Dynamic simulation tools for the analysis and optimization of novel collection, filtration and sample preparation systems

The focus of research effort described here is to develop novel simulation tools to address design and optimization needs in the general class of problems that involve species and fluid (liquid and gas phases) transport through sieving media. This was primarily motivated by the heightened attention on Chem/Bio early detection systems, which among other needs, have a need for high efficiency filtration, collection and sample preparation systems. Hence, the said goal was to develop the computational analysis tools necessary to optimize these critical operations. This new capability is designed to characterize system efficiencies based on the details of the microstructure and environmental effects. To accomplish this, new lattice Boltzmann simulation capabilities where developed to include detailed microstructure descriptions, the relevant surface forces that mediate species capture and release, and temperature effects for both liquid and gas phase systems. While developing the capability, actual demonstration and model systems (and subsystems) of national and programmatic interest were targeted to demonstrate the capability. As a result, where possible, experimental verification of the computational capability was performed either directly using Digital Particle Image Velocimetry or published results

The Analysis of Thin Wires Using Higher-Order Elements and Basis Functions

Thin wire analysis was applied to curved wire segments in [1], but a special procedure was needed to evaluate the self and near-self terms. The procedure involved associating the singular behavior with a straight segment tangent to the curved source segment, permitting use of algorithms for straight wires. Recently, a procedure that avoids the singularity extraction for straight wires was presented in [2-4]. In this paper, the approach in [4] is applied to curved (or higher-order) wires using a procedure similar to that used in [1] for singularity extraction. Here, the straight tangent segment is used to determine the quadrature rules to be used on the curved segment. The result is a formulation that allows for a general mixture of higher-order basis functions [5] and higher-order wire segments

An Explicit Time-Domain Hybrid Formulation Based on the Unified Boundary Condition

An approach to stabilize the two-surface, time domain FEM/BI hybrid by means of a unified boundary condition is presented. The first-order symplectic finite element formulation [1] is used along with a version of the unified boundary condition of Jin [2] reformulated for Maxwell's first-order equations in time to provide both stability and accuracy over the first-order ABC. Several results are presented to validate the numerical solutions. In particular the dipole in a free-space box is analyzed and compared to the Dirchlet boundary condition of Ziolkowski and Madsen [3] and to a Neuman boundary condition approach

Pharmacological levels of withaferin A (Withania somnifera) trigger clinically relevant anticancer effects specific to triple negative breast cancer cells

Withaferin A (WA) isolated from Withania somnifera (Ashwagandha) has recently become an attractive phytochemical under investigation in various preclinical studies for treatment of different cancer types. In the present study, a comparative pathway-based transcriptome analysis was applied in epithelial-like MCF-7 and triple negative mesenchymal MDA-MB-231 breast cancer cells exposed to different concentrations of WA which can be detected systemically in in vivo experiments. Whereas WA treatment demonstrated attenuation of multiple cancer hallmarks, the withanolide analogue Withanone (WN) did not exert any of the described effects at comparable concentrations. Pathway enrichment analysis revealed that WA targets specific cancer processes related to cell death, cell cycle and proliferation, which could be functionally validated by flow cytometry and real-time cell proliferation assays. WA also strongly decreased MDA-MB-231 invasion as determined by single-cell collagen invasion assay. This was further supported by decreased gene expression of extracellular matrix-degrading proteases (uPA, PLAT, ADAM8), cell adhesion molecules (integrins, laminins), pro-inflammatory mediators of the metastasis-promoting tumor microenvironment (TNFSF12, IL6, ANGPTL2, CSF1R) and concomitant increased expression of the validated breast cancer metastasis suppressor gene (BRMS1). In line with the transcriptional changes, nanomolar concentrations of WA significantly decreased protein levels and corresponding activity of uPA in MDA-MB-231 cell supernatant, further supporting its anti-metastatic properties. Finally, hierarchical clustering analysis of 84 chromatin writer-reader-eraser enzymes revealed that WA treatment of invasive mesenchymal MDA-MB-231 cells reprogrammed their transcription levels more similarly towards the pattern observed in non-invasive MCF-7 cells. In conclusion, taking into account that sub-cytotoxic concentrations of WA target multiple metastatic effectors in therapy-resistant triple negative breast cancer, WA-based therapeutic strategies targeting the uPA pathway hold promise for further (pre)clinical development to defeat aggressive metastatic breast cancer

Fiscal Year 2006

This is the final report for LDRD 01-ERD-005. The Principle Investigator was Robert Sharpe. Collaborators included Niel Madsen, Benjamin Fasenfest, John D. Rockway, of the Defense Sciences Engineering Division (DSED), Vikram Jandhyala and James Pingenot from the University of Washington, and Mark Stowell of the Center for Applications Development and Software Engineering (CADSE). It should be noted that Benjamin Fasenfest and Mark Stowell were partially supported under other funding. The purpose of this LDRD effort was to enhance LLNL's computational electromagnetics capability in the area of broadband radiation and scattering. For radiation and scattering problems our transient EM codes are limited by the approximate Radiation Boundary Conditions (RBC's) used to model the radiation into an infinite space. Improved RBC's were researched, developed, and incorporated into the existing EMSolve finite-element code to provide a 10-100x improvement in the accuracy of the boundary conditions. Section I provides an introduction to the project and the project goals. Section II provides a summary of the project's research and accomplishments as presented in the attached papers

A Hybrid FEM-BEM Unified Boundary Condition with Sub-Cycling for Electromagnetic Radiation

Hybrid solutions to time-domain electromagnetic problems offer many advantages when solving open-region scattering or radiation problems. Hybrid formulations use a finite-element or finite-difference discretization for the features of interest, then bound this region with a layer of planar boundary elements. The use of volume discretization allows for intricate features and many changes in material within the structure, while the boundary-elements provide a highly accurate radiating boundary condition. This concept has been implemented previously, using the boundary elements to set the E-field, H-field, or both for an FDTD grid, for example in [1][2][3], or as a mixed boundary condition for the second order wave equation solved by finite elements [4]. Further study has focused on using fast methods, such as the Plane Wave Time Domain method [3][4] to accelerate the BEM calculations. This paper details a hybrid solver using the coupled first-order equations for the E and H fields in the finite-element region. This formulation is explicit, with a restriction on the time step for stability. When this time step is used in conjunction with the boundary elements forming either a inhomogeneous Dirichlet or Neuman boundary condition on the finite-element mesh, late time instabilities occur. To combat this, a Unified Boundary Condition (UBC), similar to the one in [4] for the second-order wave equation, is used. Even when this UBC is used, the late time instabilities are merely delayed if standard testing in time is used. However, the late time instabilities can be removed by replacing centroid based time interpolation with quadrature point based time interpolation for the boundary elements, or by sub-cycling the boundary element portion of the formulation. This sub-cycling, used in [3] for FDTD to reduce complexity, is shown here to improve stability and overall accuracy of the technique