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At least 451 records · Page 25Linked to original sources
PubMed2006

Rat plasma proteomics: effects of abundant protein depletion on proteomic analysis.

The proteomic analysis of plasma and serum samples represents a formidable challenge due to the presence of a few highly abundant proteins such as albumin and immunoglobulins. Detection of low abundance protein biomarkers requires therefore either the specific depletion of high abundance proteins with immunoaffinity columns and/or optimized protein fractionation methods based on charge, size or hydrophobicity. Here we describe the depletion of seven abundant rat plasma proteins with an immunoaffinity column with coupled antibodies directed against albumin, IgG, transferrin, IgM, haptoglobin, fibrinogen and alpha1-anti-trypsin. The IgY-R7-LC2 (Beckman Coulter) column showed high specificity for the targeted proteins and was able to efficiently remove most of the albumin, IgG and transferrin from rat plasma samples as judged by Western blot analysis. Depleted rat plasma protein samples were analyzed by SELDI-TOF MS, 2D SDS-PAGE and 2D-LC and compared to non-depleted plasma samples as well as to the abundant protein fraction that was eluted from the immunoaffinity column. Analysis of the depleted plasma protein fraction revealed improved signal to noise ratios, regardless of which proteomic method was applied. However, only a small number of new proteins were observed in the depleted protein fraction. Immunoaffinity depletion of abundant plasma proteins results in the significant dilution of the original sample which complicates subsequent analysis. Most proteomic approaches require specialized sample preparation procedures during which significant losses of less abundant proteins and potential biomarkers can occur. Even though abundant protein depletion reduces the dynamic range of the plasma proteome by about 2-3 orders of magnitude, the difference between medium-abundant and low abundant plasma proteins is still in the range of 7-8 orders of magnitude and beyond the dynamic range of current proteomic technologies. Thus, exploring the plasma proteome in greater detail remains a daunting task.

Animals↗
PubMed2004

Detecting small flaws near the interface in pulse-echo.

Flaw detection near the interface surface is a common problem in many pulse-echo NDT applications due to interference with the interface echo, orders of magnitude above the flaw echoes. Several digital signal processing techniques like deconvolution, Hilbert transform and cepstrum analysis have been proposed to improve axial resolution. However, they require strict linearity, which takes a large portion of the system dynamic range just to fit the interface echo, thus reducing the dynamic range available for flaw detection. This work presents a new alternative based on the time-domain phase analysis of the received signals. Differently from conventional approaches, it works quite well with saturated signals resulting when a high gain is applied to detect small flaws. These can be detected in a range of a fraction of one wavelength from the interface surface, even using narrow-band transducers, as it has been experimentally verified. The method can be easily hardware implemented for real-time processing.

Journal Article↗
PubMed1996

Compression? Yes, but for low or high frequencies, for low or high intensities, and with what response times?

Several rationales for using compression in hearing aids are outlined. These rationales comprise discomfort avoidance, loudness normalization, noise reduction, short term signal dynamic range reduction, empirically determined compression, and long-term signal dynamic range reduction. The compression systems needed to implement each of these differ greatly, and these differences can be viewed as differences in the frequency range undergoing most compression, the intensity range undergoing most compression, and the speed at which the compressor(s) operate. A classification system along these lines is introduced and examples of currently available hearing aids falling into each category are given. The effects of each type of compression on speech intelligibility is investigated via a review of published research. The results of this indicate that, for speech in quiet at a comfortable level, no compression scheme yet tested offers better intelligibility than individually selected linear amplification. If input level is then decreased and the aid wearer is prevented from adjusting the volume control, many types of compression provide intelligibility superior to that available from linear amplification. In broadband noise, only one system, containing wideband compression followed by fast acting high-frequency compression, has so far been shown to provide significant intelligibility advantages.

Equipment Design↗
PubMed2002

Scaling of the interface roughness in Fe-Cr superlattices: self-affine versus non-self-affine.

We have analyzed kinetic roughening in Fe-Cr superlattices by energy-filtered transmission electron microscopy. The direct access to individual interfaces provides both static and dynamic roughness exponents. We find an anomalous non-self-affine scaling of the interface roughness with a time dependent local roughness at short length scales. While the deposition conditions affect strongly the long-range dynamics, the anomalous short-range exponent remains unchanged. The different short- and long-range dynamics outline the importance of long-range interactions in kinetic roughening.

Journal Article↗
PubMed2006

T1rho relaxation mapping in human osteoarthritis (OA) cartilage: comparison of T1rho with T2.

