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At least 991 records · Page 55Linked to original sources
PubMed1996

Feature extraction and clustering of EEG epileptic spikes.

This paper treats algorithms for feature extraction and clustering of multichannel EEG transients occurring in epilepsy, so called spikes. Hermite functions with a variable width parameter is used as features. We study nonlinear optimization of a series expansion for multichannel spikes. For the clustering problem, the nearest mean (NM) algorithm, generalized to matrix features, is used. The number of classes is assumed to be known a priori. The series expansion gives good signal description while reducing information. A simulation to estimate the space resolution capability of the algorithms indicates that perfect clustering requires approximately one head radius distance between the dipoles, which each generate one cluster. The NM algorithm was used to cluster two sets of clinically recorded spikes, and the clustering was compared to the manual clustering obtained by a neurophysiologist. For both spike sets evaluated, the clusters obtained by the algorithms had high accordance with the result of the neurophysiologist.

Algorithms↗
PubMed1996

In vivo stationary flux analysis by 13C labeling experiments.

Stationary flux analysis is an invaluable tool for metabolic engineering. In the last years the metabolite balancing technique has become well established in the bioengineering community. On the other hand metabolic tracer experiments using 13C isotopes have long been used for intracellular flux determination. Only recently have both techniques been fully combined to form a considerably more powerful flux analysis method. This paper concentrates on modeling and data analysis for the evaluation of such stationary 13C labeling experiments. After reviewing recent experimental developments, the basic equations for modeling carbon labeling in metabolic systems, i.e. metabolite, carbon label and isotopomer balances, are introduced and discussed in some detail. Then the basics of flux estimation from measured extracellular fluxes combined with carbon labeling data are presented and, finally, this method is illustrated by using an example from C. glutamicum. The main emphasis is on the investigation of the extra information that can be obtained with tracer experiments compared with the metabolite balancing technique alone. As a principal result it is shown that the combined flux analysis method can dispense with some rather doubtful assumptions on energy balancing and that the forward and backward flux rates of bidirectional reaction steps can be simultaneously determined in certain situations. Finally, it is demonstrated that the variant of fractional isotopomer measurement is even more powerful than fractional labeling measurement but requires much higher numerical effort to solve the balance equations.

Biological Transport↗
PubMed2005

Protein self-association in the cell: a mechanism for fine tuning the level of macromolecular crowding?

A new role for protein self-association in the cell is discussed. An argument is advanced that when cellular protein is in its associated state the excluded volume component of the solution is minimized. Conversely, when cellular protein is in its dissociated state the excluded volume component of the solution is maximized. For proteins that make up a substantial fraction of the intracellular protein concentration, control of the self-association event thus presents itself as a means of regulating cellular processes that are influenced by different levels of volume exclusion. In this communication we examine how the control of protein association/dissociation might influence one such important process, namely the folding of a protein to a compact state.

Computer Simulation↗
PubMed1998

Cardiovascular responses to orthostatic tests after a 42-day head-down bed-rest.

Cardiovascular responses to orthostatic tests were studied before and after a prolonged 42 day-head-down bed-rest (HDBR;-6 degrees) experiment simulating a long duration space flight. Seven men participating in the experiment underwent stand tests (10 min) and lower body negative pressure (LBNP) tests (5 min at -25, -35, -45 mmHg). Heart rate variability and spontaneous baroreflex response slope (SBS) were analysed to assess autonomic nervous system responses. Changes in plasma volume (PV) were assessed at the end of HDBR. At the end of HDBR, four subjects could not complete the stand tests and one could not complete the LBNP test. A higher stressed heart rate with standing (+ 44% before and + 57% after HDBR) and LBNP exposure (+ 19% before and + 34% after HDBR) were observed. A decrease in blood pressure (BP) reflecting a reduced vasomotor response was only observed with standing (mean BP + 21% before and -8% after HDBR); LBNP was less sensitive probably because it was performed 6 h after the stand test. The PV decreased by 10.6%. A decline in spectrum total power reflecting a reduced variance of RR-interval, a decrease in parasympathetic activity and an increase in sympathetic one were observed at the end of HDBR. The reduced parasympathetic indicator and SBS would suggest that the vagal nerve component of the cardiovascular control had been diminished. Except for a lower BP when standing after HDBR, no significant difference was observed between finishers and non-finishers. Autonomic nervous system changes including reduced vasomotor responses constituted important contributors to the orthostatic intolerance observed here and after space flights. Some autonomic and PV changes seemed to be opposite to those observed with training and would suggest a role of reduced physical activity in cardiovascular changes induced by HDBR.

