Tissue dynamics spectroscopy for three-dimensional tissue-based drug screening

Tissue dynamics spectroscopy combines dynamic light scattering with short-coherence digital holography to capture intracellular motion inside multicellular tumor spheroid tissue models. The cellular mechanical activity becomes an endogenous imaging contrast agent for motility contrast imaging. Fluctuation spectroscopy is performed on dynamic speckle from the proliferating shell and hypoxic core to generate drug-response spectrograms that are frequency versus time representations of the changes in spectral content induced by an applied compound or an environmental perturbation. A combination of 28 reference compounds and conditions applied to rat osteogenic UMR-106 spheroids generated spectrograms that were crosscorrelated in a similarity matrix used for unsupervised hierarchical clustering of similar compound responses. This work establishes the feasibility of tissue dynamics spectroscopy for three-dimensional tissue-based phenotypic profiling of drug response as a fully endogenous probe of the response of tissue to reference compounds.     

Effects of woody elements on simulated canopy reflectance: Implications for forest chlorophyll content retrieval

An important bio-indicator of actual plant health status, the foliar content of chlorophyll a and b (Cab), can be estimated using imaging spectroscopy. For forest canopies, however, the relationship between the spectral response and leaf chemistry is confounded by factors such as background (e.g. understory), canopy structure, and the presence of non-photosynthetic vegetation (NPV, e.g. woody elements)—particularly the appreciable amounts of standing and fallen dead wood found in older forests. We present a sensitivity analysis for the estimation of chlorophyll content in woody coniferous canopies using radiative transfer modeling, and use the modeled top-of-canopy reflectance data to analyze the contribution of woody elements, leaf area index (LAI), and crown cover (CC) to the retrieval of foliar Cab content. The radiative transfer model used comprises two linked submodels: one at leaf level (PROSPECT) and one at canopy level (FLIGHT). This generated bidirectional reflectance data according to the band settings of the Compact High Resolution Imaging Spectrometer (CHRIS) from which chlorophyll indices were calculated. Most of the chlorophyll indices outperformed single wavelengths in predicting Cab content at canopy level, with best results obtained by the Maccioni index ([R₇₈₀ − R₇₁₀] / [R₇₈₀ − R₆₈₀]). We demonstrate the performance of this index with respect to structural information on three distinct coniferous forest types (young, early mature and old-growth stands). The modeling results suggest that the spectral variation due to variation in canopy chlorophyll content is best captured for stands with medium dense canopies. However, the strength of the up-scaled Cab signal weakens with increasing crown NPV scattering elements, especially when crown cover exceeds 30%. LAI exerts the least perturbations. We conclude that the spectral influence of woody elements is an important variable that should be considered in radiative transfer approaches when retrieving foliar pigment estimates in heterogeneous stands, particularly if the stands are partly defoliated or long-lived.     

Regularization parameter estimation for large-scale Tikhonov regularization using a priori information

Solutions of numerically ill-posed least squares problems for A∈R^m×n by Tikhonov regularization are considered. For D∈R^p×n, the Tikhonov regularized least squares functional is given by where matrix W is a weighting matrix and is given. Given a priori estimates on the covariance structure of errors in the measurement data , the weighting matrix may be taken as which is the inverse covariance matrix of the mean 0 normally distributed measurement errors in . If in addition is an estimate of the mean value of , and σ is a suitable statistically-chosen value, J evaluated at its minimizer approximately follows a χ² distribution with degrees of freedom. Using the generalized singular value decomposition of the matrix pair , σ can then be found such that the resulting J follows this χ² distribution. But the use of an algorithm which explicitly relies on the direct solution of the problem obtained using the generalized singular value decomposition is not practical for large-scale problems. Instead an approach using the Golub-Kahan iterative bidiagonalization of the regularized problem is presented. The original algorithm is extended for cases in which is not available, but instead a set of measurement data provides an estimate of the mean value of . The sensitivity of the Newton algorithm to the number of steps used in the Golub-Kahan iterative bidiagonalization, and the relation between the size of the projected subproblem and σ are discussed. Experiments presented contrast the efficiency and robustness with other standard methods for finding the regularization parameter for a set of test problems and for the restoration of a relatively large real seismic signal. An application for image deblurring also validates the approach for large-scale problems. It is concluded that the presented approach is robust for both small and large-scale discretely ill-posed least squares problems.     

