29 research outputs found
Global Stationary Phase and the Sign Problem
We present a computational strategy for reducing the sign problem in the
evaluation of high dimensional integrals with non-positive definite weights.
The method involves stochastic sampling with a positive semidefinite weight
that is adaptively and optimally determined during the course of a simulation.
The optimal criterion, which follows from a variational principle for analytic
actions S(z), is a global stationary phase condition that the average gradient
of the phase Im(S) along the sampling path vanishes. Numerical results are
presented from simulations of a model adapted from statistical field theories
of classical fluids.Comment: 9 pages, 3 figures, submitted for publicatio
Effective Soft-Core Potentials and Mesoscopic Simulations of Binary Polymer Mixtures
Mesoscopic molecular dynamics simulations are used to determine the large
scale structure of several binary polymer mixtures of various chemical
architecture, concentration, and thermodynamic conditions. By implementing an
analytical formalism, which is based on the solution to the Ornstein-Zernike
equation, each polymer chain is mapped onto the level of a single soft colloid.
From the appropriate closure relation, the effective, soft-core potential
between coarse-grained units is obtained and used as input to our mesoscale
simulations. The potential derived in this manner is analytical and explicitly
parameter dependent, making it general and transferable to numerous systems of
interest. From computer simulations performed under various thermodynamic
conditions the structure of the polymer mixture, through pair correlation
functions, is determined over the entire miscible region of the phase diagram.
In the athermal regime mesoscale simulations exhibit quantitative agreement
with united atom simulations. Furthermore, they also provide information at
larger scales than can be attained by united atom simulations and in the
thermal regime approaching the phase transition.Comment: 19 pages, 11 figures, 3 table
Activation of the PI3K/AKT Pathway in Merkel Cell Carcinoma
Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with an increasing incidence. The understanding of the molecular carcinogenesis of MCC is limited. Here, we scrutinized the PI3K/AKT pathway, one of the major pathways activated in human cancer, in MCC. Immunohistochemical analysis of 41 tumor tissues and 9 MCC cell lines revealed high levels of AKT phosphorylation at threonine 308 in 88% of samples. Notably, the AKT phosphorylation was not correlated with the presence or absence of the Merkel cell polyoma virus (MCV). Accordingly, knock-down of the large and small T antigen by shRNA in MCV positive MCC cells did not affect phosphorylation of AKT. We also analyzed 46 MCC samples for activating PIK3CA and AKT1 mutations. Oncogenic PIK3CA mutations were found in 2/46 (4%) MCCs whereas mutations in exon 4 of AKT1 were absent. MCC cell lines demonstrated a high sensitivity towards the PI3K inhibitor LY-294002. This finding together with our observation that the PI3K/AKT pathway is activated in the majority of human MCCs identifies PI3K/AKT as a potential new therapeutic target for MCC patients
The HSP70 modulator MAL3-101 inhibits Merkel cell carcinoma
Merkel Cell Carcinoma (MCC) is a rare and highly aggressive neuroendocrine skin cancer for which no effective treatment is available. MCC represents a human cancer with the best experimental evidence for a causal role of a polyoma virus. Large T antigens (LTA) encoded by polyoma viruses are oncoproteins, which are thought to require support of cellular heat shock protein 70 (HSP70) to exert their transforming activity. Here we evaluated the capability of MAL3-101, a synthetic HSP70 inhibitor, to limit proliferation and survival of various MCC cell lines. Remarkably, MAL3-101 treatment resulted in considerable apoptosis in 5 out of 7 MCC cell lines. While this effect was not associated with the viral status of the MCC cells, quantitative mRNA expression analysis of the known HSP70 isoforms revealed a significant correlation between MAL3-101 sensitivity and HSC70 expression, the most prominent isoform in all cell lines. Moreover, MAL3-101 also exhibited in vivo antitumor activity in an MCC xenograft model suggesting that this substance or related compounds are potential therapeutics for the treatment of MCC in the future. © 2014 Adam et al
Grand canonical auxiliary field Monte Carlo: a new technique for simulating open systems at high density
The computation of open many-particle systems at high densities is a
major challenge since many decades due to the inherent limitations of
grand canonical simulation methods based on particle exchange
algorithms. In this paper we report on the statistical convergence
behavior in the high density regime of a recently developed alternative
called the grand canonical auxiliary field Monte Carlo method. We show
on a common soft matter model widely used in polymer simulation that it
possesses a more appropriate statistical behavior in the dense regime
than the currently employed grand canonical Monte Carlo methods relying
on particle exchange algorithms. (C) 2003 Elsevier B.V. All rights
reserved
Method of Gaussian equivalent representation: A new technique for reducing the sign problem of functional integral methods
We report on the specific features of the sign problem in the
classical auxiliary field methodology and the strategies
employed for its alleviation. In particular, we focus on a new
technique based on the method of Gaussian equivalent
representation of Efimov and Nogovitsin [Physica (Amsterdam)
234A, 506 (1996)] with which we could ameliorate the
convergence properties significantly. We believe that this
technique can also provide an interesting possibility to reduce
the sign problem of other methods of computer simulation based
on a functional integral approach
The stationary phase auxiliary field Monte Carlo method: a new strategy for reducing the sign problem of auxiliary field methodologies
A field-theoretical approach to simulation in the classical canonical and grand canonical ensemble
In this paper we present a new approach to simulation methods
for classical statistical mechanics relying on a field-
theoretical formalism. It is based on applying the complex
Hubbard-Stratonovich transformation to the canonical and grand-
canonical partition function, which allows one to reexpress
their particle representation in terms of a functional integral
over a fluctuating auxiliary field. The thermodynamic averages
from the resulting field representations can then be calculated
with a conventional Monte Carlo algorithm. We explored the
applicability of the auxiliary field methodology for both the
canonical and grand-canonical ensemble using a system of
particles interacting through a purely repulsive Gaussian pair
potential in a broad range of external parameters. In the
grand-canonical case this technique represents an alternative
to standard grand-canonical Monte Carlo methods. Generally
providing a framework for simulating classical particle systems
within a continuum formalism can be useful for multiscale
modeling where the field or continuum description naturally
appears within quantum mechanics on smaller length scales and
within classical mechanics on larger ones. (C) 2002 American
Institute of Physics