SEARCH · PubMed Health

Results for “Compaction simulator”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 919 records · Page 51Linked to original sources

PubMed1990

The proline-activating activity of the multienzyme gramicidin S synthetase 2 can be recovered on a 115-kDa tryptic fragment.

The multienzyme gramicidin S synthetase 2 was treated with trypsin to obtain fragments capable of activating proline. Three different active fragments were detected. The course of proteolysis was simulated by using a concentration range of trypsin; the cleavage pattern indicated that one of the fragments was particularly stable. This fragment was purified and shown to have a molecular mass of 115 kDa. It was compared chromatographically, by SDS/PAGE, and enzymatically to a Pro-activating fragment produced by a gramicidin-S-negative mutant. It can be concluded that the proteolytic fragment represents a structure which is contained on a continuous part of the polypeptide chain of gramicidin S synthetase 2 and has a relatively compact structure. This provides evidence that the multienzyme gramicidin S synthetase 2 is, at least in part, constructed from functional domains. An approach towards extending these studies to other parts of the gramicidin S synthetase 2 molecule has also been devised. This work complements recombinant DNA studies in the area, providing stable functional fragments.

Adenosine Triphosphate↗

PubMed1997

De novo protein design: fully automated sequence selection.

The first fully automated design and experimental validation of a novel sequence for an entire protein is described. A computational design algorithm based on physical chemical potential functions and stereochemical constraints was used to screen a combinatorial library of 1.9 x 10(27) possible amino acid sequences for compatibility with the design target, a betabetaalpha protein motif based on the polypeptide backbone structure of a zinc finger domain. A BLAST search shows that the designed sequence, full sequence design 1 (FSD-1), has very low identity to any known protein sequence. The solution structure of FSD-1 was solved by nuclear magnetic resonance spectroscopy and indicates that FSD-1 forms a compact well-ordered structure, which is in excellent agreement with the design target structure. This result demonstrates that computational methods can perform the immense combinatorial search required for protein design, and it suggests that an unbiased and quantitative algorithm can be used in various structural contexts.

Algorithms↗

PubMed2002

Internal quality control system for non-stationary, non-ergodic analytical processes based upon exponentially weighted estimation of process means and process standard deviation.

The analytical processes in clinical laboratories should be considered to be non-stationary, non-ergodic and probably non-stochastic processes. Both the process mean and the process standard deviation vary. The variation can be different at different levels of concentration. This behavior is shown in five examples of different analytical systems: alkaline phosphatase on the Hitachi 911 analyzer (Roche), vitamin B12 on the Access analyzer (Beckman), prothrombin time and activated partial thromboplastin time on the STA Compact analyzer (Roche) and PO2 on the ABL 520 analyzer (Radiometer). A model is proposed to assess the status of a process. An exponentially weighted moving average and standard deviation was used to estimate process mean and standard deviation. Process means were estimated overall and for each control level. The process standard deviation was estimated in terms of within-run standard deviation. Limits were defined in accordance with state of the art- or biological variance-derived cut-offs. The examples given are real, not simulated, data. Individual control sample results were normalized to a target value and target standard deviation. The normalized values were used in the exponentially weighted algorithm. The weighting factor was based on a process time constant, which was estimated from the period between two calibration or maintenance procedures. The proposed system was compared with Westgard rules. The Westgard rules perform well, despite the underlying presumption of ergodicity. This is mainly caused by the introduction of the starting rule of 12s, which proves essential to prevent a large number of rule violations. The probability of reporting a test result with an analytical error that exceeds the total allowable error was calculated for the proposed system as well as for the Westgard rules. The proposed method performed better. The proposed algorithm was implemented in a computer program running on computers to which the analyzers were linked on-line. Each result was evaluated on-line, and a limit violation was immediately reported. The system has performed satisfactorily in our laboratory for ten analyzers for over 1 year.

Biometry↗

PubMed2006

Structural characterization of the binding of MyosinADPPi to actin in permeabilized rabbit psoas muscle.

