Modeling DNA methylation dynamics with approaches from phylogenetics

Methylation of CpG dinucleotides is a prevalent epigenetic modification that is required for proper development in vertebrates, and changes in CpG methylation are essential to cellular differentiation. Genome-wide DNA methylation assays have become increasingly common, and recently distinct stages across differentiating cellular lineages have been assayed. How- ever, current methods for modeling methylation dynamics do not account for the dependency structure between precursor and dependent cell types. We developed a continuous-time Markov chain approach, based on the observation that changes in methylation state over tissue differentiation can be modeled similarly to DNA nucleotide changes over evolutionary time. This model explicitly takes precursor to descendant relationships into account and enables inference of CpG methylation dynamics. To illustrate our method, we analyzed a high-resolution methylation map of the differentiation of mouse stem cells into several blood cell types. Our model can successfully infer unobserved CpG methylation states from observations at the same sites in related cell types (90% correct), and this approach more accurately reconstructs missing data than imputation based on neighboring CpGs (84% correct). Additionally, the single CpG resolution of our methylation dynamics estimates enabled us to show that DNA sequence context of CpG sites is informative about methylation dynamics across tissue differentiation. Finally, we identified genomic regions with clusters of highly dynamic CpGs and present a likely functional example. Our work establishes a framework for inference and modeling that is well-suited to DNA methylation data, and our success suggests that other methods for analyzing DNA nucleotide substitutions will also translate to the modeling of epigenetic phenomena.Comment: 8 pages, 5 figure

Kinetics and crystallization path of a Fe-based metallic glass alloy

The thermal stability and the quantification of the different transformation processes involved in the overall crystallization of the Fe50Cr15Mo14C15B6 amorphous alloy were investigated by several characterization techniques. Formation of various metastable and stable phases during the devitrification process in the sequence a-Fe, ¿-Cr6Fe18Mo5, M23(C,B)6, M7C3, ¿-Fe3Mo3C and FeMo2B2 (with M = Fe, Cr, Mo), was observed by in-situ synchrotron high energy X-ray diffraction and in-situ transmission electron microscopy. By combining these techniques with differential scanning calorimetry data, the crystallization states and their temperature range of stability under continuous heating were related with the evolution of the crystallized fraction and the phase sequence as a function of temperature, revealing structural and chemical details of the different transformation mechanisms.Postprint (published version

Influence of composition and precipitation evolution on damage at grain boundaries in a crept polycrystalline Ni-based superalloy

© 2018 Acta Materialia Inc. The microstructural and compositional evolution of intergranular carbides and borides prior to and after creep deformation at 850 °C in a polycrystalline nickel-based superalloy was studied. Primary MC carbides, enveloped within intergranular γ′ layers, decomposed resulting in the formation of layers of the undesirable η phase. These layers have a composition corresponding to Ni3Ta as measured by atom probe tomography and their structure is consistent with the D024 hexagonal structure as revealed by transmission electron microscopy. Electron backscattered diffraction reveals that they assume various misorientations with regard to the adjacent grains. As a consequence, these layers act as brittle recrystallized zones and crack initiation sites. The composition of the MC carbides after creep was altered substantially, with the Ta content decreasing and the Hf and Zr contents increasing, suggesting a beneficial effect of Hf and Zr additions on the stability of MC carbides. By contrast, M5B3 borides were found to be microstructurally stable after creep and without substantial compositional changes. Borides at 850 °C were found to coarsen, resulting in some cases into γ′- depleted zones, where, however, no cracks were observed. The major consequences of secondary phases on the microstructural stability of superalloys during the design of new polycrystalline superalloys are discussed

Finite element simulation of sintering of metal-bonded grinding wheels

The grinding wheel properties porosity, particle distribution and the grain holding force influence the surface roughness of the machined workpiece and the performance of the grinding process. These properties of a grinding wheel are in turn defined during tool production. However, the adaptation of the properties of a grinding wheel to the specific grinding task is currently based on empirical knowledge and experience. Understanding the interdependencies from the initial manufacturing to the final grinding results is the key to achieve the target-oriented generation of the grinding wheel properties for the grinding task at hand. With regard to the large number of powder particles for the manufacturing of metal-bonded grinding wheels, an analytical investigation of the powder metallurgical processes is not suitable. Numerical simulations offer a cost and time saving alternative to provide information on the sintering behavior and gain knowledge on the acting mechanism. In this article the sintering of a metal-bonded diamond grinding wheel is modelled and the obtained results are connected to material properties of the resulting grinding layer

