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At least 865 records · Page 48Linked to original sources
PubMed2006

Cerebral hemodynamics during orthostatic stress assessed by nonlinear modeling.

The effects of orthostatic stress, induced by lower body negative pressure (LBNP), on cerebral hemodynamics were examined in a nonlinear context. Spontaneous fluctuations of beat-to-beat mean arterial blood pressure (MABP) in the finger, mean cerebral blood flow velocity (MCBFV) in the middle cerebral artery, as well as breath-by-breath end-tidal CO2 concentration (P(ET(CO2))) were measured continuously in 10 healthy subjects under resting conditions and during graded LBNP to presyncope. A two-input nonlinear Laguerre-Volterra network model was employed to study the dynamic effects of MABP and P(ET(CO2)) changes, as well as their nonlinear interactions, on MCBFV variations in the very low (VLF; below 0.04 Hz), low (LF; 0.04-0.15 Hz), and high frequency (HF; 0.15-0.30 Hz) ranges. Dynamic cerebral autoregulation was described by the model terms corresponding to MABP, whereas cerebral vasomotor reactivity was described by the model P(ET(CO2)) terms. The nonlinear model terms reduced the output prediction normalized mean square error substantially (by 15-20%) and had a prominent effect in the VLF range, both under resting conditions and during LBNP. Whereas MABP fluctuations dominated in the HF range and played a significant role in the VLF and LF ranges, changes in P(ET(CO2)) accounted for a considerable fraction of the VLF and LF MCBFV variations, especially at high LBNP levels. The magnitude of the linear and nonlinear MABP-MCBFV Volterra kernels increased substantially above -30 mmHg LBNP in the VLF range, implying impaired dynamic autoregulation. In contrast, the magnitude of the P(ET(CO2))-MCBFV kernels reduced during LBNP at all frequencies, suggesting attenuated cerebral vasomotor reactivity under dynamic conditions. We speculate that these changes may reflect a progressively reduced cerebrovascular reserve to compensate for the increasingly unstable systemic circulation during orthostatic stress that could ultimately lead to cerebral hypoperfusion and syncope.

Adult↗
PubMed1980

A design for a real-time fluorescence polarization computer.

We have developed hardware components for our flow cytometer cell sorter which can perform real-time calculations of either fluorescence polarization (FP) or anisotropy on a cell-by-cell basis and which can provide gating signals for the sorting of these cells into two populations. Artificial FP measurements, using electronic pulses varied over a 40dB range, were used to evaluate the computer's useful dynamic range. Real FP measurements, using human peripheral blood lymphocytes stimulated with phytohemagglutinin and labeled with fluorescein diacetate in saline, are presented to allow comparison with earlier work.

Computers↗
PubMed1980

Flash photolysis study of ligand binding by modified myoglobins at low temperatures.

The CO-binding kinetics of myoglobin containing proto-, meso- and deutero-hemes were studied by flash photolysis over the temperature range 50-300 K. Results recorded over a large dynamic range of time (microseconds to many seconds) reveal processes that are non-exponential in time and multiphasic. The data are explained by a model in which the CO molecule must surmount four barriers in migrating from the solvent to the heme iron. At least two of these barriers have heights that vary from one molecule to another. Varying the nature of the heme group affects mainly the innermost of these barriers and, to a lesser degree, the second-outermost barrier.

Binding Sites↗
PubMed2004

Monolithically integrated bacteriorhodopsin/semiconductor opto-electronic integrated circuit for a bio-photoreceiver.

The light-sensitive protein, bacteriorhodopsin (BR), is monolithically integrated with an InP-based amplifier circuit to realize a novel opto-electronic integrated circuit (OEIC) which performs as a high-speed photoreceiver. The circuit is realized by epitaxial growth of the field-effect transistors, currently used semiconductor device and circuit fabrication techniques, and selective area BR electro-deposition. The integrated photoreceiver has a responsivity of 175 V/W and linear photoresponse, with a dynamic range of 16 dB, with 594 nm photoexcitation. The dynamics of the photochemical cycle of BR has also been modeled and a proposed equivalent circuit simulates the measured BR photoresponse with good agreement.

