics can increase substantially the dynamic range and number of metabolites that one can detect, and these can be exploited as disease markers and in the consequent and principled generation of hypotheses that are consistent with the data and achieve this in a value-free manner. Much of classical biochemistry and signalling pathway analysis has concentrated on the analyses of changes in the concentrations of intermediates, with 'local' equations - such as that of Michaelis and Menten v=(Vmax x S)/(S+K m) - that describe individual steps being based solely on the instantaneous values of these concentrations. Recent work using single cells (that are not subject to the intellectually unsupportable averaging of the variable displayed by heterogeneous cells possessing nonlinear kinetics) has led to the recognition that some protein signalling pathways may encode their signals not (just) as concentrations (AM or amplitude-modulated in a radio analogy) but via changes in the dynamics of those concentrations (the signals are FM or frequency-modulated). This contributes in principle to a straightforward solution of the crosstalk problem, leads to a profound reassessment of how to understand the downstream effects of dynamic changes in the concentrations of elements in these pathways, and stresses the role of signal processing (and not merely the intermediates) in biological signalling. It is this signal processing that lies at the heart of understanding the languages of cells. The resolution of many of the modern and postgenomic problems of biochemistry requires the development of a myriad of new technologies (and maybe a new culture), and thus regular input from the physical sciences, engineering, mathematics and computer science. One solution, that we are adopting in the Manchester Interdisciplinary Biocentre (http://www.mib.ac.uk/) and the Manchester Centre for Integrative Systems Biology (http://www.mcisb.org/), is thus to colocate individuals with the necessary combinations of skills. Novel disciplines that require such an integrative approach continue to emerge. These include fields such as chemical genomics, synthetic biology, distributed computational environments for biological data and modelling, single cell diagnostics/bionanotechnology, and computational linguistics/text mining.

Artificial Intelligence↗
PubMed1998

Barstar has a highly dynamic hydrophobic core: evidence from molecular dynamics simulations and nuclear magnetic resonance relaxation data.

The dynamic behavior of the ribonuclease inhibitor barstar has been investigated by molecular dynamics (MD) simulations in explicit water. Two 2.5 ns MD simulations were performed, and an ensemble of 25 000 structures was generated. This ensemble reproduces the solution structures and is consistent with the experimental structural restraints from NMR spectroscopy. Reorientation of the backbone NH bond vectors and side chain methyl groups was monitored by calculation of autocorrelation functions and the generalized S2 order parameters. Order parameters derived for motion in the approximately 100 ps time scale were compared with those obtained from NMR relaxation measurements. Consistent with experiment, the backbone NH bond vectors were relatively rigid. In contrast, the side chain methyl groups exhibited a wide dynamic range, from restricted motion comparable to that of the backbone to rapid unrestricted motion. The order parameters for the methyl groups correlate well with their spatial separation from the backbone and are residue-type dependent. Smaller S2axis values were observed for leucine methyl groups, in part due to side chain hopping between two predominant rotamers (g+t and tg-). Motions such as the flipping of aromatic rings and the hopping of leucine side chains were prevalent within the hydrophobic core, suggesting that the core is fluid-like with low energy barriers between native conformational substates. Thus, our studies suggest that the entropy of the native state can be significant and should not be discounted in thermodynamic considerations of protein folding. On the basis of our results, the side chain motion represents the primary source of the residual entropy of the native state and entropic considerations based solely on backbone dynamics would be incomplete.

Bacillus↗
PubMed1989

Cell responses to acoustic stimuli in the pterothoracic ganglion of two noctuoid moths.

