A volume-preserving sharpening approach for the propagation of sharp phase boundaries in multiphase lattice Boltzmann simulations

Lattice Boltzmann models that recover a macroscopic description of multiphase flow of immiscible liquids typically represent the boundaries between phases using a scalar function, the phase field, that varies smoothly over several grid points. Attempts to tune the model parameters to minimise the thicknesses of these interfaces typically lead to the interfaces becoming fixed to the underlying grid instead of advecting with the fluid velocity. This phenomenon, known as lattice pinning, is strikingly similar to that associated with the numerical simulation of conservation laws coupled to stiff algebraic source terms. We present a lattice Boltzmann formulation of the model problem proposed by LeVeque and Yee [J. Comput. Phys. 86, 187] to study the latter phenomenon in the context of computational combustion, and offer a volume-conserving extension in multiple space dimensions. Inspired by the random projection method of Bao and Jin [J. Comput. Phys. 163, 216] we further generalise this formulation by introducing a uniformly distributed quasi-random variable into the term responsible for the sharpening of phase boundaries. This method is mass conserving and the statistical average of this method is shown to significantly delay the onset of pinning

Domain Growth, Wetting and Scaling in Porous Media

The lattice Boltzmann (LB) method is used to study the kinetics of domain growth of a binary fluid in a number of geometries modeling porous media. Unlike the traditional methods which solve the Cahn-Hilliard equation, the LB method correctly simulates fluid properties, phase segregation, interface dynamics and wetting. Our results, based on lattice sizes of up to $4096\times 4096$, do not show evidence to indicate the breakdown of late stage dynamical scaling, and suggest that confinement of the fluid is the key to the slow kinetics observed. Randomness of the pore structure appears unnecessary.Comment: 13 pages, latex, submitted to PR

Educational outcomes in extremely preterm children : neuropsychological correlates and predictors of attainment

This study assessed the impact of extremely preterm birth on academic attainment at 11 years of age, investigated neuropsychological antecedents of attainment in reading and mathematics, and examined early predictors of educational outcomes. Children born extremely preterm had significantly poorer academic attainment and a higher prevalence of learning difficulties than their term peers. General cognitive ability and specific deficits in visuospatial skills or phoneme deletion at 6 years were predictive of mathematics and reading attainment at 11 years in both extremely preterm and term children. Phonological processing, attention, and executive functions at 6 years were also associated with academic attainment in children born extremely preterm. Furthermore, social factors, neonatal factors (necrotizing enterocolitis, breech delivery, abnormal cerebral ultrasound, early breast milk provision), and developmental factors at 30 months (head circumference, cognitive development), were independent predictors of educational outcomes at 11 years. Neonatal complications combined with assessments of early cognitive function provide moderate prediction for educational outcomes in children born extremely preterm

Museum epigenomics: Characterizing cytosine methylation in historic museum specimens

Museum genomics has transformed the field of collections‐based research, opening up a range of new research directions for paleontological specimens as well as natural history specimens collected over the past few centuries. Recent work demonstrates that it is possible to characterize epigenetic markers such as DNA methylation in well preserved ancient tissues. This approach has not yet been tested in traditionally prepared natural history specimens such as dried bones and skins, the most common specimen types in vertebrate collections. In this study, we developed and tested methods to characterize cytosine methylation in dried skulls up to 76 years old. Using a combination of ddRAD and bisulphite treatment, we characterized patterns of cytosine methylation in two species of deer mouse (Peromyscus spp.) collected in the same region in Michigan in 1940, 2003, and 2013–2016. We successfully estimated methylation in specimens of all age groups, although older specimens yielded less data and showed greater interindividual variation in data yield than newer specimens. Global methylation estimates were reduced in the oldest specimens (76 years old) relative to the newest specimens (1–3 years old), which may reflect post‐mortem hydrolytic deamination. Methylation was reduced in promoter regions relative to gene bodies and showed greater bimodality in autosomes relative to female X chromosomes, consistent with expectations for methylation in mammalian somatic cells. Our work demonstrates the utility of historic specimens for methylation analyses, as with genomic analyses; however, studies will need to accommodate the large variance in the quantity of data produced by older specimens.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162784/5/men13115.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162784/4/men13115-sup-0003-AppendixS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162784/3/men13115-sup-0001-FigS1-S2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162784/2/men13115_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162784/1/men13115-sup-0002-TableS1-S2.pd

Peroxisomal membrane channel Pxmp2 in the mammary fat pad is essential for stromal lipid homeostasis and for development of mammary gland epithelium in mice

AbstractTo understand the functional role of the peroxisomal membrane channel Pxmp2, mice with a targeted disruption of the Pxmp2 gene were generated. These mice were viable, grew and bred normally. However, Pxmp2−/− female mice were unable to nurse their pups. Lactating mammary gland epithelium displayed secretory lipid droplets and milk proteins, but the size of the ductal system was greatly reduced. Examination of mammary gland development revealed that retarded mammary ductal outgrowth was due to reduced proliferation of epithelial cells during puberty. Transplantation experiments established the Pxmp2−/− mammary stroma as a tissue responsible for suppression of epithelial growth. Morphological and biochemical examination confirmed the presence of peroxisomes in the mammary fat pad adipocytes, and functional Pxmp2 was detected in the stroma of wild-type mammary glands. Deletion of Pxmp2 led to an elevation in the expression of peroxisomal proteins in the mammary fat pad but not in liver or kidney of transgenic mice. Lipidomics of Pxmp2−/−mammary fat pad showed a decrease in the content of myristic acid (C14), a principal substrate for protein myristoylation and a potential peroxisomal β-oxidation product. Analysis of complex lipids revealed a reduced concentration of a variety of diacylglycerols and phospholipids containing mostly polyunsaturated fatty acids that may be caused by activation of lipid peroxidation. However, an antioxidant-containing diet did not stimulate mammary epithelial proliferation in Pxmp2−/− mice.The results point to disturbances of lipid metabolism in the mammary fat pad that in turn may result in abnormal epithelial growth. The work reveals impaired mammary gland development as a new category of peroxisomal disorders

Sequence analysis and editing for bisulphite genomic sequencing projects

Bisulphite genomic sequencing is a widely used technique for detailed analysis of the methylation status of a region of DNA. It relies upon the selective deamination of unmethylated cytosine to uracil after treatment with sodium bisulphite, usually followed by PCR amplification of the chosen target region. Since this two-step procedure replaces all unmethylated cytosine bases with thymine, PCR products derived from unmethylated templates contain only three types of nucleotide, in unequal proportions. This can create a number of technical difficulties (e.g. for some base-calling methods) and impedes manual analysis of sequencing results (since the long runs of T or A residues are difficult to align visually with the parent sequence). To facilitate the detailed analysis of bisulphite PCR products (particularly using multiple cloned templates), we have developed a visually intuitive program that identifies the methylation status of CpG dinucleotides by analysis of raw sequence data files produced by MegaBace or ABI sequencers as well as Staden SCF trace files and plain text files. The program then also collates and presents data derived from independent templates (e.g. separate clones). This results in a considerable reduction in the time required for completion of a detailed genomic methylation project

Simulation of Flow of Mixtures Through Anisotropic Porous Media using a Lattice Boltzmann Model

We propose a description for transient penetration simulations of miscible and immiscible fluid mixtures into anisotropic porous media, using the lattice Boltzmann (LB) method. Our model incorporates hydrodynamic flow, diffusion, surface tension, and the possibility for global and local viscosity variations to consider various types of hardening fluids. The miscible mixture consists of two fluids, one governed by the hydrodynamic equations and one by diffusion equations. We validate our model on standard problems like Poiseuille flow, the collision of a drop with an impermeable, hydrophobic interface and the deformation of the fluid due to surface tension forces. To demonstrate the applicability to complex geometries, we simulate the invasion process of mixtures into wood spruce samples.Comment: Submitted to EPJ

Hydrodynamic Spinodal Decomposition: Growth Kinetics and Scaling Functions

We examine the effects of hydrodynamics on the late stage kinetics in spinodal decomposition. From computer simulations of a lattice Boltzmann scheme we observe, for critical quenches, that single phase domains grow asymptotically like $t^{\alpha}$, with $\alpha \approx .66$ in two dimensions and $\alpha \approx 1.0$ in three dimensions, both in excellent agreement with theoretical predictions.Comment: 12 pages, latex, Physical Review B Rapid Communication (in press

Epigenetics as a mechanism driving polygenic clinical drug resistance

Aberrant methylation of CpG islands located at or near gene promoters is associated with inactivation of gene expression during tumour development. It is increasingly recognised that such epimutations may occur at a much higher frequency than gene mutation and therefore have a greater impact on selection of subpopulations of cells during tumour progression or acquisition of resistance to anticancer drugs. Although laboratory-based models of acquired resistance to anticancer agents tend to focus on specific genes or biochemical pathways, such 'one gene : one outcome' models may be an oversimplification of acquired resistance to treatment of cancer patients. Instead, clinical drug resistance may be due to changes in expression of a large number of genes that have a cumulative impact on chemosensitivity. Aberrant CpG island methylation of multiple genes occurring in a nonrandom manner during tumour development and during the acquisition of drug resistance provides a mechanism whereby expression of multiple genes could be affected simultaneously resulting in polygenic clinical drug resistance. If simultaneous epigenetic regulation of multiple genes is indeed a major driving force behind acquired resistance of patients' tumour to anticancer agents, this has important implications for biomarker studies of clinical outcome following chemotherapy and for clinical approaches designed to circumvent or modulate drug resistance