Internal Reference Signal Research Articles

Application of Quantitative Nuclear Magnetic Resonance Spectroscopy for the Determination of Amantadine and Acyclovir in Plasma and Pharmaceutical Samples

Rapid, simple, and selective methods for determining amantadine HCI and acyclovir antiviral drugs in pharmaceutical and plasma samples were developed using 1H-NMR spectroscopy with dimethyl sulfoxide (DMSO-d6) as the solvent. Integrations of the 1H-NMR signals at 2.07 and 7.82 ppm were used, respectively, for quantifying the two drugs, with the malonic acid signal at 3.24 ppm as the internal reference signal. Average recoveries of 98.24-101.00 +/- 4.82% and 97.7-100.38 +/- 3.36% were obtained for amantadine HCI and acyclovir in pharmaceutical samples, respectively. Average recoveries of 97.36-103.68 +/- 2.99 and 93.81-99.80 +/- 2.93 were obtained, respectively, for both drugs in plasma samples. The statistical Student's t-test gave t-values < or = 1.41 for analyzed pharmaceutical samples and t-values < or = 0.29 for analyzed plasma samples. These values indicated insignificant difference between the real and measured contents at the 95% confidence level. Application of the statistical F-test for the analytical results of amantadine HCI gave F-values < or = 6.44 and 2.80 in pharmaceutical and plasma samples, respectively. F-values < or = 6.82 and 3.86 were obtained for acyclovir in pharmaceutical and plasma, respectively. These values indicated insignificant differences in precisions between the developed NMR methods and arbitrarily chosen HPLC methods reported for determining both drugs in pharmaceutical and plasma samples.

A Narrowband Active Noise Control System With Frequency Corrector

The performance of narrowband active noise control (ANC) systems degenerates significantly under the frequency mismatch between the synthesized reference signal and the primary noise. This paper proposes a new narrowband ANC system that incorporates a frequency corrector for the internal reference signal generator to mitigate the ill-effects caused by the frequency mismatch. The proposed frequency estimator uses the iterative frequency estimation algorithm based on the minimum variance distortionless response spectrum that has advantages of accuracy and fast convergence. The performance of the new narrowband ANC system is analyzed under the conditions of frequency mismatch and the secondary-path phase estimation error. The frequency and amplitude of the primary noise are modeled as time-varying variables in the theoretical analysis. Computer simulations are conducted to demonstrate the performance of the new ANC system and to verify the analysis results.

An internal reference model–based PRF temperature mapping method with Cramer‐Rao lower bound noise performance analysis

The conventional phase difference method for MR thermometry suffers from disturbances caused by the presence of lipid protons, motion-induced error, and field drift. A signal model is presented with multi-echo gradient echo (GRE) sequence using a fat signal as an internal reference to overcome these problems. The internal reference signal model is fit to the water and fat signals by the extended Prony algorithm and the Levenberg-Marquardt algorithm to estimate the chemical shifts between water and fat which contain temperature information. A noise analysis of the signal model was conducted using the Cramer-Rao lower bound to evaluate the noise performance of various algorithms, the effects of imaging parameters, and the influence of the water:fat signal ratio in a sample on the temperature estimate. Comparison of the calculated temperature map and thermocouple temperature measurements shows that the maximum temperature estimation error is 0.614 degrees C, with a standard deviation of 0.06 degrees C, confirming the feasibility of this model-based temperature mapping method. The influence of sample water:fat signal ratio on the accuracy of the temperature estimate is evaluated in a water-fat mixed phantom experiment with an optimal ratio of approximately 0.66:1.

