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Distortion product otoacoustic emissions and tympanometric measurements in an adult population-based study.

OBJECTIVE: Otoacoustic emissions (OAEs) are useful clinical tools that can be used as a test to reflect hearing, especially cochlear function. When OAEs are recorded, the sound energy is conducted inwards and outwards through the middle ear system, but the degree to which the middle ear condition affects the OAEs level remains obscure. The objectives of the present study were to estimate the effect of the condition of the middle ear expressed by multifrequency tympanometry on the distortion product otoacoustic emissions (DPOAEs) adjusting for age and the corresponding pure-tone thresholds. SUBJECTS AND METHODS: The evaluation was conducted using 1,043 subjects without a history of ear disease or occupational noise exposure out of a population-based sample of 2,259 adults aged 40-82 years. Multifrequency tympanometry, DPOAEs, and pure-tone audiometry were administered. The resonance frequency (RF), static admittance (SA) and tympanometric peak pressure (PP) were taken as variables representing middle ear function. Subjects were categorized into three groups of variables < or = 5th percentile, between 5th and 95th percentile, and > or = 95th percentile. The signal-to-noise ratio in DPOAE levels were compared among three groups adjusting for age and the pure-tone threshold level. RESULTS: Both abnormally high and low RF exerted a negative effect on DPOAEs. Smaller RF values were related to smaller DPOAEs for the frequency around 1000 Hz, and greater RF values were related to smaller DPOAEs for the frequency around 4000 Hz. The tendency was similar between genders. Abnormally high SA had a negative influence on DPOAEs, while abnormally low SA had no significant effect on either gender. Smaller PP values were significantly related to smaller DPOAEs. CONCLUSIONS: We interpreted the findings of the present study as verification of the effect of the condition of the middle ear on DPOAEs after adjustment for age and the pure-tone threshold level, although ears out of normal range in tympanometric variables might conceivably include not only middle ear dysfunction but also inner ear abnormality. Tympanometric assessment must always be taken into account when OAEs are analyzed for an estimation of the cochlea function.

Acoustic Impedance Tests↗

The sequential hypothesis on sleep function. II. A correlative study between sleep variables and newly synthesized brain DNA.

The information acquired by brain during wakefulness (W) may be processed in two sequential steps occurring during synchronized sleep (SS) and paradoxical sleep (PS), respectively. On the assumption that brain molecules synthesized during the acquisition step undergo a comparable sleep processing, we have designed an experiment aimed at the verification of the sequential hypothesis. Groups of adult female Wistar rats received [3H-methyl] thymidine by intraventricular injection 30 min before being exposed to a 4 hr session of a two-way active avoidance training. Animals failing to achieve the learning criterion were further allowed a period of 3 hr during which they were left free to sleep, or were deprived of PS or of total sleep. Control rats were similarly treated, but were left in their home cages in the same training room during the period of acquisition. The results of correlative study among behavioral, sleep and biochemical variables demonstrate that the specific radioactivity of DNA in the cerebral cortex, cerebellum and brainstem is correlated with several variables of postacquisition sleep, mostly SS parameters. The correlations depend on the previous waking experience of the rats. The data substantiate the two main consequences of the hypothesis, i.e., (1) the involvement of SS in brain information processing; and (2) the dependence of the operations performed by the sleeping brain on the nature of the previous waking experience. The results also provide some insight into the kind of processing which occurs in the sleeping brain.

Animals↗

A hybrid neural-genetic algorithm for reservoir water quality management.

A combined neural network and genetic algorithm (GA) was developed for water quality management of Feitsui Reservoir in Taiwan. First, an artificial neural network (ANN) model was employed to simulate the behavior of nutrient loads into the reservoir. The data from watershed loads, precipitation in the watershed, and outflow were used in the ANN model to forecast the total phosphorus concentration in the reservoir. A 6-year (1992-97) record of water quality data was used for network training, and additional data collected in 1998-2000 were used for model verification. Further, a GA was used with this ANN model to optimize the control of nutrient loads from the watershed. The GA was used as a search strategy to determine the proper reduction rates of nutrient loads from the watershed so that the objective function could be as close to the optimal value as possible. The study results indicate that the ANN model can effectively simulate the dynamics of reservoir water quality. The GA is able to identify control schemes that reduce the in-reservoir total phosphorus concentration by as much as 60%, and water quality in the reservoir can be expected to achieve an oligotrophic (most of the time) or mesotrophic level if the watershed nutrient loads are reduced by 10-80%.