The spike activity of various types of cell responses in the pterothoracic ganglion of Ascalapha odorata (Noctuidae) and Empyreuma pugione (Arctiidae) was studied. Pure tones (16 kHz for A. odorata and 20 kHz for E. pugione, 45 ms pulses) were presented at a 1 Hz rate over 9 s and at intensities ranging from 25 to 95 dB SPL. The values of the latency period and the interspike intervals allowed us to describe the intensity-latency and intensity-response functions as well as the spike distribution during the responses, the latter being given by the 'instantaneous frequency', i.e., as the inverse value of the mean of the nine measurements of each interspike interval during the response time. 'Repeater' (RA1 and RA2) is a type of cell response that shows a phasic-tonic spike distribution similar to that of the receptor cells (A1 and A2), but that differs from the latter in a longer (ca. 1.0 ms) latency period, a lower number of spikes per pulse, and a lower instantaneous frequency during the response time. Another repeater type of cell response (RA) differs from the receptors and the other two repeaters in the form of its intensity-latency function, having the widest dynamic range (from 40 to 50 dB), and exhibiting the highest maximal number of spikes per pulse of all the response types recorded. We recorded also strictly phasic responses (1 or 2 spikes per pulse), which are considered as pulse markers. Of these, one (PM1) has a shorter latency period (ca. 10 ms) and higher sensitivity than the other (PM2). Two other types of cell responses showed significant differences in their latency period and the number of spikes per pulse under binaural and monoaural stimulation and are assumed to be the consequence of binaural summation, one by inhibition (BSI) and the other by excitation (BSE); they also differ in the spike distribution during the response. For the other types of cell responses recorded we used names that reflect the form of their spike distribution: chopper, build, On-S, tonic, and suppression. The spike distributions during the response time recorded in the pterothoracic ganglion of these two noctuoid moths are compared with the temporal patterns of discharge described in the auditory neurons of the first relay stations of birds and mammals.(ABSTRACT TRUNCATED AT 400 WORDS)

Acoustic Stimulation↗
PubMed2003

Molecular compasses and gyroscopes with polar rotors: synthesis and characterization of crystalline forms.

We report the highly convergent synthesis and solid-state characterization of six crystalline "molecular compasses" consisting of a central phenylene rotor with polar substituents, or compass needle, and two trityl groups axially connected by acetylene linkages to the 1,4-positions. Compounds with fluoro-, cyano-, nitro-, amino-, diamino-, and nitroamino substituents are expected to emulate the parent compound which was shown to form crystals where the central phenylene can rotate about its 1,4-axis with rate constants in the 10(3) -10(6) s(-)(1) dynamic ranges near ambient temperature, depending on crystal morphology. With data from single-crystal X-ray diffraction analysis, solid-state CPMAS (13)C NMR, differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA), it is shown that a relatively small structural perturbation by a single polar group (F, CN, NO(2), NH(2)) results in isomorphous structures with analogous properties. In analogy to the parent compound, crystals grown from benzene formed clathrate structures in the space group Ponemacr; with one molecular compass and two benzene molecules per unit cell. Solvent-free crystals with the same space group obtained by a first-order phase transition between 60 and 130 degrees C were shown to be spectroscopically identical to those obtained by slow solvent evaporation from a mixture of CH(2)Cl(2) and hexanes. A qualitative analysis of the positionally disordered phenylene groups in terms of the expected solid-state rotational dynamics suggests a nonsymmetric, 2-fold rotational potential, or a process involving full 360 degrees turns.

Journal Article↗
PubMed1991

Encoding repetition rate and duration in the inferior colliculus of the big brown bat, Eptesicus fuscus.

1. Encoding of temporal stimulus parameters by inferior collicular (IC) neurons of Eptesicus fuscus was studied by recording their responses to a wide range of repetition rates (RRs) and durations at several stimulus intensities under free field stimulus conditions. 2. The response properties of 424 IC neurons recorded were similar to those reported in previous studies of this species. 3. IC neurons were classified as low-pass, band-pass, and high-pass according to their preference for RRs and/or durations characteristic of, respectively, search, approach, or terminal phases of echolocation. These neurons selectively process stimuli characteristic of the various phases of hunting. 4. Best RRs and best durations were not correlated with either the BFs or recording depths This suggests that each isofrequency lamina is capable of processing RRs and durations of all hunting phases. 5. Responses of one half of IC neurons studied were correlated with the stimulus duty cycle. These neurons may preferentially process terminal phase information when the bat's pulse emission duty cycle increases. 6. While the stimulus RR affected the dynamic range and overall profile of the intensity rate function, only little effect was observed with different stimulus durations.

