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At least 1,225 records · Page 68Linked to original sources
PubMed2000

Is all ventricular fibrillation the same? Influence of mode of induction on characteristics of ventricular fibrillation.

INTRODUCTION: Little information is available on the relationship between the mode of induction of ventricular fibrillation (VF) to VF characteristics. METHODS AND RESULTS: VF was induced from the anterior left ventricle by programmed electrical stimulation, burst pacing, alternating current (AC), high current S2 at a site remote from S1, T wave shock, and intersecting wavefronts in seven normal dogs and seven dogs with chronic myocardial infarction. Using two electrode arrays, 112 electrograms were recorded from the anterior and lateral wall. Cycle lengths were analyzed and activation vectors were created by summing orthogonally recorded bipolar electrograms. The magnitude of the vector loops was integrated over time to produce an "ensemble vector" index (EVI) whose magnitude is high when beat-to-beat activation direction is consistent and low when activation direction is variable. T wave shock-induced VF had a significantly longer cycle length 1 to 5 seconds after VF onset than other modes of induction (P < 0.05). The frequency-corrected EVI was significantly larger for AC current and T wave shock-induced VF as opposed to all other modes of VF induction in early VF (P < 0.0001). After 10 seconds of VF, these differences persisted only on the anterior wall. CONCLUSION: VF induced in animals by T wave shock and AC current had different characteristics than VF induced by other methods. These findings may have implications for our understanding of VF pathophysiology.

Animals↗
PubMed1999

Determination of mean and standard deviation of dihedral angles.

Backbone torsional angles are a characteristic and useful parameter for the description and characterisation of protein structures determined by x-ray crystallography or NMR spectroscopy. For the comparison of an ensemble of three-dimensional structures the calculation of the statistical parameters mean and standard deviation would be very useful. However, they are not defined unambiguously for periodic quantities such as the dihedral angles. In this paper a plausible and unique definition of these parameters is introduced and a straightforward method for their calculation is given.

Bacillus subtilis↗
PubMedDate not supplied

Fine tuning of physical properties of designed polypeptide multilayer films by control of pH.

Adjustment of pH can alter the ensemble of three-dimensional structures of a polypeptide in solution by changing the distribution of charge and Coulombic interactions. The role of pH in layer-by-layer self-assembly (LbL) of designed 32mer peptides containing the amino acid cysteine has been investigated using a combination of physical methods. Results show that pH can have a substantial influence on the mass of adsorbed peptide, surface roughness, and film density over a range of 1.5 pH units. Peptide film thickness depends on the number of layers, as with "conventional" polyelectrolytes. Film density and morphology, however, vary more with pH than does thickness, translating into a change in density on the order of 70% over the pH range 7.4-8.9. Results of this work provide insight on the physical basis of LbL and suggest that peptides are a promising class of polyelectrolytes for the creation of designer thin films for applications in biotechnology and other areas.

Amino Acid Sequence↗
PubMed2004

Identification of pre-sliding friction dynamics.

The hysteretic nonlinear dependence of pre-sliding friction force on displacement is modeled using different physics-based and black-box approaches including various Maxwell-slip models, NARX models, neural networks, nonparametric (local) models and dynamical networks. The efficiency and accuracy of these identification methods is compared for an experimental time series where the observed friction force is predicted from the measured displacement. All models, although varying in their degree of accuracy, show good prediction capability of pre-sliding friction. Finally, we show that even better results can be achieved by using an ensemble of the best models for prediction.

Journal Article↗
PubMed2006

Accelerating molecular simulations by reversible mapping between local minima.

A new framework is presented for performing Monte Carlo simulations of condensed matter based on a recently developed bijective mapping between local energy minima. The framework is used to implement a range of new multiparticle Monte Carlo moves, which are investigated by simulating atomic Lennard-Jones fluids in the canonical and grand canonical ensembles. Important aspects of the simulation protocol and their effect on performance are analyzed in detail. Using the mapping accelerates the simulations by many orders of magnitude when compared to the equivalent moves without the mapping, and leads to particularly efficient configurational sampling at low temperatures and high densities. The method appears to be suitable for adapting to quantitative simulations of more complex molecular systems over long effective time scales.

