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Syllabic compression: effective compression ratios for signals modulated at different rates.

Compression circuits are being used increasingly in hearing aids to reduce the dynamic range of signals. Their performance is usually characterized by: (1) the threshold sound level above which the compression starts to operate; (2) the compression ratio, which is the change in input level (in dB) required to achieve a 1 dB change in output level; and (3) the attack and release times over which the signal is integrated to determine the necessary gain change. In many practical situations, the effective compression ratio obtained with dynamically varying signals such as speech is less than the compression ratio obtained using standard test signals (slow square-wave modulation with large modulation depth). This article describes the effective compression ratios achieved with sinusoidal modulation, as a function of modulation rate, level relative to the compression threshold, compression ratio and time constants. The effects of compression on a typical speech signal are also discussed.

Acoustic Stimulation↗

Quantitation of metallothionein mRNA by RT-PCR and chemiluminescence.

A general procedure has been developed for the determination of mRNA expression by reverse transcription polymerase chain reaction (RT-PCR), over a wide concentration range, with quick quantitation of amplified products by luminescence. The discriminating power of this approach is the specific hybridization of PCR product to ruthenium-labeled oligonucleotide probe(s). This method is sensitive enough to detect increases in the formation of PCR product by the 6th cycle. The accumulation of PCR product was successfully modeled with a recursive relationship. This procedure was capable of accurately determining starting template copies over a 9-log dynamic range, with a sensitivity limit of 10(2) copies. Inclusion of an mRNA internal standard (identical to amplified template except for a 6-bp deletion) corrected variabilities in the reverse transcriptase as well as PCR, allowing for the expression of data as mRNA copy number/micrograms total tissue RNA. This procedure was used to detect changes in levels of winter flounder (Pleuronectes americanus) liver metallothionein mRNA. Liver metallothionein mRNA levels ranged from 1.0 x 10(6) copies/micrograms total tissue RNA in control samples to 1.0 x 10(9) copies/micrograms total tissue RNA in samples treated with Cd (a known metallothionein mRNA inducer).

Animals↗

[Contrast media in MR mammography].

A standardized relationship between concentration of contrast media and normalized signal intensity should be the basis of a diagnostic evaluation of MR-mammography at different sites and with different sequences. In this work we compared the dynamic range of the MR-compatible contrast medium Magnevist at different sequences and machines. For this purpose we made measurements with a phantom, consisting of MR-compatible glass tubes filled with contrast medium of different concentrations. The glass tubes were placed in a water bath. All measurements were made with breast coils. The signal intensity of the glass tubes was normalized to the signal intensity of the native probe (water = 1). These normalized dynamic curves were compared with each other in order to find, for the different machines, the sequence which is nearest to a defined "Standard-Curve". As this task proved not possible for all machines, we measured how the dynamic curves of the different machines related to the "Standard-Curve". For all sequences we made also measurements with a female student to assure the quality of the pictures. Thus the participating radiologists can now compare their dynamic measurements of breast lesions with each other.

Breast↗

Evaluation of a wide range of amplitude-frequency responses for the hearing impaired.

The long-term average frequency spectrum of speech was modified to 25 target frequency spectra in order to determine the effect of each of these spectra on speech intelligibility in noise and on sound quality. Speech intelligibility was evaluated using the test as developed by Plomp and Mimpen (1979), whereas sound quality was examined through judgments of loudness, sharpness, clearness, and pleasantness of speech fragments. Subjects had different degrees of sensorineural hearing loss and sloping audiograms, but not all of them were hearing aid users. The 25 frequency spectra were defined such that the entire dynamic range of each listener, from 5 dB above threshold to 5 dB below UCL, was covered. Frequency shaping of the speech was carried out on-line by means of Finite Impulse Response (FIR) filters. The tests on speech reception in noise indicated that the Speech-Reception Thresholds (SRTs) did not differ significantly for the majority of spectra. Spectra with high levels, especially at low frequencies (probably causing significant upward spread of masking), and also those with steep negative slopes resulted in significantly higher SRTs. Sound quality judgments led to conclusions virtually identical to those from the SRT data: frequency spectra with an unacceptably low sound quality were in most of the cases significantly worse on the SRT test as well. Because the SRT did not vary significantly among the majority of frequency spectra, it was concluded that a wide range of spectra between the threshold and UCL levels of listeners with hearing losses is suitable for the presentation of speech energy. This is very useful in everyday listening, where the frequency spectrum of speech may vary considerably.