Acoustic Stimulation↗
PubMed1990

Stimulus-response function studies of esophageal mechanosensitive nociceptors in sympathetic afferents of opossum.

1. Single-unit activity was recorded from afferent fibers in either the paravertebral sympathetic chain or the splanchnic nerves. Forty-three fibers that responded to distension of the smooth-muscle portion of esophagus were selected for further study. 2. Out of the 43 fibers, 27 (62%) had ongoing resting activity, and 16 (38%) were silent. The mean resting activity of these fibers was 0.28 +/- 0.06 imp/s (range, 0-2.6 imp/s). 3. Repeated distensions of the esophagus to a fixed pressure (80 mmHg) evoked spike discharge at a reproducible rate. There was no evidence of facilitation or inhibition of subsequent responses. The mean coefficient of variation (CV) was 0.17 +/- 0.05 imp/s (n = 5). 4. The stimulus-response function (SRF) to intraluminal graded distension was studied in 35 fibers. Thirty-three fibers showed linear increase in firing that did not saturate up to 120 mmHg. Two fibers reached maximal discharge rate at 60 mmHg. The mean discharge rate at 120 mmHg pressure was 14.87 +/- 1.52 imp/s. 5. Threshold pressure for activation of each fiber was calculated by a least-squares linear-regression plot of the SRF. The threshold pressure varied from 0 to 50 mmHg (mean, 16.21 +/- 2.86 mmHg). The distribution profile of the threshold values showed that there were two separate populations of mechanosensitive receptors: 1) wide-dynamic-range mechanonociceptors (WDR-MN) with mean threshold pressure of 2.89 +/- 0.75 mmHg (range, 0-7 mmHg; n = 22); and 2) high-threshold mechanonociceptors (HT-MN) with mean threshold of 33.26 +/- 2.52 mmHg (range, 19-50 mmHg; n = 13). 6. Discharge evoked by esophageal peristalsis was studied in five WDR-MN and five HT-MN units. Whereas all five WDR-MN units (threshold value, 2.6 +/- 0.96 mmHg) responded to peristalsis, none of the HT-MN units (threshold value, 31.2 +/- 4.01 mmHg) did so. The mean response to peristaltic contraction in WDR-MN units was 5.32 +/- 1.36 imp/s, which was 24.7% of the maximal response (21.53 +/- 1.92 imp/s; n = 5) at 120 mmHg. The duration of evoked response to peristaltic contraction was 10-12 s. 7. The activity profile of the units to 60-s balloon distension at near threshold and higher pressures showed three patterns: 1) rapid adaptation, 2) slow adaptation, and 3) slow adaptation with after discharge. The rapidly adapting fibers became slowly adapting with greater degrees of esophageal distension. The units that showed rapid or slow adaptation at low-distension pressure became indistinguishable from one another at high-distension pressure.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2005

Homeostatic-like plasticity of the primary motor hand area is impaired in focal hand dystonia.

The excitability of inhibitory circuits in patients with writer's cramp is reduced at multiple levels within the sensorimotor system, including the primary motor hand area (M1). Although this may play a major role in the pathophysiology of writer's cramp, it is still unclear what factors may cause the imbalance between inhibition and excitation to arise. One possibility is that homeostatic mechanisms that keep cortical excitability within a normal physiological range are impaired. In eight patients with writer's cramp and eight healthy age-matched controls, we combined low-frequency repetitive transcranial magnetic stimulation (rTMS) with transcranial direct current stimulation (TDCS) to probe regional homeostatic plasticity of the left M1. Confirming our previous study (Siebner et al., J Neurosci 2004; 24: 3379-85), 'facilitatory' preconditioning of the M1 with anodal TDCS enhanced the inhibitory effect of subsequent 1 Hz rTMS on corticospinal excitability. Conversely, 'inhibitory' preconditioning with cathodal TDCS reversed the after effect of 1 Hz rTMS, producing an increase in corticospinal excitability. The results were quite different in patients with writer's cramp. Following preconditioning with TDCS, 1 Hz rTMS induced no consistent changes in corticospinal excitability, indicating a loss of the normal 'homeostatic' response pattern. In addition, the normal inhibitory effect of preconditioning with cathodal TDCS was absent. The present data suggest that homeostatic mechanisms that stabilize excitability levels within a useful dynamic range are impaired in patients with writer's cramp. We propose that a faulty homeostatic response to acute increases in corticospinal excitability favours maladaptive motor plasticity. The role of homeostatic-like plasticity in the pathophysiology of task-specific dystonias warrants further study.

