The effect of the top 20 Alzheimer disease risk genes on gray-matter density and FDG PET brain metabolism

INTRODUCTION: We analyzed the effects of the top 20 Alzheimer disease (AD) risk genes on gray-matter density (GMD) and metabolism. METHODS: We ran stepwise linear regression analysis using posterior cingulate hypometabolism and medial temporal GMD as outcomes and all risk variants as predictors while controlling for age, gender, and APOE ε4 genotype. We explored the results in 3D using Statistical Parametric Mapping 8. RESULTS: Significant predictors of brain GMD were SLC24A4/RIN3 in the pooled and mild cognitive impairment (MCI); ZCWPW1 in the MCI; and ABCA7, EPHA1, and INPP5D in the AD groups. Significant predictors of hypometabolism were EPHA1 in the pooled, and SLC24A4/RIN3, NME8, and CD2AP in the normal control group. DISCUSSION: Multiple variants showed associations with GMD and brain metabolism. For most genes, the effects were limited to specific stages of the cognitive continuum, indicating that the genetic influences on brain metabolism and GMD in AD are complex and stage dependent

The Pioneer Anomaly

Radio-metric Doppler tracking data received from the Pioneer 10 and 11 spacecraft from heliocentric distances of 20-70 AU has consistently indicated the presence of a small, anomalous, blue-shifted frequency drift uniformly changing with a rate of ~6 x 10^{-9} Hz/s. Ultimately, the drift was interpreted as a constant sunward deceleration of each particular spacecraft at the level of a_P = (8.74 +/- 1.33) x 10^{-10} m/s^2. This apparent violation of the Newton's gravitational inverse-square law has become known as the Pioneer anomaly; the nature of this anomaly remains unexplained. In this review, we summarize the current knowledge of the physical properties of the anomaly and the conditions that led to its detection and characterization. We review various mechanisms proposed to explain the anomaly and discuss the current state of efforts to determine its nature. A comprehensive new investigation of the anomalous behavior of the two Pioneers has begun recently. The new efforts rely on the much-extended set of radio-metric Doppler data for both spacecraft in conjunction with the newly available complete record of their telemetry files and a large archive of original project documentation. As the new study is yet to report its findings, this review provides the necessary background for the new results to appear in the near future. In particular, we provide a significant amount of information on the design, operations and behavior of the two Pioneers during their entire missions, including descriptions of various data formats and techniques used for their navigation and radio-science data analysis. As most of this information was recovered relatively recently, it was not used in the previous studies of the Pioneer anomaly, but it is critical for the new investigation.Comment: 165 pages, 40 figures, 16 tables; accepted for publication in Living Reviews in Relativit

Associations of the Top 20 Alzheimer Disease Risk Variants With Brain Amyloidosis

Importance: Late-onset Alzheimer disease (AD) is highly heritable. Genome-wide association studies have identified more than 20 AD risk genes. The precise mechanism through which many of these genes are associated with AD remains unknown. Objective: To investigate the association of the top 20 AD risk variants with brain amyloidosis. Design, Setting, and Participants: This study analyzed the genetic and florbetapir F 18 data from 322 cognitively normal control individuals, 496 individuals with mild cognitive impairment, and 159 individuals with AD dementia who had genome-wide association studies and 18F-florbetapir positron emission tomographic data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), a prospective, observational, multisite tertiary center clinical and biomarker study. This ongoing study began in 2005. Main Outcomes and Measures: The study tested the association of AD risk allele carrier status (exposure) with florbetapir mean standard uptake value ratio (outcome) using stepwise multivariable linear regression while controlling for age, sex, and apolipoprotein E ε4 genotype. The study also reports on an exploratory 3-dimensional stepwise regression model using an unbiased voxelwise approach in Statistical Parametric Mapping 8 with cluster and significance thresholds at 50 voxels and uncorrected P < .01. Results: This study included 977 participants (mean [SD] age, 74 [7.5] years; 535 [54.8%] male and 442 [45.2%] female) from the ADNI-1, ADNI-2, and ADNI-Grand Opportunity. The adenosine triphosphate-binding cassette subfamily A member 7 (ABCA7) gene had the strongest association with amyloid deposition (χ2 = 8.38, false discovery rate-corrected P < .001), after apolioprotein E ε4. Significant associations were found between ABCA7 in the asymptomatic and early symptomatic disease stages, suggesting an association with rapid amyloid accumulation. The fermitin family homolog 2 (FERMT2) gene had a stage-dependent association with brain amyloidosis (FERMT2 × diagnosis χ2 = 3.53, false discovery rate-corrected P = .05), which was most pronounced in the mild cognitive impairment stage. Conclusions and Relevance: This study found an association of several AD risk variants with brain amyloidosis. The data also suggest that AD genes might differentially regulate AD pathologic findings across the disease stages

