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Long-term enhancement of CA1 synaptic transmission is due to increased quantal size, not quantal content.

Quantal components of Schaffer collateral synaptic transmission recorded intracellularly from CA1 pyramidal cells were examined using 2 methods: simultaneous recordings of CA3-CA1 cell-pairs, and minimal electrical stimulation in stratum radiatum. Quantal parameters estimated by the method of failures and by a computer algorithm that optimized parameter estimates using deconvolution of background noise were highly correlated. EPSP-amplitude histograms of CA3-CA1 cell pairs (N = 10) and minimal electrical stimulation (N = 33) could be adequately described either by Poisson or binomial statistics, or by both, and exhibited similar estimates of unit quantal size (q) and mean quantal content (m). Paired-pulse stimulation with 50 msec between stimuli resulted in an expected facilitation in the EPSP amplitude and increase in m during the second response, as estimated by noise deconvolution, by the decrease in apparent failures, and by a decrease in the coefficient of variation of the EPSP. Tetanization of the Schaffer collaterals that induced long-term enhancement (LTE/LTP) of the population response was associated with an average increase in q for minimal-stimulation responses, with no significant change in any estimate of m. Taken together, these data indicate that, under the present experimental conditions, LTE is expressed as an increase in quantal size, rather than an increase in the number of quanta released per presynaptic impulse. Although this is not definitive evidence for a postsynaptic mechanism, these findings do further restrict the classes of possible presynaptic mechanisms that may be proposed to account for LTE expression.

Action Potentials↗

[Frequency specific auditory evoked responses. Experiments on stimulus polarity, sweep frequency, stimulus duration, notched-noise masking level, and threshold estimation in volunteers with normal hearing].

Auditory evoked responses to tone-pips in notched-noise provide frequency specific estimations of thresholds. Most often, test frequencies are 0.5-4 kHz. Thresholds are expected to match with a high degree to behavioral thresholds. However, only few studies are available containing data on stimulus and averaging parameters, especially at a test frequency of 0.25 kHz. In order to find "optimal" parameters for a widely used device (Nicolet Spirit Version 1.6), we designed five experiments on stimulus polarity (Exp.I), sweep frequency (Exp.II), stimulus duration (Exp.III), notched noise level (Exp.IV), and threshold estimation (Exp.V). The experiments also included a low test frequency of 0.25 kHz. These experiments were applied to 29 healthy volunteers (n=29, aged 20-41 years with normal hearing and no history of illness of the ear). We found that alternating stimulus polarity and a sweep frequency of 43.5/s evoked responses that were highest with respect to amplitudes (0.2-0.4 mV) and correlations (0.49-0.91). A novel finding of the study was that the highest amplitudes and correlations could be achieved if stimulus durations and notched-noise-levels were specifically adjusted to the test frequencies (stimulus durations 0.25 kHz: 4 ms, 0.5 Hz: 2 ms, 1-4 kHz: 1 ms, notched-noise-levels 0.25-0.5 Hz: +10 dB, 1-4 kHz: +/-0 dB). Deviations from behavioral thresholds did not exceed +/-5 dB in 93% of the measures. The results indicate that frequency specific auditory evoked responses provide reliable threshold estimations. Future experiments are required to confirm the threshold deviations for hard of hearing individuals.

Acoustic Stimulation↗

MRI-based treatment planning for radiotherapy: dosimetric verification for prostate IMRT.

PURPOSE: Magnetic resonance (MR) and computed tomography (CT) image fusion with CT-based dose calculation is the gold standard for prostate treatment planning. MR and CT fusion with CT-based dose calculation has become a routine procedure for intensity-modulated radiation therapy (IMRT) treatment planning at Fox Chase Cancer Center. The use of MRI alone for treatment planning (or MRI simulation) will remove any errors associated with image fusion. Furthermore, it will reduce treatment cost by avoiding redundant CT scans and save patient, staff, and machine time. The purpose of this study is to investigate the dosimetric accuracy of MRI-based treatment planning for prostate IMRT. METHODS AND MATERIALS: A total of 30 IMRT plans for 15 patients were generated using both MRI and CT data. The MRI distortion was corrected using gradient distortion correction (GDC) software provided by the vendor (Philips Medical System, Cleveland, OH). The same internal contours were used for the paired plans. The external contours were drawn separately between CT-based and MR imaging-based plans to evaluate the effect of any residual distortions on dosimetric accuracy. The same energy, beam angles, dose constrains, and optimization parameters were used for dose calculations for each paired plans using a treatment optimization system. The resulting plans were compared in terms of isodose distributions and dose-volume histograms (DVHs). Hybrid phantom plans were generated for both the CT-based plans and the MR-based plans using the same leaf sequences and associated monitor units (MU). The physical phantom was then irradiated using the same leaf sequences to verify the dosimetry accuracy of the treatment plans. RESULTS: Our results show that dose distributions between CT-based and MRI-based plans were equally acceptable based on our clinical criteria. The absolute dose agreement for the planning target volume was within 2% between CT-based and MR-based plans and 3% between measured dose and dose predicted by the planning system in the physical phantom. CONCLUSIONS: Magnetic resonance imaging is a useful tool for radiotherapy simulation. Compared with CT-based treatment planning, MR imaging-based treatment planning meets the accuracy for dose calculation and provides consistent treatment plans for prostate IMRT. Because MR imaging-based digitally reconstructed radiographs do not provide adequate bony structure information, a technique is suggested for producing a wire-frame image that is intended to replace the traditional digitally reconstructed radiographs that are made from CT information.