Adult↗
PubMed2003

Oxidase enzyme immobilisation through electropolymerised films to assemble biosensors for batch and flow injection analysis.

Glucose oxidase, lactate oxidase, L-aminoacid oxidase and alcohol oxidase were immobilised on new films based on 2,6-dihydroxynaphthalene (2,6-DHN) copolymerised with 2-(4-aminophenyl)-ethylamine (AP-EA) onto the Pt electrodes. The electropolymerisation was performed by cyclic voltammetry. Different scan rates and scan potential ranges were investigated and selected according to the monomers used. These sensors were tested for hydrogen peroxide, ascorbic acid and acetaminophen by cyclic voltammetry and amperometry. The amperometric studies were carried out in batch as well as in a flow injection analysis (FIA) system. Analytical parameters such as reproducibility, interference rejection, response time, buffer, storage and operational time of the sensors have been studied. These films were also characterised by X-ray photoelectron spectroscopy (XPS). Different strategies for enzyme immobilisation were performed and discussed: enzyme entrapment in the film during the electropolymerisation and covalent attachment of the enzyme to the film via a carbodiimide (1-ethtl-3-(3-dimethylaminopropyl)carbodiimide, EDC) or glutaraldehyde. Different parameters were considered in order to optimise the immobilisation procedures. Results provide a guide to design high sensitive, stable and interference-free biosensors. In addition, studies were performed using these probes in an original FIA based on solenoidal valves. Sensor stability, life time and dynamic range were also optimised in these conditions.

Biosensing Techniques↗
PubMedDate not supplied

Hearing at low and infrasonic frequencies.

The human perception of sound at frequencies below 200 Hz is reviewed. Knowledge about our perception of this frequency range is important, since much of the sound we are exposed to in our everyday environment contains significant energy in this range. Sound at 20-200 Hz is called low-frequency sound, while for sound below 20 Hz the term infrasound is used. The hearing becomes gradually less sensitive for decreasing frequency, but despite the general understanding that infrasound is inaudible, humans can perceive infrasound, if the level is sufficiently high. The ear is the primary organ for sensing infrasound, but at levels somewhat above the hearing threshold it is possible to feel vibrations in various parts of the body. The threshold of hearing is standardized for frequencies down to 20 Hz, but there is a reasonably good agreement between investigations below this frequency. It is not only the sensitivity but also the perceived character of a sound that changes with decreasing frequency. Pure tones become gradually less continuous, the tonal sensation ceases around 20 Hz, and below 10 Hz it is possible to perceive the single cycles of the sound. A sensation of pressure at the eardrums also occurs. The dynamic range of the auditory system decreases with decreasing frequency. This compression can be seen in the equal-loudness-level contours, and it implies that a slight increase in level can change the perceived loudness from barely audible to loud. Combined with the natural spread in thresholds, it may have the effect that a sound, which is inaudible to some people, may be loud to others. Some investigations give evidence of persons with an extraordinary sensitivity in the low and infrasonic frequency range, but further research is needed in order to confirm and explain this phenomenon.

Acoustics↗
PubMed2006

Quantitative determination of wine highly volatile sulfur compounds by using automated headspace solid-phase microextraction and gas chromatography-pulsed flame photometric detection. Critical study and optimization of a new procedure.