Demonstration of an eye-movement-induced visual motion illusion (Filehne illusion) in Rhesus monkeys

During pursuit eye movements, the world around us remains perceptually stable despite the retinal-image slip induced by the eye movement. It is commonly held that this perceptual invariance is achieved by subtracting an internal reference signal, reflecting the eye movement, from the retinal motion signal. However, if the reference signal is too small or too large, a false eye-movement-induced motion of the external world, the Filehne illusion (FI), will be perceived. A reference signal of inadequate size can be simulated experimentally by asking human subjects to pursue a target across backgrounds with externally added motion that are perceived as moving. In the present study we asked if non-human primates respond to such manipulation in a way comparable to humans. Using psychophysical methods, we demonstrate that Rhesus monkeys do indeed experience a percept of pursuit-induced background motion. In this study we show that an FI can be predictably induced in Rhesus monkeys. The monkey FI shows dependencies on the size and direction of background movement, which is very similar to the ones characterizing the human FI. This congruence suggests that the perception of self-induced visual motion is based on similar inferential mechanisms in non-human and human primates.

Neuronal correlates of perceptual stability during eye movements

We are usually unaware of retinal image motion resulting from our own movement. For instance, during slow-tracking eye movements the world around us remains perceptually stable despite the retinal image slip induced by the eye movement. It is commonly held that this example of perceptual invariance is achieved by subtracting an internal reference signal, reflecting the eye movement, from the retinal motion signal. If the two cancel each other, visual objects, which do not move, will also be perceived as non-moving. If, however, the reference signal is too small or too large, a false eye movement-induced motion of the external world, the Filehne illusion, will be perceived. We have exploited our ability to manipulate the size of the reference signal in an attempt to identify neurons in the visual cortex of monkeys, influenced by the percept of self-induced visual motion or the reference signal rather than the retinal motion signal. We report here that such 'percept-related' neurons can already be found in the primary visual cortex area, although few in numbers. They become more frequent in areas middle temporal and medial superior temporal in the superior temporal sulcus, and comprise almost 50% of all neurons in area visual posterior sylvian (VPS) in the posterior part of the lateral sulcus. In summary, our findings suggest that our ability to perceive a visual world, which is stable despite self-motion, is based on a neuronal network, which culminates in the VPS located in the lateral sulcus below the classical dorsal stream of visual processing.

Human cortical areas involved in sustaining perceptual stability during smooth pursuit eye movements

Because both, eye movements and object movements induce an image motion on the retina, eye movements must be compensated to allow a coherent and stable perception of our surroundings. The inferential theory of perception postulates that retinal image motion is compared with an internal reference signal related to eye movements. This mechanism allows to distinguish between the potential sources producing retinal image motion. Referring to this theory, we investigated referential calculation during smooth pursuit eye movements (SPEM) in humans using event-related functional magnetic resonance imaging (fMRI). The blood oxygenation level dependent (BOLD) response related to SPEM in front of a stable background was measured for different parametric steps of preceding motion stimuli and therefore assumed for different states of the referential system. To achieve optimally accurate anatomy and more detectable fMRI signal changes in group analysis, we applied cortex-based statistics both to all brain volumes and to defined regions of interest. Our analysis revealed that the activity in a temporal region as well as the posterior parietal cortex (PPC) depended on the velocity of the preceding stimuli. Previous single-cell recordings in monkeys demonstrated that the visual posterior sylvian area (VPS) is relevant for perceptual stability. The activation apparent in our study thus may represent a human analogue of this area. The PPC is known as being strongly related to goal-directed eye movements. In conclusion, temporal and parietal cortical areas may be involved in referential calculation and thereby in sustaining visual perceptual stability during eye movements.

Quantitative 2D HSQC NMR determination of polymer structures by selecting suitable internal standard references

A new analytical method based on the 2D HSQC NMR sequence is presented, which can be applied for quantitative structural determination of complicated polymers. The influence of T1 and T2 relaxations, off-resonance effects, coupling constants and homonuclear couplings are discussed. It was found that the T2 values measured on polymeric samples with the conventional HSQC-CPMG sequence could not be used to correct the errors caused by T2 relaxations during the polarization transfer delay. A unique way of selecting the proper internal standard reference signal(s) is therefore proposed to eliminate the major errors caused by T2 relaxations, resonance offsets, coupling constant deviations and homonuclear couplings. Two polymer samples, a cellulose triacetate and an acetylated lignin, have been used to illustrate the principles. The methodology developed in this work is robust to instrument miss-setting and it can find wide-spread applications in areas where a quantitative analysis of structurally complicated polymers is necessary.