Algorithms↗

On the independence of time and strain effects in the stress relaxation of ligaments and tendons.

The hypothesis of variables separation, namely the time and the strain separation in the relaxation function, is widely used in soft tissue biomechanics. Although this hypothesis is central to several biomechanical models, only few experimental works have tried to verify it. From these studies, contradictory results have been found. Moreover, it has recently been noted that no such experimental verification has been performed for ligament tissues. In this paper, an experimental method is developed to test the hypothesis of variables separation. This method is then used with human cruciate ligaments and patellar tendons. It is shown that the use of the variables separation hypothesis is justified at least for strain values lower than 16% for anterior cruciate ligament, lower than 12% for posterior cruciate ligament and lower than 6% for patellar tendon. The method presented in this paper could be used to verify the validity of variables separation for other tissues.

Anterior Cruciate Ligament↗

Probing the hydrophobic interactions in the skeletal actomyosin subfragment 1 and its nucleotide complexes by zero-length cross-linking with a nickel-peptide chelate.

The complex of Ni(II) and the tripeptide Gly-Gly-His catalyzes, in the presence of monoperoxyphthalic acid, a zero-length protein-protein cross-linking via an oxidative radical pathway involving mainly aromatic amino acids and not at all nucleophilic residues [Brown, K. C., Yang, S.-H., and Kodadek, T. (1995) Biochemistry 34, 4733-4739]. We have taken advantage of this unprecedented cross-linking system to directly and selectively probe the solution structure and functioning of the hydrophobic interface between F-actin and skeletal myosin subfragment 1 (S-1) at the level of its aromatic components, in the absence and in the presence of nucleotides (ATP and ADP) or nucleotide analogs (AMPPNP, PPi, and ADP. AlF4). Following verification of the structure of the Ni(II)-peptide chelate and of its oxidized active form by electrospray mass spectrometry, complexes of F-actin and S-1 or proteolytic S-1 derivatives and complexes of S-1 and proteolytic F-actin derivatives were readily cross-linked under various controlled conditions without apparent alteration of the acto-S-1 recognition. The covalent adducts were identified on electrophoretic gels using specific protein labeling with the oxidation-resistant fluorophor, monobromobimane, combined with immunochemical staining. Two types of actin-heavy chain conjugates were produced. One, with a mass of 180 kDa, was formed in the rigor state or with ADP bound; the other one, with a mass of 200 kDa, was generated from the ternary complexes comprising a gamma-P-containing ligand. They were accumulated with an efficiency of 8 and 6%, respectively. For each reversible complex, the 180 kDa:200 kDa band ratio was essentially as predicted from the nucleotide-dependent A to R equilibrium mechanism of the acto-S-1 interaction in solution [Geeves, A. M., and Conibear, P. B. (1995) Biosphys. J. 68, 194s-201s]. Both covalent species resulted from the cross-linking of an actin monomer to the central 50 kDa segment, and their distinct mobilities reflect gamma-P-mediated structural changes at or near the actin-50 kDa fragment interface. Peptide mapping showed the cross-linking to take place between the 506-561 S-1 segment and the 48-113 actin stretch. The localization of these regions in the atomic F-actin-S-1 model implies that nucleotide-modulated close contacts, involving aromatic residues, are operating between the C-terminal helix of the hydrophobic strong actin-binding motif of S-1 bound to the primary actin monomer and the top portion of the adjacent lower actin subunit. The specificity of the nickel-peptide cross-linking, as assessed with the acto-S-1 complex, makes it a candidate for potential general use in investigations of the hydrophobic interactions within other protein motor-based assemblies.

Adenosine Diphosphate↗

Intracellular domain of nicotinic acetylcholine receptor: the importance of being unfolded.

Bioinformatics methods with subsequent verification by experimental data were applied to the structural investigation of the intracellular loop of the delta-subunit of the nicotinic acetylcholine receptor (nAChR). Three complementary methods were used: prediction of secondary structure elements, prediction of ordered/disordered protein regions and prediction of short functional binding motifs. The output of five different algorithms was used for the secondary structure construction. Most of the intracellular domain is predicted to be unfolded. The predictions correlate well with the experimental data of limited proteolysis and NMR performed on the mostly monomeric fraction of heterologously expressed Torpedo intracellular domain protein. Twelve functional binding motifs within the disordered regions of the nAChR intracellular domain are predicted. Identification of proteins that interact with the intracellular domain will provide a better understanding of protein-protein interactions involved in nAChR assembly, trafficking and clustering.

Amino Acid Sequence↗

A new clinical technique for verification of hearing aid response.