Amplifiers, Electronic↗
PubMed2006

Quantitation of atenolol, metoprolol, and propranolol in postmortem human fluid and tissue specimens via LC/APCI-MS.

Hypertension is a growing medical concern in the United States. With the number of Americans suffering from hypertension increasing, the use of antihypertensives such as beta-blockers is increasing as well. In fact, three beta-blockers - atenolol, metoprolol and propranolol - were among the 200 most prescribed medications in the United States in 2003. Pilots that successfully manage their hypertension can remain certified to fly. The Federal Aviation Administration currently designates approximately 8% of active pilots as "hypertensive with medication". The Civil Aerospace Medical Institute (CAMI) performs toxicological evaluation on victims of fatal aviation accidents. At CAMI beta-blockers are analyzed using gas chromatography with mass spectrometric detection. We have, however, recently developed a liquid chromatography with mass spectrometric detection (LC/MS) method for the simultaneous quantitation of three commonly prescribed beta-blockers, atenolol, metoprolol and propranolol. One advantage of our LC/MS method is the specificity provided by an ion trap MS. Utilizing an ion trap MS, we were able to conduct MS/MS and MS/MS/MS on each analyte. This method also eliminates the time-consuming and costly derivitization step necessary during GC/MS analysis. Additionally, by utilizing this novel method, any concerns about beta-blocker metabolite and/or sample matrix interference are eliminated. The limits of detection for this method ranged from 0.39 to 0.78 ng/mL and the linear dynamic range was generally 1.6-3200 ng/mL. The extraction efficiencies for each analyte ranged from 58% to 82%. This method was successfully applied to postmortem fluid and tissue specimens obtained from victims of three separate aviation accidents.

Adrenergic beta-Antagonists↗
PubMed2004

Determination of cocaine, its metabolites, pyrolysis products, and ethanol adducts in postmortem fluids and tissues using Zymark automated solid-phase extraction and gas chromatography-mass spectrometry.

Demonstrating the presence or absence of cocaine (COC) and COC-related molecules in postmortem fluids and/or tissues can have serious legal consequences and may help determine the cause of impairment and/or death. We have developed a simple method for the simultaneous determination of COC and the COC metabolites benzoylecgonine (BE), norbenzoylecgonine (NBE), ecgonine methyl ester (EME), ecgonine (E), and norcocaine (NCOC), as well as anhydroecgonine methyl ester (AEME) (a unique byproduct of COC smoking), cocaethylene (a molecule formed by the concurrent use of COC and ethanol) and their related metabolites, anhydroecgonine (AE), norcocaethylene (NCE), and ecgonine ethyl ester (EEE). This method incorporates a Zymark RapidTrace automated solid-phase extraction (SPE) system, gas chromatography/mass spectrometry (GC/MS) and 2,2,3,3,3-pentafluoro-1-propanol (PFP)/pentafluoropropionic anhydride (PFPA) derivatives. The lower limits of detection ranged from 0.78 to 12.5 ng/mL and the linear dynamic range for most analytes was 0.78-3200 ng/mL. The extraction efficiencies were from 26 to 84% with the exception of anhydroecgonine and ecgonine, which were from 1 to 4%. We applied this method to five aviation fatalities. This method has proven to be simple, robust and accurate for the simultaneous determination of COC and 11 COC metabolites in postmortem fluids and tissues.

Automation↗
PubMed1998

Basic response characteristics of auditory nerve fibers in the grassfrog (Rana temporaria).

Responses to free-field sound of 401 fibers from the VIIIth nerve of the grassfrog, Rana temporaria, are described. The spontaneous activities of the fibers ranged from 0 to 75 spikes/s, showing only weak correlation with frequency or sensitivity of the fibers. The highest spontaneous activities were approximately twice as high as reported previously for frogs. Best frequencies ranged from 100 to 1600 Hz and thresholds ranged from 21 to 80 dB SPL. The median dynamic range was 20 dB and the slopes of the rate-level curves ranged from 5 to 20 spikes/(s-dB). Most of the units showed post-excitatory suppression (PS) of their spontaneous activity. The duration of PS increased with sound level, also in fibers showing a decrease in firing rate at high intensities. Most fibers showing one-tone suppression did not show PS at their best suppression frequencies. Strong suppression was observed also in very phasic cells giving one spike per stimulation. Therefore, the mechanism underlying PS is probably different from that underlying adaptation. The sharpening of the neural encoding of temporal parameters and the strong encoding of sound offset as well as onset caused by PS very likely is biologically important.

