Bilinear forms on Grothendieck groups of triangulated categories

We extend the theory of bilinear forms on the Green ring of a finite group developed by Benson and Parker to the context of the Grothendieck group of a triangulated category with Auslander-Reiten triangles, taking only relations given by direct sum decompositions. We examine the non-degeneracy of the bilinear form given by dimensions of homomorphisms, and show that the form may be modified to give a Hermitian form for which the standard basis given by indecomposable objects has a dual basis given by Auslander-Reiten triangles. An application is given to the homotopy category of perfect complexes over a symmetric algebra, with a consequence analogous to a result of Erdmann and Kerner.Comment: arXiv admin note: substantial text overlap with arXiv:1301.470

Quantifying the impact of BOReal forest fires on Tropospheric oxidants over the Atlantic using Aircraft and Satellites (BORTAS) experiment: design, execution and science overview

We describe the design and execution of the BORTAS (Quantifying the impact of BOReal forest fires on Tropospheric oxidants over the Atlantic using Aircraft and Satellites) experiment, which has the overarching objective of understanding the chemical aging of air masses that contain the emission products from seasonal boreal wildfires and how these air masses subsequently impact downwind atmospheric composition. The central focus of the experiment was a two-week deployment of the UK BAe-146-301 Atmospheric Research Aircraft (ARA) over eastern Canada, based out of Halifax, Nova Scotia. Atmospheric ground-based and sonde measurements over Canada and the Azores associated with the planned July 2010 deployment of the ARA, which was postponed by 12 months due to UK-based flights related to the dispersal of material emitted by the Eyjafjallajökull volcano, went ahead and constituted phase A of the experiment. Phase B of BORTAS in July 2011 involved the same atmospheric measurements, but included the ARA, special satellite observations and a more comprehensive ground-based measurement suite. The high-frequency aircraft data provided a comprehensive chemical snapshot of pyrogenic plumes from wildfires, corresponding to photochemical (and physical) ages ranging from 45 sr 10 days, largely by virtue of widespread fires over Northwestern Ontario. Airborne measurements reported a large number of emitted gases including semi-volatile species, some of which have not been been previously reported in pyrogenic plumes, with the corresponding emission ratios agreeing with previous work for common gases. Analysis of the NOy data shows evidence of net ozone production in pyrogenic plumes, controlled by aerosol abundance, which increases as a function of photochemical age. The coordinated ground-based and sonde data provided detailed but spatially limited information that put the aircraft data into context of the longer burning season in the boundary layer. Ground-based measurements of particulate matter smaller than 2.5 μm (PM2.5) over Halifax show that forest fires can on an episodic basis represent a substantial contribution to total surface PM2.5

Development and validation of a targeted gene sequencing panel for application to disparate cancers

Next generation sequencing has revolutionised genomic studies of cancer, having facilitated the development of precision oncology treatments based on a tumour’s molecular profile. We aimed to develop a targeted gene sequencing panel for application to disparate cancer types with particular focus on tumours of the head and neck, plus test for utility in liquid biopsy. The final panel designed through Roche/Nimblegen combined 451 cancer-associated genes (2.01 Mb target region). 136 patient DNA samples were collected for performance and application testing. Panel sensitivity and precision were measured using well-characterised DNA controls (n = 47), and specificity by Sanger sequencing of the Aryl Hydrocarbon Receptor Interacting Protein (AIP) gene in 89 patients. Assessment of liquid biopsy application employed a pool of synthetic circulating tumour DNA (ctDNA). Library preparation and sequencing were conducted on Illumina-based platforms prior to analysis with our accredited (ISO15189) bioinformatics pipeline. We achieved a mean coverage of 395x, with sensitivity and specificity of >99% and precision of >97%. Liquid biopsy revealed detection to 1.25% variant allele frequency. Application to head and neck tumours/cancers resulted in detection of mutations aligned to published databases. In conclusion, we have developed an analytically-validated panel for application to cancers of disparate types with utility in liquid biopsy

­­LUBAC deficiency perturbs TLR3 signaling to cause immunodeficiency and autoinflammation

The linear ubiquitin chain assembly complex (LUBAC), consisting of SHANK-associated RH-domain–interacting protein (SHARPIN), heme-oxidized IRP2 ubiquitin ligase-1 (HOIL-1), and HOIL-1–interacting protein (HOIP), is a critical regulator of inflammation and immunity. This is highlighted by the fact that patients with perturbed linear ubiquitination caused by mutations in the Hoip or Hoil-1 genes, resulting in knockouts of these proteins, may simultaneously suffer from immunodeficiency and autoinflammation. TLR3 plays a crucial, albeit controversial, role in viral infection and tissue damage. We identify a pivotal role of LUBAC in TLR3 signaling and discover a functional interaction between LUBAC components and TLR3 as crucial for immunity to influenza A virus infection. On the biochemical level, we identify LUBAC components as interacting with the TLR3-signaling complex (SC), thereby enabling TLR3-mediated gene activation. Absence of LUBAC components increases formation of a previously unrecognized TLR3-induced death-inducing SC, leading to enhanced cell death. Intriguingly, excessive TLR3-mediated cell death, induced by double-stranded RNA present in the skin of SHARPIN-deficient chronic proliferative dermatitis mice (cpdm), is a major contributor to their autoinflammatory skin phenotype, as genetic coablation of Tlr3 substantially ameliorated cpdm dermatitis. Thus, LUBAC components control TLR3-mediated innate immunity, thereby preventing development of immunodeficiency and autoinflammation

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

Principle and pragmatism: a study of competition between Australia’s major parties at the 2004 and other recent Federal elections

This brief study addresses a number of questions about pragmatism and principle in the context of recent electoral competition between the Australian Labor Party and the Liberal Party of Australia, particularly at the 2004 election. Some of these questions are about priorities, and some are about meanings. How strongly has the incentive to be pragmatic in policy encroached on principled policy formation in these parties? What does it mean for policy to be principled, and where does the line between principled and pragmatic policy formation lie? How different have the two parties been in the ideals they advocate, and how faithful have their respective policies been to these ideals