Adult↗

Eccentricity-dependent scaling of the limits for short-range apparent motion perception.

The ability to report the direction of apparent motion when an array of random dots is displaced fails when the displacement exceeds a limiting value (dmax). We find that dmax increases rapidly with retinal eccentricity, in a manner different from spatial measures such as acuity which are believed to depend on the "magnification factor" of projection to area 17. The minimum displacement giving detectable motion (dmin) shows a shallower increase with eccentricity which is more compatible with the variation of cortical magnification. The dependence of apparent motion on the timing variables (exposure duration, inter-stimulus interval) changes negligibly with eccentricity. Consequently the dynamic range and the upper limit of detectable velocities increases greatly with eccentricity. The increase of dmax with eccentricity means that the perception of apparent motion will show an approximate invariance with display scale, even though dmax has a locally fixed value depending on receptive field structure.

Fixation, Ocular↗

Top down mass spectrometry of < 60-kDa proteins from Methanosarcina acetivorans using quadrupole FRMS with automated octopole collisionally activated dissociation.

A fragmentation geometry based upon axial acceleration of m/z-selected protein ions into a linear octopole ion trap allowed simultaneous production and external accumulation of fragment ions prior to m/z measurement in a FT mass spectrometer. Improved dynamic range resulting from this octopole collisionally activated dissociation resulted in a 2.5x increase in experimental throughput and a 2x increase in fragment ion matches to gene products identified and characterized in the top down fashion. The acceleration voltage for optimal fragmentation has a m/z and mass dependence, knowledge of which facilitated an automated platform for top down MS/MS on a quadrupole FT hybrid mass spectrometer. Controlled by improved software for data acquisition (e.g. using dynamic exclusion of previously identified species), automated octopole collisionally activated dissociation of samples fractionated using chromatofocusing and reversed-phase liquid chromatography achieved a significant increase in protein identification rate versus previous benchmarks. Also a batch analysis version of ProSight PTM facilitated probability-based identification of intact proteins obtained in a higher throughput fashion. In total, 101 unique proteins (5-59 kDa) were identified from whole cell lysates of Methanosarcina acetivorans grown anaerobically, including the characterization of several mispredicted start sites and biologically relevant mass discrepancies.

Amino Acid Sequence↗

Group III metabotropic glutamate receptors and exocytosed protons inhibit L-type calcium currents in cones but not in rods.

Light responses of photoreceptors (rods and cones) are transmitted to the second-order neurons (bipolar cells and horizontal cells) via glutamatergic synapses located in the outer plexiform layer of the retina. Although it has been well established that postsynaptic group III metabotropic glutamate receptors (mGluRs) of ON bipolar cells contribute to generating the ON signal, presynaptic roles of group III mGluRs remain to be elucidated at this synaptic connection. We addressed this issue by applying the slice patch-clamp technique to the newt retina. OFF bipolar cells and horizontal cells generate a steady inward current in the dark and a transient inward current at light offset, both of which are mediated via postsynaptic non-NMDA receptors. A group III mGluR-specific agonist, L-2-amino-4-phosphonobutyric acid (L-AP-4), inhibited both the steady and off-transient inward currents but did not affect the glutamate-induced current in these postsynaptic neurons. L-AP-4 inhibited the presynaptic L-type calcium current (ICa) in cones by shifting the voltage dependence of activation to more positive membrane potentials. The inhibition of ICa was most prominent around the physiological range of cone membrane potentials. In contrast, L-AP-4 did not affect L-type ICa in rods. Paired recordings from photoreceptors and the synaptically connected second-order neurons confirmed that L-AP-4 inhibited both ICa and glutamate release in cones but not in rods. Furthermore, we found that exocytosed protons also inhibited ICa in cones but not in rods. Selective modulation of ICa in cones may help broaden the dynamic range of synaptic transfer by controlling the amount of transmitter release from cones.

Animals↗

Microscale protein expression profiling during disease evolvement.