Cerebrocerebellar Circuits for the Perceptual Cancellation of Eye-movement-induced Retinal Image Motion

Despite smooth pursuit eye movements, we are unaware of resultant retinal image motion. This example of perceptual invariance is achieved by comparing retinal image slip with an internal reference signal predicting the sensory consequences of the eye movement. This prediction can be manipulated experimentally, allowing one to vary the amount of self-induced image motion for which the reference signal compensates and, accordingly, the resulting percept of motion. Here we were able to map regions in CRUS I within the lateral cerebellar hemispheres that exhibited a significant correlation between functional magnetic resonance imaging signal amplitudes and the amount of motion predicted by the reference signal. The fact that these cerebellar regions were found to be functionally coupled with the left parieto-insular cortex and the supplementary eye fields points to these cortical areas as the sites of interaction between predicted and experienced sensory events, ultimately giving rise to the perception of a stable world despite self-induced retinal motion.

Redox-Sensitive Copolymer: A Single-Component pH Sensor

A novel redox-active copolymer has been developed, capable of sensing pH. The polymer incorporates the redox-active but pH-insensitive vinylferrocene moiety as the internal reference signal, alongside the redox-active and pH-sensitive vinylanthracene moiety. The anthracene moiety undergoes a Nernstian potential shift with pH. The various monomer and homopolymer components have been examined in turn and the electrochemical response of the polymer characterized. Furthermore, the pH response was found to be stable over a wide temperature range.

Quantitative Deuterium Isotopic Profiling at Natural Abundance Indicates Mechanistic Differences for Δ12-Epoxidase and Δ12-Desaturase in Vernonia galamensis

Quantitative (2)H NMR spectroscopy can determine the natural abundance ((2)H/(1)H) ratio at each site of a molecule. In natural products, variation in these values is related to the reaction mechanisms in the pertinent biosynthetic pathway. For the first time, this novel approach has been exploited to probe for mechanistic differences in the introduction of different functionalities into a long-chain fatty acid. Vernolic acid, a major component of the seed oil of Vernonia galamensis, contains both an epoxide and a desaturation. The site-specific isotopic distribution ((2)H/(1)H)(i) has been determined for both vernolic acid and linoleic acid isolated from the same V. galamensis oil. It is found that the ((2)H/(1)H) ratio of vernolic acid shows a pattern along the entire length of the chain, consistent with linoleic acid being its immediate precursor. Notably, the C13 relates to the C13 of linoleic acid but not to the C13 of oleic acid. Furthermore, the C12 and C13 positions in vernolic acid are less depleted, consistent with a change in hybridization state from sp(2) to sp(3). However, the C11 position shows a marked relative enrichment in the vernolic acid, implying that it plays a role in the epoxidase but not the desaturase mechanism. Thus, although it can be concluded that the catalytic mechanisms for the epoxidase and desaturase activities are similar, marked differences in the residual ((2)H/(1)H) patterns indicate that the reaction mechanisms are not identical.

A new 2 methylalanine-PVC ESR dosimeter

The use of polyvinyl chloride (PVC) as a binder to 2-methylalanine (2MA) dosimeters was investigated. It was recently shown by Olsson et al. (Radiat. Res. 157 (2002) 113), that 2MA is approximately 70% more sensitive than L-alanine which makes this substance a good candidate to replace alanine in ESR dosimetry. PVC is a low yield material for free radical production by ionizing radiation and a good binding material easily processed and widely available. PVC can be prepared at room temperature and mixed up to 50% in weight with 2MA to produce a pellet stable in mass and physical dimensions, in large quantities and with low background signal. Pure PVC pellet irradiated at 50 Gy gave weaker ESR signals compared to 2MA at the region of spectral interest. Spectrometer settings such as microwave power, and modulation amplitude were optimized for the measurements. This dosimeter production scheme allows the addition of Mn 2+ ions for an internal reference signal, leading to a self-calibrated dosimeter (J. Radional. Nucl. Chem. 240 (1999) 215).

