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Effect of spinal morphine after long-term potentiation of wide dynamic range neurones in the rat.

BACKGROUND: Studies have shown that long-term increase in the excitability of single wide dynamic range neurones in the spinal dorsal horn of rats may be induced after tetanic stimulation to the sciatic nerve. This sensory event is possibly an in vivo counterpart of long-term potentiation, described in the brain. This study investigated whether this phenomenon occurs in the halothane-anesthetized rat and whether the antinociceptive effects of spinally administered morphine are altered when tested on the enhanced activity. METHODS: Single unit extracellular recordings were made in three different groups of halothane-anesthetized rats (n = 6 in each group). In group 1, the evoked neuronal responses of wide dynamic range neurones by a single electrical stimulus to the peripheral nerve were recorded every 4 min, for 1 h before (baseline) and for 3 h after brief high-frequency conditioning stimulation of the sciatic nerve. In group 2, morphine was applied onto the spinal cord after long-term potentiation had been established. Increasing concentrations of morphine were added until the C fiber-evoked responses were abolished; this was followed by naloxone reversal. In group 3, the same protocol as in group 2 was used except a waiting period substituted for the electrical conditioning. RESULTS: The C fiber-evoked responses were significantly increased (P < 0.001) after conditioning compared with baseline and those in control animals. Further, significantly higher concentrations of morphine (P = 0.008) were needed to abolish the C fiber-evoked responses in tetanized animals than in control animals. Naloxone reversed the effects of morphine to the predrug potentiated baseline in group 2, showing that opioids do not block the maintenance of spinal long-term potentiation. CONCLUSIONS: Long-term potentiation of C fiber-evoked responses also can be induced in halothane-anesthetized rats, and morphine seems to have less potency during such conditions. These data suggest that long-term potentiation-like mechanisms may underlie some forms of hyperalgesia associated with a reduced effect of morphine.

Analgesics, Opioid↗

Simultaneous quantitative detection of multiple low-frequency variants by high-dynamic-range capillary electrophoresis.

Sensitive and quantitative detection of low-frequency variants across multiple loci is critical for nucleic acid-based diagnostics, yet clinical implementation requires a balance among sensitivity, multiplexing capacity, cost, and operational simplicity. We previously developed a high-dynamic-range capillary electrophoresis system capable of detecting variants at allele frequencies below 1%; however, its application was limited to single-locus analysis. Here, we expanded this platform to multiplex detection by incorporating mobility-shift strategies into the assay design. This approach enabled simultaneous analysis of 15 hotspot variants across three clinically relevant loci: KRAS codons 12 and 13 and GNAS codon 201. Validation using synthetic oligonucleotides, formalin-fixed paraffin-embedded tissue, and liquid specimens demonstrated high quantitative accuracy over clinically relevant variant allele frequency ranges, with measured values closely matching expected values (R2 > 0.97). The assay showed high concordance with targeted amplicon sequencing and digital polymerase chain reaction for all variants at variant allele frequencies &#x2265;1%, while also detecting selected variants below this threshold. Collectively, these results establish a multiplexed high-dynamic-range capillary electrophoresis assay for simultaneous, quantitative detection of low-frequency variants, offering a scalable and cost-effective approach for disease-focused gene panels in clinical laboratory settings.

HiDy↗

Use of a variably sensitive selected reaction monitoring method to extend the linear dynamic range for quantitative high-performance liquid chromatography/tandem mass spectrometry.

A method has been devised with the capacity to extend the linear dynamic range of a triple quadrupole mass spectrometer operated in the selected reaction monitoring (SRM) mode of analysis. This extended range experiment can be realized by simultaneously acquiring variably sensitive data, via collision energy adjustment, for the same precursor-to-product ion transition within a single SRM method. While this method can be applied universally to many different study types without any detrimental effect to the analysis or throughput, it was applied herein to acquire and quantify, within a single analysis, the concentrations of GSK-A in a multiple-dose rodent study, that previously required a dilution scheme. Using this methodology, the linear dynamic range of GSK-A was increased over traditional methods by nearly two orders of magnitude, from 2.00-10,000 ng/mL to 0.500-100,000 ng/mL.

