1,468 research outputs found
Atlas/Centaur flight performance reserve Monte Carlo analysis AC-7
Monte Carlo method for computing Atlas/Centaur flight performance reserv
Probability tree algorithm for general diffusion processes
Motivated by path-integral numerical solutions of diffusion processes,
PATHINT, we present a new tree algorithm, PATHTREE, which permits extremely
fast accurate computation of probability distributions of a large class of
general nonlinear diffusion processes
Monte Carlo flight performance reserve program
Computer program for evaluating flight performance reserve requirements for Centaur vehicle using Monte Carlo metho
Internal Stress in a Model Elasto-Plastic Fluid
Plastic materials can carry memory of past mechanical treatment in the form
of internal stress. We introduce a natural definition of the vorticity of
internal stress in a simple two-dimensional model of elasto-plastic fluids,
which generates the internal stress. We demonstrate how the internal stress is
induced under external loading, and how the presence of the internal stress
modifies the plastic behavior.Comment: 4 pages, 3 figure
Method and system for measurement of mechanical properties of molecules and cells
Mechanical stresses and deformations are applied directly to cell surface receptors or molecules and measured using a system including a magnetic twisting device in combination with ferromagnetic microbeads coated with ligands for integrins or any other surface receptors. The system can be used diagnostically to characterize cells and molecules and to determine the effect of transformation and compounds, including drugs, on the cells and molecules. The system can also be used to induce cells to grow or alter production of molecules by the cells
Spherical harmonic decomposition applied to spatial-temporal analysis of human high-density EEG
We demonstrate an application of spherical harmonic decomposition to analysis
of the human electroencephalogram (EEG). We implement two methods and discuss
issues specific to analysis of hemispherical, irregularly sampled data.
Performance of the methods and spatial sampling requirements are quantified
using simulated data. The analysis is applied to experimental EEG data,
confirming earlier reports of an approximate frequency-wavenumber relationship
in some bands.Comment: 12 pages, 8 figures, submitted to Phys. Rev. E, uses APS RevTeX
style
Bio-inspired Tensegrity Soft Modular Robots
In this paper, we introduce a design principle to develop novel soft modular
robots based on tensegrity structures and inspired by the cytoskeleton of
living cells. We describe a novel strategy to realize tensegrity structures
using planar manufacturing techniques, such as 3D printing. We use this
strategy to develop icosahedron tensegrity structures with programmable
variable stiffness that can deform in a three-dimensional space. We also
describe a tendon-driven contraction mechanism to actively control the
deformation of the tensegrity mod-ules. Finally, we validate the approach in a
modular locomotory worm as a proof of concept.Comment: 12 pages, 7 figures, submitted to Living Machine conference 201
Endothelial Cilia Are Fluid Shear Sensors That Regulate Calcium Signaling and Nitric Oxide Production Through Polycystin-1
Background— When challenged with extracellular fluid shear stress, vascular endothelial cells are known to release nitric oxide, an important vasodilator. Here, we show that the ability of cultured endothelial cells to sense a low range of fluid shear depends on apical membrane organelles, called cilia, and that cilia are compartments required for proper localization and function of the mechanosensitive polycystin-1 molecule. Methods and Results— Cells with the Pkd1null/null or Tg737orpk/orpk mutation encoded for polycystin-1 or polaris, respectively, are unable to transmit extracellular shear stress into intracellular calcium signaling and biochemical nitric oxide synthesis. Cytosolic calcium and nitric oxide recordings further show that fluid shear sensing is a cilia-specific mechanism because other mechanical or pharmacological stimulation does not abolish calcium and nitric oxide signaling in polycystin-1 and polaris mutant endothelial cells. Polycystin-1 localized in the basal body of Tg737orpk/orpk endothelial cells is insufficient for a fluid shear stress response. Furthermore, the optimal shear stress to which the cells respond best does not alter the apical cilia structure but modifies the responsiveness of cells to higher shear stresses through proteolytic modification of polycystin-1. Conclusions— We demonstrate for the first time that polycystin-1 (required for cilia function) and polaris (required for cilia structure) are crucial mechanosensitive molecules in endothelial cells. We propose that a distinctive communication with the extracellular microenvironment depends on the proper localization and function of polycystin-1 in cilia
PAR1 Agonists Stimulate APC-Like Endothelial Cytoprotection and Confer Resistance to Thromboinflammatory Injury
Stimulation of protease-activated receptor 1 (PAR1) on endothelium by activated protein C (APC) is protective in several animal models of disease, and APC has been used clinically in severe sepsis and wound healing. Clinical use of APC, however, is limited by its immunogenicity and its anticoagulant activity. We show that a class of small molecules termed “parmodulins” that act at the cytosolic face of PAR1 stimulates APC-like cytoprotective signaling in endothelium. Parmodulins block thrombin generation in response to inflammatory mediators and inhibit platelet accumulation on endothelium cultured under flow. Evaluation of the antithrombotic mechanism showed that parmodulins induce cytoprotective signaling through Gβγ, activating a PI3K/Akt pathway and eliciting a genetic program that includes suppression of NF-κB–mediated transcriptional activation and up-regulation of select cytoprotective transcripts. STC1 is among the up-regulated transcripts, and knockdown of stanniocalin-1 blocks the protective effects of both parmodulins and APC. Induction of this signaling pathway in vivo protects against thromboinflammatory injury in blood vessels. Small-molecule activation of endothelial cytoprotection through PAR1 represents an approach for treatment of thromboinflammatory disease and provides proof-of-principle for the strategy of targeting the cytoplasmic surface of GPCRs to achieve pathway selective signaling
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Silencing HoxA1 by Intraductal Injection of siRNA Lipidoid Nanoparticles Prevents Mammary Tumor Progression in Mice
With advances in screening, the incidence of detection of premalignant breast lesions has increased in recent decades; however, treatment options remain limited to surveillance or surgical removal by lumpectomy or mastectomy. We hypothesized that disease progression could be blocked by RNA interference (RNAi) therapy and set out to develop a targeted therapeutic delivery strategy. Using computational gene network modeling, we identified HoxA1 as a putative driver of early mammary cancer progression in transgenic C3(1)-SV40TAg mice. Silencing this gene in cultured mouse or human mammary tumor spheroids resulted in increased acinar lumen formation, reduced tumor cell proliferation, and restoration of normal epithelial polarization. When the HoxA1 gene was silenced in vivo via intraductal delivery of nanoparticle-formulated small interfering RNA (siRNA) through the nipple of transgenic mice with early-stage disease, mammary epithelial cell proliferation rates were suppressed, loss of estrogen and progesterone receptor expression was prevented, and tumor incidence was reduced by 75%. This approach that leverages new advances in systems biology and nanotechnology offers a novel noninvasive strategy to block breast cancer progression through targeted silencing of critical genes directly within the mammary epithelium.Engineering and Applied Science
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