Advances in technology, such as laser capture microdissection (LCM), have allowed for the specific sampling of cells within their natural functional micro-environment. In model systems using LCM, we have studied the global protein expression profiles of airway epithelial cells during a response to allergen provocation. Bronchial epithelial cells were first identified and phenotyped histologically in snap frozen lung samples of experimentally sensitised mice. Consecutive thin sections of whole lung were then sampled using preparative LCM procedures. Lysates of the captured epithelium (7500 shots) or whole lung were prepared for two-dimensional gel electrophoretic separation and 1400 protein spots were annotated by image analysis. Protein identities were established by matching peptide masses detected using matrix-assisted laser desorption ionization time-of-flight MS as well as electrospray ionization MS-MS sequencing. Using the Mascot database of protein/peptide identities high significance scores in terms of sequence coverage (range 22-70%) and number of peptides (range 7-22 peptides/protein) were obtained for approximately 500 proteins, with examples listed in Table 1. In quantitative terms, the LCM procedure allows the statistical sampling of singular populations of cells distributed throughout tissues and organs. The absolute number of cells required for "entry level" measurements of protein profiles will vary over an order of magnitude depending on the physical size and frequency of the cells being studied within each biological compartment as well as the dynamic range of the proteins being measured, and the absolute limits of detection within the technologies being employed.

Animals↗

Differences in phonetogram features between male and female subjects with and without vocal training.

Singing not only requires good voluntary control over phonation and a musical ear, it also demands certain capacities of the voice source. These capacities include a desirable range of sound intensity and frequency, which can be measured and represented in a phonetogram. The influence of specific factors on voice capacities may be ascertained by the analysis of phonetograms. To determine the influence of the factors gender and voice training, phonetograms of 224 subjects, subdivided accordingly into four groups, were analyzed in two different ways. One is based on the rescaling of phonetograms, whereas the other derives analytic variables from the features' shape, area, and dynamic range. Analysis showed that, regarding gender, male subjects are able to produce softer phonations, whereas female subjects produced louder phonations at specific parts of their comparable frequency ranges. Trained subjects have a larger enclosed area of the phonetogram, which is primarily based on extended soft voice capabilities in both genders and the significantly larger frequency range in trained female subjects. The shape analysis, performed with Fourier Descriptors, revealed differences for the factors gender and training.

Adolescent↗

Dual lifetime referencing as applied to a chloride optical sensor.

A membrane with an optical response to chloride has been developed that contains two luminophores that display two largely different decay times. The first luminophore (the "reference") is a chloride-insensitive ruthenium metal-ligand complex possessing a decay time in the microsecond range. The second luminophore is the short-lived chloride-quenchable fluorescent probe lucigenin. Both are contained in a hydrogel matrix and are excited by a blue LED emitting sinusoidally modulated light. Under these conditions, the chloride-dependent fluorescence intensity of lucigenin can be converted in an analyte-dependent fluorescence phase shift that depends on the ratio of the two luminescence intensities and can be measured at modulation frequencies of typically 45 kHz. The dynamic range of this sensor can be adjusted by either varying the ratio of the two luminophores or selecting a particular optical filter combination.

Acridines↗

A portable diffuse reflectance spectrophotometer for the rapid and automatic measurement of meat pigments.

A portable reflectance spectrophotometry system, which can measure a wide range of absorbance and has an adhesive pad type fibre optic probe, was developed to improve the availability of non-invasive reflectance spectrophotometry. A Czerny-Turner type spectrometer, which can be connected to an optical fibre probe, was developed, and a linear charge coupled device (CCD) was used as its light detector to increase data acquisition speed. The scanning time of the linear CCD is automatically controlled in accordance with the reflectance of meat to increase the dynamic range of absorption. We tried to apply this instrument to samples of meat pigments in order to demonstrate whether reflectance spectrophotometry is suitable for evaluating the freshness of meat. We examined the myoglobin solution in the form of the met-derivative in order to detect the concentration of myoglobin. The absorbance spectrum of myoglobin in the range of 0-4 mg dl(-1) was successfully distinguished with this instrument.

Animals↗

Mass spectrometry: analytical capabilities and potentials.

The mass range of mass spectrometers has been extended by almost an order of magnitude in the past decade, ionization procedures have been introduced which allow ionic, nonvolatile compounds to be examined, and new capabilities have been achieved through the successful integration of separation and analysis techniques. In combination with other techniques, mass spectrometry has been used in biological and environmental research to characterize constituents of mixtures, including those present in trace amounts; in metabolic profiling, where high throughput and large dynamic range are important; and in protein structure determinations. Measurements of stable isotope abundances by mass spectrometry have been used in enzymology, studies of photosynthesis, and carbon dating. Outside the area of chemical analysis, mass spectrometry has been used to study gas-phase acidities and basicities and to study organic reaction mechanisms in the gas phase. Trends in mass spectrometry include multidimensional experiments, use of ionization methods, direct analysis without extensive sample preparation, and the development of advanced instrumentation including an ion trap and an inductively coupled plasma mass spectrometer. It is likely that mass spectrometry will come to be much more widely used and that data will increasingly be other than conventional mass spectra.