Algorithms↗

[The dynamic range of a digital X-ray diagnostic system operating in a counting mode].

A method is described in the paper that is designed to assess the values of the dynamic range of digital X-Ray diagnostic systems operating in the counting mode. The dynamic range is shown to be determined from the bottom by static limitations of the image quality, while from the top it is determined by system's counting errors caused by the terminal temporal resolution.

Models, Theoretical↗

Dynamic-range reduction by peak clipping or compression and its effects on phoneme perception in hearing-impaired listeners.

In this study, differences between dynamic-range reduction by peak clipping and single-channel compression for phoneme perception through conventional hearing aids have been investigated. The results from 16 hearing-impaired listeners show that compression limiting yields significantly better phoneme identification scores than does peak clipping if a strong reduction of the dynamic range has to be effected. In addition, some qualitative differences in confusion patterns could be established: the perception of low-frequency information appears to be relatively important in compression limiting; the perception of plosiveness is less important.

Adolescent↗

Predicting dynamic range and intensity discrimination for electrical pulse-train stimuli using a stochastic auditory nerve model: the effects of stimulus noise.

This work investigates dynamic range and intensity discrimination for electrical pulse-train stimuli that are modulated by noise using a stochastic auditory nerve model. Based on a hypothesized monotonic relationship between loudness and the number of spikes elicited by a stimulus, theoretical prediction of the uncomfortable level has previously been determined by comparing spike counts to a fixed threshold, Nucl. However, no specific rule for determining Nucl has been suggested. Our work determines the uncomfortable level based on the excitation pattern of the neural response in a normal ear. The number of fibers corresponding to the portion of the basilar membrane driven by a stimulus at an uncomfortable level in a normal ear is related to Nucl at an uncomfortable level of the electrical stimulus. Intensity discrimination limens are predicted using signal detection theory via the probability mass function of the neural response and via experimental simulations. The results show that the uncomfortable level for pulse-train stimuli increases slightly as noise level increases. Combining this with our previous threshold predictions, we hypothesize that the dynamic range for noise-modulated pulse-train stimuli should increase with additive noise. However, since our predictions indicate that intensity discrimination under noise degrades, overall intensity coding performance may not improve significantly.

Acoustic Stimulation↗

Dynamic range extension of cine velocity measurements using motion-registered spatiotemporal phase unwrapping.

A motion-registered spatiotemporal phase-unwrapping method for extending the dynamic range of cine magnetic resonance phase velocity measurements is presented. The interframe cardiac movement is estimated from the magnitude image derived from the velocity encoded raw data, which ensures that the phase signal is unwrapped in the temporal direction with reference to pixels belonging to the same anatomic flow region. An extra step of spatial phase correction is then used to further eliminate any residual errors. The combination of spatial and temporal information for phase unwrapping provides a robust way of extending the dynamic range of cine velocity data in the presence of large phase aliasing errors.

Algorithms↗

Clinical study of the sensitivity and dynamic range of three digital systems, E-speed film and digitized film.

The objective of the present study was to clinically evaluate the sensitivity and dynamic range of three digital systems (Sens-A-Ray, CDR, Digora), digitized film and E-speed film. Five objects were submitted to three different kilovoltages and seven exposure times. In order to evaluate the relationship between exposure time and dosage, measurements were made in a dental x-ray unit with an ion chamber, X-ray timer and kVp meter. For each system, 105 radiographs were taken, totalling 525 images, that were evaluated by six trained observers by means of scoring from 0 to 4. The scores attributed to the images for each of the systems were submitted to analysis of variance and Turkey's test. The results showed statistically significant differences (p < 0.01) with the storage phosphor system producing the wider dynamic range, followed by the digitized film. The CDR system showed the greater sensitivity, followed by the Digora system.

