Quantifying unobserved protein-coding variants in human populations provides a roadmap for large-scale sequencing projects

As new proposals aim to sequence ever larger collection of humans, it is critical to have a quantitative framework to evaluate the statistical power of these projects. We developed a new algorithm, UnseenEst, and applied it to the exomes of 60,706 individuals to estimate the frequency distribution of all protein-coding variants, including rare variants that have not been observed yet in the current cohorts. Our results quantified the number of new variants that we expect to identify as sequencing cohorts reach hundreds of thousands of individuals. With 500K individuals, we find that we expect to capture 7.5% of all possible loss-of-function variants and 12% of all possible missense variants. We also estimate that 2,900 genes have loss-of-function frequency of <0.00001 in healthy humans, consistent with very strong intolerance to gene inactivation.United States. National Institutes of Health (U54DK105566)United States. National Institutes of Health (R01GM104371

Differential Games with (A) symmetric Players and Heterogeneous Strategies

One family of heterogeneous strategies in differential games with (a)symmetric players is developed in which one player adopts an anticipating open-loop strategy and the other adopts a standard Markovian strategy. Via conjecturing principle, the anticipating open-loop strategic player plans her strategy based on the possible updating the rival player may take. These asymmetric strategies should be appropriate choices in some modelling circumstances and they frame one of the infinitely many non-degenerate Markovian Nash Equilibrium. Except the stationary path, this kind of strategy makes the study of short-run trajectory possible, which usually are not subgame perfect. However, the short-run non-perfection may provide very important policy suggestions

A Unified Approach to the Classical Statistical Analysis of Small Signals

We give a classical confidence belt construction which unifies the treatment of upper confidence limits for null results and two-sided confidence intervals for non-null results. The unified treatment solves a problem (apparently not previously recognized) that the choice of upper limit or two-sided intervals leads to intervals which are not confidence intervals if the choice is based on the data. We apply the construction to two related problems which have recently been a battle-ground between classical and Bayesian statistics: Poisson processes with background, and Gaussian errors with a bounded physical region. In contrast with the usual classical construction for upper limits, our construction avoids unphysical confidence intervals. In contrast with some popular Bayesian intervals, our intervals eliminate conservatism (frequentist coverage greater than the stated confidence) in the Gaussian case and reduce it to a level dictated by discreteness in the Poisson case. We generalize the method in order to apply it to analysis of experiments searching for neutrino oscillations. We show that this technique both gives correct coverage and is powerful, while other classical techniques that have been used by neutrino oscillation search experiments fail one or both of these criteria.Comment: 40 pages, 15 figures. Changes 15-Dec-99 to agree more closely with published version. A few small changes, plus the two substantive changes we made in proof back in 1998: 1) The definition of "sensitivity" in Sec. V(C). It was inconsistent with our actual definition in Sec. VI. 2) "Note added in proof" at end of the Conclusio

Evidence for e+e−→γχc1,2e^+e^-\to\gamma\chi_{c1, 2} at center-of-mass energies from 4.009 to 4.360 GeV

Using data samples collected at center-of-mass energies of $\sqrt{s}$ = 4.009, 4.230, 4.260, and 4.360 GeV with the BESIII detector operating at the BEPCII collider, we perform a search for the process $e^+e^-\to\gamma\chi_{cJ}$ $(J = 0, 1, 2)$ and find evidence for $e^+e^-\to\gamma\chi_{c1}$ and $e^+e^-\to\gamma\chi_{c2}$ with statistical significances of 3.0$\sigma$ and 3.4$\sigma$, respectively. The Born cross sections $\sigma^{B}(e^+e^-\to\gamma\chi_{cJ})$, as well as their upper limits at the 90% confidence level are determined at each center-of-mass energy.Comment: 8 pages, 7 figures, 3 table

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

Observation of χc1\chi_{c1} decays into vector meson pairs ϕϕ\phi\phi, ωω\omega\omega, and ωϕ\omega\phi

Decays of $\chi_{c1}$ to vector meson pairs $\phi\phi$, $\omega\omega$ and $\omega\phi$ are observed for the first time using $(106\pm4)\times 10^6$ \psip events accumulated at the BESIII detector at the BEPCII $e^+e^-$ collider. The branching fractions are measured to be $(4.4\pm 0.3\pm 0.5)\times 10^{-4}$, $(6.0\pm 0.3\pm 0.7)\times 10^{-4}$, and $(2.2\pm 0.6\pm 0.2)\times 10^{-5}$, for $\chi_{c1}\to \phi\phi$, $\omega\omega$, and $\omega\phi$, respectively. The observation of $\chi_{c1}$ decays into a pair of vector mesons $\phi\phi$, $\omega\omega$ and $\omega\phi$ indicates that the hadron helicity selection rule is significantly violated in $\chi_{cJ}$ decays. In addition, the measurement of $\chi_{cJ}\to \omega\phi$ gives the rate of doubly OZI-suppressed decay. Branching fractions for $\chi_{c0}$ and $\chi_{c2}$ decays into other vector meson pairs are also measured with improved precision.Comment: 4 pages, 2 figure

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.

Systematic study of charged-pion and kaon femtoscopy in Au++Au collisions at sNN\sqrt{s_{_{NN}}}=200 GeV

We present a systematic study of charged pion and kaon interferometry in Au$+$Au collisions at $\sqrt{s_{_{NN}}}$=200 GeV. The kaon mean source radii are found to be larger than pion radii in the outward and longitudinal directions for the same transverse mass; this difference increases for more central collisions. The azimuthal-angle dependence of the radii was measured with respect to the second-order event plane and similar oscillations of the source radii were found for pions and kaons. Hydrodynamic models qualitatively describe the similar oscillations of the mean source radii for pions and kaons, but they do not fully describe the transverse-mass dependence of the oscillations.Comment: 499 authors, 27 pages, 13 figures, and 11 tables. v2 is the version accepted for publication in 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