Are digital natives a myth or reality? University students’ use of digital technologies

This study investigated the extent and nature of university students’ use of digital technologies for learning and socialising. The findings show that students use a limited range of mainly established technologies. Use of collaborative knowledge creation tools, virtual worlds, and social networking sites was low. ‘Digital natives’ and students of a technical discipline (Engineering) used more technology tools when compared to ‘digital immigrants’ and students of a non-technical discipline (Social Work). This relationship may be mediated by the finding that Engineering courses required more intensive and extensive access to technology than Social Work courses. However, the use of technology between these groups is only quantitatively rather than qualitatively different. The study did not find evidence to support popular claims that young people adopt radically different learning styles. Their attitudes to learning appear to be influenced by lecturers’ teaching approaches. Students appear to conform to traditional pedagogies, albeit with minor uses of tools delivering content. The outcomes suggest that although the calls for transformations in education may be legitimate it would be misleading to ground the arguments for such change in students’ shifting patterns of learning and technology use.     

A Variational Aggregation Framework for Patch-Based Optical Flow Estimation

We propose a variational aggregation method for optical flow estimation. It consists of a two-step framework, first estimating a collection of parametric motion models to generate motion candidates, and then reconstructing a global dense motion field. The aggregation step is designed as a motion reconstruction problem from spatially varying sets of motion candidates given by parametric motion models. Our method is designed to capture large displacements in a variational framework without requiring any coarse-to-fine strategy. We handle occlusion with a motion inpainting approach in the candidates computation step. By performing parametric motion estimation, we combine the robustness to noise of local parametric methods with the accuracy yielded by global regularization. We demonstrate the performance of our aggregation approach by comparing it to standard variational methods and a discrete aggregation approach on the Middlebury and MPI Sintel datasets.     

A Newton-like finite element scheme for compressible gas flows

Semi-implicit and Newton-like finite element methods are developed for the stationary compressible Euler equations. The Galerkin discretization of the inviscid fluxes is potentially oscillatory and unstable. To suppress numerical oscillations, the spatial discretization is performed by a high-resolution finite element scheme based on algebraic flux correction. A multidimensional limiter of TVD type is employed. An important goal is the efficient computation of stationary solutions in a wide range of Mach numbers, which is a challenging task due to oscillatory correction factors associated with TVD-type flux limiters. A semi-implicit scheme is derived by a time-lagged linearization of the nonlinear residual, and a Newton-like method is obtained in the limit of infinite CFL numbers. Special emphasis is laid on the numerical treatment of weakly imposed characteristic boundary conditions. Numerical evidence for unconditional stability is presented. It is shown that the proposed approach offers higher accuracy and better convergence behavior than algorithms in which the boundary conditions are implemented in a strong sense.     

Using meta‐modeling in design and implementation of component‐based systems: the SOFA case study

To allow efficient and user‐friendly development of a component‐based application, component systems have to provide a rather complex development infrastructure, including a tool for component composition, component repository, and a run‐time infrastructure. In this paper, we present and evaluate benefits of using meta‐modeling during the process of defining a component system and also during creation of the development and run‐time infrastructures. Most of the presented arguments are based on a broad practical experience with designing the component systems SOFA and SOFA 2; the former designed in a classical ad hoc ‘manual’ way, whereas the latter with the help of meta‐modeling. Copyright © 2010 John Wiley & Sons, Ltd.     

Conversion electron Mössbauer spectroscopy of the surface crystallization of the Fe75Co9B16 amorphous alloy

Using a new design of helium-methane gas-flow detector of conversion electrons for Mössbauer spectroscopy, non-uniform nucleation of the primary -Fe-Co phase on both contact and free surfaces of the Ar(+H₂) annealed amorphous Fe₇₅Co₉B₁₆ alloy was observed in its early crystallization stage. In this state the amount of crystalline phase on the contact ribbon side surpasses that on the free one by a factor of three, whereas no traces of volume crystallization were observed in the transmission spectra. By applying ion implantation to both ribbon surfaces, a slight reduction of the crystalline phase contribution was found. Magnetic domain structure observations were performed in order to evaluate the influence of surface crystallization on magnetic properties.