Tissue-specific and mosaic imprinting defects underlie opposite congenital growth disorders in mice

Differential DNA methylation defects of H19/IGF2 are associated with congenital growth disorders characterized by opposite clinical pictures. Due to structural differences between human and mouse, the mechanisms by which mutations of the H19/IGF2 Imprinting Control region (IC1) result in these diseases are undefined. To address this issue, we previously generated a mouse line carrying a humanized IC1 (hIC1) and now replaced the wildtype with a mutant IC1 identified in the overgrowth-associated Beckwith-Wiedemann syndrome. The new humanized mouse line shows pre/post-natal overgrowth on maternal transmission and pre/post-natal undergrowth on paternal transmission of the mutation. The mutant hIC1 acquires abnormal methylation during development causing opposite H19/Igf2 imprinting defects on maternal and paternal chromosomes. Differential and possibly mosaic Igf2 expression and imprinting is associated with asymmetric growth of bilateral organs. Furthermore, tissue-specific imprinting defects result in deficient liver- and placenta-derived Igf2 on paternal transmission and excessive Igf2 in peripheral tissues on maternal transmission, providing a possible molecular explanation for imprinting-associated and phenotypically contrasting growth disorders

Formation of dense partonic matter in relativistic nucleus-nucleus collisions at RHIC: Experimental evaluation by the PHENIX collaboration

Extensive experimental data from high-energy nucleus-nucleus collisions were recorded using the PHENIX detector at the Relativistic Heavy Ion Collider (RHIC). The comprehensive set of measurements from the first three years of RHIC operation includes charged particle multiplicities, transverse energy, yield ratios and spectra of identified hadrons in a wide range of transverse momenta (p_T), elliptic flow, two-particle correlations, non-statistical fluctuations, and suppression of particle production at high p_T. The results are examined with an emphasis on implications for the formation of a new state of dense matter. We find that the state of matter created at RHIC cannot be described in terms of ordinary color neutral hadrons.Comment: 510 authors, 127 pages text, 56 figures, 1 tables, LaTeX. Submitted to Nuclear Physics A as a regular article; v3 has minor changes in response to referee comments. 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

System Size and Energy Dependence of Jet-Induced Hadron Pair Correlation Shapes in Cu+Cu and Au+Au Collisions at sqrt(s_NN) = 200 and 62.4 GeV

We present azimuthal angle correlations of intermediate transverse momentum (1-4 GeV/c) hadrons from {dijets} in Cu+Cu and Au+Au collisions at sqrt(s_NN) = 62.4 and 200 GeV. The away-side dijet induced azimuthal correlation is broadened, non-Gaussian, and peaked away from \Delta\phi=\pi in central and semi-central collisions in all the systems. The broadening and peak location are found to depend upon the number of participants in the collision, but not on the collision energy or beam nuclei. These results are consistent with sound or shock wave models, but pose challenges to Cherenkov gluon radiation models.Comment: 464 authors from 60 institutions, 6 pages, 3 figures, 2 tables. Submitted to Physical Review Letters. 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

Improved Measurement of Double Helicity Asymmetry in Inclusive Midrapidity pi^0 Production for Polarized p+p Collisions at sqrt(s)=200 GeV

We present an improved measurement of the double helicity asymmetry for pi^0 production in polarized proton-proton scattering at sqrt(s) = 200 GeV employing the PHENIX detector at the Relativistic Heavy Ion Collider (RHIC). The improvements to our previous measurement come from two main factors: Inclusion of a new data set from the 2004 RHIC run with higher beam polarizations than the earlier run and a recalibration of the beam polarization measurements, which resulted in reduced uncertainties and increased beam polarizations. The results are compared to a Next to Leading Order (NLO) perturbative Quantum Chromodynamics (pQCD) calculation with a range of polarized gluon distributions.Comment: 389 authors, 4 pages, 2 tables, 1 figure. Submitted to Phys. Rev. D, Rapid Communications. 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

Optimizing Management of Patients With Barrett's Esophagus and Low-Grade or No Dysplasia Based on Comparative Modeling

Background & Aims: Endoscopic treatment is recommended for patients with Barrett's esophagus (BE) with high-grade dysplasia, yet clinical management recommendations are inconsistent for patients with BE without dysplasia (NDBE) or with low-grade dysplasia (LGD). We used a comparative modeling analysis to identify optimal management strategies for these patients. Methods: We used 3 independent population-based models to simulate cohorts of 60-year-old individuals with BE in the United States. We followed up each cohort until death without surveillance and treatment (natural disease progression), compared with 78 different strategies of management for patients with NDBE or LGD. We determined the optimal strategy using cost-effectiveness analyses, at a willingness-to-pay threshold of $100,000 per quality-adjusted life-year (QALY). Results: In the 3 models, the average cumulative incidence of esophageal adenocarcinoma was 111 cases, with costs totaling$5.7 million per 1000 men with BE. Surveillance and treatment of men with BE prevented 23% to 75% of cases of esophageal adenocarcinoma, but increased costs to $6.2 to$17.3 million per 1000 men with BE. The optimal strategy was surveillance every 3 years for men with NDBE and treatment of LGD after confirmation by repeat endoscopy (incremental cost-effectiveness ratio, $53,044/QALY). The average results for women were consistent with the results for men for LGD management, but the optimal surveillance interval for women with NDBE was 5 years (incremental cost-effectiveness ratio,$36,045/QALY). Conclusions: Based on analyses from 3 population-based models, the optimal management strategy for patient with BE and LGD is endoscopic eradication, but only after LGD is confirmed by a repeat endoscopy. The optimal strategy for patients with NDBE is endoscopic surveillance, using a 3-year interval for men and a 5-year interval for women

