Cosmological Model with a Local Void: New Supernova Constraints

A simple inhomogeneous cosmological model with a local void is constrained with the latest Union supernova compilation. To fit the supernova data, a large local void on the scales of 1 Gpc is found, contrary to the small scales of 200 Mpc in the previous finding. A more realistic inhomogeneous cosmological model may be required to fit the supernova data. Alternatively, a clumpy universe with clumpiness parameter < 1 can fit the supernova data with reduced local void scales.Comment: 7 pages, 6 figures, to appears in the proceedings of Particle Physics, Astrophysics & Quantum Field Theory: 75 Years since Solvay, Singapore, 27-29 November 200

Evidence for the h_b(1P) meson in the decay Upsilon(3S) --> pi0 h_b(1P)

Using a sample of 122 million Upsilon(3S) events recorded with the BaBar detector at the PEP-II asymmetric-energy e+e- collider at SLAC, we search for the $h_b(1P)$ spin-singlet partner of the P-wave chi_{bJ}(1P) states in the sequential decay Upsilon(3S) --> pi0 h_b(1P), h_b(1P) --> gamma eta_b(1S). We observe an excess of events above background in the distribution of the recoil mass against the pi0 at mass 9902 +/- 4(stat.) +/- 2(syst.) MeV/c^2. The width of the observed signal is consistent with experimental resolution, and its significance is 3.1sigma, including systematic uncertainties. We obtain the value (4.3 +/- 1.1(stat.) +/- 0.9(syst.)) x 10^{-4} for the product branching fraction BF(Upsilon(3S)-->pi0 h_b) x BF(h_b-->gamma eta_b).Comment: 8 pages, 4 postscript figures, submitted to Phys. Rev. D (Rapid Communications

Drug Repurposing: The Anthelmintics Niclosamide and Nitazoxanide Are Potent TMEM16A Antagonists That Fully Bronchodilate Airways

There is an unmet need in severe asthma where approximately 40% of patients exhibit poor β-agonist responsiveness, suffer daily symptoms and show frequent exacerbations. Antagonists of the Ca2+-activated Cl− channel, TMEM16A, offers a new mechanism to bronchodilate airways and block the multiple contractiles operating in severe disease. To identify TMEM16A antagonists we screened a library of ∼580,000 compounds. The anthelmintics niclosamide, nitazoxanide, and related compounds were identified as potent TMEM16A antagonists that blocked airway smooth muscle depolarization and contraction. To evaluate whether TMEM16A antagonists resist use- and inflammatory-desensitization pathways limiting β-agonist action, we tested their efficacy under harsh conditions using maximally contracted airways or airways pretreated with a cytokine cocktail. Stunningly, TMEM16A antagonists fully bronchodilated airways, while the β-agonist isoproterenol showed only partial effects. Thus, antagonists of TMEM16A and repositioning of niclosamide and nitazoxanide represent an important additional treatment for patients with severe asthma and COPD that is poorly controlled with existing therapies. It is of note that drug repurposing has also attracted wide interest in niclosamide and nitazoxanide as a new treatment for cancer and infectious disease. For the first time we identify TMEM16A as a molecular target for these drugs and thus provide fresh insights into their mechanism for the treatment of these disorders in addition to respiratory disease

A Genome-wide Framework for Mapping Gene Regulation via Cellular Genetic Screens

Over one million candidate regulatory elements have been identified across the human genome, but nearly all are unvalidated and their target genes uncertain. Approaches based on human genetics are limited in scope to common variants and in resolution by linkage disequilibrium. We present a multiplex, expression quantitative trait locus (eQTL)-inspired framework for mapping enhancer-gene pairs by introducing random combinations of CRISPR/Cas9-mediated perturbations to each of many cells, followed by single-cell RNA sequencing (RNA-seq). Across two experiments, we used dCas9-KRAB to perturb 5,920 candidate enhancers with no strong a&nbsp;priori hypothesis as to their target gene(s), measuring effects by profiling 254,974 single-cell&nbsp;transcriptomes. We identified 664 (470 high-confidence) cis enhancer-gene pairs, which were enriched for specific transcription factors, non-housekeeping status, and genomic and 3D conformational proximity to their target genes. This framework will facilitate the large-scale mapping of enhancer-gene regulatory interactions, a critical yet largely uncharted component of the cis-regulatory landscape of the human genome

Searches for rare or forbidden semileptonic charm decays

We present searches for rare or forbidden charm decays of the form X(c)(+) -> h(+/-)l(+/-)l((l)+), where X(c)(+) is a charm hadron (D(+), D(s)(+), or A(c)(+)), h +/- is a pion, kaon, or proton, and l((l)+/-) is an electron or muon. The analysis is based on 384 fb(-1) of e(+)e(-) annihilation data collected at or close to the gamma(4S) resonance with the BABAR detector at the SLAC National Accelerator Laboratory. No significant signal is observed for any of the 35 decay modes that are investigated. We establish 90% confidence-level upper limits on the branching fractions between 1 x 10(-6) and 44 x 10(-6) depending on the channel. In most cases, these results represent either the first limits or significant improvements on existing limits for the decay modes studied

A study of radiative bottomonium transitions using converted photons

19 pages, 7 figures, submitted to Phys. Rev. DWe use 111+/-1 million Upsilon(3S) and 89+/-1 million Upsilon(2S) events recorded by the BaBar detector at the PEP-II B-factory at SLAC to perform a study of radiative transitions between bottomonium states using photons that have been converted to e+e- pairs by the detector material. We observe Upsilon(3S) -> gamma chi_b0,2(1P) decay, make precise measurements of the branching fractions for chi_b1,2(1P,2P) -> gamma Upsilon(1S) and chi_b1,2(2P) -> gamma Upsilon(2S) decays, and search for radiative decay to the eta_b(1S) and eta_b(2S) states

Analysis of the D^{+}→K^{-}π^{+}e^{+}ν_{e} decay channel

Using 347.5  fb-1 of data recorded by the BABAR detector at the PEP-II electron-positron collider, 244×103 signal events for the D+→K-π+e+νe decay channel are analyzed. This decay mode is dominated by the K̅ *(892)0 contribution. We determine the K̅ *(892)0 parameters: mK*(892)0=(895.4±0.2±0.2)  MeV/c2, ΓK*(892)00=(46.5±0.3±0.2)  MeV/c2, and the Blatt-Weisskopf parameter rBW=2.1±0.5±0.5  (GeV/c)-1, where the first uncertainty comes from statistics and the second from systematic uncertainties. We also measure the parameters defining the corresponding hadronic form factors at q2=0 (rV=V(0)/A1(0)=1.463±0.017±0.031, r2=A2(0)/A1(0)=0.801±0.020±0.020) and the value of the axial-vector pole mass parametrizing the q2 variation of A1 and A2: mA=(2.63±0.10±0.13)  GeV/c2. The S-wave fraction is equal to (5.79±0.16±0.15)%. Other signal components correspond to fractions below 1%. Using the D+→K-π+π+ channel as a normalization, we measure the D+ semileptonic branching fraction: B(D+→K-π+e+νe)=(4.00±0.03±0.04±0.09)×10-2, where the third uncertainty comes from external inputs. We then obtain the value of the hadronic form factor A1 at q2=0: A1(0)=0.6200±0.0056±0.0065±0.0071. Fixing the P-wave parameters, we measure the phase of the S wave for several values of the Kπ mass. These results confirm those obtained with Kπ production at small momentum transfer in fixed target experiments