Analysis of Variance↗

Using multichannel wide-dynamic range compression in severely hearing-impaired listeners: effects on speech recognition and quality.

OBJECTIVE: The objective of this study was to compare speech recognition across a sampling of amplification choices available for listeners with severe loss. This includes conventional options (linear with peak clipping and linear with compression limiting) and newer strategies (multichannel wide-dynamic range compression [WDRC]) theorized to better accommodate reduced dynamic range. A second objective was to compare speech quality across the same conditions using a paired-comparison test. DESIGN: Participants were 13 adults with severe sensorineural hearing loss and a control group of seven adults with normal hearing. Test materials included consonant-vowel syllables (speech recognition) and sentences (speech quality). Four amplification conditions were included: peak clipping; compression limiting; two-channel WDRC; and three-channel WDRC, with overall audibility similar across conditions. In the WDRC conditions, the compression ratio was fixed at 3:1 in each channel. Consonant recognition was measured using a closed-set task, and speech quality was measured using a paired-comparison test. RESULTS: For the listeners with severe loss, recognition and preference were lower for a three-channel WDRC system than for a compression limiting system. Specific errors were consistent with poorer transmission of amplitude envelope information by the multichannel WDRC systems. CONCLUSIONS: Under some conditions, the benefit of fast-acting, multichannel WDRC systems relative to more linear amplification strategies may be reduced in listeners with severe loss. Performance decrements with these systems are consistent with consequences of broader auditory filters.

Acoustic Stimulation↗

A ratiometric fluorescence sensor with broad dynamic range based on two pH-sensitive fluorophores.

This paper describes a novel ratiometric fluorescence sensor for pH measurement. Two pH-sensitive fluorophores, N-allyl-4-(4'-methyl-piperazinyl)-1,8-naphthalimide (AMPN) and meso-5,10,15,20-tetra-(4-allyloxyphenyl)porphyrin (TAPP), which served as referencing indicators for each other, were co-polymerized with acrylamide, hydroxyethyl methacrylate and triethylene glycol dimethacrylate on the silanized glass surface. The proposed sensor is based on the pH-dependent fluorescence intensities of the two fluorophores in different pH ranges. The sensor covers a broad dynamic range of pH 1.5-9.0. It exhibits satisfactory analytical performance in terms of selectivity, reproducibility and stability. The successful fabrication of the proposed sensor provides an alternative concept to utilizing two or more fluorophores for the development of ratiometric sensors covering a broad range of pH.

1-Naphthylamine↗

Short communication: use of the output video signal for dynamic range, brightness control and image memory assessment in X-ray fluoroscopy.

The output video signal from three X-ray fluoroscopy machines was recorded with a storage oscilloscope to calculate the dynamic range of their image intensifier television camera chains. The two MERATE MTH90 and MGR50hf machines employed the same imaging chain but the response of the former to exposure was significantly lower because of a three channel light distribution optical system which was installed but not used. The CGR Stenoscope machine was found to have a very narrow dynamic range to the extent that it was not usable. Additional measurements on the CGR machine showed that the image intensifier brightness control mechanism would produce stabilized brightness in less than 0.4 s and it proved to be faster than the manual selection of exposure parameters. The quality of the image stored in the memory device on the same system was compared with the original by subtracting the two video signals on the oscilloscope and thus acquiring a quantitative measure of their difference.

Fluoroscopy↗

Extending the dynamic range of electrochemical sensors using multiple modified electrodes.

