Supporting 64-bit global indices in Epetra and other Trilinos packages -- Techniques used and lessons learned

The Trilinos Project is an effort to facilitate the design, development, integration and ongoing support of mathematical software libraries within an object-oriented framework. It is intended for large-scale, complex multiphysics engineering and scientific applications. Epetra is one of its basic packages. It provides serial and parallel linear algebra capabilities. Before Trilinos version 11.0, released in 2012, Epetra used the C++ int data-type for storing global and local indices for degrees of freedom (DOFs). Since int is typically 32-bit, this limited the largest problem size to be smaller than approximately two billion DOFs. This was true even if a distributed memory machine could handle larger problems. We have added optional support for C++ long long data-type, which is at least 64-bit wide, for global indices. To save memory, maintain the speed of memory-bound operations, and reduce further changes to the code, the local indices are still 32-bit. We document the changes required to achieve this feature and how the new functionality can be used. We also report on the lessons learned in modifying a mature and popular package from various perspectives -- design goals, backward compatibility, engineering decisions, C++ language features, effects on existing users and other packages, and build integration

Non-parabolicity of the conduction band of wurtzite GaN

Using cyclotron resonance, we measure the effective mass, $m$*, of electrons in AlGaN/GaN heterostructures with densities, $n_{2D}\sim 1-6\times10^{12}$cm$^{-2}$. From our extensive data, we extrapolate a band edge mass of $(0.208\pm0.002) m_e$. By comparing our $m$* data with the results of a multi-band \textbf{k.p} calculation we infer that the effect of remote bands is essential in explaining the observed conduction band non-parabolicity (NP). Our calculation of polaron mass corrections -- including finite width and screening - suggests those to be negligible. It implies that the behavior of $m*(n_{2D})$ can be understood solely in terms of NP. Finally, using our NP and polaron corrections, we are able to reduce the large scatter in the published band edge mass values

Parallel programming of industrial applications

In the introductory material, we overview the typical MPP environment for real application computing and the special tools available such as parallel debuggers and performance analyzers. Next, we draw from a series of real applications codes and discuss the specific challenges and problems that are encountered in parallelizing these individual applications. The application areas drawn from include biomedical sciences, materials processing and design, plasma and fluid dynamics, and others. We show how it was possible to get a particular application to run efficiently and what steps were necessary. Finally we end with a summary of the lessons learned from these applications and predictions for the future of industrial parallel computing. This tutorial is based on material from a forthcoming book entitled: �Industrial Strength Parallel Computing� to be published by Morgan Kaufmann Publishers (ISBN l-55860-54)

Abstract: Analysis of acute skin rejection in non-human primate models of face and hand allotransplantation

Introduction: The incidence of acute rejection (AR) of the skin within the first year after hand or face transplantation is approximately 85% and up to 56% of patients experience multiple episodes1. Significant immunosuppression is required to prevent allograft loss, and recent studies suggest that repeated AR episodes can lead to VCA dysfunction and loss2. The mechanisms underlying variability in AR presentation remain poorly defined however. Materials and Methods: 8 cynomolgus monkeys received either an orthotopic hand (n=2) or heterotopic face VCA (n=6) from MHC-mismatched donors following induction with anti-thymocyte globulin. Post-operatively, triple immunosuppression – tacrolimus, mycophenolate mofetil, methylprednisolone – was maintained for up to 120 days before bone marrow transplantation (BMT) was performed. Protocol biopsies of VCA skin were performed at 30-day intervals for histopathology and flow cytometric analysis of resident skin leukocyte populations; VCA-resident cells were differentiated by H38 status (mouse antihuman HLA class I monoclonal antibody that cross reacts with cynomolgus monkeys) for donor or recipient derivation. Clinical AR was treated with steroids and further biopsies were taken for histologic confirmation; corresponding anti-donor responses were evaluated by mixed lymphocyte reaction (MLR) and allo-antibody formation. Results: Up to three episodes of AR (from POD 14, Banff I to II) developed while recipient animals were maintained on triple immunosuppression. Corresponding flow cytometric analyses demonstrate > 80% of skin-resident T lymphocytes (CD4+, CD8+) within VCA dermis were of recipient origin, suggesting rapid immigration of various lineages into the VCA. These observations coincided with the first episode of AR in fully mismatched recipients but haplomatched animals remained rejection-free. All but one episode of AR were successfully treated. No allo-antibodies were detected and anti-donor responses by MLR were comparable to that against third-party. Following BMT, mixed chimerism was detected and enabled immunosuppression withdrawal. However, this was transient and once lost, clinical AR developed and nearly 100% of both dermal and epidermal lymphocytes were recipient-derived. Conclusion: We report a clinically-relevant model for studying AR in VCA. Our results suggest that further understanding of the relative importance of MHC differences in transplant pairs may lead to differences in outcomes for VCA recipients maintained under standard immunosuppression. Immunosuppression-free tolerance of non-hematopoietic antigens in composite tissues can be achieved, but require additional strategies to achieve stable, rather than transient mixed chimerism following BMT