A new miniature wide-range electret microphone with a flat frequency response is available to the audiology clinic to measure sound pressure in the patient's ear canal. This article describes the clinical application of this new microphone for the selection and monitoring of hearing aid response. Preliminary results of the relationship between ear canal measurements and functional gain are also provided. This new clinical technique can provide the audiologist with quick objective data on the response of a hearing aid while it is being worn by the patient.

Acoustics↗

Verification of effects on the nervous system of low level occupational exposure to CS2.

Neurotoxic effects associated with long term low level occupational exposure to CS2 were reinvestigated four years after the initial study in the same group of workers. The second study concerned 44 exposed and 31 matched control workers. For both studies a personal cumulative exposure Ec was calculated based on function specific exposure levels and the occupational histories, which were carefully re-established. The exposed workers' average Ec was 192 and 213 ppm-years (first and second study respectively). Where possible the values of both data sets were used in a final combined analysis. Effects were found on the motor nerve conduction velocity of the fast (-0.9 m/s) and slow (-1.0 m/s) fibres of the peroneal nerve, the sensory nerve conduction velocity in the hand and arm segment of the median (-2.1 m/s) and ulnar (-1.3 m/s) nerves, and in the sural nerve (-1.3 m/s). An increased refractory period was found in the sural nerve (+ 0.2 ms, + 11%), but not in the peroneal nerve. For the autonomic nervous system an effect was found on the heart frequency response to isometric muscle contraction (-4.7 beats/min, -26%) and maximal forced respiration (-3.2 beats/min, -16%). This study shows the importance of a detailed evaluation of past exposure data. The reinvestigation enabled a more precise estimation of the effects of CS2, which is particularly desirable at around threshold exposure.

Autonomic Nervous System Diseases↗

Microarray analysis of gene expression after transverse aortic constriction in mice.

Cardiac hypertrophy is a compensatory response initially beneficial to heart function but can ultimately lead to cardiac decompensation. It is an integrated process involving multiple cellular signaling pathways and their cross talk. Microarray GeneChip technology is a powerful new tool to identify gene expression profiles of cardiac hypertrophy. To identify well-characterized as well as novel adaptive mechanisms, we utilized a murine model of compensated pressure overload hypertrophy (transverse aortic constriction, TAC). At 48 h, 10 days, and 3 wk, hearts were harvested and total RNA hybridized to Affymetrix U74Av2 GeneChips, which contain a 12,488-gene/EST probe set. Verification of gene expression was performed by SYBR quantitative real-time RT-PCR (QRT-PCR) for selected genes. A rigorous evaluation of the adequacy of the control condition was also performed. For statistical analysis we generated a four-step filtering criteria. Our results show an upregulation of 38 genes (48 h), 269 genes (10 days), and 203 genes (3 wk) and downregulation of 15 genes (48 h), 160 genes (10 days), and 124 genes (3 wk). Transcripts differentially expressed after TAC were categorized into 12 functional groups and revealed the presence of several intriguing transcripts, e.g., cell proliferation-related Ki-67 and several apoptosis-related genes. Overall changes in QRT-PCR were in accordance with GeneChip data, with the highest correlation for genes with the largest up- or downregulation with TAC. Thus TAC results in altered expression of genes in several pathways regulating both cardiac structure and function. However, for in vivo gene microarray experiments, it is critical to define adequate controls, perform rigorous statistical analysis, and provide validation by alternative methods.

Acute Disease↗

Resolution- versus sensitivity-effective diameter in pinhole collimation: experimental verification.

To account for photon penetration, the formulae used to calculate the geometric resolution of a pinhole collimator use an effective diameter d(e) rather than the physical diameter of the aperture. The expressions commonly used for d(e), however, were originally derived to include penetration in sensitivity calculations. To predict the full width at half maximum (FWHM) resolution of the point-spread function (PSF) of a knife-edge pinhole collimator, we have previously proposed simple expressions for a resolution-effective diameter d(re). Unlike those for d(e), expressions for d(re) predict both a dependence on the polar angle of the source (theta) and a non-isotropic PSF. In this paper, the new theory was tested by measuring experimentally the FWHM of the PSF. Results confirm the theoretical predictions that (a) d(re) provides the best estimates of the experimental FWHM as a function of theta and of the direction in the plane of the pinhole, (b) Paix's expression for d(e) tends to overestimate the FWHM, (c) Anger's is a better approximation, but still cannot predict the dependence on theta, and (d) the FWHM decreases with decreasing theta, i.e. resolution improves for sources at the edge of the field-of-view.

