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PubMed1999

Electrically evoked potentials recorded in adult and pediatric CLARION implant users.

The purpose of this study was to record electrical auditory brain stem responses (EABRs) and electrical middle latency responses (EMLRs) in the clinic from 3 adult CLARION Multi-Strategy Cochlear Implant subjects and to record EABRs in the operating room from 3 pediatric subjects. For 2 of the 3 adult subjects, EABR thresholds were within the subject's behavioral dynamic range, whereas 1 adult subject's EABR thresholds were either absent or, when present, exceeded the upper limit of the dynamic range. For this subject, EMLRs were absent or of poor morphology for the channels tested. Moreover, this subject was not able to understand speech in an open-set, auditory-only format. The EABR thresholds obtained with children were within the behavioral dynamic range for 2 of the 3 subjects, but exceeded comfortable loudness levels for 1 subject. Although the EABR thresholds were measured at stimulus levels that were audible for all subjects, the relationship of the EABR threshold levels to behavioral measures of loudness varied. Evoked potentials that originate more centrally, such as the EMLR, should be investigated further to determine the possible relationship to postimplant performance.

Adult↗
PubMed1994

Topographic representation of tone intensity along the isofrequency axis of cat primary auditory cortex.

The sound pressure level (SPL), henceforth termed intensity, of acoustic signals is encoded in the central auditory system by neurons with different forms of intensity sensitivity. However, knowledge about the topographic organization of neurons with these different properties and hence about the spatial representation of intensity, especially at higher levels of the auditory pathway, is limited. Here we show that in the tonotopically organized primary auditory cortex (AI) of the cat there are orderly topographic organizations, along the isofrequency axis, of several neuronal properties related to the coding of the intensity of tones, viz. minimum threshold, dynamic range, best SPL, and non-monotonicity of spike count--intensity functions to tones of characteristic frequency (CF). Minimum threshold, dynamic range, and best SPL are correlated and alter periodically along isofrequency strips. The steepness of the high-intensity descending slope of spike count--intensity functions also varies systematically, with steepest slopes occurring in the regions along an isofrequency strip where low thresholds, narrow dynamic ranges and low best SPLs are found. As a consequence, CF-tones of various intensities are represented by orderly and, for most intensities, periodic, spatial patterns of distributed neuronal activity along an isofrequency strip. For low--to--moderate intensities, the mean relative activity along the entire isofrequency strip increases rapidly with intensity, with the spatial pattern of activity remaining quite constant along the strip. At higher intensities, however, the mean relative activity along the strip remains fairly constant with changes in intensity, but the spatial patterns change markedly. As a consequence of these effects, low- and high-intensity tones are represented by complementary distributions of activity alternating along an isofrequency strip. We conclude that in AI tone intensity is represented by two complementary modes, viz. discharge rate and place. Furthermore, the magnitude of the overall changes in the representation of tone intensity in AI appears to be closely related to psychophysical measures of loudness and of intensity discrimination.

Acoustic Stimulation↗
PubMedDate not supplied

Design of the cochlear prosthesis: effects of the flow of current in the implanted ear.

When structures within the temporal bone are stimulated electrically it is desirable to maximize the dynamic range of the stimulus. The maximum dynamic range of electrical stimulus seems to be found when the threshold of stimulation is minimum. The minimum threshold of stimulus is likely to be reached when the electrical current that flow through regions containing excitable cells is maximized. By implanting electrodes throughout the temporal bone, it is possible to apply electrical currents to the ear and to measure the distributions of current flowing within the ear. The results of these measurements demonstrate that when current flow is directed outside the scala tympani, lower thresholds can be obtained. Frequency dependence of the paths of current flow cannot be used to explain the frequency dependence of the frequency-threshold functions measured in animals.

Animals↗
PubMed1977

Radio frequency clipping in hearing aids.

For those patients with reduced dynamic range of hearing, accomodation of normal dynamic range of speech has always presented a problem. This paper describes a method of overcoming the problem, a method which has the added benefit of offering improved speech discrimination as well as limiting the output from a hearing aid system. The principle employed is the presentation of taped speech material processed through clipping of a radio frequency single side side band suppressed carrier signal, which is filtered to remove the Fourier components and demodulated to obtain the modified speech material. Groups of normally hearing and hearing impaired subjects undergo speech audiometry testing to assess what improvement can be effected by this system. The majority of subjects tested both normal and hearing impaired achieve improved speech discrimination when using the system described. Further once the output was set no increase in the input signal could produce a level in excess of that set by the output control.

