Cartesian Off-Body Grid Adaption for Viscous Time- Accurate Flow Simulation

An improved solution adaption capability has been implemented in the OVERFLOW overset grid CFD code. Building on the Cartesian off-body approach inherent in OVERFLOW and the original adaptive refinement method developed by Meakin, the new scheme provides for automated creation of multiple levels of finer Cartesian grids. Refinement can be based on the undivided second-difference of the flow solution variables, or on a specific flow quantity such as vorticity. Coupled with load-balancing and an inmemory solution interpolation procedure, the adaption process provides very good performance for time-accurate simulations on parallel compute platforms. A method of using refined, thin body-fitted grids combined with adaption in the off-body grids is presented, which maximizes the part of the domain subject to adaption. Two- and three-dimensional examples are used to illustrate the effectiveness and performance of the adaption scheme

6'-Methoxy Raloxifene-analog enhances mouse bone properties with reduced estrogen receptor binding

Raloxifene (RAL) is an FDA-approved drug used to treat osteoporosis in postmenopausal women. RAL suppresses bone loss primarily through its role as a selective estrogen receptor modulator (SERM). This hormonal estrogen therapy promotes unintended side effects, such as hot flashes and increased thrombosis risk, and prevents the drug from being used in some patient populations at-risk for fracture, including children with bone disorders. It has recently been demonstrated that RAL can have significant positive effects on overall bone mechanical properties by binding to collagen and increasing bone tissue hydration in a cell-independent manner. A Raloxifene-Analog (RAL-A) was synthesized by replacing the 6-hydroxyl substituent with 6-methoxy in effort to reduce the compound's binding affinity for estrogen receptors (ER) while maintaining its collagen-binding ability. It was hypothesized that RAL-A would improve the mechanical integrity of bone in a manner similar to RAL, but with reduced estrogen receptor binding. Molecular assessment showed that while RAL-A did reduce ER binding, downstream ER signaling was not completely abolished. In-vitro, RAL-A performed similarly to RAL and had an identical concentration threshold on osteocyte cell proliferation, differentiation, and function. To assess treatment effect in-vivo, wildtype (WT) and heterozygous (OIM+/-) female mice from the Osteogenesis Imperfecta (OI) murine model were treated with either RAL or RAL-A from 8 weeks to 16 weeks of age. There was an untreated control group for each genotype as well. Bone microarchitecture was assessed using microCT, and mechanical behavior was assessed using 3-point bending. Results indicate that both compounds produced analogous gains in tibial trabecular and cortical microarchitecture. While WT mechanical properties were not drastically altered with either treatment, OIM+/- mechanical properties were significantly enhanced, most notably, in post-yield properties including bone toughness. This proof-of-concept study shows promising results and warrants the exploration of additional analog iterations to further reduce ER binding and improve fracture resistance

Contributions to HiLiftPW-3 Using Structured, Overset Grid Methods

The High-Lift Common Research Model (HL-CRM) and the JAXA Standard Model (JSM) were analyzed computationally using both the OVERFLOW and LAVA codes for the third AIAA High-Lift Prediction Workshop. Geometry descriptions and the test cases simulated are described. With the HL-CRM, the effects of surface smoothness during grid projection and the effect of partially sealing a flap gap were studied. Grid refinement studies were performed at two angles of attack using both codes. For the JSM, simulations were performed with and without the nacelle/pylon. Without the nacelle/pylon, evidence of multiple solutions was observed when a quadratic constitutive relation is used in the turbulence modeling; however, using time-accurate simulation seemed to alleviate this issue. With the nacelle/pylon, no evidence of multiple solutions was observed. Laminar-turbulent transition modeling was applied to both JSM configuration, and had an overall favorable impact on the lift predictions

Peripheral T-Cell Lymphoma with Aberrant Expression of CD19, CD20, and CD79a: Case Report and Literature Review

