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 73 records · Page 4Linked to original sources

PubMed1978

Analysis of the penetrable space within the nucleus.

Radioactive glycogen molecules have been used as passive probes to compare cavity systems within nuclei and isolated chromatin. Isolated chromatin was found to possess a narrow range of microspaces with mean effective diameters between 4.0 and 4.5 nm (40 and 45 A) depending on shape assumptions. Intact nuclei contained a far larger class of free spaces with average diameters in the order of 11.0-15.0 nm. This clearly shows that DNase-I (diam. 4.1 nm) can penetrate and occupy a large proportion of nuclear space even though this enzyme does not readily attack the undisturbed nuclear structure. A structure which simulated the pattern of penetrability and incorporated other known properties of chromatin was used to explain this DNase-I resistance of intact nuclei in terms of an ordered, compact, local structure interspersed by much larger spaces. A system for this local packing is suggested and the functional implications of this type of organization considered.

Animals↗

PubMed2026

In silico identification of DNMT1 inhibitors from the PlantCyc database through computational approach to assess the anti-cancer potential of nutraceutical compounds in breast cancer.

Breast cancer accounts for a disproportionate share of global cancer-related deaths, with 670,000 fatalities and 2.3 million new diagnoses recorded in women during 2022 alone. Existing treatment modalities carry considerable toxicity burdens, and resistance to available agents remains an unresolved clinical problem. DNA methyltransferase 1 (DNMT1), the enzyme chiefly responsible for maintaining genome-wide methylation patterns during DNA replication, has been mapped out as a high-value target in breast cancer because its dysregulation silences tumour suppressor genes through promoter hypermethylation. The present work involves hierarchical in silico workflow to screen 4549 plant-derived compounds from the PlantCyc database (v16.0.3) against the human DNMT1 catalytic domain (PDB ID: 4WXX). Ten top-scoring compounds were taken forward for molecular docking via AutoDock Vina; Quercetin and Kaempferol both recorded the highest binding affinities at -9.5 kcal/mol, Wogonin (-9.3 kcal/mol) and Xanthohumol (-8.1 kcal/mol) also emerged as strong binders. Pharmacokinetic evaluation using ADMET-AI confirmed that all 10 compounds met Lipinski's rule of five, with human intestinal absorption values at or above 0.98. Wogonin and Xanthohumol were selected for a 100 ns all-atom molecular dynamics (MD) simulation in GROMACS due to their well-rounded ADMET profiles and limited existing data on their specific interactions with DNMT1 in breast cancer. Across all measured trajectory metrics, backbone RMSD, residue fluctuation, radius of gyration, solvent-accessible surface area, and intermolecular hydrogen bond count, Wogonin formed a more stable, compact complex. These findings suggest that Wogonin and Xanthohumol are non-toxic nutraceutical candidates suitable for DNMT1 targeted epigenetic therapy, with computational foundation strong enough to facilitate future in vitro and in vivo validation work.

Humans↗

PubMed1992

PETSIM: Monte Carlo simulation of all sensitivity and resolution parameters of cylindrical positron imaging systems.

Monte Carlo simulation techniques are applied to track the annihilation photons from positron decay, and store the photon histories. Reasonably realistic models of the isotope distribution in the brain and heart during typical PET studies, as well as the traditional phantoms used for measuring PET scanner performance can be built out of up to 10 hollow or solid cylinders. Separate programs model the source distribution and its attenuation characteristics, the collimators and the detectors. These modules are connected by compact gamma history files which are stored on disc or tape. Over 50 million gamma ray histories can be saved on a 1 Gbyte disc, representing the decay of several billion atoms. This allows for good precision even for single thin slices in scanners with wide axial acceptance. The simulation results include spectrum analysis, sensitivity to true coincident events, scattered coincident and single rays, and the effects on these parameters of detector dead time. The storage of intermediate results on tape reduces simulation time, since most common source geometries need be generated only once. The sensitivities in multi-slice systems are presented as matrices of coincident crystal planes. The matrix shows the true count sensitivity and the scatter fraction together for each valid combination of planes. This presentation is very useful for assessing the effects of various degrees of inter-plane collimation. The spatial resolution analysis includes the effects of positron range, non-collinearity of the gamma rays, multiple interaction within the detectors, and the effects of quantization into single crystals in multiple-crystal block detectors. Each of these effects can be turned on or off without repeating the simulation. Both in-plane and axial resolutions are calculated as a function of location of the positron-emitting nucleus and the angle of incidence of gamma rays on the crystals. Single crystals, blocks and crystals with depth of interaction encoding can be specified, as can the method of backprojection (planar, or 3D), so that the detector geometry can be optimized.