Adult↗
PubMed2002

Analytical validation of a real-time reverse transcription-polymerase chain reaction quantitation of different transcripts of the Wilms' tumor suppressor gene (WT1).

Transcript variants of the same gene may play distinct functions in the tissue where they are expressed. Absolute quantitation of different transcript variants in malignant and normal tissues can address the specific role of each particular isoform in cancer development and progression. We have recently demonstrated differential expression of the wild-type Wilms' tumor transcript (wtWT1) and a novel truncated WT1 transcript (trWT1) which lacks the first five exons of wtWT1, among human prostate cancer, leukemia, and breast cancer cell lines. Here we report the analytical validation of a real-time RT-PCR assay for the absolute quantitation of these two different WT1 transcripts with specific primers and probes that ensure specificity for each WT1 variant. By cloning each WT1 transcript in a T3 promoter-containing plasmid, we obtained two WT1 transcript-specific in vitro-generated RNA calibrators for absolute quantitation. Serial dilution of each RNA calibrator demonstrated a 5 log linear dynamic range (5 x 10(1) to 5 x 10(6) copies/reaction, R(2)=0.9963 for wtWT1 and R(2)=0.9993 for trWT1). Dilution of the calibrators in total RNA from 1 x 10(3) non-WT1-expressing cells showed a decreased sensitivity without affecting the linear dynamic range. Precision studies for values within the linear dynamic range showed a coefficient of variation of less than 4% for both transcripts. The described method provides a sensitive and reliable technique for quantitating different WT1 mRNA transcripts.

Calibration↗
PubMed1975

White noise analysis of Phycomyces light growth response system. II. Extended intensity ranges.

By means of white gaussian noise stimulation, the Wiener kernels are derived for the Phycomyces light growth response for a variety of intensity conditions. In one experiment the intensity I, rather than log I, is used as the input variable. Under the very limited dynamic range of that experiment, the response is fairly linear. To examine the dependence of the kernels on dynamic range, a series of experiments were performed in which the range of log I was halved and doubled relative to normal. The amplitude of the kernels, but not the time course, is affected strongly by the choice of dynamic range, and the dependence reveals large-scale nonlinearities not evident in the kernels themselves. In addition kernels are evaluated for experiments at a number of absolute intensity levels ranging from 10(-12) to 10(-3) W/cm2. The kernel amplitudes are maximal at about 10(-6) W/cm2. At 10(-12) W/cm2, just above the absolute threshold, the respond is very small. The falloff at high intensity, attributable to inactivation of the photoreceptor, is analyzed in the framework of a first-order pigment kinetics model, yielding estimates for the partial extinction coefficient for inactivation epsilonI455 = (1.5 +/- 0.2) X 10(4) liter/mol-cm and a regeneration time constant of tau = (2.7 +/- 0.6) min. A model is introduced which associates the processes of adaptation and photoreceptor inactivation. The model predicts that the time constants for adaptation and pigment should be identical. This prediction is consistent with values in this and the preceding paper. The effects of pigment inactivation are simulated by a linear electronic analog circuit element, which may be cascaded with the linear simulator circuit in the preceding paper.

Adaptation, Physiological↗
PubMed2026

Reframing Proteomics Measurement: Super Mass Spectrometry Framework and the Role of Delayed Electrospray Ionization Technique.

Dynamic range, repeatability, and reproducibility remain the central limitations of data-independent acquisition (DIA) proteomics. Current workflows emphasize protein group identification counts and throughput, but these metrics mask the fundamental measurement challenge: generating a repeatable, reproducible, high-fidelity, and relatively complete digital representation of complex proteomes. In particular, plasma proteomics spans more than 10 orders of magnitude in protein abundance, far exceeding the capacity and dynamic range of any single mass spectrometer. Incremental advances have not closed this gap. In this Perspectives article, I introduce the Super Mass Spectrometry framework and then highlight the Delayed Electrospray Ionization (Delayed-ESI) technique, as a practical approach to address these limitations. By producing compositionally identical but temporally staggered ion beams, the Delayed-ESI technique enables deterministic remeasurement of the same analyte profile, supporting various novel strategies to improve analytical figures of merit. While recent implementations of the Delayed-ESI technique have emphasized throughput, I argue that the broader value of the Delayed-ESI technique lies in extending dynamic range and improving repeatability and reproducibility─objectives that should take precedence if proteomics is to evolve into a robust measurement science capable of supporting population-scale proteomics studies.