A case of lymphoma of T-cell derivation with aberrant expression of three B-cell lineage markers (CD19, CD20, and CD79a), which was diagnosed on a left axillary excision, is described. Immunohistochemical studies and flow cytometry analysis demonstrated neoplastic cells expressing CD3, CD19, CD20, and CD79a with absence of CD4, CD8, CD10, CD30, CD34, CD56, CD68, TDT, MPO, PAX-5, and surface immunoglobulin. Gene rearrangement studies performed on paraffin blocks demonstrated monoclonal T-cell receptor gamma chain rearrangement with no evidence of clonal heavy chain rearrangement. The neoplastic cells were negative for Epstein-Barr virus (EBV) or Human Herpes Virus 8 (HHV-8). At the time of diagnosis, the PET scan demonstrated hypermetabolic neoplastic cells involving the left axilla, bilateral internal jugular areas, mediastinum, right hilum, bilateral lungs, and spleen. However, bone marrow biopsy performed for hemolytic anemia revealed normocellular bone marrow with trilineage maturation. The patient had no evidence of immunodeficiency or infection with EBV or HHV-8. This is the first reported case of a mature T-cell lymphoma with aberrant expression of three B-cell lineage markers. The current report also highlights the need for molecular gene rearrangement studies to determine the precise lineage of ambiguous neoplastic clones

Peripheral T-Cell Lymphoma with Aberrant Expression of CD19, CD20, and CD79a: Case Report and Literature Review

A case of lymphoma of T-cell derivation with aberrant expression of three B-cell lineage markers (CD19, CD20, and CD79a), which was diagnosed on a left axillary excision, is described. Immunohistochemical studies and flow cytometry analysis demonstrated neoplastic cells expressing CD3, CD19, CD20, and CD79a with absence of CD4, CD8, CD10, CD30, CD34, CD56, CD68, TDT, MPO, PAX-5, and surface immunoglobulin. Gene rearrangement studies performed on paraffin blocks demonstrated monoclonal T-cell receptor gamma chain rearrangement with no evidence of clonal heavy chain rearrangement. The neoplastic cells were negative for Epstein-Barr virus (EBV) or Human Herpes Virus 8 (HHV-8). At the time of diagnosis, the PET scan demonstrated hypermetabolic neoplastic cells involving the left axilla, bilateral internal jugular areas, mediastinum, right hilum, bilateral lungs, and spleen. However, bone marrow biopsy performed for hemolytic anemia revealed normocellular bone marrow with trilineage maturation. The patient had no evidence of immunodeficiency or infection with EBV or HHV-8. This is the first reported case of a mature T-cell lymphoma with aberrant expression of three B-cell lineage markers. The current report also highlights the need for molecular gene rearrangement studies to determine the precise lineage of ambiguous neoplastic clones

OVERFLOW Contribution to HiLiftPW-3

We plan to perform the following sets of computations: For all our contributions (except where stated) Code: OVERFLOW, Turbulence model: SAnegRCQCR2000. - 1. Results will be submitted for both the full chord flap gap (Case 1a) and partially-sealed Chord Flap gap (Case 1c): 1. Grid Refinement Study; 2. Grids: structured overset grids supplied by HiLiftPW committee; 3. Connectivity: Domain Connectivity Framework, DCF. - 2. Results will be submitted for JAXA Standard Model and Nacelle/Pylon Off (Case 2a), Nacelle/Pylon On (Case 2c): 1. Alpha Study; 2. Grids: structured overset grids supplied by HiLiftPW committee; 3. Connectivity: Pegasus 5 (Peg5). - 3. A study of the effects of different connectivity paradigms: 1. DCF vs Peg5 for HLCRM cases; 2. DCF vs. C3P (NASA Ames) vs. Peg5 for JSM cases; 3. JSM grids will be the focus where we will hopefully see some type of trends with reference to wind tunnel data. - 4. Adaption cases will be attempted for (and submitted where appropriate): 1. Cases 1c,1d: HLCRM; 2. Cases 2c and 2d: JSM; 3. Grid: Near Body grids provided by committee, OffBody grids Cartesian; 4. AMR NearBody and OffBody Adaption. - 5. Case 3 Turbulence model verification study: 1. Grid: Series of 3 finest grids as defined on http://turbmodels.larc.nasa.gov/airfoilwakeverif.html; 2. Turbulence models: SAneg and SAneg RCQCR2000. OVERFLOW 2.2 is a Reynolds-averaged Navier-Stokes (RANS) code developed by NASA..

