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This paper contains the main ideas for an AMGe (algebraic multigrid for finite elements) method based on element agglomeration. In the method, coarse grid elements are formed by agglomerating fine grid elements. Compatible interpolation operators are constructed which yield coarse grid basis functions with a minimal energy property. Heuristics based on interpolation quality measures are used to guide the agglomeration procedure. The performance of the resulting method is demonstrated in two-level numerical experiments.

Algebraic multigrid (AMG) is currently undergoing a resurgence in popularity, due in part to the dramatic increase in the need to solve physical problems posed on very large, unstructured grids. While AMG has proved its usefulness on various problem types, it is not commonly understood how wide a range of applicability the method has. In this study, we demonstrate that range of applicability, while describing some of the recent advances in AMG technology. Moreover, in light of the imperatives of modern computer environments, we also examine AMG in terms of algorithmic scalability. Finally, we show some of the situations in which standard AMG does not work well and indicate the current directions taken by AMG researchers to alleviate these difficulties.

This paper presents the results of a scalability study for a three-dimensional semicoarsening multigrid solver on a distributed memory computer. In particular, we are interested in the scalability of the solver---how the solution time varies as both problem size and number of processors are increased. For an iterative linear solver, scalability involves both algorithmic issues and implementation issues. We examine the scalability of the solver theoretically by constructing a simple parallel model and experimentally by results obtained on an IBM SP. The results are compared with those obtained for other solvers on the same computer.

A key ingredient in the simulation of flow in porous media is the accurate determination of the velocities that drive the flow. Large-scale irregularities of the geology, such as faults, fractures, and layers, suggest the use of irregular grids in the simulation. In this study, the approach to this problem was to apply the finite volume element methodology, developed by McCormick, in conjunction with mixed methods, developed by Raviart and Thomas. The resulting mixed finite volume element discretization scheme developed here can be applied in a clear and straightforward way to irregular grids and is appealing because of its local conservation properties and its direct and accurate representation of physical intercell flux terms. Several multilevel algorithms are developed that provide efficient methods for solving the set of equations that this discretization produces. This thesis includes numerical results from a variety of test problems, from Poisson's equation to problems with anisotropic, discontinuous, and tensor diffusion coefficients. These results show that this approach has the potential to generate accurate approximate fluid velocities and that the multilevel methods can provide fast solvers.

This chapter presents an element agglomeration method to nonlinear elliptic problems discretized by the finite element method on general unstructured meshes. The method constructs coarse discretization spaces and corresponding coarse nonlinear operators as well as their Jacobians. The chapter introduces both standard (fairly quasiuniformly coarsened) and nonstandard (coarsened away) coarse meshes and respective finite element spaces. It use both kind of spaces in FAS type coarse subspace correction (or Schwarz) algorithms. Their performance is illustrated on a number of model problems. The coarsened away spaces seem to perform better than the standard spaces for problems with nonlinearities in the principal part of the elliptic operator.

Central nervous system-expressed long non-coding RNAs (lncRNAs) are often located in the genome close to protein coding genes involved in transcriptional control. Such lncRNA-protein coding gene pairs are frequently temporally and spatially co-expressed in the nervous system and are predicted to act together to regulate neuronal development and function. Although some of these lncRNAs also bind and modulate the activity of the encoded transcription factors, the regulatory mechanisms controlling co-expression of neighbouring lncRNA-protein coding genes remain unclear. Here, we used high resolution NG Capture-C to map the cis -regulatory interaction landscape of the key neuro-developmental Paupar-Pax6 lncRNA-mRNA locus. The results define chromatin architecture changes associated with high Paupar - Pax6 expression in neurons and identify both promoter selective as well as shared cis -regulatory-promoter interactions involved in regulating Paupar - Pax6 co-expression. We discovered that the TCF7L2 transcription factor, a regulator of chromatin architecture and major effector of the Wnt signalling pathway, binds to a subset of these candidate cis -regulatory elements to coordinate Paupar and Pax6 co-expression. We describe distinct roles for Paupar in Pax6 expression control and show that the Paupar DNA locus contains a TCF7L2 bound transcriptional silencer whilst the Paupar transcript can act as an activator of Pax6 . Our work provides important insights into the chromatin interactions, signalling pathways and transcription factors controlling co-expression of adjacent lncRNAs and protein coding genes in the brain.

