Adding a MOAB Geometry Interface to SHARP Structural Mechanics

The authors briefly summarize the development of, and test experience with, an initial data interface between the structural mechanics code Diablo and the SHARP reactor simulation system data hub MOAB. That interface has been exercised both to write MOAB databases from Diablo, and then also to use such a database to read in part of a simulation definition for a subsequent Diablo execution. All enhancements are integrated into the central Diablo source repository. The SHARP software system for advanced simulation of nuclear reactors and power plant systems is sponsored by DOE's Nuclear Energy Advanced Modeling and Simulation (NEAMS) program. SHARP has been architected as a federation of single-physics simulation tools to permit flexibility in programming langugages and leveraging of past and on-going investments. Solution of multi-physics problems will be coordinated by, and data passed through, a central 'hub'. SHARP's hub implementation is utilizing MOAB: a Mesh-Oriented datABase. This same data hub approach is also intended to enable multi-resolution simulations, e.g, lower-dimension plant-scale simulations can be informed by high-fidelity 3D models of particular critical components

Protective Intestinal Effects of Pituitary Adenylate Cyclase Activating Polypeptide

Pituitary adenylate cyclase activating polypeptide (PACAP) is an endogenous neuropeptide widely distributed throughout the body, including the gastrointestinal tract. Several effects have been described in human and animal intestines. Among others, PACAP infl uences secretion of intestinal glands, blood fl ow, and smooth muscle contraction. PACAP is a well-known cytoprotective peptide with strong anti-apoptotic, anti-infl ammatory, and antioxidant effects. The present review gives an overview of the intestinal protective actions of this neuropeptide. Exogenous PACAP treatment was protective in a rat model of small bowel autotransplantation. Radioimmunoassay (RIA) analysis of the intestinal tissue showed that endogenous PACAP levels gradually decreased with longer-lasting ischemic periods, prevented by PACAP addition. PACAP counteracted deleterious effects of ischemia on oxidative stress markers and cytokines. Another series of experiments investigated the role of endogenous PACAP in intestines in PACAP knockout (KO) mice. Warm ischemia–reperfusion injury and cold preservation models showed that the lack of PACAP caused a higher vulnerability against ischemic periods. Changes were more severe in PACAP KO mice at all examined time points. This fi nding was supported by increased levels of oxidative stress markers and decreased expression of antioxidant molecules. PACAP was proven to be protective not only in ischemic but also in infl ammatory bowel diseases. A recent study showed that PACAP treatment prolonged survival of Toxoplasma gondii infected mice suffering from acute ileitis and was able to reduce the ileal expression of proinfl ammatory cytokines. We completed the present review with recent clinical results obtained in patients suffering from infl ammatory bowel diseases. It was found that PACAP levels were altered depending on the activity, type of the disease, and antibiotic therapy, suggesting its probable role in infl ammatory events of the intestine

Osiris: A Modern, High-Performance, Coupled, Multi-Physics Code For Nuclear Reactor Core Analysis

To meet the simulation needs of the GNEP program, LLNL is leveraging a suite of high-performance codes to be used in the development of a multi-physics tool for modeling nuclear reactor cores. The Osiris code project, which began last summer, is employing modern computational science techniques in the development of the individual physics modules and the coupling framework. Initial development is focused on coupling thermal-hydraulics and neutral-particle transport, while later phases of the project will add thermal-structural mechanics and isotope depletion. Osiris will be applicable to the design of existing and future reactor systems through the use of first-principles, coupled physics models with fine-scale spatial resolution in three dimensions and fine-scale particle-energy resolution. Our intent is to replace an existing set of legacy, serial codes which require significant approximations and assumptions, with an integrated, coupled code that permits the design of a reactor core using a first-principles physics approach on a wide range of computing platforms, including the world's most powerful parallel computers. A key research activity of this effort deals with the efficient and scalable coupling of physics modules which utilize rather disparate mesh topologies. Our approach allows each code module to use a mesh topology and resolution that is optimal for the physics being solved, and employs a mesh-mapping and data-transfer module to effect the coupling. Additional research is planned in the area of scalable, parallel thermal-hydraulics, high-spatial-accuracy depletion and coupled-physics simulation using Monte Carlo transport

Over-Expression of DSCAM and COL6A2 Cooperatively Generates Congenital Heart Defects

A significant current challenge in human genetics is the identification of interacting genetic loci mediating complex polygenic disorders. One of the best characterized polygenic diseases is Down syndrome (DS), which results from an extra copy of part or all of chromosome 21. A short interval near the distal tip of chromosome 21 contributes to congenital heart defects (CHD), and a variety of indirect genetic evidence suggests that multiple candidate genes in this region may contribute to this phenotype. We devised a tiered genetic approach to identify interacting CHD candidate genes. We first used the well vetted Drosophila heart as an assay to identify interacting CHD candidate genes by expressing them alone and in all possible pairwise combinations and testing for effects on rhythmicity or heart failure following stress. This comprehensive analysis identified DSCAM and COL6A2 as the most strongly interacting pair of genes. We then over-expressed these two genes alone or in combination in the mouse heart. While over-expression of either gene alone did not affect viability and had little or no effect on heart physiology or morphology, co-expression of the two genes resulted in ≈50% mortality and severe physiological and morphological defects, including atrial septal defects and cardiac hypertrophy. Cooperative interactions between DSCAM and COL6A2 were also observed in the H9C2 cardiac cell line and transcriptional analysis of this interaction points to genes involved in adhesion and cardiac hypertrophy. Our success in defining a cooperative interaction between DSCAM and COL6A2 suggests that the multi-tiered genetic approach we have taken involving human mapping data, comprehensive combinatorial screening in Drosophila, and validation in vivo in mice and in mammalian cells lines should be applicable to identifying specific loci mediating a broad variety of other polygenic disorders