Dynamic simulation of heart mitral valve with transversely isotropic material model

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2005.Includes bibliographical references (p. 63-69).This thesis develops two methods for simulating, in the finite element setting, the material behavior of heart mitral valve leaflet tissue. First, a mixed pressure-displacement formulation is used to implement the constitutive material behavior with general 3D elements. Second, a shell is formulated that incorporates the 3D material behavior by use of a local plane stress iteration method. Both of these works are based on an existing invariant-based strain energy function that has been experimentally determined for the mitral valve leaflet tissue. Since this material is considered to be nearly incompressible, a mixed pressure-displacement (u/p) formulation is needed to apply the material model in 3D elements. The standard (u/p) formulation is; employed with a modification to ensure positive definiteness of the constitutive tensor at low strains. The shell formulation is introduced as a computationally less expensive alternative to the use of 3D elements. A 4-node shell with mixed interpolation of transverse shears is implemented. To incorporate the 3D material model into this shell, a local plane stress iteration is used to enforce that the shell stress assumption at each integration point. Comparisons of numerical results to analytical predictions verify the accuracy of both the (u/p) formulation and shell element. These methods provide useful bases for finite element simulations of mitral heart valve behavior.by Eli Weinberg.S.M

Multiscale simulations of the aortic heart valve : applications in disease and surgery

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2008.Includes bibliographical references (p. 136-148).This thesis presents mathematical models describing the mechanical behavior of the human aortic heart valve over a range of length and time scales. In the human heart, the valves perform the vital function of controlling the direction of blood flow. Each valve is an intricate mechanical structure, with distinct features and functions at multiple scales. This effort first develops a framework of reference configurations that enables communication between simulations of the different length scales. Three simulations are created within that framework. At the cell scale, the interaction between a single valvular interstitial cell and its surrounding matrix is described. At the tissue scale, a model is created for the valve cusp tissue mechanical behavior, including the multilayered, nonuniform geometry and nonlinear, anisotropic material properties. At the organ scale, a dynamic, three-dimensional model with fluid-structure interaction predicts the motion of the valve, blood, and surrounding tissue. Each simulation is verified against a number of experimental measures. These three simulations together constitute a model for the dynamic, three-dimensional, multiscale mechanical behavior of the healthy human aortic heart valve throughout the cardiac cycle. The model is employed to perform multiscale investigation into the mechanisms of the disease calcific aortic stenosis in three ways. First, the model of the healthy valve is extended to describe disease progression on the decade time scale. Calcification is introduced at the tissue level and the effects on valve function are monitored at the organ level. Second, the role of mechanical deformations in the disease process is examined by comparing multiscale deformations between the normal valve case and a known disease-prone case.(cont.) Finally, a combined computational and experimental study investigates the role of fluid shear in calcific disease. Shears computed in the organ-scale simulation are applied to endothelial cells in vitro. The cells express disease-related genes in a manner consistent with the region-specific nature of calcific disease, providing evidence for a role of shear in the disease process. The multiscale model presented in this thesis has further utility in investigating function, disease, and therapy of the human aortic valve.by Eli J. Weinberg.Ph.D

A Computational Model of Aging and Calcification in the Aortic Heart Valve

The aortic heart valve undergoes geometric and mechanical changes over time. The cusps of a normal, healthy valve thicken and become less extensible over time. In the disease calcific aortic stenosis (CAS), calcified nodules progressively stiffen the cusps. The local mechanical changes in the cusps, due to either normal aging or pathological processes, affect overall function of the valve. In this paper, we propose a computational model for the aging aortic valve that connects local changes to overall valve function. We extend a previous model for the healthy valve to describe aging. To model normal/uncomplicated aging, leaflet thickness and extensibility are varied versus age according to experimental data. To model calcification, initial sites are defined and a simple growth law is assumed. The nodules then grow over time, so that the area of calcification increases from one model to the next model representing greater age. Overall valve function is recorded for each individual model to yield a single simulation of valve function over time. This simulation is the first theoretical tool to describe the temporal behavior of aortic valve calcification. The ability to better understand and predict disease progression will aid in design and timing of patient treatments for CAS

2D Multi-Angle, Multi-Group Neutrino Radiation-Hydrodynamic Simulations of Postbounce Supernova Cores