Humans↗

Sensitivity analysis for high quantiles of ochratoxin A exposure distribution.

Using available data from a consumption survey and contamination data on ochratoxin A (OA) in food, a sensitivity analysis (SA) for high quantiles (95th and 99th quantiles) of OA exposure distribution was carried out, obtained by a Monte Carlo simulation in French children. Exposure assessment for food contaminants is important to control the risk of foodborne diseases. Risk assessors are interested in high quantiles of contaminant exposure distributions. As these exposure distributions are generally very asymmetrical, it is difficult to obtain relevant and stable high quantiles in such a context. Determining OA exposure distribution is complex because it is based on the sum of elementary exposure distributions (eight foodstuffs are analysed here), and each one of these is the product of a consumption distribution and a contamination distribution. The SA enables us to quantify the influences of the parameter variability of the consumption and contamination probability density functions (pdf) which have been fitted to the data, our simulation model inputs, on the 95th and 99th quantiles of the output exposure distribution. After some preliminary trials, we have postulated a quadratic polynomial regression model for the quantiles of OA exposure distribution in view of undertaking this SA. This regression model comprises 32 main factors, their 496 two-factor interactions and their 32 quadratic terms. The 32 factors are the parameters of the fitted pdf: 16 parameters of Gamma distributions relative to the eight consumed foods and 16 parameters of Gamma distributions relative to the eight food OA contaminations. For an optimal parameter estimation of such a large model, we used an experimental design approach depending on a resolution-V fractional factorial design of 6561 experiments. The factor ranges are established by a preliminary study of bootstrap sampling. From the bootstrap samples, the factor ranges are obtained taking into account the correlation between the two parameters of the fitted Gamma pdf. A full exposure distribution is simulated for each of the 6561 experiments. The consumption dependencies are taken into account by the Iman and Conover method. On the basis of this analysis, validated and useful models for each desired quantile are obtained showing a major influence of the parameters of "Cereals" (consumption and contamination) and slightly less so for parameter of "Pork" consumption in the sensitivity of the quantiles.

Adolescent↗

Validation of a more sensitive method for using spotted oligonucleotide DNA microarrays for functional genomics studies on bacterial communities.

Spotted oligonucleotide microarrays potentially offer a wide scope of applications for microbial ecology, especially as they improve the flexibility of design and the specificity of detection compared to PCR product based microarrays. Sensitivity, however, was expected to be problematic, as studies with the more sensitive PCR-based cDNA microarrays indicate that only genes from populations contributing to more than 5% of the community DNA can be detected. We evaluated several parameters to increase sensitivity and then tested applicability for bacterial functional genomics. The optimal parameters were the use of 5'-C6-amino-modified 70-mers printed on CMT-GAPS II substrates at a 40 micro M concentration combined with the use of Tyramide Signal Amplification labelling. This protocol allowed detection of single copy genes belonging to an organism contributing to 1% or more of the total community. To demonstrate its application, we detected the specific aromatic oxygenase genes in a soil community degrading polychlorinated biphenyls (PCBs). This increase in sensitivity is important if oligonucleotide microarrays are to be used for simultaneous monitoring of a range of functions performed by different microorganisms in the environment.

Bacteria↗

The velocity-response curves of the cat's superior colliculus neurons.