The quantitative determination of wine volatile sulfur compounds by automated headspace solid-phase microextraction (HS-SPME) with a carboxen-polydimethylsiloxane (CAR-PDMS) fiber and subsequent gas chromatography-pulsed flame photometric detection (GC-PFPD) has been evaluated. The direct extraction of the sulfur compounds in 5 ml of wine has been found to suffer from matrix effects and short linear ranges, problems which could not be solved by the use of different internal standards or by multiple headspace SPME. These problems were attributed to saturation of the fiber and to competitive effects between analytes, internal standards and other wine volatiles. Another problem was the oxidation of analytes during the procedure. The reduction in sample volume by a factor 50 (0.1 ml diluted with water or brine) brought about a reduction in the amount of sulfur compounds taken in the fiber by a factor just 3.3. Consequently, a new procedure has been proposed. In a sealed vial containing 4.9 ml of saturated NaCl brine, the air is thoroughly displaced with nitrogen, and the wine (0.1 ml) and the internal standards (0.02 ml) are further introduced with a syringe through the vial septum. This sample is extracted at 35 degrees C for 20 min. This procedure makes a satisfactory determination possible of hydrogen sulfide, methanethiol, ethanethiol, dimethyl sulfide, diethyl sulfide and dimethyl disulfide. The linear dynamic ranges cover the normal ranges of occurrence of these analytes in wine with typical r2 between 0.9823 and 0.9980. Reproducibility in real samples ranges from 10 to 20% and repeatability is better than 10% in most cases. The method accuracy is satisfactory, with errors below 20% for hydrogen sulfide and mostly below 10% for the other compounds. The proposed method has been applied to the analysis of 34 Spanish wines.

Automation↗
PubMed1996

Three-dimensional organization of otolith-ocular reflexes in rhesus monkeys. II. Inertial detection of angular velocity.

1. The dynamic contribution of otolith signals to three-dimensional angular vestibuloocular reflex (VOR) was studied during off-vertical axis rotations in rhesus monkeys. In an attempt to separate response components to head velocity from those to head position relative to gravity during low-frequency sinusoidal oscillations, large oscillation amplitudes were chosen such that peak-to-peak head displacements exceeded 360 degrees. Because the waveforms of head position and velocity differed in shape and frequency content, the particular head position and angular velocity sensitivity of otolith-ocular responses could be independently assessed. 2. During both constant velocity rotation and low-frequency sinusoidal oscillations, the otolith system generated two different types of oculomotor responses: 1) modulation of three-dimensional eye position and/or eye velocity as a function of head position relative to gravity, as presented in the preceding paper, and 2) slow-phase eye velocity as a function of head angular velocity. These two types of otolith-ocular responses have been analyzed separately. In this paper we focus on the angular velocity responses of the otolith system. 3. During constant velocity off-vertical axis rotations, a steady-state nystagmus was elicited that was maintained throughout rotation. During low-frequency sinusoidal off-vertical axis oscillations, dynamic otolith stimulation resulted primarily in a reduction of phase leads that characterize low-frequency VOR during earth-vertical axis rotations. Both of these effects are the result of an internally generated head angular velocity signal of otolithic origin that is coupled through a low-pass filter to the VOR. No change in either VOR gain or phase was observed at stimulus frequencies larger than 0.1 Hz. 4. The dynamic otolith contribution to low-frequency angular VOR exhibited three-dimensional response characteristics with some quantitative differences in the different response components. For horizontal VOR, the amplitude of the steady-state slow-phase velocity during constant velocity rotation and the reduction of phase leads during sinusoidal oscillation were relatively independent of tilt angle (for angles larger than approximately 10 degrees). For vertical and torsional VOR, the amplitude of steady-state slow-phase eye velocity during constant velocity rotation increased, and the phase leads during sinusoidal oscillation decreased with increasing tilt angle. The largest steady-state response amplitudes and smallest phase leads were observed during vertical/torsional VOR about an earth-horizontal axis. 5. The dynamic range of otolith-borne head angular velocity information in the VOR was limited to velocities up to approximately 110 degrees/s. Higher head velocities resulted in saturation and a decrease in the amplitude of the steady-state response components during constant velocity rotation and in increased phase leads during sinusoidal oscillations. 6. The response characteristics of otolith-borne angular VORs were also studied in animals after selective semicircular canal inactivation. Otolith angular VORs exhibited clear low-pass filtered properties with a corner frequency of approximately 0.05-0.1 Hz. Vectorial summation of canal VOR alone (elicited during earth-vertical axis rotations) and otolith VOR alone (elicited during off-vertical axis oscillations after semicircular canal inactivation) could not predict VOR gain and phase during off-vertical axis rotations in intact animals. This suggests a more complex interaction of semicircular canal and otolith signals. 7. The results of this study show that the primate low-frequency enhancement of VOR dynamics during off-vertical axis rotation is independent of a simultaneous activation of the vertical and torsional "tilt" otolith-ocular reflexes that have been characterized in the preceding paper. (ABSTRACT TRUNCATED)