Multiple electrodes, combined with a chemometric strategy to calibrate the measurement response, have been used for the determination of an analyte across a broader dynamic range than is possible with a single electrode. The model system used for the detection of copper comprised electrodes modified with a self-assembled monolayer. The electrodes were modified with the copper-complexing species (3-mercaptopropionic acid, thioctic acid, and the peptides cysteine and Gly-Gly-His) and copper was determined over concentrations ranging from nanomolar to millimolar using voltammetric analysis. We have demonstrated that by combining the calibration functions from the four electrodes a better estimate (i.e. with smaller variance) of the concentration of the analyte is obtained. Measurement uncertainty is expressed for independently prepared electrodes, which allows the possibility of commercial production and factory calibration. The principles of using multiple electrodes modified with recognition elements with different affinities for the target analyte to extend the dynamic range of sensors is a general one that could be applied to other analytes.

3-Mercaptopropionic Acid↗

Principles of digital dynamic-range compression.

This article provides an overview of dynamic-range compression in digital hearing aids. Digital technology is becoming increasingly common in hearing aids, particularly because of the processing flexibility it offers and the opportunity to create more-effective devices. The focus of the paper is on the algorithms used to build digital compression systems. Of the various approaches that can be used to design a digital hearing aid, this paper considers broadband compression, multi-channel filter banks, a frequency-domain compressor using the FFT, the side-branch design that separates the filtering operation from the frequency analysis, and the frequency-warped version of the side-branch approach that modifies the analysis frequency spacing to more closely match auditory perception. Examples of the compressor frequency resolution, group delay, and compression behavior are provided for the different design approaches.

Algorithms↗

The dynamic range of TMJ sounds.

It is of clinical interest to record the amplitudes of temporomandibular joint (TMJ) sounds. The aim was to test the hypothesis that sealing the meatus, when placing a microphone in the ear canal affects such recording by increasing the sound pressure level (SPL). Bilateral recordings of 249 TMJ clickings were made from three subjects, using sampling rates of 48 or 96 kHz and 24 bits A/D conversion, with and without the ear canals sealed by Silicone putty. The peak-to-peak equivalent sound pressure level (peSPL) was higher (P < 0.001) when the ear canal was sealed (range of mean differences was 8.3-24.9 dB peSPL). This means that the signal to noise ratio can be improved by sealing the meatus because the electronic noise level is not increased. Most important is that the dynamic range of the clicking sounds was 62 dB that is larger than the effective dynamic range of a 16 bits sound card. Future studies are needed to establish normative peSPL values. However, cards with at least 24 bits A/D conversion will be required, especially in patients with suspected disc displacement with reduction, where the difference in loudness between opening and closing clicking often is large.

Auscultation↗

Alternative splicing and interaction with di- and polyvalent cations control the dynamic range of acid-sensing ion channel 1 (ASIC1).

Homomeric acid-sensing ion channel 1 (ASIC1) can be activated by extracellular H(+) in the physiological pH range and may, therefore, contribute to neurotransmission and peripheral pain perception. ASIC1a and ASIC1b are alternative splice products of the ASIC1 gene. Here we show that both splice variants show steady-state inactivation when exposed to slightly decreased pH, limiting their operational range. Compared with ASIC1a, steady-state inactivation and pH activation of ASIC1b are shifted to more acidic values by 0.25 and 0.7 pH units, respectively, extending the dynamic range of ASIC1. Shifts of inactivation and activation are intimately linked; only two amino acids in the ectodomain, which are exchanged by alternative splicing, control both properties. Moreover, we show that extracellular, divalent cations like Ca(2+) and Mg(2+) as well as the polyvalent cation spermine shift the steady-state inactivation of ASIC1a and ASIC1b to more acidic values. This leads to a potentiation of the channel response and is due to a stabilization of the resting state. Our results indicate that ASIC1b is an effective sensor of transient H(+) signals during slight acidosis and that, in addition to alternative splicing, interaction with di- and polyvalent cations extends the dynamic range of ASIC H(+) sensors.

Acid Sensing Ion Channels↗

3-(4-Carboxybenzoyl)quinoline-2-carboxaldehyde, a reagent with broad dynamic range for the assay of proteins and lipoproteins in solution.