PURPOSE: To quantify the spin-lattice relaxation time in the rotating frame (T1rho) in various clinical grades of human osteoarthritis (OA) cartilage specimens obtained from total knee replacement surgery, and to correlate the T1rho with OA disease progression and compare it with the transverse relaxation time (T2). MATERIALS AND METHODS: Human cartilage specimens were obtained from consenting patients (N = 8) who underwent total replacement of the knee joint at the Pennsylvania Hospital, Philadelphia, PA, USA. T2- and T1rho-weighted images were obtained on a 4.0 Tesla whole-body GE Signa scanner (GEMS, Milwaukee, WI, USA). A 7-cm diameter transmit/receive quadrature birdcage coil tuned to 170 MHz was employed. RESULTS: All of the surgical knee replacement OA cartilage specimens showed elevated relaxation times (T2 and T1rho) compared to healthy cartilage tissue. In various grades of OA specimens, the T1rho relaxation times varied from 62 +/- 5 msec to 100 +/- 8 msec (mean +/- SEM) depending on the degree of cartilage degeneration. However, T2 relaxation times varied only from 32 +/- 2 msec to 45 +/- 4 msec (mean +/- SEM) on the same cartilage specimens. The increase in T2 and T1rho in various clinical grades of OA specimens were approximately 5-50% and 30-120%, respectively, compared to healthy specimens. The degenerative status of the cartilage specimens was also confirmed by histological evaluation. CONCLUSION: Preliminary results from a limited number of knee specimens (N = 8) suggest that T1rho relaxation mapping is a sensitive noninvasive marker for quantitatively predicting and monitoring the status of macromolecules in early OA. Furthermore, T1rho has a higher dynamic range (>100%) for detecting early pathology compared to T2. This higher dynamic range can be exploited to measure even small macromolecular changes with greater accuracy compared to T2. Because of these advantages, T1rho relaxation mapping may be useful for evaluating early OA therapy.

Arthroplasty, Replacement, Knee↗
PubMed2003

Non-linearity in the quadrupole detector system: implications for the determination of the 13C mass distribution of an ion fragment.

Some biomedical (13)C tracer applications to study glucose/lactate metabolism require the determination of up to 7 mass isotopomers of glucose, generated by the (13)C-labeling. Isotopomer ratios determined by GC-Quadrupole-MS can depend on the analyte amount being measured and may differ from expected theoretical values. A calibration is necessary to correct these effects. However, the large number of different isotopomers prevents an empirical calibration, that is based on known isotopomer mixtures. Neither insufficient mass separation in the quadrupole nor proton adducts or losses of the ionized fragment can account for the observed deviation from expected values and the dependency on the sample size. We explain the deviations with a nonlinear mapping of the isotopomer amount being analyzed to the area under the elution curve for the corresponding mass channel. The nonlinear relation allows to estimate potential errors in the determination of isotopomer ratios. It also allows to define a dynamic range as the range of signal areas, for which the systematic error in the isotopomer ratio determination is below 5% of the nominal value. It is 1 : 200 and 1 : 500 for two different fragments of glucose, measured under EI and CI and is smaller than the range imposed by the measurement precision. After correcting the nonlinearities the dynamic range improved by the factor 10 in both cases.

Carbon Isotopes↗
PubMed2006

Enhanced mass resolution method development, validation and assay application to support preclinical studies of a new drug candidate.

A very highly sensitive and highly selective liquid chromatographic/tandem mass spectrometric (LC/MS/MS) method was developed to evaluate and quantify a new drug candidate in different biological matrices. Following a simple plasma protein precipitation using acetonitrile, the post-treatment samples were analyzed on a C18 column interfaced with a new generation of triple-quadrupole mass spectrometer. The recently introduced triple-quadrupole mass spectrometer, the TSQ Quantum Ultra, with enhanced mass-resolution capability, demonstrated improved sensitivity (0.05 ng/mL), coupled with suitable accuracy and precision, over a broad linear dynamic range (0.05-1000 ng/mL). A comparison of the assay performance data (dynamic range, calibration curve equation, precision and accuracy) of the enhanced resolution method against a unit resolution method under optimized conditions showed the performance improvement of the enhanced mass resolution method for bioanalytical high-throughput applications. The enhanced mass resolution method herein described was successfully applied to the evaluation of the pharmacokinetic profile of a new drug candidate in rat, rabbit and dog plasma samples.