Computer Simulation↗

PubMed1991

[Obturation of curved canals: in vitro study of lateral compaction].

The instrumentation and filling of teeth with curved canals are always difficult, therefore, the current study indicates solutions to problems encountered while preparing curved canals. The gutta condensation techniques and their ability to seal curved canals are also discussed. This study uses endodontic simulators to show the incidence of protocols and instrumentation on the ability of the lateral condensation technique to fill curved canals. This study, also, evaluate the lateral condensation technique combined with the thermomechanical in filling curved canals.

Dental Cavity Preparation↗

PubMed1988

Evaluation of a typology of reading disability.

A typology of reading disability was derived from a cluster analysis of psychological and educational tests administered to 63 moderately to severely reading-disabled children and adolescents. The quality of the cluster solution was evaluated through the use of statistics designed to measure the degree to which the clusters were compact and well separated. The values of the evaluation statistics for the reading clusters were compared to the distribution of these statistics in a sample of 100 cluster solutions from comparable simulated data sets. The results of this comparison suggest that the derived reading-disability clusters represent true subtypes rather than a random partitioning of a homogeneous group of subjects. The commonalities among subjects in the same clusters appear to be such as to permit hypotheses about treatment based on cluster membership. The clusters included a language disorder with associated deficits in auditory memory and sound blending, an auditory processing disorder, a mixed auditory and visual processing disorder, and an auditory memory and visual processing disorder. This study did not find the "normal" and visual-perceptual subtypes reported in some other recent investigations.

Adolescent↗

PubMed1992

[Choice of respirators for anesthesia].

Criteria of quality of gases and vapours supply, ventilator, patient's circle circuit and monitoring devices are recalled to help the anesthetist to choose his anesthesia machine. Advantages of compact or modular apparatus are discussed. Four, now wellknown, anesthesia machines (modulus II+, Siemens 900 D+SAC985, Roche Kontron 4300 and Engstrom Elsa) were analysed in clinical controlled ventilation and in simulated spontaneous ventilation to study the imposed work of breathing. Results are discussed with regard to safety rules and to ergonomics, bearing in mind their respective prices. Comparison is made with an original "bisontin" prototype.

Anesthesia, Inhalation↗

PubMed1989

[Mechanical analysis of the denture bases using the photoelastic-coating method. 2. Upper complete denture bases under uniform bending moment load].

Deformation of the anterior teeth and palatal regions on upper complete dentures was investigated using the photoelastic coating method and strain gages. In this experiment, an uniform-moment bending load method was employed to simulate the occlusal situation, and the distribution of strain in epoxy resin, stainless swaged and Co-Cr alloy cast dentures were measured and analyzed. The 030-series reflection polariscope is compact and lightweight with its main components consisting of two polarizer/quarter-wave-plate assemblies attached to a common frame. The highest level of strain was seen in the anterior region of the palate and the low strain was observed in other regions. Differences in strain magnitude of the three dentures were not observed with test at the same point. But, when denture base materials with high flexural rigidity and bending strength were used on the palatal region of the denture base, strain was decreased in the anterior and other regions of the palate. Therefore, dentures using those materials could be effectively reinforced.

Dental Stress Analysis↗

PubMed1990

Comparison and testing of least-squares time domain inverse solutions in electrocardiography.

The use of several mathematical methods for estimating epicardial ECG potentials from arrays of body surface potentials has been reported in the literature; most of these methods are based on least-squares reconstruction principles and operate in the time-space domain. In this paper we introduce a general Bayesian maximum a posteriori (MAP) framework for time domain inverse solutions in the presence of noise. The two most popular previously applied least-squares methods, constrained (regularized) least-squares and low-rank approximation through the singular value decomposition, are placed in this framework, each of them requiring the a priori knowledge of a 'regularization parameter', which defines the degree of smoothing to be applied to the inversion. Results of simulations using these two methods are presented; they compare the ability of each method to reconstruct epicardial potentials. We used the geometric configuration of the torso and internal organs of an individual subject as reconstructed from CT scans. The accuracy of each method at each epicardial location was tested as a function of measurement noise, the size and shape of the subarray of torso sensors, and the regularization parameter. We paid particular attention to an assessment of the potential of these methods for clinical use by testing the effect of using compact, small-size subarrays of torso potentials while maintaining a high degree of resolution on the epicardium.

Algorithms↗

PubMed1985

Efficiency of lod scores for representing multiple locus linkage data.