The velocity-response curves of the cat's superior colliculus neurons responding to moving stimuli mere studied quantitatively. They were fitted by logarithmic Gaussian curves described by three parameters: optimal stimulus velocity, amplitude and dispersion of the curve. Since reversal of the stimulus movement direction changed neither optimal stimulus velocity nor dispersion of the velocity tuning curve, then the fourth parameter, directional asymmetry, is postulated to describe fully, in conjunction with three parameters mentioned above, the dependence of the neuron response to velocity and direction on the stimulus motion. All parameters were roughly normally distributed and uncorrelated with each other in the sample of cells investigated. Some implications of our results for the classification of cells, and some arguments for population coding” against single cell trigger feature coding are discussed.

Animals↗

Increasing peptide identification in tandem mass spectrometry through automatic function switching optimization.

Comprehensive proteomic studies that employ MS directed peptide sequencing are limited by optimal peptide separation and MS and tandem MS data acquisition routines. To identify the optimal parameters for data acquisition, we developed a system that models the automatic function switching behavior of a mass spectrometer using an MS-only dataset. Simulations were conducted to characterize the number and the quality of simulated fragmentation as a function of the data acquisition routines and used to construct operating curves defining tandem mass spectra quality and the number of peptides fragmented. Results demonstrated that one could optimize for quality or quantity, with the number of peptides fragmented decreasing as quality increased. The predicted optimal operating curve indicated that significant improvements can be realized by selecting the appropriate data acquisition parameters. The simulation results were confirmed experimentally by testing 10 LC MS/MS data acquisition parameter sets on an LC-Q-TOF-MS. Database matching of the experimental fragmentation returned peptide scores consistent with the predictions of the model. The results of the simulations of mass spectrometer data acquisition routines reveal an inverse relationship between the quality and the quantity of peptide identifications and predict an optimal operating curve that can be used to select an optimal data acquisition parameter for a given (or any) sample.

Algorithms↗

Quinoprotein glucose dehydrogenase modified thick-film electrodes for the amperometric detection of phenolic compounds in flow injection analysis.

The use of thick-film electrodes as basic transducers for highly sensitive amperometric biosensors using PQQ (pyrroloquinoline quinone) dependent glucose dehydrogenase (GDH) with short response times is described. The enzyme is embedded in a polyurethane matrix on top of a platinum based thick film electrode and its ability to reduce oxidized phenolic compounds is exploited. The electrochemical amplification is based on the oxidation of the analyte on the surface of the electrode followed by its enzymatic reduction. Different parameters of the glucose dehydrogenase electrode system using dopamine as a model analyte were optimized, e.g., membrane thickness, pH value, buffer system, flow rate and storage conditions. Using optimized parameters the sensitivity and detection limits for various phenolic compounds were evaluated. The comparison of electrodes from the identical as well as from different batches shows the ability to produce a number of well reproducible sensors showing remarkably small differences with respect to parameters as sensitivity, response times and measuring range.

Acinetobacter calcoaceticus↗

The mechanism of reaction of ferricyanide-pretreated mixed-valence-state membrane-bound cytochrome oxidase with oxygen at 173 K.

1. The results of non-linear optimization studies on the mechanism of reaction of ferricyanide-pretreated mixed-valence-state cytochrome oxidase with O2 at 173 K are presented. The analysis is carried out on data obtained by means of dual-wavelength multi-channel spectroscopy at four wavelength pairs (444-463 nm, 604-630 nm, 608-630 nm and 830-940 nm) and at two O2 concentrations (360 micron and 520 micron). The only model that satisfies the triple requirement of a standard deviation within the standard error of the experimental data, a random distribution of residuals and good determination of the optimized parameters, is a three-intermediate sequential mechanism. 2. On the basis of the optimized values of the relative absorption coefficients of the intermediates at each wavelength obtained from the present paper together with data from optical wavelength scanning and e.p.r. spectroscopy obtained by low-temperature trapping studies, the possible valence states of the metal centres in each of the intermediates are discussed.

Chemical Phenomena↗

Developmental increase in CA3-CA1 presynaptic function in the hippocampal slice.

1. We recorded extracellular and intracellular CA3-CA1 synaptic responses in hippocampal slices from neonatal rats [postnatal day (P) 15-21 and P29-35]. Presynaptic function was examined by measuring input-output relationships and paired-pulse facilitation and by quantal analysis of minimally evoked responses. 2. Extracellular recording revealed no difference in excitatory postsynaptic potential (EPSP) threshold or the fiber potential response for a given stimulus intensity between the two age groups. However, the slope of the field EPSP was consistently larger in older animals. The increase in EPSP slope was associated with a decrease in paired-pulse facilitation, suggesting an increase in presynaptic function with postnatal development. 3. Extracellular results were confirmed by intracellular recordings that revealed no difference in the minimal stimulation intensity needed to evoke a response, an increase in mean EPSP amplitude with development, and a decrease in paired-pulse facilitation. Quantal parameters were extracted by three separate methods including method of failures, coefficient of variance, and parameter optimization through noise deconvolution. All methods supported presynaptic mediation of facilitation. Comparison of quantal parameters during development indicated an increase in mean quantal content. 4. The results demonstrate that synaptic strength is altered over the course of development because of, at least in part, changes in presynaptic release mechanisms. Developmental differences in presynaptic function provide an explanation of differences in mechanisms for expression of long-term potentiation. The lower initial probability of transmitter release in neonates may permit increased presynaptic change.