Algorithms↗

Characterization of a transmission ionization beam-imager for radiotherapy verification.

A system for radiotherapy treatment verification is proposed, using an air-ionization chamber with 1600 simultaneously readable 1 cm pixels. An image of the entire beam may be used to calibrate a portal image, to verify the position of the multi-leaf collimator with respect to delivered dose (either before or during treatment) and to check beam flatness and symmetry. This study characterizes the physical behaviour of such a system. A test chamber has been constructed and its temporal and spatial resolution and noise characteristics are evaluated. Several parameters of the design are varied, and their effects assessed. Temporal resolution is adequate to allow readout between each linear accelerator pulse at 400 pulses per second. Application of low atomic-number build-up and reduction of plate separation were the most effective methods to improve spatial resolution. The full width at half maximum of the line-spread function is shown to be 4.5 mm using a pre-sampling technique. The peak pixel-signal to x-ray quantum noise ratio exceeds 100. Prototype electronics have been tested, demonstrating that electronic noise could be reduced to a level below the x-ray quantum noise. The results of the study allow the simulation of any possible application to evaluate the proposed verification system.

Algorithms↗

A single amino-acid difference confers major pharmacological variation between human and rodent 5-HT1B receptors.

Neuropsychiatric disorders such as anxiety, depression, migraine, vasospasm and epilepsy may involve different subtypes of the 5-hydroxytryptamine (5-HT) receptor. The 1B subtype, which has a unique pharmacology, was first identified in rodent brain. But a similar receptor could not be detected in human brain, suggesting the absence in man of a receptor with equivalent function. Recently a human receptor gene was isolated (designated 5-HT1B receptor, 5-HT1D beta receptor, or S12 receptor) which shares 93% identity of the deduced protein sequence with rodent 5-HT1B receptors. Although this receptor is identical to rodent 5-HT1B receptors in binding to 5-HT, it differs profoundly in binding to many drugs. Here we show that replacement of a single amino acid in the human receptor (threonine at residue 355) with a corresponding asparagine found in rodent 5-HT1B receptors renders the pharmacology of the receptors essentially identical. This demonstrates that the human gene does indeed encode a 1B receptor, which is likely to have the same biological functions as the rodent 5-HT1B receptor. In addition, these findings show that minute sequence differences between homologues of the same receptor from different species can cause large pharmacological variation. Thus, drug-receptor interactions should not be extrapolated from animal to human species without verification.

Alprenolol↗

Human teeth exposed to argon laser irradiation: determination of power-time-temperature working conditions.

OBJECTIVE: This study was conducted to establish the operating parameters of the argon laser without thermal damage to the pulp tissue for clinical applications. SUMMARY BACKGROUND DATA: Previous studies have mainly compared the temperature modifications of the pulp chamber in a very limited situation, where a complete view of the thermal history cannot be obtained nor even extrapolated to new applications. METHODS: We used samples of molar and premolar tooth where a class V cavity was prepared and illuminated with an argon laser at different power levels, fixing the exposition area for all cases. Situations including open cavity and teeth restoration were analyzed. High-precision thermistors were placed in four different positions, one of which was inside the pulp chamber. The temperature evolution was monitored continuously by an interfaced computer during all laser exposure. Special attention was paid to the intrapulpal temperature variation because it is considered the most vulnerable thermal region. The temperature time evolution allowed the determination of the operating conditions (power-time-temperature variation) in which the use of the argon laser causes no pulpal damage. As a function of temperature variation, we divided the whole parameter space (power-time-temperature) into zones and the optimum zone of operation was determined. CONCLUSIONS: We created a diagram called power-time-temperature (PTT) where zones of temperature increased under laser irradiation allow the verification of which condition is safe for clinical laser application. The results have a broad use when this type of analysis is applicable.

Argon↗

Microarray gene analysis and expression profiles of Dupuytren's contracture.

Dupuytren's disease, although not altogether uncommon, has eluded scientists who have sought to explain the cause of this palmar fibroproliferative disorder. It can lead to severe limitations of hand function if left untreated. This study is the first broad genetic survey using microarray technology to find gene products that are overexpressed or underexpressed in diseased tissues. The authors found 23 genes with levels that differ consistently from control levels. Nine were selected for further verification using reverse transcription-polymerase chain reaction. These genes hold potential promise in explaining some of the demographic trends seen with disease, such as correlation with alcoholism and the striking predisposition for the male gender.

Aged↗

Photoacoustic detection of triplet state and singlet oxygen in highly absorbing samples.