Fourier Analysis↗

[Laryngeal registers as shown in the voice range profile].

Voice range profile (VRP) is a well-known vocal test. Usually, it consists of a single diagram based on the whole voice range. When practised separately in each individual laryngeal mechanism, VRP may offer much information on both the relative development of the different mechanisms used by the subject and the extension of the common area between two consecutive mechanisms. We present the results obtained from 42 subjects of both sexes who have different singing technique levels: professional singers, student and amateur singers, as well as subjects without any experience in singing. For each mechanism, the global VRP area and the dynamic range were computed. Results are discussed in relation to sex category and vocal training of subjects. Exploring systematically VRP for each mechanism gives new and valuable information on register managing in singing practice.

Adult↗

Damus-Stansel-Kaye procedure: current indications and results.

Between October 1983 and August 1991, 29 consecutive Damus-Stansel-Kaye procedures were performed. Indications for operation included restrictive bulboventricular foramen or subaortic stenosis associated with complex univentricular congenital heart disease (25) and Taussig-Bing heart, subaortic stenosis, or both associated with complex biventricular congenital heart disease (4). Twelve patients underwent concurrent Fontan procedures. Average age at operation was 39.8 months (range, 1 to 132 months). Average outflow tract gradient was 28 mm Hg (range, dynamic to 80 mm Hg). Of the 29 patients, 23 were male and 6 were female. There were three early deaths (10%), two in patients who had a concurrent Fontan procedure. Although there was a trend toward lower age and higher outflow tract gradients in nonsurvivors, these and other factors were not statistically significant predictors of death. Actuarial freedom from cardiac-related death was 88% at 5 years (n = 7). In a mean follow-up of 3.5 years (range, 0.1 to 7.7 years), 3 patients have required reoperation (10%), 2 for aortic valve insufficiency (5 days and 2.75 years) and 1 for a gradient across the anastomosis (5.75 years). Actuarial freedom from reoperation related to a failed Damus-Stansel-Kaye procedure was 90% at 4 years and 75% at 6 years (n = 7).

Actuarial Analysis↗

Europium-labelled streptavidin as a highly sensitive universal label. Indirect time-resolved immunofluorometry of FSH and TSH.

Labelling of streptavidin with a fluorogenic europium ion was optimized with the aim of obtaining a universal, stable and highly sensitive non-isotopic label for time-resolved fluorometric immunoassays (TR-FIA) based on dissociative fluorescence enhancement (DELFIA). Even the conjugation of all the free amino groups of streptavidin with Eu chelates had only a minor effect on the binding capacity of the protein or its affinity. The labelled streptavidin was evaluated in indirect time-resolved immunofluorometric assays of human follicle and thyroid stimulating hormones (FSH and TSH). The interassay imprecision was below 3% within the concentration range from 2.5 to 94 U/l for the FSH samples and below 5% in the range from 2.4 to 35 mIU/l for the TSH samples. The detection limits of the assays for FSH and TSH were 0.05-0.10 U/l and 0.01-0.025 mIU/l, respectively, when a CV of 15% was regarded as the acceptable upper limit of imprecision. The results obtained by the indirect assays correlated closely with those obtained by corresponding direct sandwich assays. The model assays demonstrated the utility of Eu-labelled streptavidin as a universal reagent for immunoassays requiring a wide dynamic range and high sensitivity.

Bacterial Proteins↗

Determination of steroid sex hormones in water and urine matrices by stir bar sorptive extraction and liquid chromatography with diode array detection.