Proteomics↗
PubMed2000

Effect of electrical stimulation of peripheral nerves on neuropathic pain.

STUDY DESIGN: Changes in the electrophysiologic response of spinal dorsal horn neurons elicited by peripheral electrical stimulation were examined. OBJECTIVE: To investigate whether the electrical stimulation of peripheral nerves causes an inhibition of pain at the spinal cord level. SUMMARY OF BACKGROUND DATA: The wide dynamic range neurons studied were known to be excited by primary afferent fibers, not only combined A (delta) and C nociceptive fibers, but also low-threshold mechanoreceptive A (beta) fibers and A (delta) fibers of down hairs. The wide dynamic range neurons are classified as nociceptive neurons. METHODS: Responses of wide dynamic range neurons in the lumbosacral dorsal horn to input from C fibers were studied in urethane chloralose-anesthetized cats. The posterior tibial nerve and sciatic nerve were stimulated simultaneously to examine the effect on the C fiber responses elicited by superficial peroneal nerve stimulation. RESULTS: Simultaneous stimulation of the posterior tibial nerve and sciatic nerve was performed with superficial peroneal nerve C fiber stimulation. CONCLUSIONS: This study demonstrated that electrical stimulation of peripheral nerves leads to inhibitory input to the pain pathways at the spinal cord level.

Action Potentials↗
PubMed2000

Quantitative NMR characterization of long-range chain dynamics prior to reptation: polyethylene-oxide

The thorough analysis of the transverse magnetic relaxation of protons, attached to highly entangled polyethylene-oxide chains in the melt, reveals two striking chain-length dependent properties; these are interpreted from the description (reminiscent of the Rouse model) of the long-range chain dynamics supposed to occur prior to the reptation motion. Experimental results are well matched by this specific NMR approach which accounts for the novel properties and provides the monomeric friction coefficient and the terminal relaxation time, over the molecular weight range 65K to 760K.

Journal Article↗
PubMed2005

DIMSCAN: a microcomputer fluorescence-based cytotoxicity assay for preclinical testing of combination chemotherapy.

DIMSCAN is a semiautomatic fluorescence-based digital image microscopy system that quantifies relative total (using a DNA stain) or viable (using fluorescein diacetate [FDA]) cell numbers in tissue culture multiwell plates ranging from 6 to 384 wells per plate. DIMSCAN is a rapid and efficient tool for conducting in vitro cytotoxicity assays across a 4 log dynamic range. The specificity of detecting viable cells with FDA is achieved by using digital image processing and chemical quenching of fluorescence in nonviable cells with eosin Y. Average scan time for the most commonly used format, a 96-well plate, is 6 min. Cytotoxicity for neuroblastoma cell lines measured by DIMSCAN was found to be comparable to manual Trypan blue dye exclusion counts or colony formation in soft agar, but with a significantly wider dynamic range, which enables drug combination studies used to detect synergistic or antagonistic interactions. The linearity of DIMSCAN was validated (r2 = 0.99967 +/- 0.0003) for cells stained with FDA deposited using a fluorescence-activated cell sorter, documenting a dynamic range > 4 logs, and the ability to detect a single viable cell in a well 93% of the time. DIMSCAN has been used to demonstrate preclinical activity of cytotostatic and cytotoxic drugs and drug combinations that have subsequently shown activity in clinical trials.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Enhanced instrumental sensitivity and selectivity for aminopeptidase profiling.

Laser-excited fluorimetry has been applied to the identification of bacteria and fungus. The instrumental sensitivity and selectivity of the aminopeptidase profiling method has been enhanced by the use of laser excitation in conjunction with improved spectral and temporal background rejection. The linear dynamic range for the aminopeptidase technique has been increased by achieving a reduced lower limit of detection of the fluorescent tag, beta-naphthylamine. Standard aminopeptidase methodology only provides a linear dynamic range of 1.5 orders of magnitude. The laser-based method expanded the range to three orders of magnitude allowing the inherent specificity of aminopeptidase enzymes within the pathogen to be observed. The enhanced linear dynamic range was observed in profiles of Agrobacterium tumefaciens rubi and Phytophthora megasperma var. sojae.