Adult↗
PubMed1999

Effect of head-down tilt on brain water distribution.

Vascular and tissue fluid dynamics in the microgravity of space environments is commonly simulated by head-down tilt (HDT). Previous reports have indicated that intracranial pressure and extracranial vascular pressures increase during acute HDT and may cause cerebral edema. Tissue water changes within the cranium are detectable by T2 magnetic resonance imaging. We obtained T2 images of sagittal slices from five subjects while they were supine and during -13 degrees HDT using a 1.5-Tesla whole-body magnet. The analysis of difference images demonstrated that HDT leads to a 21% reduction of T2 in the subarachnoid cerebrospinal fluid (CSF) compartment and a 11% reduction in the eyes, which implies a reduction of water content; no increase in T2 was observed in other brain regions that have been associated with cerebral edema. These findings suggest that water leaves the CSF and ocular compartments by exudation as a result of increased transmural pressure causing water to leave the cranium via the spinal CSF compartment or the venous circulation.

Adult↗
PubMed1979

Orbital hemorrhage.

Seventeen patients had spontaneous orbital hemorrhages. The usual symptoms were acute onset of pain, proptosis, and vomiting with decreased vision, limitation of motility, and ecchymosis of the eyelids occurring in some patients. The children often developed a progressive space occupying lesion that simulated a neoplasm. Most patients had underlying venous anomalies, although several elderly patients with atherosclerosis developed arterial hemorrhages with more abrupt and dramatic symptoms. Other associated conditions included hypertension, anemia, labor, and von Willebrand's disease. The visual outcome was good except in the elderly patients, half of whom had severe and permanent visual loss.

Adolescent↗
PubMed1991

Determination of in vitro simulated blood cell velocity by laser-Doppler with state space methods.

In this paper a signal processing method based on an important tool of numerical analysis, the singular value decomposition (SVD), is used. This method is applied to the unprocessed output of a Laser-Doppler fluxmeter to obtain parameters that are more sensitive to blood velocity than to hematocrit. The SVD-based method utilizes the exponential shape of the frequency spectrum of the laser light scattered from the moving red blood cells and demonstrates an inverse relationship between the damping constant beta associated with the exponential shape and the blood velocity. This method was applied to samples of rat blood of several known hematocrit values that were rotated at different velocities on a turntable. The method extracted one dominant singular value from the spectra, indicating that the spectra can be modeled as a single exponential dominated by scatterings with a single moving red blood cell. A 68% change in inverse velocity resulted in a 50% change in the damping constant (hematocrit 29.5% vol). On the other hand, a 37% change in hematocrit resulted in a far smaller change in the damping constant beta of only 17%. Analysis of the extracted parameters shows that the damping constants are far more influenced by blood velocity than by blood hematocrit.

Animals↗
PubMed1993

Spectral analysis and modelling of ACh and NE effects on shark nervus terminalis activity.

We investigated the effects of acetylcholine (ACh) and norepinephrine (NE) on activity in the nervus terminalis (NT) ganglion of the bonnethead shark (Sphyrna tiburo) using an in vitro preparation and whole nerve recordings. Spectral analysis indicated that ACh (10 and 100 microM) had a variable effect on the total spectral power of whole nerve activity but produced a consistent decrease in half power frequency (HPF; the median frequency of the power spectrum). Norepinephrine (10 microM) reduced baseline activity and total spectral power but produced an increase in HPF in all NT preparations. Computer simulations of extracellular recordings suggested a general explanation for these findings. Acetylcholine may have opposite effects on activity in two NT cell populations with axons in the central nerve trunk, increasing activity in cells whose axons have broad spikes (low spectral frequency) and decreasing activity in cells whose axons have narrow spikes (high spectral frequency). The NE effects are consistent with a decrease in activity of cells whose axons have broad spikes (low spectral frequency) and little or no change in cells whose axons have narrow spikes (high spectral frequency). The physiological data, together with the theoretical analysis, suggest that cholinergic and catecholaminergic neurotransmitter systems are active in the bonnethead NT ganglion, and that ACh and NE have different effects on two populations of ganglion cells.

