Bayesian field theoretic reconstruction of bond potential and bond mobility in single molecule force spectroscopy

Quantifying the forces between and within macromolecules is a necessary first step in understanding the mechanics of molecular structure, protein folding, and enzyme function and performance. In such macromolecular settings, dynamic single-molecule force spectroscopy (DFS) has been used to distort bonds. The resulting responses, in the form of rupture forces, work applied, and trajectories of displacements, have been used to reconstruct bond potentials. Such approaches often rely on simple parameterizations of one-dimensional bond potentials, assumptions on equilibrium starting states, and/or large amounts of trajectory data. Parametric approaches typically fail at inferring complex-shaped bond potentials with multiple minima, while piecewise estimation may not guarantee smooth results with the appropriate behavior at large distances. Existing techniques, particularly those based on work theorems, also do not address spatial variations in the diffusivity that may arise from spatially inhomogeneous coupling to other degrees of freedom in the macromolecule, thereby presenting an incomplete picture of the overall bond dynamics. To solve these challenges, we have developed a comprehensive empirical Bayesian approach that incorporates data and regularization terms directly into a path integral. All experiemental and statistical parameters in our method are estimated empirically directly from the data. Upon testing our method on simulated data, our regularized approach requires fewer data and allows simultaneous inference of both complex bond potentials and diffusivity profiles.Comment: In review - Python source code available on github. Abridged abstract on arXi

Slowdown and splitting of gap solitons in apodized Bragg gratings

We study the motion of gap solitons in two models of apodized nonlinear fiber Bragg gratings (BGs), with the local reflectivity (LR) varying along the fiber. A single step of LR, and a periodic array of alternating steps with opposite signs (a "Bragg superstructure") are considered. A challenging possibility is to slow down and eventually halt the soliton by passing it through the step of increasing reflectivity, thus capturing a pulse of standing light. First, we develop an analytical approach, assuming adiabatic evolution of the soliton, and making use of the energy conservation and balance equation for the momentum. Comparison with simulations shows that the analytical approximation is quite accurate (unless the inhomogeneity is too steep): the soliton is either transmitted across the step or bounces back. If the step is narrow, systematic simulations demontrate that the soliton splits into transmitted and reflected pulses (splitting of a BG soliton which hits a chirped grating was observed in experiments). Moving through the periodic "superstructure", the soliton accummulates distortion and suffers radiation loss if the structure is composed of narrow steps. The soliton moves without any loss or irreversible deformation through the array of sufficiently broad steps.Comment: to appear in a special issue on Wave-Optical Engineering, Journal of Modern Optic

Knowledge Discovery in Biological Databases for Revealing Candidate Genes Linked to Complex Phenotypes

Genetics and “omics” studies designed to uncover genotype to phenotype relationships often identify large numbers of potential candidate genes, among which the causal genes are hidden. Scientists generally lack the time and technical expertise to review all relevant information available from the literature, from key model species and from a potentially wide range of related biological databases in a variety of data formats with variable quality and coverage. Computational tools are needed for the integration and evaluation of heterogeneous information in order to prioritise candidate genes and components of interaction networks that, if perturbed through potential interventions, have a positive impact on the biological outcome in the whole organism without producing negative side effects. Here we review several bioinformatics tools and databases that play an important role in biological knowledge discovery and candidate gene prioritization. We conclude with several key challenges that need to be addressed in order to facilitate biological knowledge discovery in the future.&nbsp

Strong scaling of general-purpose molecular dynamics simulations on GPUs

We describe a highly optimized implementation of MPI domain decomposition in a GPU-enabled, general-purpose molecular dynamics code, HOOMD-blue (Anderson and Glotzer, arXiv:1308.5587). Our approach is inspired by a traditional CPU-based code, LAMMPS (Plimpton, J. Comp. Phys. 117, 1995), but is implemented within a code that was designed for execution on GPUs from the start (Anderson et al., J. Comp. Phys. 227, 2008). The software supports short-ranged pair force and bond force fields and achieves optimal GPU performance using an autotuning algorithm. We are able to demonstrate equivalent or superior scaling on up to 3,375 GPUs in Lennard-Jones and dissipative particle dynamics (DPD) simulations of up to 108 million particles. GPUDirect RDMA capabilities in recent GPU generations provide better performance in full double precision calculations. For a representative polymer physics application, HOOMD-blue 1.0 provides an effective GPU vs. CPU node speed-up of 12.5x.Comment: 30 pages, 14 figure

Variability of the NGC 1333 IRAS 4A Outflow: Molecular Hydrogen and Silicon Monoxide Images

The NGC 1333 region was observed in the H2 1-0 S(1) line. The H2 images cover a 5' x 7' region around IRAS 4. Numerous H2 emission features were detected. The northeast-southwest bipolar outflow driven by IRAS 4A was studied by combining the H2 images with SiO maps published previously. The SiO-H2 outflows are continuous on the southwestern side but show a gap on the northeastern side. The southwestern outflow lobe curves smoothly, and the position angle increases with the distance from the driving source. The base and the outer tip of the northeastern outflow lobe are located at positions opposite to the corresponding parts of the southwestern lobe. This point-symmetry suggests that the outflow axis may be drifting or precessing clockwise in the plane of the sky and that the cause of the axis drift may be intrinsic to the outflow engine. The axis drift model is supported by the asymmetric lateral intensity profile of the SiO outflow. The axis drift rate is about 0.011 deg yr-1. The middle part of the northeastern outflow does not exactly follow the point symmetry because of the superposition of two different kinds of directional variability: the axis drift of the driving source and the deflection by a dense core. The axis drift model provides a good explanation for the large deflection angle of the northeastern outflow. Other H2 emission features around the IRAS 4 region are discussed briefly. Some of them are newly found outflows, and some are associated with outflows already known before

Multi-Modal Synthesis and Variable Modulus Effects in Resonant Column Tests by Random Excitations

To extend current measurement and data synthesis techniques for resonant column testing, random vibration transfer functions measured using a modified 6 inch (152.4 mm) diameter Drnevich free-free resonant column device are evaluated against viscoelastic theories of homogeneous and heterogeneous soil models. By means of the transfer function approach, it is found that the first four resonant peaks of the soil column response can be captured experimentally with some instrumental adaptations. By calibration against theoretical transfer functions, the ability to characterize the modulus and damping properties of the soil samples over a broad range of frequencies is demonstrated. As a generalization of the analytical theory for resonant column tests to a number of practical applications, the sensitivity of the experimental procedure to the specimen’s vertical material heterogeneity is examined for a linear variation in shear modulus. The feasibility of applying the experimental and analytical techniques to investigations of the frequency-dependence of damping properties is demonstrated. Calibration of theoretical models against measured resonant column soil behavior over a wide range of frequencies is anticipated to lead to more accurate material characterization across the spectrum of frequencies encountered in seismic and foundation vibration applications