When myosin is attached to actin in a muscle cell, various structures in the filaments are formed. The two strongly bound states (A*M*ADP and A*M) and the weakly bound A*M*ATP states are reasonably well understood. The orientation of the strongly bound myosin heads is uniform ("stereospecific" attachment), and the attached heads exhibit little spatial fluctuation. In the prehydrolysis weakly bound A*M*ATP state, the orientations of the attached myosin heads assume a wide range of azimuthal and axial angles, indicating considerable flexibility in the myosin head. The structure of the other weakly bound state, A*M*ADP*P(i), however, is poorly understood. This state is thought to be the critical pre-power-stroke state, poised to make the transition to the strongly binding, force-generating states, and hence it is of particular interest for understanding the mechanism of contraction. However, because of the low affinity between myosin and actin in the A*M*ADP*P(i) state, the structure of this state has eluded determination both in isolated form and in muscle cells. With the knowledge recently gained in the structures of the weakly binding M*ATP, M*ADP*P(i) states and the weakly attached A*M*ATP state in muscle fibers, it is now feasible to delineate the in vivo structure of the attached state of A*M*ADP*P(i). The series of experiments presented in this article were carried out under relaxing conditions at 25 degrees C, where approximately 95% of the myosin heads in the skinned rabbit psoas muscle contain the hydrolysis products. The affinity for actin is enhanced by adding polyethylene glycol (PEG) or by lowering the ionic strength in the bathing solution. Solution kinetics and binding constants were determined in the presence and in the absence of PEG. When the binding between actin and myosin was increased, both the myosin layer lines and the actin layer lines increased in intensity, but the intensity profiles did not change. The configuration (mode) of attachment in the A*M*ADP*P(i) state is thus unique among the intermediate attached states of the cross-bridge ATP hydrolysis cycle. One of the simplest explanations is that both myosin filaments and actin filaments are stabilized (e.g., undergo reduced spatial fluctuations) by the attachment. The alignment of the myosin heads in the thick filaments and the alignment of the actin monomers in the thin filaments are improved as a result. The compact atomic structure of M*ADP*P(i) with strongly coupled domains may contribute to the unique attachment configuration: the "primed" myosin heads may function as "transient struts" when attached to the thin filaments.

Actins↗

PubMed2005

The use of stationarity and nonstationarity in the detection and analysis of neural oscillations.

Using available signal (i.e., spectral and time-frequency) analysis methods, it can be difficult to detect neural oscillations because of their continuously changing properties (i.e., nonstationarities) and the noise in which they are embedded. Here, we introduce fractally scaled envelope modulation (FSEM) estimation which is sensitive specifically to the changing properties of oscillatory activity. FSEM utilizes the fractal characteristic of wavelet transforms to produce a compact, two-dimensional representation of time series data where signal components at each frequency are made directly comparable according to the spectral distribution of their envelope modulations. This allows the straightforward identification of neural oscillations and other signal components with an envelope structure different from noise. For stable oscillations, we demonstrate how partition-referenced spectral estimation (PRSE) removes the noise slope from spectral estimates, yielding a level estimate where only peaks signifying the presence of oscillatory activity remain. The functionality of these methods is demonstrated with simulations and by analyzing MEG data from human auditory brain areas. FSEM uncovered oscillations in the 9- to 12-Hz and 15- to 18-Hz ranges whereas traditional spectral estimates were able to detect oscillations only in the former range. FSEM further showed that the oscillations exhibited envelope modulations spanning 3-7 s. Thus, FSEM effectively reveals oscillations undetectable with spectral estimates and allows the use of EEG and MEG for studying cognitive processes when the common approach of stimulus time-locked averaging of the measured signal is unfeasible.

Acoustic Stimulation↗

PubMed2002

Scaling behavior of the surface in ballistic deposition.

Using a dynamical scaling form for the surface fractal dimension as well as efficient algorithms for the simulation and analysis of the surface in three-dimensional ballistic deposition, we show that while the top of the surface is self-affine, the complete surface including overhangs has fractal dimension D(f) approximately 3. The existence of such a fractal surface is a consequence of the difficulty of closing off voids in three and higher dimensions. By studying a modified ballistic deposition model in which sticking is allowed with a given probability p, we show that the surface undergoes a phase transition from fractal to compact at a finite value of p. Our results also have implications for understanding the surface morphology in sedimentary rocks and low-temperature thin films.

Journal Article↗

PubMed1983

Dependence of the shape of the plasma fibronectin molecule on solvent composition. Ionic strength and glycerol content.

