The Relation between Approximation in Distribution and Shadowing in Molecular Dynamics

Molecular dynamics refers to the computer simulation of a material at the atomic level. An open problem in numerical analysis is to explain the apparent reliability of molecular dynamics simulations. The difficulty is that individual trajectories computed in molecular dynamics are accurate for only short time intervals, whereas apparently reliable information can be extracted from very long-time simulations. It has been conjectured that long molecular dynamics trajectories have low-dimensional statistical features that accurately approximate those of the original system. Another conjecture is that numerical trajectories satisfy the shadowing property: that they are close over long time intervals to exact trajectories but with different initial conditions. We prove that these two views are actually equivalent to each other, after we suitably modify the concept of shadowing. A key ingredient of our result is a general theorem that allows us to take random elements of a metric space that are close in distribution and embed them in the same probability space so that they are close in a strong sense. This result is similar to the Strassen-Dudley Theorem except that a mapping is provided between the two random elements. Our results on shadowing are motivated by molecular dynamics but apply to the approximation of any dynamical system when initial conditions are selected according to a probability measure.Comment: 21 pages, final version accepted in SIAM Dyn Sy

The main transition in the Pink membrane model: finite-size scaling and the influence of surface roughness

We consider the main transition in single-component membranes using computer simulations of the Pink model [D. Pink {\it et al.}, Biochemistry {\bf 19}, 349 (1980)]. We first show that the accepted parameters of the Pink model yield a main transition temperature that is systematically below experimental values. This resolves an issue that was first pointed out by Corvera and co-workers [Phys. Rev. E {\bf 47}, 696 (1993)]. In order to yield the correct transition temperature, the strength of the van der Waals coupling in the Pink model must be increased; by using finite-size scaling, a set of optimal values is proposed. We also provide finite-size scaling evidence that the Pink model belongs to the universality class of the two-dimensional Ising model. This finding holds irrespective of the number of conformational states. Finally, we address the main transition in the presence of quenched disorder, which may arise in situations where the membrane is deposited on a rough support. In this case, we observe a stable multi-domain structure of gel and fluid domains, and the absence of a sharp transition in the thermodynamic limit.Comment: submitted to PR

Elemental energy spectra of cosmic rays measured by CREAM-II

We present new measurements of the energy spectra of cosmic-ray (CR) nuclei from the second flight of the balloon-borne experiment CREAM (Cosmic Ray Energetics And Mass). The instrument (CREAM-II) was comprised of detectors based on different techniques (Cherenkov light, specific ionization in scintillators and silicon sensors) to provide a redundant charge identification and a thin ionization calorimeter capable of measuring the energy of cosmic rays up to several hundreds of TeV. The data analysis is described and the individual energy spectra of C, O, Ne, Mg, Si and Fe are reported up to ~ 10^14 eV. The spectral shape looks nearly the same for all the primary elements and can be expressed as a power law in energy E^{-2.66+/-0.04}. The nitrogen absolute intensity in the energy range 100-800 GeV/n is also measured.Comment: 4 pages, 3 figures, presented at ICRC 2009, Lodz, Polan

Measurements of cosmic-ray energy spectra with the 2nd CREAM flight

During its second Antarctic flight, the CREAM (Cosmic Ray Energetics And Mass) balloon experiment collected data for 28 days, measuring the charge and the energy of cosmic rays (CR) with a redundant system of particle identification and an imaging thin ionization calorimeter. Preliminary direct measurements of the absolute intensities of individual CR nuclei are reported in the elemental range from carbon to iron at very high energy.Comment: 4 pages, 3 figures, presented at XV International Symposium on Very High Energy Cosmic Ray Interactions (ISVHECRI 2008

A high-content imaging assay for the quantification of the Burkholderia pseudomallei induced multinucleated giant cell (MNGC) phenotype in murine macrophages

BACKGROUND: Burkholderia pseudomallei (Bp), a Gram-negative, motile, facultative intracellular bacterium is the causative agent of melioidosis in humans and animals. The Bp genome encodes a repertoire of virulence factors, including the cluster 3 type III secretion system (T3SS-3), the cluster 1 type VI secretion system (T6SS-1), and the intracellular motility protein BimA, that enable the pathogen to invade both phagocytic and non-phagocytic cells. A unique hallmark of Bp infection both in vitro and in vivo is its ability to induce cell-to-cell fusion of macrophages to form multinucleated giant cells (MNGCs), which to date are semi-quantitatively reported following visual inspection. RESULTS: In this study we report the development of an automated high-content image acquisition and analysis assay to quantitate the Bp induced MNGC phenotype. Validation of the assay was performed using T6SS-1 (∆hcp1) and T3SS-3 (∆bsaZ) mutants of Bp that have been previously reported to exhibit defects in their ability to induce MNGCs. Finally, screening of a focused small molecule library identified several Histone Deacetylase (HDAC) inhibitors that inhibited Bp-induced MNGC formation of macrophages. CONCLUSIONS: We have successfully developed an automated HCI assay to quantitate MNGCs induced by Bp in macrophages. This assay was then used to characterize the phenotype of the Bp mutants for their ability to induce MNGC formation and identify small molecules that interfere with this process. Successful application of chemical genetics and functional reverse genetics siRNA approaches in the MNGC assay will help gain a better understanding of the molecular targets and cellular mechanisms responsible for the MNGC phenotype induced by Bp, by other bacteria such as Mycobacterium tuberculosis, or by exogenously added cytokines

Molecular inversion probe-based SPR biosensing for specific, label-free and real-time detection of regional DNA methylation

DNA methylation has the potential to be a clinically important biomarker in cancer. This communication reports a real-time and label-free biosensing strategy for DNA methylation detection in the cancer cell line. This has been achieved by using surface plasmon resonance biosensing combined with the highly specific molecular inversion probe based amplification method, which requires only 50 ng of bisulfite treated genomic DNA

Energy spectra of cosmic-ray nuclei at high energies

We present new measurements of the energy spectra of cosmic-ray (CR) nuclei from the second flight of the balloon-borne experiment Cosmic Ray Energetics And Mass (CREAM). The instrument included different particle detectors to provide redundant charge identification and measure the energy of CRs up to several hundred TeV. The measured individual energy spectra of C, O, Ne, Mg, Si, and Fe are presented up to $\sim 10^{14}$ eV. The spectral shape looks nearly the same for these primary elements and it can be fitted to an $E^{-2.66 \pm 0.04}$ power law in energy. Moreover, a new measurement of the absolute intensity of nitrogen in the 100-800 GeV/$n$ energy range with smaller errors than previous observations, clearly indicates a hardening of the spectrum at high energy. The relative abundance of N/O at the top of the atmosphere is measured to be $0.080 \pm 0.025$(stat.)$\pm 0.025$(sys.) at $\sim$800 GeV/$n$, in good agreement with a recent result from the first CREAM flight.Comment: 32 pages, 10 figures. Accepted for publication in Astrophysical Journa