Acoustic Stimulation↗
PubMed2006

Performance evaluation of a hybrid linear ion trap/orbitrap mass spectrometer.

Design and performance of a novel hybrid mass spectrometer is described. It couples a linear ion trap mass spectrometer to an orbitrap mass analyzer via an rf-only trapping quadrupole with a curved axis. The latter injects pulsed ion beams into a rapidly changing electric field in the orbitrap wherein they are trapped at high kinetic energies around an inner electrode. Image current detection is subsequently performed after a stable electrostatic field is achieved. Fourier transformation of the acquired transient allows wide mass range detection with high resolving power, mass accuracy, and dynamic range. The entire instrument operates in LC/MS mode (1 spectrum/s) with nominal mass resolving power of 60,000 and uses automatic gain control to provide high-accuracy mass measurements, within 2 ppm using internal standards and within 5 ppm with external calibration. The maximum resolving power exceeds 100,000 (fwhm). Rapid, automated data-dependent capabilities enable real-time acquisition of up to three high-mass accuracy MS/MS spectra per second.

Journal Article↗
PubMedDate not supplied

Quantitative analysis of modified proteins by LC-MS/MS of peptides labeled with phenyl isocyanate.

Stable isotope tagging methods have enabled relative quantitation of proteins between samples in LC-MS/MS analyses. However, most such methods are not applicable to the differential quantitation of modified proteins because the isotope tagging reagents only react with certain peptides or because the reagents incorporate a mass increment that is too small to allow reliable quantitation on low resolution ion trap MS instruments. Here, we describe the use of d0- and d5-phenyl isocyanate (PIC) as N-terminal reactive tags for essentially all peptides in proteolytic digests. PIC reacts quantitatively with peptide N-terminal amines within minutes at neutral pH and the PIC-labeled peptides undergo informative MS/MS fragmentation. Ratios of d0- and d5-PIC-labeled derivatives of several model peptides were linear across a 10000-fold range of peptide concentration ratios, thus indicating a wide dynamic range for quantitation. Application of PIC labeling enabled relative quantitation of several styrene oxide adducts of human hemoglobin in LC-MS/MS analyses. PIC labeling offers a versatile means of quantifying changes in modified or variant protein forms in paired samples.

Chemistry Techniques, Analytical↗
PubMed2004

Simulated annealing of microarray data reduces noise and enables cross-experimental comparisons.

Microarrays are a powerful tool for assessing the genome-wide induction of a transcriptional response to internal or external stimuli, but are not considered quantitatively rigorous (i.e., the signal intensity of hybridized probe is normally used to quantify relative transcript abundance). Thus, it is difficult, if not impossible, to accurately compare separate microarray experiments without a reference standard. However, even among replicated microarray experiments, each gene varies significantly in the amount of signal detected, suggesting no single gene would be appropriate as a standard. We propose and test a method to "align" experimental transcription profiles to a set of reference experiments using simulated annealing (SA), essentially using the relative positions of all genes as a reference standard. SA attempts to find a globally optimal adjustment factor for the relative expression level of each experimental gene expression signal, given a previously observed range of gene expression measurements. By defining a relative dynamic range of gene expression under control conditions for all genes, we can more accurately compare transcription profiles between separate experiments and, potentially, between species--enabling comparative transcriptomics. Testing SA on a published dataset, we find that it significantly reduces interexperimental variation, suggesting it holds promise to accomplish this goal.

Oligonucleotide Array Sequence Analysis↗
PubMed1987

Simulation of sensorineural hearing impairment.