This paper describes the application of 3-(4-carboxybenzoyl)quinoline-2-carboxaldehyde (CBQCA), a sensitive fluorogenic reagent for detection of amines, to the assay of proteins in solution. The sensitivity and dynamic range of CBQCA in the determination of protein concentration is modulated by the number of accessible amines present in the protein assayed. Thus, this method bears the same limitations as other reagents used in fluorogenic assays based on fluorescent amine adducts such as those obtained with fluorescamine or o-phthaldialdehyde, or of other spectrophotometric methods, where the color development is determined by the abundance in the protein of certain amino acids. However, in comparison to other fluorescence-based protein detection methods, CBQCA has proven to be an extremely sensitive reagent with a very broad, essentially linear dynamic range, capable of detecting from 10 ng to 150 micrograms of protein (in a 100- to 200-microL assay volume). The CBQCA reagent also functions well in the presence of substances, such as lipids, known to interfere in many other protein determination methods.

Benzoates↗

Sex differences in the responses of spinal wide-dynamic range neurons to subcutaneous formalin and in the effects of different frequencies of conditioning electrical stimulation.

The purpose of this study was to investigate sex-related differences in nociception elicited by s.c. injection of different concentrations (1-5%) of formalin. S.c. formalin-induced biphasic (early and late phases) persistent nociception was assessed by extracellularly recording the spontaneous activities of single spinal dorsal horn wide-dynamic range neurons in anesthetized male and female rats. The nociceptive responses of the dorsal horn wide-dynamic range neurons following s.c. injection of 5%, but not 1% and 2.5%, formalin in female rats were significantly stronger than the responses obtained in male rats. However, these concentration-dependent differences with respect to different sexes existed only in the late, but not the early, phase of formalin-induced nociception in intact, not spinal rats. The 5% formalin-induced late phase nociception in male rats was significantly depressed by 15 min of repeated conditioning electrical stimulation at a frequency of 5 Hz as well as 50 Hz during and after the period of conditioning electrical stimulation (intensity: 1 mA; pulse duration: 1 ms). In contrast, the inhibitory effect of 50 Hz conditioning electrical stimulation on the 5% formalin-elicited late phase response in female rats was markedly greater in magnitude and longer in duration than that of 5 Hz conditioning electrical stimulation. No significant depressive effects of 5 Hz conditioning electrical stimulation on formalin-induced nociception were found in female rats, indicating that the distinct effects of conditioning electrical stimulation at different frequencies are different in animals of opposite sexes. In conclusion, s.c. administration of different concentrations of formalin shows a distinct sex-related difference in its late tonic nociception of spinal nociceptive sensory neurons. Sex differences in formalin-induced tonic nociception are stimulus intensity dependent and related to the modulation from the supraspinal regions. S.c. formalin-induced late phase nociception in female rats is only sensitive to depression at a frequency of 50 Hz, but not 5 Hz, of conditioning electrical stimulation. This suggests that the involvement of the central mechanisms in the antinociceptive effects of conditioning electrical stimulation may be different at various frequencies of stimulation.

Afferent Pathways↗

Electrodes modified with the phase transition polymer and heme peptide: biocatalysis and biosensing with tunable activity and dynamic range.

An electrode was modified with a phase transition polymer, poly(N-isopropylacrylamide), and the polymer was further modified with a peroxidase model compound, heme peptide (HP). As the polymer layer shrank at temperatures above 30-40 degrees C, the catalytic activity of the HP molecules for H(2)O(2) reduction improved, and simultaneously, the number of HP molecules that can communicate electrochemically with the electrode increased. As a result, the catalytic current for H(2)O(2) reduction in the shrunken state was 4 times larger than that in the swollen state. This reversible change was exploited for tuning the sensitivity and dynamic range of the HP electrode in H(2)O(2) biosensing. The dynamic range in inhibition-based biosensing of imidazole derivatives was also tunable.

Acrylic Resins↗