Animals↗
PubMed2004

What does measure the scaling exponent of the correlation sum in the case of human heart rate?

It is shown that in the case of human heart rate, the scaling behavior of the correlation sum (calculated by the Grassberger-Procaccia algorithm) is a result of the interplay of various factors: finite resolution of the apparatus (finite-size effects), a wide dynamic range of mean heart rate, the amplitude of short-time variability being a decreasing function of the mean heart rate. This is done via constructing a simple model of heart rhythm: a signal with functionally modulated Gaussian noise. This model reproduces the scaling behavior of the correlation sum of real medical data. The value of the scaling exponent depends on all the above-mentioned factors, and is a certain measure of short-time variability of the signal.

Algorithms↗
PubMed2001

Modeling temporal and compressive properties of the normal and impaired auditory system.

Three modifications of a psychoacoustically and physiologically motivated processing model [Dau et al., J. Acoust. Soc. Am. 102 (1997a) 2892-2905] are presented and tested. The modifications aim at simulating sensorineural hearing loss and incorporate a level-dependent peripheral compression whose properties are affected by hearing impairment. Model 1 realizes this difference by introducing for impaired listeners an instantaneous level-dependent expansion prior to the adaptation stage of the model. Model 2 and Model 3 realize a level-dependent compression with time constants of 5 and 15 ms, respectively, for normal hearing and a reduced compression for impaired hearing. In Model 2, the compression occurs after the envelope extraction stage, while in Model 3, envelope extraction follows compression. All models account to a similar extent for the recruitment phenomenon measured with narrow-band stimuli and for forward-masking data of normal-hearing and hearing-impaired subjects using a 20-ms, 2-kHz tone signal and a 1-kHz-wide bandpass noise masker centered at 2 kHz. A clear difference between the different models occurs for the processing of temporally fluctuating stimuli. A modulation-rate-independent increase in modulation-response level for simulating impaired hearing is only predicted by Model 1 while the other two models realize a modulation-rate-dependent increase. Hence, the predictions of Model 2 and Model 3 are in conflict with the results of modulation-matching experiments reported in the literature. It is concluded that key properties of sensorineural hearing loss (altered loudness perception, reduced dynamic range, normal temporal properties but prolonged forward-masking effects) can effectively be modeled by incorporating a fast-acting expansion within the current processing model prior to the nonlinear adaptation stage. Based on these findings, a model of both normal and impaired hearing is proposed which incorporates a fast-acting compressive nonlinearity, representing the cochlear nonlinearity (which is reduced in impaired listeners), followed by an instantaneous expansion and the nonlinear adaptation stage which represent aspects of the retro-cochlear information processing in the auditory system.

Auditory Pathways↗
PubMed1996

Heterogeneous axonal arborizations of rat thalamic reticular neurons in the ventrobasal nucleus.

