3,070 research outputs found
Piezoelectric Display Speaker Design with Enclosure System Using Boundary Element Analysis
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Developing a reduced order model for pulsatile blood flow simulations using minimal three-dimensional simulation data
No full textBackground and Objective: Pulsatile blood flow simulations are essential for understanding cardiovascular physiology but are often constrained by the computational cost of full 3D modeling. While reduced-order models (ROMs) offer efficiency, many depend on empirical parameters, limiting their accuracy in complex subject-specific geometries. This study introduces a 1D ROM that minimizes empirical assumptions by deriving parameters directly from 3D simulation data. Methods: The proposed ROM estimates pressure-flow relationships by fitting parameters of a simplified 1D blood flow equation to results from three 3D simulations under distinct flow conditions. Validation was performed against full 3D Computational Fluid Dynamics (CFD) simulations for three cases: an idealized stenotic cylinder, a patient-specific coarcted aorta, and a coronary artery model with serial lesions. The model was also compared with a widely used empirical stenosis model. Results: The ROM achieved mean relative errors below 2.0 % in all cases and under 1.0 % in the coronary model with multiple lesions. It significantly outperformed the empirical model in complex geometries and delivered up to 3000 times faster computation on a desktop compared to 3D simulations performed on a 64-core high-performance computing system. Conclusions: By leveraging 3D simulation data, the proposed 1D ROM combines high accuracy with exceptional computational efficiency across various geometries. Its robustness and speed make it well suited for clinical applications, optimization tasks, and uncertainty quantification.
IFN-γ Up-Regulates IL-18 Gene Expression Via IFN Consensus Sequence-Binding Protein and Activator Protein-1 Elements in Macrophages
No full textConstitutive IL-18 expression is detected from many different cells, including macrophages, keratinocytes, and osteoblasts. It has been known that IL-18 gene expression is regulated by two different promoters (p1 promoter and p2 promoter). When RAW 264.7 macrophages were treated with IFN-γ, IL-18 gene expression was increased in a dose- and time-dependent manner. IFN-γ activated the inducible promoter 1, but not the constitutive promoter 2. Mutagenesis studies indicated that an IFN consensus sequence-binding protein (ICSBP) binding site between -39 and -22 was critical for the IFN-γ inducibility. EMSA using an ICSBP oligonucleotide probe showed that IFN-γ treatment increased the formation of DNA-binding complex, which was supershifted with anti-IFN regulatory factor-1 Ab and anti-ICSBP Ab. Another element, an AP-1 site between -1120 and -1083, was important. EMSA using an AP-1-specific oligonucleotide demonstrated that IFN-γ or LPS treatment increased the AP-1-binding activity. The addition of anti-c-Jun Ab or anti-c-Fos Ab to IFN-γ- or LPS-treated nuclear extracts resulted in the reduction of AP-1 complex or the formation of a supershifted complex. Taken together, these results indicate that IFN-γ increased IL-18 gene expression via ICSBP and AP-1 elements.open
Interleukin-6-induced tyrosine phosphorylation of phospholipase C-γ1 in PC12 cells
No full textPhospholipase C (PLC)-γ1 plays a pivotal role in the signal transduction pathway mediated by growth factors. In this study, we found that neurite outgrowth of pheochromocytoma (PC12) cells was significantly induced by interleukin-6 (IL-6). Stimulation of PC12 cells with IL-6 led to tyrosine phosphorylation of PLC-γ1 in a dose- and time-dependent manner. IL-6 stimulation also increased the hydrolysis of phosphatidylinositol 4,5-bisphosphate. Accumulation of total inositol phosphate as well as tyrosine phosphorylation of PLC-γ1 was inhibited by the pretreatment of protein kinase inhibitors such as genistein and staurosporine. These results suggest that PLC-γ1 may be involved in the signal transduction pathway of IL-6-induced PC12 cell differentiation.open
Franny Choi, 41st Annual ODU Literary Festival
No full textFranny Choi is a queer, Korean-American poet, playwright, teacher, organizer, pottymouth, GryffinClaw, and general overachiever. She is the author of Floating, Brilliant, Gone (2014), and a chapbook, Death by Sex Machine (2017). She has received awards from the Poetry Foundation and the Helen Zell Writers Program, as well as fellowships from the Vermont Studio Center and the Rhode Island State Council on the Arts. Her poems have appeared in journals including Poetry magazine, American Poetry Review, New England Review, and her work has been featured by the Huffington Post, PBS NewsHour, and Angry Asian Man
Sensitivity of Pulsatile Parameters of Computed Fractional Flow Reserve using a Reduced-order Model
