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PubMed2006

Studies of human visual pathophysiology with visual evoked potentials.

Visual evoked potentials (VEPs) offer reproducible and quantitative data on the function of the visual pathways and the visual cortex. Pattern reversal VEPs to full-field stimulation are best suited to evaluate anterior visual pathways while hemi-field stimulation is most effective in the assessment of post-chiasmal function. However, visual information is processed simultaneously via multiple parallel channels and each channel constitutes a set of sequential processes. We outline the major parallel pathways of the visual system from the retina to the primary visual cortex and higher visual areas via lateral geniculate nucleus that receive visual input. There is no best method of stimulus selection, rather visual stimuli and VEPs' recording should be tailored to answer specific clinical and/or research questions. Newly developed techniques that can assess the functions of extrastriate as well as striate cortices are discussed. Finally, an algorithm of sequential steps to evaluate the various levels of visual processing is proposed and its clinical use revisited.

Brain Diseases↗
PubMed2005

An object-oriented designed finite-difference time-domain simulator for electromagnetic analysis and design in MRI--applications to high field analyses.

This paper presents a finite-difference time-domain (FDTD) simulator for electromagnetic analysis and design applications in MRI. It is intended to be a complete FDTD model of an MRI system including all RF and low-frequency field generating units and electrical models of the patient. The program has been constructed in an object-oriented framework. The design procedure is detailed and the numerical solver has been verified against analytical solutions for simple cases and also applied to various field calculation problems. In particular, the simulator is demonstrated for inverse RF coil design, optimized source profile generation, and parallel imaging in high-frequency situations. The examples show new developments enabled by the simulator and demonstrate that the proposed FDTD framework can be used to analyze large-scale computational electromagnetic problems in modern MRI engineering.

Algorithms↗
PubMed2006

Analytically exact correction scheme for signal extraction from noisy magnitude MR signals.

An analytically exact method is proposed to extract the signal intensity and the noise variance simultaneously from noisy magnitude MR signals. This method relies on a fixed point formula of signal-to-noise ratio (SNR) and a correction factor. The correction factor, which is a function of SNR, establishes a fundamental link between the variance of the magnitude MR signal and the variance of the underlying Gaussian noise in the two quadrature channels. A more general but very similar method is developed for parallel signal acquisitions with multiple receiver coils. In the context of MR imaging, the proposed method can be carried out on a pixel-by-pixel basis if the mean and the standard deviation of the magnitude signal are available.

Algorithms↗
PubMed2003

Dispersion reduction in open-channel liquid electrochromatographic columns via pressure-driven back flow.

Application of electrokinetic forces to drive the mobile phase diminishes analyte dispersion in open-channel liquid chromatographic columns due to minimization of shear in the flow field. However, the retentive layer coating the inner walls of such devices slows down the average convective velocity of solute molecules in its vicinity, inherently causing dispersion of analyte bands. In this article, we explore the possibility of reducing such dispersion in electrochromatographic columns by imposing a pressure-driven back flow in the system. Analysis shows that although such a strategy introduces shear in the flow field, the overall dispersion in the mobile phase is reduced. This occurs as the streamline velocity in such a system is greater near the channel walls than that in the center of the conduit, thereby allowing fluid dispersion to counteract wall retention effects. For an optimally chosen magnitude of the back flow, hydrodynamic dispersion of any target species in the mobile phase may be shown to diminish by a factor of 3 and 10/3 in a circular tube and a parallel-plate geometry, respectively. A similar reduction in slug dispersion is also realized in rectangular conduits for all aspect ratios. In trapezoidal geometries with large wedge angles or isotropically etched profiles, this reduction factor may attain values of 10 or greater.

Algorithms↗
PubMed1990

Influence of plasma glucose concentration on lumped constant of the deoxyglucose method: effects of hyperglycemia in the rat.