Nihon Ketjen targeting 10,000 tonnes of ultra-deep HDS catalysts

In this work, a novel ascorbic acid (AA) ratiometric biosensor was prepared by using the PCN-333 (Al) metal-organic frameworks (MOFs) (PCN stands for porous coordination network) to encapsulate Ketjen black (KB) as catalyst for catalyzing oxidation of AA and thionine (Thi) as an internal reference signal simultaneously. The encapsulation of KB and Thi in the pores of PCN-333 (Al) MOFs not only improved efficiency of KB and Thi greatly because PCN-333 (Al) MOFs could effectively avoid the cohesion or aggregation of KB and Thi on electrode surface but also enhanced the stability of biosensors because they were immobilized in the pore firmly. Furthermore, PCN-333 (Al) MOFs could also selectively accumulate target analytes into their pores to enhance the selectivity of biosensors. The oxidation peak current of AA catalyzed by KB at −0.05 V increased with the increasing concentration of AA, while the oxidation peak current of Thi at −0.24 V kept constant, which resulted in a novel ratiometric biosensor for AA detection. The ratiometric biosensor exhibited a wider linear range from 14.1 ± 0.2 to (5.5 ± 0.1) х103 μM (R2 = 0.998) and a lower detection limit of 4.6 ± 0.1 μM with high accuracy, selectivity, reproducibility and sensitivity. The ratiometric electrochemical approach is not only a new method for AA detection but also opens a new way for sensitive detection of other analytes.

Cortical Substrates of Perceptual Stability during Eye Movements

We are usually unaware of retinal image motion resulting from our own movement. For instance, during slow-tracking eye movements, the world around us remains perceptually stable despite the retinal image slip induced by the eye movement. This example of perceptual invariance is achieved by subtracting an internal reference signal, reflecting the eye movement, from the retinal motion signal. If the two cancel each other, visual structures, which do not move, will also be perceived as nonmoving. If, however, the reference signal is too small or too large, a false eye-movement-induced motion of the external world will be perceived. We have exploited our ability to manipulate the size of the reference signal in an attempt to reveal the structures in visual cortex, encoding the perception of self-induced visual motion rather than the retinal motion signal. Using EEG and lately also MEG recordings in human subjects and single-unit recordings in monkeys, we have been able to show that our ability to perceive the world as stationary despite eye-movement-induced retinal image slip is based on “late” parts of the cortical hierarchy of motion processing, sparing the early stages up to cortical area MT and, among others, involving cortex at the junction between the parietal and temporal lobes close to the parieto-insular-vestibular cortex. Lesions of this network in humans render the visual system unable to compensate for the visual consequences of eye movements, giving rise to severe dizziness, whenever the eyes move smoothly.

Temperature mapping using the water proton chemical shift: Self-referenced method with echo-planar spectroscopic imaging

An echo-planar spectroscopic imaging method of temperature mapping is proposed. This method is sufficiently faster than the so-called 3D magnetic resonance spectroscopic imaging (3D-MRSI) method and does not require image subtractions, unlike the conventional phase mapping method when an internal reference signal is detectable. The water proton chemical shift measured by using the tissue lipid as an internal reference clearly visualized the temperature change in a porcine liver sample in vitro. It was also demonstrated that the internally referenced echo-planar spectroscopic imaging method could markedly reduce a temperature error caused by a simple, translational motion between scans compared with the phase-mapping method. Magn Reson Med 43:220–225, 2000. © 2000 Wiley-Liss, Inc.

An electrophysiological correlate of visual motion awareness in man.