Fibronectin has been purified to apparent homogeneity according to measurements of molecular weight and diffusion constant from light scattering and sedimentation in the analytical ultracentrifuge. This gives two estimates of molecular weight close to 500,000. (The difference with the gel electrophoretic value of 440,000 may indicate the presence of some material of molecular weight higher than that of the monomer.) The (corrected) diffusion constant is found to decrease with ionic strength, much more rapidly in 30% glycerol than in water. A corresponding change occurs when the glycerol content is varied from 0 to 30% at moderate ionic strength, but at very low ionic strength the diffusion constant does not depend on glycerol content. It is concluded that fibronectin can occur in two extreme conformations: the open form, in 30% glycerol at moderate ionic strength, should correspond to the extended shapes visualized by others by electron microscopy of samples prepared from solutions containing glycerol, while the closed form occurs under more physiological conditions. The Stokes radii of these forms, 14.5 and 9.6 nm, respectively, have been compared with calculated Stokes radii of chains of beads of overall length 140 nm having varying stiffness, simulated by a Monte Carlo procedure. These have a Stokes radius of 14.5 nm when made relatively extended to where the distance between chain ends averages 90 nm, as observed in the electron micrographs. When these chains are made very flexible, the Stokes radius reaches a limit of about 10 nm, apparently a lower limit to which a randomly coiled molecule of this size and volume may collapse in a disordered fashion. These results and electron micrographs obtained at low ionic strength suggest a tangled model of the compact form, rather than the ordered model recently proposed by others. Finally, some speculation is offered in regard to a possible physiological role of a conformation change of fibronectin.

Fibronectins↗

PubMed2005

A fast flow tube study of gas phase H/D exchange of multiply protonated ubiquitin.

An electrospray ionization (ESI)/fast-flow technique has been applied to the study of gas phase hydrogen/deuterium (H/D) exchange kinetics. Multiply charged ubiquitin ions [ubiquitin + nH](n)(+), in charge states n = 7-13, were reacted with ND(3). The behavior of ND(3) as exchange reagent is different from that of the previously studied reagents, D(2)O and CH(3)OD. Contrary to those, the maximum number of exchanged hydrogen atoms and the overall exchange rate were observed to increase with increasing charge state of the ubiquitin ions. The results are reagent-dependent because the exchange mechanisms are different for the different reagents. This observation is in agreement with a recent conclusion by Beauchamp and co-workers that contrary to the assumption often expressed in earlier studies, H/D exchange kinetics may not directly reflect ion structures. The results for all three reagents are, however, consistent with observations of previous ion mobility experiments that with increasing charge state the conformers change from more compact, partially folded structures to elongated nearly linear ones. H/D exchange of (ubiquitin + 13H)(13+) with ND(3) leads to two separated ion populations reflecting the possible existence of two conformers with different exchange rates. The ions (ubiquitin + 8H)(8+) and (ubiquitin + 11H)(11+) represent a partially folded structure and an unfolded structure, respectively, and were studied in greater detail. The relative abundances of ions were measured in steps of 0.5 m/z (mass-to-charge ratio), as a function of the ND(3) flow rate. The experimental results were simulated by computer fitted curves based on a recently developed algorithm. The algorithm allows the extraction of sets of grouped rate constants. Eight rate constant groups were deduced for each of the two ions. These rate constants correspond to 32 and 44 H/D exchanges for the 8+ and 11+ charged ions, respectively. The results indicate higher individual rates for most of the exchanged atoms in the 11+ ion compared to the 8+ ion.

Computer Simulation↗

PubMed2005

On the difference in scattering behavior of cyclic and linear polymers in bulk.