The lumped constant of the deoxyglucose method was determined by the steady-state, model-independent method in the brain of normal conscious rats with arterial plasma glucose concentrations varying from normoglycemia (i.e., 8 mM) to hyperglycemia (i.e., 31 mM). The lumped constant for brain was found to decrease very gradually with increasing arterial plasma glucose concentration from a value of approximately 0.45 in the midnormoglycemic range (i.e., 7-8 mM) to approximately 0.38 at 28-31 mM. 3-O-[14C]Methylglucose was used to assess the distribution of glucose within the brain structures in hyperglycemia; the results indicated that the glucose concentration, and therefore also the values for the lumped constant, remain relatively uniform in hyperglycemia with arterial plasma glucose concentrations as high as 34 mM. The values for the lumped constant for rat brain determined in the present studies were combined with those previously determined in this laboratory for hypoglycemia and normoglycemia by the same method to provide a single source for the values for the lumped constant to be used over the full range of arterial plasma glucose concentrations. In several rats the lumped constant for cephalic extracerebral tissues was also evaluated in parallel with those for the brain. The lumped constant for the cephalic extracerebral tissues was found to be about twice that for brain and to be unaffected by changes in arterial plasma glucose levels.

Algorithms↗
PubMed2004

Towards an accurate representation of electrostatics in classical force fields: efficient implementation of multipolar interactions in biomolecular simulations.

The accurate simulation of biologically active macromolecules faces serious limitations that originate in the treatment of electrostatics in the empirical force fields. The current use of "partial charges" is a significant source of errors, since these vary widely with different conformations. By contrast, the molecular electrostatic potential (MEP) obtained through the use of a distributed multipole moment description, has been shown to converge to the quantum MEP outside the van der Waals surface, when higher order multipoles are used. However, in spite of the considerable improvement to the representation of the electronic cloud, higher order multipoles are not part of current classical biomolecular force fields due to the excessive computational cost. In this paper we present an efficient formalism for the treatment of higher order multipoles in Cartesian tensor formalism. The Ewald "direct sum" is evaluated through a McMurchie-Davidson formalism [L. McMurchie and E. Davidson, J. Comput. Phys. 26, 218 (1978)]. The "reciprocal sum" has been implemented in three different ways: using an Ewald scheme, a particle mesh Ewald (PME) method, and a multigrid-based approach. We find that even though the use of the McMurchie-Davidson formalism considerably reduces the cost of the calculation with respect to the standard matrix implementation of multipole interactions, the calculation in direct space remains expensive. When most of the calculation is moved to reciprocal space via the PME method, the cost of a calculation where all multipolar interactions (up to hexadecapole-hexadecapole) are included is only about 8.5 times more expensive than a regular AMBER 7 [D. A. Pearlman et al., Comput. Phys. Commun. 91, 1 (1995)] implementation with only charge-charge interactions. The multigrid implementation is slower but shows very promising results for parallelization. It provides a natural way to interface with continuous, Gaussian-based electrostatics in the future. It is hoped that this new formalism will facilitate the systematic implementation of higher order multipoles in classical biomolecular force fields.

Algorithms↗
PubMed2004

Properties of branched confined polymers.

A model of star-branched polymer chains confined in a slit formed by two parallel surfaces was studied. The chains were embedded to a simple cubic lattice and consisted of f=3 branches of equal length. The macromolecules had the excluded volume and the confining surfaces were impenetrable for polymer segments. No attractive interactions between polymer segments and then between polymer segments and the surfaces were assumed and therefore the system was a thermal. Monte Carlo simulations were carried out employing the sampling algorithm based on chain's local changes of conformation. Lateral diffusion of star-branched chains was studied. Dynamic properties of star-branched chains between the walls with impenetrable rod-like obstacles were also studied and compared to the previous case. The density profiles of polymer segments on the slit were determined. The analysis of contacts between the polymer chain and the surfaces was also carried out.

Journal Article↗
PubMed1998

Computational space reduction and parallelization of a new clustering approach for large groups of sequences.