We perform axisymmetric (2D) multi-angle, multi-group neutrino radiation-hydrodynamic calculations of the postbounce phase of core-collapse supernovae using a genuinely 2D discrete-ordinate (S_n) method. We follow the long-term postbounce evolution of the cores of one nonrotating and one rapidly-rotating 20-solar-mass stellar model for ~400 milliseconds from 160 ms to ~550 ms after bounce. We present a multi-D analysis of the multi-angle neutrino radiation fields and compare in detail with counterpart simulations carried out in the 2D multi-group flux-limited diffusion (MGFLD) approximation to neutrino transport. We find that 2D multi-angle transport is superior in capturing the global and local radiation-field variations associated with rotation-induced and SASI-induced aspherical hydrodynamic configurations. In the rotating model, multi-angle transport predicts much larger asymptotic neutrino flux asymmetries with pole to equator ratios of up to ~2.5, while MGFLD tends to sphericize the radiation fields already in the optically semi-transparent postshock regions. Along the poles, the multi-angle calculation predicts a dramatic enhancement of the neutrino heating by up to a factor of 3, which alters the postbounce evolution and results in greater polar shock radii and an earlier onset of the initially rotationally weakened SASI. In the nonrotating model, differences between multi-angle and MGFLD calculations remain small at early times when the postshock region does not depart significantly from spherical symmetry. At later times, however, the growing SASI leads to large-scale asymmetries and the multi-angle calculation predicts up to 30% higher average integral neutrino energy deposition rates than MGFLD.Comment: 20 pages, 21 figures. Minor revisions. Accepted for publication in ApJ. A version with high-resolution figures may be obtained from http://www.stellarcollapse.org/papers/Ott_et_al2008_multi_angle.pd

Buzzard to Cardinal: Improved Mock Catalogs for Large Galaxy Surveys

We present the Cardinal mock galaxy catalogs, a new version of the Buzzard simulation that has been updated to support ongoing and future cosmological surveys, including the Dark Energy Survey (DES), DESI, and LSST. These catalogs are based on a one-quarter sky simulation populated with galaxies out to a redshift of z = 2.35 to a depth of mr = 27. Compared to the Buzzard mocks, the Cardinal mocks include an updated subhalo abundance matching model that considers orphan galaxies and includes mass-dependent scatter between galaxy luminosity and halo properties. This model can simultaneously fit galaxy clustering and group–galaxy cross-correlations measured in three different luminosity threshold samples. The Cardinal mocks also feature a new color assignment model that can simultaneously fit color-dependent galaxy clustering in three different luminosity bins. We have developed an algorithm that uses photometric data to further improve the color assignment model and have also developed a novel method to improve small-scale lensing below the ray-tracing resolution. These improvements enable the Cardinal mocks to accurately reproduce the abundance of galaxy clusters and the properties of lens galaxies in the DES data. As such, these simulations will be a valuable tool for future cosmological analyses based on large sky surveys

Hemodynamic Environments from Opposing Sides of Human Aortic Valve Leaflets Evoke Distinct Endothelial Phenotypes In Vitro

The regulation of valvular endothelial phenotypes by the hemodynamic environments of the human aortic valve is poorly understood. The nodular lesions of calcific aortic stenosis (CAS) develop predominantly beneath the aortic surface of the valve leaflets in the valvular fibrosa layer. However, the mechanisms of this regional localization remain poorly characterized. In this study, we combine numerical simulation with in vitro experimentation to investigate the hypothesis that the previously documented differences between valve endothelial phenotypes are linked to distinct hemodynamic environments characteristic of these individual anatomical locations. A finite-element model of the aortic valve was created, describing the dynamic motion of the valve cusps and blood in the valve throughout the cardiac cycle. A fluid mesh with high resolution on the fluid boundary was used to allow accurate computation of the wall shear stresses. This model was used to compute two distinct shear stress waveforms, one for the ventricular surface and one for the aortic surface. These waveforms were then applied experimentally to cultured human endothelial cells and the expression of several pathophysiological relevant genes was assessed. Compared to endothelial cells subjected to shear stress waveforms representative of the aortic face, the endothelial cells subjected to the ventricular waveform showed significantly increased expression of the “atheroprotective” transcription factor Kruppel-like factor 2 (KLF2) and the matricellular protein Nephroblastoma overexpressed (NOV), and suppressed expression of chemokine Monocyte-chemotactic protein-1 (MCP-1). Our observations suggest that the difference in shear stress waveforms between the two sides of the aortic valve leaflet may contribute to the documented differential side-specific gene expression, and may be relevant for the development and progression of CAS and the potential role of endothelial mechanotransduction in this disease.National Institutes of Health (U.S.) (Molecular, Cellular, and Tissue Biomechanics training grant (T32 EB006348))National Institutes of Health (U.S.) (NHLBI RO1-HL7066686)Charles Stark Draper Laboratory (Fellowship