2-Naphthylamine↗
PubMed2004

The limits of log-ratios.

BACKGROUND: DNA microarray assays typically compare two biological samples and present the results of those comparisons gene-by-gene as the logarithm base two of the ratio of the measured expression levels for the two samples. RESULTS: Because of the fixed dynamic range of fluorescence and other detection systems, there is a limit to the range of comparisons that can be made using any array technology, and this must be taken into account when interpreting the results of any such analysis. CONCLUSIONS: The dynamic range of microarray data collection systems results in limits in the comparative analyses that can be derived from such measurements and suggests that optimal results can be obtained by making measurements that avoid the boundaries of that dynamic range.

Algorithms↗
PubMed2000

Regional variations of noise-induced changes in operating range in cat AI.

Regional differences in spectral integration of neurons in cat primary auditory cortex (AI) suggest that regions differ in effects of background noise on operating characteristics of neurons. Therefore, tone-response threshold, best level (peak-rate intensity), dynamic range, and sharpness of tuning in quiet and in continuous broadband noise were mapped for single neurons along the isofrequency domain of AI. Neurons did not show an excitatory response to the noise. Noise invariably increased the tone-response threshold and best levels. Consequently, the dynamic ranges and receptive fields shifted to higher intensity levels without changes of average sharpness of tuning. These shifts were linearly related to noise level and showed little inter-neuronal variability for neurons in the central, mostly sharply tuned part of AI. In more dorsal and ventral parts of AI, neurons were more variable in tone-response threshold, dynamic range and best level, and no systematic relationship between increase in noise level, threshold increase and best-level increase was observed. We conclude that linear shifts in the operating range of neurons in central AI in the presence of continuous noise backgrounds do not affect other response properties and may relate to the unaltered analysis and representation of spectral components of sounds. In contrast, neurons in dorsal and ventral AI change response properties in a non-predictable way in the presence of noise in accordance with the more complex receptive field properties in those areas.

Acoustic Stimulation↗
PubMed2004

Optimized conditions for diluting and reusing a fluorescent protein gel stain.

This study elucidates the optimum conditions at the minimum cost for using SYPRO Ruby protein gel stain. It deals with the effects of gel fixation and staining times, as well as dilution and reuse of SYPRO Ruby protein gel stain in one-dimensional (1-D) gels. Signal strength and dynamic range were highest in gels that were fixed thoroughly before staining, followed by overnight staining. Using the optimized protocol, dilution or reuse of the stain reduces the dynamic range and signal intensity. Sensitivity remains high if the stain is reused up to two times, but signal intensity is reduced up to 2.5-fold in twice used stain. Sensitivity also remains high if the stain is diluted 1:2 in water, but signal intensity is reduced up to 6-fold. Of the two options, reuse or dilution, reuse better retains signal intensity and dynamic range.

Electrophoresis, Polyacrylamide Gel↗
PubMed1985

Effects of adenosine 5'-monophosphate and adenosine 5'-triphosphate on functionally identified units in the cat spinal dorsal horn. Evidence for a differential effect of adenosine 5'-triphosphate on nociceptive vs non-nociceptive units.

A study was done of the effects of iontophoretic application of adenosine 5'-monophosphate (AMP) and adenosine 5'-triphosphate (ATP) on functionally identified neurones in the spinal dorsal horn of the cat. AMP depressed nearly two-thirds of the 32 neurones tested regardless of functional type; the remainder were unaffected. ATP, on the other hand, had three types of effect: depression, excitation and a biphasic effect which consisted of excitation followed by depression. A significant difference was found when a comparison was made of the frequency of occurrence of each of these three types of effect in the samples of non-nociceptive (n = 18) and of wide dynamic range neurones (n = 42): of non-nociceptive neurones 61% were excited, 11% were depressed, 6% had a biphasic response and 22% were unaffected; of wide dynamic range neurones 45% had a biphasic response, 19% were depressed, 14% were excited and 21% were unaffected (chi 2 = 16.2, P less than 0.005). The depressant effects of both AMP and ATP and the depressant phase of the biphasic effect of ATP seem to be mediated through activation of P1-purinergic receptors because these effects were blocked by theophylline, a P1-purinergic antagonist [Burnstock (1978) In Cell Membrane Receptors for Drugs and Hormones: A Multidisciplinary Approach, pp. 107-118]. Thus the biphasic effect appears to consist of excitatory and depressant responses in the same neurone. The differential effects of ATP on non-nociceptive vs wide dynamic-range neurones are similar to the differential effects on these neurones observed during activation of low-threshold primary afferents. This similarity, together with evidence that ATP can be released from primary afferent neurones [Holton and Holton (1954) J. Physiol., Lond. 126, 124-140; Holton (1959) J. Physiol., Lond. 145, 494-504], prompts us to suggest that ATP may be a chemical mediator of effects of low-threshold primary afferent inputs in the spinal dorsal horn.

