p16 Mutation Spectrum in the Premalignant Condition Barrett's Esophagus

Background: Mutation, promoter hypermethylation and loss of heterozygosity involving the tumor suppressor gene p16 (CDKN2a/INK4a) have been detected in a wide variety of human cancers, but much less is known concerning the frequency and spectrum of p16 mutations in premalignant conditions. Methods and Findings: We have determined the p16 mutation spectrum for a cohort of 304 patients with Barrett’s esophagus, a premalignant condition that predisposes to the development of esophageal adenocarcinoma. Forty seven mutations were detected by sequencing of p16 exon 2 in 44 BE patients (14.5%) with a mutation spectrum consistent with that caused by oxidative damage and chronic inflammation. The percentage of patients with p16 mutations increased with increasing histologic grade. In addition, samples from 3 out of 19 patients (15.8%) who underwent esophagectomy were found to have mutations. Conclusions: The results of this study suggest the environment of the esophagus in BE patients can both generate an

The interplay between gonadal steroids and immune defence in affecting a carotenoid-dependent trait

The hypothesis that sexual ornaments are honest signals of quality because their expression is dependent on hormones with immune-depressive effects has received ambiguous support. The hypothesis might be correct for those signals that are carotenoid-dependent because the required carotenoid deposition in the signal, stimulated by testosterone, might lower the carotenoid-dependent immune defence of the organism. Two pathways underlying this androgen-dependent honest signaling have been suggested. Firstly, androgens that are needed for ornament expression may suppress immune defence, a cost that only high-quality animals can afford. Alternatively, immune activation may downregulate the production of androgens in low-quality individuals. Which of these alternatives is correct, and to what extent these effects are mediated by the different metabolites of androgens, remain open questions. To provide answers to these questions, we manipulated the levels of testosterone (T), 5α-dihydrotestosterone (DHT), and 17-β-estradiol (E2) in diamond doves Geopelia cuneata, a species in which both sexes exhibit a carotenoid-dependent, androgen-regulated red–orange periorbital ring of bare skin. On the first day of the experiment (day 0), we inserted steroid-releasing implants into groups of birds and on day 14, we subjected half of the birds to an immunological challenge by immunizing them with sheep red blood cells (SRBC). In females, but not in males, androgen but not estradiol treatments reduced antibody production to SRBC. In addition, the immunological challenge reduced redness and size of the trait as well as androgens levels in both sexes and in all treatments. This indicates that an immunological challenge can lower circulating T at the cost of the trait expression. These findings are in accordance with both pathways postulated in the immunocompetence-handicap hypothesis, but do not entirely support the idea that the immunosuppressive effect of androgens yields honest signaling since both T and DHT were not immunosuppressive in males, for which sexual signaling is supposed to be especially important

Search for rare quark-annihilation decays, B --> Ds(*) Phi

We report on searches for B- --> Ds- Phi and B- --> Ds*- Phi. In the context of the Standard Model, these decays are expected to be highly suppressed since they proceed through annihilation of the b and u-bar quarks in the B- meson. Our results are based on 234 million Upsilon(4S) --> B Bbar decays collected with the BABAR detector at SLAC. We find no evidence for these decays, and we set Bayesian 90% confidence level upper limits on the branching fractions BF(B- --> Ds- Phi) Ds*- Phi)<1.2x10^(-5). These results are consistent with Standard Model expectations.Comment: 8 pages, 3 postscript figues, submitted to Phys. Rev. D (Rapid Communications

Observation of CP violation in B ->eta/K-0 decays

We present measurements of the time-dependent CP-violation parameters S and C in B-0 -> eta K-'(0) decays. The data sample corresponds to 384 x 10(6) B (B) over bar pairs produced by e(+)e(-) annihilation at the Upsilon(4S). The results are S = 0.58 +/- 0.10 +/- 0.03 and C = -0.16 +/- 0.07 +/- 0.03. We observe mixing-induced CP violation with a significance of 5.5 standard deviations in this b -> s penguin dominated mode

Measurement of branching fractions and resonance contributions for B-0 ->(D)over-bar(0)K(+)pi(-) and search for B-0 ->(DK+)-K-0 pi(-) decays

Using 226x10(6) Upsilon(4S)-> B (B) over bar events collected with the BABAR detector at the PEP-II e(+)e(-) storage ring at the Stanford Linear Accelerator Center, we measure the branching fraction for B-0->(D) over bar (0)K(+)pi(-), excluding B-0-> D*-K+, to be B(B-0->(0)K(+)pi(-))=(88 +/- 15 +/- 9)x10(-6). We observe B-0->(D) over bar K-0(*)(892)(0) and B-0-> D-2(*)(2460)K--(+) contributions. The ratio of branching fractions B(B-0-> D*-K+)/B(B-0-> D(*-)pi(+))=(7.76 +/- 0.34 +/- 0.29)% is measured separately. The branching fraction for the suppressed mode B-0-> D(0)K(+)pi(-) is B(B-0-> D(0)K(+)pi(-))< 19x10(-6) at the 90% confidence level

Determinations of vertical bar V-ub vertical bar from inclusive semileptonic B decays with reduced model dependence