Journal Article↗
PubMed2001

Lumbar spine mechanical response to axial compression load in vivo.

STUDY DESIGN: Lumbar spine kinematic response to a 1.0 body weight compressive load was measured in vivo by comparison of relaxed and loaded magnetic resonance image sets in the sagittal plane. OBJECTIVES: To identify and measure acute response mechanisms of the lumbar spine during compression loading. SUMMARY OF BACKGROUND DATA: The isolated ligamentous spine buckles under small loads (88 N); yet, the spine supports >10 times that load in daily activities. Mechanical function of the lumbar spine in vivo is not well understood, and only a few studies examined the spine during in vivo loading. METHODS: Magnetic resonance imaging scans of subjects were taken while subjects were relaxed and while supporting a 1.0 body weight compressive load. Vertebral bodies and disc perimeters were digitized, and relative centroid positions were measured and compared between conditions. Lumbar rotation, bending, compression, and disc translation were determined. Two parameter ensembles were analyzed to describe mechanisms of "spine shrinkage" (decrease of projected spine length) and lumbosacral response. RESULTS: All subjects underwent spine shrinkage (-3.9 +/- 1.2 mm) dominated by cumulative bending, except in three subjects where the rotation component dominated. Levels L2-L4 extended, while L5 flexed, and dL2 through dL4 translated anterior, while dL5 translated posterior. Significant segmental deformations were as follows: L3 extension (-3.3 +/- 3.1 degrees ), dL5 disc translation (-1.4 +/- 1.4 mm), and posterior sacral rotation (3.2 +/- 4.7 degrees ). CONCLUSIONS: Spine shrinkage occurred mainly from spine bending and rotation, with only small contribution from spine compression (shortening along the spine curvature). Response pattern groupings indicated at least two unique subgroups, but the cause remains to be determined.

Adult↗
PubMedDate not supplied

Common model of normal cell differentiation and oncogenesis based on the mutation--recombination effects of transposable genetic elements and of provirus states.

Cell differentiation would result from a sequence of mutation--recombination events that occur in quantal cell cycles, initiating cell lineages. The cytogenomic proviruses--transposable elements ensemble would represent the mutation--recombination equipment of differentiation. Carcinogenesis, as a consequence of multicausally induced mutation--recombination events, would likewise occur in a particular quantal cell cycle resulting in the malignant cell lineage. Superposing the environmental causes of malignancy over those of genetic diseases, the model suggests common prevention methods.

Animals↗
PubMed2002

Second-generation mimics of ganglioside GM1 oligosaccharide: a three-dimensional view of their interactions with bacterial enterotoxins by NMR and computational methods.

As a step to delineate a strategy of ligand design for cholera toxin (CT), NMR studies were performed on several mimics of the GM1 ganglioside oligosaccharide. The conformation of these analogues was investigated first in solution and then upon binding to cholera toxin by transferred nuclear Overhauser effect (TR-NOE) measurements. It was demonstrated that CT selects a conformation similar to the global minima of the free saccharides from the ensemble of presented conformations. No evidence of major conformational distortions was obtained, but one or two of the available conformers of the hydroxyacid side chain appear to be selected in the bound state. The NMR data were interpreted with the aid of computer models, generated and analyzed by using a combination of different approaches (MacroModels' MC/EM and MC/SD, Autodock, and GRID). Analysis of the NMR data supported by computational studies allowed us to interpret the experimental observations and to derive workable models of the ligand:toxin complexes. These models suggest that the higher affinity of the (R)-lactic acid derivative 3 may stem from lipophilic interactions with a hydrophobic area in the toxin binding site located in the vicinity of the sialic acid side chain binding region of the CT:GM1 complex, and formed by the side chain of Ile-58 and Lys-34. Thus, the models obtained have allowed us to make useful design suggestions for the improvement of ligand affinity.

Journal Article↗
PubMed2002

Second-generation mimics of ganglioside GM1 oligosaccharide: a three-dimensional view of their interactions with bacterial enterotoxins by NMR and computational methods.

As a step to delineate a strategy of ligand design for cholera toxin (CT), NMR studies were performed on several mimics of the GM1 ganglioside oligosaccharide. The conformation of these analogues was investigated first in solution and then upon binding to cholera toxin by transferred nuclear Overhauser effect (TR-NOE) measurements. It was demonstrated that CT selects a conformation similar to the global minima of the free saccharides from the ensemble of presented conformations. No evidence of major conformational distortions was obtained, but one or two of the available conformers of the hydroxyacid side chain appear to be selected in the bound state. The NMR data were interpreted with the aid of computer models, generated and analyzed by using a combination of different approaches (MacroModels' MC/EM and MC/SD, Autodock, and GRID). Analysis of the NMR data supported by computational studies allowed us to interpret the experimental observations and to derive workable models of the ligand:toxin complexes. These models suggest that the higher affinity of the (R)-lactic acid derivative 3 may stem from lipophilic interactions with a hydrophobic area in the toxin binding site located in the vicinity of the sialic acid side chain binding region of the CT:GM1 complex, and formed by the side chain of Ile-58 and Lys-34. Thus, the models obtained have allowed us to make useful design suggestions for the improvement of ligand affinity.

Binding Sites↗
PubMed1998

A protein engineering analysis of the transition state for protein folding: simulation in the lattice model.

BACKGROUND: Protein engineering has been used extensively to evaluate the properties of transition states in protein folding. Although the method has proved useful, its limitations and the details of interpretation of the obtained results remain largely unexplored. RESULTS: Lattice model simulations are used to test and verify the protein engineering analysis of the transition state in protein folding. It is shown that in some cases - but not always - this method is able to determine the transition state with reasonable accuracy. Limitations of protein engineering are revealed and analyzed. In particular, the change in non-native interactions as a result of mutations is shown to influence the results of the protein engineering analysis. Furthermore, the temperature dependencies of phi values (which are a measure of the participation of a residue in the transition state) and the character of the transition state ensemble are studied. It is shown that as a general trend phi values decrease when the temperature decreases, a finding consistent with recent experimental results. Our analysis suggests that this trend results primarily from the formation of some contacts (native and non-native) in the unfolded state at a lower temperature, when the barrier for folding is energetic. CONCLUSIONS: Our analysis helps to interpret the results of protein engineering and allows observed &phi; values to be directly related to structural features of the unfolded state, the transition state and the native state.

Amino Acid Sequence↗
PubMed2006

Omnibus permutation tests of the association of an ensemble of genetic markers with disease in case-control studies.

An omnibus permutation test of the overall null hypothesis can be used to assess the association of an entire ensemble of genetic markers with disease in case-control studies. In this approach, p-values for univariate marker-specific Armitage trend tests are combined to form a scalar statistic, which is then used in a permutation test to determine an overall p-value. Two previously described competing methods utilize either a standard two-sample Hotelling's T2 statistic or a global U statistic that is a weighted sum of univariate U statistics. In contrast to Hotelling's test, omnibus tests are much less sensitive to missing data, and utilize all available data. In contrast to the global U test, omnibus tests do not require that the direction of the effects of the individual markers on the risk of disease be correctly specified in advance; in fact, any combination of one- and two-sided univariate tests can be used. Simulations show that, even under circumstances favoring the competing tests (no missing data; direction of effects known), omnibus permutation tests based on Fisher's combining function or the Anderson-Darling statistic typically have power comparable to or greater than Hotelling's and the global U tests.

Case-Control Studies↗
PubMed2004

The International Protein Index: an integrated database for proteomics experiments.

Despite the complete determination of the genome sequence of several higher eukaryotes, their proteomes remain relatively poorly defined. Information about proteins identified by different experimental and computational methods is stored in different databases, meaning that no single resource offers full coverage of known and predicted proteins. IPI (the International Protein Index) has been developed to address these issues and offers complete nonredundant data sets representing the human, mouse and rat proteomes, built from the Swiss-Prot, TrEMBL, Ensembl and RefSeq databases.