It has been suggested that, due to topological constraints, rings in the melt may assume a more compact shape than Gaussian chains. In this paper, we exploit the availability of narrow fractions of perdeuterated linear and cyclic polydimethylsiloxane (PDMS) and, through the analysis of the small angle neutron scattering (SANS) profiles, demonstrate the difference in scattering properties of linear and cyclic PDMS molecules. As expected for Gaussian chains, for the H/D linear PDMS samples, log-log plots of the scattered intensity versus scattering vector Q display a Q((-2)) dependence. However, for H/D cyclic blends, the scaling exponent is higher than 2, as predicted by computer simulations reported in the literature. We show that cyclic molecules in bulk display the characteristic maximum in plots of scattered intensity versus Q((-2)) that is expected on the basis of Monte Carlo calculations and from the Casassa equation [E. F. Casassa, J. Polym. Sci. A 3, 605 (1965)]. It is also shown that, for rings, the Debye equation [P. Debye, J. Appl. Phys. 15, 338 (1944)] is no longer appropriate to describe the SANS profiles of H/D cyclic blends, at least up to M(w) approximately 10 000. For these samples, the Casassa form factor gives a better representation of the SANS data and we show that this function which was developed for monodisperse cyclics is still adequate to describe our slightly polydisperse samples. Deviations from all above observations are noted for M(w)>11 000 and are attributed to partial contamination of cyclic samples with linear chains. The failure of both the Debye and the Casassa form factors could be due to contamination of the cyclic fractions by linear polymers or to a real conformational change.

Journal Article↗

PubMed1989

Cell-to-cell interaction: a mechanism to explain wave-front progression of myocardial necrosis.

Histological sections performed 24 h after coronary occlusion in eight pigs displayed compact infarcts extending transmurally with well-defined edges; reconstruction and inspection of the area of necrosis showed a geometric distribution of the infarcts with very irregular, interdigitating edges always in continuity with the main mass of necrosis. Reperfusion in 32 pigs after periods of coronary occlusion of 90, 60, 45, and 30 min exponentially reduced infarct size and transmural extension of the infarct but did not modify its geometry. The two-dimensional size, progression, and geometry of the infarcts could be reproduced by a computer model. In the simulated infarcts, each myocardial cell within the area at risk was represented by a pixel. The algorithm included an inner loop, which determined at random at each iteration a status of reversible or irreversible damage to all pixels. The number of iterations could reproduce infarct of various sizes. With the addition of an index of transmural sensitivity to ischemia, progression of the infarct area could also be reproduced. The only possible means of reproducing the geometry of the infarct was to enter into the program a contiguity condition requiring a direct contact between irreversibly damaged pixels. These observations suggest that the physical interaction between cells is an important determinant of progression of necrosis during coronary occlusion.

Animals↗

PubMed2005

Linear-Nonlinear-Poisson models of primate choice dynamics.

The equilibrium phenomenon of matching behavior traditionally has been studied in stationary environments. Here we attempt to uncover the local mechanism of choice that gives rise to matching by studying behavior in a highly dynamic foraging environment. In our experiments, 2 rhesus monkeys (Macacca mulatta) foraged for juice rewards by making eye movements to one of two colored icons presented on a computer monitor, each rewarded on dynamic variable-interval schedules. Using a generalization of Wiener kernel analysis, we recover a compact mechanistic description of the impact of past reward on future choice in the form of a Linear-Nonlinear-Poisson model. We validate this model through rigorous predictive and generative testing. Compared to our earlier work with this same data set, this model proves to be a better description of choice behavior and is more tightly correlated with putative neural value signals. Refinements over previous models include hyperbolic (as opposed to exponential) temporal discounting of past rewards, and differential (as opposed to fractional) comparisons of option value. Through numerical simulation we find that within this class of strategies, the model parameters employed by animals are very close to those that maximize reward harvesting efficiency.

Animals↗

PubMed1991

Exciton microscopy and reaction kinetics in restricted spaces.