A hearing loss simulation system (HELOS) was designed and constructed to simulate various aspects of sensorineural hearing impairment. The theoretical bases for HELOS were several threshold and suprathreshold auditory phenomena typically exhibited by people with sensorineural hearing losses. In addition to providing differential attenuation of acoustic signals across the frequency range, HELOS simulated loudness recruitment, loudness discomfort thresholds, reduced dynamic range, and reduced frequency selectivity. Three basic audiometric configurations were chosen to investigate the effects of the aforementioned components of a sensorineural hearing impairment on the auditory perception of speech. They were: (1) a sloping high-frequency hearing loss; (2) a flat, severe hearing loss; (3) a severe/profound hearing loss. The battery of tests administered to a group of normal-hearing adults consisted of pure-tone audiometry and PB-word recognition tests, as well as vowel and consonant identification tests. For comparable audiometric configurations, the results from the speech-perception tests were in good agreement with the published results of similar tests administered to persons with sensorineural hearing losses.

Adult↗
PubMed2000

Performance of the COBAS AMPLICOR HCV MONITOR test, version 2.0, an automated reverse transcription-PCR quantitative system for hepatitis C virus load determination.

A clinical evaluation of an automated quantitative PCR assay, the COBAS AMPLICOR HCV MONITOR test, version 2.0 (v2.0), was carried out to assess the performance of this test in comparison with that of the previous, manual version, the AMPLICOR HCV MONITOR test, and with that of nested PCR. Serial dilutions of serum samples infected with genotype 1b, 2a, or 3, as well as synthetic RNA transcripts and serum samples derived from 87 patients with chronic hepatitis C and infected with genotype 1a, 1b, 2a, 2b, 3a, 3b, 4, or 5, were analyzed to determine the ability of the system to efficiently quantify various hepatitis C virus (HCV) genotypes. These experiments showed that the COBAS AMPLICOR HCV MONITOR test, v2.0, has mean intra-assay, interassay, and interoperator coefficients of variation that range from 22 to 34.5% and a 3-logarithm dynamic range, which spans from 10(3) to 10(6) copies/ml. Compared to the previous, manual version of the test, the COBAS AMPLICOR HCV MONITOR test, v2.0, showed an improved efficacy for all genotypes, especially genotypes 2, 3, and 4, whose estimated concentrations were on average 1 logarithm higher. When used to monitor patients under treatment, however, both versions showed the same patterns of viremia, indicating that the COBAS AMPLICOR HCV MONITOR test, v2.0, and the AMPLICOR HCV MONITOR test were equally effective at detecting relative viremia changes in serial samples. As expected, the automated test was less sensitive than nested PCR; among specimens from a cohort of patients treated with interferon, nested PCR identified three more viremic specimens, which probably contained very low concentrations of HCV RNA.

Hepacivirus↗
PubMed2003

Interferometer for optical coherence tomography.

We describe a new interferometer setup for optical coherence tomography (OCT). The interferometer is based on a fiber arrangement similar to Young's two-pinhole interference experiment with spatial coherent and temporal incoherent light. Depth gating is achieved detection of the interference signal on a linear CCD array. Therefore no reference optical delay scanning is needed. The interference signal, the modulation of the signal, the axial resolution, and the depth range are derived theoretically and compared with experiments. The dynamic range of the setup is compared with OCT sensors in the time domain. To our knowledge, the first images of porcine brain and heart tissue and human skin are presented.

Animals↗
PubMed1975

[Types of receptive field in the external geniculate body and its functional model].

The functional differences between receptive fields of types I and II of lateral geniculate nucleus were investigated in cat. Some characteristics of these fields are shown to coincide with transient (Y-type ) and sustanied (X-type) receptive fields. Receptive fields of type I possess a limited range for transmission of information on luminance, those of type II--a normal dynamic range (2 log. unit). The investigation of a dynamic functional model showed that type of the receptive field is determined by the depth of inhibition mediated through an interneuron. The depth of inhibition is larger in type I. Types I and II have different frequency characteristics. It is suggested that receptive fields of type I serve to transmit information on the shape of the image (spatial and time contrasts) and those of type II on luminance.

Animals↗
PubMed1989

[Examination of the vocal range in school children].

The author examined in 50 children (pupils of the 1st 50 5th form of primary school), selected at random, the vocal field. The group comprised 22 boys and 28 girls, always 10 children from the same form. Their mean vocal range was 17 semi-tones from G sharp to C2. The maximal dynamic range varied between 10 and 13 dB and did not exceed the intensity of 75 dB A. These results suggest relatively limited dynamics of the singing voice in children and indicate the optimal vocal position and range. Marked transcendence of these limits is probably one of the reasons which lead in some children singing in choirs to overburdening of the vocal organ and may lead to the development of hyperkinetic dysphonia.