Animals↗
PubMed2002

Electrophoretic motion of a slightly deformed sphere with a nonuniform zeta potential distribution.

Electrophoretic motion is analyzed for a rigid, slightly deformed sphere with a nonuniform zeta potential distribution. Hydrodynamics and electrostatics solutions for the deformed sphere with an arbitrary double-layer thickness are determined by using the domain perturbation method. The surface shape and the zeta potential distribution for the deformed sphere are expressed by using the multipole expansion representation. In terms of monopole, dipole, and quadrupole moments of the surface shape and the zeta potential distribution, explicit expressions are obtained for the translational and rotational electrophoretic mobility tensors. The ensemble average for the mobility of the deformed sphere with a uniform orientation distribution is also derived. The utility of the general mobility expression is demonstrated by studying the electrophoretic motion of axisymmetric and ellipsoidal particles. The translational and rotational mobilities of axisymmetric particles are both affected by the monopole, dipole, and quadrupole moments of the zeta potential. For ellipsoidal particles, however, the dipole moment of the zeta potential does not affect the translational mobility, while the rotational mobility depends only on the dipole moment. The mobility of the deformed sphere with either a thick or a thin double layer is also derived.

Journal Article↗
PubMed1999

On the pH-conformational dependence of the unblocked SYPYD peptide.

Simulations were carried out for an unblocked pentapeptide with the sequence Ser-Tyr-Pro-Tyr-Asp (SYPYD) with explicit consideration of the coupling between the conformation of the molecule and the ionization equilibria at a given pH. The available NMR experimental data indicate a high preference for the cis isomeric turn-like form of Tyr-Pro at intermediate pH (approximately 6) and a destabilization of the cis form at both high (approximately 9) and low (approximately 3) pH. In order to identify the source of the stability of the conformation of this pentapeptide as a function of pH, Monte Carlo simulations were used to generate an ensemble of low-energy conformations at different pH values (viz. 3, 6 and 9). The total free energy function used in these calculations includes terms that account for the solvation free energy and free energy of ionization. These terms are evaluated by means of a fast multigrid boundary element (MBE) method. In good qualitative agreement with the experiments, our results indicate that the Boltzmann averaged population of the cis isomeric form of the pentapeptide has a maximum (45 %) at pH 6 and is significantly smaller (25 % and 23 %) for higher and lower pH values, respectively, following the trend of the experimental data. Also, the degree of charge for the lowest-energy conformations, as well as the contribution of electrostatic interactions to the stability of the preferred conformations, vary widely at the different pH values. Different kinds of packing of the aromatic side-chains of Tyr2 and Tyr4 against the proline ring are observed at different pH values, indicating that their contribution to the stability of the low-energy conformations is also pH-dependent. In summary, our results provide a basis for discussing the nature of the interactions that stabilize turn-like conformations of the peptide SYPYD as a function of pH.

Algorithms↗
PubMed2006

Single molecule force spectroscopy reveals a weakly populated microstate of the FnIII domains of tenascin.

The native states of proteins exist as an ensemble of conformationally similar microstates. The fluctuations among different microstates are of great importance for the functions and structural stability of proteins. Here, we demonstrate that single molecule atomic force microscopy (AFM) can be used to directly probe the existence of multiple folded microstates. We used the AFM to repeatedly stretch and relax a recombinant tenascin fragment TNfnALL to allow the fibronectin type III (FnIII) domains to undergo repeated unfolding/refolding cycles. In addition to the native state, we discovered that some FnIII domains can refold from the unfolded state into a previously unrecognized microstate, N* state. This novel state is conformationally similar to the native state, but mechanically less stable. The native state unfolds at approximately 120 pN, while the N* state unfolds at approximately 50 pN. These two distinct populations of microstates constitute the ensemble of the folded states for some FnIII domains. An unfolded FnIII domain can fold into either one of the two microstates via two distinct folding routes. These results reveal the dynamic and heterogeneous picture of the folded ensemble for some FnIII domains of tenascin, which may carry important implications for the mechanical functions of tenascins in vivo.

