Radiologic evaluation of images from computed tomography (CT) or magnetic resonance imaging for diagnostic purposes is based on the analysis of single slices, occasionally supplementing this information with 3D reconstructions as well as surface or volume rendered images. However, due to the complexity of anatomical or pathological structures in biomedical imaging, innovative visualization techniques are required to display morphological characteristics three dimensionally. Virtual reality is a modern tool of representing visual data, The observer has the impression of being "inside" a virtual surrounding, which is referred to as immersive imaging. Such techniques are currently being used in technical applications, e.g. in the automobile industry. Our aim is to introduce a workflow realized within one simple program which processes common image stacks from CT, produces 3D volume and surface reconstruction and rendering, and finally includes the data into a virtual reality device equipped with a motion head tracking cave automatic virtual environment system. Such techniques have the potential to augment the possibilities in non-invasive medical imaging, e.g. for surgical planning or educational purposes to add another dimension for advanced understanding of complex anatomical and pathological structures. To this end, the reconstructions are based on advanced mathematical techniques and the corresponding grids which we can export are intended to form the basis for simulations of mathematical models of the pathogenesis of different diseases.
When a realistic modelling of radioactive contaminant transport in flowing groundwater is required, very large systems of coupled partial and ordinary differential equations can arise that have to be solved numerically. For that purpose, the software package r(3)t is developed in which several advanced numerical methods are implemented to solve such models efficiently and accurately. Using software tools of r(3)t one can treat successfully nontrivial mathematical problems like advection-dominated system with different retardation of transport for each component and with nonlinear Freundlich sorption and/or precipitation. Additionally, long time simulations on complex 3D geological domains using unstructured grids can be realized. In this paper we introduce and summarize the most important and novel features of numerical simulation for radioactive contaminant transport in porous media when using r(3)t.
Advanced simulations within biophysical applications ask for advanced algorithms and implementations which are running efficiently on massively parallel high performance computers. The software framework UG fulfills these preconditions. Therefore, we present insight into the experimental basics, the modelling and simulation details, and the biophysical meaning of the estimation of the diffusion constant of a major player in the replication of the genetic information of the Hepatitis C virus (HCV), namely the NS5A viral protein. NS5A movement is restricted to the surface of the Endoplasmatic Reticulum (ER, a medusa-hair like important cell compartment). Hence, the dynamics of NS5A are described by surface PDEs (sPDE) which mimic experimental FRAP (fluorescence recovery after photobleaching) time series data. The sPDE computations were performed with UG upon large unstructured grids representing realistic reconstructed ER surfaces. We explain the context of the parameter estimations which asked for a substantial amount of single sPDE evaluations which we performed on the HLRS Stuttgart Hermit and Hornet supercomputers for various experimental data sets and for various geometric setups. This enabled us to derive valid final values for the diffusion constant of NS5A on the ER surface. The estimated diffusion constant values are intended to enter spatio-temporal resolved models of HCV replication dynamics at a cellular level.
Human pluripotent stem cell (hPSC) density is an important factor in self-renewal and differentiation fates; however, the mechanisms through which hPSCs sense cell density and process this information in making cell fate decisions remain to be fully understood. One particular pathway that may prove important in density-dependent signaling in hPSCs is the Hippo pathway, which is regulated by cell-cell contact and mechanosensing through the cytoskeleton and has been linked to the maintenance of stem cell pluripotency. To probe regulation of Hippo pathway activity in hPSCs, we assessed whether Hippo pathway transcriptional activator YAP was differentially modulated by cell density. At higher cell densities, YAP phosphorylation and localization to the cytoplasm increased, which led to decreased YAP-mediated transcriptional activity. Furthermore, total YAP protein levels diminished at high cell density due to the phosphorylation-targeted degradation of YAP. Inducible shRNA knockdown of YAP reduced expression of YAP target genes and pluripotency genes. Finally, the density-dependent increase of neuroepithelial cell differentiation was mitigated by shRNA knockdown of YAP. Our results suggest a pivotal role of YAP in cell density-mediated fate decisions in hPSCs.
