A whole-rock data set for the Skaergaard intrusion, East Greenland

We report a compilation of new and published whole-rock major and trace element analyses for 646 samples of the Skaergaard intrusion, East Greenland. The samples were collected in 14 stratigraphic profiles either from accessible and well-exposed surface areas or from drill core, and they cover most regions of the intrusion. This includes the Layered Series, the Upper Border Series, the Marginal Border Series and the Sandwich Horizon. The geochemical data were obtained by a combination of X-ray fluorescence and inductively coupled plasma mass spectrometry. This data set can, for example, be used to constrain processes of igneous differentiation and ore formation.

Melt diffusion-moderated crystal growth and its effect on euhedral crystal shapes

Crystal growth is often described as either interface-controlled or diffusion-controlled. Here, we study crystal growth in an intermediate scenario where reaction rates at the crystal-melt interface are similar to the rates of diffusive transport of ions through the melt to the advancing crystal surface. To this end, we experimentally investigated euhedral plagioclase crystal shapes in dry mafic (basaltic) and hydrous silicic (haplodacitic) melts. Aspect ratios and inferred relative growth rates of the 3D short (S) and intermediate (I) crystal dimensions vary significantly between mafic and silicic melts, with δS:δI = 1:6 – 1:20 in basalt and 1:2.5 – 1:8 in hydrous haplodacite. The lower aspect ratios of plagioclase grown in the silicic melt coincide with 10-100x lower melt diffusion rates than in the mafic melt. Using an anisotropic growth model, we show that such differences in melt diffusivity can explain the discrepancy in plagioclase aspect ratios: if interface reaction and melt diffusion rates are of similar magnitude, then the growth of a crystal facet with high interfacial reaction rates may be limited by melt diffusion while another facet of the same crystal with lower interfacial reaction rates may grow uninhibited by melt diffusivity. This selective control of melt diffusion on crystal growth rates results in progressively more equant crystal shapes as diffusivity decreases, consistent with our experimental observations. Importantly, crystals formed in this diffusion-moderated, intermediate growth regime may not show any classical diffusion-controlled growth features. The proposed model was developed for plagioclase microlites, but should be generalisable to all anisotropic microlite growth in volcanic rocks

Evidence for the formation of silicic lava by pyroclast sintering

Silicic lavas can be produced by the sintering of pyroclasts in the volcanic sub-surface, and then advected out of the vent. Here, we provide evidence for this mechanism preserved in the exposed post-glacial remnants of a silicic volcanic conduit at Hrafntinnuhryggur, Krafla volcano, Iceland. We show that the conduit margins are a clast-supported pumice lapilli tuff deposit that grades continuously into dense obsidian and that the obsidian contains cuspate relict clast boundaries and country rock lithic fragments throughout. Transects of H2O concentrations across the conduit show that the magma was degassed to different degrees laterally with systematic spatial variation that is consistent with progressive conduit clogging and final gas pressurisation. Textures in the overlying effusive lavas record the variably sheared and brecciated remnant of the same in-conduit sintering. This record of a silicic conduit system connected to upper eruptive deposits provides support for the ‘cryptic fragmentation model’ for effusive silicic volcanism

Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with prognosis of estrogen receptor-negative breast cancer after chemotherapy

Introduction: Tumor lymphocyte infiltration is associated with clinical response to chemotherapy in estrogen receptor (ER) negative breast cancer. To identify variants in immunosuppressive pathway genes associated with prognosis after adjuvant chemotherapy for ER-negative patients, we studied stage I-III invasive breast cancer patients of European ancestry, including 9,334 ER-positive (3,151 treated with chemotherapy) and 2,334 ER-negative patients (1,499 treated with chemotherapy). Methods: We pooled data from sixteen studies from the Breast Cancer Association Consortium (BCAC), and employed two independent studies for replications. Overall 3,610 single nucleotide polymorphisms (SNPs) in 133 genes were genotyped as part of the Collaborative Oncological Gene-environment Study, in which phenotype and clinical data were collected and harmonized. Multivariable Cox proportional hazard regression was used to assess genetic associations with overall survival (OS) and breast

Polymorphisms in a Putative Enhancer at the 10q21.2 Breast Cancer Risk Locus Regulate NRBF2 Expression.

