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At least 577 records · Page 32Linked to original sources

Artefacts in multi-echo T2 imaging for high-precision gel dosimetry: III. Effects of temperature drift during scanning.

In high-precision 3D gel dosimetry, long MR measurement times together with a high amount of RF energy being absorbed by the phantom are very common, and result in a spatially dependent temperature rise in the gel. As T2 of the dosimeter gel is temperature dependent, dose estimation will be affected. In this study we assess the temperature rise in the dosimeter gel by use of MR temperature mapping and computer modelling. It is shown that in conventional MR sequences. where linear k-space sampling is used, a temperature rise of 3 C results in a dose underestimation of 10% over the whole dose map. To correct for these dose errors, a compensation method involving centric k-space ordering is suggested. Computer simulations have been performed to analyse the robustness of the proposed method. Applying the compensated sequence, a temperature rise of 3 C leads to a narrow dose artefact of the order of 3% for a 'worst case' situation in which a single pixel dose gradient is assumed. Negligible deviations are found in the rest of the dose map.

Acrylamide↗

Hydrodynamic shear stimulates osteocalcin expression but not proliferation of bone marrow stromal cells.

Bone marrow stromal cells (BMSCs) are a promising component for engineered bone tissues, but in vitro formation of a bonelike tissue requires culture conditions that direct these multipotent cells toward osteoblastic maturation. Fluid flow has been postulated to stimulate bone tissue development in vivo, but the effect of shear stress on proliferation and differentiation of osteoprogenitor cell cultures in vitro has not been examined closely. In this study BMSCs were cultured on fibronectin-coated substrates and exposed intermittently (for 30 min 3, 5, 7, 9, 11, and 13 days after seeding) to a spatially dependent range of shear stresses (0.36 to 2.7 dyn/cm(2)) using a radial-flow chamber. After 7 days cell density did not vary between sheared and control cell layers. In contrast, after 21 days the accumulation of osteocalcin protein (OC) in cell layers was increased significantly relative to static controls, while the quantity of multilayer cell aggregates (i.e., bone nodules) was diminished. Neither of these effects varied systematically with shear magnitude. Finally, pretreatment of cultures with the cyclooxygenase (COX)-2-specific inhibitor NS-398 blocked prostaglandin secretion in response to shearing flow and significantly reduced OC accumulation in cell layers. These results provide evidence that flow stimulates osteoblastic maturation but not proliferation of bone marrow stromal cells and that prostaglandin signaling is involved in this effect.

Animals↗

CURVATURE: software for the analysis of curved DNA.

Software is presented to plot the sequence-dependent spatial trajectory of the DNA double helix and/or distribution of curvature along the DNA molecule. The nearest-neighbor wedge model is implemented to calculate overall DNA path using local helix parameters: helix twist angle, wedge (deflection) angle and direction (of deflection) angle. The procedures described proved to be very convenient as tools for investigation of a relationship between overall DNA curvature and its gel electrophoretic mobility. All parameters of the model had been estimated from experimental data. Using these wedge parameters the program takes, as input, any DNA sequence and calculates the likely degree of curvature at each point along the molecule. This information is displayed both graphically and in the form of simplified representations of curved double helices. The Software, CURVATURE, can thus be used to investigate possible roles of curvature in modulation of gene expression and for location of curved portions of DNA, which may play an important role in sequence-specific protein--DNA interactions.

Algorithms↗

Detection of cell-type-specific differentially methylated regions in epigenome-wide association studies.

MOTIVATION: DNA methylation at cytosine-phosphate-guanine (CpG) sites is one of the most important epigenetic markers. Therefore, epidemiologists are interested in investigating DNA methylation in large cohorts through epigenome-wide association studies (EWAS). However, the observed EWAS data are bulk data with signals aggregated from distinct cell types. Deconvolution of cell-type-specific signals from EWAS data is challenging because phenotypes can affect both cell-type proportions and cell-type-specific methylation levels. Recently, there has been active research on detecting cell-type-specific risk CpG sites for EWAS data. However, existing methods all assume that the methylation levels of different CpG sites are independent and perform association detection for each CpG site separately. Although these methods significantly improve the detection at the aggregated-level-identifying a CpG site as a risk CpG site as long as it is associated with the phenotype in any cell type, they have low power in detecting cell-type-specific associations for EWAS with typical sample sizes. RESULTS: Here, we develop a new method, Fine-scale inference for Differentially Methylated Regions (FineDMR), to borrow strengths of nearby CpG sites to improve the cell-type-specific association detection. Via a Bayesian hierarchical model built upon Gaussian process functional regression, FineDMR takes advantage of the spatial dependencies between CpG sites. FineDMR can provide cell-type-specific association detection as well as output subject-specific and cell-type-specific methylation profiles for each subject. Simulation studies and real data analysis show that FineDMR substantially improves the power in detecting cell-type-specific associations for EWAS data. AVAILABILITY AND IMPLEMENTATION: FineDMR is freely available at https://github.com/JiaRuofan/Detection-of-Cell-type-specific-DMRs-in-EWAS.

DNA Methylation↗

Detection of DNA copy number alterations using penalized least squares regression.

MOTIVATION: Genomic DNA copy number alterations are characteristic of many human diseases including cancer. Various techniques and platforms have been proposed to allow researchers to partition the whole genome into segments where copy numbers change between contiguous segments, and subsequently to quantify DNA copy number alterations. In this paper, we incorporate the spatial dependence of DNA copy number data into a regression model and formalize the detection of DNA copy number alterations as a penalized least squares regression problem. In addition, we use a stationary bootstrap approach to estimate the statistical significance and false discovery rate. RESULTS: The proposed method is studied by simulations and illustrated by an application to an extensively analyzed dataset in the literature. The results show that the proposed method can correctly detect the numbers and locations of the true breakpoints while appropriately controlling the false positives. AVAILABILITY: http://bioinformatics.med.yale.edu/DNACopyNumber CONTACT: hongyu.zhao@yale.edu SUPPLEMENTARY INFORMATION: http://bioinformatics.med.yale.edu/DNACopyNumber.

Algorithms↗

A spatial statistical approach to malaria mapping.

BACKGROUND: Good maps of malaria risk have long been recognized as an important tool for malaria control. The production of such maps relies on modelling to predict the risk for most of the map, with actual observations of malaria prevalence usually only known at a limited number of specific locations. Estimation is complicated by the fact that there is often local variation of risk that cannot be accounted for by the known covariates and because data points of measured malaria prevalence are not evenly or randomly spread across the area to be mapped. METHOD: We describe, by way of an example, a simple two-stage procedure for producing maps of predicted risk: we use logistic regression modelling to determine approximate risk on a larger scale and we employ geo-statistical ('kriging') approaches to improve prediction at a local level. Malaria prevalence in children under 10 was modelled using climatic, population and topographic variables as potential predictors. After the regression analysis, spatial dependence of the model residuals was investigated. Kriging on the residuals was used to model local variation in malaria risk over and above that which is predicted by the regression model. RESULTS: The method is illustrated by a map showing the improvement of risk prediction brought about by the second stage. The advantages and shortcomings of this approach are discussed in the context of the need for further development of methodology and software.

Child↗

Interleukin-6: a cytokine to forget.

It is known that proinflammatory cytokines such as interleukin-6 (IL-6) are expressed in the central nervous system (CNS) during disease conditions and affect several brain functions including memory and learning. In contrast to these effects observed during pathological conditions, here we describe a physiological function of IL-6 in the "healthy" brain in synaptic plasticity and memory consolidation. During long-term potentiation (LTP) in vitro and in freely moving rats, IL-6 gene expression in the hippocampus was substantially increased. This increase was long lasting, specific to potentiation, and was prevented by inhibition of N-methyl-D-aspartate receptors with (+/-)-2-amino-5-phosphonopentanoic acid (AP-5). Blockade of endogenous IL-6 by application of a neutralizing anti-IL-6 antibody 90 min after tetanus caused a remarkable prolongation of LTP. Consistently, blockade of endogenous IL-6, 90 min after hippocampus-dependent spatial alternation learning resulted in a significant improvement of long-term memory. In view of the suggested role of LTP in memory formation, these data implicate IL-6 in the mechanisms controlling the kinetics and amount of information storage.

Animals↗

Sources of error in lung densitometry with CT.

RATIONALE AND OBJECTIVES: To determine and analyze the most important error sources in lung CT densitometry in vivo. METHODS: The authors examined the influences of CT acquisition errors, physiologic changes, and image segmentation errors on lung densitometry. Among others, spatial dependency and long-term reproducibility of the density measurements of blood and air were examined over a period of 4 years in a group of 28 patients with pulmonary emphysema. These results were related to the measured lung densities in this group. RESULTS: The density measurement of blood and air is strongly dependent on the position in the thorax. Despite full-scanner calibrations, x-ray tube replacement can induce a significant increase in measured blood density. CONCLUSIONS: A change in a lung density parameter over time can actually be the result of tube replacement or changing blood density. A simple postprocessing technique can correct for these changes.

Absorptiometry, Photon↗

Saline-enhanced radiofrequency ablation of breast tissue: an in vitro feasibility study.

RATIONALE AND OBJECTIVES: The feasibility of radiofrequency (RF) ablation for the treatment of breast tumors was investigated in vitro. The best parameters for ablation of breast tissue were chosen. METHODS: Saline-enhanced RF ablation was performed in human breast tissue specimens and cow udder tissue. Temperature profiles were measured depending on RF power (20, 28, 36 W) and NaCl infusion rate (15, 30, 60 mL/h) using eight thermocouples. Lesion development was monitored by ultrasound. Thermolysis efficiency was measured by tissue weight determinations before and after ablation. RESULTS: After RF ablation of tissue samples, 73.6% turned into a fat/saline emulsion. Ultrasound monitoring showed a cone-shaped hyperechoic area during the first 2 minutes of RF ablation, followed by an irregular expansion of the area. Time-dependent spatial temperature curves were more homogeneous at low infusion rates (15 mL/h). Peak temperatures up to 160 degrees C were measured. CONCLUSIONS: Controlled RF ablation of breast tissue is feasible. The irregular expansion of RF lesions in fatty breast tissue is due to liquefied fat. Low saline interstitial infusion rates result in better control of lesioning.

Animals↗

Chaotic advection in compressible helical flow.

Compressible helical flow with div v not equal to 0 drastically increases the area of chaotic dynamics and mixing properties when the helicity parameter is spatially dependent. We show that the density dependence on the z coordinate can be incorporated in new variables in a way that leads to a Hamiltonian formulation of the system. This permits the application of various important results like the Kolmogorov-Arnold-Moser theory and, particularly, an understanding of why and in which sense the compressible helical flow is "more chaotic" than the incompressible one. Simulation demonstrates this property for an analog of the ABC flow. An interesting type of the dynamical system with "dense" island chains is described.

Journal Article↗

Model for spatial microtubule oscillations.

Under particular in vitro conditions, oscillating spatial and temporal waves of assembled microtubules can be observed. A reaction-diffusion model is presented to reproduce these results. This model is based on a set of chemical reaction equations and extended to include spatial dependence and diffusion. The basic properties of the model are presented and the results are demonstrated to connect the observable waves with turbidimetric measurements. The results of the model are consistent with experimental findings.

Animals↗

Magnetic-field-induced periodic deformations in planar nematic layers.

Periodic deformations of strongly anchored planar nematic layers subjected to magnetic fields were studied numerically. Two magnetic-field configurations, giving rise to the so-called periodic splay-twist and periodic twist-splay patterns, were taken into account. The stationary director distribution was calculated for various values of elastic anisotropy and magnetic-field strength. Some alternative conclusions that shed light on the properties of the periodic deformations were drawn: (i) the transition from the periodically deformed structure to the homogeneously deformed one, which occurs in high field, is due to the divergence of the spatial period of the deformations to infinity; (ii) the spatial dependence of the angles determining the high-field director distribution strongly deviates from the theoretically predicted functions of sinusoidal form. The diagrams showing the ranges of parameters, for which the periodic deformations can realize, were built. The stable wave-number bands were determined numerically.

Journal Article↗

Influence of ions on the "V-shaped" electro-optic response of ferroelectric liquid crystals.

It has recently been shown that in surface-stabilized ferroelectric liquid crystal cells with high spontaneous polarization, the polarization charge self-interaction leads to a "V-shaped" optical response to an applied voltage. The presence of ionic free charges in the liquid crystal changes the internal electric field, and therefore also the spatial dependence of the polarization and optic axis orientation. We have numerically solved the nonlinear ion diffusion equation in the electric field due to external voltage, spontaneous polarization, and ions, and calculated the electro-optic response to a triangular applied voltage. When the period of the driving voltage is smaller than the zero-field diffusion time of the ions across the cell, and larger than the ion transit time in the applied field, an inverse hysteresis in the electro-optic response is obtained. At these time scales ions also cause characteristic changes in the shape of the electro-optic response.

Journal Article↗

Higher-order transverse modes of ultrashort isodiffracting pulses.

We present a family of space-time nonseparable analytic solutions describing spatiotemporal dynamics of isodiffracting single-cycle and few-cycle pulses with Hermite-Gaussian and Laguerre-Gaussian transverse profiles. These solutions are space-time localized wave packets propagating in free space. The transverse field profile acts as a spatially dependent filter, modifying the pulse spectrum and removing certain frequencies. The consequences of those effects in the time domain are the distortions of pulse envelope and temporal wave form and the creation of "dark pulses" at certain transverse positions. In addition, due to the space-time coupling, the instantaneous transverse field pattern changes inside the pulse, as well as with propagation distance. These higher-order mode solutions can be used to analyze reflected or scattered terahertz pulses, and to understand the wave-form distortions of terahertz signals in applications. They are also capable of modeling pulsed fields of phase locking of both transverse and longitudinal modes in total mode-locked lasers.

Journal Article↗

Orientational transitions in a nematic liquid crystal confined by competing surfaces.

The effect of confinement on the orientational structure of a nematic liquid crystal model has been investigated by using a version of density-functional theory. We have focused on the case of a nematic confined by opposing flat surfaces, in slab geometry (slit pore), which favor planar molecular alignment (parallel to the surface) and homeotropic alignment (perpendicular to the surface), respectively. The spatial dependence of the tilt angle of the director with respect to the surface normal has been studied, as well as the tensorial order parameter describing the molecular order around the director. For a pore of given width, we find that, for weak surface fields, the alignment of the nematic director is perpendicular to the surface in a region next to the surface favoring homeotropic alignment, and parallel along the rest of the pore, with a sharp interface separating these regions (S phase). For strong surface fields, the director is distorted uniformly, the tilt angle exhibiting a linear dependence on the distance normal to the surface (L phase). Our calculations reveal the existence of a first-order transition between the two director configurations, which is driven by changes in the surface field strength, and also by changes in the pore width. In the latter case the transition occurs, for a given surface field, between the S phase for narrow pores and the L phase for wider pores. A link between the L-S transition and the anchoring transition observed for the semi-infinite case is proposed.

Journal Article↗

Boltzmann equation description of electron transport in an electric field with cylindrical or spherical symmetry.

The spatially dependent description of the electron kinetics in nonuniform electric fields is of primary importance for the modeling of gas-filled proportional counters and other plasma devices. For a typical example, the amplification of the gain signal in the gas counters is determined by the behavior of electron ionization processes in the cylindrically or spherically symmetric electric field around thin wire or tiny sphere anode. In this paper, the general formalism of the Boltzmann equation in these types of the nonuniform electric fields is presented for specifying the electron swarm dynamics affected by the field geometry. The behavior of electrons in the cylindrical or spherical field configuration is investigated by a Monte Carlo technique to exemplify the description, and the effects associated with the angular momentum of electrons are discussed in terms of the ionization coefficient.

Journal Article↗

Stretched exponential relaxation in a diffusive lattice model.

We studied the single dimer dynamics in a lattice diffusive model as a function of particle density in the high densification regime. The mean square displacement is found to be subdiffusive both in one and two dimensions. The spatial dependence of the self-part of the van Hove correlation function displays as a function of r a single peak and signals a dramatic slow down of the system for high density. The self-intermediate scattering function is fitted to the Kohlrausch-Williams-Watts law. The exponent beta extracted from the fits is density independent while the relaxation time tau follows a scaling law with an exponent 2.5.

Journal Article↗

Pinning stationary planar fronts in diffusion-convection-reaction systems.

This paper considers various strategies for controlling a stationary planar front solution, in a rectangular domain with a diffusion-reaction distributed system, by pinning the solution to one or few points and using actuators with the simplest possible spatial dependence. We review previous results obtained for one-dimensional diffusion-reaction (with or without convection) systems, for which we applied two approaches: an approximate model reduction to a form that follows the front position while approximating the front velocity, and linear stability analysis. We apply the same two approaches for the planar fronts. The approximate model reduction allows us to analyze qualitatively various control strategies and to predict the critical width below which the control mode of the one-dimensional system is sufficient. These results are corroborated by linear analysis of a truncated model with the spectral methods representation, using concepts of finite and infinite zeros of linear multidimensional systems.

Journal Article↗