Self-organizing magnetic beads for biomedical applications

In the field of biomedicine magnetic beads are used for drug delivery and to treat hyperthermia. Here we propose to use self-organized bead structures to isolate circulating tumor cells using lab-on-chip technologies. Typically blood flows past microposts functionalized with antibodies for circulating tumor cells. Creating these microposts with interacting magnetic beads makes it possible to tune the geometry in size, position and shape. We developed a simulation tool that combines micromagnetics and discrete particle dynamics, in order to design micropost arrays made of interacting beads. The simulation takes into account the viscous drag of the blood flow, magnetostatic interactions between the magnetic beads and gradient forces from external aligned magnets. We developed a particle-particle particle-mesh method for effective computation of the magnetic force and torque acting on the particles

A unique regulatory phase of DNA methylation in the early mammalian embryo

Summary DNA methylation is highly dynamic during mammalian embryogenesis. It is broadly accepted that the paternal genome is actively depleted of 5-methyl cytosine at fertilization, followed by passive loss that reaches a minimum at the blastocyst stage. However, this model is based on limited data, and to date no base-resolution maps exist to support and refine it. Here, we generated genome-scale DNA methylation maps in mouse gametes and through post-implantation embryogenesis. We find that the oocyte already exhibits global hypomethylation, most prominently at specific families of long interspersed element-1 and long terminal repeat retro-elements, which are disparate between gametes and resolve to lower methylation values in zygote. Surprisingly, the oocyte contributes a unique set of Differentially Methylated Regions (DMRs), including many CpG Island promoter regions, that are maintained in the early embryo but are lost upon specification and absent from somatic cells. In contrast, sperm-contributed DMRs are largely intergenic and resolve to hypermethylation after the blastocyst stage. Our data provide a complete genome-scale, base-resolution timeline of DNA methylation in the pre-specified embryo, when this epigenetic modification is most dynamic, before returning to the canonical somatic pattern.Stem Cell and Regenerative Biolog

A unique regulatory phase of DNA methylation in the early mammalian embryo

DNA methylation is highly dynamic during mammalian embryogenesis. It is broadly accepted that the paternal genome is actively depleted of 5-methylcytosine at fertilization, followed by passive loss that reaches a minimum at the blastocyst stage. However, this model is based on limited data, and so far no base-resolution maps exist to support and refine it. Here we generate genome-scale DNA methylation maps in mouse gametes and from the zygote through post-implantation. We find that the oocyte already exhibits global hypomethylation, particularly at specific families of long interspersed element 1 and long terminal repeat retroelements, which are disparately methylated between gametes and have lower methylation values in the zygote than in sperm. Surprisingly, the oocyte contributes a unique set of differentially methylated regions (DMRs)—including many CpG island promoters—that are maintained in the early embryo but are lost upon specification and absent from somatic cells. In contrast, sperm-contributed DMRs are largely intergenic and become hypermethylated after the blastocyst stage. Our data provide a genome-scale, base-resolution timeline of DNA methylation in the pre-specified embryo, when this epigenetic modification is most dynamic, before returning to the canonical somatic pattern.Burroughs Wellcome (Career Award)National Institutes of Health (U.S.) (5RC1AA019317)National Institutes of Health (U.S.) (U01ES017155)National Institutes of Health (U.S.) (P01GM099117)National Human Genome Research Institute (U.S.) (1P50HG006193-01

Frequency drift in MR spectroscopy at 3T

Purpose Heating of gradient coils and passive shim components is a common cause of instability in the B0 field, especially when gradient intensive sequences are used. The aim of the study was to set a benchmark for typical drift encountered during MR spectroscopy (MRS) to assess the need for real-time field-frequency locking on MRI scanners by comparing field drift data from a large number of sites. Method A standardized protocol was developed for 80 participating sites using 99 3T MR scanners from 3 major vendors. Phantom water signals were acquired before and after an EPI sequence. The protocol consisted of: minimal preparatory imaging; a short pre-fMRI PRESS; a ten-minute fMRI acquisition; and a long post-fMRI PRESS acquisition. Both pre- and post-fMRI PRESS were non-water suppressed. Real-time frequency stabilization/adjustment was switched off when appropriate. Sixty scanners repeated the protocol for a second dataset. In addition, a three-hour post-fMRI MRS acquisition was performed at one site to observe change of gradient temperature and drift rate. Spectral analysis was performed using MATLAB. Frequency drift in pre-fMRI PRESS data were compared with the first 5:20 minutes and the full 30:00 minutes of data after fMRI. Median (interquartile range) drifts were measured and showed in violin plot. Paired t-tests were performed to compare frequency drift pre- and post-fMRI. A simulated in vivo spectrum was generated using FID-A to visualize the effect of the observed frequency drifts. The simulated spectrum was convolved with the frequency trace for the most extreme cases. Impacts of frequency drifts on NAA and GABA were also simulated as a function of linear drift. Data from the repeated protocol were compared with the corresponding first dataset using Pearson's and intraclass correlation coefficients (ICC). Results Of the data collected from 99 scanners, 4 were excluded due to various reasons. Thus, data from 95 scanners were ultimately analyzed. For the first 5:20 min (64 transients), median (interquartile range) drift was 0.44 (1.29) Hz before fMRI and 0.83 (1.29) Hz after. This increased to 3.15 (4.02) Hz for the full 30 min (360 transients) run. Average drift rates were 0.29 Hz/min before fMRI and 0.43 Hz/min after. Paired t-tests indicated that drift increased after fMRI, as expected (p < 0.05). Simulated spectra convolved with the frequency drift showed that the intensity of the NAA singlet was reduced by up to 26%, 44 % and 18% for GE, Philips and Siemens scanners after fMRI, respectively. ICCs indicated good agreement between datasets acquired on separate days. The single site long acquisition showed drift rate was reduced to 0.03 Hz/min approximately three hours after fMRI. Discussion This study analyzed frequency drift data from 95 3T MRI scanners. Median levels of drift were relatively low (5-min average under 1 Hz), but the most extreme cases suffered from higher levels of drift. The extent of drift varied across scanners which both linear and nonlinear drifts were observed.publishedVersio

The role of E1-E2 interplay in multiphonon Coulomb excitation

In this work we study the problem of a charged particle, bound in a harmonic-oscillator potential, being excited by the Coulomb field from a fast charged projectile. Based on a classical solution to the problem and using the squeezed-state formalism we are able to treat exactly both dipole and quadrupole Coulomb field components. Addressing various transition amplitudes and processes of multiphonon excitation we study different aspects resulting from the interplay between E1 and E2 fields, ranging from classical dynamic polarization effects to questions of quantum interference. We compare exact calculations with approximate methods. Results of this work and the formalism we present can be useful in studies of nuclear reaction physics and in atomic stopping theory.Comment: 10 pages, 6 figure

Counteridenticals

A counteridentical is a counterfactual with an identity statement in the antecedent. While counteridenticals generally seem non-trivial, most semantic theories for counterfactuals, when combined with the necessity of identity and distinctness, attribute vacuous truth conditions to such counterfactuals. In light of this, one could try to save the orthodox theories either by appealing to pragmatics or by denying that the antecedents of alleged counteridenticals really contain identity claims. Or one could reject the orthodox theory of counterfactuals in favor of a hyperintensional semantics that accommodates non-trivial counterpossibles. In this paper, I argue that none of these approaches can account for all the peculiar features of counteridenticals. Instead, I propose a modified version of Lewis’s counterpart theory, which rejects the necessity of identity, and show that it can explain all the peculiar features of counteridenticals in a satisfactory way. I conclude by defending the plausibility of contingent identity from objections