Quality Output Checklist and Content Assessment (QuOCCA): a new tool for assessing research quality and reproducibility

Research must be well designed, properly conducted and clearly and transparently reported. Our independent medical research institute wanted a simple, generic tool to assess the quality of the research conducted by its researchers, with the goal of identifying areas that could be improved through targeted educational activities. Unfortunately, none was available, thus we devised our own. Here, we report development of the Quality Output Checklist and Content Assessment (QuOCCA), and its application to publications from our institute's scientists. Following consensus meetings and external review by statistical and methodological experts, 11 items were selected for the final version of the QuOCCA: research transparency (items 1-3), research design and analysis (items 4-6) and research reporting practices (items 7-11). Five pairs of raters assessed all 231 articles published in 2017 and 221 in 2018 by researchers at our institute. Overall, the results were similar between years and revealed limited engagement with several recommended practices highlighted in the QuOCCA. These results will be useful to guide educational initiatives and their effectiveness. The QuOCCA is brief and focuses on broadly applicable and relevant concepts to open, high-quality, reproducible and well-reported science. Thus, the QuOCCA could be used by other biomedical institutions and individual researchers to evaluate research publications, assess changes in research practice over time and guide the discussion about high-quality, open science. Given its generic nature, the QuOCCA may also be useful in other research disciplines

