Secondary Ion Mass Spectrometry And Its Application To Studies In Geochemistry

Secondary ion mass spectrometry (SIMS) with specimen isolation conditions (an extreme form of energy filtering) is useful in geochemical studies. The presence of molecular ion interferences in SIMS spectra is greatly reduced when analyzing high energy secondary ions (i.e. specimen isolation conditions), thus simplifying the interpretation of mass spectra.;High energy secondary ions were found to be less susceptible to the dramatic changes in ionization yield resulting from the effect of the matrix in secondary ion production. Correlation of ion intensities for glass and crystalline materials of identical composition is possible for most elements when using some form of energy filtering, and thus the use of glass standards for SIMS analysis of minerals is possible. Some matrix effects are still present in the high energy ion population. However, in a given concentration range with a reliable set of standards, quantitative analysis down to the ppm level is available with specimen isolation or conventional energy filtering methods. This has been demonstrated for the rare-earth elements at both trace and major element concentration levels in various mineral grains.;The ionization probability of high energy ions was studied as a function of kinetic energy, first ionization potential, and oxide bond strength. A simple mechanism for the production of high energy secondary ions could not be obtained from these results.;Besides the elimination of molecular ion interferences, the method of specimen isolation is an excellent technique for the analysis of non-conducting samples. Leached, or altered zones up to several hundreds of angstroms in thickness have been observed in SIMS depth profiles of naturally and laboratory dissolved plagioclase. Dissolution of plagioclase in relatively simple laboratory experiments (pH 3.5 and 5.7) forms altered zones depleted of sodium, calcium and aluminum, and enriched (residually) in silicon. For specimens undergoing a more complex set of reactions (dissolution in nature), layers enriched in aluminum were observed in the SIMS profiles. Each of these layers are believed to form during the dissolution process. Qualitatively similar results were obtained using X-ray photoelectron spectroscopy, while SEM analysis has shown the sample surfaces to be clean and free of secondary precipitates

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Abstracts from the NIHR INVOLVE Conference 2017

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Functional annotation of the 2q35 breast cancer risk locus implicates a structural variant in influencing activity of a long-range enhancer element

A combination of genetic and functional approaches has identified three independent breast cancer risk loci at 2q35. A recent fine-scale mapping analysis to refine these associations resulted in 1 (signal 1), 5 (signal 2), and 42 (signal 3) credible causal variants at these loci. We used publicly available in silico DNase I and ChIP-seq data with in vitro reporter gene and CRISPR assays to annotate signals 2 and 3. We identified putative regulatory elements that enhanced cell-type-specific transcription from the IGFBP5 promoter at both signals (30-to 40-fold increased expression by the putative regulatory element at signal 2, 2- to 3-fold by the putative regulatory element at signal 3). We further identified one of the five credible causal variants at signal 2, a 1.4 kb deletion (esv3594306), as the likely causal variant; the deletion allele of this variant was associated with an average additional increase in IGFBP5 expression of 1.3-fold (MCF-7) and 2.2-fold (T-47D). We propose a model in which the deletion allele of esv3594306 juxtaposes two transcription factor binding regions (annotated by estrogen receptor alpha ChIP-seq peaks) to generate a single extended regulatory element. This regulatory element increases cell-type-specific expression of the tumor suppressor gene IGFBP5 and, thereby, reduces risk of estrogen receptor-positive breast cancer (odds ratio = 0.77, 95% CI 0.74-0.81, p = 3.1 x 10(-31)).Peer reviewe

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170.

We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER(+) or ER(-)) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER(-) tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.352