‘Blind time’ – current limitations on laser ablation multi-collector inductively coupled plasma mass spectrometry (LA-MC-ICP-MS) for ultra-transient signal isotope ratio analysis and application to individual sub-micron sized uranium particles

The application of laser ablation multi-collector inductively coupled plasma mass spectrometry (LA-MC-ICP-MS) to the isotope ratio analysis of UOx particles has the potential to improve the isotopic determination of these particles when compared to currently utilised ICP-MS techniques. To investigate this a high-speed, integrated ablation cell and dual concentric injector design was tested in the expectation that the resulting increase in signal to noise ratio and sample ion yield would improve the determination of 234U/238U, 235U/238U and 236U/238U for such materials. However, when compared to a slower washout, more established low-volume cell design, the highly transient signals of the new design proved challenging for the mixed detector array of the multi-collector mass spectrometer, introducing a new bias. We describe a major component of this bias, referred to as ‘blind time’, and model its impact on UOx particle analysis. After accounting for blind time, average precisions for the uranium isotopic composition of sub-micron sized UOx particles using LA-MC-ICP-MS were 3% 1RSD for 235U/238U and 8% 1RSD for 234U/238U. When ablating a glass rather than a UOx particle, uncertainties of 1.3% 1RSD for 235U/238U were achieved for 150 nm equivalent particle sizes using LA-MC-ICP-MS

ESTIMATING GENOME-WIDE COPY NUMBER USING ALLELE SPECIFIC MIXTURE MODELS

Genomic changes such as copy number alterations are thought to be one of the major underlying causes of human phenotypic variation among normal and disease subjects [23,11,25,26,5,4,7,18]. These include chromosomal regions with so-called copy number alterations: instead of the expected two copies, a section of the chromosome for a particular individual may have zero copies (homozygous deletion), one copy (hemizygous deletions), or more than two copies (amplifications). The canonical example is Down syndrome which is caused by an extra copy of chromosome 21. Identification of such abnormalities in smaller regions has been of great interest, because it is believed to be an underlying cause of cancer. More than one decade ago comparative genomic hybridization (CGH)technology was developed to detect copy number changes in a high-throughput fashion. However, this technology only provides a 10 MB resolution which limits the ability to detect copy number alterations spanning small regions. It is widely believed that a copy number alteration as small as one base can have significant downstream effects, thus microarray manufacturers have developed technologies that provide much higher resolution. Unfortunately, strong probe effects and variation introduced by sample preparation procedures have made single-point copy number estimates too imprecise to be useful. CGH arrays use a two-color hybridization, usually comparing a sample of interest to a reference sample, which to some degree removes the probe effect. However, the resolution is not nearly high enough to provide single-point copy number estimates. Various groups have proposed statistical procedures that pool data from neighboring locations to successfully improve precision. However, these procedure need to average across relatively large regions to work effectively thus greatly reducing the resolution. Recently, regression-type models that account for probe-effect have been proposed and appear to improve accuracy as well as precision. In this paper, we propose a mixture model solution specifically designed for single-point estimation, that provides various advantages over the existing methodology. We use a 314 sample database, constructed with public datasets, to motivate and fit models for the conditional distribution of the observed intensities given allele specific copy numbers. With the estimated models in place we can compute posterior probabilities that provide a useful prediction rule as well as a confidence measure for each call. Software to implement this procedure will be available in the Bioconductor oligo packagehttp://www.bioconductor.org)

Equatorial circular orbits in the Kerr-de Sitter spacetimes

Equatorial motion of test particles in the Kerr-de Sitter spacetimes is considered. Circular orbits are determined, their properties are discussed for both the black-hole and naked-singularity spacetimes, and their relevance for thin accretion discs is established.Comment: 24 pages, 19 figures, REVTeX

A combined risk score enhances prediction of type 1 diabetes among susceptible children

This is the author accepted manuscript. The final version is available from Nature Research via the DOI in this recordType 1 diabetes (T1D)-an autoimmune disease that destroys the pancreatic islets, resulting in insulin deficiency-often begins early in life when islet autoantibody appearance signals high risk1. However, clinical diabetes can follow in weeks or only after decades, and is very difficult to predict. Ketoacidosis at onset remains common2,3 and is most severe in the very young4,5, in whom it can be life threatening and difficult to treat6-9. Autoantibody surveillance programs effectively prevent most ketoacidosis10-12 but require frequent evaluations whose expense limits public health adoption13. Prevention therapies applied before onset, when greater islet mass remains, have rarely been feasible14 because individuals at greatest risk of impending T1D are difficult to identify. To remedy this, we sought accurate, cost-effective estimation of future T1D risk by developing a combined risk score incorporating both fixed and variable factors (genetic, clinical and immunological) in 7,798 high-risk children followed closely from birth for 9.3 years. Compared with autoantibodies alone, the combined model dramatically improves T1D prediction at ≥2 years of age over horizons up to 8 years of age (area under the receiver operating characteristic curve ≥ 0.9), doubles the estimated efficiency of population-based newborn screening to prevent ketoacidosis, and enables individualized risk estimates for better prevention trial selection.National Institutes of Health/National Center for Advancing Translational Sciences Clinical and Translational ScienceDiabetes Research CenterDiabetes UKWellcome TrustJDR

