821 research outputs found

    Approaches for modeling magnetic nanoparticle dynamics

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    Magnetic nanoparticles are useful biological probes as well as therapeutic agents. There have been several approaches used to model nanoparticle magnetization dynamics for both Brownian as well as N\'eel rotation. The magnetizations are often of interest and can be compared with experimental results. Here we summarize these approaches including the Stoner-Wohlfarth approach, and stochastic approaches including thermal fluctuations. Non-equilibrium related temperature effects can be described by a distribution function approach (Fokker-Planck equation) or a stochastic differential equation (Langevin equation). Approximate models in several regimes can be derived from these general approaches to simplify implementation

    Generalized Scaling and the Master Variable for Brownian Magnetic Nanoparticle Dynamics

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    Understanding the dynamics of magnetic particles can help to advance several biomedical nanotechnologies. Previously, scaling relationships have been used in magnetic spectroscopy of nanoparticle Brownian motion (MSB) to measure biologically relevant properties (e.g., temperature, viscosity, bound state) surrounding nanoparticles in vivo. Those scaling relationships can be generalized with the introduction of a master variable found from non-dimensionalizing the dynamical Langevin equation. The variable encapsulates the dynamical variables of the surroundings and additionally includes the particles’ size distribution and moment and the applied field’s amplitude and frequency. From an applied perspective, the master variable allows tuning to an optimal MSB biosensing sensitivity range by manipulating both frequency and field amplitude. Calculation of magnetization harmonics in an oscillating applied field is also possible with an approximate closed-form solution in terms of the master variable and a single free parameter

    Brief of Genformatic LLC as Amicus Curiae in Support of Petitioners

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    Amicus ("friend of the court") brief written by Genformatic, LLC in support of petitioners in AMP v. Myriad Genetics (Supreme Court Case Docket No. 12-398)

    Empirical Validation of a New Data Product from the Interstellar Boundary Explorer Satellite

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    Since 2008, the Interstellar Boundary Explorer (IBEX) satellite has been gathering data on heliospheric energetic neutral atoms (ENAs) while being exposed to various sources of background noise, such as cosmic rays and solar energetic particles. The IBEX mission initially released only a qualified triple-coincidence (qABC) data product, which was designed to provide observations of ENAs free of background contamination. Further measurements revealed that the qABC data was in fact susceptible to contamination, having relatively low ENA counts and high background rates. Recently, the mission team considered releasing a certain qualified double-coincidence (qBC) data product, which has roughly twice the detection rate of the qABC data product. This paper presents a simulation-based validation of the new qBC data product against the already-released qABC data product. The results show that the qBCs can plausibly be said to share the same signal rate as the qABCs up to an average absolute deviation of 3.6%. Visual diagnostics at an orbit, map, and full mission level provide additional confirmation of signal rate coherence across data products. These approaches are generalizable to other scenarios in which one wishes to test whether multiple observations could plausibly be generated by some underlying shared signal

    The influence of increased passive stiffness of the trunk and hips on balance control during reactive stepping

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    The final publication is available at Elsevier via https://doi.org/10.1016/j.gaitpost.2019.05.018. © 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/Background Age-related changes, which include increased trunk and hip stiffness, negatively influence postural balance. While previous studies suggest no net-effect of trunk and hip stiffness on initial trip-recovery responses, no study to date has examined potential effects during the dynamic restabilisation phase following foot contact. Research question Does increased trunk and hip stiffness, in isolation from other ageing effects, negatively influence balance during the restabilisation phase of reactive stepping. Methods Balance perturbations were applied using a tether-release paradigm, which required participants to react with a single-forward step. Sixteen young adults completed two blocks of testing: a baseline and an increased stiffness (corset) condition. Whole-body kinematics were utilized to estimate spatial step parameters, center of mass (COM), COM incongruity (peak - final position) and time to restabilisation, in anteroposterior (AP) and mediolateral (ML) directions. Results In the corset condition, peak COM displacement was increased in both directions (p  0.233). Increased passive stiffness also increased the magnitude and variability of peak shear ground reaction force, COM incongruity, and time to restabilisation in the ML (but not AP) direction (p < 0.027). Significance In contrast to previous literature, increased stiffness resulted in greater peak COM displacement in both directions. Our results suggest increased trunk and hip stiffness have detrimental effects on dynamic stability following a reactive step, particularly in the ML direction. Observed increases in magnitude and variability of COM incongruity suggest the likelihood of a sufficiently large loss of ML stability - requiring additional steps - was increased by stiffening of the hips and trunk. The current findings suggest interventions aiming to mobilize the trunk and hips, in conjunction with strengthening, could improve balance and reduce the risk of falls.This research was funded in part by grants from the Natural Sciences and Engineering Research Council of Canada (RGPIN-2015-03636), the Canadian Foundation for Innovation (Grant #25351) and the Ontario Ministry of Research and Innovation (Grant #25351 and ER14-10-236)

    Molecular Beams

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    Contains research objectives, summary of research and reports on eight research projects.Joint Services Electronics Programs (U. S. Army, U. S. Navy, and U. S. Air Force) under Contract DAAB07-71-C-030

    Multicellular Architecture of Malignant Breast Epithelia Influences Mechanics

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    Cell–matrix and cell–cell mechanosensing are important in many cellular processes, particularly for epithelial cells. A crucial question, which remains unexplored, is how the mechanical microenvironment is altered as a result of changes to multicellular tissue structure during cancer progression. In this study, we investigated the influence of the multicellular tissue architecture on mechanical properties of the epithelial component of the mammary acinus. Using creep compression tests on multicellular breast epithelial structures, we found that pre-malignant acini with no lumen (MCF10AT) were significantly stiffer than normal hollow acini (MCF10A) by 60%. This difference depended on structural changes in the pre-malignant acini, as neither single cells nor normal multicellular acini tested before lumen formation exhibited these differences. To understand these differences, we simulated the deformation of the acini with different multicellular architectures and calculated their mechanical properties; our results suggest that lumen filling alone can explain the experimentally observed stiffness increase. We also simulated a single contracting cell in different multicellular architectures and found that lumen filling led to a 20% increase in the “perceived stiffness” of a single contracting cell independent of any changes to matrix mechanics. Our results suggest that lumen filling in carcinogenesis alters the mechanical microenvironment in multicellular epithelial structures, a phenotype that may cause downstream disruptions to mechanosensing

    Variation in the Large-Scale Organization of Gene Expression Levels in the Hippocampus Relates to Stable Epigenetic Variability in Behavior

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    Despite sharing the same genes, identical twins demonstrate substantial variability in behavioral traits and in their risk for disease. Epigenetic factors-DNA and chromatin modifications that affect levels of gene expression without affecting the DNA sequence-are thought to be important in establishing this variability. Epigenetically-mediated differences in the levels of gene expression that are associated with individual variability traditionally are thought to occur only in a gene-specific manner. We challenge this idea by exploring the large-scale organizational patterns of gene expression in an epigenetic model of behavioral variability.To study the effects of epigenetic influences on behavioral variability, we examine gene expression in genetically identical mice. Using a novel approach to microarray analysis, we show that variability in the large-scale organization of gene expression levels, rather than differences in the expression levels of specific genes, is associated with individual differences in behavior. Specifically, increased activity in the open field is associated with increased variance of log-transformed measures of gene expression in the hippocampus, a brain region involved in open field activity. Early life experience that increases adult activity in the open field also similarly modifies the variance of gene expression levels. The same association of the variance of gene expression levels with behavioral variability is found with levels of gene expression in the hippocampus of genetically heterogeneous outbred populations of mice, suggesting that variation in the large-scale organization of gene expression levels may also be relevant to phenotypic differences in outbred populations such as humans. We find that the increased variance in gene expression levels is attributable to an increasing separation of several large, log-normally distributed families of gene expression levels. We also show that the presence of these multiple log-normal distributions of gene expression levels is a universal characteristic of gene expression in eurkaryotes. We use data from the MicroArray Quality Control Project (MAQC) to demonstrate that our method is robust and that it reliably detects biological differences in the large-scale organization of gene expression levels.Our results contrast with the traditional belief that epigenetic effects on gene expression occur only at the level of specific genes and suggest instead that the large-scale organization of gene expression levels provides important insights into the relationship of gene expression with behavioral variability. Understanding the epigenetic, genetic, and environmental factors that regulate the large-scale organization of gene expression levels, and how changes in this large-scale organization influences brain development and behavior will be a major future challenge in the field of behavioral genomics
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