MOTIVATION: The explosive growth of the biological sequences databases stimulated by genome projects has modified the framework of several applications in the biological sequence analysis area. In most cases, this new scenario is characterized by studies on large sets of sequences, suggesting the need for effective and automatic methods for their clustering. A more effective clustering of the database could be followed by the application of common family analysis schemes to the groups so formed. RESULTS: In this work, we present a new strategy to reduce the computational cost associated with the clustering of large sets of sequences which are expected to contain several families. The strategy is based on the grouping of the sequences into families by using a dynamic threshold on a pairwise sequence similarity criterion. Routine clustering of large data sets can now be done very efficiently. The method developed here achieves a computational space reduction of about an order of magnitude over more traditional ones of all-versus-all comparisons. The outcome of this approach produces family groupings that reproduce closely already accepted biological results. Our work includes a parallel implementation for distributed memory multiprocessors with a dynamic scheduling strategy for performance optimization. AVAILABILITY: By anonymous ftp at ftp.ac.uma.es (/pub/ots/pCluster directory), or from our Web site http://www.cnb. uam.es/www/software/software_index.html CONTACT: ots@ac.uma.es

Algorithms↗
PubMed2006

Speech feature extraction method using subband-based periodicity and nonperiodicity decomposition.

This paper proposes a speech feature extraction method that utilizes periodicity and nonperiodicity for robust automatic speech recognition. The method was motivated by the auditory comb filtering hypothesis proposed in speech perception research. The method divides input signals into subband signals, which it then decomposes into their periodic and nonperiodic components using comb filters independently designed in each subband. Both features are used as feature parameters. This representation exploits the robustness of periodicity measurements as regards noise while preserving the overall speech information content. In addition, periodicity is estimated independently in each subband, providing robustness as regards noise spectrum bias. The framework is similar to that of a previous study [Jackson et al., Proc. of Eurospeech. (2003), pp. 2321-2324], which is based on cascade processing motivated by speech production. However, the proposed method differs in its design philosophy, which is based on parallel distributed processing motivated by speech perception. Continuous digit speech recognition experiments in the presence of noise confirmed that the proposed method performs better than conventional methods when the noise in the training and test data sets differs.

Algorithms↗
PubMed1993

Digital neural networks for high-speed divisions and root extractions.

The instruction set of digital integer-valued VLSIs implementing neural networks is typically restricted to weighted sums, threshold activation functions and weight assignments. However, neural networks also need divisions (for data normalizations) and root extractions (for distance or vector norm computations). This paper presents neural networks which perform the latter operations by using only the above basic instructions. These networks thus provide "macros" to the overall network which calls them. This yields a homogeneous environment. Moreover, a "virtual base" is introduced to exploit the available parallelism. It is freely chosen so as to achieve the desired trade-off between the speed and complexity of the proposed networks (with a minimum of only two neurons). This high-speed capability also makes these structures attractive independently from neural applications.

Algorithms↗
PubMed1997

Method-based differences in the automated analysis of the three-dimensional morphology of trabecular bone.

The three-dimensional (3D) morphology of trabecular bone is frequently quantified using computer programs. However, there are no standardized implementations of morphology programs and many variations are possible. Even though programs may use the same basic method, results can be significantly different because of differences in implementation. Morphology data from different laboratories therefore may not be comparable. The method of directed secants, with parallel plate assumptions, is commonly used to quantify 3D morphology. We examined the effect of several variations in the implementation of this method on measurements of trabecular plate number (Tb.N), trabecular thickness, and trabecular spacing. Three-dimensional micromagnetic resonance images of 10 bovine trabecular bone specimens were analyzed using several variations of the directed secant method. An analysis of covariance with repeated measures suggested that variations in the algorithm used to count test line intersections, variations in the criteria used to classify a test coordinate as bone or marrow, and variations in the number of test grid rotations had significant effects on Tb.N (p < 0.0001). The largest difference in Tb.N (52%) was due to the method used to count test line intersections with the bone-marrow interface. Variations in the classification algorithm and variations in the number of test line grid rotations resulted in a 6% difference in Tb.N. The spacing of the test line grids did not affect Tb.N (p = 0.28), and all differences were independent of volume fraction (p = 0.67). These data show that there can be significant differences in trabecular bone morphology measurements due only to the method used for the measurements. To facilitate comparisons between laboratories, we have made validated computer programs to measure trabecular bone morphology available over the Internet.

Algorithms↗
PubMed2004

PPARs: molecular targets in the pharmacogenomics era.