The problem of compact, fully efficient representation of multilocus data has not yet been solved. Lod scores can be used to map multilocus data, but because of certain statistical problems, this method loses some information. However, simulation studies show that for distances less than 10 or 20 cMo, where there is little danger of huge overestimates of distance, the lod score method yields estimators just as good as maximum likelihood (ML). Since short distances are the most important, the lod method is quite efficient. Its main drawback is misrepresentation of the likelihood under wrong gene orders. This problem can be ameliorated with a single multipoint calculation under each order. Thus, representation of multipoint data with lod scores can be very practical.

Biometry↗

PubMed1989

Dendritic current flow in relay cells and interneurons of the cat's lateral geniculate nucleus.

We used a passive, steady-state cable model to simulate current flow within the dendritic arbors of relay cells and interneurons in the cat's lateral geniculate nucleus. In confirmation of our previous work on relay cells, we found them to be electronically compact; thus a postsynaptic potential generated anywhere in a relay cell's dendritic arbor spreads with relatively little attenuation throughout the arbor and to its soma. An interneuron is very different. Its arbor is much more extensive electronically with the result that a postsynaptic potential significantly affects only local areas of the dendritic arbor, and only inputs to proximal dendrites or to the soma will much affect the soma. Since much of the interneuron's synaptic output derives from dendritic terminals that are both presynaptic and postsynaptic, its dendritic arbor may contain many local circuits that perform neuronal computations independently of each other, and this processing might be invisible to the soma. Furthermore, these interneurons possess conventional axonal outputs, and these contact postsynaptic profiles that are quite different from the postsynaptic targets of the dendritic terminals. Presumably, the axonal output reflects the integrated computations performed on proximal synaptic inputs, and it uses conventional action potentials to convey this output. We suggest that the interneuron does double duty: its dendritic arbor is used for many independent local circuits that perform one set of neuronal computations, and its axonal output represents conventional neuronal integration of proximal synaptic inputs.

Animals↗

PubMed1983

Classroom use of personal computers in medical education: a practical approach.

Classroom lectures in medical schools have traditionally employed a blackboard and slides. We have developed a compact, durable, and relatively low-priced system for computer-assisted instruction which introduces audiovisual material in a random-access manner. When this system was used in the classroom to provide flexible, clinical simulations, it promoted a high level of audience-instructor interaction and facilitated problem-based learning. The system has been used successfully in lectures in our medical school, at other medical schools, at community hospitals and at national scientific meetings.

Computer-Assisted Instruction↗

PubMed2025

Molecular dynamics simulations reveal subtle consequences of H3K9 and H3K27 tri-methylation on chromatin constituents.

Epigenetic modifications of histone tails are key mechanisms of genome regulation. In particular, tri-methylation of lysines (K) 9 and K27 of the histone H3 tail is important for genome silencing. In this work, we explore, using all-atom molecular dynamics simulations, the effect of these two epigenetic marks on the structure and interactions of the H3 tail in several contexts: isolated tails, nucleosomes, chromatosomes, and stacked nucleosomes. Overall, we find that although the isolated tails do not show significant conformational changes upon methylation, a more flexible and extended H3 tail compared to the native tail results in the nucleosome systems, with K9 methylation effects more pronounced. This change could facilitate the interaction of the tail with protein readers like heterochromatin protein 1 or Polycomb group. We also observe that both methylations increase the interactions of the H3 tail with the linker DNA in the context of the chromatosome, producing a chromatosome with tighter linker DNA, which could favor chromatin compaction. For stacked nucleosomes mimicking i±2 zigzag interactions, methylation of either K9 or K27 reduces the interactions of one of the H3 tails with its parental nucleosome and increases its interactions with the nonparental nucleosome, which could also help compact the chromatin fiber. In the three nucleosome-containing systems, we observe an asymmetry between the two tails, especially in the chromatosome, where one tail extends to interact with the linker DNA. This asymmetry modulates the effect that methylation has on each tail. Thus, overall, methylations of K9 and K27 have a subtle but notable impact on the H3 tail structure and its interactions within the chromatin fiber. These results help explain how this epigenetic modification compacts chromatin fibers and promotes longer-range interactions; these changes also guide how to approximate these effects in coarse-grained chromatin models.

Histones↗

PubMed1990

Determination of the conformation of Lewis blood group oligosaccharides by simulation of two-dimensional nuclear Overhauser data.

Through control of both the nmr probe temperature and of the solvent viscosity, phase-sensitive two-dimensional 1H nuclear Overhauser data (NOESY) at 300 and 500 MHz are obtained with excellent signal-to-noise ratios for Lewis blood group penta- and hexasaccharides isolated from human milk. Relatively long mixing times are required to produce measurable NOE intensities in these oligosaccharides, which makes a full relaxation matrix analysis necessary. By measurements of selective T1 for a few isolated 1H resonances, it was possible to generate a simulation of the complete NOESY spectrum at arbitrary mixing time for comparison with the experimental data. From an exhaustive search of the conformational space, it was found that only a small range of glycosidic dihedral angles of the nonreducing terminal Lewis blood group determinant fragments of the milk oligosaccharides LNF-2 and LND-1 produce simulated spectra agreeing within experimental error to the data. Conformational energy calculations reveal that each of these conformations is also one of minimum energy. It is concluded that the Lewis(a) and Lewis(b) oligosaccharides adopt relatively compact rigid structures in solution, as shown by the observation of cross peaks between protons in nonadjacent residues. Like the blood group A and H oligosaccharides, there exists only a small dependence of the conformation for Lewis(a) and Lewis(b) oligosaccharides on solvent. The apparent lack of dependence of conformation of these oligosaccharides on DMSO in D2O suggests that modification of solvent viscosity with mixtures of DMSO:D2O may provide a useful general strategy of NOESY studies of oligosaccharides.

Carbohydrate Conformation↗

PubMed1989

A hexagonal orthogonal-oriented pyramid as a model of image representation in visual cortex.

Retinal ganglion cells represent the visual image with a spatial code, in which each cell conveys information about a small region in the image. In contrast, cells of primary visual cortex employ a hybrid space-frequency code in which each cell conveys information about a region that is local in space, spatial frequency, and orientation. Despite the presumable importance of this transformation, we lack any comprehensive notion of how it occurs. Here we describe a mathematical model for this transformation. The hexagonal orthogonal-oriented quadrature pyramid (HOP) transform, which operates on a hexagonal input lattice, employs basis functions that are orthogonal, self-similar, and localized in space, spatial frequency, orientation, and phase. The basis functions, which are generated from seven basic types through a recursive process, form an image code of the pyramid type. The seven basis functions, six bandpass and one low-pass, occupy a point and a hexagon of six nearest neighbors on a hexagonal sample lattice. The six bandpass basis functions consist of three with even symmetry, and three with odd symmetry. The three even kernels are rotations of 0, 60, and 120 degrees of a common kernel; likewise for the three odd kernels. At the lowest level, the inputs are image samples. At each higher level, the input lattice is provided by the low-pass coefficients computed at the previous level. At each level, the output is subsampled in such a way as to yield a new hexagonal lattice with a spacing square root 7 larger than the previous level, so that the number of coefficients is reduced by a factor of seven at each level. In the biological model, the input lattice is the retinal ganglion cell array. The resulting scheme provides a compact, efficient code of the image and generates receptive fields that resemble those of the primary visual cortex.

Computer Simulation↗

PubMed1992

Structure and dynamics of des-pentapeptide-insulin in solution: the molten-globule hypothesis.

Structures of insulin in different crystal forms exhibit significant local and nonlocal differences, including correlated displacement of elements of secondary structure. Here we describe the solution structure and dynamics of a monomeric insulin analogue, des-pentapeptide-(B26-B30)-insulin (DPI), as determined by two-dimensional NMR spectroscopy and distance geometry/restrained molecular dynamics (DG/RMD). Although the solution structure of DPI exhibits a general similarity to its crystal structure, individual DG/RMD structures in the NMR ensemble differ by rigid-body displacements of alpha-helices that span the range of different crystal forms. These results suggest that DPI exists as a partially folded state formed by coalescence of distinct alpha-helix-associated microdomains. The physical reality of this model is investigated by comparison of the observed two-dimensional nuclear Overhauser enhancement (NOE) spectroscopy (NOESY) spectrum with that predicted from crystal and DG/RMD structures. The observed NOESY spectrum contains fewer tertiary contacts than predicted by any single simulation, but it matches their shared features; such "ensemble correspondence" is likely to reflect the effect of protein dynamics on observed NOE intensities. We propose (i) that the folded state of DPI is analogous to that of a compact protein-folding intermediate rather than a conventional native state and (ii) that the molten state is the biologically active species. This proposal (the molten-globule hypothesis) leads to testable thermodynamic predictions and has general implications for protein design.

Calorimetry↗

PubMed1985

Systems model for pupil size effect. II. Feedback model.