Contributions to the Sixth Drag Prediction Workshop Using Structured, Overset Grid Methods

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143028/1/1.C034486.pd

Characteristics of Mantle Fabrics beneath the South-Central United States: Constraints from Shear-Wave Splitting Measurements

New shear-wave splitting measurements at permanent broadband seismic stations in the south-central United States reveal the orientation and degree of polarization of mantle fabrics, and provide constraints on models for the formation of these fabrics. For stations on the stable North American craton, correspondence between observed polarization direction of the fast wave and the trend of Proterozoic and Paleozoic structures associated with rifts and orogenic belts implies a lithospheric origin for the observed anisotropy. The largest splitting times (up to 1.6 s) are observed at stations located in the ocean-continent transition zone, in which the fast directions are parallel to the Gulf of Mexico continental margin. The parallelism and the geometry of the keel of the craton beneath the study area suggest that asthenospheric flow around the keel of the North American craton, lithospheric fabrics developed during Mesozoic rifting, or a combination of these factors are responsible for the observed anisotropy on stations above the transitional crust

Wing-Body Aeroelasticity Using Finite-Difference Fluid/Finite-Element Structural Equations on Parallel Computers

This paper presents a procedure for computing the aeroelasticity of wing-body configurations on multiple-instruction, multiple-data (MIMD) parallel computers. In this procedure, fluids are modeled using Euler equations discretized by a finite difference method, and structures are modeled using finite element equations. The procedure is designed in such a way that each discipline can be developed and maintained independently by using a domain decomposition approach. A parallel integration scheme is used to compute aeroelastic responses by solving the coupled fluid and structural equations concurrently while keeping modularity of each discipline. The present procedure is validated by computing the aeroelastic response of a wing and comparing with experiment. Aeroelastic computations are illustrated for a High Speed Civil Transport type wing-body configuration

Protein kinase A-mediated phosphorylation regulates STAT3 activation and oncogenic EZH2 activity

Polycomb Repressive Complex 2 (PRC2) member enhancer of zeste homologue 2 (EZH2) trimethylates histone H3 lysine 27 (H3K27me3), alters chromatin structure and contributes to epigenetic regulation of gene expression in normal and disease processes. Phosphorylation of EZH2 augmented EZH2 oncogenic activity in cancer but observations have been limited to serine 21 (S21) residue by protein kinase B. In addition, phosphorylation of the evolutionarily conserved T372 motif of EZH2 by p38 resulted in EZH2 interaction with Ying Yang 1 and promoted muscle stem cell differentiation. In the present study, we used epithelial ovarian cancer (OC) cells as a model to demonstrate that phosphorylation of EZH2 at T372 by protein kinase A (PKA) induced a dominant-negative EZH2 phenotype, inhibited OC cell proliferation and migration in vitro and decreased ovarian xenograft tumor growth in vivo. Phosphorylation of T372 by PKA enhanced the interaction between EZH2 and signal transducer and activator of transcription 3 (STAT3), and STAT3 binding to pT372-EZH2 reduced cellular levels of pSTAT3 and downregulated interleukin 6 receptor expression in OC. Furthermore, PKA-mediated pT372-EZH2 decreased ATP levels and altered mitochondrial gene expression, resulting in mitochondrial dysfunction and reduced OC cell growth. These findings demonstrate that PKA-mediated T372 phosphorylation reduces oncogenic EZH2 activity and reveal a novel role for pT372 in regulating EZH2 in OC and possibly other cancers