The recent global increase in prevalence of diseases like obesity, type 2 diabetes and hypertension in westernized societies is unfortunately not paralleled by our full understanding of the causative mechanisms. It is now firmly established that the interacting genetic and environmental (diet, smoking) components together determine the development and severity of the particular condition, which makes detailed dissection of such complex traits even more complicated. In effect, there is an unmet urgent need for molecular targets so we can directly modulate the causative factors and devise effective preventive and therapeutic algorithms. Among the most promising molecular targets for treatment of metabolic syndrome-related conditions identified so far, the group of three lipid-sensors, the peroxisome proliferator-activated receptors (PPARs) clearly stands out. The review focuses on pharmacogenetic aspects of recent developments in PPAR biology.

Animals↗
PubMed1994

Rate-related and autonomic effects on atrioventricular conduction assessed through beat-to-beat PR interval and cycle length variability.

INTRODUCTION: Atrioventricular (AV) conduction time varies on a beat-by-beat basis in response to the influences of cardiac efferent autonomic activity and rate-dependent electrical recovery processes. The goals of this study were to distinguish these effects on AV conduction time and to compare the variability in sinoatrial and AV nodal function. METHODS AND RESULTS: The PR interval on the surface ECG served as an index of AV conduction time in this study of 14 adult human subjects undergoing a random interval breathing protocol. P and R waves were located by a template-matching algorithm. Spectral analysis allowed frequency-domain comparisons between PR and RR interval variability. Spectra of PR and RR intervals had similar power distributions, although the power of the RR interval spectra was much greater. Autonomic blockade with atropine plus propranolol reduced the power of both spectra. Standing significantly decreased the spectral power from 0.15 to 0.5 Hz for PR and RR spectra, and introduced a peak near 0.1 Hz in the mean PR and RR spectra, although the latter finding was significant only for the RR interval spectra. Propranolol had no significant effects on the PR and RR interval spectra. Linear regression analysis allowed quantification of the autonomic and recovery effects on AV conduction and showed which effect predominated. Simple linear regression confirmed in adults a previous finding in children that conduction time may be either positively or negatively correlated with cycle length. By multiple regression and transfer function analysis, the inverse relation seen in some subjects was attributed to the effect of recovery from the preceding cycle. With the preceding recovery period accounted for, the conduction time and cycle length of the current beat were positively correlated, presumably due to the parallel autonomic effects on the sinoatrial and AV nodes. The magnitude of the recovery effect predicted by the regression analysis was similar to published values. CONCLUSION: A noninvasive evaluation of the surface ECG can be used to compare variability in AV conduction time and cycle length and characterize the effects of autonomic efferent activity and rate-related recovery on AV nodal function.

Adult↗
PubMed1989

The analysis of titration studies in phase III clinical trials.

Clinical trials commonly employ the titration design for certain drugs such as antihypertensives. In a Phase III trial the design has purposes distinct from those of a Phase I or II trial, as well as from those of a trial with a parallel design. In this paper we compare the titration design with the usual parallel design in their respective purposes for Phase III trials, explore the relevant questions addressed, and examine typical data from such trials. We also discuss work which focuses primarily on the Phase I or II titration trials. We formulate the problem in the framework of one-way contingency table augmented with incomplete data and obtain the maximum likelihood estimates of the parameters and their estimated variances/covariances via the EM algorithm. An example of a Phase III study of an antihypertensive agent illustrates the proposed procedure.

Analysis of Variance↗
PubMed2006

Improving systems of care in primary angioplasty.

AMI is a life-threatening condition. Poor performance on the part of caregivers can result in the death of a patient. It is critical that a PPCI capability be developed in such a way that error is minimized. It is not enough that the system works well or very well. Aviation is often used as the example that medical systems should emulate. In developing the many interrelated systems required to function properly to ensure safe, effective,prompt, and appropriate application of PPCI,an aviation parallel should be kept in mind. If you were walking on the jetway toward a plane and were greeted by the pilot who said to you, "You know, I can land this thing 99% of the time," you would never get on that plane. It is important to develop a PPCI system that is absolutely never the cause of harm to any patient. Doing so requires exquisite attention to detail, algorithms of care when possible, redundancy, and clear orders for all drugs and procedures.