Colonization of the Americas, 'Little Ice Age' climate, and bomb-produced carbon: their role in defining the Anthropocene

A recently published analysis by Lewis and Maslin (Lewis SL and Maslin MA (2015) Defining the Anthropocene. Nature 519: 171–180) has identified two new potential horizons for the Holocene−Anthropocene boundary: 1610 (associated with European colonization of the Americas), or 1964 (the peak of the excess radiocarbon signal arising from atom bomb tests). We discuss both of these novel suggestions, and consider that there is insufficient stratigraphic basis for the former, whereas placing the latter at the peak of the signal rather than at its inception does not follow normal stratigraphical practice. Wherever the boundary is eventually placed, it should be optimized to reflect stratigraphical evidence with the least possible ambiguity

Azimuthally anisotropic emission of low-momentum direct photons in Au++Au collisions at sNN=200\sqrt{s_{_{NN}}}=200 GeV

The PHENIX experiment at the Relativistic Heavy Ion Collider has measured 2nd and 3rd order Fourier coefficients of the azimuthal distributions of direct photons emitted at midrapidity in Au$+$Au collisions at $\sqrt{s_{_{NN}}}=200$ GeV for various collision centralities. Combining two different analysis techniques, results were obtained in the transverse momentum range of $0.4<p_{T}<4.0$ GeV/$c$. At low $p_T$ the second-order coefficients, $v_2$, are similar to the ones observed in hadrons. Third order coefficients, $v_3$, are nonzero and almost independent of centrality. These new results on $v_2$ and $v_3$, combined with previously published results on yields, are compared to model calculations that provide yields and asymmetries in the same framework. Those models are challenged to explain simultaneously the observed large yield and large azimuthal anisotropies.Comment: 552 authors, 15 pages, 9 figures, 3 tables, 2007 and 2010 data. v2 is version accepted for publication by Phys. Rev. C. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Single electron yields from semileptonic charm and bottom hadron decays in Au++Au collisions at sNN=200\sqrt{s_{NN}}=200 GeV

The PHENIX Collaboration at the Relativistic Heavy Ion Collider has measured open heavy-flavor production in minimum bias Au$+$Au collisions at $\sqrt{s_{_{NN}}}=200$ GeV via the yields of electrons from semileptonic decays of charm and bottom hadrons. Previous heavy-flavor electron measurements indicated substantial modification in the momentum distribution of the parent heavy quarks due to the quark-gluon plasma created in these collisions. For the first time, using the PHENIX silicon vertex detector to measure precision displaced tracking, the relative contributions from charm and bottom hadrons to these electrons as a function of transverse momentum are measured in Au$+$Au collisions. We compare the fraction of electrons from bottom hadrons to previously published results extracted from electron-hadron correlations in $p$$+$$p$ collisions at $\sqrt{s_{_{NN}}}=200$ GeV and find the fractions to be similar within the large uncertainties on both measurements for $p_T>4$ GeV/$c$. We use the bottom electron fractions in Au$+$Au and $p$$+$$p$ along with the previously measured heavy flavor electron $R_{AA}$ to calculate the $R_{AA}$ for electrons from charm and bottom hadron decays separately. We find that electrons from bottom hadron decays are less suppressed than those from charm for the region $3<p_T<4$ GeV/$c$.Comment: 432 authors, 33 pages, 23 figures, 2 tables, 2011 data. v2 is version accepted for publication by Phys. Rev. C. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Transverse energy production and charged-particle multiplicity at midrapidity in various systems from sNN=7.7\sqrt{s_{NN}}=7.7 to 200 GeV

