Relativistic MHD and black hole excision: Formulation and initial tests

A new algorithm for solving the general relativistic MHD equations is described in this paper. We design our scheme to incorporate black hole excision with smooth boundaries, and to simplify solving the combined Einstein and MHD equations with AMR. The fluid equations are solved using a finite difference Convex ENO method. Excision is implemented using overlapping grids. Elliptic and hyperbolic divergence cleaning techniques allow for maximum flexibility in choosing coordinate systems, and we compare both methods for a standard problem. Numerical results of standard test problems are presented in two-dimensional flat space using excision, overlapping grids, and elliptic and hyperbolic divergence cleaning.Comment: 22 pages, 8 figure

Variants in autophagy-related genes and clinical characteristics in melanoma: a population-based study

Autophagy has been linked with melanoma risk and survival, but no polymorphisms in autophagy-related (ATG) genes have been investigated in relation to melanoma progression. We examined five single-nucleotide polymorphisms (SNPs) in three ATG genes (ATG5; ATG10; and ATG16L) with known or suspected impact on autophagic flux in an international population-based case-control study of melanoma. DNA from 911 melanoma patients was genotyped. An association was identified between (GG) (rs2241880) and earlier stage at diagnosis (OR 0.47; 95% Confidence Intervals (CI) = 0.27-0.81, P = 0.02) and a decrease in Breslow thickness (P = 0.03). The ATG16L heterozygous genotype (AG) (rs2241880) was associated with younger age at diagnosis (P = 0.02). Two SNPs in ATG5 were found to be associated with increased stage (rs2245214 CG, OR 1.47; 95% CI = 1.11-1.94, P = 0.03; rs510432 CC, OR 1.84; 95% CI = 1.12-3.02, P = 0.05). Finally, we identified inverse associations between ATG5 (GG rs2245214) and melanomas on the scalp or neck (OR 0.20, 95% CI = 0.05-0.86, P = 0.03); ATG10 (CC) (rs1864182) and brisk tumor infiltrating lymphocytes (TILs) (OR 0.42; 95% CI = 0.21-0.88, P = 0.02), and ATG5 (CC) (rs510432) with nonbrisk TILs (OR 0.55; 95% CI = 0.34-0.87, P = 0.01). Our data suggest that ATG SNPs might be differentially associated with specific host and tumor characteristics including age at diagnosis, TILs, and stage. These associations may be critical to understanding the role of autophagy in cancer, and further investigation will help characterize the contribution of these variants to melanoma progression

Confrontational scavenging as a possible source for language and cooperation

The emergence of language and the high degree of cooperation found among humans seems to require more than a straightforward enhancement of primate traits. Some triggering episode unique to human ancestors was likely necessary. Here it is argued that confrontational scavenging was such an episode. Arguments for and against an established confrontational scavenging niche are discussed, as well as the probable effects of such a niche on language and co-operation. Finally, several possible directions for future research are suggested

Crop Updates 2010 - Crop Specific

This session covers twenty four papers from different authors: PLENARY 1. Challenges facing western Canadian cropping over the next 10 years, Hugh J Beckie, Research Centre, Agriculture and Agri-Food Canada, Saskatoon, Saskatchewan CROP SPECIFIC Breeding 2. The challenge of breeding canola hybrids – new opportunities for WA growers, Wallace Cowling, Research Director, Canola Breeders Western Australia Pty Ltd 3. Chickpea 2009 crop variety testing of germplasm developed by DAFWA/CLIMA/ICRISAT/COGGO alliance. Khan, TN1,3, Adhikari, K1,3, Siddique, K2, Garlinge, J1, Smith, L1, Morgan, S1 and Boyd, C1 1Department of Agriculture and Food, Western Australia (DAFWA), 2Insititute of Agriculture, The University of Western Australia (UWA), 3Centre for Legumes in Mediterranean Agriculture (CLIMA), The University of Western Australia 4. PBA Pulse Breeding Australia – 2009 Field Pea Results, Ian Pritchard1, Chris Veitch1, Colin Boyd1, Stuart Morgan1, Alan Harris1 and Tony Leonforte2, 1Department of Agriculture and Food, Western Australia, 2Department of Primary Industries, Victoria 5. PBA Pulse Breeding Australia – 2009 Chickpea Results, Ian Pritchard1, Chris Veitch1, Colin Boyd1, Murray Blyth1, Shari Dougal1 and Kristy Hobson2 1Department of Agriculture and Food, Western Australia, 2Department of Primary Industries, Victoria Decision Support 6. A tool for identifying problems in wheat paddocks, Ben Curtis and Doug Sawkins, Department of Agriculture and Food 7. DAFWA Seasonal Forecast for 2010, Stephens, D, Department of Agriculture and Food, Western Australian, Climate and Modelling Group Disease 8. Enhancement of black spot resistance in field pea, Kedar Adhikari, T Khan, S Morgan and C Boyd, Department of Agriculture and Food, 9. fungicide management of yellow spot in wheat, Ciara Beard, Kith Jayasena, Kazue Tanaka and Anne Smith, Department of Agriculture and Food 10. Resistance to infection by Beet western yellows virus in four Australian canola varieties, Brenda Coutts and Roger Jones, Department of Agriculture and Food 11. Yellow spot carryover risk from stubble in wheat-on-wheat rotations, Jean Galloway, Pip Payne and Tess Humphreys, Department of Agriculture and Food 12. Fungicides for the future: Management of Barley Powdery Mildew and Leaf Rust, Kith Jayasena, Kazue Tanaka and William MacLeod, Department of Agriculture and Food 13. 2009 canola disease survey and management options for blackleg and Sclerotinia in 2010, Ravjit Khangura, WJ MacLeod, M Aberra and H Mian, Department of Agriculture and Food 14. Impact of variety and fungicide on carryover of stubble borne inoculum and yellow spot severity in continuous wheat cropping, Geoff Thomas, Pip Payne, Tess Humphreys and Anne Smith, Department of Agriculture and Food 15. Limitations to the spread of Wheat streak mosaic virus by the Wheat curl mite in WA during 2009, Dusty Severtson, Peter Mangano, Brenda Coutts, Monica Kehoe and Roger Jones, Department of Agriculture and Food 16. Viable solutions for barley powdery mildew, Madeline A. Tucker, Australian Centre for Necrotrophic Fungal Pathogens, Murdoch University Marketing 17. The importance of varietal accreditation in a post-deregulation barley marketing environment, Neil Barker, Barley Australia 18. Can Australia wheat meet requirements for a new middle east market? Robert Loughman, Larisa Cato, Department of Agriculture and Food, and Ken Quail, BRI Australia VARIETY PERFORMANCE 19. Sowing rate and time for hybrid vs open-pollinated canola, Mohammad Amjad and Mark Seymour, Department of Agriculture and Food 20. HYOLA® National Hybrid vs OP Canola Hybrid F1 vs Retained Seed Generation Trial Results and recommendations for growers, Justin Kudnig, Mark Thompson, Anton Mannes, Michael Uttley, Chris Fletcher, Andrew Etherton, Nick Joyce and Kate Light, Pacific Seeds Australia 21. HYOLA® National Hybrid vs OP Canola Sowing Rate Trial Results and plant population recommendations for Australian growers, Justin Kudnig, Mark Thompson, Anton Mannes, Michael Uttley, Andrew Etherton, Chris Fletcher, Nick Joyce and Kate Light, Pacific Seeds Australia; Peter Hamblin, Agritech Research Young, NSW, Michael Lamond, Agrisearch, York, Western Australia 22. Desi chickpea agronomy for 2010, Alan Meldrum, Pulse Australia and Wayne Parker, Department of Agriculture and Food 23. New wheat varieties – exploit the benefits and avoid the pitfalls, Steve Penny, Sarah Ellis, Brenda Shackley, Christine Zaicou, Shahajahan Miyan, Darshan Sharma and Ben Curtis, Department of Agriculture and Food 24. The influence of genetics and environment on the level of seed alkaloid in narrow-leafed lupins, Greg Shea1, Bevan Buirchell1, David Harris2 and Bob French1, 1Department of Agriculture and Food, 2ChemCentr

ACSL6 Is Associated with the Number of Cigarettes Smoked and Its Expression Is Altered by Chronic Nicotine Exposure

Individuals with schizophrenia tend to be heavy smokers and are at high risk for tobacco dependence. However, the nature of the comorbidity is not entirely clear. We previously reported evidence for association of schizophrenia with SNPs and SNP haplotypes in a region of chromosome 5q containing the SPEC2, PDZ-GEF2 and ACSL6 genes. In this current study, analysis of the control subjects of the Molecular Genetics of Schizophrenia (MGS) sample showed similar pattern of association with number of cigarettes smoked per day (numCIG) for the same region. To further test if this locus is associated with tobacco smoking as measured by numCIG and FTND, we conducted replication and meta-analysis in 12 independent samples (n>16,000) for two markers in ACSL6 reported in our previous schizophrenia study. In the meta-analysis of the replication samples, we found that rs667437 and rs477084 were significantly associated with numCIG (p = 0.00038 and 0.00136 respectively) but not with FTND scores. We then used in vitro and in vivo techniques to test if nicotine exposure influences the expression of ACSL6 in brain. Primary cortical culture studies showed that chronic (5-day) exposure to nicotine stimulated ACSL6 mRNA expression. Fourteen days of nicotine administration via osmotic mini pump also increased ACSL6 protein levels in the prefrontal cortex and hippocampus of mice. These increases were suppressed by injection of the nicotinic receptor antagonist mecamylamine, suggesting that elevated expression of ACSL6 requires nicotinic receptor activation. These findings suggest that variations in the ACSL6 gene may contribute to the quantity of cigarettes smoked. The independent associations of this locus with schizophrenia and with numCIG in non-schizophrenic subjects suggest that this locus may be a common liability to both conditions

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.3448Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.We thank all participants of all the studies included for enabling this research by their participation in these studies. Computer resources for this project have been provided by the high-performance computing centers of the University of Michigan and the University of Regensburg. Group-specific acknowledgments can be found in the Supplementary Note. The Center for Inherited Diseases Research (CIDR) Program contract number is HHSN268201200008I. This and the main consortium work were predominantly funded by 1X01HG006934-01 to G.R.A. and R01 EY022310 to J.L.H

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Phenotypic Characterization of EIF2AK4 Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease with an emerging genetic basis. Heterozygous mutations in the gene encoding the bone morphogenetic protein receptor type 2 (BMPR2) are the commonest genetic cause of PAH, whereas biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene (EIF2AK4) are described in pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Here, we determine the frequency of these mutations and define the genotype-phenotype characteristics in a large cohort of patients diagnosed clinically with PAH. METHODS: Whole-genome sequencing was performed on DNA from patients with idiopathic and heritable PAH and with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis recruited to the National Institute of Health Research BioResource-Rare Diseases study. Heterozygous variants in BMPR2 and biallelic EIF2AK4 variants with a minor allele frequency of <1:10 000 in control data sets and predicted to be deleterious (by combined annotation-dependent depletion, PolyPhen-2, and sorting intolerant from tolerant predictions) were identified as potentially causal. Phenotype data from the time of diagnosis were also captured. RESULTS: Eight hundred sixty-four patients with idiopathic or heritable PAH and 16 with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis were recruited. Mutations in BMPR2 were identified in 130 patients (14.8%). Biallelic mutations in EIF2AK4 were identified in 5 patients with a clinical diagnosis of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Furthermore, 9 patients with a clinical diagnosis of PAH carried biallelic EIF2AK4 mutations. These patients had a reduced transfer coefficient for carbon monoxide (Kco; 33% [interquartile range, 30%-35%] predicted) and younger age at diagnosis (29 years; interquartile range, 23-38 years) and more interlobular septal thickening and mediastinal lymphadenopathy on computed tomography of the chest compared with patients with PAH without EIF2AK4 mutations. However, radiological assessment alone could not accurately identify biallelic EIF2AK4 mutation carriers. Patients with PAH with biallelic EIF2AK4 mutations had a shorter survival. CONCLUSIONS: Biallelic EIF2AK4 mutations are found in patients classified clinically as having idiopathic and heritable PAH. These patients cannot be identified reliably by computed tomography, but a low Kco and a young age at diagnosis suggests the underlying molecular diagnosis. Genetic testing can identify these misclassified patients, allowing appropriate management and early referral for lung transplantation

Comprehensive Cancer-Predisposition Gene Testing in an Adult Multiple Primary Tumor Series Shows a Broad Range of Deleterious Variants and Atypical Tumor Phenotypes.

Multiple primary tumors (MPTs) affect a substantial proportion of cancer survivors and can result from various causes, including inherited predisposition. Currently, germline genetic testing of MPT-affected individuals for variants in cancer-predisposition genes (CPGs) is mostly targeted by tumor type. We ascertained pre-assessed MPT individuals (with at least two primary tumors by age 60 years or at least three by 70 years) from genetics centers and performed whole-genome sequencing (WGS) on 460 individuals from 440 families. Despite previous negative genetic assessment and molecular investigations, pathogenic variants in moderate- and high-risk CPGs were detected in 67/440 (15.2%) probands. WGS detected variants that would not be (or were not) detected by targeted resequencing strategies, including low-frequency structural variants (6/440 [1.4%] probands). In most individuals with a germline variant assessed as pathogenic or likely pathogenic (P/LP), at least one of their tumor types was characteristic of variants in the relevant CPG. However, in 29 probands (42.2% of those with a P/LP variant), the tumor phenotype appeared discordant. The frequency of individuals with truncating or splice-site CPG variants and at least one discordant tumor type was significantly higher than in a control population (χ2 = 43.642; p ≤ 0.0001). 2/67 (3%) probands with P/LP variants had evidence of multiple inherited neoplasia allele syndrome (MINAS) with deleterious variants in two CPGs. Together with variant detection rates from a previous series of similarly ascertained MPT-affected individuals, the present results suggest that first-line comprehensive CPG analysis in an MPT cohort referred to clinical genetics services would detect a deleterious variant in about a third of individuals.JW is supported by a Cancer Research UK Cambridge Cancer Centre Clinical Research Training Fellowship. Funding for the NIHR BioResource – Rare diseases project was provided by the National Institute for Health Research (NIHR, grant number RG65966). ERM acknowledges support from the European Research Council (Advanced Researcher Award), NIHR (Senior Investigator Award and Cambridge NIHR Biomedical Research Centre), Cancer Research UK Cambridge Cancer Centre and Medical Research Council Infrastructure Award. The University of Cambridge has received salary support in respect of EM from the NHS in the East of England through the Clinical Academic Reserve. The views expressed are those of the authors and not necessarily those of the NHS or Department of Health. DGE is an NIHR Senior Investigator and is supported by the all Manchester NIHR Biomedical Research Centre