Child↗
PubMed1989

A new linear plot for standard curves in kinetic substrate assays extended above the Michaelis-Menten constant: application to a luminometric assay of glycerol.

In conventional kinetic substrate assays the standard curve is plotted as observed reaction rate, upsilon obs, versus added substrate concentration, Sadd, and has a linearity limited to Sadd much less than Km. From this plot the blank reaction rate, upsilon bl, is easily estimated but not the contaminating substrate concentration, Scon, present in reagents (unless it is the only blank source). Thus the actual substrate concentration, S = Scon + Sadd, cannot be estimated as required for the various linear plots based on the Michaelis-Menten equation. We have derived an expression, (upsilon obs - upsilon bl)/Vapp = Sadd/(Kmapp + Sadd), containing only those parameters measured for a conventional standard curve (Vapp and Kmapp are obtained from a plot of (upsilon obs - upsilon bl) versus (upsilon obs - upsilon bl)/Sadd). A plot of (upsilon obs - upsilon bl)/Vapp versus Sadd/(Kmapp + Sadd) can be used as a standard curve with the following advantages over the conventional standard curve: (a) For all kinetic substrate assays it is identical and connects the points (0, 0) and (1, 1). Thus deviations from true Michaelis-Menten kinetics or erroneous kinetic constants are easily detected. (b) Since it is linear even above Km, the analytically useful range is considerably extended. (c) For assays with a wide dynamic range it can be used in lin-lin or log-log form. The procedure is illustrated for a kinetic assay of glycerol (Kmapp = 40 mumol/liter). The plot was found to be entirely linear in the range 0.07-100 mumol/liter (glycerol concentration in cuvette).

Adenosine Triphosphate↗
PubMed2006

Enzyme electrodes based on sono-gel containing ferrocenyl compounds.

An amperometric-mediated glucose sensor has been developed by employing a silica sono-gel carbon composite electrode (SCC). The chosen mediators, ferrocene (Fc) and 1,2-diferrocenylethane (1), have been immobilized in the sono-gel composite matrix. The complex 1 has been employed for the first time as an electron transfer mediator for signal transduction from the active centre of the enzyme to the electrode conductive surface. After the optimisation of the construction procedure the best operative conditions for the analytical performance of the biosensor have been investigated in terms of pH, temperature and applied potential. Cyclic voltammetric and amperometric measurements have been used to study the response of both the glucose sensors, which exhibit a fast response and good reproducibility. The sensitivity to glucose is quite similar (6.7+/-0.1 microA/mM versus 5.3+/-0.1 microA/mM) when either Fc or 1 are used as mediators as are the detection limit ca. 1.0 mM (S/N=3) and the range of linear response (up to 13.0 mM). However, the dynamic range for glucose determination results wider when using 1 (up to 25.0 mM). The apparent Michaelis-Menten constants, calculated from the reciprocal plot under steady state conditions, are 27.7 and 31.6 mM for SCC-Fc/GOx and SCC-1/GOx electrodes, respectively, in agreement with a slightly higher electrocatalytic efficiency for the mediator 1.

Aspergillus niger↗
PubMed2006

Comparison of three multiplex cytokine analysis systems: Luminex, SearchLight and FAST Quant.

Multiplex cytokine analysis technologies have become readily available in the last five years. Two main formats exist: multiplex sandwich ELISA and bead based assays. While these have each been compared to individual ELISAs, there has been no direct comparison between the two formats. We report here the comparison of two multiplex sandwich ELISA procedures (FAST Quant and SearchLight) and a bead based assay (UpState Luminex). All three kits differed from each other for different analytes and there was no clear pattern of one system giving systematically different results than another for any analyte studied. We suggest that each system has merits and several factors including range of analytes available, prospect of development of new analytes, dynamic range of the assay, sensitivity of the assay, cost of equipment, cost of consumables, ease of use and ease of data analysis need to be considered when choosing a system for use. We also suggest that results obtained from different systems cannot be combined.

CD8-Positive T-Lymphocytes↗