348 research outputs found
JAK2V617F promotes replication fork stalling with disease-restricted impairment of the intra-S checkpoint response
Cancers result from the accumulation of genetic lesions, but the cellular consequences of driver mutations remain unclear, especially during the earliest stages of malignancy. The V617F mutation in the JAK2 non-receptor tyrosine kinase (JAK2V617F) is present as an early somatic event in most patients with myeloproliferative neoplasms (MPNs), and the study of these chronic myeloid malignancies provides an experimentally tractable approach to understanding early tumorigenesis. Introduction of exogenous JAK2V617F impairs replication fork progression and is associated with activation of the intra-S checkpoint, with both effects mediated by phosphatidylinositide 3-kinase (PI3K) signaling. Analysis of clonally derived JAK2V617F-positive erythroblasts from MPN patients also demonstrated impaired replication fork progression accompanied by increased levels of replication protein A (RPA)-containing foci. However, the associated intra-S checkpoint response was impaired in erythroblasts from polycythemia vera (PV) patients, but not in those from essential thrombocythemia (ET) patients. Moreover, inhibition of p53 in PV erythroblasts resulted in more gamma-H2Ax (Îł-H2Ax)âmarked double-stranded breaks compared with in like-treated ET erythroblasts, suggesting the defective intra-S checkpoint function seen in PV increases DNA damage in the context of attenuated p53 signaling. These results demonstrate oncogene-induced impairment of replication fork progression in primary cells from MPN patients, reveal unexpected disease-restricted differences in activation of the intra-S checkpoint, and have potential implications for the clonal evolution of malignancies
The curious nonexistence of Gaussian 2-designs
2-designs -- ensembles of quantum pure states whose 2nd moments equal those
of the uniform Haar ensemble -- are optimal solutions for several tasks in
quantum information science, especially state and process tomography. We show
that Gaussian states cannot form a 2-design for the continuous-variable
(quantum optical) Hilbert space L2(R). This is surprising because the affine
symplectic group HWSp (the natural symmetry group of Gaussian states) is
irreducible on the symmetric subspace of two copies. In finite dimensional
Hilbert spaces, irreducibility guarantees that HWSp-covariant ensembles (such
as mutually unbiased bases in prime dimensions) are always 2-designs. This
property is violated by continuous variables, for a subtle reason: the
(well-defined) HWSp-invariant ensemble of Gaussian states does not have an
average state because the averaging integral does not converge. In fact, no
Gaussian ensemble is even close (in a precise sense) to being a 2-design. This
surprising difference between discrete and continuous quantum mechanics has
important implications for optical state and process tomography.Comment: 9 pages, no pretty figures (sorry!
Noncommutative brane-world, (Anti) de Sitter vacua and extra dimensions
We investigate a curved brane-world, inspired by a noncommutative D3-brane,
in a type IIB string theory. We obtain, an axially symmetric and a spherically
symmetric, (anti) de Sitter black holes in 4D. The event horizons of these
black holes possess a constant curvature and may be seen to be governed by
different topologies. The extremal geometries are explored, using the
noncommutative scaling in the theory, to reassure the attractor behavior at the
black hole event horizon. The emerging two dimensional, semi-classical, black
hole is analyzed to provide evidence for the extra dimensions in a curved
brane-world. It is argued that the gauge nonlinearity in the theory may be
redefined by a potential in a moduli space. As a result, D=11 and D=12
dimensional geometries may be obtained at the stable extrema of the potential.Comment: 17 pages, 1 figur
Epidemiologic Study of Dental Caries Experience and Between-Meal Eating Patterns
The relationship between dental caries and between-meal snacks was investigated in a study of 1,486 high school students. The participants completed a questionnaire on between-meal habits and then were given dental examinations. The lack of differences in dental caries between racial and geographic groups was not related to the frequency of sucrose-containing, between-meal snacks.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66591/2/10.1177_00220345730520022501.pd
Why Does Inflation Start at the Top of the Hill?
We show why the universe started in an unstable de Sitter state. The quantum
origin of our universe implies one must take a `top down' approach to the
problem of initial conditions in cosmology, in which the histories that
contribute to the path integral, depend on the observable being measured. Using
the no boundary proposal to specify the class of histories, we study the
quantum cosmological origin of an inflationary universe in theories like trace
anomaly driven inflation in which the effective potential has a local maximum.
We find that an expanding universe is most likely to emerge in an unstable de
Sitter state, by semiclassical tunneling via a Hawking-Moss instanton. Since
the top down view is forced upon us by the quantum nature of the universe, we
argue that the approach developed here should still apply when the framework of
quantum cosmology will be based on M-Theory.Comment: 21 pages, 1 figur
Parametrization of Born-Infeld Type Phantom Dark Energy Model
Applying the parametrization of dark energy density, we can construct
directly independent-model potentials. In Born-Infeld type phantom dark energy
model, we consider four special parametrization equation of state parameter.
The evolutive behavior of dark energy density with respect to red-shift ,
potentials with respect to and are shown mathematically. Moreover,
we investigate the effect of parameter upon the evolution of the
constructed potential with respect to . These results show that the
evolutive behavior of constructed Born-Infeld type dark energy model is quite
different from those of the other models.Comment: 5 pages, 4 figures, Accepted for publication in Astrophysics & Space
Scienc
Noncommutative Topological Theories of Gravity
The possibility of noncommutative topological gravity arising in the same
manner as Yang-Mills theory is explored. We use the Seiberg-Witten map to
construct such a theory based on a SL(2,C) complex connection, from which the
Euler characteristic and the signature invariant are obtained. This gives us a
way towards the description of noncommutative gravitational instantons as well
as noncommutative local gravitational anomalies.Comment: 17+1 pages, LaTeX, no figures, some clarifications, comments and
references added, style improve
Heat kernel regularization of the effective action for stochastic reaction-diffusion equations
The presence of fluctuations and non-linear interactions can lead to scale
dependence in the parameters appearing in stochastic differential equations.
Stochastic dynamics can be formulated in terms of functional integrals. In this
paper we apply the heat kernel method to study the short distance
renormalizability of a stochastic (polynomial) reaction-diffusion equation with
real additive noise. We calculate the one-loop {\emph{effective action}} and
its ultraviolet scale dependent divergences. We show that for white noise a
polynomial reaction-diffusion equation is one-loop {\emph{finite}} in and
, and is one-loop renormalizable in and space dimensions. We
obtain the one-loop renormalization group equations and find they run with
scale only in .Comment: 21 pages, uses ReV-TeX 3.
Holographic Dark Energy Model and Scalar-Tensor Theories
We study the holographic dark energy model in a generalized scalar tensor
theory. In a universe filled with cold dark matter and dark energy, the effect
of potential of the scalar field is investigated in the equation of state
parameter. We show that for a various types of potentials, the equation of
state parameter is negative and transition from deceleration to acceleration
expansion of the universe is possible.Comment: 11 pages, no figure. To appear in General Relativity and Gravitatio
A Rigorous Geometric Derivation of the Chiral Anomaly in Curved Backgrounds
We discuss the chiral anomaly for a Weyl field in a curved background and show that a novel index theorem for the Lorentzian Dirac operator can be applied to describe the gravitational chiral anomaly. A formula for the total charge generated by the gravitational and gauge field background is derived directly in Lorentzian signature and in a mathematically rigorous manner. It contains a term identical to the integrand in the AtiyahâSinger index theorem and another term involving the η -invariant of the Cauchy hypersurfaces
- âŠ