We describe the development of a new biologically non-invasive ultraresolution light microscopy, based on combining the energy transfer "spectral ruler" method with the micro-movement technology employed in scanning tunneling microscopy (STM). We use near-field scanning optical microscopy, with micropipettes containing crystals of energy packaging donor molecules in the tips that can have apertures below 5 nm. The excitation of these tips extends near field microscopy well beyond the 50 nm limit. The theoretical resolution limit for this spectrally sensitive light microscopy is well below 1 nm. Exciton microscopy is ideally suited for kinetic studies that are spatially resolved on the molecular scale, i.e., at a single molecule site. Moreover, the successful operation of the scanning exciton tip depends on an understanding of reaction kinetics in restricted spaces. In contrast to the many recent reviews on scanning tip microscopies, there is no adequate review of the recent revolutionary developments in the area of reaction kinetics in confined geometries. We thus attempt such a review in this paper. Reactions in restricted spaces rarely get stirred vigorously by convection and are thus often controlled by diffusion. Furthermore, the compactness of the Brownian motion leads to both anomalous diffusion and anomalous reaction kinetics. Elementary binary reactions of the type A + A----Products, A + B----Products and A + C----C + Products are discussed theoretically for both batch and steady-state conditions. The anomalous reaction orders and time exponents (for the rate coefficients) are discussed for various situations. Global and local rate laws are related to particle distribution functions. Only Poissonian distributions guarantee the classical rate laws. Reactant self-organization leads to interesting new phenomena. These are demonstrated by theory, simulations, and experiments. The correlation length of reactant production affects the self-ordering length-scale. These effects are demonstrated experimentally, including the stability of reactant segregation observed in chemical reactions in one-dimensional spaces, e.g., capillaries and microcapillaries. The gap between the reactant A (cation) and B (anion) actually increases in time, and extends over millimeters. Excellent agreement is found among theory, simulation, and experiment for the various scaling exponents.

Kinetics↗

PubMed2005

Mass fractal dimension and the compactness of proteins.

Vibrational dynamics and energy flow in a protein are related by Alexander-Orbach theory to the protein's mass fractal dimension D and spectral dimension d . Proteins: Struct., Funct. Bioinf. 55, 529 (2004)] recently proposed a relation between d and protein size based on their computational analysis of a set of proteins ranging from about 100 to several thousand amino acids. We report here values for D computed for 200 proteins from the Protein Data Bank (PDB) ranging from about 100 to over 10 000 amino acids and examine variation of D with protein size. The average D is found to be 2.5, significantly smaller than a completely compact three-dimensional collapsed polymer. Indeed, we find that on average a protein in its PDB configuration fills about three-quarters of the volume within the protein surface. Protein mass is also found to scale with radius of gyration with an exponent of 2.5 for this set of proteins.

Amino Acid Sequence↗

PubMed2003

CTSS: a robust and efficient method for protein structure alignment based on local geometrical and biological features.

We present a new method for conducting protein structure similarity searches, which improves on the accuracy, robustness, and efficiency of some existing techniques. Our method is grounded in the theory of differential geometry on 3D space curve matching. We generate shape signatures for proteins that are invariant, localized, robust, compact, and biologically meaningful. To improve matching accuracy, we smooth the noisy raw atomic coordinate data with spline fitting. To improve matching efficiency, we adopt a hierarchical coarse-to-fine strategy. We use an efficient hashing-based technique to screen out unlikely candidates and perform detailed pairwise alignments only for a small number of candidates that survive the screening process. Contrary to other hashing based techniques, our technique employs domain specific information (not just geometric information) in constructing the hash key, and hence, is more tuned to the domain of biology. Furthermore, the invariancy, localization, and compactness of the shape signatures allow us to utilize a well-known local sequence alignment algorithm for aligning two protein structures. One measure of the efficacy of the proposed technique is that we were able to discover new, meaningful motifs that were not reported by other structure alignment methods.

Algorithms↗

PubMed2005

Atypical recognition of particular DNA sequences by the archaeal chromosomal MC1 protein.

The MC1 protein is a chromosomal protein likely involved in the DNA compaction of some methanogenic archaea. This small and monomeric protein, structurally unrelated to other DNA binding proteins, bends DNA sharply. By studying the protein binding to various kinds of kinked DNA, we have previously shown that MC1 is able to discriminate between different deformations of the DNA helix. Here we investigate its capacity to recognize particular DNA sequences by using a SELEX procedure. We find that MC1 is able to preferentially bind to a 15 base pair motif [AAAAACACAC(A/C)CCCC]. The structural parameters of this sequence are characterized by molecular dynamics simulation experiments, and the binding mode of the protein to the DNA is studied by footprinting experiments. Our results strongly suggest that the protein realizes an indirect readout of the DNA sequence by binding to the DNA minor groove.

Archaeal Proteins↗

PubMed1998

The ICRP age-specific biokinetic model for lead: validations, empirical comparisons, and explorations.