In this study, stir bar sorptive extraction and liquid desorption followed by high performance liquid chromatography with diode array detection (SBSE-LD-HPLC/DAD) were combined for the simultaneous determination of nine steroid sex hormones (estrone, 17alpha-estradiol, 17beta-estradiol, 17alpha-ethynylestradiol, diethylstilbestrol, mestranol, progesterone, 19-norethisterone and norgestrel) in water and urine matrices. During the method development, it has been demonstrated that equilibrium time, ionic strength and back extraction solvents are the most important parameters to control, for determining the nine-hormones in water matrices, in which stir bars coated with 126 microl of polydimethylsiloxane were used. Assays performed on 30 ml water samples spiked at 10 microg/l levels under optimised experimental conditions, yielded recoveries ranging from 11.1+/-4.9% (17beta-estradiol) to 100.2+/-10.4% (mestranol), showed that the methodology is well described by the octanol-water partition coefficients (K(PDMS/W) approximately K(O/W)) for the latter, while pronounced deviations to the theoretical efficiency (K(PDMS/W) not equal K(O/W)) were observed for the remaining hormones. From calibration studies, a good analytical performance for all hormones was attained, including a suitable precision (2.1-17.1%), low limits of detection (0.3-1.0 microg/l) and an excellent linear dynamic range (1.25-50.0 microg/l). Assays on environmental water and urine matrices showed recovery yields in worthy good agreement with the spiking level (10 microg/l), and suitability for profiling low microg/l levels of natural hormones in urine samples taken from pregnant women. The present methodology is easy, reliable and sensitive at the trace level, only requiring a low sample volume, showing to be a good analytical alternative to routine quality control for environmental and biomedical laboratories.

Chromatography, High Pressure Liquid↗

High-performance liquid chromatography of azobenzene derivatives with spectrophotometric and electrochemical detection.

The chromatographic behaviour of azobenzene and fourteen of its derivatives was studied by reversed-phase high-performance liquid chromatography with a C18 stationary phase. The optimal composition of the mobile phase is 9:1 methanol-0.01 M aqueous sodium dihydrogen phosphate which is 0.0002 M in ethylenediaminetetraacetic acid, with a pH of 4.5. The solutes can be detected spectrophotometrically, voltammetrically or polarographically. Spectrophotometric measurement in the visible range is more sensitive than in the UV range (detection limits of 0.04-0.1 ng at 410 nm compared with 0.3-0.5 ng at 265 nm). Voltammetric detection is highly sensitive for hydroxy and amino derivatives [detection limits 0.02-0.09 ng at +0.8 V (Ag-AgCl)], whereas for other substances the detection limits are a few nanograms. Polarographic detection is the least sensitive [detection limits 4-8 ng at -0.6 V (Ag-AgCl)]. All the calibration graphs exhibit good linearity, but spectrophotometric detection yields a wider linear dynamic range. Voltammetric detection is more precise at low solute concentrations (relative standard deviations of the peak heights 0.5-1.0% and 1.0-1.5% for voltammetric and spectrophotometric detection, respectively, with amounts of solute from 1 to 10 ng).

Azo Compounds↗

Indwelling blood compatible chemical sensors.

Progress in surgery has frequently been preceded by progress in technology. Thus positive clinical results may be anticipated with the emerging use of catheter-tip chemical probes. In these devices, the sensor is based on fluorometric or colorimetric sensing, coupled via a fiberoptic light guide to the external environment, or the potentiometric determination of ionic species via catheter-tip ISFET devices. The stages of development for these devices range from laboratory formulations, with some in vitro testing, to limited clinical experience with production prototype models. Advantages reported for the fiberoptic-based devices include no electrical interference, no reference electrode requirement, potentially low-cost fabrication, O2 tension analysis capability, and the possibility of multi-wave-length determinations to improve stability. Disadvantages of the fiberoptic-based probes include ambient light and temperature sensitivity, long-term instability of some reagents, halocarbon anesthetic sensitivity, slow response time, limited dynamic range, and trade-offs between amount of reagent phase, quenching of probe radiation, and stability. The semiconductor-based devices respond only to ionic species but feature the possibility of determining multiple species in a single-chip, low-cost fabrication, on-chip signal processing, clinically useful frequency response, robust design, and long shelf life. Disadvantages are as follows: long-term instability in situ, requirement for a reference electrode, ambient light and temperature sensitivity, and interference (in some cases) by competing ions, necessitating signal compensation. Both types of probes require treatment to avoid fouling of the probe surface and danger to the patient from thromboembolism. Some approaches to resolution of the outstanding problems are outlined. It appears that, given the current pace of industrial development, several of these probes will become a clinical reality in the near future.

Colorimetry↗