Computer Simulation↗
PubMed1997

A comparison of ECG cancellation techniques applied to the surface recording of somatosensory evoked potentials.

The use of somatosensory evoked potentials (SEPs) for determining spinal cord integrity in a clinical setting is well known. The poor signal-to-noise (SNR) ratio of such measurements has led to ensemble averaging being employed to extract the signal from the background noise. Over the thoracic region, the poor SNR is largely the result of interference generated by the cardiac musculature. Therefore, any reduction in the level of this cardiac interference will greatly improve the performance of any SEP monitoring system. Three methods were investigated as techniques to reduce the cardiac interference in SEP measurements. These were clipping, gating and adaptive noise cancellation (ANC). It was found that, although clipping and gating performed as well as, if not better than, ANC, these techniques were both very sensitive to the setting of a threshold level. The linear ANC scheme employed circumvented the problem associated with a threshold level, and with an order of 50, SNR improvement figures of approximately sixfold were achievable over the entire thoracic region.

Biomedical Engineering↗
PubMed1988

Characterization of voltage-gated sodium channels in ovine gonadotrophs: relationship to hormone secretion.

1. The properties of whole-cell Na+ currents (INa) were studied in immunocytochemically identified ovine gonadotrophs using the patch clamp technique. 2. Voltage recording under current clamp revealed that gonadotrophs did not fire spontaneously, and fired only a single action potential in response to a depolarizing current clamp step. 3. Under voltage clamp, INa was found to be sensitive to tetrodotoxin (TTX) and had an activation threshold of about -75 mV, with peak current occurring at -20 to -30 mV. 4. Using a two-pulse protocol a delay in the onset of inactivation was observed, suggesting that inactivation is dependent on and preceded by the activation phenomenon. 5. Kinetics of recovery from inactivation of the Na+ channels were studied with test pulses applied at various times after a depolarizing pre-pulse. Recovery from inactivation showed an initial delay, in contrast to the predictions of the Hodgkin-Huxley equations. 6. Recovery from inactivation was examined by using a repetitive pulse protocol, showing approximately 1 s is required for the channels to achieve a 95% recovery. 7. The steady-state inactivation (h infinity -V) curve was sigmoidal and fitted by a logistic growth curve model. The half-inactivation value of the Na+ current occurred at a membrane potential of -70 +/- 8 mV. 8. Noise power spectra derived from fluctuations of INa could be fitted with a single Lorentzian function, and the time constant value was slower at more depolarizing potentials. 9. The single-Na+-channel conductance was estimated from fluctuation analysis under conditions of reduced Na+ current amplitude by depolarizing pre-pulses. The single-channel conductance derived by the above method (approximately equal to 11 pS) corresponded to the single-channel conductance derived from single-channel current measurements using the outside-out version of the patch clamp technique (approximately equal to 13 pS). 10. Inactivation of INa was slowed by including 15 mM-iodate in the pipette. Ensemble fluctuation analysis of INa under these conditions was carried out using the steady state portion of the inactivation phase of the modified INa records, revealing a process best fitted by a double Lorentzian power spectrum, consistent with inactivation kinetics involving both a fast and a slow process. The time constant values correlated well with those obtained from a double-exponential fit to the decaying inactivation phase of the iodate-modified INa.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2003

Direct visualisation of homogeneous and heterogeneous crystallisation in an ensemble of confined domains of poly(ethylene oxide).

We present a study of homogeneous and heterogeneous nucleation in polymer crystallisation. In bulk samples the crystallization is typically dominated by nucleation from defects (heterogeneous nucleation), and consequently studies must rely on sample preparation to minimize this effect. We present a study of nucleation within discrete droplets of poly(ethylene oxide) that are formed by the dewetting of a thin film on an unfavourable substrate. The samples provide an ensemble of impurity-free droplets, with length scales that can easily be measured. We show that the data for heterogeneous and homogeneous nucleation is qualitatively different, and that the data mirrors the fundamental differences in the underlying mechanisms for the two nucleation processes. The experiments presented here provide a simple method that can be used to study heterogeneous and homogeneous nucleation in great detail.

Journal Article↗