Animals↗
PubMed1992

Sensitivity of neurons in cat primary auditory cortex to tones and frequency-modulated stimuli. I: Effects of variation of stimulus parameters.

In the primary auditory cortex (AI) of barbiturate-anesthetized cats multi-unit responses to tones and to frequency-modulated (FM) tonal stimuli were analyzed. Characteristic frequency (CF), sharpness of tuning, minimum threshold, and dynamic range of spike count--intensity functions were determined. Minimum threshold and dynamic range were positively correlated. The response functions to unidirectional FM sweeps of varying linear rate of change of frequency (RCF) that traversed the excitatory frequency response areas (FRAs) displayed a variety of shapes. Preferences for fast RCFs (> 1000 kHz/s) were most common. Best RCF was not correlated with measures of sharpness of tuning. Directional preference and sensitivity were quantified by a DS index which varied with RCF. About two-thirds of the multi-unit responses showed a preference for downward sweeps. Directional sensitivity was independent of CF and independent of best RCF. Measurements of latencies of phasic responses to unidirectional FM sweeps of different RCF demonstrated that the discharges of a given multi-unit over its effective RCF range were initiated at the same instantaneous frequency (effective Fi), independent of RCF. Effective Fis fell within the excitatory FRA of a given multi-unit. The relationships of effective Fis to CF show that responses were evoked only when the frequency of the signal was modulated towards CF and not when modulated away from it, and that responses were initiated before the modulation reached CF. Changes in the range and depth of modulation had only minor, if any, effects on RCF response characteristics, FM directional sensitivity, and effective Fis, as long as the beginning and ending frequencies of FM sweeps fell outside a multi-unit's FRA. Stimulus intensity also had only moderate effects on RCF response characteristics and DS. However, effective Fis were influenced in systematic fashions; with increases in intensity, effective Fis to upward and downward sweeps decreased and increased, respectively. Thus, for higher intensities FM responses were initiated at instantaneous frequencies occurring earlier in the signal. The results are compared with previous data on tone and FM sensitivity of auditory neurons in cortical and subcortical structures, and mechanisms of FM rate and directional sensitivity are discussed. The topographic representations of these neuronal properties in AI are reported in the companion report.

Acoustic Stimulation↗
PubMedDate not supplied

Comparison of multiplexed techniques for detection of bacterial and viral proteins.

Immobilized antibody microarrays were compared to the Luminex flow cytometry system that utilizes suspensions of polystyrene microbeads covalently coupled with capture antibodies. The two immunoassays were performed for comparison of reproducibility, limits of detection and dynamic range. The Luminex system showed lower limits of detection and increased dynamic range among samples whereas the protein microarrays could be more amenable to miniaturization. Both technologies were capable of sensitive multiplexed detection.

Antibodies, Bacterial↗
PubMed2004

Ferrocene-containing polyelectrolyte multilayer film-covered electrodes: electrocatalytic determination of ascorbic acid and use of inner blocking layers to improve the upper detection limit of the electrodes.

A multilayer film composed of ferrocene(Fc)-appended poly(allylamine hydrochloride) (Fc-PAH) and poly(potassium vinylsulfate) (PVS) has been prepared on the surface of a gold(Au) electrode by using a layer-by-layer self-assembly technique. Fc-containing polyelectrolyte multilayer (PEM) film-modified electrodes can electrochemically catalyze the oxidation of ascorbic acid successfully. For a 2 (Fc-PAH/PVS) bilayer-covered electrode the catalytic current increased linearly with increasing concentration of ascorbic acid over the concentration range 6 micromol L(-1)-3 mmol L(-1). To extend the dynamic range for ascorbic acid, the surface of the Au electrode was first covered with a (PAH/PVS)(2) film on which an additional (Fc-PAH/PVS)(5) film was coated. This strategy successfully extended the dynamic range of the electrode up to 25 mmol L(-1) ascorbic acid, because the (PAH/PVS)(2) layer blocked access of ascorbic acid to the electrode surface. The upper detection limit of the (PAH/PVS)(2) (Fc-PAH/PVS)(5) film-modified electrode is much higher than those of Fc-based ascorbic acid sensors reported so far. Electron transfer is diffusion-controlled within the (PAH/PVS)(2)(Fc-PAH/PVS)(5) film.

Ascorbic Acid↗
PubMed1994

Relations between voice range profiles and physiological and perceptual voice characteristics in ten-year-old children.