Photoproduction of J/psi and of high mass e+e- in ultra-peripheral Au+Au collisions at sqrt(s_NN) = 200 GeV

We present the first measurement of photoproduction of J/psi and of two-photon production of high-mass e+e- pairs in electromagnetic (or ultra-peripheral) nucleus-nucleus interactions, using Au+Au data at sqrt(s_NN) = 200 GeV. The events are tagged with forward neutrons emitted following Coulomb excitation of one or both Au^{star} nuclei. The event sample consists of 28 events with m_{e+e-} > 2 GeV/c^2 with zero like-sign background. The measured cross sections at midrapidity of d\sigma / dy (J/psi + Xn, y=0) = 76 +/- 33 (stat) +/- 11 (syst) micro b and d^2\sigma/dm dy (e^+e^- + Xn, y=0) = 86 +/- 23 (stat) +/- 16 (syst) micro b/(GeV/c^2) for m_{e+e-} \in [2.0,2.8] GeV/c^2 are consistent with various theoretical predictions.Comment: 345 authors from 52 institutions, 20 pages, 4 figures, 3 tables. Submitted to Physics Letters B. 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

Scaling properties of azimuthal anisotropy in Au+Au and Cu+Cu collisions at sqrt(s_NN) = 200 GeV

Detailed differential measurements of the elliptic flow for particles produced in Au+Au and Cu+Cu collisions at sqrt(s_NN) = 200 GeV are presented. Predictions from perfect fluid hydrodynamics for the scaling of the elliptic flow coefficient v_2 with eccentricity, system size and transverse energy are tested and validated. For transverse kinetic energies KE_T ~ m_T-m up to ~1 GeV, scaling compatible with the hydrodynamic expansion of a thermalized fluid is observed for all produced particles. For large values of KE_T, the mesons and baryons scale separately. A universal scaling for the flow of both mesons and baryons is observed for the full transverse kinetic energy range of the data when quark number scaling is employed. In both cases the scaling is more pronounced in terms of KE_T rather than transverse momentum.Comment: 422 authors from 58 institutions, 6 pages, 3 figures. Submitted to Physical Review Letters. 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

Saturation of azimuthal anisotropy in Au + Au collisions at sqrt(s_NN) = 62 - 200 GeV

New measurements are presented for charged hadron azimuthal correlations at mid-rapidity in Au+Au collisions at sqrt(s_NN) = 62.4 and 200 GeV. They are compared to earlier measurements obtained at sqrt(s_NN) = 130 GeV and in Pb+Pb collisions at sqrt(s_NN) = 17.2 GeV. Sizeable anisotropies are observed with centrality and transverse momentum (p_T) dependence characteristic of elliptic flow (v_2). For a broad range of centralities, the observed magnitudes and trends of the differential anisotropy, v_2(p_T), change very little over the collision energy range sqrt(s_NN) = 62-200 GeV, indicating saturation of the excitation function for v_2 at these energies. Such a saturation may be indicative of the dominance of a very soft equation of state for sqrt(s_NN) = 62-200 GeV.Comment: 432 authors, 7 pages text, 4 figures, REVTeX4. To be submitted to Physical Review Letters. 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

Correlated Production of p and p^bar in Au+Au Collisions at sqrt(s_NN) = 200 GeV

Correlations between p and pbar's at transverse momenta typical of enhanced baryon production in Au+Au collisions are reported. The PHENIX experiment measures same and opposite sign baryon pairs in Au+Au collisions at sqrt(s_NN) = 200 GeV. Correlated production of p and p^bar with the trigger particle from the range 2.5 < p_T < 4.0 GeV/c and the associated particle with 1.8 < p_T < 2.5 GeV/c is observed to be nearly independent of the centrality of the collisions. Same sign pairs show no correlation at any centrality. The conditional yield of mesons triggered by baryons (and anti-baryons) and mesons in the same pT range rises with increasing centrality, except for the most central collisions, where baryons show a significantly smaller number of associated mesons. These data are consistent with a picture in which hard scattered partons produce correlated p and p^bar in the p_T region of the baryon excess.Comment: 420 authors from 58 institutions, 21 pages,5 figures. Submitted to Physics Letters B. 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