A fast sparse block circulant matrix vector product

In the context of computed tomography (CT), iterative image reconstruction techniques are gaining attention because high-quality images are becoming computationally feasible. They involve the solution of large systems of equations, whose cost is dominated by the sparse matrix vector product (SpMV). Our work considers the case of the sparse matrices being block circulant, which arises when taking advantage of the rotational symmetry in the tomographic system. Besides the straightforward storage saving, we exploit the circulant structure to rewrite the poor-performance SpMVs into a high-performance product between sparse and dense matrices. This paper describes the implementations developed for multi-core CPUs and GPUs, and presents experimental results with typical CT matrices. The presented approach is up to ten times faster than without exploiting the circulant structure.Romero Alcalde, E.; Tomás Domínguez, AE.; Soriano Asensi, A.; Blanquer Espert, I. (2014). A fast sparse block circulant matrix vector product. En Euro-Par 2014 Parallel Processing. Springer. 548-559. doi:10.1007/978-3-319-09873-9_46S548559Bian, J., Siewerdsen, J.H., Han, X., Sidky, E.Y., Prince, J.L., Pelizzari, C.A., Pal, X.: Evaluation of sparse-view reconstruction from flat-panel-detector cone-beam ct. Physics in Medicine and Biology 55, 6575–6599 (2010)Dalton, S., Bell, N.: CUSP: A C++ templated sparse matrix library version 0.4.0 (2014), http://cusplibrary.github.com/Feldkamp, L., Davis, L., Kress, J.: Practical cone-beam algorithm. Journal of the Optical Society of America 1, 612–619 (1984)Ganine, V., Legrand, M., Michalska, H., Pierre, C.: A sparse preconditioned iterative method for vibration analysis of geometrically mistuned bladed disks. Computers & Structures 87(5-6), 342–354 (2009)Hara, A.K., Paden, R.G., Silva, A.C., Kujak, J.L., Lawder, H.J., Pavlicek, W.: Iterative reconstruction technique for reducing body radiation dose at CT: Feasibility study. American Journal of Roentgenology 193, 764–771 (2009)Heroux, M.A., Bartlett, R.A., Howle, V.E., Hoekstra, R.J., Hu, J.J., Kolda, T.G., Lehoucq, R.B., Long, K.R., Pawlowski, R.P., Phipps, E.T., Salinger, A.G., Thornquist, H.K., Tuminaro, R.S., Willenbring, J.M., Williams, A., Stanley, K.S.: An overview of the Trilinos project. ACM Trans. Math. Softw. 31(3), 397–423 (2005)Im, E.J., Yelick, K., Vuduc, R.: Sparsity: Optimization framework for sparse matrix kernels. International Journal of High Performance Computing Applications 18(1), 135–158 (2004)Jones, E., Oliphant, T., Peterson, P., et al.: SciPy: Open source scientific tools for Python (2001), http://www.scipy.org/Kaveh, A., Rahami, H.: Block circulant matrices and applications in free vibration analysis of cyclically repetitive structures. Acta Mechanica 217(1-2), 51–62 (2011)Kourtis, K., Goumas, G., Koziris, N.: Optimizing sparse matrix-vector multiplication using index and value compression. In: Proceedings of the 5th Conference on Computing Frontiers, CF 2008, pp. 87–96. ACM, New York (2008)Krotkiewski, M., Dabrowski, M.: Parallel symmetric sparse matrix–vector product on scalar multi-core CPUs. Parallel Computing 36(4), 181–198 (2010)Lee, B., Vuduc, R., Demmel, J., Yelick, K.: Performance models for evaluation and automatic tuning of symmetric sparse matrix-vector multiply. In: International Conference on Parallel Processing, ICPP 2004, vol. 1, pp. 169–176 (2004)Leroux, J.D., Selivanov, V., Fontaine, R., Lecomte, R.: Accelerated iterative image reconstruction methods based on block-circulant system matrix derived from a cylindrical image representation. In: Nuclear Science Symposium Conference Record, NSS 2007, vol. 4, pp. 2764–2771. IEEE (2007)NVIDIA: CUSPARSE library (2014), https://developer.nvidia.com/cusparsePan, X., Sidky, E.Y., Vannier, M.: Why do commercial CT scanners still employ traditional, filtered back-projection for image reconstruction? Inverse Problems 25, 123009 (2008)Rodríguez-Alvarez, M.J., Soriano, A., Iborra, A., Sánchez, F., González, A.J., Conde, P., Hernández, L., Moliner, L., Orero, A., Vidal, L.F., Benlloch, J.M.: Expectation maximization (EM) algorithms using polar symmetries for computed tomography CT image reconstruction. Computers in Biology and Medicine 43(8), 1053–1061 (2013)Sheep, L., Vardi, Y.: Maximum likelihood reconstruction for emmision tomography. IEEE Transactions on Medical Imaging 1, 113–122 (1982)Sidky, E.Y., Pan, X.: Image reconstruction in circular cone-beam computed tomography by constrained, total-variation minimization. Physics in Medicine and Biology 53, 4777–4807 (2008)Soriano, A., Rodríguez-Alvarez, M.J., Iborra, A., Sánchez, F., Carles, M., Conde, P., González, A.J., Hernández, L., Moliner, L., Orero, A., Vidal, L.F., Benlloch, J.M.: EM tomographic image reconstruction using polar voxels. Journal of Instrumentation 8, C01004 (2013)Thibaudeau, C., Leroux, J.D., Pratte, J.F., Fontaine, R., Lecomte, R.: Cylindrical and spherical ray-tracing for ct iterative reconstruction. In: 2011 IEEE Nuclear Science Symposium and Medical Imaging Conference (NSS/MIC), pp. 4378–4381 (2011)Vuduc, R., Demmel, J.W., Yelick, K.A.: OSKI: A library of automatically tuned sparse matrix kernels. Journal of Physics: Conference Series 16(1), 521 (2005)Vuduc, R.W., Moon, H.-J.: Fast sparse matrix-vector multiplication by exploiting variable block structure. In: Yang, L.T., Rana, O.F., Di Martino, B., Dongarra, J. (eds.) HPCC 2005. LNCS, vol. 3726, pp. 807–816. Springer, Heidelberg (2005)Williams, S., Oliker, L., Vuduc, R., Shalf, J., Yelick, K., Demmel, J.: Optimization of sparse matrix-vector multiplication on emerging multicore platforms. Parallel Computing 35(3), 178–194 (2009

A qualitative study of independent fast food vendors near secondary schools in disadvantaged Scottish neighbourhoods

Background: Preventing and reducing childhood and adolescent obesity is a growing priority in many countries. Recent UK data suggest that children in more deprived areas have higher rates of obesity and poorer diet quality than those in less deprived areas. As adolescents spend a large proportion of time in school, interventions to improve the food environment in and around schools are being considered. Nutrient standards for school meals are mandatory in the UK, but many secondary pupils purchase foods outside schools at break or lunchtime that may not meet these standards. Methods: Qualitative interviews were conducted with fast food shop managers to explore barriers to offering healthier menu options. Recruitment targeted independently-owned shops near secondary schools (pupils aged c.12-17) in low-income areas of three Scottish cities. Ten interviews were completed, recorded, and transcribed for analysis. An inductive qualitative approach was used to analyse the data in NVivo 10. Results: Five themes emerged from the data: pride in what is sold; individual autonomy and responsibility; customer demand; profit margin; and neighbourhood context. Interviewees consistently expressed pride in the foods they sold, most of which were homemade. They felt that healthy eating and general wellbeing are the responsibility of the individual and that offering what customers want to eat, not necessarily what they should eat, was the only way to stay in business. Most vendors felt they were struggling to maintain a profit, and that many aspects of the low-income neighbourhood context would make change difficult or impossible. Conclusions: Independent food shops in low-income areas face barriers to offering healthy food choices, and interventions and policies that target the food environment around schools should take the neighbourhood context into consideration