Genome-wide association studies have identified SNPs near ZNF365 at 10q21.2 that are associated with both breast cancer risk and mammographic density. To identify the most likely causal SNPs, we fine mapped the association signal by genotyping 428 SNPs across the region in 89,050 European and 12,893 Asian case and control subjects from the Breast Cancer Association Consortium. We identified four independent sets of correlated, highly trait-associated variants (iCHAVs), three of which were located within ZNF365. The most strongly risk-associated SNP, rs10995201 in iCHAV1, showed clear evidence of association with both estrogen receptor (ER)-positive (OR = 0.85 [0.82-0.88]) and ER-negative (OR = 0.87 [0.82-0.91]) disease, and was also the SNP most strongly associated with percent mammographic density. iCHAV2 (lead SNP, chr10: 64,258,684:D) and iCHAV3 (lead SNP, rs7922449) were also associated with ER-positive (OR = 0.93 [0.91-0.95] and OR = 1.06 [1.03-1.09]) and ER-negative (OR = 0.95 [0.91-0.98] and OR = 1.08 [1.04-1.13]) disease. There was weaker evidence for iCHAV4, located 5' of ADO, associated only with ER-positive breast cancer (OR = 0.93 [0.90-0.96]). We found 12, 17, 18, and 2 candidate causal SNPs for breast cancer in iCHAVs 1-4, respectively. Chromosome conformation capture analysis showed that iCHAV2 interacts with the ZNF365 and NRBF2 (more than 600 kb away) promoters in normal and cancerous breast epithelial cells. Luciferase assays did not identify SNPs that affect transactivation of ZNF365, but identified a protective haplotype in iCHAV2, associated with silencing of the NRBF2 promoter, implicating this gene in the etiology of breast cancer.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.ajhg.2015.05.002

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Crystallization of Interstitial Liquid and Latent Heat Buffering in Solidifying Gabbros: Skaergaard Intrusion, Greenland

New compositional profiles across plagioclase grains from the Layered Series (LS), Marginal Border Series (MBS) and Upper Border Series (UBS) of the Skaergaard intrusion are used to understand the mechanisms of cumulate rock solidification and the fate of the interstitial liquid. The data show that plagioclase crystals display three types of compositional profile over the whole intrusion, as follows. (1) Grains with normal zoning, which dominate the MBS and UBS. These are interpreted as having formed at the top of a crystal mush and then buried in the cumulate pile. Crystallization of the interstitial melt resulted in liquid differentiation and produced normally zoned rims on plagioclase cores. (2) Unzoned crystals, which dominate the upper part of the LS, also crystallized at the top of the mush and were then buried in mush with a low interstitial liquid fraction or one experiencing convective movements that kept the liquid to a constant composition. (3) Crystals with a mantle of decreasing An content followed by a rim of constant composition. Grains showing this complex zoning mostly occur in the lower parts of the LS. Depending on the stratigraphic position within the intrusion, the composition of the rim can be An56, An51 or An40. In the main magma body, these compositions (An contents) correspond to those of plagioclase primocrysts (e.g. cores) at the appearance of cumulus clinopyroxene (An56), Fe–Ti oxides (An51) and apatite (An40). Compositional buffering of plagioclase rims is interpreted as being a consequence of enhanced release of latent heat of crystallization at the appearance of new interstitial phases in the crystal mush. When a new phase saturates, the latent heat contribution to the global enthalpy budget of the system becomes sufficiently high to keep the interstitial melt at its liquidus temperature for a period of time that could exceed thousands of years. Under these conditions, equilibrium, adcumulus growth together with diffusion and possibly advection of chemical components result in the formation of plagioclase rims of constant composition (An content). Efficient thermal buffering of the mush liquid depends on the porosity (i.e. fraction of liquid within the mush) and the degree of compositional homogeneity of the mush. In a heterogeneous and highly porous mush, saturation of the new phase occurs in the coldest part of the mush and the enhanced latent heat release at the saturation of this phase is quickly dissipated to the whole volume of liquid, including the warmest part that is not yet saturated in a new phase. As a consequence, no thermal buffering occurs and interstitial crystallization produces grains with normal zoning. The distribution of the various types of plagioclase grains throughout the Skaergaard intrusion can therefore be used to infer the spatial variability in the physical properties of the crystal mush, such as the residual porosity, both at an intrusion-wide scale and at a millimetre- to centimetre-scale