Cosmological Constraints from the SDSS maxBCG Cluster Catalog

We use the abundance and weak lensing mass measurements of the SDSS maxBCG cluster catalog to simultaneously constrain cosmology and the richness--mass relation of the clusters. Assuming a flat \LambdaCDM cosmology, we find \sigma_8(\Omega_m/0.25)^{0.41} = 0.832\pm 0.033 after marginalization over all systematics. In common with previous studies, our error budget is dominated by systematic uncertainties, the primary two being the absolute mass scale of the weak lensing masses of the maxBCG clusters, and uncertainty in the scatter of the richness--mass relation. Our constraints are fully consistent with the WMAP five-year data, and in a joint analysis we find \sigma_8=0.807\pm 0.020 and \Omega_m=0.265\pm 0.016, an improvement of nearly a factor of two relative to WMAP5 alone. Our results are also in excellent agreement with and comparable in precision to the latest cosmological constraints from X-ray cluster abundances. The remarkable consistency among these results demonstrates that cluster abundance constraints are not only tight but also robust, and highlight the power of optically-selected cluster samples to produce precision constraints on cosmological parameters.Comment: comments welcom

Determining the main-sequence mass of Type II supernova progenitors

We present radiation-hydrodynamics simulations of core-collapse supernova (SN) explosions, artificially generated by driving a piston at the base of the envelope of a rotating or non-rotating red-supergiant progenitor star. We search for trends in ejecta kinematics in the resulting Type II-Plateau (II-P) SN, exploring dependencies with explosion energy and pre-SN stellar-evolution model. We recover the trivial result that larger explosion energies yield larger ejecta velocities in a given progenitor. However, we emphasise that for a given explosion energy, the increasing helium-core mass with main-sequence mass of such Type II-P SN progenitors leads to ejection of core-embedded oxygen-rich material at larger velocities. We find that the photospheric velocity at 15d after shock breakout is a good and simple indicator of the explosion energy in our selected set of pre-SN models. This measurement, combined with the width of the nebular-phase OI6303-6363A line, can be used to place an upper-limit on the progenitor main-sequence mass. Using the results from our simulations, we find that the current, but remarkably scant, late-time spectra of Type II-P SNe support progenitor main-sequence masses inferior to ~20Msun and thus, corroborate the inferences based on the direct, but difficult, progenitor identification in pre-explosion images. The narrow width of OI6303-6363A in Type II-P SNe with nebular spectra does not support high-mass progenitors in the range 25-30Msun. Combined with quantitative spectroscopic modelling, such diagnostics offer a means to constrain the main-sequence mass of the progenitor, the mass fraction of the core ejected, and thus, the mass of the compact remnant formed.Comment: accepted to MNRA

Nectin like-5 overexpression correlates with the malignant phenotype in cutaneous melanoma

NECL-5 is involved in regulating cell–cell junctions, in cooperation with cadherins, integrins and platelet-derived growth factor receptor, that are essential for intercellular communication. Its role in malignant transformation was previously described. It has been reported that transformation of melanocytes is associated with altered expression of adhesion molecules suggesting the potential involment of NECL-5 in melanoma development and prognosis. To shed light on this issue, the expression and the role of NECL-5 in melanoma tissues was investigated by bioinformatic and molecular approaches. NECL-5 was up-regulated both at the mRNA and the protein levels in WM35, M14 and A375 cell lines compared with normal melanocytes. A subsequent analysis in primary and metastatic melanoma specimens confirmed “in vitro� findings. NECL-5 overexpression was observed in 53 of 59 (89.8%) and 12 of 12 (100%), primary melanoma and melanoma metastasis, respectively; while, low expression of NECL-5 was detected in 12 of 20 (60%) benign nevi. A significant correlation of NECL-5 overexpression was observed with most of known negative melanoma prognostic factors, including lymph-node involvement (P = 0.009) and thickness (P = 0.004). Intriguingly, by analyzing the large series of melanoma samples in the Xu dataset, we identified the transcription factor YY1 among genes positively correlated with NECL-5 (r = 0.5). The concordant computational and experimental data of the present study indicate that the extent of NECL-5 expression correlates with melanoma progression