No full textFractional flow reserve (FFR) is the clinical gold standard for diagnosing coronary artery disease, yet many computational methods rely on steady flow assumptions even though clinical FFR values are measured under pulsatile flow conditions. To address the computational cost and uncertainty associated with pulsatile blood flow simulations, we present a reduced-order model combined with a polynomial chaos expansion (PCE) method. The coronary geometry is represented by thin slabs defined by consecutive centerline points and radius, while a polynomial function approximates pressure differences as a function of flow and its time derivative based on minimal three-dimensional simulations. Diverse pulsatile flow conditions are modeled using lumped parameter models which approximate a wide range of pulsatile flow conditions. Uncertainties in pulsatile parameters, including cardiac output, heart rate, and pulse pressure, are modeled using a third-order Chebyshev PCE to maintain a mean relative error below 1.0%. Validation was conducted using a cylindrical model across stenosis severities from 40% to 90%, as well as a patient-specific model with diverse disease conditions. In both cases, the computed FFR distributions agreed with clinical observations. Sensitivity analysis showed that myocardial compression, distal aortic resistance, and contractility are the primary factors influencing FFR variability, with FFR variation exhibiting a linear correlation with its value. This reduced-order approach enables efficient pulsatile FFR simulations and provides valuable insights into key parameters affecting FFR
SENSITIVITY OF PULSATILE PARAMETERS OF COMPUTED FRACTIONAL FLOW RESERVE USING A REDUCED ORDER MODEL
No full textFractional flow reserve (FFR) has been recognized as a gold standard in diagnosing coronary artery disease and many endeavors have been conducted to compute FFR using computational methods. The majority of them, however, have utilized steady flow analysis but FFR in reality is measured by averaging pulsatile pressure quantities. Pulsatile blood flow simulations are often avoided due to the computational expense and the uncertainties in approximating pulsatile blood flow conditions.To address these two limitations, we develop a reduced-order model to efficiently approximate three-dimensional pulsatile blood flow simulations and integrate with a non-invasive polynomial chaos expansion (PCE) method for the uncertainty quantification of the pulsatile parameters, such as cardiac outputs and heart rates. A three-dimensional coronary geometry is approximated as a collection of thin slabs comprising two consecutive centerline points and the corresponding radius values. The relationship between the flow and pressure difference for each slab is approximated by conducting three-dimensional simulations at three different flow conditions and fitting to a polynomial function of flow and flow time derivative. A lumped parameter model is coupled to the boundaries of the geometry as a boundary condition and the parameter values are chosen to span a wide, physiologically realistic pressure and flow values. For the PCE method, the Chebyshev polynomial order of three is chosen to maintain the mean relative error of the PCE results within 1.0%.The methodology was validated using both a simple cylindrical geometry with degrees of stenosis ranging from 40% to 90% and a patient-specific coronary model with a randomly generated degree of stenosis between 40% and 90% and varying numbers of serial lesions between one and three. In both cases, the variations in the computed FFR values were comparable to those of the clinical data. The sensitivity analysis revealed that among the pulsatile parameters, myocardial pressure effect, aortic distal resistance, and heart contractility significantly influence the pulsatile FFR computation. Further, the variation in FFR was found to exhibit a linear correlation with its value. We show that the developed methodology can simulate FFR with uncertainties in pulsatile parameters at a reasonable computational expense, while also providing insights into the key factors affecting FFR
Protein Phosphatase 2A Modulates the Proliferation of Human Multiple Myeloma Cells via Regulation of the Production of Reactive Oxygen Intermediates and Anti-Apoptotic Factors
No full textTo understand the roles of reactive oxygen intermediates (ROI) in Fas-mediated apoptosis of myeloma cells, the effects of antioxidants were tested. Fas-mediated apoptosis was further increased in the presence of antioxidants such as N-acetyl-L-cysteine and glutathione, but it was decreased when hydrogen peroxide was added. The intracellular ROI level was significantly decreased in myeloma cells treated with okadaic acid, an inhibitor of protein phosphatases 1 and 2A (PP1/PP2A). To clarify the direct roles of PP2A in myeloma cell growth, the PP2A transfected cell lines, sense- or antisense-PP2A transfectants, were established. Spontaneous cell growth of antisense-PP2A transfectants was reduced compared with that of vector transfectants. The intracellular ROI level was significantly decreased in antisense-PP2A transfectants but increased in sense-PP2A transfectants compared with vector controls. In addition, anti-apoptotic factors such as bcl-2 and IL-6 were reduced in antisense-PP2A transfectants. Taken together, these results indicate that PP2A is an essential factor for survival and growth of myeloma cells via regulation of intracellular ROI and anti-apoptotic factors.open
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