Acetylcholine↗
PubMed1995

Projections of the individual vestibular end-organs in the brain stem of the squirrel monkey.

The central nervous system (CNS) projections of primary afferent neurons from individual vestibular receptors were studied using horseradish peroxidase (HRP) or biocytin labeling in 14 ears from 7 adult squirrel monkeys using the technique developed in the chinchilla (Lee et al., 1989, 1992). The specificity of labeling was verified by examining the location of the labeled fibers and cell bodies in the vestibular nerve and Scarpa's ganglion. Labeled fibers and cells were restricted to nerves and areas belonging to groups of cells in either the superior or the inferior ganglion of the vestibular nerve. In the vestibular nerve root, labeled primary afferent fibers also exhibited a receptor-dependent segregation at the entrance to the medulla. Fibers from the HSC and the SSC were found rostrally and those from the PSC and the SAC were found in the caudal area. The UTR fibers were situated intermediate between these two groups of fibers. (A bundle of fibers, probably vestibular efferents, was identified immediately rostrally and ventromedially to the UTR fibers.) The primary afferent fibers bifurcated into secondary ascending and descending fibers at the lateral border of the vestibular nuclei, forming a longitudinal rostrocaudal vestibular tract. The secondary fibers from individual end-organs occupied specific locations in the tract: the UTR fibers were dorsal to the SSC and the HSC fibers, PSC fibers were found most medially, and the SAC fibers occupied the lateralmost area. The secondary UTR fibers overlapped considerably with those of the SSC and the HSC. The orderly receptor-dependent segregation of fibers was more prominent in the descending tracts than in the ascending tracts. In the vestibular nuclei complex the location of the tertiary branches of various end-organs exhibited considerable overlap within the major vestibular nuclei (SN, superior nucleus; LN, lateral nucleus; MN, medial nucleus; DN, descending nucleus). There were still differences, however, in the projection pattern. Fibers from the SAC ran primarily in the lateral area, fibers from the SSC and the UTR were found ventromedially to the SAC fibers, and the HSC projected slightly medially to the fibers from the SSC. The PSC fibers projected most medially. The UTR and SAC sent numerous fibers to the cerebellum. Fibers from the semicircular canals projected through the rostrodorsal region of the SN and presumably also projected to the cerebellum. The precise termination of fibers was evaluated by studying the location of labeled boutons, which were identified in all major vestibular nuclei. Labeled boutons from all the receptors were in the rostral and central areas of the SN, and in the MN mainly in the rostral two-thirds. In the LN, boutons from all the receptors were in the rostroventral part, most of which were from the UTR and SAC. No labeled boutons were in the caudodorsal part of this nucleus. Labeled boutons in the DN primarily surrounded the descending tract fibers and were particularly prominent medially. In specimens in which superior vestibular nerve receptor organs were scratched vestibular efferent fibers were also labeled. These fibers traveled in the most ventral part of the vestibular nerve root and projected in the ventral aspect of the LN to labeled soma in the ipsilateral and contralateral brain stem. Specificity the in projection patterns of efferent fibers from different end-organs could not be ascertained.

Animals↗
PubMed2006

The influence of perceptual speed regulation on speed perception, choice, and control: tunnel wall characteristics and influences.

The present work sought to determine if the type of visual pattern and presence of texture applied to transportation tunnel walls differentially affected driving performance. Choice of speed and speed control were measured with 32 participants who drove through a simulated transportation tunnel environment. Participants experienced three visual patterns consisting of vertical segments that decreased, increased, and remained a constant width throughout the length of the tunnel. Participants also drove a baseline control condition in which no visual pattern was present. Each of these conditions was presented either with or without a homogenous texture. When compared to the baseline condition, results indicated drivers gradually decreased speed when exposed to the decreasing width visual pattern and increased speed with the increasing width visual pattern. The presence of texture served to attenuate overall driving speed. Results suggest drivers' perception of speed and their subsequent response to such perceptions were modified by the visual pattern and texture expressed on the tunnel wall. The evident speed control opportunities afforded to the traffic engineer are discussed.

Acceleration↗
PubMed2005

Kinetics of HCV envelope proteins' interaction with CD81 large extracellular loop.