Pitch and intensity range of 60 children were recorded and plotted in voice range profiles (VRPs). Different aspects were investigated: minimum phonation threshold, pitch range, and maximum dynamic range. Vocal fold status was determined via laryngoscopic examination. Ten percent of the children had vocal nodules, 23% glottal chinks. Seven voice experts listened to the voices recorded on two separate occasions and rated their properties along 16 parameters including hoarseness. Fourteen percent were rated as hoarse on both recordings and were thus classified as being chronically hoarse. Departures from normal in VRP characteristics were found for children suffering from chronic hoarseness, nodules, and glottal chinks. Children in general seem to have somewhat compressed VRP contours compared with adults, reflecting restricted dynamic vocal capabilities; however, children with mutational voices exhibited an approximation to adult upper VRP contours.

Auditory Perception↗
PubMed1982

Predictive coding: a fresh view of inhibition in the retina.

Interneurons exhibiting centre--surround antagonism within their receptive fields are commonly found in peripheral visual pathways. We propose that this organization enables the visual system to encode spatial detail in a manner that minimizes the deleterious effects of intrinsic noise, by exploiting the spatial correlation that exists within natural scenes. The antagonistic surround takes a weighted mean of the signals in neighbouring receptors to generate a statistical prediction of the signal at the centre. The predicted value is subtracted from the actual centre signal, thus minimizing the range of outputs transmitted by the centre. In this way the entire dynamic range of the interneuron can be devoted to encoding a small range of intensities, thus rendering fine detail detectable against intrinsic noise injected at later stages in processing. This predictive encoding scheme also reduces spatial redundancy, thereby enabling the array of interneurons to transmit a larger number of distinguishable images, taking into account the expected structure of the visual world. The profile of the required inhibitory field is derived from statistical estimation theory. This profile depends strongly upon the signal: noise ratio and weakly upon the extent of lateral spatial correlation. The receptive fields that are quantitatively predicted by the theory resemble those of X-type retinal ganglion cells and show that the inhibitory surround should become weaker and more diffuse at low intensities. The latter property is unequivocally demonstrated in the first-order interneurons of the fly's compound eye. The theory is extended to the time domain to account for the phasic responses of fly interneurons. These comparisons suggest that, in the early stages of processing, the visual system is concerned primarily with coding the visual image to protect against subsequent intrinsic noise, rather than with reconstructing the scene or extracting specific features from it. The treatment emphasizes that a neuron's dynamic range should be matched to both its receptive field and the statistical properties of the visual pattern expected within this field. Finally, the analysis is synthetic because it is an extension of the background suppression hypothesis (Barlow & Levick 1976), satisfies the redundancy reduction hypothesis (Barlow 1961 a, b) and is equivalent to deblurring under certain conditions (Ratliff 1965).

Animals↗
PubMed1989

Hot-film anemometry for measuring lateral line stimuli.

A hot-film anemometer system has been calibrated and evaluated for the measurement of sinusoidal water motions used in stimulating the mechanosensory lateral line system of a teleost fish. The response of the anemometer system to water motions created by a vibrating sphere was measured over a wide range of frequencies, intensities, and distances from the sphere. The amplitude response of the system to signals along the axis of sphere vibration was found to be linear over a 50-dB range for frequencies from 10-200 Hz, with the lowest end of the dynamic range (between 10(-8) and 10(-9) m) corresponding to physiological measures of best sensitivity in the lateral line system of the mottled sculpin, Cottus bairdi. The measured attenuation of the signal with distance was also linear over this frequency range out to distances of six times the radius ( = 3 mm) of the sphere and followed the predicted falloff rate for a dipolar source. The linear response of the anemometer system over a wide dynamic range encompassing the detection range of the lateral line system, and the match between predicted and measured motions at varying distances from a dipolar source, indicates that hot-film anemometry is a useful technique for measuring low-level, low-frequency signals likely to stimulate the lateral line system and other hydrodynamic detectors.

Animals↗
PubMed1992

Speciation of tissue and cellular iron with on-line detection by inductively coupled plasma-mass spectrometry.