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Search for a W' boson decaying to a bottom quark and a top quark in pp collisions at sqrt(s) = 7 TeV

Results are presented from a search for a W' boson using a dataset corresponding to 5.0 inverse femtobarns of integrated luminosity collected during 2011 by the CMS experiment at the LHC in pp collisions at sqrt(s)=7 TeV. The W' boson is modeled as a heavy W boson, but different scenarios for the couplings to fermions are considered, involving both left-handed and right-handed chiral projections of the fermions, as well as an arbitrary mixture of the two. The search is performed in the decay channel W' to t b, leading to a final state signature with a single lepton (e, mu), missing transverse energy, and jets, at least one of which is tagged as a b-jet. A W' boson that couples to fermions with the same coupling constant as the W, but to the right-handed rather than left-handed chiral projections, is excluded for masses below 1.85 TeV at the 95% confidence level. For the first time using LHC data, constraints on the W' gauge coupling for a set of left- and right-handed coupling combinations have been placed. These results represent a significant improvement over previously published limits.Comment: Submitted to Physics Letters B. Replaced with version publishe

Measurement of the Lambda(b) cross section and the anti-Lambda(b) to Lambda(b) ratio with Lambda(b) to J/Psi Lambda decays in pp collisions at sqrt(s) = 7 TeV

The Lambda(b) differential production cross section and the cross section ratio anti-Lambda(b)/Lambda(b) are measured as functions of transverse momentum pt(Lambda(b)) and rapidity abs(y(Lambda(b))) in pp collisions at sqrt(s) = 7 TeV using data collected by the CMS experiment at the LHC. The measurements are based on Lambda(b) decays reconstructed in the exclusive final state J/Psi Lambda, with the subsequent decays J/Psi to an opposite-sign muon pair and Lambda to proton pion, using a data sample corresponding to an integrated luminosity of 1.9 inverse femtobarns. The product of the cross section times the branching ratio for Lambda(b) to J/Psi Lambda versus pt(Lambda(b)) falls faster than that of b mesons. The measured value of the cross section times the branching ratio for pt(Lambda(b)) > 10 GeV and abs(y(Lambda(b))) < 2.0 is 1.06 +/- 0.06 +/- 0.12 nb, and the integrated cross section ratio for anti-Lambda(b)/Lambda(b) is 1.02 +/- 0.07 +/- 0.09, where the uncertainties are statistical and systematic, respectively.Comment: Submitted to Physics Letters

Search for new physics in events with opposite-sign leptons, jets, and missing transverse energy in pp collisions at sqrt(s) = 7 TeV

A search is presented for physics beyond the standard model (BSM) in final states with a pair of opposite-sign isolated leptons accompanied by jets and missing transverse energy. The search uses LHC data recorded at a center-of-mass energy sqrt(s) = 7 TeV with the CMS detector, corresponding to an integrated luminosity of approximately 5 inverse femtobarns. Two complementary search strategies are employed. The first probes models with a specific dilepton production mechanism that leads to a characteristic kinematic edge in the dilepton mass distribution. The second strategy probes models of dilepton production with heavy, colored objects that decay to final states including invisible particles, leading to very large hadronic activity and missing transverse energy. No evidence for an event yield in excess of the standard model expectations is found. Upper limits on the BSM contributions to the signal regions are deduced from the results, which are used to exclude a region of the parameter space of the constrained minimal supersymmetric extension of the standard model. Additional information related to detector efficiencies and response is provided to allow testing specific models of BSM physics not considered in this paper.Comment: Replaced with published version. Added journal reference and DO

Measurement of isolated photon production in pp and PbPb collisions at sqrt(sNN) = 2.76 TeV

Isolated photon production is measured in proton-proton and lead-lead collisions at nucleon-nucleon centre-of-mass energies of 2.76 TeV in the pseudorapidity range |eta|<1.44 and transverse energies ET between 20 and 80 GeV with the CMS detector at the LHC. The measured ET spectra are found to be in good agreement with next-to-leading-order perturbative QCD predictions. The ratio of PbPb to pp isolated photon ET-differential yields, scaled by the number of incoherent nucleon-nucleon collisions, is consistent with unity for all PbPb reaction centralities.Comment: Submitted to Physics Letters