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At least 1,207 records · Page 67Linked to original sources
PubMed2007

SODOCK: swarm optimization for highly flexible protein-ligand docking.

Protein-ligand docking can be formulated as a parameter optimization problem associated with an accurate scoring function, which aims to identify the translation, orientation, and conformation of a docked ligand with the lowest energy. The parameter optimization problem for highly flexible ligands with many rotatable bonds is more difficult than that for less flexible ligands using genetic algorithm (GA)-based approaches, due to the large numbers of parameters and high correlations among these parameters. This investigation presents a novel optimization algorithm SODOCK based on particle swarm optimization (PSO) for solving flexible protein-ligand docking problems. To improve efficiency and robustness of PSO, an efficient local search strategy is incorporated into SODOCK. The implementation of SODOCK adopts the environment and energy function of AutoDock 3.05. Computer simulation results reveal that SODOCK is superior to the Lamarckian genetic algorithm (LGA) of AutoDock, in terms of convergence performance, robustness, and obtained energy, especially for highly flexible ligands. The results also reveal that PSO is more suitable than the conventional GA in dealing with flexible docking problems with high correlations among parameters. This investigation also compared SODOCK with four state-of-the-art docking methods, namely GOLD 1.2, DOCK 4.0, FlexX 1.8, and LGA of AutoDock 3.05. SODOCK obtained the smallest RMSD in 19 of 37 cases. The average 2.29 A of the 37 RMSD values of SODOCK was better than those of other docking programs, which were all above 3.0 A.

Algorithms↗
PubMed1976

Development of a stable sublingual nitroglycerin tablet II: formulation and evaluation of tablets containing povidone.

Stable and pharmaceutically elegant sublingual nitroglycerin tablets were formulated using povidone to retard volatilization of the drug. Formulation and processing variables were investigated to produce an acceptable product. A blend of two grades of povidone, of different degrees of cross-linkage and water solubility, provided stable tablets which exhibited rapid disintegration. Directly compressed sublingual tablets made in this study retained over 80% of the initial nitroglycerin when exposed to the atmosphere at room temperature for 2 months. The direct compression tablets are of good appearance and low friability, and the formulation is readily compressed without problems. An interesting relationship among the hardness, disintegration time, and compaction pressure is described.

Drug Compounding↗
PubMed2005

Iterative RF pulse design for multidimensional, small-tip-angle selective excitation.

The excitation k-space perspective on small-tip-angle selective excitation has facilitated RF pulse designs in a range of MR applications. In this paper, k-space-based design of multidimensional RF pulses is formulated as a quadratic optimization problem, and solved efficiently by the iterative conjugate-gradient (CG) algorithm. Compared to conventional design approaches, such as the conjugate-phase (CP) method, the new design approach is beneficial in several regards. It generally produces more accurate excitation patterns. The improvement is particularly significant when k-space is undersampled, and it can potentially shorten pulse lengths. A prominent improvement in accuracy is also observed when large off-resonance gradients are present. A further boost in excitation accuracy can be accomplished in regions of interest (ROIs) if they are specified together with "don't-care" regions. The density compensation function (DCF) is no longer required. In addition, regularization techniques allow control over integrated and peak pulse power.

Algorithms↗
PubMed2006

Evaluation of lipid-based carrier systems and inclusion complexes of diethyldithiocarbamate-iron to trap nitric oxide in biological systems.

The success of spin trapping techniques in vivo hinges on whether spin traps with high trapping efficiency and biocompatibility can be developed. Currently, two iron chelates based on the dithiocarbamate structure (hydrophilic ferro-di(N-methyl-D-glucamine-dithiocarbamate, or Fe(II)-MGD, and lipophilic ferro-di(diethyldithiocarbamate), or Fe(II)-DETC), are used for spin trapping of nitric oxide (NO) in biologic systems. However, detection efficiency is hampered by a complex redox chemistry for Fe(II)-MGD and by the insolubility of Fe(II)-DETC in water. To circumvent these problems, two new spin trap formulations based on Fe(II)-DETC were developed: a lipid-based carrier system stabilized by lecithin and inclusion complexes in hydroxypropyl-beta-cyclodextrin. The capability of these two systems to trap NO was determined and compared to the standard spin traps in vitro (in the presence of an NO donor) and in vivo (after induction of septic shock in mice). The sensitivity of the detection of NO was significantly increased (by a factor of 4) using the lipid-based carrier systems or inclusion complexes compared to the standard spin trap agents.

Animals↗
PubMed2006

Spatial domain method for the design of RF pulses in multicoil parallel excitation.

Parallel excitation has been introduced as a means of accelerating multidimensional, spatially-selective excitation using multiple transmit coils, each driven by a unique RF pulse. Previous approaches to RF pulse design in parallel excitation were either formulated in the frequency domain or restricted to echo-planar trajectories, or both. This paper presents an approach that is formulated as a quadratic optimization problem in the spatial domain and allows the use of arbitrary k-space trajectories. Compared to frequency domain approaches, the new design method has some important advantages. It allows for the specification of a region of interest (ROI), which improves excitation accuracy at high speedup factors. It allows for magnetic field inhomogeneity compensation during excitation. Regularization may be used to control integrated and peak pulse power. The effects of Bloch equation nonlinearity on the large-tip-angle excitation error of RF pulses designed with the method are investigated, and the utility of Tikhonov regularization in mitigating this error is demonstrated.

Algorithms↗
PubMed2003

Post-column infusion study of the 'dosing vehicle effect' in the liquid chromatography/tandem mass spectrometric analysis of discovery pharmacokinetic samples.

It has become increasingly popular in drug development to conduct discovery pharmacokinetic (PK) studies in order to evaluate important PK parameters of new chemical entities (NCEs) early in the discovery process. In these studies, dosing vehicles are typically employed in high concentrations to dissolve the test compounds in dose formulations. This can pose significant problems for the liquid chromatography/tandem mass spectrometric (LC/MS/MS) analysis of incurred samples due to potential signal suppression of the analytes caused by the vehicles. In this paper, model test compounds in rat plasma were analyzed using a generic fast gradient LC/MS/MS method. Commonly used dosing vehicles, including poly(ethylene glycol) 400 (PEG 400), polysorbate 80 (Tween 80), hydroxypropyl beta-cyclodextrin, and N,N-dimethylacetamide, were fortified into rat plasma at 5 mg/mL before extraction. Their effects on the sample analysis results were evaluated by the method of post-column infusion. Results thus obtained indicated that polymeric vehicles such as PEG 400 and Tween 80 caused significant suppression (> 50%, compared with results obtained from plasma samples free from vehicles) to certain analytes, when minimum sample cleanup was used and the analytes happened to co-elute with the vehicles. Effective means to minimize this 'dosing vehicle effect' included better chromatographic separations, better sample cleanup, and alternative ionization methods. Finally, a real-world example is given to illustrate the suppression problem posed by high levels of PEG 400 in sample analysis, and to discuss steps taken in overcoming the problem. A simple but effective means of identifying a 'dosing vehicle effect' is also proposed.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed1994

Numerical calculation of the potential distribution due to dipole sources in a spherical model of the head.

A three-dimensional spherical model of the head was investigated numerically. The model consists of four conductive layers representing the scalp, the skull, the cerebrospinal fluid, and the cortex with a dipole current source. The potential created by the dipole was calculated using quasistatic formulation and a linear medium. The volume conduction equation was discretized by the finite volume method to ensure the conservation of fluxes and efficient solution method. The large set of algebraic equations for the electric potential was solved iteratively by the successive over relaxation method. The new formulation of the volume conduction problem was validated by comparing the numerical results with two analytical solutions. The first test-case considers a homogeneous spherical model with a dipole in the center. The potential on the outer surface, as well as within the volume conductor, was calculated and very good agreement was obtained with the analytical solution. In the second test-case, the scalp potential due to a radially oriented eccentric dipole in a four concentric spheres model was compared with an analytic solution. It was found that a grid of 90 x 90 x 90 volume elements yielded accurate results on the scalp surface with errors on the order of 1%. The present numerical model can be extended to general cases with any volume conductor shape or with any distribution or orientation of the current dipoles. Compared to other numerical methods, this approach offers enhanced accuracy for given computational resources (both in CPU time and memory). The gain might be more than one order of magnitude, allowing simulation with considerably larger meshes.

Body Surface Area↗
PubMed2001

Theoretical Study of Aerosol Filtration by Nucleopore Filters: The Intermediate Crossover Regime of Brownian Diffusion and Direct Interception.

We study the problem of aerosol filtration by formulating a unified approach that incorporates the dominant mechanisms of particle capture in cylindrical pores. The theoretical approach presented here takes into account the effects of flow slip at the pore wall and predicts an enhanced efficiency in the intermediate crossover regime between Brownian diffusion and direct interception. We also suggest how the results obtained for cylindrical pores can be used to estimate the efficiency of granular ceramic filters in the region of the most penetrating particle size, where the enhanced efficiency effects are strongly amplified by the large number of pores, or more generally unit bed elements, acting in series. Copyright 2001 Academic Press.

Journal Article↗
PubMed1993

Lattice neural network minimization. Application of neural network optimization for locating the global-minimum conformations of proteins.

A way of formulating the protein-folding problem in neural network optimization terms is presented in this paper. This is accomplished by representing the conformation of a protein as an array of the amino acid sequence versus position on a three-dimensional face-centered cubic lattice with an energy function defined in terms of the array variables. The method is called lattice neural network minimization (LNNM). Using the neural network minimization method, the energy function is minimized to locate the global minimum energy for the conformation of the protein. The energy function consisted of site exclusion and bond connectivity penalty terms and a pairwise contact energy potential. The contact energy potential used in the procedure is the united-residue potential of Miyazawa, Jernigan and Covell. The LNNM method found the global minimum for a seven-residue peptide in all of the 15 runs carried out. The time for each run was approximately 30 seconds on one processor of an IBM 3090 computer. For a nine-residue peptide, the global minimum was found in 7 out of 15 runs (47%) in approximately 50 seconds per run. For this peptide, LNNM found the global minimum or the second lowest minimum in 10 of the runs. In the same total CPU times (approximately 750 seconds), a Monte Carlo simulated annealing method found the global minimum or the second lowest minimum in only two runs, demonstrating the superiority of LNNM over the standard Monte Carlo simulated annealing method for this nine-residue peptide. Starting from a uniform array for the protein crambin (46 residues) on the lattice, the energy of the crambin array was minimized and a compact low-energy structure was found in approximately 25 minutes of CPU time. Its energy was much lower than that of the native protein, suggesting that there are inadequacies in the Miyazawa-Jernigan-Covell potential. The LNNM method was applied to the prediction of what was previously called nucleation but more properly called chain-folding initiation sites (CFIS) of a protein. LNNM correctly predicted the CFIS for the two proteins examined, RNase S and T4 lysozyme. The LNNM method was also applied to another chain optimization problem, minimization of the root-mean-square distance error (r.m.s.d.) (a measure similar to r.m.s. deviation) in fitting X-ray structures to a lattice, with good results.

Models, Chemical↗
PubMed1993

The discrete nature of biological membrane conductance, channel interaction through electrolyte layers and the cable equation.

An initial value problem for membrane potential is formulated and solved to allow for the discrete (non-continuous) nature of biological membrane conductance. The discrete model solutions are discussed and compared with those resulting from the cable equation. It is shown that the solutions of the discrete model approach the latter when the channel distance becomes smaller than the space constant of the system. This convergence is interpreted as a consequence of "channel interaction" through electrolyte layers surrounding the membrane. In the case of an axon (channel distance "space constant) the effect of the discreteness on both the potential profile and the kinetics of the membrane response may be regarded as negligible, the physical reason for this behavior being the "mean-field like" properties of the system.

Animals↗
PubMed2005

Unbiased atlas formation via large deformations metric mapping.

The construction of population atlases is a key issue in medical image analysis, and particularly in brain mapping. Large sets of images are mapped into a common coordinate system to study intra-population variability and inter-population differences, to provide voxel-wise mapping of functional sites, and to facilitate tissue and object segmentation via registration of anatomical labels. We formulate the unbiased atlas construction problem as a Fréchet mean estimation in the space of diffeomorphisms via large deformations metric mapping. A novel method for computing constant speed velocity fields and an analysis of atlas stability and robustness using entropy are presented. We address the question: how many images are required to build a stable brain atlas?

Algorithms↗
PubMed1981

A posteriori time-varying filtering of averaged evoked potentials. I. Introduction and conceptual basis.

This paper forms a preface and introduction to a new method for the estimation of evoked potentials: a posteriori time-varying filtering. A simple evoked potential model, consisting of a transient signal and additive noise, is discussed and the underlying assumptions explicitly formulated. Assuming this model, the problem of estimating the signal from an ensemble is considered from the statistical and communication engineering point of view, along with a brief survey of he pertinent literature. It is explained why ensemble averaging, in general, does not provide the best estimate in the mean-square error sense. After a summary of the controversial aspects of time-invariant "a posteriori "Wiener' filtering", it is indicated how that method can be generalized to a time-varying counterpart, which is able to handle the essentially transient character of evoked potential waveforms. Finally, the new method is presented on a conceptual level and its application illustrated by examples.

Brain↗
PubMed1984

Fundamentals of fluid transport through cartilage in compression.