Animals↗

[Basic evaluation of a new technique, tailored contrast truck-fluid-attenuated driven inversion-recovery (TACT-FLADIR), to attenuate the signals of both cerebrospinal fluid and inflow artifacts].

The aim of the present study was to evaluate the new tailored contrast truck-fluid-attenuated driven inversion-recovery (TACT-FLADIR) sequence. Technically, this sequence uses a nonselectively driven inversion (DI) pulse as the inversion pulse. The DI pulse has two parameters, number of refocus pulses (NR) and preparation time (TP). Using normal volunteers, we optimized NR and TP to measure signal-to-noise ratios (SNR) and contrast-to-noise ratios (CNR) of gray matter (GM) and white matter (WM), and to obtain CSF inflow artifacts. TACT-FLADIR was compared with conventional FLAIR using volunteers and patients. Among the optimized parameters, SNR and CNR were dependent on TP, and inflow artifacts were reduced by increasing NR. In brain imaging, TACT-FLADIR provided improvement in both SNR and CNR compared with conventional imaging with suppressed CSF signal and saturated flow artifacts.

Adult↗

Feasibility of using intracardiac impedance measurements for capture detection.

Energy consumption and longevity of modern pacemakers are determined by the controlling electronic circuitry and by the stimulation energy. While with technological progress the electronics' energy consumption has been reduced significantly, clinical practice shows that many cardiac pacemakers are programmed to suboptimal settings with regard to minimization of pacing energy consumption. Several methods for optimizing pacemaker output settings have been proposed in the past. The most promising concept is an output parameter optimizing pacemaker with automatic capture detection. We examined whether it is possible to distinguish between effective and ineffective pacemaker stimulus capture by analyzing high pass filtered intracardiac impedance signals that are derived from standard bipolar pacing leads. In one series of 11 patients undergoing replacement or implantation of chronic bipolar pacemakers, four patients during electrophysiology studies, and eight volunteers undergoing invasive electrophysiology trials, we examined intracardiac impedance signals obtained with various stimulation rates and output parameter settings. Additionally we analyzed a series of five patients with implanted pacemakers that can measure and telemeter intracardiac impedance signals. Several evaluation concepts have been analyzed regarding their ability to discriminate between effective and ineffective stimuli. We developed an adequate algorithm that detects capture or loss of capture at different output parameter settings based on intracardiac impedance analysis. The sensitivity is 98.5% and specificity is 91% to loss of capture for the currently investigated algorithm and this can be used to determine the optimal setting of pulse width and amplitude with regard to energy consumption. This concept is currently under realization in the external programmer and in the future an implementation of these algorithms within the pacemaker itself is intended.

Algorithms↗

Data assimilation for short range atmospheric dispersion of radionuclides: a case study of second-order sensitivity.

This article presents the application of variational data assimilation to a simple Gaussian plume model for radionuclides. Adjoint modeling is applied to the model in order to minimize discrepancies between contamination observations and model outputs. The interest of such an approach is to get a better estimation of some parameters such as emissions or dispersion parameters. A second-order analysis is also performed to assess the sensitivity of the optimized parameters to some poorly known parameters. Sensitivity with respect to network design is also done.

Air Movements↗

Systematic performance evaluation of a continuous-scale sleep depth measure.

In this article, systematic performance evaluation of a continuous-scale sleep depth measure will be discussed. Our main objective has been to select the adjustable analysis parameters such that the best possible correspondence between method output and standard visual sleep staging could be achieved. Sleep depth estimation was based on continuous monitoring of short-time EEG synchronization through the local mean frequency of the EEG. During the experiments, total amount of 752 different combinations of four adjustable parameters were compared based on all-night sleep EEG recordings of 15 healthy subjects. Optimization strategy applied was based on maximizing the weighted average of pair-wise separabilities of EEG mean frequency distributions in all the standard sleep stage pairs. Finally, robustness of the optimized parameters was verified with an independent dataset of 34 all-night sleep recordings. Our results show that clear topological differences between brain hemispheres and different electrode locations exist. Performance improvements of even 20-30% units can be achieved by proper selection of analysis parameters and the EEG derivation used for the analysis. Remarkable independence of system performance on the analysis window length leads to improved temporal resolution compared to that achieved through standard visual analysis. In addition to giving practical suggestions on the parameter selection, we also propose a possible method for improving stage separability especially between S2 and REM.