We report two novel determinations of vertical bar V-ub vertical bar with reduced model dependence, based on measurements of the mass distribution of the hadronic system in semileptonic B decays. Events are selected by fully reconstructing the decay of one B meson and identifying a charged lepton from the decay of the other B meson from Y(4S) -> B (B) over bar events. In one approach, we combine the inclusive (B) over bar -> X(u)l (v) over bar rate, integrated up to a maximum hadronic mass m(X) X-s gamma photon energy spectrum. We obtain vertical bar V-ub vertical bar = (4.43 +/- 0.38(stat) +/- 0.25(syst) +/- 0.29(theo)) x 10(-3). In another approach we measure the total (B) over bar -> X(u)l (v) over bar rate over the full phase space and find vertical bar V-ub vertical bar = 3.84 +/- 0.70(stat) +/- 0.30(syst) +/- 0.10(theo)) x 10(-3)

Dalitz plot analysis of the decay B±→K±K±K∓

We analyze the three-body charmless decay B-+/-->(KKK -/+)-K-+/--K-+/- using a sample of 226.0 +/- 2.5 million B (B) over bar pairs collected by the BABAR detector. We measure the total branching fraction and CP asymmetry to be B=(35.2 +/- 0.9 +/- 1.6)x10(-6) and A(CP)=(-1.7 +/- 2.6 +/- 1.5)%. We fit the Dalitz plot distribution using an isobar model and measure the magnitudes and phases of the decay coefficients. We find no evidence of CP violation for the individual components of the isobar model. The decay dynamics is dominated by the K+K- S-wave, for which we perform a partial-wave analysis in the region m(K+K-)< 2 GeV/c(2). Significant production of the f(0)(980) resonance, and of a spin zero state near 1.55 GeV/c(2) are required in the isobar model description of the data. The partial-wave analysis supports this observation.This work is supported by DOE and NSF (USA), NSERC (Canada), IHEP (China), CEA and CNRS-IN2P3 (France), BMBF and DFG (Germany), INFN (Italy), FOM (The Netherlands), NFR (Norway), MIST (Russia), and PPARC (United Kingdom). Individuals have received support from CONACyT (Mexico), Marie Curie EIF (European Union), the A. P. Sloan Foundation, the Research Corporation, and the Alexander von Humboldt Foundation

Branching fraction measurements of B+->rho(+)gamma, B-0 ->rho(0)gamma, and B-0 ->omega gamma

We present a study of the decays B+->rho(+)gamma, B-0 ->rho(0)gamma, and B-0 ->omega gamma. The analysis is based on data containing 347x10(6) B (B) over bar events recorded with the BABAR detector at the PEP-II asymmetric B factory. We measure the branching fractions B(B+->rho(+)gamma)=(1.10(-0.33)(+0.37)+/- 0.09)x10(-6) and B(B-0 ->rho(0)gamma)=(0.79(-0.20)(+0.22)+/- 0.06)x10(-6), and set a 90% C.L. upper limit B(B-0 ->omega gamma)(rho/omega)gamma)=(1.25(-0.24)(+0.25)+/- 0.09)x10(-6), from which we determine vertical bar V-td/V-ts vertical bar=0.200(-0.020)(+0.021)+/- 0.015, where the first uncertainty is experimental and the second is theoretical

Measurements of CP-violating asymmetries in B-0 -> a(1)(+/-)(1260)pi(-/+) decays

We present measurements of CP-violating asymmetries in the decay B-0 -> a(1)(+/-)(1260)pi(-/+) with a(1)(+/-)(1260)->pi(-/+)pi(+/-)pi(+/-). The data sample corresponds to 384x10(6) B(b) over bar pairs collected with the BABAR detector at the PEP-II asymmetric B factory at SLAC. We measure the CP-violating asymmetry A(CP)(a1 pi)=-0.07 +/- 0.07 +/- 0.02, the mixing-induced CP violation parameter S-a1 pi=0.37 +/- 0.21 +/- 0.07, the direct CP violation parameter C-a1 pi=-0.10 +/- 0.15 +/- 0.09, and the parameters Delta C-a1 pi=0.26 +/- 0.15 +/- 0.07 and Delta S-a1 pi=-0.14 +/- 0.21 +/- 0.06. From these measured quantities we determine the angle alpha(eff)=78.6 degrees +/- 7.3 degrees

Measurement of the CP asymmetry and branching fraction of B-0 ->rho K-0(0)

We present a measurement of the branching fraction and time-dependent CP asymmetry of B-0 -> POKO. The results are obtained from a data sample of 227 x 10(6) Y(4S) -> BB decays collected with the BABAR detector at the PEP-II asymmetric-energy B factory at Stanford Linear Accelerator Center. From a time-dependent maximum likelihood fit yielding 111 +/- 19 signal events, we find B(B-0 -> rho K-0(0)) = (4.9 +/- 0.8 +/- 0.9) x 10(-6), where the first error is statistical and the second systematic. We report the measurement of the CP parameters S-rho 0KS0 = 0.20 +/- 0.52 +/- 0.24 and C-rho 0KS0 = 0.64 +/- 0.41 +/- 0.20