A photoacoustic (PA) effect theory taking into account two heat sources corresponding to the radiationless relaxation processes of two states of different lifetimes and to the heat diffusion across the sample is herewith presented. Results obtained demonstrate that the amplitude and the phase of the PA signal depend on the sample's thermal properties, on its optical absorption coefficient, on the lifetime of the long-lived excited state, and on the ratio of the two heat sources. This ratio can be expressed as a function of the product of the energy of the excited state times the quantum yield of its production. Simulations of PA amplitude and phase variations vs light modulation frequency exhibit new features of the PA signal:phase inversion and fast decrease of the amplitude. Experimental verifications were carried out on solutions and gels. Fitting of the amplitude and phase variations allow us to measure the lifetime and conversion yield of the intermediate state which can be a triplet state or singlet oxygen, O2(1 delta g). The addition of an acceptor, specific to O2(1 delta g), induces changes in the amplitude of the PA signal which can be used to study the production and deactivation of this excited form of oxygen. This work demonstrates the usefulness of PA in the detection of metastable excited states such as the triplet state and singlet oxygen and in their quantitative analysis.

Coloring Agents↗

A comparison of psychophysical procedures for level-discrimination thresholds.

Five different psychophysical procedures were used to measure level-discrimination (also called intensity discrimination) thresholds for 1-kHz tones at two levels (30 and 90 dB SPL) and two durations (10 and 500 ms). The procedures were the classic transformed up-down staircase method with a two-alternative forced-choice (2AFC) paradigm (UPD), 15- and 50-trial implementations of the method of maximum likelihood (MML) with a cued yes-no paradigm, and 18-trial implementations of ZEST using both cued yes-no and 2AFC paradigms. Results obtained from nine normal listeners show that estimates of level-discrimination thresholds for the four conditions are similar across all five procedures when different points of convergence are accounted for. The variance of threshold estimates within listener and condition was smallest for UPD, largest for the MML with 15 trials, and statistically indistinguishable among the others. The sweat factors ranged from 5.5 for MML with 50 trials to about 1.4 for UPD and ZEST. Simulations show that ideal performance of procedures may be far from real-life experience and that these deviations are likely to depend on complex interactions between listener behavior and parameter choices used for implementing the procedures. Therefore, empirical verification is important for judging the effectiveness of psychophysical procedures.

Adolescent↗

Mice deficient in the fused homolog do not exhibit phenotypes indicative of perturbed hedgehog signaling during embryonic development.

Hedgehog (Hh) signaling plays a major role in multiple aspects of embryonic development. To understand how a single Hh signal is capable of generating distinct readouts in Hh-responsive cells requires elucidation of the signal transduction cascade at the molecular level. Key components that mediate Hh signal transduction downstream of the receptor include Fused (Fu), Suppressor of fused (Sufu), and Costal-2 (Cos2) or the vertebrate homologs Kif27/Kif7. Studies with both invertebrates and vertebrates have led to a model in which a protein complex composed of Fu, Sufu, and Cos2 controls the processing, activity, and subcellular distribution of the Ci/Gli transcription factors responsible for Hh target gene activation. These converging results obtained with different species reaffirm the prevailing view of pathway conservation during evolution. Genetic studies of Fu, Sufu, and Kif27/Kif7 in mice are required to provide further verification of Hh pathway conservation. To this end, we generated a gene-targeted allele of Fu in mice. Surprisingly, our analysis indicates that Fu-deficient mice do not exhibit any embryonic phenotypes indicative of perturbed Hh signaling. This could be due to either functional redundancy or Hh pathway divergence and clearly indicates greater complexity of Hh signaling in vertebrates.

Alleles↗

Temporary health effects from exposure to water-borne paints.

Temporary health effects of exposure to experimental paints were studied. Ten painters feeling nuisance from water-borne paints and eight painters not feeling such nuisance applied eight experimental water-borne paints according to normal work routines. The effects were a decrease in forced vital capacity, forced expiratory volume in 1 s and peak expiratory flow, an increase in urine excretion, and a decrease in urine density. A small, but statistically highly significant, increase in the mean volume of erythrocytes was observed. The effects were similar in the two groups, but the "nuisance group" reacted with a larger urine excretion and a larger increase in the mean volume of erythrocytes. The effects did not influence physical work capacity. The effects on the lungs and urinary excretion were probably not associated with the organic solvents or ammonia in the paints. Instead, they were probably due to derivatives of isothiazolinone. This assumption needs verification.

Adult↗