Adenosine Monophosphate↗
PubMedDate not supplied

Optical image processing with liquid-crystal display for image intensifier/television systems.

We have studied the effect of real-time optical image processing (OIP) in an image intensifier/television (II-TV) radiographic imaging system by using a liquid-crystal display (LCD) placed between the II and the TV camera. The LCD compresses the dynamic range of the transmitted image by modulating the spatial distribution of the light intensity of the image from the output phosphor of the II. The degree of dynamic-range compression can be designed so that the dependence of the signal-to-noise ratio (SNR) of the LCD-TV system on x-ray intensity matches that of the quantum noise. We measured the physical properties of an LCD and evaluated its capability for OIP. Our experimental results demonstrate that it is feasible to use an LCD to compress the dynamic range and to improve the SNR of the image. The advantages of implementing OIP with an LCD in image acquisition systems in which a TV camera is used are discussed.

Humans↗
PubMed1998

Analytical performance of Elecsys 2010--a multicentre evaluation.

The analytical performance of Elecsys 2010 has been assessed in a multicentre evaluation, which involved twelve laboratories from eight countries worldwide. Eleven alanytes (TSH, T4, FT4, T3, FT3, T-up, TNT, CK-MB, HCG, CEA and PSA) were tested using a protocol related to the ECCLS guidelines and the Standard Operating Procedures of the manufacturer. The evaluation was supported by a "Computer Aided Evaluation" (CAEv) program system and telecommunications. Within-run and between-day imprecision for the various analytes with 3% CV and 3 to 8% CV, resp. was comparable to homogeneous immunoassays e.g. for specific proteins on clinical chemistry analysers. The functional sensitivity for TSH, TNT and PSA was met by low concentrations: < 0.02 microIU/ml TSH, < 0.05 ng/ml TNT and < 0.07 ng/ml PSA. TSH is an assay of the third generation according to the recommendation of Spencer. The measured lower detection limit was less or equal to the manufacturer's specifications with the exception of the PSA assay. Drift effects (over eight hours) and signal carry-over effects were not observed. A high-dose hook effect became relevant for concentrations higher than 430,000 IU/HCG--an assay with a dynamic range of 10,000 IU/I. The Elecsys assays showed a high dynamic range and rarely necessary predilutions could be performed by the Elecsys instrument using the Elecsys multidiluent. Endogenous interferences were not observed. Calibration stability was confirmed for one week and data indicated that it could be extended at least for three weeks. The quality assurance experiment showed a good transferability of the results between the participating laboratories. The assigned values of two interlaboratory survey materials were found for most of the analytes within a deviation of +/- 10%. Higher deviations could be explained by differences in standardization and methods. The Elecsys 2010 system offers a high analytical sensitivity in combination with relatively low sample volumes and short measuring times (< or = 18 minutes); a high dynamic measuring range reduces the number of reruns and makes the work-flow more convenient. The electrochemiluninescence technology of Elecsys 2010 shows advantages in system performance without having any drawbacks compared to existing technologies.

Biomarkers↗
PubMed1995

The input/output formula: a theoretical approach to the fitting of personal amplification devices.

There is a growing trend for hearing aids to incorporate wide dynamic range compression. The input/output (I/O) hearing aid formula, presented in this report, is a general frequency-specific mathematical approach which describes the relationship between the input level of a signal delivered to a hearing aid and the output level produced by the hearing aid. The I/O formula relates basic psychoacoustic parameters, including hearing threshold level and uncomfortable listening level, to the electroacoustic characteristics of hearing aids. The main design goal of the I/O formula was to fit the acoustic region corresponding to the "extended" normal auditory dynamic range into the hearing-impaired individual's residual auditory dynamic range. The I/O approach can be used to fit hearing aids utilizing linear gain, linear compression or curvilinear compression to a hearing-impaired individual's residual auditory area.

Auditory Threshold↗