We used BIAcore to analyze the kinetics of interactions between CD81 and hepatitis C virus (HCV) envelope proteins. We immobilized different forms of HCV envelope proteins (E1E2, E2, and E2(661)) on the sensor and monitored their interaction with injected fusion proteins of CD81 large extracellular loop (CD81LEL) and glutathione-S-transferase (CD81LEL-GST) or maltose binding protein (CD81LEL-MBP). The difference between the GST and MBP fusion proteins was their multimeric and monomeric forms, respectively. The association rate constants between CD81LEL-GST or CD81LEL-MBP and the E1E2, E2 or E2(661) HCV envelope proteins were similar. However, the dissociation rate constants of CD81LEL-MBP were higher than those of CD81LEL-GST. Interestingly, the dissociation rate constant of CD81LEL-GST from E1E2 was much lower than from E2 or E2(661). The interaction between both forms of the CD81LEL fusion proteins and the HCV envelope proteins best-fitted the "heterogeneous ligand" model. This model implies that two kinds of interactions occur between envelope proteins and CD81LEL: one is strong, the other is weak. It also implies that the heterogeneity is likely due to the HCV envelope proteins, which are known to form non-covalently linked heterodimers and disulfide-linked aggregate.

Antigens, CD↗
PubMed2004

New perspectives on multiple-copy, mean-field molecular dynamics methods.

Mean-field molecular dynamics (MD) techniques are designed to improve phase-space sampling in MD simulations. Reviewed here are theoretical and practical contributions from our group, and the ideas our contributions are based upon, beginning with the original time-dependent Hartree technique, locally enhanced sampling (LES), and a new, purely classical derivation of multiple-copy, mean-field equations of motion. This view is used to provide new insights into approximations inherent in LES, as well as the basis for a recently proposed method, ensembles eXtracted from atomic coordinate transformations (the EXACT approximation).

Algorithms↗
PubMedDate not supplied

Reaction kinetics in intracellular environments with macromolecular crowding: simulations and rate laws.

We review recent evidence illustrating the fundamental difference between cytoplasmic and test tube biochemical kinetics and thermodynamics, and showing the breakdown of the law of mass action and power-law approximation in in vivo conditions. Simulations of biochemical reactions in non-homogeneous media show that as a result of anomalous diffusion and mixing of the biochemical species, reactions follow a fractal-like kinetics. Consequently, the conventional equations for biochemical pathways fail to describe the reactions in in vivo conditions. We present a modification to fractal-like kinetics following the Zipf-Mandelbrot distribution which will enable the modelling and analysis of biochemical reactions occurring in crowded intracellular environments.

Biopolymers↗
PubMed2004

Competition between near and far dispersers in spatially structured habitats.

Competitive interactions and invasibility between short- and long-distance dispersal was investigated in a population on a heterogeneous landscape with spatial correlations in habitat types, and where the driving interaction between individuals is competition for space. Stochastic spatially explicit simulations were used, along with differential equation models based on pair approximations. Conditions under which either dispersal strategy can successfully invade the other were determined, as a function of the amount and clustering of suitable habitat and the relative costs involved in the two dispersal strategies. Long-distance dispersal, which reduces intraspecific competition, is sometimes advantageous even where aggregation of suitable habitat would otherwise favor short-distance dispersal, although certain habitat distributions can lead to either strategy being dominant. Coexistence is also possible on some landscapes, where the spatial structure of the populations partitions suitable sites according to the number of suitable neighboring sites. Mutual competitive exclusion, where whichever strategy is established first cannot be invaded, is also possible. All of these results are observed even when there is no intrinsic difference in the two strategies' costs, such as mortality or competitive abilities.

Animals↗
PubMed2002

Structure modeling of the chemokine receptor CCR5: implications for ligand binding and selectivity.

