Alien Registration- Key, Richard G. (Portland, Cumberland County)

https://digitalmaine.com/alien_docs/22095/thumbnail.jp

Breast clinic and life style study BLLISS

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Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression

Associations between single nucleotide polymorphisms (SNPs) at 5p15 and multiple cancer types have been reported. We have previously shown evidence for a strong association between prostate cancer (PrCa) risk and rs2242652 at 5p15, intronic in the telomerase reverse transcriptase (TERT) gene that encodes TERT. To comprehensively evaluate the association between genetic variation across this region and PrCa, we performed a fine-mapping analysis by genotyping 134 SNPs using a custom Illumina iSelect array or Sequenom MassArray iPlex, followed by imputation of 1094 SNPs in 22 301 PrCa cases and 22 320 controls in The PRACTICAL consortium. Multiple stepwise logistic regression analysis identified four signals in the promoter or intronic regions of TERT that independently associated with PrCa risk. Gene expression analysis of normal prostate tissue showed evidence that SNPs within one of these regions also associated with TERT expression, providing a potential mechanism for predisposition to disease

Laser generated electron transport experiment in a novel wire nail target

The transport of high intensity (2x1020 W/cm2) laser generated relativistic electrons with a solid target has been studied in a novel geometry. The targets were 20 um diameter solid copper wires, coated with ~ 2um of titanium, with an 80 um diameter hemispherical termination. They were illuminated by an ~500fs, ~200J pulse of 1.053um laser light focused to a ~ 20um diameter spot centered on the flat face of the hemisphere. K-alpha fluorescence from the Cu and Ti regions was imaged together with extreme ultraviolet (X-UV) emission at 68 and 256eV. Results showed a quasi exponential decline in K-alpha emission along the wire over a distance of a few hundred microns from the laser focus, consistent with bulk Ohmic inhibition of the relativistic electron transport. Weaker Ka and X-UV emission on a longer scale length showed limb brightening suggesting a transition to enhanced transport at the surface of the wire

Circulating vitamin D concentrations and risk of breast and prostate cancer: a Mendelian randomization study.

BACKGROUND: Observational studies have suggested an association between circulating vitamin D concentrations [25(OH)D] and risk of breast and prostate cancer, which was not supported by a recent Mendelian randomization (MR) analysis comprising 15 748 breast and 22 898 prostate-cancer cases. Demonstrating causality has proven challenging and one common limitation of MR studies is insufficient power. METHODS: We aimed to determine whether circulating concentrations of vitamin D are causally associated with the risk of breast and prostate cancer, by using summary-level data from the largest ever genome-wide association studies conducted on vitamin D (N = 73 699), breast cancer (Ncase = 122 977) and prostate cancer (Ncase = 79 148). We constructed a stronger instrument using six common genetic variants (compared with the previous four variants) and applied several two-sample MR methods. RESULTS: We found no evidence to support a causal association between 25(OH)D and risk of breast cancer [OR per 25 nmol/L increase, 1.02 (95% confidence interval: 0.97-1.08), P = 0.47], oestrogen receptor (ER)+ [1.00 (0.94-1.07), P = 0.99] or ER- [1.02 (0.90-1.16), P = 0.75] subsets, prostate cancer [1.00 (0.93-1.07), P = 0.99] or the advanced subtype [1.02 (0.90-1.16), P = 0.72] using the inverse-variance-weighted method. Sensitivity analyses did not reveal any sign of directional pleiotropy. CONCLUSIONS: Despite its almost five-fold augmented sample size and substantially improved statistical power, our MR analysis does not support a causal effect of circulating 25(OH)D concentrations on breast- or prostate-cancer risk. However, we can still not exclude a modest or non-linear effect of vitamin D. Future studies may be designed to understand the effect of vitamin D in subpopulations with a profound deficiency

Quantifying the drivers of ocean-atmosphere CO2 fluxes

A mechanistic framework for quantitatively mapping the regional drivers of air-sea CO2 fluxes at a global scale is developed. The framework evaluates the interplay between (1) surface heat and freshwater fluxes that influence the potential saturated carbon concentration, which depends on changes in sea surface temperature, salinity and alkalinity, (2) a residual, disequilibrium flux influenced by upwelling and entrainment of remineralized carbon- and nutrient-rich waters from the ocean interior, as well as rapid subduction of surface waters, (3) carbon uptake and export by biological activity as both soft tissue and carbonate, and (4) the effect on surface carbon concentrations due to freshwater precipitation or evaporation. In a steady state simulation of a coarse-resolution ocean circulation and biogeochemistry model, the sum of the individually determined components is close to the known total flux of the simulation. The leading order balance, identified in different dynamical regimes, is between the CO2 fluxes driven by surface heat fluxes and a combination of biologically driven carbon uptake and disequilibrium-driven carbon outgassing. The framework is still able to reconstruct simulated fluxes when evaluated using monthly averaged data and takes a form that can be applied consistently in models of different complexity and observations of the ocean. In this way, the framework may reveal differences in the balance of drivers acting across an ensemble of climate model simulations or be applied to an analysis and interpretation of the observed, real-world air-sea flux of CO2

Genetics and prognostication in splenic marginal zone lymphoma: revelations from deep sequencing

PURPOSE: Mounting evidence supports the clinical significance of gene mutations and immunogenetic features in common mature B-cell malignancies.EXPERIMENTAL DESIGN: We undertook a detailed characterization of the genetic background of splenic marginal zone lymphoma (SMZL), using targeted re-sequencing and explored potential clinical implications in a multinational cohort of 175 SMZL patients.RESULTS: We identified recurrent mutations in TP53 (16%), KLF2 (12%), NOTCH2 (10%), TNFAIP3 (7%), MLL2 (11%), MYD88 (7%) and ARID1A (6%), all genes known to be targeted by somatic mutation in SMZL. KLF2 mutations were early, clonal events, enriched in patients with del(7q) and IGHV1-2*04 B-cell receptor immunoglobulins, and were associated with a short median time-to-first-treatment (0.12 vs. 1.11 yrs; P=0.01). In multivariate analysis mutations in NOTCH2 (HR 2.12, 95%CI 1.02-4.4, P=0.044) and 100% germline IGHV gene identity (HR 2.19, 95%CI 1.05-4.55, P=0.036) were independent markers of short time-to-first-treatment, while TP53 mutations were an independent marker of short overall survival (HR 2.36, 95% CI 1.08-5.2, P=0.03).CONCLUSIONS: We identify key associations between gene mutations and clinical outcome, demonstrating for the first time that NOTCH2 and TP53 gene mutations are independent markers of reduced treatment-free and overall survival, respectively.<br/