Stellar Wind Accretion in GX301-2: Evidence for a High-density Stream

The X-ray binary system GX301-2 consists of a neutron star in an eccentric orbit accreting from the massive early-type star WRAY 977. It has previously been shown that the X-ray orbital light curve is consistent with existence of a gas stream flowing out from Wray 977 in addition to its strong stellar wind. Here, X-ray monitoring observations by the Rossi X-ray Timing Explorer (RXTE)/ All-Sky-Monitor (ASM) and pointed observations by the RXTE/ Proportional Counter Array (PCA) over the past decade are analyzed. We analyze both the flux and column density dependence on orbital phase. The wind and stream dynamics are calculated for various system inclinations, companion rotation rates and wind velocities, as well as parametrized by the stream width and density. These calculations are used as inputs to determine both the expected accretion luminosity and the column density along the line-of-sight to the neutron star. The model luminosity and column density are compared to observed flux and column density vs. orbital phase, to constrain the properties of the stellar wind and the gas stream. We find that the change between bright and medium intensity levels is primarily due to decreased mass loss in the stellar wind, but the change between medium and dim intensity levels is primarily due to decreased stream density. The mass-loss rate in the stream exceeds that in the stellar wind by a factor of 2.5. The quality of the model fits is significantly better for lower inclinations, favoring a mass for WRAY 977 of 53 to 62 Msun.Comment: 19 pages, 6 figure

Posttranslational protein transport in yeast reconstituted with a purified complex of Sec proteins and Kar2p

AbstractWe have reproduced the posttranslational mode of protein translocation across the endoplasmic reticulum membrane with reconstituted proteoliposomes containing a purified complex of seven yeast proteins. This Sec complex includes a heterotrimeric Sec61p complex, homologous to that in mammals, as well as all other membrane proteins found in genetic screens for translocation components. Efficient posttranslational translocation also requires the addition of lumenal Kar2p(BIP) and ATP. The trimeric Sec61p complex also exists as a separate entity that, in contrast with the large Sec complex, is associated with membrane-bound ribosomes. We therefore hypothesize that distinct membrane protein complexes function in co- and posttranslational translocation pathways

Decomposition of fractional quantum Hall states: New symmetries and approximations

We provide a detailed description of a new symmetry structure of the monomial (Slater) expansion coefficients of bosonic (fermionic) fractional quantum Hall states first obtained in Ref. 1, which we now extend to spin-singlet states. We show that the Haldane-Rezayi spin-singlet state can be obtained without exact diagonalization through a differential equation method that we conjecture to be generic to other FQH model states. The symmetry rules in Ref. 1 as well as the ones we obtain for the spin singlet states allow us to build approximations of FQH states that exhibit increasing overlap with the exact state (as a function of system size). We show that these overlaps reach unity in the thermodynamic limit even though our approximation omits more than half of the Hilbert space. We show that the product rule is valid for any FQH state which can be written as an expectation value of parafermionic operators.Comment: 22 pages, 8 figure

Correlation of Microstructure and Properties of Cold Gas Sprayed INCONEL 718 Coatings

In the cold gas spray process, deposition of particles takes place through intensive plastic deformation upon impact in a solid state at temperatures well below their melting point. The high particle impact velocities and corresponding peening effects can lead to high compressive residual stresses in cold spray coatings. This can be advantageous with regard to mechanical properties as fatigue life and hence, cold spray is an ideal process for repair applications. In this study, INCONEL 718 particles were cold sprayed by using nitrogen as propellant gas. The deposited coatings with different thicknesses were characterized using electron microscopy techniques to study grain refinement and precipitates in the coating. In addition, depth-resolved residual stress measurements have been performed by the incremental hole drilling method. The residual stress depth profiles in the coatings indicate compressive residual stresses of several hundred MPa which are hardly influenced by the coating thickness. In addition, large compressive stress levels are found in surface- near regions of the substrate due to the grit blasting process. Furthermore, a post-heat treatment analysis was performed to investigate its influence on residual stresses and bonding strength. These findings are used to develop a consistent explanation of the dependence of strength values on thickness