Oomycete pathogens cause diverse plant diseases. To successfully colonize their hosts, they deliver a suite of effector proteins that can attenuate plant defenses. In the oomycete downy mildews, effectors carry a signal peptide and an RxLR motif. Hyaloperonospora arabidopsidis (Hpa) causes downy mildew on the model plant Arabidopsis thaliana (Arabidopsis). We investigated if candidate effectors predicted in the genome sequence of Hpa isolate Emoy2 (HaRxLs) were able to manipulate host defenses in different Arabidopsis accessions. We developed a rapid and sensitive screening method to test HaRxLs by delivering them via the bacterial type-three secretion system (TTSS) of Pseudomonas syringae pv tomato DC3000-LUX (Pst-LUX) and assessing changes in Pst-LUX growth in planta on 12 Arabidopsis accessions. The majority (~70%) of the 64 candidates tested positively contributed to Pst-LUX growth on more than one accession indicating that Hpa virulence likely involves multiple effectors with weak accession-specific effects. Further screening with a Pst mutant (ΔCEL) showed that HaRxLs that allow enhanced Pst-LUX growth usually suppress callose deposition, a hallmark of pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI). We found that HaRxLs are rarely strong avirulence determinants. Although some decreased Pst-LUX growth in particular accessions, none activated macroscopic cell death. Fewer HaRxLs conferred enhanced Pst growth on turnip, a non-host for Hpa, while several reduced it, consistent with the idea that turnip's non-host resistance against Hpa could involve a combination of recognized HaRxLs and ineffective HaRxLs. We verified our results by constitutively expressing in Arabidopsis a sub-set of HaRxLs. Several transgenic lines showed increased susceptibility to Hpa and attenuation of Arabidopsis PTI responses, confirming the HaRxLs' role in Hpa virulence. This study shows TTSS screening system provides a useful tool to test whether candidate effectors from eukaryotic pathogens can suppress/trigger plant defense mechanisms and to rank their effectiveness prior to subsequent mechanistic investigation. © 2011 Fabro et al.

7 de Novembro de 2006 - Pesquisas confirmam preferência por democratas sobre os republicanos para eleições legislativas. Hoje é Dia de Eleição - o principal evento nos Estados Unidos nesta semana - quando todas as mais de 400 cadeiras da Câmara dos Representantes estarão em disputa. Quem prevê que os democratas conquistarão o controle do Congresso têm mais chance de acertar do que quem acredita que o controle do Senado passará para os democratas. Só 30 das 100 cadeiras do Senado estarão em jogo hoje e os democratas necessitam de um ganho líquido de seis para assumir o controle. A enquete mostrou também que o presidente George W. Bush, chega a estas eleições legislativas com o índice de popularidade mais baixo em décadas. O ex-presidente Ronald Reagan tinha índice de aprovação de 63% nas eleições legislativas de 1986 e seu sucessor, George H. W. Bush, tinha 54% de aprovação nas eleições legislativas de 1990. Bill Clinton enfrentou as legislativas de 1994 com nível de aprovação de 46% e chegou às de 1998 com uma aprovação de 66%. Bush, que tinha índice de aprovação de 63% nas eleições legislativas de 2002, chega a este pleito com nível de aprovação de 38%, segundo a Gallup. O instituto revelou que, em meados de setembro, 48% dos eleitores prováveis preferiam os candidatos democratas, e 48% apoiavam os republicanos. Em 6 de outubro, a enquete do Gallup mostrou que havia uma definição mais clara do eleitorado: 60% preferiam candidatos democratas e 36%, republicanos.

Purpose Cancer has long-term financial consequences. Adolescent and young adult (AYA) and middle-aged cancer survivors may experience more financial toxicity than older adults. This study examined age differences in financial distress in hematopoietic cell transplant survivors and whether these differences result from measurement bias, more financial barriers to care, or an overall higher level of distress. Methods Hematologic malignancy survivors ( n  = 1135, 2–10 years post-transplant) completed the Cancer and Treatment Distress Scale (CTXD) and demographics as part of the baseline assessment for a randomized clinical trial. The CTXD has seven subscales, but for this study, we examined the financial distress subscale and the overall score. Item response theory analyses tested for bias by age and gender. Multivariate linear regression tested the association of age and gender with the CTXD scores while controlling for financial barriers to care. Results No bias was found on the CTXD. AYA ( p  < 0.01) and middle-aged adults ( p  < 0.001) reported more financial and overall distress than older (age 65+) adults. The same association of age and financial distress was observed in women ( p  < 0.01). However, only middle-aged men ( p  < 0.01) reported more financial and overall distress than older men; AYA men did not ( p  > 0.18). Financial barriers to care were not associated with financial or overall distress. Conclusions Part of the increase in financial distress with younger age may be due to a higher risk of general distress. Policy initiatives to control cancer costs should consider life stage and the unique financial challenges at different ages for men and women.

Contagious cancers that pass between individuals as an infectious cell line are highly unusual pathogens. Devil facial tumor disease (DFTD) is one such contagious cancer that emerged 16 y ago and is driving the Tasmanian devil to extinction. As both a pathogen and an allograft, DFTD cells should be rejected by the host–immune response, yet DFTD causes 100% mortality among infected devils with no apparent rejection of tumor cells. Why DFTD cells are not rejected has been a question of considerable confusion. Here, we show that DFTD cells do not express cell surface MHC molecules in vitro or in vivo, due to down-regulation of genes essential to the antigen-processing pathway, such as β ₂-microglobulin and transporters associated with antigen processing. Loss of gene expression is not due to structural mutations, but to regulatory changes including epigenetic deacetylation of histones. Consequently, MHC class I molecules can be restored to the surface of DFTD cells in vitro by using recombinant devil IFN-γ, which is associated with up-regulation of the MHC class II transactivator, a key transcription factor with deacetylase activity. Further, expression of MHC class I molecules by DFTD cells can occur in vivo during lymphocyte infiltration. These results explain why T cells do not target DFTD cells. We propose that MHC-positive or epigenetically modified DFTD cells may provide a vaccine to DFTD. In addition, we suggest that down-regulation of MHC molecules using regulatory mechanisms allows evolvability of transmissible cancers and could affect the evolutionary trajectory of DFTD.