Adult↗

Balancing solvation and intramolecular interactions: toward a consistent generalized Born force field.

The efficient and accurate characterization of solvent effects is a key element in the theoretical and computational study of biological problems. Implicit solvent models, particularly generalized Born (GB) continuum electrostatics, have emerged as an attractive tool to study the structure and dynamics of biomolecules in various environments. Despite recent advances in this methodology, there remain limitations in the parametrization of many of these models. In the present work, we demonstrate that it is possible to achieve a balanced implicit solvent force field by further optimizing the input atomic radii in combination with adjusting the protein backbone torsional energetics. This parameter optimization is guided by the potentials of mean force (PMFs) between amino acid polar groups, calculated from explicit solvent free energy simulations, and by conformational equilibria of short peptides, obtained from extensive folding and unfolding replica exchange molecular dynamics (REX-MD) simulations. Through the application of this protocol, the delicate balance between the competing solvation forces and intramolecular forces appears to be better captured, and correct conformational equilibria for a range of both helical and beta-hairpin peptides are obtained. The same optimized force field also successfully folds both beta-hairpin trpzip2 and mini-protein Trp-Cage, indicating that it is quite robust. Such a balanced, physics-based force field will be highly applicable to a range of biological problems including protein folding and protein structural dynamics.

Amino Acid Sequence↗

Wall compliance and violin cavity modes.

Violin corpus wall compliance, which has a substantial effect on cavity mode frequencies, was added to Shaw's two-degree-of-freedom (2DOF) network model for A0 ("main air") and A1 (lowest length mode included in "main wood") cavity modes. The 2DOF model predicts a V(-0.25) volume dependence for A0 for rigid violin-shaped cavities, to which a semiempirical compliance correction term, V(-x(c)) (optimization parameter x(c)) consistent with cavity acoustical compliance and violin-based scaling was added. Optimizing x(c) over A0 and A1 frequencies measured for a Hutchins-Schelleng violin octet yielded x(c) approximately 0.08. This markedly improved A0 and A1 frequency predictions to within approximately +/- 10% of experiment over a range of about 4.5:1 in length, 10:1 in f-hole area, 3:1 in top plate thickness, and 128:1 in volume. Compliance is a plausible explanation for A1 falling close to the "main wood" resonance, not increasingly higher for the larger instruments, which were scaled successively shorter compared to the violin for ergonomic and practical reasons. Similarly incorporating compliance for A2 and A4 (lowest lower-/upper-bout modes, respectively) improves frequency predictions within +/-20% over the octet.

Journal Article↗

[Electrostimulation of the phrenic nerve in dogs].

Respiratory parameters have been studied by electrical stimulation of phrenic nerves (EPN) in 12 dogs. The optimal parameters of an electrical stimulus were found for long-term EPN. EPN increased minute respiratory volume, when respiratory rate raised to 18 per min, and decreased, when respiratory rate diminished to 6 per min. Another parameter--oxygen utilization index--diminished at high respiratory rate and increased at low one, which reflected hyper- or hypoventilation status, respectively. The data obtained indicate that controlled lung ventilation may maintain living status of dogs for a long time without alteration of general respiratory parameters.

Animals↗

Measurement of ultrasound biomicroscopy images: intraobserver and interobserver reliability.

PURPOSE: To evaluate intraobserver and interobserver reproducibility of measurement of images obtained during ultrasound biomicroscopy. METHODS: Four anterior segment images of four normal patients were obtained by a single examiner. The measurements of three independent observers were compared to assess interobserver reproducibility in quantifying the images. Thirteen different anterior segment parameters were measured by each observer on each image. Intraobserver and interobserver reproducibility of measurement were assessed by calculating the coefficient of variation for each individual observer and by using the F test to detect a difference among observers. RESULTS: Intraobserver reproducibility was high. Interobserver reproducibility for the measured parameters varied considerably and was affected by subjective interpretation of visualized anatomic landmarks. CONCLUSIONS: The optimal parameters for quantitative ultrasound biomicroscopy require refinement. Measurements of alterable parameters are best measured presently by a single observer. Ultrasound biomicroscopy has the potential to elucidate anatomic relationships underlying much anterior segment disease, but caution in interpreting quantitative differences is warranted.

Anterior Eye Segment↗