This paper describes the flow patterns and related viscoelastic behaviors of articular cartilage under four different loading configurations: 1) confined compression, 2) unconfined compression, 3) translating parabolic surface traction of constant loading span over a cartilage layer, and 4) spreading parabolic surface traction of periodically varying span on a cartilage layer. Brief summaries of formulations and solutions of these problems are given and discussed. For the first two cases, emphasis is given to the differences in the flow mechanisms giving rise to the observed compressive viscoelastic behavior of the tissue. These two fundamental solutions can provide a basis for interpreting the results of the deformation and flow patterns obtained from more complicated loading configurations. The last two cases simulate two main geometric features of joint articulations. Fluid efflux patterns at the articulating surface depend on the kinematics of loading as well as the intrinsic material properties of the tissue: the moduli and permeability of the solid matrix. The predominant mechanism controlling the viscoelastic behavior of the tissue in compression is determined by the relative magnitude of the fluid drag and the intrinsic stiffness of the organic solid matrix.

Biomechanical Phenomena↗
PubMed1991

Control of FES-induced cyclical movements of the lower leg.

The control of a cyclical movement of the lower leg with electrical stimulation of the quadriceps muscles is formulated as an optimal control problem. The time integral of knee torque is taken as the optimisation criterion. As an additional condition, every cycle a certain reference maximum angle should be reached. A model study indicates that one stimulation burst per cycle at the maximum recruitment level is a suboptimal solution to this problem. To compensate for the influence of muscle fatigue, the burst time is adaptively adjusted by a discrete time PID-controller on the basis of the performance in the previous cycles. This strategy appeared to be successful in experimental tests. A considerable time difference (about 0.15 s) was found between the end of the stimulation burst and the tracking of the passive state trajectory, which satisfies the maximum angle condition.

Biomechanical Phenomena↗
PubMed2004

On the logic of hypothesis testing in functional imaging.

Statistics is nowadays the customary language of functional imaging. It is common to express an experimental setting as a set of null hypotheses over complex models and to present results as maps of p-values derived from sophisticated probability distributions. However, the growing interest in the development of advanced statistical algorithms is not always paralleled by similar attention to how these techniques may regiment the ways in which users draw inferences from their data. This article investigates the logical bases of current statistical approaches in functional imaging and probes their suitability to inductive inference in neuroscience. The frequentist approach to statistical inference is reviewed with attention to its two main constituents: Fisherian "significance testing" and Neyman-Pearson "hypothesis testing". It is shown that these conceptual systems, which are similar in the univariate testing case, dissociate into two quite different methods of inference when applied to the multiple testing problem, the typical framework of functional imaging. This difference is explained with reference to specific issues, like small volume correction, which are most likely to generate confusion in the practitioner. Further insight into this problem is achieved by recasting the multiple comparison problem into a multivariate Bayesian formulation. This formulation introduces a new perspective where the inferential process is more clearly defined in two distinct steps. The first one, inductive in form, uses exploratory techniques to acquire preliminary notions on the spatial patterns and the signal and noise characteristics. The (smaller) set of likely spatial patterns generated is then tested with newer data and a more rigorous multiple hypothesis testing technique (deductive step).

Algorithms↗
PubMed2006

Simulating complex tumor dynamics from avascular to vascular growth using a general level-set method.

A comprehensive continuum model of solid tumor evolution and development is investigated in detail numerically, both under the assumption of spherical symmetry and for arbitrary two-dimensional growth. The level set approach is used to obtain solutions for a recently developed multi-cell transport model formulated as a moving boundary problem for the evolution of the tumor. The model represents both the avascular and the vascular phase of growth, and is able to simulate when the transition occurs; progressive formation of a necrotic core and a rim structure in the tumor during the avascular phase are also captured. In terms of transport processes, the interaction of the tumor with the surrounding tissue is realistically incorporated. The two-dimensional simulation results are presented for different initial configurations. The computational framework, based on a Cartesian mesh/narrow band level-set method, can be applied to similar models that require the solution of coupled advection-diffusion equations with a moving boundary inside a fixed domain. The solution algorithm is designed so that extension to three-dimensional simulations is straightforward.

Algorithms↗
PubMed1989

Migration equilibrium and variational inequalities.

"In this paper, an equilibrium model of human migration is presented which can handle many classes of migrants and locations, in addition to equalities and inequalities. The equilibrium conditions are stated and then formulated as a variational inequality problem. Qualitative properties and computational aspects are briefly discussed."

Demography↗