Molecular basis of association of receptor activity-modifying protein 3 with the family B G protein-coupled secretin receptor

The three receptor activity-modifying proteins (RAMPs) have been recognized as being important for the trafficking and function of a subset of family B G protein-coupled receptors, although the structural basis for this has not been well established. In the current work, we use morphological fluorescence techniques, bioluminescence resonance energy transfer, and bimolecular fluorescence complementation to demonstrate that the secretin receptor associates specifically with RAMP3, but not with RAMP1 or RAMP2. We use truncation constructs, peptide competition experiments, and chimeric secretin-GLP1 receptor constructs to establish that this association is structurally specific, dependent on the intramembranous region of the RAMP and TM6 and TM7 of this receptor. There were no observed changes in secretin-stimulated cAMP, intracellular calcium, ERK1/2 phosphorylation, or receptor internalization in receptor-bearing COS or CHO-K1 cells in the presence or absence of exogenous RAMP transfection, although the secretin receptor trafficks normally to the cell surface in these cells in a RAMP-independent manner, resulting in both free and RAMP-associated receptor on the cell surface. RAMP3 association with this receptor was shown to be capable of rescuing a receptor mutant (G241C) that is normally trapped intracellularly in the biosynthetic machinery. Similarly, secretin receptor expression had functional effects on adrenomedullin activity, with increasing secretin receptor expression competing for RAMP3 association with the calcitonin receptor-like receptor to yield a functional adrenomedullin receptor. These data provide important new insights into the structural basis for RAMP3 interaction with a family B G protein-coupled receptor, potentially providing a highly selective target for drug action. This may be representative of similar interactions between other members of this receptor family and RAMP proteins

Triggering Threshold Spacecraft Charging with Changes in Electron Emission from Materials

Modest changes in spacecraft charging conditions can lead to abrupt changes in the spacecraft equilibrium, from small positive potentials to large negative potentials relative to the space plasma; this phenomenon is referred to as threshold charging. It is well known that temporal changes of the space plasma environment (electron plasma temperature or density) can cause threshold charging. Threshold charging can also result from by temporal changes in the juxtaposition of the spacecraft to the environment, including spacecraft orbit, orientation, and geometry. This study focuses on the effects of possible changes in electron emission properties of representative spacecraft materials. It is found that for electron-induced emission, the possible threshold scenarios are very rich, since this type of electron emission can cause either positive or negative charging. Alternately, modification of photon- or ion-induced electron emission is found to induce threshold charging only in certain favorable cases. Changes of emission properties discussed include modifications due to: contamination, degradation and roughening of surfaces and layered materials; biasing and charge accumulation; bandstructure occupation and density of states caused by heat, optical or particle radiation; optical reflectivity and absorptivity; and inaccuracies and errors in measurements and parameterization of materials properties. An established method is used here to quantitatively gauge the relative extent to which these various changes in electron emission alter a spacecraft’s charging behavior and possibly lead to threshold charging. The absolute charging behavior of a hypothetical flat, two-dimensional satellite panel of a single material (either polycrystalline conductor Au or the polymeric polyimide Kapton™ H) is modeled as it undergoes modification and concomitant changes in spacecraft charging in three representative geosynchronous orbit environments, from full sunlight to full shade (eclipse) are considered

Structure of a highly conserved domain of rock1 required for shroom-mediated regulation of cell morphology

Rho-associated coiled coil containing protein kinase (Rho-kinase or Rock) is a well-defined determinant of actin organization and dynamics in most animal cells characterized to date. One of the primary effectors of Rock is non-muscle myosin II. Activation of Rock results in increased contractility of myosin II and subsequent changes in actin architecture and cell morphology. The regulation of Rock is thought to occur via autoinhibition of the kinase domain via intramolecular interactions between the N-terminus and the C-terminus of the kinase. This autoinhibited state can be relieved via proteolytic cleavage, binding of lipids to a Pleckstrin Homology domain near the C-terminus, or binding of GTP-bound RhoA to the central coiled-coil region of Rock. Recent work has identified the Shroom family of proteins as an additional regulator of Rock either at the level of cellular distribution or catalytic activity or both. The Shroom-Rock complex is conserved in most animals and is essential for the formation of the neural tube, eye, and gut in vertebrates. To address the mechanism by which Shroom and Rock interact, we have solved the structure of the coiled-coil region of Rock that binds to Shroom proteins. Consistent with other observations, the Shroom binding domain is a parallel coiled-coil dimer. Using biochemical approaches, we have identified a large patch of residues that contribute to Shrm binding. Their orientation suggests that there may be two independent Shrm binding sites on opposing faces of the coiled-coil region of Rock. Finally, we show that the binding surface is essential for Rock colocalization with Shroom and for Shroom-mediated changes in cell morphology. © 2013 Mohan et al