The G-protein coupled receptor CCR5 is the main co-receptor for macrophage-tropic HIV-1 strains. I have built a structural model of the chemokine receptor CCR5 and used it to explain the binding and selectivity of the antagonist TAK779. Models of the extracellular (EC) domains of CCR5 have been constructed and used to rationalize current biological data on the binding of HIV-1 and chemokines. Residues spanning the transmembrane region of CCR5 have been modeled after rhodopsin, and their functional significance examined using the evolutionary trace method. The receptor cavity shares six residues with CC-chemokine receptors CCR1 through CCR4, while seven residues are unique to CCR5. The contribution of these residues to ligand binding and selectivity is tested by molecular docking simulations of TAK779 to CCR1, CCR2, and CCR5. TAK779 binds to CCR5 in the cavity formed by helices 1, 2, 3, and 7 with additional interactions with helices 5 and 6. TAK779 did not dock to either CCR1 or CCR2. The results are consistent with current site-directed mutagenesis data and with the observed selectivity of TAK779 for CCR5 over CCR1 and CCR2. The specific residues responsible for the observed selectivity are identified. The four EC regions of CCR5 have been modeled using constrained simulated annealing simulations. Applied dihedral angle constraints are representative of the secondary structure propensities of these regions. Tertiary interactions, in the form of distance constraints, are generated from available epitope mapping data. Analysis of the 250 simulated structures provides new insights to the design of experiments aimed at determining residue-residue contacts across the EC domains and for mapping CC-chemokines on the surface of the EC domains.

Amides↗
PubMed2002

Solution studies and structural model of the extracellular domain of the human amyloid precursor protein.

The amyloid precursor protein (APP) is the precursor of the beta-amyloid peptide (Abeta), which is centrally related to the genesis of Alzheimer's disease (AD). In addition, APP has been suggested to mediate and/or participate in events that lead to neuronal degeneration in AD. Despite the fact that various aspects of the cell biology of APP have been investigated, little information on the structure of this protein is available. In this work, the solution structure of the soluble extracellular domain of APP (sAPP, composing 89% of the amino acid residues of the whole protein) has been investigated through a combination of size-exclusion chromatography, circular dichroism, and synchrotron radiation small-angle x-ray scattering (SAXS) studies. sAPP is monomeric in solution (65 kDa obtained from SAXS measurements) and exhibits an anisometric molecular shape, with a Stokes radius of 39 or 51 A calculated from SAXS or chromatographic data, respectively. The radius of gyration and the maximum molecular length obtained by SAXS were 38 A and 130 A, respectively. Analysis of SAXS data further allowed building a structural model for sAPP in solution. Circular dichroism data and secondary structure predictions based on the amino acid sequence of APP suggested that a significant fraction of APP (30% of the amino acid residues) is not involved in standard secondary structure elements, which may explain the elongated shape of the molecule recovered in our structural model. Possible implications of the structure of APP in ligand binding and molecular recognition events involved in the biological functions of this protein are discussed.

Amyloid beta-Protein Precursor↗
PubMed2004

The orientations of core antenna chlorophylls in photosystem II are optimized to maximize the quantum yield of photosynthesis.

In photosystem II (PSII) the probability that energy absorbed by core antenna chlorophyll (Chl) is transferred to the reaction center (RC) is extremely high. Although close proximity between antenna Chl ensures a high transfer efficiency, relative pigment orientation can fractionally modify it. This level of refinement has often been assumed to be superfluous as so many subsequent processes limit the overall efficiency of photosynthesis. Nevertheless, did natural selection act on the most efficient step of energy conversion in PSII by optimizing the orientation of antenna Chl? Our Monte Carlo simulations sampled the orientation space of Chls in kinetic models for excitation energy transfer based on the X-ray structures of PSII from Thermosynechococcus vulcanus and Synechocystis elongatus. Our results revealed that the orientations of key antenna Chls are optimized to maximize photosynthesis while the orientations of the two peripheral RC Chls (Chl(Z)) are not.

Anisotropy↗
PubMed1997

Effects of microgravity on the structure and function of plant cell walls.

The structural, biochemical, cytofluorimetric and electron cytochemical features of the cell walls of higher plants grown under weightlessness and simulated microgravity are described. Space flight and laboratory clinostatic experiments with plants show that the ultrastructure of the cell wall, its polysaccharide composition, and metabolic organization depend on the type of tissue and the duration of weightlessness. Horizontal clinostating that reproduced the biological effects of microgravity on cell walls showed that the structure of the external walls of the epidermis of aboveground organs is very sensitive to microgravity. Various responses occur in the primary and secondary walls under weightlessness and clinorotation: rearrangement of cell walls and organelles and changes in the content of cellulose, lignin, callose, and hemicelluloses. It is shown that plant cell wall changes under microgravity are connected with changes in cellulase, pectinase, and peroxidase activity and a change in the calcium balance in the cytoplasm and apoplast.

Calcium↗