It is usually held that perceptual spatial stability, despite smooth pursuit eye movements, is accomplished by comparing a signal reflecting retinal image slip with an internal reference signal, encoding the eye movement. The important consequence of this concept is that our subjective percept of visual motion reflects the outcome of this comparison rather than retinal image slip. In an attempt to localize the cortical networks underlying this comparison and therefore our subjective percept of visual motion, we exploited an imperfection inherent in it, which results in a movement illusion. If smooth pursuit is carried out across a stationary background, we perceive a tiny degree of illusionary background motion (Filehne illusion, or FI), rather than experiencing the ecologically optimal percept of stationarity. We have recently shown that this illusion can be modified substantially and predictably under laboratory conditions by visual motion unrelated to the eye movement. By making use of this finding, we were able to compare cortical potentials evoked by pursuit-induced retinal image slip under two conditions, which differed perceptually, while being identical physically. This approach allowed us to discern a pair of potentials, a parieto-occipital negativity (N300) followed by a frontal positivity (P300), whose amplitudes were solely determined by the subjective perception of visual motion irrespective of the physical attributes of the situation. This finding strongly suggests that subjective awareness of visual motion depends on neuronal activity in a parieto-occipito-frontal network, which excludes the early stages of visual processing.

False perception of motion in a patient who cannot compensate for eye movements

We are usually unaware of the motion of an image across our retina that results from our own movement. For instance, during slow-tracking eye movements we do not mistake the shift of the image projected onto the retina for motion of the world around us, but instead perceive a stable world. Following early suggestions by von Helmholtz, it is commonly believed that this spatial stability is achieved by subtracting the retinal motion signal from an internal reference signal, such as a copy of the movement command (efference copy). Object motion is perceived only if the two differ. Although this concept is widely accepted, its anatomical underpinning remains unknown. Here we describe the case of a patient with bilateral extrastriate cortex lesions, suffering from false perception of motion due to an inability to take eye movements into account when faced with self-induced retinal image slip. This is indicated by the fact that during smooth-pursuit eye movements, he perceives motion of the stationary world at a velocity that corresponds to the velocity of his eye movement; that is, he perceives the raw retinal image slip uncorrected for his own eye movements. We suspect that this deficiency reflects damage of a distinct parieto-occipital region that disentangles self-induced and externally induced visual motion by comparing retinal signals with a reference signal encoding eye movements and possibly ego-motion in general.

Fluorescent Probes for Monitoring Temperature in Organic Solvents

We report two fluorophores, N-(1-pyrenylmethyl)-1-pyrenebutanamide and N-(1-pyrenylmethyl)-1-pyreneacetamide, that exhibit temperature-dependent emission spectra over the temperature range of 20−100 °C. The fluorophores are readily synthesized via a one-pot process and can be used in dilute form (<1 μM) for measuring the temperature of various organic solvents nonintrusively. The fluorophores allow measurement of temperatures within a precision of ±1 °C and provide an internal reference signal that allows factors such as fluorophore concentration, optical path, and excitation light intensity to be ignored.

A simple and effective method for improving the accuracy of selective audio-frequency voltage measurements

An examination of the results of the accuracy measurements of a bench top audio-frequency selective voltmeter, based on the superheterodyne principle, showed that an accuracy of the order of only 10% of measured values could be achieved if no internal error correction procedure in the measurements had been used. The temperature variations of the parameters of the quartz band-pass filter have been identified as the main source of the measurement error. An application of the internal reference signal from a relatively simple and inexpensive source improved the overall accuracy up to the order of 3%. Finally, it was shown that by combining the wide band and selective measurements of the signals from the built-in tracking generator further improved the overall accuracy to better than 1% and eliminated altogether the need for using any separate source of internal reference signals.

A digital video equalizer for cancelling transmission distortion

The authors have developed a novel video equalizing system and its LSI with good cost performance which provides appropriate image quality by reducing the transmission distortion and short ghosts. Good detection performance of minute distortions (-35 dB) is achieved even in weak electrical fields as a result of the 128 time additions. A wide equalizing range (-0.7 approximately +3.5 mu s) is realized. Accurate phase matching of the input GCR (ghost cancel reference) signal with the internal reference signal (the phase error being less than 9 nsec) is achieved. High-speed (a minimum of four seconds) equalization is made possible by a novel algorithm. >

Compensation of instrumental imperfections by deconvolution using an internal reference signal

Compensation of instrumental imperfections by deconvolution using an internal reference signal