Angioplasty, Balloon, Coronary↗
PubMed2006

A neural mass model for the simulation of cortical activity estimated from high resolution EEG during cognitive or motor tasks.

Neural mass models have been used for many years to study the macroscopic dynamics of neural populations in a simple and computationally inexpensive way. In this paper, we modified a model proposed by Wendling et al. [Wendling F, Bartolomei F, Bellanger JJ, Chauvel P. Epileptic fast activity can be explained by a model of impaired GABAergic dendritic inhibition. Eur J Neurosci 2002;15:1499-508] to simulate EEG power spectral density (PSD) in some regions of interest (ROIs) during simple tasks (finger movement or working memory tests). The work consists of two subsequent stages: (1) in the first we evaluated the role of some model parameters (i.e., average gain of synapses and their time constants) in affecting power spectral density. This analysis confirmed the possibility to simulate various EEG rhythms (in the alpha, beta and gamma frequency ranges) by modifying just the time constants of the synapses. The position of the individual rhythms (i.e., the corresponding peaks in the PSD) can be finely tuned acting on the average gain of fast inhibitory synapses. This analysis suggested that a single neural mass model produces a unimodal spectrum, which can be finely adjusted, but cannot mimic the overall complexity of EEG in an entire cortical area. (2) Hence, in the second stage we built a model of a ROI by combining three neural mass models arranged in parallel. With this model, and using an automatic fitting procedure, we carefully reproduced the PSD of cortical EEG in several ROIs during finger movement, and their temporal changes during a working memory task, by estimating nine parameters. The estimated parameters represent the excitation of each population (mean value and variance of exogenous input noise) and the average gain of fast inhibitory synapses. Cortical EEGs were computed with an inverse propagation algorithm, starting from measurement performed with a high number of electrodes on the scalp (46-96). Results show that the proposed model is able to mimic PSD of cortical activity acting on a few parameters, which represent external activation and short-time synaptic changes. This information may be exploited to reach a quantitative summary of electrical activity in ROIs during a task, and to derive information on connectivity, starting from non-invasive EEG measurements.

Algorithms↗
PubMed2000

A general mixture model approach for mapping quantitative trait loci from diverse cross designs involving multiple inbred lines.

Most current statistical methods developed for mapping quantitative trait loci (QTL) based on inbred line designs apply to crosses from two inbred lines. Analysis of QTL in these crosses is restricted by the parental genetic differences between lines. Crosses from multiple inbred lines or multiple families are common in plant and animal breeding programmes, and can be used to increase the efficiency of a QTL mapping study. A general statistical method using mixture model procedures and the EM algorithm is developed for mapping QTL from various cross designs of multiple inbred lines. The general procedure features three cross design matrices, W, that define the contribution of parental lines to a particular cross and a genetic design matrix, D, that specifies the genetic model used in multiple line crosses. By appropriately specifying W matrices, the statistical method can be applied to various cross designs, such as diallel, factorial, cyclic, parallel or arbitrary-pattern cross designs with two or multiple parental lines. Also, with appropriate specification for the D matrix, the method can be used to analyse different kinds of cross populations, such as F2 backcross, four-way cross and mixed crosses (e.g. combining backcross and F2). Simulation studies were conducted to explore the properties of the method, and confirmed its applicability to diverse experimental designs.

Animals↗
PubMedDate not supplied

Optimization of MoVSb oxide catalyst for partial oxidation of isobutane by combinatorial approaches.

Optimization of the Mo-V-Sb mixed-oxide system for the selective oxidation of isobutane to methacrolein by true combinatorial methods primarily is intended to reduce the number of experiments in a broad parameter space. Therefore, an evolutionary approach based on a genetic algorithm has been chosen to screen three generations of 30 catalysts. With the help of automated sol-gel synthesis techniques, a high-throughput continuous flow reactor (16UPCFR), and appropriate software for experimental design, a new catalyst composition with improved performance has been obtained. Finally, the best catalysts were scaled-up to gram quantities and tested in a continuous-flow reactor unit that was equipped with four parallel reactors (4UPCFR). The final catalyst showed a significantly higher selectivity toward methacrolein at the same isobutane conversion, compared to the initial Mo8V2Sb90O(x) catalyst.

Journal Article↗