Measurements of midrapidity charged particle multiplicity distributions, $dN_{\rm ch}/d\eta$, and midrapidity transverse-energy distributions, $dE_T/d\eta$, are presented for a variety of collision systems and energies. Included are distributions for Au$+$Au collisions at $\sqrt{s_{_{NN}}}=200$, 130, 62.4, 39, 27, 19.6, 14.5, and 7.7 GeV, Cu$+$Cu collisions at $\sqrt{s_{_{NN}}}=200$ and 62.4 GeV, Cu$+$Au collisions at $\sqrt{s_{_{NN}}}=200$ GeV, U$+$U collisions at $\sqrt{s_{_{NN}}}=193$ GeV, $d$$+$Au collisions at $\sqrt{s_{_{NN}}}=200$ GeV, $^{3}$He$+$Au collisions at $\sqrt{s_{_{NN}}}=200$ GeV, and $p$$+$$p$ collisions at $\sqrt{s_{_{NN}}}=200$ GeV. Centrality-dependent distributions at midrapidity are presented in terms of the number of nucleon participants, $N_{\rm part}$, and the number of constituent quark participants, $N_{q{\rm p}}$. For all $A$$+$$A$ collisions down to $\sqrt{s_{_{NN}}}=7.7$ GeV, it is observed that the midrapidity data are better described by scaling with $N_{q{\rm p}}$ than scaling with $N_{\rm part}$. Also presented are estimates of the Bjorken energy density, $\varepsilon_{\rm BJ}$, and the ratio of $dE_T/d\eta$ to $dN_{\rm ch}/d\eta$, the latter of which is seen to be constant as a function of centrality for all systems.Comment: 706 authors, 32 pages, 20 figures, 34 tables, 2004, 2005, 2008, 2010, 2011, and 2012 data. v2 is version accepted for publication in Phys. Rev.

Nuclear matter effects on J/ψJ/\psi production in asymmetric Cu+Au collisions at sNN\sqrt{s_{_{NN}}} = 200 GeV

We report on $J/\psi$ production from asymmetric Cu+Au heavy-ion collisions at $\sqrt{s_{_{NN}}}$=200 GeV at the Relativistic Heavy Ion Collider at both forward (Cu-going direction) and backward (Au-going direction) rapidities. The nuclear modification of $J/\psi$ yields in Cu$+$Au collisions in the Au-going direction is found to be comparable to that in Au$+$Au collisions when plotted as a function of the number of participating nucleons. In the Cu-going direction, $J/\psi$ production shows a stronger suppression. This difference is comparable in magnitude and has the same sign as the difference expected from shadowing effects due to stronger low-$x$ gluon suppression in the larger Au nucleus. The relative suppression is opposite to that expected from hot nuclear matter dissociation, since a higher energy density is expected in the Au-going direction.Comment: 349 authors, 10 pages, 4 figures, and 4 tables. Submitted to Phys. Rev. C. For v2, fixed LaTeX error in 3rd-to-last sentence. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Search for dark matter in events with heavy quarks and missing transverse momentum in pp collisions with the ATLAS detector

This article reports on a search for dark matterpair production in association with bottom or top quarks in20.3fb−1ofppcollisions collected at√s=8TeVbytheATLAS detector at the LHC. Events with large missing trans-verse momentum are selected when produced in associationwith high-momentum jets of which one or more are identifiedas jets containingb-quarks. Final states with top quarks areselected by requiring a high jet multiplicity and in some casesa single lepton. The data are found to be consistent with theStandard Model expectations and limits are set on the massscale of effective field theories that describe scalar and tensorinteractions between dark matter and Standard Model par-ticles. Limits on the dark-matter–nucleon cross-section forspin-independent and spin-dependent interactions are alsoprovided. These limits are particularly strong for low-massdark matter. Using a simplified model, constraints are set onthe mass of dark matter and of a coloured mediator suitableto explain a possible signal of annihilating dark matter

Measurement of higher cumulants of net-charge multiplicity distributions in Au++Au collisions at sNN=7.7−200\sqrt{s_{_{NN}}}=7.7-200 GeV

We report the measurement of cumulants ($C_n, n=1\ldots4$) of the net-charge distributions measured within pseudorapidity ($|\eta|<0.35$) in Au$+$Au collisions at $\sqrt{s_{_{NN}}}=7.7-200$ GeV with the PHENIX experiment at the Relativistic Heavy Ion Collider. The ratios of cumulants (e.g. $C_1/C_2$, $C_3/C_1$) of the net-charge distributions, which can be related to volume independent susceptibility ratios, are studied as a function of centrality and energy. These quantities are important to understand the quantum-chromodynamics phase diagram and possible existence of a critical end point. The measured values are very well described by expectation from negative binomial distributions. We do not observe any nonmonotonic behavior in the ratios of the cumulants as a function of collision energy. The measured values of $C_1/C_2 = \mu/\sigma^2$ and $C_3/C_1 = S\sigma^3/\mu$ can be directly compared to lattice quantum-chromodynamics calculations and thus allow extraction of both the chemical freeze-out temperature and the baryon chemical potential at each center-of-mass energy.Comment: 512 authors, 8 pages, 4 figures, 1 table. v2 is version accepted for publication in Phys. Rev. C as a Rapid Communication. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm