3,513 research outputs found
Epigenetic regulation of key developmental genes during early mouse development
In undifferentiated ES cells, many Polycomb Repressive Complex 2 (PRC2) target genes carry not only repressive H3K27me3 but are also enriched for conventional indicators of active chromatin including methylated H3K4. This so-called bivalent domain structure is thought to silence key developmental regulators while keeping them poised for future activation (or repression). Consistent with this hypothesis, bivalent genes assemble RNAP II preferentially phosphorylated on Serine 5 residues (poised RNAP II) and are transcribed at low levels. Productive expression is, however, prevented by the action of PRC1. Here, I have focused on the pre-implantation stage of mouse development to evaluate whether bivalent or poised chromatin signatures are indeed specific attributes of emerging pluripotent cells and investigate how the fate of key developmental genes is specified while the first lineage decision event (extra-embryonic lineage formation) occurs. Using blastocyst-derived stem cells and chromatin immunoprecipitation (ChIP), I have shown that lineage-inappropriate genes retain bivalent histone marking in extra-embryonic trophoblast stem (TS). However, and in contrast to ES cells, PRC1 (Ring1B) and poised RNAP II are not recruited to these loci in TS cells, indicating that gene priming is a unique hallmark of pluripotent cells in the early embryo.
To investigate the intricate relationship between lineage identity and dynamic chromatin changes, I exploited the potential to convert ES cells into trophoblast-like stem (TSL) cells using a previously established artificial system dependent on doxycycline (Dox) induced repression of an Oct4 transgene. I demonstrated that Suv39h1-mediated H3K9me3 alongside DNA methylation is targeted to PRC2-bound bivalent, lineage-inappropriate genes upon trophectoderm lineage commitment. A change in chromatin conformation was observed upon differentiation of ES cells to TSL cells comparable to that seen in TS cells derived in the traditional manner from the trophectoderm (TE) of blastocyst stage embryos. Most importantly, I have begun to explore when epigenetic differences are specified, at the locus level, from 8-cell stage embryos onwards using newly designed Carrier ChIP technology. This data validated the occurrence of bivalent chromatin domains in vivo and further support the view that alternative strategies operate in the TE to silence key developmental regulators upon blastocyst lineage segregation
A Thermodynamically-Consistent Non-Ideal Stochastic Hard-Sphere Fluid
A grid-free variant of the Direct Simulation Monte Carlo (DSMC) method is
proposed, named the Isotropic DSMC (I-DSMC) method, that is suitable for
simulating dense fluid flows at molecular scales. The I-DSMC algorithm
eliminates all grid artifacts from the traditional DSMC algorithm; it is
Galilean invariant and microscopically isotropic. The stochastic collision
rules in I-DSMC are modified to yield a non-ideal structure factor that gives
consistent compressibility, as first proposed in [Phys. Rev. Lett. 101:075902
(2008)]. The resulting Stochastic Hard Sphere Dynamics (SHSD) fluid is
empirically shown to be thermodynamically identical to a deterministic
Hamiltonian system of penetrable spheres interacting with a linear core pair
potential, well-described by the hypernetted chain (HNC) approximation. We
apply a stochastic Enskog kinetic theory for the SHSD fluid to obtain estimates
for the transport coefficients that are in excellent agreement with particle
simulations over a wide range of densities and collision rates. The fluctuating
hydrodynamic behavior of the SHSD fluid is verified by comparing its dynamic
structure factor against theory based on the Landau-Lifshitz Navier-Stokes
equations. We also study the Brownian motion of a nano-particle suspended in an
SHSD fluid and find a long-time power-law tail in its velocity autocorrelation
function consistent with hydrodynamic theory and molecular dynamics
calculations.Comment: 30 pages, revision adding some clarifications and a new figure. See
also arXiv:0803.035
Intermediate energy Coulomb excitation as a probe of nuclear structure at radioactive beam facilities
The effects of retardation in the Coulomb excitation of radioactive nuclei in
intermediate energy collisions (Elab ~100 MeV/nucleon) are investigated. We
show that the excitation cross sections of low-lying states in 11Be,
{38,40,42}S and {44,46}Ar projectiles incident on gold and lead targets are
modified by as much as 20% due to these effects. The angular distributions of
decaying gamma-rays are also appreciably modified.Comment: 21 pages, 3 figures, Phys. Rev. C, in pres
Stacking Entropy of Hard Sphere Crystals
Classical hard spheres crystallize at equilibrium at high enough density.
Crystals made up of stackings of 2-dimensional hexagonal close-packed layers
(e.g. fcc, hcp, etc.) differ in entropy by only about per sphere
(all configurations are degenerate in energy). To readily resolve and study
these small entropy differences, we have implemented two different
multicanonical Monte Carlo algorithms that allow direct equilibration between
crystals with different stacking sequences. Recent work had demonstrated that
the fcc stacking has higher entropy than the hcp stacking. We have studied
other stackings to demonstrate that the fcc stacking does indeed have the
highest entropy of ALL possible stackings. The entropic interactions we could
detect involve three, four and (although with less statistical certainty) five
consecutive layers of spheres. These interlayer entropic interactions fall off
in strength with increasing distance, as expected; this fall-off appears to be
much slower near the melting density than at the maximum (close-packing)
density. At maximum density the entropy difference between fcc and hcp
stackings is per sphere, which is roughly 30% higher
than the same quantity measured near the melting transition.Comment: 15 page
Phase transition in inelastic disks
This letter investigates the molecular dynamics of inelastic disks without
external forcing. By introducing a new observation frame with a rescaled time,
we observe the virtual steady states converted from asymptotic energy
dissipation processes. System behavior in the thermodynamic limit is carefully
investigated. It is found that a phase transition with symmetry breaking occurs
when the magnitude of dissipation is greater than a critical value.Comment: 9 pages, 6 figure
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