The objective of this manuscript is to provide a description of the International Commission for Radiation Protection (ICRP) model and a comparison to other models (the integrated exposure uptake biokinetic [IEUBK] and O'Flaherty models), including the software used with the models, and a comparison of the model predictions for selected situations. The ICRP biokinetic model for Pb is a multicompartmental model for Pb uptake and disposition in children and in adults. The model describes deposition and retention of absorbed Pb in numerous tissues, removal from tissues to plasma, and movement along various routes of excretion. Long-term skeletal behavior of Pb is described in terms of age-specific rates of restructuring of compact and trabecular bone. The ICRP model is more flexible and has wider applicability than the IEUBK model. The major disadvantages are that application of the computer model requires some basic computer skills, and the user must convert the Pb concentrations in food, air, soil, dust, paint, or other media to the amount of Pb ingested or inhaled per day. Direct comparisons between the ICRP model and the IEUBK model are provided by modeling blood Pb levels using the IEUBK v0.99d default Pb uptakes and intake values. The model is used to simulate occupational exposure cases and a controlled Pb inhalation experiment in adult humans. Finally, use of the model to explore situations with limited data is illustrated by simulating the kinetics and disposition of Pb during acute Pb poisoning and chelation therapy in a child.

Animals↗

PubMed1995

Preparation and evaluation of sodium diclofenac controlled-release tablets. II. Dibasic calcium phosphate as a retardant in mixtures for direct compression.

The dissolution behaviour of a direct compression compact prepared with sodium diclofenac and dibasic calcium phosphate (DCP) in different weight ratios with or without Biosoluble polymer (acrylic-based resin) was investigated in distilled water and in a medium with changing pH. The results indicate that the amount of sodium diclofenac released from the compact was dependent on the amount of drug and DCP used in the compact, and was also controlled by the amount of Biosoluble polymer added. A chemical reaction forming diclofenac acid might occur on the surface of the sodium diclofenac compact during exposure to the acidic medium, which was confirmed by diffuse-reflectance spectroscopy. The tablet with a 1:2 weight ratio of sodium diclofenac to DCP exhibited a sustained-release behaviour, similar to commercial sustained-release products (Voltaren SR-100 and Grofenac Retard), but a lower release rate was found as compared to the commercial products. The dissolution behaviour of the study tablet and the commercial products was found to be dependent on the dissolution medium and the rotating speeds. Glass beads were added to the dissolution assembly to simulate the influence of food, and the enhanced friction between tablet and glass beads might result in a higher dissolution rate of the tablet and the commercial products.

Acrylates↗

PubMed2004

Solution structure of Eucommia antifungal peptide: a novel structural model distinct with a five-disulfide motif.

The three-dimensional structure in aqueous solution of Eucommia antifungal peptide 2 (EAFP2) from Eucommia ulmoides Oliv was determined using (1)H NMR spectroscopy. EAFP2 is a newly discovered 41-residue peptide distinct with a five-disulfide cross-linked motif. This peptide exhibits chitin-binding activity and inhibitory effects on the growth of cell wall chitin-containing fungi and chitin-free fungi. The structure was calculated by using torsion angle dynamic simulated annealing with a total of 614 distance restraints and 16 dihedral restraints derived from NOESY and DQF-COSY spectra, respectively. The five disulfide bonds were assigned from preliminary structures using a statistical analysis of intercystinyl distances. The solution structure of EAFP2 is presented as an ensemble of 20 conformers with a backbone RMS deviation of 0.65 (+/-0.13) A for the well-defined Cys3-Cys39 segment. The tertiary structure of EAFP2 represents the first five-disulfide cross-linked structural model of the plant antifungal peptide. EAFP2 adopts a compact global fold composed of a 3(10) helix (Cys3-Arg6), an alpha-helix (Gly26-Cys30), and a three-strand antiparallel beta-sheet (Cys16-Ser18, Tyr22-Gly24, and Arg36-Cys37). The tertiary structure of EAFP2 shows a chitin-binding domain (residues 11-30) with a hydrophobic face and a characteristic sector formed by the N-terminal 10 residues and the C-terminal segment cross-linked through the unique disulfide bond Cys7-Cys37, which brings all four positively charged residues (Arg6, Arg9, Arg36, and Arg40) onto a cationic face. On the basis of such a structural feature, the possible structural basis for the functional properties of EAFP2 is discussed.

Amino Acid Sequence↗