Iron accumulating to excess in tissues of humans and animal models occurs mainly as complexes with transferrin, ferritin, other hemoproteins, and insoluble hemosiderin particles. To determine the distribution of Fe amongst these molecular species, we have used inductively coupled plasma-mass spectrometry as a means of on-line, isotope-specific detection for their liquid chromatographic separation. The stable isotope 57Fe is a suitable isotope for monitoring the Fe content of each fraction, and its availability at high isotopic enrichment makes it an attractive choice for tracer studies when the use of a radioisotope is undesirable, e.g., in human subjects. The detection system offers the advantages of high sensitivity (detection limits in the parts per billion range), a wide dynamic range (linearity of the calibration curve over several orders of magnitude), and on-line analysis facilitating real-time evaluation of the chromatographic separation, in addition to isotope-specific information. The Fe distributions in healthy rat livers, liver and heart tissue from Fe-loaded human subjects, and human hepatocyte cultures are reported. The ferritin:hemosiderin ratio in these samples is shown to be an indicator of the degree of Fe loading and correlates well with that determined by Zeeman-corrected electrothermal atomic absorption as an alternative means of detection.

Animals↗
PubMed2005

Enhancing resolution along multiple imaging dimensions using assorted pixels.

Multisampled imaging is a general framework for using pixels on an image detector to simultaneously sample multiple dimensions of imaging (space, time, spectrum, brightness, polarization, etc.). The mosaic of red, green, and blue spectral filters found in most solid-state color cameras is one example of multisampled imaging. We briefly describe how multisampling can be used to explore other dimensions of imaging. Once such an image is captured, smooth reconstructions along the individual dimensions can be obtained using standard interpolation algorithms. Typically, this results in a substantial reduction of resolution (and, hence, image quality). One can extract significantly greater resolution in each dimension by noting that the light fields associated with real scenes have enormous redundancies within them, causing different dimensions to be highly correlated. Hence, multisampled images can be better interpolated using local structural models that are learned offline from a diverse set of training images. The specific type of structural models we use are based on polynomial functions of measured image intensities. They are very effective as well as computationally efficient. We demonstrate the benefits of structural interpolation using three specific applications. These are 1) traditional color imaging with a mosaic of color filters, 2) high dynamic range monochrome imaging using a mosaic of exposure filters, and 3) high dynamic range color imaging using a mosaic of overlapping color and exposure filters.

Algorithms↗
PubMed1983

Assessment of ultrasound scanners by acoustic signal injection.

A new technique has been introduced whereby test signals are injected acoustically into a diagnostic scanner under test--no direct electrical connection is therefore needed. A simple battery operated instrument has been produced which will operate with all types of imaging equipment and which is particularly suitable for the routine checking of velocity and caliper calibrations, the assessment of scale factors, measurement of dynamic range and the effect of signal processing options on grey-scale dynamic range and the effect of signal processing options on grey-scale behaviour and for the adjustment of display and hard copy units.

Acoustics↗
PubMed1995

Quantitative analysis of lymphokine mRNA expression by an automated, non-radioactive method.

Variable gene expression, thus giving rise to variable mRNA levels, constitutes a major mechanism for controlling cell development and cell function. In order to investigate these changed mRNA levels, a sensitive and quantitative assay is required. A quick and easy method is described to quantify specific mRNA's by a combination of the polymerase chain reaction (PCR) and an electro-chemiluminescenct (ECL) detection of the amplified products. Total cellular RNA is reverse transcribed and amplified with a biotinylated forward primer and a TBR (Tris (2,2'-bipyridine) ruthenium (II)) labelled reverse primer. The amplification product is captured on streptavidin-coated paramagnetic beads and quantified by ECL detection using the QPCR system 5000. The results can be converted to quantitative values with an external standard curve. In the present study, cytokine mRNA expression in T lymphocytes was quantified. Cytokine mRNA was measured at the attomolar range in a dynamic range up to three orders of magnitude. The ECL detection is quantitative, rapid and accurate.

Base Sequence↗
PubMedDate not supplied

[The use of sigma-delta analog-digital conversion in multichannel electrocardiographs].

With advances in the manufacture of super great integrated circuits, a commercially available element base that realizes the sigma-delta (sigma-delta) analog-to-digital conversion principle in one microcircuit has appeared. The sigma-delta analog-to-digital converters (ADC) have a high resolving power (above 12 bits), they are largely based on the signal digital filtration principles, which may moderate requirements for the analog filtration of signals and use direct-current amplifiers as alternatives to instrument ones. For electrocardiograph operation, the sigma-delta ADC of an AD 7716 (Analog Devices) with 22 bits were used in this study. The use of sigma-delta ADC in the electrocardiographs has been shown to be a rather useful alternative of traditional ADC. Moreover, sigma-delta ADC may be also useful for other systems for collecting and processing biomedical signals which are close in their requirements for a frequency range and a dynamic range, i.e. encephalographic, myographic, rheographic and other input signals.

Analog-Digital Conversion↗