The human pupillary control system has been the subject of interest to biologists and engineers as an example of a sensorimotor reflex which can be embedded in a control system paradigm. We present a nonlinear feedback model whose compact structure allows us to hypothesize possible physiological mechanisms which generate the proper behavior of the pupil system. The important pupil responses, including pupil size effect, asymmetry, and response the high-frequency stimuli, are defined. This model was simulated on a digital computer and comparisons to the paradigm experimental responses were performed, demonstrating a fit to each of the observed conditions. Improvements on previous models are discussed.

Feedback↗

PubMed1992

Molecular dynamics simulations of a monofucosylated biantennary glycan of the N-acetyllactosamine type: the human lactotransferrin glycan.

Molecular dynamics simulations were carried out to explore the conformational flexibility of the antennae of N-linked glycans. They were performed over 200 ps in vacuo on the complete disialylated monofucosylated biantennary glycan of the N-acetyllactosaminic type. Starting from a bird-conformation, the 3-D-structure evolved through 9 successive transitional states to a new, compact and energetically favorable conformation which had never been previously described. In this conformation, both antennae are organized in two coplanar loops rolled in a contrary direction and oriented perpendicularly to the plane of the di-N-acetyl chitobiose residue leading to a 'lobster conformation'. All the glycosidic linkages of the disialylated monofucosylated biantennary glycan, except the Fuc(alpha 1-6)GlcNAc(beta 1-), were modified by a phase transition. Particularly, the Man(beta 1-4) GlcNAc(beta 1-) linkage, which was previously described by NMR and X-ray diffraction as a rigid one, was involved in numerous conformational changes during 83 ps, even before the first transition phase. The freedom of mobility of the torsional angles of the Man(alpha 1-6)Man(beta 1-) linkage was limited, under these simulation conditions, to the angle psi which took three values: 30 degrees, 90 degrees and 180 degrees. Moreover, from 150 ps up to the end of the simulation, the value of the torsional angle omega of the NeuAc(alpha 2-6)Gal(beta 1-) linkage of the alpha-1,6-antenna continuously swung between 60 degrees and -60 degrees. Finally, we observed that the values of the torsional angles of the three linkages: NeuAc(alpha 2-6)Gal(beta 1-), Gal(beta 1-4)GlcNAc(beta 1-) and GlcNAc(beta 1-2)Man(beta 1-) of each of the two antennae were different, demonstrating their asymmetric conformation.

Amino Sugars↗

PubMed1992

Supercoiled DNA energetics and dynamics by computer simulation.

A new formulation is presented for investigating supercoiled DNA configurations by deterministic techniques. Thus far, the computational difficulties involved in applying deterministic methods to supercoiled DNA studies have generally limited computer simulations to stochastic approaches. While stochastic methods, such as simulated annealing and Metropolis-Monte Carlo sampling, are successful at generating a large number of configurations and estimating thermodynamic properties of topoisomer ensembles, deterministic methods offer an accurate characterization of the minima and a systematic following of their dynamics. To make this feasible, we model circular duplex DNA compactly by a B-spline ribbon-like model in terms of a small number of control vertices. We associate an elastic deformation energy composed of bending and twisting integrals and represent intrachain contact by a 6-12 Lennard Jones potential. The latter is parameterized to yield an energy minimum at the observed DNA-helix diameter inclusive of a hydration shell. A penalty term to ensure fixed contour length is also included. First and second partial derivatives of the energy function have been derived by using various mathematical simplifications. First derivatives are essential for Newton-type minimization as well as molecular dynamics, and partial second-derivative information can significantly accelerate minimization convergence through preconditioning. Here we apply a new large-scale truncated-Newton algorithm for minimization and a Langevin/implicit-Euler scheme for molecular dynamics. Our truncated-Newton method exploits the separability of potential energy functions into terms of differing complexity. It relies on a preconditioned conjugate gradient method that is efficient for large-scale problems to solve approximately for the search direction at every step. Our dynamics algorithm is numerically stable over large time steps. It also introduces a frequency-discriminating mechanism so that vibrational modes with frequencies greater than a chosen cutoff frequency are essentially frozen by the method. With these tools, we rapidly identify corresponding circular and interwound energy minima for small DNA rings for a series of imposed linking-number differences. These structures are consistent with available electron microscopy data. The energetic exchange of stability between the circle and the figure-8, in very good agreement with analytical results, is also detailed. Molecular dynamics trajectories at 100 femtosecond time steps then reveal the rapid folding of the unstable circular state into supercoiled forms. Significant bending and twisting motions of the interwound structures are also observed. Such information may be useful for understanding transition states along the folding pathway and the role of enzymes that regulate supercoiling.(ABSTRACT TRUNCATED AT 400 WORDS)

Algorithms↗