Fisher information matrix for single molecules with stochastic trajectories

Tracking of objects in cellular environments has become a vital tool in molecular cell biology. A particularly important example is single molecule tracking which enables the study of the motion of a molecule in cellular environments and provides quantitative information on the behavior of individual molecules in cellular environments, which were not available before through bulk studies. Here, we consider a dynamical system where the motion of an object is modeled by stochastic differential equations (SDEs), and measurements are the detected photons emitted by the moving fluorescently labeled object, which occur at discrete time points, corresponding to the arrival times of a Poisson process, in contrast to uniform time points which have been commonly used in similar dynamical systems. The measurements are distributed according to optical diffraction theory, and therefore, they would be modeled by different distributions, e.g., a Born and Wolf profile for an out-of-focus molecule. For some special circumstances, Gaussian image models have been proposed. In this paper, we introduce a stochastic framework in which we calculate the maximum likelihood estimates of the biophysical parameters of the molecular interactions, e.g., diffusion and drift coefficients. More importantly, we develop a general framework to calculate the Cram\'er-Rao lower bound (CRLB), given by the inverse of the Fisher information matrix, for the estimation of unknown parameters and use it as a benchmark in the evaluation of the standard deviation of the estimates. There exists no established method, even for Gaussian measurements, to systematically calculate the CRLB for the general motion model that we consider in this paper. We apply the developed methodology to simulated data of a molecule with linear trajectories and show that the standard deviation of the estimates matches well with the square root of the CRLB

Magnetic fields in molecular clouds: Limitations of the analysis of Zeeman observations

Context. Observations of Zeeman split spectral lines represent an important approach to derive the structure and strength of magnetic fields in molecular clouds. In contrast to the uncertainty of the spectral line observation itself, the uncertainty of the analysis method to derive the magnetic field strength from these observations is not been well characterized so far. Aims. We investigate the impact of several physical quantities on the uncertainty of the analysis method, which is used to derive the line-of-sight (LOS) magnetic field strength from Zeeman split spectral lines. Methods. We simulate the Zeeman splitting of the 1665 MHz OH line with the 3D radiative transfer (RT) extension ZRAD. This extension is based on the line RT code Mol3D (Ober et al. 2015) and has been developed for the POLArized RadIation Simulator POLARIS (Reissl et al. 2016). Results. Observations of the OH Zeeman effect in typical molecular clouds are not significantly affected by the uncertainty of the analysis method. We derived an approximation to quantify the range of parameters in which the analysis method works sufficiently accurate and provide factors to convert our results to other spectral lines and species as well. We applied these conversion factors to CN and found that observations of the CN Zeeman effect in typical molecular clouds are neither significantly affected by the uncertainty of the analysis method. In addition, we found that the density has almost no impact on the uncertainty of the analysis method, unless it reaches values higher than those typically found in molecular clouds. Furthermore, the uncertainty of the analysis method increases, if both the gas velocity and the magnetic field show significant variations along the line-of-sight. However, this increase should be small in Zeeman observations of most molecular clouds considering typical velocities of ~1 km/s.Comment: 9 pages, 6 figure

Cramer-Rao Lower Bound for Point Based Image Registration with Heteroscedastic Error Model for Application in Single Molecule Microscopy

The Cramer-Rao lower bound for the estimation of the affine transformation parameters in a multivariate heteroscedastic errors-in-variables model is derived. The model is suitable for feature-based image registration in which both sets of control points are localized with errors whose covariance matrices vary from point to point. With focus given to the registration of fluorescence microscopy images, the Cramer-Rao lower bound for the estimation of a feature's position (e.g. of a single molecule) in a registered image is also derived. In the particular case where all covariance matrices for the localization errors are scalar multiples of a common positive definite matrix (e.g. the identity matrix), as can be assumed in fluorescence microscopy, then simplified expressions for the Cramer-Rao lower bound are given. Under certain simplifying assumptions these expressions are shown to match asymptotic distributions for a previously presented set of estimators. Theoretical results are verified with simulations and experimental data

Differences in High-School Student Learning by Instruction Type and MBTI Personality Type

Differentiated instruction is a part of the education process today, and it is a time-consuming process used to attempt to reach more students and increase their learning and education. There is currently little empirical research dedicated to measuring the academic effects of differentiated instruction in the classroom. This research examined differentiated instruction in the form of learning styles (audio and visual) combined with personality types in an attempt to determine if there is a measurable significant effect on the academic achievement of students based on their own personality types and different applied learning styles in the classroom. No statistically significant differences were found between different personality types and instruction types

The effect of a nucleating agent on lamellar growth in melt-crystallizing polyethylene oxide

The effects of a (non co-crystallizing) nucleating agent on secondary nucleation rate and final lamellar thickness in isothermally melt-crystallizing polyethylene oxide are considered. SAXS reveals that lamellae formed in nucleated samples are thinner than in the pure samples crystallized at the same undercoolings. These results are in quantitative agreement with growth rate data obtained by calorimetry, and are interpreted as the effect of a local decrease of the basal surface tension, determined mainly by the nucleant molecules diffused out of the regions being about to crystallize. Quantitative agreement with a simple lattice model allows for some interpretation of the mechanism.Comment: submitted to Journal of Applied Physics (first version on 22 Apr 2002

State Space Formulas for Coprime Factorization

In this paper we will give a uniform approach to the derivation of state space formulas of coprime factorizations, of different types, for rational matrix functions

Higher Order Variational Integrators: a polynomial approach

We reconsider the variational derivation of symplectic partitioned Runge-Kutta schemes. Such type of variational integrators are of great importance since they integrate mechanical systems with high order accuracy while preserving the structural properties of these systems, like the symplectic form, the evolution of the momentum maps or the energy behaviour. Also they are easily applicable to optimal control problems based on mechanical systems as proposed in Ober-Bl\"obaum et al. [2011]. Following the same approach, we develop a family of variational integrators to which we refer as symplectic Galerkin schemes in contrast to symplectic partitioned Runge-Kutta. These two families of integrators are, in principle and by construction, different one from the other. Furthermore, the symplectic Galerkin family can as easily be applied in optimal control problems, for which Campos et al. [2012b] is a particular case.Comment: 12 pages, 1 table, 23rd Congress on Differential Equations and Applications, CEDYA 201