The gamma-aminobutyric acid (GABA)-containing neurons of the thalamic reticular nucleus (nRt) are a major source of inhibitory innervation in dorsal thalamic nuclei. Individual nRt neurons were intracellularly recorded and labelled in an in vitro rat thalamic slice preparation to investigate their projection into ventrobasal thalamic nuclei (VB). Camera lucida reconstructions of 37 neurons indicated that nRt innervation ranges from a compact, focal projection to a widespread, diffuse projection encompassing large areas of VB. The main axons of 65% of the cells gave rise to intra-nRt collaterals prior to leaving the nucleus and, once within VB, ramified into one of three branching patterns: cluster, intermediate, and diffuse. The cluster arborization encompassed a focal region averaging approximately 25,000 mu m2 and contained a high density of axonal swellings, indicative of a topographic projection. The intermediate structure extended across an area approximately fourfold greater and also contained numerous axonal swellings. The diffuse arborization of nRt neurons covered a large region of VB and contained a relatively low density of axonal swellings. Analysis of somatic size and shape revealed that diffuse arborizations arose from significantly smaller, fusiform-shaped somata. Cytochrome oxidase reactivity or parvalbumin immunoreactivity was used to delineate a discontinuous staining pattern representing thalamic barreloids. The size of a cluster arborization closely approximated that of an individual barreloid. The heterogeneous arborizations from nRt neurons may reflect a dynamic range of inhibitory influences of nRt on dorsal thalamic activity.

Animals↗
PubMed2005

The calibration of experimental self-developing Gafchromic HXR film for the measurement of radiation dose in computed tomography.

A prototype, self-developing Gafchromic HXR film has sensitivity an order of magnitude larger than that of the commercially available Gafchromic XR film used in interventional radiological applications. The higher sensitivity of the HXR film allows the possibility of acquisition of high-resolution calibrated dose profiles within the diagnostic range of exposure levels, below 10 R (87.7 mGy). We employed a commercially available, optical flatbed scanner for digitization of the film and image analysis software to determine the response of the HXR films to ionizing radiation. Spatial uniformity and temporal repeatability of the flatbed scanner were determined and used in optimization of the digitization protocol. The HXR film postexposure density growth and sensitivity to ambient light were determined using multiple scans of two simultaneously exposed sheets, one stored in light-tight conditions and the other continuously illuminated with white light. A calibrated step wedge of the HXR film was obtained by simultaneous irradiation of a portion of a film strip and a calibrated ionization chamber using a radiographic x-ray tube with beam characteristics matched to a typical CT scanner (8 mm Al HVL, 120 kVp). Repeated digitization of the calibration film was used to determine the precision of the film response measurements. The precision, as measured by the standard deviation of multiple measurements, was better than 1% over the full dynamic range of film response. This precision was measured using exposures ranging from 0.5 to 12 R (4.4 to 105.3 mGy). This exposure range is highly relevant to x-ray computed tomography. Preliminary radiation dose profiles demonstrate the utility of this technique.

Abdomen↗
PubMed1999

Monosyllabic word recognition at higher-than-normal speech and noise levels.

The effects of intensity on monosyllabic word recognition were studied in adults with normal hearing and mild-to-moderate sensorineural hearing loss. The stimuli were bandlimited NU#6 word lists presented in quiet and talker-spectrum-matched noise. Speech levels ranged from 64 to 99 dB SPL and S/N ratios from 28 to -4 dB. In quiet, the performance of normal-hearing subjects remained essentially constant in noise, at a fixed S/N ratio, it decreased as a linear function of speech level. Hearing-impaired subjects performed like normal-hearing subjects tested in noise when the data were corrected for the effects of audibility loss. From these and other results, it was concluded that: (1) speech intelligibility in noise decreases when speech levels exceed 69 dB SPL and the S/N ratio remains constant; (2) the effects of speech and noise level are synergistic; (3) the deterioration in intelligibility can be modeled as a relative increase in the effective masking level; (4) normal-hearing and hearing-impaired subjects are affected similarly by increased signal level when differences in speech audibility are considered; (5) the negative effects of increasing speech and noise levels on speech recognition are similar for all adult subjects, at least up to 80 years; and (6) the effective dynamic range of speech may be larger than the commonly assumed value of 30 dB.

Adult↗