Substrate composition significantly impacts human pluripotent stem cell (hPSC) self-renewal and differentiation, but relatively little is known about the role of endogenously produced extracellular matrix (ECM) components in regulating hPSC fates. Here we identify α-5 laminin as a signature ECM component endogenously synthesized by undifferentiated hPSCs cultured on defined substrates. Inducible shRNA knockdown and Cas9-mediated disruption of the LAMA5 gene dramatically reduced hPSC self-renewal and increased apoptosis without affecting the expression of pluripotency markers. Increased self-renewal and survival was restored to wild-type levels by culturing the LAMA5-deficient cells on exogenous laminin-521. Furthermore, treatment of LAMA5-deficient cells with blebbistatin or a ROCK inhibitor partially restored self-renewal and diminished apoptosis. These results demonstrate that endogenous α-5 laminin promotes hPSC self-renewal in an autocrine and paracrine manner. This finding has implications for understanding how stem cells dynamically regulate their microenvironment to promote self-renewal and provides guidance for efforts to design substrates for stem cell bioprocessing.
We present a theoretical and numerical study of mass transport in a porous medium saturated with a fluid and characterised by an evolving internal structure. The dynamics of the porous medium and the fluid as well as their reciprocal interactions are described at a coarse scale, so that the fundamental tools of Mixture Theory and Continuum Mechanics can be used. The evolution of the internal structure of the porous medium, which is here primarily imputed either to growth or to mass exchange with the fluid, is investigated by enriching the space of kinematic variables of the mixture with a set of structural descriptors, each of which is power-conjugate to generalised forces satisfying a balance law. Establishing the influence of the structural change of the porous medium on the transport properties of the mixture and, thus, on the quantities characterising fluid flow is the crux of our contribution.
The modeling of physical phenomena in a variety of fields of scientific interest lead to a formulation in terms of partial differential equations. Especially when complex geometries as the domain of definition are involved, a direct and exact solution is not accessible, but numerical schemes are used to compute an approximate discrete solution. In this report, we focus on elliptic and parabolic types of equations that include spatial operators of second order. When discretizing such problems using commonly known discretization schemes such as finite element methods or finite volume methods, large systems of linear equations arise naturally. Their solution takes the largest amount of the overall computing time.
We investigate salinity- and thermohaline-driven flow in a heterogeneous porous medium in which the heterogeneity is due to the presence of fractures. In our study, fractures delimit thin regions of space occupied by a porous medium whose properties are markedly different from those of the porous medium enclosing them. We formulate some benchmark problems in which fractures are present, and solve them by adopting two approaches: (i) The fractures have the same dimension, d, as the enclosing medium and are said to be d dimensional; (ii) the fractures are viewed as (d - 1)-dimensional manifolds, and the equations of density-driven flow are obtained by averaging the d-dimensional laws over the fracture width. We use both approaches as long as salinity-driven problems are considered, and we use the first approach only for the solution of the thermohaline problems. Our aim is twofold: (a) testing the reliability of the (d - 1)-dimensional approach for the considered examples, and (b) studying the effect of fractures on heat transport.
UG [2] is a software framework for the numerical solution of problems that are described by systems of partial differential equations. It provides functionality for unstructured grids, adaptive local grid refinement, robust multigrid methods for the solution of systems of linear equations, and parallelization of all these algorithms on MIMD-style computers. In this contribution, we present results of an application built upon UG, a finite-volume simulator for thermohaline-driven flow called d(3)f [3], on HLRS' Nehalem cluster.
We investigate some aspects of thermodiffusion in saturated porous media in the presence of both density- and temperature-driven single-phase flow. This type of flow is sometimes referred to as thermohaline flow. We also review some fundamental thermodynamic concepts that are necessary for the formulation of the examined problem and compare our approach with some other models of thermodiffusion available in the literature. Our constitutive description and mathematical modeling are framed with in the hybrid mixture theory. Finally, we show and discuss the results of numerical simulations of some selected test cases in which thermodiffusion as well as thermohaline flow are considered.
We provide three-dimensional numerical simulations of the thermohaline-driven buoyancy of a brine “parcel” immersed in an initially homogeneous porous medium of hydrological interest. Our purpose is to improve our understanding of the thermohaline flow through the 3D visualization of the evolving patterns generated by the distributions of brine, temperature, and fluid density in the porous medium. We propose a possible physical interpretation of our results, which are obtained within the approximations usually employed in the context of density- and temperature-driven flow.
This study focuses on the further development and testing of an existing Mouse Movement Biometric Identification system. Building on the research and work from a previous implementation of a mouse biometric system, the study focuses on enhancing the data capture program to enrich the data with more features to identify the user, collecting more samples of data, normalization of the data into the required format and comparing the results to previous conclusions. A total of 205 data files were collected from users to further develop and test the software. All features of the Mouse Movement system are discussed as well as final recommendations for future research and improvement has been included.